Staff Publications

Staff Publications

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    'Staff publications' is the digital repository of Wageningen University & Research

    'Staff publications' contains references to publications authored by Wageningen University staff from 1976 onward.

    Publications authored by the staff of the Research Institutes are available from 1995 onwards.

    Full text documents are added when available. The database is updated daily and currently holds about 240,000 items, of which 72,000 in open access.

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Feeling full and being full : how gastric content relates to appetite, food properties and neural activation
Camps, Guido - \ 2017
Wageningen University. Promotor(en): Kees de Graaf, co-promotor(en): Paul Smeets; Monica Mars. - Wageningen : Wageningen University - ISBN 9789463438124 - 202
appetite - appetite control - magnetic resonance imaging - neurophysiology - brain - eetlust - eetlustcontrole - kernspintomografie - neurofysiologie - hersenen

Aim: This thesis aimed to further determine how gastric content relates to subjective experiences regarding appetite, how this relation is affected by food properties and whether this is visible in neural activation changes.

Method: This was studied using questionnaires, MRI of the stomach and fMRI of the brain. Randomized, controlled crossover experiments with healthy men and for one experiment women were performed.

Results: MRI measurements of the stomach as opposed to an indirect measurement by proxy, such as 13C breath testing are to be preferred. We show that gastric emptying is affected by energy load, and to a much smaller extent by viscosity. Additionally we show that a thick shake containing 100 kcal will yield higher fullness sensations than a thin shake containing 500 kcal. In the chapter we name this phenomenon ‘phantom fullness’, i.e., a sense of fullness and satiation caused by the taste and mouthfeel of a food which is irrespective of actual stomach fullness. A liquid meal followed by a drink of water empties about twice as fast in the first 35 minutes compared to the same amount of water incorporated within the liquid meal. Using MRI we were able to show layering within the stomach and increased emptying of this watery layer. With 300mL of increased gastric content inducing distention, appetite was lowered. Ingestion led to significant changes in activation in the right insula and parts of the left and right inferior frontal cortices over time. Women retain significantly more fluid after a carbonated drink in their stomach than men. When comparing correlations between subjective ratings and intragastric liquid and gas and total gastric volume, nausea and fullness correlated strongest with the liquid fraction within the stomach, bloating strongest with total gastric volume.

Conclusion: There are marked differences betweengastric content and subjective experiences regarding appetite. Viscosity is a main driver of these differences. Combined gastric MRI and brain fMRI measurements need to be performed to understand this further.

Waarom kun je door blijven eten terwijl je eigenlijk al vol zit?
Witkamp, R.F. - \ 2015
Universiteit van Nederland
voedselconsumptie - overeten - voedingsgedrag - fysiologie - neurofysiologie - verslaving - biologie - food consumption - overeating - feeding behaviour - physiology - neurophysiology - addiction - biology
Je hebt al een amuse, voorgerecht, hoofdgerecht en toetje op, en dan is-ie daar ineens: de kaasplank. Hoe is het mogelijk dat je door kunt blijven eten terwijl je al vol zit? Renger Witkamp, hoogleraar Voeding en Farmacologie (Wageningen UR), legt je uit wat hier de verklaring voor is en waarom dat ooit nuttig was.
Ongewis vissengedrag: discussie over onderzoek aan cognitie en pijn bij vissen (interview met Hans van de Vis)
Hoog, A. van 't; Vis, J.W. van de - \ 2011
Visionair : het vakblad van sportvisserij Nederland 5 (2011)22. - ISSN 1569-7533 - p. 14 - 19.
vissen - pijn - stress - neurofysiologie - bewustzijn (consciousness) - visserij - visserijbiologie - dierenwelzijn - diergezondheid - dierethiek - fishes - pain - neurophysiology - consciousness - fisheries - fishery biology - animal welfare - animal health - animal ethics
Hoe staat het met onze kennis van bewustzijn, emoties en pijn bij vissen? Een verslag van een gesprek tussen drie deskundigen over hersenen, cognitieve vaardigheden, subject taalgebruik en de scheiding tussen biologische feiten en morele oordelen. "De wetenschap kan die vraag niet beantwoorden."
Unravelling the malaria mosquito's sense of smell: neural and behavioural responses to human-derived compounds
Suer, R.A. - \ 2011
Wageningen University. Promotor(en): Willem Takken; Marcel Dicke, co-promotor(en): Joop van Loon. - S.l. : s.n. - ISBN 9789085858584 - 204
anopheles gambiae - reuk - geurstoffen - mens - neurofysiologie - receptoren - diergedrag - smell - odours - man - neurophysiology - receptors - animal behaviour
Op zoek naar de flexhen
Napel, J. ten - \ 2008
pluimveehouderij - pluimvee - hennen - diergedrag - stress - verenpikken - huisvesting van kippen - dierenwelzijn - heritability - neurofysiologie - onderzoeksprojecten - poultry farming - poultry - hens - animal behaviour - feather pecking - chicken housing - animal welfare - neurophysiology - research projects
Een van de manieren waarop kippen onder stress ontsporen, is verenpikken. Dat is minder onschuldig dan het klinkt, hele plukken veren rukken ze uit elkaars verenkleed, soms tot bloedens toe. Bovendien is er een sneeuwbaleffect: begint er een met pikken, dan doen de buren al gauw mee. En vloeit er eenmaal bloed, dan ontpopt menige suffe leghen zich als genadeloze kannibaal. De WUR probeert via een onderzoeksproject na te gaan in hoeverre erfelijkheid een rol speelt bij stressgevoeligheid, bangigheid en geneigdheid tot verenpikken bij leghennen
Associative learning in two closely related parasitoid wasps: a neuroecological approach
Bleeker, M.A.K. - \ 2005
Wageningen University. Promotor(en): Louise Vet, co-promotor(en): Hans Smid; Joop van Loon. - [S.l.] : S.n. - ISBN 9085043204 - 135
nuttige insecten - cotesia glomerata - cotesia rubecula - leervermogen - geurstoffen - reuk - neurofysiologie - vespidae - neurobiologie - beneficial insects - learning ability - odours - smell - neurophysiology - neurobiology
Neuroendocrine adaptation to stress in pigs, CRH and vasopressin in the paraventricular nucleus
Karman, A.G. - \ 2003
Wageningen University. Promotor(en): V.M. Wiegant, co-promotor(en): E.M. van der Beek. - [S.I.] : S.n. - ISBN 9058089304 - 157
varkens - stress - stressreactie - neurofysiologie - endocrinologie - adaptatie - neuropeptiden - vasopressine - corticoliberine - hypothalamus - persoonlijkheid - individuele kenmerken - diergedrag - neurobiologie - pigs - stress response - neurophysiology - endocrinology - adaptation - neuropeptides - vasopressin - corticoliberin - personality - individual characteristics - animal behaviour - neurobiology
Fertility, aging and the brain neuroendocrinological studies in female rats
Franke, A.N. - \ 2003
Wageningen University. Promotor(en): V.M. Wiegant, co-promotor(en): E.M. van der Beek. - [S.l.] : S.n. - ISBN 9058088790 - 176
ratten - vruchtbaarheid - voortplantingsvermogen - verouderen - hersenen - neurofysiologie - endocrinologie - rats - fertility - reproductive performance - aging - brain - neurophysiology - endocrinology
Neuroendocrine-immune interactions in carp: a role for cortisol and interleukin-1
Engelsma, M. - \ 2002
Wageningen University. Promotor(en): W.B. van Muiswinkel; B.M.L. Verburg-van Kemenade. - S.l. : S.n. - ISBN 9789058086655 - 158
karper - cyprinus - hydrocortison - interleukine 1 - endocrien systeem - immuunsysteem - leukocyten - interacties - stress - neurofysiologie - carp - hydrocortisone - interleukin 1 - endocrine system - immune system - leukocytes - interactions - neurophysiology
<font size="2"><p></font><FONT FACE="TIMES" SIZE=2>Maintaining a dynamic internal equilibrium, homeostasis, is crucial for survival of an organism. Disturbances in the environment may threaten the homeostasis and this will subsequently evoke an adaptive response in order to restore homeostasis. In vertebrates the adaptive response is mediated via the neuroendocrine system by adrenocortical and adrenergic activation. Glucocorticoids (GC) and catecholamines are the main actors in the response and can affect a whole range of processes, including those in the immune system. In response to pathogenic challenges the immune system is triggered, resulting in activation of components of innate and acquired immunity. Bi-directional communication between the Hypothalamus-Pituitary-Adrenal (HPA)-axis, sympathetic nervous system and the immune system is crucial to ensure homeostasis in mammals. Shared use of ligands and especially receptors forms a key component of this mutual interaction.</p><p> The Hypothalamus-Pituitary-Interrenal (HPI)-axis is the teleost equivalent of the HPA-axis. Stress induced immuno-suppression in fish is mostly attributed to actions of cortisol, major GC in fish and end-product of the HPI-axis. Stress in aquaculture is one of the potential factors causing increased susceptibility of fish to pathogens and subsequently considerable losses in production.</p><p> As part of a programme investigating adaptive strategies of carp ( <em>Cyprinus carpio</em> L.) after temperature stress, this study focuses on the possible neuroendocrine modulation of immune functioning during acute stress. We studied the effects of in vitro cortisol and in vivo acute temperature stress on carp leucocytes and functioning of these leucocytes. Moreover, the cortisol influence on gene expression of the cytokine interleukin-1</font><FONT FACE="Symbol" SIZE=2>b</font><FONT FACE="TIMES" SIZE=2>(IL-1</font><FONT FACE="Symbol" SIZE=2>b</font><FONT FACE="TIMES" SIZE=2>) was studied. IL-1</font><FONT FACE="Symbol" SIZE=2>b</font><FONT FACE="TIMES" SIZE=2>in mammals is part of the reciprocal signalling between neuroendocrine and immune system, therefore it may be an important candidate for modulating hormone secretion in carp.</p><p> Cortisol acts upon lymphocytes differentially; in previous research it was demonstrated that in carp, in particular the B lymphocytes are affected. In vertebrates B lymphocytes play an important role in acquired immunity as precursors of antibody producing cells. Maturation and activation state of B lymphocytes may have consequences for the influence cortisol has on these cells. Therefore, carp B lymphocytes were isolated from different tissues and compared with regard to their proliferation, apoptosis and the effects of cortisol on these processes. Head kidney and spleen B lymphocytes were characterised by high basal proliferation. Peripheral blood B lymphocytes showed a low basal proliferation which could be up-regulated by stimulation with lipopolysaccharide (LPS), a major constituent of the cell wall of gram-negative bacteria. LPS could not alter proliferation of head kidney B lymphocytes. In addition, Ig-crosslinking induced higher intracellular calcium responses in circulating B lymphocytes compared with B lymphocytes from head kidney or spleen origin. With respect to apoptosis, stimulation could enhance cell viability in all organs. However, in combination with cortisol high levels of apoptosis were induced. Especially activated peripheral blood B lymphocytes were sensitive to cortisol-induced apoptosis. Also head kidney and to a lesser extent spleen B lymphocytes, although less sensitive than their equivalent in circulation, underwent cortisol-induced apoptosis irrespective of extra stimulation. Proliferation was suppressed by cortisol in blood and spleen B lymphocytes and to a more limited extent in head kidney, regardless of LPS stimulation. It is suggested that cortisol may be important for immunoregulation in both stress and non-stress conditions, because the relatively modest concentration of cortisol used (compared to plasma values measured during stress conditions) could induce a significant increase in apoptosis in all three populations of B lymphocytes. This implies an impact of stress on B lymphocyte development and activity.</p><p> Stress-induced immunological changes that may contribute to a decreased disease resistance in carp were investigated. A 3 h drop in ambient water temperature was used as model for a relative mild and acute stressor for carp. After single or multiple temperature shocks, the relative number of circulating B lymphocytes decreased significantly within 4 h after the onset of the stressor, which was even more pronounced than after challenging the immune system. After a single temperature shock the relative number of B lymphocytes returned to control levels within 24 hours. In head kidney, an increase was measured in the relative number of B lymphocytes. Migration of B lymphocytes resulting in a redistribution of these cells to other body compartments may contribute to the relative drop in B lymphocytes in the circulation. Granulocyte numbers showed opposite reactions, doubling in circulation and decreasing significantly in head kidney. This demonstrates differential modulation of immune cells <em>in vivo</em> by a relative mild stressor. Freshly isolated blood lymphocytes from stressed carp showed a considerable higher number of apoptotic cells than lymphocytes from unstressed animals. Besides B lymphocytes, Ig <sup>-</SUP>lymphocytes contributed significantly to this stress-induced apoptosis. Glucocorticoid receptors could be detected in the vast majority of the B lymphocytes and also part of the Ig <sup>-</SUP>lymphocytes. As distribution of B lymphocytes was substantially affected by temperature stress, the effects of multiple temperature shocks on humoral antibody responses were determined. The kinetics of the antibody response to both, T lymphocyte independent (TI) antigens and T lymphocyte dependent (TD) antigens consistently showed a trend to decreased antibody response in stressed carp. In carp immunised with the TI-antigen TNP-LPS the antibody response was significantly slower in the stressed carp. These observations confirm the effect of temperature stress on the B lymphocyte population.</p><p> These results show that even a mild stressor can affect distribution of B lymphocyte and granulocyte cell populations reversibly with differential effects and thus can have implications for a subsequent immune response. However, during acute stress, the role of cortisol is most probably not purely immunosuppressive but more immunomodulatory. A stress-induced enhancement of an innate type of response could facilitate a fast and effective reaction of the immune system.</p><p> Cytokines, like IL-1</font><FONT FACE="Symbol" SIZE=2>b</font><FONT FACE="TIMES" SIZE=2>, play a pivotal role in the regulation of the immune system. Macrophages and a whole range of other cells release IL-1</font><FONT FACE="Symbol" SIZE=2>b</font><FONT FACE="TIMES" SIZE=2>as a response to infection or tissue damage. IL-1</font><FONT FACE="Symbol" SIZE=2>b</font><FONT FACE="TIMES" SIZE=2>has pleiotropic effects as an immune and inflammatory mediator. Furthermore, IL-1</font><FONT FACE="Symbol" SIZE=2>b</font><FONT FACE="TIMES" SIZE=2>is an important candidate able to affect the HPI-axis by altering the release of corticotropin releasing hormone (CRH) and adrenocorticotropic hormone (ACTH).</p><p> In fish, most interleukin molecules await identification but the IL-1</font><FONT FACE="Symbol" SIZE=2>b</font><FONT FACE="TIMES" SIZE=2>sequences of several teleost fishes were recently elucidated. In the tetraploid carp we describe gene organisation and expression of two IL-1</font><FONT FACE="Symbol" SIZE=2>b</font><FONT FACE="TIMES" SIZE=2>genes: IL-1</font><FONT FACE="Symbol" SIZE=2>b</font><FONT FACE="TIMES" SIZE=2>1 and IL-1</font><FONT FACE="Symbol" SIZE=2>b</font><FONT FACE="TIMES" SIZE=2>2. The two carp mRNA sequences share about 74% amino acid identity. The existence of two IL-1</font><FONT FACE="Symbol" SIZE=2>b</font><FONT FACE="TIMES" SIZE=2>copies in the carp genome probably originates from the tetraploid nature of the species. In contrast to carp IL-1</font><FONT FACE="Symbol" SIZE=2>b</font><FONT FACE="TIMES" SIZE=2>1, the IL-1</font><FONT FACE="Symbol" SIZE=2>b</font><FONT FACE="TIMES" SIZE=2>2 locus is represented by multiple sequences with 95-99% identity. Detection of up to 6 distinct IL-1</font><FONT FACE="Symbol" SIZE=2>b</font><FONT FACE="TIMES" SIZE=2>2 sequences within single homozygous fish suggests the presence of multiple copies of the IL-1</font><FONT FACE="Symbol" SIZE=2>b</font><FONT FACE="TIMES" SIZE=2>2 gene in the carp genome. Both IL-1</font><FONT FACE="Symbol" SIZE=2>b</font><FONT FACE="TIMES" SIZE=2>1 and IL-1</font><FONT FACE="Symbol" SIZE=2>b</font><FONT FACE="TIMES" SIZE=2>2 comprise seven exons with typical IL-1 characteristics as an IL-1 family motif and instability motifs in the 3'-untranslated region. A general discrepancy of teleost IL-1</font><FONT FACE="Symbol" SIZE=2>b</font><FONT FACE="TIMES" SIZE=2>sequences described thus far with mammalian IL-1b, is the lack of a clear caspase-1 (interleukin- 1</font><FONT FACE="Symbol" SIZE=2>b</font><FONT FACE="TIMES" SIZE=2>-converting enzyme; ICE) cleavage site. Three IL-1</font><FONT FACE="Symbol" SIZE=2>b</font><FONT FACE="TIMES" SIZE=2>1 RNA transcripts could be detected in carp: (1) a fully spliced product, (2) exon 1-7 with introns 5 and 6 and (3) exon 1-7 with intron 5 only. Intron-containing products were also detected for IL-1</font><FONT FACE="Symbol" SIZE=2>b</font><FONT FACE="TIMES" SIZE=2>2. These intron-containing products probably represent partially spliced transcripts.</p><p> IL-1</font><FONT FACE="Symbol" SIZE=2>b</font><FONT FACE="TIMES" SIZE=2>mRNA expression in carp was semi-quantitatively analysed by RT-PCR in multiple organs, including brain and pituitary. <em>In vivo</em> , mRNA of both IL-1</font><FONT FACE="Symbol" SIZE=2>b</font><FONT FACE="TIMES" SIZE=2>sequences were constitutively expressed in healthy carp, for IL-1</font><FONT FACE="Symbol" SIZE=2>b</font><FONT FACE="TIMES" SIZE=2>1 this was predominantly in the immune organs head kidney and spleen. Furthermore, a scattered distribution of IL-1</font><FONT FACE="Symbol" SIZE=2>b</font><FONT FACE="TIMES" SIZE=2>1 producing cells was shown by <em>in situ</em> hybridisations of head kidney tissue. Administration of phorbol-myristate-acetate (PMA) or LPS to phagocytes isolated from the head kidney, resulted in up-regulation of IL-1</font><FONT FACE="Symbol" SIZE=2>b</font><FONT FACE="TIMES" SIZE=2>1 expression. Also IL-1</font><FONT FACE="Symbol" SIZE=2>b</font><FONT FACE="TIMES" SIZE=2>2 transcripts could be up-regulated by <em>in vitro</em> LPS stimulation of head kidney phagocytes. Interestingly, by determining the ratio of expression it was demonstrated that IL-1</font><FONT FACE="Symbol" SIZE=2>b</font><FONT FACE="TIMES" SIZE=2>2 is expressed at a maximum of one tenth of the amount of the IL-1</font><FONT FACE="Symbol" SIZE=2>b</font><FONT FACE="TIMES" SIZE=2>1 sequence. Together with the high number of amino acid substitutions in the IL-1</font><FONT FACE="Symbol" SIZE=2>b</font><FONT FACE="TIMES" SIZE=2>2 sequences this suggests either that IL-1</font><FONT FACE="Symbol" SIZE=2>b</font><FONT FACE="TIMES" SIZE=2>2 is approaching a pseudogene status or IL-1</font><FONT FACE="Symbol" SIZE=2>b</font><FONT FACE="TIMES" SIZE=2>2 is part of a complex receptor - ligand interaction network. The involvement of nuclear factor (NF)-</font><FONT FACE="Symbol" SIZE=2>k</font><FONT FACE="TIMES" SIZE=2>B in carp IL-1</font><FONT FACE="Symbol" SIZE=2>b</font><FONT FACE="TIMES" SIZE=2>1 expression was shown with suppression of the LPS-induced IL-1</font><FONT FACE="Symbol" SIZE=2>b</font><FONT FACE="TIMES" SIZE=2>expression by the NF-</font><FONT FACE="Symbol" SIZE=2>k</font><FONT FACE="TIMES" SIZE=2>B inhibitor, pyrrolidine dithiocarbamate (PDTC). Data suggests also that carp IL-1</font><FONT FACE="Symbol" SIZE=2>b</font><FONT FACE="TIMES" SIZE=2>2 is regulated via NF-</font><FONT FACE="Symbol" SIZE=2>k</font><FONT FACE="TIMES" SIZE=2>B and consequently both IL-1</font><FONT FACE="Symbol" SIZE=2>b</font><FONT FACE="TIMES" SIZE=2>sequences appear to have similar promoter regions.</p><p> Cortisol, as endocrine-derived factor potentially mediating carp IL-1</font><FONT FACE="Symbol" SIZE=2>b</font><FONT FACE="TIMES" SIZE=2>expression, was able to inhibit constitutive expression of IL-1</font><FONT FACE="Symbol" SIZE=2>b</font><FONT FACE="TIMES" SIZE=2>1 as well as IL-1</font><FONT FACE="Symbol" SIZE=2>b</font><FONT FACE="TIMES" SIZE=2>2 transcripts in vitro. However, when cortisol was added in combination with LPS at a physiological dose, cortisol could not inhibit LPS-induced expression. Moreover, it appears that cortisol synergistically enhances LPS-induced IL-1</font><FONT FACE="Symbol" SIZE=2>b</font><FONT FACE="TIMES" SIZE=2>expression in carp. Probably LPS overrules the glucocorticoid receptor mediated inhibition via the NF-</font><FONT FACE="Symbol" SIZE=2>k</font><FONT FACE="TIMES" SIZE=2>B pathway. This might imply that cortisol can not suppress IL-1</font><FONT FACE="Symbol" SIZE=2>b</font><FONT FACE="TIMES" SIZE=2>activation during infection. At a tenfold higher cortisol dose, however, the expression is inhibited.</p><p> In conclusion, data presented in this thesis show that carp leucocytes are differentially sensitive to cortisol and in vivo stress, with regard to cell type, location and maturation or activation state. This affects cell viability, replication and migration with subsequent consequences for the immune status of carp. Also interaction of the neuroendocrine system with immune regulating factors was demonstrated: cortisol affects carp IL-1</font><FONT FACE="Symbol" SIZE=2>b</font><FONT FACE="TIMES" SIZE=2>mRNA expression. IL-1</font><FONT FACE="Symbol" SIZE=2>b</font><FONT FACE="TIMES" SIZE=2>in carp consists of multiple forms and is part of an immune regulating mechanism which probably matches that of mammals in complexity.
An electrophysiological investigation of the effects of cholecystokinin on enteric neurons
Schutte, I.W.M. - \ 1998
Agricultural University. Promotor(en): L.M.A. Akkermans; A.B.A. Kroese. - S.l. : Schutte - ISBN 9789054857990 - 125
neurofysiologie - zenuwstelsel - neurologie - neuropeptiden - hystricidae - caviidae - zintuigorganen - hormonen - endocrinologie - darmen - neurophysiology - nervous system - neurology - neuropeptides - sense organs - hormones - endocrinology - intestines
<br/>Cholecystokinin (CCK) is a peptide, which is present in the gastrointestinat tract in endocrine cells and in the enteric nervous system (ENS). A possible function in the control of motility of the small intestine has been attributed to neuronal CCK. The aim of this thesis was to obtain a fundamental insight into the action and effects of CCK on enteric neurons. Therefore, intracelluiar recordings were made of myenteric neurons in an isolated preparation of the guinea-pig ileum. Two types of excitable myenteric neurons were distinguished. Neurons in which the action potential showed a pronounced inflexion (shoulder) on the falling phase, were classified as AH neurons, the others as S neurons. The effects of CCK-8 and CCK-8NS on both types of neurons were determined. Application of CCK evoked dissimilar excitatory effects in the two types of neurons, which presumably are related to the function of these neurons in the ENS. Application of CCK evoked excitatory effects on almost all S neurons (inter- or motor-neurons). The effect was mediated by both CCK <sub>A</sub> and CCK <sub>B</sub> receptor subtypes and was different for both receptor subtypes with respect to action in time. Some S neurons possessed exclusively the CCK, or the CCK, receptor subtype, but others possessed both subtypes. The predominant effect of CCK on AH neurons (sensory neurons) was also slow excitation. These AH neurons were all endowed with both CCK receptor subtypes. The CCK <sub>A</sub> and CCK <sub>B</sub> , receptor subtypes on AH neurons had not only a different affinity for CCK, but also mediated the effects through different ionic channels. Results of experiments in which the effects of CCK antagonists on synaptic transmission were determined, showed that CCK in the ENS has besides a hormonal function, a function as neurotransmitter.<p>
Stress and the hypothalamus-pituitary-gonadal axis in the cyclic rat
Roozendaal, M.M. - \ 1997
Agricultural University. Promotor(en): V.M. Wiegant; J.A.M. Mattheij. - S.l. : Roozendaal - ISBN 9789054857518 - 136
ratten - zenuwstelsel - stress - voortplanting - geslachtshormonen - hypofysaire hormonen - vrouwtjes - hypothalamus - neurofysiologie - neurologie - hormonen - endocrinologie - rats - nervous system - reproduction - sex hormones - pituitary hormones - females - neurophysiology - neurology - hormones - endocrinology
<br/>The influence of stress on reproductive functions has been subject of much research. Various kinds of stress are known to affect reproductive functions. In females, the complex regulation of the ovarian cycle relies on a series of neuroendocrine events whose temporal relationship is so critical that any disruption in the orderly sequence may jeopardize reproductive success. During the oestrous cycle, especially the mechanisms which induce oestrous behaviour, the LH and FSH surge and ovulation seem to be vulnerable to stress. The evidence that stress influences reproductive functions is mainly based on studies performed with intact and castrated male rats, and with ovariectomized and ovariectomized, oestrogenprimed female rats, and mainly concern the effect of stress on basal LH secretion. The hormonal status of these animal models differs essentially from those of intact pro-oestrous female rats, and this can of course be of influence on the response to the stressor. However, only a few studies have been performed on the effects of stress on the surge of gonadotropins in the intact cyclic female rat. This thesis focusses on the effect of restraint stress on the surge of gonadotropins and ovulation in the intact cyclic female rat and the underlying mechanisms.<p>In <strong>Chapter 1</strong> a review is given of stress and reproductive functions. In addition, possible pathways via which stress may influence reproduction are briefly discussed.<p><strong>Chapter 2</strong> describes experiments on the effects of different periods of restraint stress on preovulatory LH and FSH surge profiles and ovulation in the intact cyclic female rat. In literature, the few studies performed with intact female rats have shown that: 1) the LH surge and subsequent ovulation are suppressed by footshock stress , and that ovulation is inhibited by immobilization stress ; 2) the gonadotropin surge can be delayed by one day if on pro-oestrus the surge is blocked, and 3) a partially suppressed LH surge can induce alterations in the ovulation process, since treatment of rats of which the endogenous LH surge is blocked with a small amount of LH on the morning of pro-oestrus can cause meiotic resumption and induce precocious follicle luteinization. In the experiments described in chapter 2, groups of pro-oestrous rats were subjected to restraint which was started 0, 1 or 2 h before the presumed onset of the LH surge and continued during the surge until the beginning of the dark period, thereby covering most of the period during which the surge appears. The presumed onset of the LH surge is approximately 2 h after the middle of the light period. Exposure to restraint resulted in a partial or total inhibition of the LH and FSH surge (no significant difference between the three restraint groups). In rats with a partially suppressed LH surge, ovulation occurred or the ovaries contained unaffected graafian follicles on the day following the stress. In restraint rats with a completely blocked LH surge (≤detectable levels), LH and FSH levels were not elevated the next day, indicating that the surge of gonadotropins had not been delayed by one day. The ovaries of these rats indeed contained unaffected graafian follicles. The results of this study indicate that, during pro-oestrus, restraint stress suppresses (and does not delay) the release of preovulatory gonadotropins in the intact female rat. Partial suppression of the LH surge by restraint induces ovulation or ovulation had not occurred and the graafian follicles were unaffected.<p>The following chapters are focused on the central mechanisms involved in the inhibition of the pro-oestrous surge of gonadotropins by restraint stress. An interaction of hormones and neuropeptides of the HPA axis (e.g. CRH, AVP and βEND) with those of the HPG axis (e.g. GnRH, LH and FSH) has been suggested. It has been reported that central administration of CRH (the major neuromodulator of the HPA axis) to male or ovariectomized female rats results in a suppression of LH-, but not of FSH-release. In addition, prolonged administration of CRH can cause downregulation of CRH receptors which may alter its effect on the LH and FSH surge. Therefore, <strong>Chapter 3</strong> deals with the effects of central administration of CRH on the pre-ovulatory surge of LH and FSH in the intact female rat. An icv injection (bolus) or infusion (6-h) with CRH resulted in an inhibition of the LH surge and to a lesser degree, the FSH surge. The inhibition of pro-oestrous LH surge levels lasted 3-4 h; subsequently LH increased to control surge levels. A 9-h infusion of CRH which was started 4 h before the presumed onset of the surge, however, did not affect the surge of LH and FSH. This indicates that CRH can inhibit the LH surge (and to a lesser extent the FSH rise) for only 3-4 h and that thereafter adaptive mechanisms are activated that restore LH secretion to surge levels even in the presence of CRH. Inhibition of LH by CRH can occur via activation of the endogenous opioid βEND, and AVP may mediate the CRH-induced βEND release. Therefore, we investigated if the inhibitory effect of CRH on the LH and FSH surge was modified by icv pretreatment with an AVP-antiserum. Pretreatment (icv) with AVP-antiserum did not prevent but, on the contrary, prolonged the inhibitory effect of CRH on the pro-oestrous LH surge. Pretreatment with AVP-antiserum before the start of the 9-h CRH infusion resulted in a suppression of the LH surge. AVP-antiserum alone did not influence pro-oestrous LH surge levels. These results indicate that AVP-antiserum pretreatment potentiates the inhibitory effect of CRH on the pro-oestrous LH surge. Therefore, we suggest that during high central levels of CRH, - as are obtained after icv injection and may occur during stress - AVP pathways become activated that mitigate the suppression of LH release.<p>In <strong>Chapter 4</strong> experiments are described in which we investigated the role of endogenous CRH and AVP in the inhibitory effect of restraint stress on the pro-oestrous LH surge. Many behavioural and physiological effects observed during stress can be mimicked by central administration of CRH, and CRH release is observed during stress. Additionally, in chapter 3 we showed that central administration of CRH can inhibit the LH surge in the intact cyclic female rat. A possible involvement of endogenous CRH in the restraint-induced inhibition of the LH surge was investigated by icv administration of the CRH antagonist α-helical CRH before application of restraint stress. In pro-oestrous rats, pretreatment with α-helical CRH did not affect the induced suppression, whereas the restraint-induced corticosterone response was partially prevented by both doses of the antagonist. These data suggest that CRH pathways activated during restraint stress do not mediate the inhibitory effect on LH surge levels. As suggested before, high central CRH levels may activate AVP pathways and several studies suggest some role of AVP in the control of LH secretion during stress. Therefore, we pretreated pro-oestrous rats with AVP-antiserum and then subjected them to restraint stress. In control rats, restraint stress partially inhibited the LH surge. Pretreatment (icv) with AVP-antiserum potentiated this inhibition. This result indicates that the residual surge seen in control rats is the result of a stimulatory AVP neuronal pathway activated by restraint stress. In an additional experiment, iv treatment with the GnRH agonist Ovalyse <sup><font size="-2">®</font></SUP>during restraint resulted in a steep and transient rise of LH levels, indicating that the pituitary was not rendered refractory to GnRH.<p>During the oestrous cycle opioids tonically inhibit secretion of gonadotropins through inhibition of GnRH release, except for the period during the preovulatory surge of gonadotropins. Morphine or βEND administration before the onset of the LH surge can inhibit the spontaneous or steroid-induced LH surge. Blockade of opioids receptors with the antagonist naloxone before the presumed onset of the LH surge, induces a premature surge. Several studies have suggested a role for opioids in the effects of stress on reproductive functions (inducing the inhibitory effects on LH secretion) but only a few have used intact female rats . In <strong>Chapter 5</strong> experiments are described which investigate the role of opioids in the restraint-induced inhibition of the LH surge in the intact cyclic female rat. The aim of our experiments was to distinguish between the putative role of opioids in mediating the inhibitory effect of restraint on the LH surge and their role in the cyclic regulation of LH secretion. Repeated iv injections with the opioid antagonist naloxone during restraint did not affect the restraint-induced suppression of the pro-oestrous LH surge, neither did pretreatment with naloxone or naltrexone, a longer acting opioid antagonist. This indicates that opioids are not critically involved as mediators in the restraint-induced suppression of the LH surge in the intact female rat. Pretreatment with naltrexone did induce a premature rise of LH levels, indicating, in line with results from others, that there is an inhibitory tone of endogenous opioids at that time, and that withdrawal of this inhibition can lead to initiation of an LH surge.<p>GABA is a major inhibitory neurotransmitter in the brain, and under non-stress conditions it is involved in the regulation of GnRH release. For instance, it appears to play a role in the negative feedback action of oestrogen on the GnRH release . Additionally, there is evidence that stress can alter GABAergic activity in the brain. Yet, a relationship between the stress effects on reproductive functions and GABAergic activity has not been established. In <strong>Chapter 6</strong> we investigated the role of GABA in the restraint-induced inhibition of the preovulatory LH surge. First, we determined the effect central GABA mechanisms on the prooestrous LH secretion. Indeed, icv administration of the GABA <sub>A</sub> receptor agonist muscimol as well as the GABA <sub>B</sub> receptor agonist baclofen inhibited the LH surge. These data accord with studies obtained by others in ovariectomized and ovariectomized/steroid-primed female rats. To investigate the conceivable involvement of GABA in the inhibitory effect of restraint on the LH surge, prooestrous rats were given an icv injection with the GABA <sub>A</sub> receptor antagonist bicuculline, or with the GABA <sub>B</sub> receptor antagonist phaclofen, and were subsequently subjected to restraint stress. Neither of these pretreatments, however, prevented the restraint-induced suppression of the LH surge. These data suggest that activation of GABA receptors does likely not mediate the inhibitory effect of restraint on the LH surge of the intact female rat.<p>In summary, the experiments performed with intact cyclic female rats described this thesis yielded the following conclusions;<br/>- restraint stress during pro-oestrus can lead to (partial or complete) suppression of the release of preovulatory gonadotropins. Even when the surge is largely suppressed, the residual LH surge is sufficient to induce ovulation; in case of complete suppression, the graafian follicles remain unaffected and ovulation does not occur.<p>- exogenous CRH can inhibit the pro-oestrous LH surge (and to a lesser extent the FSH surge), but this effect is only temporary even when prolonged icv infusions with high doses are given ("escape" after 3-4 h). Pretreatment with AVP-antiserurn prolongs the inhibitory effect of CRH on LH.<p>- exogenous CRH can activate a vasopressinergic mechanism that counteracts the inhibitory effects of CRH on the surge, and underlies the "escape".<p>- during restraint stress CRH pathways are activated that result in a corticosterone response, but appear not to be critically involved in the restraint-induced inhibition of the pro-oestrous LH surge.<p>- during restraint stress, a vasopressinergic mechanism is activated in the brain, that apparently stimulates LH secretion and can sustain an LH surge.<p>- endogenous opioids do likely not mediate the effect of restraint. Yet, an inhibitory opioid tone exists (also under non-stress conditions) in the period preceding the LH surge. Withdrawal of this tone can yield a premature surge.<p>- pharmacological stimulation of GABA receptors in the brain can inhibit the LH surge in the intact cyclic female rat via GAB <sub>A</sub> and GABA <sub>B</sub> receptors. GABA receptors, however, appear not to be involved in the inhibitory effect of restraint stress on the pro-oestrous LH surge of the intact female rat.
Polychlorinated biphenyl-induced alterations of thyroid hormone homeostasis and brain development in the rat
Morse, D.C. - \ 1995
Agricultural University. Promotor(en): J.H. Koeman; A. Brouwer. - S.l. : Morse - ISBN 9789054853756 - 175
toxische stoffen - polychloorbifenylen - zenuwstelsel - zintuigorganen - neurofysiologie - neurologie - osmose - tropismen - schildklier - ratten - xenobiotica - fysische factoren - chemische factoren - toxic substances - polychlorinated biphenyls - nervous system - sense organs - neurophysiology - neurology - osmosis - tropisms - thyroid gland - rats - xenobiotics - physical factors - chemical factors - cum laude
<strong>Introduction</strong><p>The work described in this thesis was undertaken to gain insight in the processes involved in the developmental neurotoxicity of polychlorinated biphenyls. It has been previously hypothesized that the alteration of thyroid hormone status by PCBs may be in part responsible for the developmental neurotoxicity of these compounds in humans (Rogan <em>et al.</em> 1986). This is a logical hypothesis, given the well-described effects of PCBs on plasma thyroid hormone levels in adult animals, and the indisputable importance of thyroid hormones in brain development.<p>Therefore the first goal was to determine the nature and mechanism of PCBinduced decreases in circulating and brain thyroid hormone levels in fetal and neonatal rats (Chapter 2,3,4 and 5). We examined the effects of maternal PCB administration on the metabolism of thyroid hormone in the brain and liver of fetal, neonatal and adult offspring in relation to the level of thyroid hormone in the plasma and brain. Vitamin A status, which may be linked to thyroid hormone status following PCB exposure, was also examined in one reproduction study (Chapter 6).<p>Since the kinetics and metabolism of PCBs may play a pivotal role in the alteration of thyroid hormones, a radiolabelled and easily metabolized PCB congener was used in <em>in vivo</em> (Chapter 2) and <em>in vitro</em> experiments (Chapter 3) to examine the kinetics and metabolism of a model compound in pregnant and fetal rats. The relevance of this model compound for complex PCB mixtures was ascertained following the administration of a commercial PCB mixture to pregnant rats (Chapter 5).<p>Lastly, neurochemical analysis were conducted on the brains of the offspring following maternal PCB exposure to determine which brain regions, cell types and neurotransmitter systems are affected during brain development (Chapter 7 and 8).<p><strong>Biotransformation of PCBs to thyroid hormone antagonists</strong><p>The metabolism and distribution of [ <sup><font size="-2">14</font></SUP>C]-3,3',4,4'-tetrachlorobiphenyI ([ <sup><font size="-2">14</font></SUP>C]- TCB) was examined in pregnant rats and their fetuses (Chapter 2 and 3, Morse <em>et al.,</em> 1995). The major metabolite found in adult liver and plasma, placental tissue, whole fetuses and fetal blood was 3,3',4',5-tetrachloro-4-biphenyloI (4-OH-tetraCB). While maternal tissue levels of [ <sup><font size="-2">14</font></SUP>C]-TCB derived radioactivity significantly decreased by 65-85% over a 7 day period, radioactivity in the fetus accumulated more than 100-fold over the same period. The fetal accumulation of radioactivity was due primarily to 4-OH-tetraCB, and on day 20 of gestation, fetal plasma levels of 4-OH- tetraCB were 14 times higher than maternal plasma levels (14 μM vs 1 μM).<p>In order to determine the source of 4-OH-tetraCB in the fetus, in vitro studies were carried out by incubating [ <sup><font size="-2">14</font></SUP>C]-TCB with maternal and fetal rat microsomes and analysing the reaction products with high pressure liquid chromatography and gas chromatographic/mass spectrometric analysis. First, incubation conditions were optimized using male rat microsomes. Under optimal incubation conditions, hepatic microsomes from pregnant rats pretreated with TCB produced 4-OH-tetraCB as the major metabolite, while no metabolites were detected in incubations with microsomes from fetuses from pregnant rats pretreated with TCB. The results indicate that 4-OH-tetraCB, found in the fetal compartment is due to transplacental transport from maternally formed 4-OH-tetraCB. This is in agreement with the observation that the biotransformation of TCB is dependent on CYP1A1 induction, and no CYP1A1 activity was observed in fetal microsomes after maternal treatment with TCB.<p>In late gestation, the high levels of 4-OH-tetraCB found in the fetal plasma were asssociated with decreases in fetal plasma thyroid hormone levels in the absence of significant decreases in maternal plasma thyroid hormones. 4-OH-tetraCB has a high affinity for transthyretin (the major plasma thyroid hormone transport protein in the rat) and competitively displaces thyroxine from this protein (Brouwer <em>et al.</em> 1990, Lans <em>et al.</em> 1993). It was therefore concluded that the accumulation of 4-OH-tetraCB in the fetus is due to the high affinity of this metabolite for transthyretin, and results in significant decreases in fetal plasma thyroxine levels.<p>Since the model compound 3,3',4,4'-TCB is present in only very low levels in the environment, it was of interest if the exposure of pregnant rats to a commercial PCB mixture (Aroclor 1254) would also result in the accumulation of phenolic metabolites in the fetal plasma (Chapter 5). Relatively high levels of hydroxylated PCB metabolites from penta, hexa. and hepta- chlorinated biphenyls have been found in the plasma of rats exposed to Aroclor 1254 and in environmentally exposed humans (Bergman <em>et al.</em> 1994). A significant accumulation of 4-OH- 2,3,3',4',5-pentachlorobiphenyI (4-OH-pentaCB) was found in the plasma of late gestational fetuses from pregnant rats exposed to Aroclor 1254 (up to 4.6 μM). This PCB metabolite has a 10-fold higher binding affinity for TTR than thyroxine, thereby confirming the relevance of work with the model compound, 3,3',4,4'-tetrachlorobiphenyl. In addition, relatively large amounts of 4-OH- pentaCB were found in the fetal (0.46 μM), but not weanling rat brain, indicating that in the absence of a functional blood-brain barrier hydroxylated PCB metabolites may enter the brain. The toxicological significance of this finding deserves investigation.<p><strong>Effects of PCB exposure on thyroid homone levels and metabolism</strong><p><em>T <sub><font size="-2">4</font></sub> -Uridine-diphospho-glucuronyl transferase</em><br/>Decreases in plasma thyroid hormone levels in adult rodents may also be caused by the induction of the hepatic glucuronidation of thyroxine (Bastomsky, 1974, Barter and Klaasen 1992). The effect of a single maternal dose of 3,3',4,4',5,5'-hexachlorobiphenyl (HCB) on day 1 of gestation and in combination with repeated maternal doses of TCB (day 2 to 18 of gestation) on maternal, fetal and neonatal hepatic microsomal and brain thyroxine metabolism is described in Chapter 4. The results indicated that although maternal administration of coplanar PCBs may result in the induction of fetal hepatic microsomal T <sub><font size="-2">4</font></sub> glucuronidation, this induction did not cause the reductions in fetal plasma T <sub><font size="-2">4</font></sub> levels. Only the combined dose of HCB with TCB resulted in significant decreases in fetal plasma T <sub><font size="-2">4</font></sub> levels. This indicates that decreased placental transport of maternally-derived T <sub><font size="-2">4</font></sub> and the blockage of fetal thyroid hormone transport by 4-OH-tetraCB resulted in the decrease of fetal T <sub><font size="-2">4</font></sub> levels. In neonates and dams, however, the induction of T <sub><font size="-2">4</font></sub> glucuronidation by lactational exposure to coplanar PCBs may contribute to the observed decreases in plasma thyroxine levels.<p>Maternal exposure to the commercial PCB mixture Aroclor 1254 also induced T <sub><font size="-2">4</font></sub> -UDPGT activity in hepatic microsomes from pregnant and weanling rats, but not in the fetus (Chapter 5). Since only the induction of maternal hepatic microsomal T <sub><font size="-2">4</font></sub> -UDPGT correlated with reductions in plasma thyroid hormones, it was concluded that the induction of T4-UDPGT activity played only a minor role in the reductions of plasma thyroid hormones in fetal and weanling rats. Large reductions in plasma thyroid hormones have also been observed following dietary Aroclor 1254 exposure in homozygous Gunn rats, which are deficient in T <sub><font size="-2">4</font></sub> -UDPGT activity (Collins and Capen, 1980a). The only long-term effect on thyroid hormone metabolism observed following maternal PCB exposure was a significant decrease in female hepatic microsomal T <sub><font size="-2">4</font></sub> glucuronidation in young adult offspring.<p><em>Type II thyroxine 5'-deiodinase</em><br/>As most of the biologically active hormone triiodothyronine (T <sub><font size="-2">3</font></sub> ) is derived from T <sub><font size="-2">4</font></sub> by deiodination in the brain by Type II thyroxine 5'-deiodinase 5'D-II Silva and Larsen, 1982, Kaplan <em>et al.</em> 1983), it was of interest to examine the effects of PCBinduced reductions in plasma T <sub><font size="-2">4</font></sub> levels on 5'D-II activity. Decreases in brain T <sub><font size="-2">4</font></sub> levels result in a slower turnover of the enzyme, yielding a higher activity per unit protein in brain homogenates (Leonard <em>et al.</em> 1984). This regulatory mechanism is important in maintaining brain T <sub><font size="-2">3</font></sub> levels. In Chapter 4, the significant decreases in fetal, neonatal and weanling rat plasma T <sub><font size="-2">4</font></sub> levels following coplanar PCB exposure were accompanied by significant increases in 5'D-II activity in brain homogenates. It was concluded that the increases in 5'D-II activity were in compensation for low T <sub><font size="-2">4</font></sub> levels in the developing rat brain, which could be detrimental for normal brain development if insufficient T <sub><font size="-2">3</font></sub> was formed from T <sub><font size="-2">4</font></sub> .<p>Following maternal exposure to Aroclor 1254, reductions in fetal plasma T <sub><font size="-2">4</font></sub> were also accompanied by increases in brain 5'D-II activity. However, in contrast to the effects observed with coplanar PCBs in weanling rats, 5'D-II activity was decreased in weanling rats with normal plasma and brain T <sub><font size="-2">4</font></sub> levels, and equal to control values when plasma and brain T, levels were decreased. This can not be explained by the current knowledge of 5'D-II regulation.<p><em>Plasma and brain thyroid hormone levels</em><br/>In the current study, the effect of maternal PCB exposure on plasma thyroid hormone levels was transient, with only mild effects observed in weanling rats. Despite the significant lactational transfer of PCBs to the neonate, the effects on neonatal thyroid hormone homeostasis are less severe in neonates as in the fetus. Several mechanisms appear to be involved that may explain the difference in responses between fetuses and weanling rats: the induction of maternal hepatic T <sub><font size="-2">4</font></sub> glucuronidation late in gestation, the accumulation of hydroxylated PCB metabolites in the fetus, and reduced placental transfer of T <sub><font size="-2">4</font></sub> . Also the dilution of the tissue PCB levels during postnatal growth and the fecal and urinary excretion of PCBs may reduce the severity of plasma T <sub><font size="-2">4</font></sub> reductions in weanling rats following gestational PCB exposure. For example, the continuous postnatal dietary exposure of maternal rats to Aroclor 1254 results in low plasma T <sub><font size="-2">4</font></sub> levels throughout the weaning period (Collins and Capen, 1980b).<p>Despite severe decreases in fetal plasma and brain T <sub><font size="-2">4</font></sub> levels following maternal PCB exposure, only marginal decreases were observed in fetal brain T <sub><font size="-2">3</font></sub> levels. This indicates that the late gestational rat fetus can maintain brain T <sub><font size="-2">3</font></sub> levels by an increase in 5'D-II activity, and is at little risk for PCB-induced hypothyroidism, at least in the brain.<p>The observation that plasma TSH levels did not increase following PCB-induced decreases in plasma T <sub><font size="-2">4</font></sub> levels in the fetus and plasma T <sub><font size="-2">3</font></sub> and T <sub><font size="-2">4</font></sub> levels in the neonate suggests that the developing brain may have been euthyroid. However, the decreases in plasma T <sub><font size="-2">4</font></sub> levels themselves could be expected to result in an increase in TSH levels. Similar decreases in plasma T <sub><font size="-2">4</font></sub> levels in late gestational fetal Wistar rats following maternal treatment with methimazole have been shown to result in an 600% increase in plasma TSH levels (Morreale de Escobar <em>et al.</em> 1993), and it is likely that fetal TSH levels are modulated predominately by plasma T <sub><font size="-2">4</font></sub> rather than T <sub><font size="-2">3</font></sub> . In adult rats, significant increases in plasma TSH levels have been observed following dietary exposure to Aroclor 1254 that resulted in that decreases in plasma T <sub><font size="-2">4</font></sub> , but not T <sub><font size="-2">3</font></sub> at the same time point (Barter and Klaassen, 1994). A weak effect of PCBs on TSH secretion has been observed following a relatively high dietary exposure to Aroclor 1254, after which the rise in plasma TSH was suprisingly low in comparison to the rise in plasma TSH following dietary exposure to polychlorinated naphthalenes, which induced similar decreases in plasma T <sub><font size="-2">4</font></sub> levels as PCBs (Barter and Klaassen, 1994).<p>In conclusion, maternal. PCB exposure during gestation results in a large decrease of fetal brain T <sub><font size="-2">4</font></sub> levels, but only marginal decreases in T <sub><font size="-2">3</font></sub> levels in the late gestational rat fetus. It is possible that earlier in gestation, before 5'D-II activity can compensate for decreases in brain T <sub><font size="-2">4</font></sub> levels, significant reductions in brain T <sub><font size="-2">3</font></sub> levels are induced by maternal PCB treatment.<p><strong>Retinoids</strong><p>Analogous to thyroid hormones, retinoids play a crucial role in brain development, although their most important effects are during early and mid-gestation (Adams, 1993). To evaluate retinoid status, plasma and hepatic retinol and retinylesters were determined following maternal Aroclor 1254 exposure. The reductions in plasma retinol levels may be caused by the accumulation of 4-OH- pentaCB; in the plasma, analogous to the disruption of the binding of retinol binding protein to transthyretin by 4-OH-tetraCB following exposure to 3,3',4,4'-tetrachlorobiphenyl. Although the effects of maternal PCB exposure on retinoid homeostasis in the fetus, neonate and young adult offspring appear to be minor, the regulation of retinoid homeostasis exhibited long-term alterations in the PCB exposed group.<p><strong>Alterations in neurochemistry</strong><p>In Chapter 8 and 9 the effects of maternal PCB (Aroclor 1254) exposure were examined on the ontogeny of biogenic amines, a glial cell marker (glial fibrillary acidic protein, GFAP) and a neuronal cell marker (synaptophysin) in diverse brain regions.<p><em>Biogenic amines</em><br/>Of the biogenic amines examined, only the levels of 5-hydroxytryptamine (5-HT, serotonin) and its metabolite, 5-hydroxy-indoleacetic acid (5-HIAA) were altered by pre- and postnatal PCB exposure. It is notable that in adult animals the dopaminergic system is the most sensitive for exposure to commercial PCB mixtures, while we found no effects on the levels of dopamine or its major metabolite in the brains of PCB-exposed offspring (Seegal <em>et al.</em> 1985, 1986a, 1986b, 1991). Pre- and postnatal exposure to the lightly chlorinated PCB mixture Aroclor 1016 resulted in transient increases in striatal dopamine levels (Seegal, 1994). Therefore the effects of PCB exposure on regional brain monoamine metabolism during development do not resemble the effects in adult animals.<p>In general, the effects can be characterized by an increase in 5-HIAA concentrations and the 5-HIAA/5-HT ratio in the lateral olfactory tract and prefrontal cortex, and an increase in 5-HIAA levels in the striatum and hippocampus on postnatal day 90. Since the effects on the serotonergic system are almost absent on day 21 postpartum when exposure to PCBs via lactation ceased, there appears to be a delayed effect on the ontogeny of serotonin metabolism.<p><em>GFAP and Synaptophysin levels</em><br/>The most consistent effects of maternal PCB exposure on GFAP levels were observed in the lateral olfactory tract and the brainstem. Increases in GFAP concentrations were observed in both male and female offspring 21 and 90 days after birth. Increases were also observed in cerebellar GFAP levels on 21 and 90 days postpartum. In the brainstem of male and female offspring maternal PCB exposure prevented the increase in GFAP concentrations that was observed in control offspring, indicating a delay in the ontogeny of brainstem GFAP expression.<p>Synaptophysin levels in the brain of the offspring were affected in a more complex manner than GFAP following maternal PCB exposure. Following maternal PCB exposure, the most sensitive brain regions from both sexes for decreases in synaptophysin concentrations on postnatal day 21 were the lateral olfactory tract and the brainstem. However, in young adult animals brainstem synaptophysin levels were significantly decreased in males and significantly increased in females. Synaptophysin levels were also significantly decreased in the striatum and hypothalamus of female, but not male offspring following maternal PCB exposure.<p>The mechanisms involved in the alterations of GFAP and synaptophysin levels in the brains of the PCB-exposed offspring are not yet been elucidated. Increases in GFAP levels accompanied by decreases in synaptophysin levels in the lateral olfactory tract and prefrontal cortex are characteristic of reactive gliosis following neuronal loss (O'Callaghan and Miller, 1989). The decreases in GFAP and synaptophysin levels in the brainstem in weanling rats may be indicative of a developmental delay in brainstem maturation. The raphe nuclei in the brainstem contain serotonergic neurons which project to the lateral olfactory tract and the prefrontal cortex (Kosofsky and Molliver, 1987). It is therfore conceivable that the alterations in serotonergic matabolism as well as GFAP and synaptophysin levels in the lateral olfactory tract and prefrontal cortex result from a developmental delay in the serotonergic innervation of these brain regions.<p><strong>Relevance of the conducted research for human development and future toxicological research</strong><p><em>Thyroid hormones</em><br/>In a recently published study of 105 mother-infant pairs, elevated maternal body burdens of polychlorinated dibenzo-p-dioxins, dibenzofurans and biphenyls (levels in milk fat) were shown to be associated with alterations of human thyroid hormone status (Koopman-Esseboom <em>et al.</em> 1994). <em></em> The effects are characterized as negative correlation of PCDD, PCDF and PCB congeners with maternal plasma TT <sub><font size="-2">3</font></sub> before delivery and maternal plasma TT <sub><font size="-2">4</font></sub> and TT <sub><font size="-2">3</font></sub> after delivery, and a positive correlation with plasma TSH levels in the infants in the second week and third month after birth. In infants with a higher exposure, plasma TT <sub><font size="-2">4</font></sub> levels were significantly lower (10%) and TSH levels were significantly higher (37%). Maternal body burden of three PCB congeners (CB 118, CB 138 and CB 153) was positively correlated with umbilical plasma TSH levels. In a similar study with 38 mother-infant pairs an increase in infant plasma TSH levels and plasma TT <sub><font size="-2">4</font></sub> levels was observed in infants with a higher exposure to the total toxic equivalents of PCDDs and PCDFs (Pluim <em>et al.,</em> 1992).<p>The relative effects of PCBs, PCDFs and PCBs on plasma thyroid hormone levels observed by Koopman-Esseboom <em>et al.</em> (1994) <em></em> in mother-infant pairs are generally the same as observed in adult mice, rats and monkeys at much higher doses. In contrast to the decreases observed in late gestational fetal rat plasma TT <sub><font size="-2">4</font></sub> and FT <sub><font size="-2">4</font></sub> following maternal exposure to Aroclor 1254, no effect was observed of maternal body burden on umbilical cord TT <sub><font size="-2">4</font></sub> and FT <sub><font size="-2">4</font></sub> levels.<p>It is unlikely that the alterations in thyroid hormone homeostasis associated with maternal PCB and PCDD levels observed in human newborns and infants will result in developmental alterations of the nervous system. Compensatory mechanisms, such as the induction of Type II 5'- thyroxine deiodinase in the brain, should offset decreases in plasma and brain T <sub><font size="-2">4</font></sub> levels. In the late gestational rat, near normal brain T <sub><font size="-2">3</font></sub> levels were maintained despite severe decreases in plasma and brain T <sub><font size="-2">4</font></sub> levels following maternal PCB exposure. However, the potential exists for significant reductions in fetal thyroid hormone levels earlier in gestation before compensatory mechanisms have fully developed or in specific brain regions not examined in this study.<p>There are several important aspects in which the thyroid hormone transport differs between humans and rats with possible consequences for the effects of PCBs. The main thyroid hormone transport protein in humans is TBG, while in rats TTR is the major protein (Robbins, 1991). Although under certain circumstances TBG may be present in rats, it has a low affinity for T <sub><font size="-2">4</font></sub> (Rouaze-Romet <em>et al.</em> 1992). <em></em> Hydroxylated PCB metabolites bind only very weakly to TBG, so it is possible that the impact of hydroxylated PCB metabolites on plasma T <sub><font size="-2">4</font></sub> levels in humans may be minor. However, the fetal mouse has both TTR and TBG as transport proteins, and mouse TBG has similar binding properties to human TBG (Vrancks <em>et al.</em> 1990), so <em></em> the mouse may be a better model than the rat for studying the effects of PCBs on thyroid hormone transport. Recent research has shown that following maternal TCB exposure 4-OH-tetraCB accumulates in the fetal mouse, binds to TTR, resulting in the decrease of fetal plasma T <sub><font size="-2">4</font></sub> levels (unpublished results, D.C. Morse and P.O. Darnerud). Therefore, it is possible that transplacental. transport of hydroxylated PCBs in humans results in the decrease plasma and brain thyroid hormone levels before the rise of fetal hypothalamic-pituitary function in mid-gestation.<p>While it is generally accepted that thyroid hormone deficiency in neonates and in late gestation has a negative effect on brain development in the rat as well as humans, the effects of thyroid hormone deficiency earlier in gestation are not clearly understood (Morreale de Escobar <em>et al.</em> 1993, review, Porterfield and Hendrich, 1993, review). Thyroid hormone and their receptors have been found in human fetuses by 10 weeks of gestation (Fisher, 1985), although the functional significance of these observations is currently unclear. The finding of Pharoah <em>et al.</em> (1972) that neurological damage of endemic cretinism could be prevented if iodized oil was given to the mother before the second trimester of pregnancy supports a role of thyroid hormones in brain development in this period.<p>Therefore several questions remain to be answered: does maternal PCB exposure result in significant decreases in brain thyroid hormones in early and mid-gestation in rodents and humans, and whether such decreases are relevant for brain development.<p><em>Effects on neurochemical development</em><br/>Gestational and lactational exposure to a commercial PCB mixture, Aroclor 1254 resulted in long-term effects on the neurochemical development of the progeny of rats (Chapter 7 and 8). The study does not support the hypothesis that PCB-induced pre- or postnatal hypothyroidism was the cause of the neurochemical alterations (Chapter 5). The study does give an indication which neurotransmitter systems, which cell types and which brain areas may be affected by in utero and lactational exposure to a higher chlorinated PCB mixture, providing a solid base for further research.<p>One of the questions which has interested researchers in PCB-induced toxicity for nearly 20 years is which PCB congeners are responsible for the toxicity of these compounds. This question has only been adequately answered for the immunotoxicity and some developmental endpoints (teratogenesis and fetotoxicity) in which the interaction of the PCB congeners with the Ah-receptor plays an important role.<p>To date, reports have been published on the behavioral neurotoxicity of only two individual PCB congeners, 3,3',4,4'-tetrachlorobiphenyl and 3,3',4,4',5-pentachlorobiphenyl, both of which are coplanar PCBs with a high affinity for the Alireceptor. 3,3',4,4'-tetrachlorbiphenyl was shown to be a developmental neurotoxin in mice following high dose gestational exposure, reducing striatal dopamine and dopamine receptor levels in mice, delaying advoidance behavior and inducing neuropathological alterations in the cranial roots (Tilson <em>et al.</em> 1979, Chou <em>et al.</em> 1979, Agrawal <em>et al.</em> 1981). Postnatal exposure of mice to 3,3',4,4'-tetrachlorobiphenyl has also been shown to affect hippocampal muscarinic receptor levels and alter spontaneous activity (Eriksson, 1988, Eriksson <em>et al.</em> 1991). Due to the rapid metabolism of 3,3',4,4'-tetrachlorobiphenyl and accumulation of hydroxylated metabolites in the fetus no conclusions can be drawn as to the role of the parent compound or its metabolites in the developmental neurotoxicity of this PCB congener (Morse <em>et al.</em> 1995).<p>On the other hand, exposure of pregnant rats to poorly metabolizable 3,3',4,4',5- pentachlorobiphenyl, delayed the onset of spontaneous activity and neuromuscular maturation in the offspring, which was related to delay in body weight gain. However, the development of reflexes and visual discrimination was not affected by maternal exposure to 3,3',4,4',5-pentachlorobiphenyl (Bernhoft et al. 1994). Taken together, these data may indicate that highly toxic coplanar PCBs may not be direct developmental neurotoxins in rodents. If this is the case, it is questionable if the use of individual PCB congeners in studies on the effects on neurochemical and behavioral development will resolve novel structure-activity relationships within the same time-frame as the structureactivity relationships for immunotoxicity or CYP1A1 induction in adult animals. First, the reproductive studies involved are much more lengthy and costly than acute studies with adult animals. Secondly, there is no general agreement on experimental protocols (timing and length of PCB administration, neurochemical and behavioral endpoints) between researchers working in this field, frustrating the comparison of data. Thirdly, it is very likely that complex interactions of Ah-receptor binding, PCB metabolism, fetal accumuation of metabolites and hormonal alterations affect brain development <em>in vivo,</em> so that the structure-activity relationships for individual congeners will not predict the effects of complex mixtures.<p>Therefore it may be more useful to characterize the effects of environmentally relevant mixtures in terms of dose-response studies, neurochemical and behavioral endpoints and species sensitivity. Environmentally relevant mixtures can be obtained by extracting contaminated foodstuffs or constructing mixtures using synthetic standards. Although mixtures will vary somewhat in their composition, the results of such studies may be more relevant for regulatory purposes than data based on studies with individual congeners. Cell culture techniques using glial cell or dissociated neural cell cultures may be useful in investigating structure-activity relationships of the direct effects of individual PCB congeners on brain development. Parameters that have been first demonstrated to be affected <em>in vivo</em> should be analysed <em>in vitro.</em><p><strong>Main conclusions:</strong><p>1) PCB congeners (3,3',4,4'-tetrachlorobiphenyl, 2,3,3',4,4'-pentachlorobiphenyl and 2,3',4',4,5-pentachlorobiphenyl) can be metabolized to hydroxylated metabolites which accumulate in the fetal plasma and brain and cause severe reductions in late gestational fetal plasma and brain thyroxine levels in rats.<p>2) The reductions in brain T <sub><font size="-2">4</font></sub> levels in late gestational fetal rats are effectively compensated by increases in Type II thyroxine 5'-deiodinase activity, so that only marginal decreases in brain T <sub><font size="-2">3</font></sub> levels are observed following maternal exposure to a commercial PCB mixture. This is an indication that PCB-induced decreases in plasma T <sub><font size="-2">4</font></sub> levels are not responsible for alterations in the development of the central nervous system.<p>3) maternal exposure to the commercial PCB mixture (Aroclor 1254) specifically alters the development of serotonin metabolism in the brain of the offspring in rats. Since the dopamine metabolism exhibits a greater sensitivity and persistency for the administration of Aroclor 1254 in adult rodents and macaques than serotonin metabolism, the mechanism of PCB-induced developmental neurotoxicity is distinct from the mechanism of alterations in biogenic amine metabolism in adult animals.<p>4) The development of both neuronal and glial cells is affected in the brains of offspring from pregnant rats treated with Aroclor 1254. The alteration in astrocyte development in the brainstem of PCB-exposed offspring is not a response to neuronal death, for levels of glial fibrillary acidic protein (GFAP) are decreased, while increased neuronal death is generally accompanied by increases in GFAP expression. It is therefore likely that PCBs affect brain development by altering cell differentiation and proliferation.<p>5) Since the brainstem is one of the first structures to develop in the brain, the observed alterations in brainstem development following pre- and postnatal PCB exposure probably have a negative effect on the subsequent development of other brain structures.
Gastrointestinal motility, prokinetic benzamides and serotonin : a study on the guinea-pig colon
Briejer, M.R. - \ 1995
Agricultural University. Promotor(en): L.M.A. Akkermans; J.A.J. Schuurkes. - S.l. : Briejer - ISBN 9789054853886 - 219
neurofysiologie - zenuwstelsel - neurologie - spijsvertering - darmen - zintuigorganen - neuropeptiden - prikkelgeleiding - neurophysiology - nervous system - neurology - digestion - intestines - sense organs - neuropeptides - neural transmission
<p>The prokinetic substituted benzamides stimulate gastrointestinal motility in animal models and in man. Studies done on the isolated guinea-pig ileum have led to the hypothesis that the benzamides act through facilitation of cholinergic transmission due to stimulation of serotonin4 (5-HT <sub>4</sub> ) receptors on the intramural enteric neurons. However, many questions as to their mode of action remain. The substituted benzamides are known to interfere with a variety of 5-HT receptor types. In this thesis the pharmacological action and interaction of substituted benzamides and 5-HT on the guinea-pig proximal colon were studied. This preparation was found to be endowed with 5-HT <sub>3</sub> and 5-HT <sub>4</sub> receptors on the nerves, mediating contraction via the release of acetylcholine and a non-cholinergic neurotransmitter (probably substance P, which stimulates smooth muscle NK <sub>1</sub> receptors), and 5-HT <sub>2A</sub> receptors on the smooth muscle. The benzamides cisapride and R 76 186 were found to be agonists at this 5-HT <sub>4</sub> receptor, but cisapride was also found to have an additional direct effect on the smooth muscle. Furthermore, an unknown neuronal 5-HT <sub>2</sub> - like receptor was found to mediate relaxation involving nitric oxide (NO) and adenosine triphosphate (ATP). Cisapride and some other benzamides, were found to selectively enhance the ATP-mediated relaxation. It is thus proposed that the benzamides do not only facilitate the excitatory cholinergic transmission, but also the inhibitory purinergic transmission. As in peristalsis coordinated contraction and relaxation are important, the benzamides might thus promote peristalsis by enhancing both relaxation and contraction on demand. An in vivo model for faecal pellet propulsion in the guinea-pig distal colon was developed to investigate this hypothesis in future studies.
Toward a new theory of feed intake regulation in ruminants
Ketelaars, J.J.M.H. ; Tolkamp, B.J. - \ 1991
Agricultural University. Promotor(en): P.W.M. van Adrichem; Martin Verstegen; D. Zwart. - S.l. : Ketelaars [etc.] - 253
herkauwers - diergeneeskunde - schapen - geiten - diervoeding - diervoedering - neurofysiologie - zenuwstelsel - neurologie - voedingsfysiologie - spijsvertering - zintuigorganen - voedersystemen - ruminants - veterinary science - sheep - goats - animal nutrition - animal feeding - neurophysiology - nervous system - neurology - nutrition physiology - digestion - sense organs - feeding systems
<p>Part I of this thesis contains a critical appraisal of the commonly accepted theory with regard to feed intake regulation in ruminants and the presentation of a new theory. This new theory assumes that feed consumption creates both benefits to the animal (in a non-reproducing animal the intake of net energy for maintenance and gain) and costs (the total oxygen consumption of the animal). It is hypothesized that, for the animal, the intake level where the ratio between benefits and costs becomes maximal, is optimal. Predictions of this optimum level for a wide range of feeds are shown to agree closely with observed voluntary feed intake in non-reproducing ruminants. Physiological processes related to the concept of an optimum feed intake are discussed. Maintenance of intracellular pH and associated energy costs may appear to be key factors in view of increases of the metabolic acid load consequent upon changes in intake. It is concluded that the concepts developed here may reflect a more universal principle governing the intensity of different forms of behaviour in ruminants as well as in monogastric animals.<p>Part II reports results of a long-term feeding experiment with small West African Dwarf goats and a larger sheep breed given pelleted roughage. Between species, intake of digestible organic matter and fasting heat production appeared to vary as a function of metabolic weight.<p>The effect of nutrient supplements on intake of low to medium quality roughages was investigated in supplementation and infusion experiments with the same species. Nutritive substances tested were by-pass protein, rumen microbial material, grass juice, intestinally digestible carbohydrates, and volatile fatty acid mixtures. Nutrient supplements usually depressed roughage intake but increased estimated intake of metabolizable energy (ME). From the theory presented in Part I it is inferred that such changes of intake are the result of changes of the efficiency of ME utilization.
Neural regulation and dynamics of prolactin secretion in the rat = Neurale regulatie en dynamiek van de prolactine secretie in de rat
Wiersma, J. - \ 1990
Agricultural University. Promotor(en): L.M. Schoonhoven; L.M.A. Akkermans. - S.l. : Wiersma - 69
ratten - prolactine - hersenen - gewervelde dieren - neurofysiologie - zenuwstelsel - neurologie - hormonen - metabolisme - rats - prolactin - brain - vertebrates - neurophysiology - nervous system - neurology - hormones - metabolism
<p><TT>The subject of this thesis was an investigation of the neural regulation and dynamics of prolactin (Prl) secretion. Experimentation was performed with freely behaving undisturbed male and female rats, chronically fitted with an atrial blood sampling catheter. In some studies rats were also equipped with a chronic intracerebroventricular cannula, or with chronic metal electrodes bilaterally implanted in the medial preoptic area (MPOA) or the median eminence (ME). Stress was always carefully avoided. The animals, therefore, had a post-operative recovery period of at least one week, during which time they were handled daily and fully accustomed to the experimental situation. During experimentation blood samples were collected between 06.00 and 22.00 h. Blood volume reduction was compensated for with blood transfusions.</TT><p><TT>The study starts with a thorough evaluation of circulating (Prl) levels in cycling and pseudopregnant (PSP) rats (chapter 1). Onehour interval studies show that diestrous (Prl) levels were low, about 15 ng/ml, and showed minor fluctuations. During the afternoon and early night of proestrus a single (Prl) surge was observed with a peak level of 1100 ng/ml at 17.00 h. On the afternoon of estrus there was also a single surge which was of a smaller magnitude and duration, with a peak level of 400 ng/ml at 16.00 h. In PSP rats two daily (Prl) surges were released during successively 11 days, one nocturnal and one diurnal. During the course of PSP these surges gradually declined in magnitude. Short-time sampling interval studies show that (Prl) secretion during PSP occurred occasionally in substantial bursts from baseline levels, whereas during the afternoon of proestrus plasma (Prl) was elevated constantly due to a more or less continuous release of (Prl) Such a difference in actual secretion patterns indicates a separate neural regulation.</TT><p><TT>These data were obtained in rats chronically fitted with a blood sampling/transfusion catheter. Since (Prl) secretion is extremely susceptible to stress, it was necessary to investigate whether the applied blood sampling/transfusion procedure was free of stress. It appeared that frequent blood sampling for several hours at rates of up to 1 sample/min did not affect normal (Prl) secretion when blood volume reduction was compensated for with blood transfusion of fresh donor blood (chapter 2). However, compensation with preserved blood affected prolactin secretion significantly (chapter 3). In all later studies, therefore, blood transfusions were performed with freshly collected donor blood. The application of high frequency blood sampling permits the assessment of the dynamics of (Prl) secretion satisfactorily. The short-time interval studies presented in chapter 1, 2 and 3 show that during a surge plasma (Prl) always increased in an unpredictable manner, discontinuously, by means of several bursts, with maximum increments of about 600 ng/ml/min. The shortest half-time values, as calculated from the disappearance of (Prl) from the circulation, were about 2.2 min. The individual release patterns indicate that (Prl) release must be the consequence of a very dynamic neural regulatory process.</TT><p><TT>In chapter 4 the effects of red light and/or surgery upon (Prl) secretion were studied in cycling and PSP rats. Nocturnal (07.00- 11.00 h), prediurnal (14.00-17.00 h) and diurnal (19.00-22.00 h) Prl secretion was differently affected by these "treatments", and the effect was dependent upon the physiological state. The data together demonstrate the existence of different regulatory mechanisms for each of the surges of (Prl) secretion: the proestrous and estrous surge in cycling rats, and the nocturnal and diurnal surge in PSP rats. Moreover, in PSP day 0 rats, on the first day of pseudopregnancy, the occurrence of a prediurnal surge, preceeding the diurnal surge, was evident, which in fact was a reflection of the estrous afternoon surge in cycling rats.</TT><p><TT>In the last three chapters the involvement of the brain in (Prl) regulation was explored by studying the effects of hormonal and electrical stimulation upon (Prl) secretion. Since (Prl) has no specific target organ, an autofeedback control mechanism was hypothesized. Therefore, the effect of intracerebroventricular infusion of (Prl) on endogenous Prl secretion was investigated. However, as far as the proestrous surge of (Prl) is concerned, there is no evidence for the existence of an autoregulatory mechanism, neither in the expression, nor in the termination of the surge (chapter 5).</TT><p><TT>In chapter 6 the role of two brain areas in the control of (Prl) was investigated: the MPOA and the ME. The MPOA shows sexual dimorphism and is concerned functionally with several parameters of homeostasis, (sexual) behavior and endocrine function. The ME contains the terminals of the tuberoinfundibular dopaminergic (TIDA) neurons. Electrical stimulation experiments show that the</TT>MPOA<TT>is involved in the control of (Prl) secretion and that this control is different in males and females: electrical stimulation produced an increase in (Prl) secretion in the male, but reduced (Prl) secretion in the proestrous female. ME stimulation data do not provide evidence that this sexually differentiated function of the</TT>MPOA<TT>could be contributed to a sexual dimorphism in prolactin- inhibiting factor or prolactin-releasing factor activity.</TT><p><TT>The data of chapter 7 show that the</TT>MPOA<TT>is involved in the control of all presently known surges of (Prl) secretion in cycling, pregnant and lactating rats: electrical stimulation consistently suppressed (Prl) secretion at the times of expected surges. So the</TT>MPOA<TT>may be considered as an "anti-surge key-control" centre for (Prl) secretion in female rats. Whether the</TT>MPOA<TT>exerts its control via one final common neural pathway represented by the tuberoinfundibular dopaminergic system, remains to be determined.</TT><p><TT>In summary: (Prl) is a multi-target and multi-functional hormone. Based on the differences in actual secretion patterns of (Prl) and the differential effects of stress on (Prl) secretion it is concluded that all yet known surges of (Prl) secretion in cycling, (pseudo) pregnant and lactating rats are controlled by different neural regulatory mechanisms. In proestrous rats there is no evidence for an autoregulatory mechanism. Release of (Prl) is the consequence of a very dynamic neural regulatory process. The release of (Prl) is finally controlled by one common neural centre, the</TT>MPOA,<TT>which control is sexually differentiated: stimulatory in the male and inhibitory in the female.</TT>
De hersenen in de darm.
Akkermans, L.M.A. - \ 1989
Wageningen : Landbouwuniversiteit Wageningen - 19
neurofysiologie - zenuwstelsel - neurologie - zintuigorganen - diergeneeskunde - colleges (hoorcolleges) - neurophysiology - nervous system - neurology - sense organs - veterinary science - lectures
Immunocytochemical studies on peptidergic neurons in the Colorado potato beetle and some other insect species
Veenstra, J.A. - \ 1984
Landbouwhogeschool Wageningen. Promotor(en): L.M. Schoonhoven, co-promotor(en): H. Schooneveld. - Wageningen : Veenstra - 97
chrysomelidae - elisa - entomologie - immunocytochemie - insecten - zenuwstelsel - neurologie - neurofysiologie - leptinotarsa decemlineata - entomology - immunocytochemistry - insects - nervous system - neurology - neurophysiology
This thesis describes the distribution, numbers, and morphology of peptidergic neurons and neurosecretory cells in the Colorado potato beetle, as detected with immunocytochemistry with antisera to various regulatory peptides from vertebrates, as well as to the molluscan cardioexcitatory peptide FMRFamide, and to the insect neuropeptide proctolin.<p/>In chapter one, a description is given of peptidergic neurons in the Colorado potato beetle which are immunoreactive with antisera to FMRFamide and bovine pancreatic polypeptide. Results from cross-adsorption experiments suggest that the antisera to FMRFamide and bovine pancreatic polypeptide cross-react and reveal the same substance(s) in the Colorado potato beetle. Some of the immunoreactive neurons branch extensively in the neuropile, suggesting that the immunoreactive substance is used as a transmitter or modulator. The corpus cardiacum contains numerous immunoreactive axon terminals from neurosecretory cells located in the suboesophageal ganglion. These cells probably use the peptide as a hormone.<p/>In chapter two, ten different antisera were used to differentiate between neurons in the neuroendocrine system of the Colorado potato beetle. Four antisera to vasopressin, three to oxytocin and one to vasotocin, neurophysin-1 and neurophysin-2 each were used. All antisera revealed immunoreactive cells, except for the two neurophysin antisera. The antisera to vasopressin all gave different results. Whereas one antiserurn revealed only a single neuron pair, the other three antisera revealed additional groups of immunoreactive cells. The three oxytocin antisera also gave different results. It was further found that the fixation procedure also greatly influenced the immunocytochemical results. It was concluded that several vasopressin and oxytocin immunoreactive peptides are present in the Colorado potato beetle, all with a different degree of resemblance to vasopressin and oxytocin.<p/>In chapter three, it was investigated whether immunocytochemical techniques could be used for the demonstration of homologous neurosecretory cells in the suboesophageal ganglion of the Colorado potato beetle and of the migratory locust. The antisera were anti-FMRFamide, anti-bovine pancreatic polypeptide, two antisera to vasopressin, which all had been used before in the work described in chapters 1 and 2, and an antiserurn to α-MSH. It is shown that neurosecretory cells are present in the suboesophageal ganglion of both species and that they occur in similar locations and have the same immunoreactivity. This suggests that the two species contain homologous neurosecretory cells. It is speculated that they also have similar functions.<p/>In chapter four, the concept of homologous neurons is further developed and ten different insect species were examined for the presence of neurons immunoreactive with a specific antiserurn to gastrin-releasing peptide. Immunoreactive neurons were revealed in seven species, belonging to seven orders. The concentration of antiserurn required to demonstrate immunoreactive cells was much higher in insects than in chicken proventriculus, known to contain gastrin-releasing peptide. Some immunoreactive neurons were found in the same numbers and approximately the same locations within the nervous system of different insect species. This suggests that the substances in these neurons have been relatively stable during evolution and that these neurons are homologous.<p/>In chapter five, a large number of antisera to various regulatory vertebrate peptides was tested on the Colorado potato beetle, to reveal peptidergic neurons and neurosecretory cells and to differentiate between these cells. Immunoreactive cells were revealed by antisera to ACTH, gastrin, cholecystokinin, α-endorphin, β-endorphin, γl-MSH, insulin, human calcitonin, motilin, growth hormone, somatostatin, corticotropin-releasing factor, ovine prolactin and rat prolactin. Some of these immunoreactive cells seem to function as neurons, whereas others function as neurosecretory cells. It is postulated that if the part of the substance recognized by the antiserurn is of physiological importance to the insect, that part is retained in several species. The antiserurn should then reveal homologous neurons in different insect species. Given the fact that insect species differ widely in their immunocytochemical responses, the criterion of staining of probably homologous neurons offers some help in separating relevant from irrelevant immunoreactions. The immunocytochemical data are evaluated according to this concept.<p/>In chapter six, neurons in the central and peripheral nervous system of the Colorado potato beetle were described which contain substances immunoreactive with antiserurn to the insect neuropeptide proctolin. This peptide was originally isolated from cockroaches, in which it stimulates contractions of the gut musculature. Immunoreactive axon terminals were also found on the muscles of the fore- and hindgut, and abdominal segments, as well as in the vas deferens of the testis. Furthermore, the nervous system was extracted to investigate whether proctolin-like bioactivity could be demonstrated. A proctolin-like bioactive peptide was demonstrated, that behaved chromatographically like proctolin. This suggests that at least some of the immunocytochemically demonstrated proctolin is identical with or at least similar to proctolin.
Verslag PAO - cursus "Neuroendocrinologie" gegeven op het Nederlands instituut voor Hersenonderzoek, 8 - 12 augustus 1977
Wiel, D.F.M. van de - \ 1977
Zeist : I.V.O. (Rapport / Instituut voor veeteeltkundig onderzoek "Schoonoord" no. C-325) - 4
endocrinologie - hormonen - metabolisme - zenuwstelsel - neurofysiologie - zintuigorganen - endocrinology - hormones - metabolism - nervous system - neurophysiology - sense organs
Neuro - endocriene integratie
Wilde, J. de - \ 1970
Wageningen : [s.n.] (Mededeling / Laboratorium voor entomologie no. 181) - 7
endocrinologie - entomologie - hormonen - insecten - zenuwstelsel - neurologie - neurofysiologie - zintuigorganen - endocrinology - entomology - hormones - insects - nervous system - neurology - neurophysiology - sense organs
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