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): K. de Graaf, co-promotor(en): P.A.M. Smeets; M. 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.

    The art of being small : brain-body size scaling in minute parasitic wasps
    Woude, Emma van der - \ 2017
    Wageningen University. Promotor(en): M. Dicke, co-promotor(en): H.M. Smid. - Wageningen : Wageningen University - ISBN 9789463436564 - 231
    brain - insects - neurons - scaling - cognitive development - vespidae - parasitoid wasps - cum laude - hersenen - insecten - neuronen - schaalverandering - cognitieve ontwikkeling - vespidae - sluipwespen

    Haller’s rule states that small animals have relatively larger brains than large animals. This brain-body size relationship may enable small animals to maintain similar levels of brain performance as large animals. However, it also causes small animals to spend an exceptionally large proportion of energy on the development and maintenance of energetically expensive brain tissue. The work that is presented in this thesis reveals how the smallest animals face the challenge to maintain ecologically required levels of cognitive performance, while being limited by small numbers of neurons and a restricted energy balance. Developing into a small adult has cognitive costs for the parasitic wasp Nasonia vitripennis, and relative brain size is strongly constrained in this species. The extremely small parasitic wasp Trichogramma evanescens forms an exception to Haller’s rule by showing isometric brain-body size scaling. Miniaturized insect species may apply this strategy to avoid the excessive energetic costs of relatively large brains, thereby achieving smaller brain and body sizes than would be possible in the situation that is described by Haller’s rule. This brain-scaling strategy does not result in affected memory performance of small T. evanescens compared to larger individuals, and appears to be facilitated by a large flexibility in the size of neural components, rather than in their number or structural complexity. Maintaining neural complexity may the underlying mechanism that maintains the cognitive abilities of the smallest brains, possibly at the cost of reduced longevity as a consequence of the small size of neuronal cell bodies. This strategy could form the art of being small.

    The interplay between mouth and mind : explaining variation in taste-related brain activation
    Rijn, Inge van - \ 2016
    Wageningen University. Promotor(en): Kees de Graaf, co-promotor(en): Paul Smeets. - Wageningen : Wageningen University - ISBN 9789462579040 - 156
    taste research - magnetic resonance imaging - brain - patterns - satiety - hunger - calories - smaakonderzoek - kernspintomografie - hersenen - patronen - verzadigdheid - honger - calorieën

    Food does not always ‘taste’ the same. During hunger, for example, food may be tastier compared to during satiety. Many other internal and external factors affect the way we experience our food and make it a dynamic process. Our brain is responsible for weighing and integrating these factors and forms the final consumption experience. Mapping the impact of all factors that influence the consumption experience is of fundamental importance for understanding why we eat the way we eat. Important drivers for food consumption are its rewarding capacity, healthiness and caloric content. Furthermore, in the current supermarket environment, advertisements and food claims are omnipresent, and may exert influence on our consumption experience by triggering all kinds of cognitive processes. Therefore, in this thesis we aimed to assess the effect of food content (caloric content and sugar type), character (personality trait reward sensitivity and attitude health-interest) and cognitive effects (labeling/claim effects and selective attention to food properties) on brain activation during tasting. Such taste-related brain responses were obtained with the use of functional Magnetic Resonance Imaging while administering small sips of liquid to young, normal weight female participants in a MRI scanner.

    To begin with, we focussed on the effect of caloric content on taste responses (Chapter 2). An important function of eating is ingesting energy, and the ability to sense energy in the oral cavity would therefore be biologically relevant. However, in this thesis we showed that oral exposure to caloric (maltodextrin and maltodextrin + sucralose) and non-caloric (sucralose) stimuli does not elicit discriminable responses in the brain when averaged over hunger and satiety. Nevertheless, energy content did interact with hunger state in several brain regions involved in inhibition (approach-avoidance behaviors) and gustation: the middle cingulate cortex, ventrolateral prefrontal cortex, anterior insula and thalamus. Thus, brain activation in response to oral calories, irrespective of sweetness, seems to be dependent on hunger state.

    In addition to the detection of oral calories in general, we examined whether different sugar types, glucose and fructose, can be sensed in the oral cavity (Chapter 3). Tasting glucose compared to fructose evoked greater food reward (anterior cingulate cortex, ACC) activation during hunger and greater food motivation (precentral gyrus) activation during hunger and satiety. Responses to oral fructose relative to glucose were greater only during satiety in an area associated with inhibitory control (superior frontal gyrus). It appears that oral glucose and fructose evoke differential brain responses, independent of sweetness.

    Secondly, we investigated in how far reward sensitivity, a personality trait, affected brain responses to calories in the oral cavity (Chapter 4). This because a food’s reward value is highly dependent on its caloric content. Sensitivity to rewards was measured with the Behavioral Activation System Drive scale and was correlated with oral calorie activation from a simple maltodextrin solution and a sucrose sweetened soft drink. Oral calorie activation was obtained by subtracting activation by a non-caloric solution (sucralose solution/non-caloric soft drink) from that by a caloric solution (maltodextrin + sucralose/sucrose sweetened soft drink). We found that neural responses to oral calories from a maltodextrin solution are modulated by reward sensitivity in reward-related areas such as the caudate, amygdala, and ACC. For soft drinks, we found no correlations with reward sensitivity in any reward related area. This discrepancy may be due to the direct detection of maltodextrin, but not sucrose in the oral cavity. However, the absence of this effect in a familiar soft drink warrants further research into its relevance for real life ingestive behavior.

    In the last part of this thesis we explored how cognitions modulate the consumption experience. Perceived, rather than actual caloric content, inflicted by calorie food labels, induces cognitive processes that may influence the consumption experience on their own. We tested this in an experiment and found that receipt of a beverage perceived as low- compared to high-caloric induced more activation in the dorsal striatum, a region involved in coding food reward (Chapter 5). As low-calorie labels may appeal especially to the health-minded consumers, we correlated brain responses to the receipt of a beverage perceived as low- compared to high-caloric with health interest (measured with the General health interest subscale of the Health and Taste Attitude Scales). Indeed, health interest scores correlated positively with activation in the dorsal striatum.

    Rather than focussing participants’ attention on differences within one food aspect, in Chapter 6 we focussed on selective attention to different food aspects, i.e. pleasantness versus taste intensity versus calories. In the supermarket, food labels and claims often do the same. In the first place, paying attention to hedonics, caloric content or taste intensity predominantly resulted in common brain activation in regions involved in the neural processing of food stimuli, e.g. the insula and thalamus. This likely resulted from ‘bottom-up’ sensory effects, which are more prominent than ‘top-down’ attentional effects. However, small differences were also observed; taste activation was higher during selective attention to intensity compared to calories in the right middle orbitofrontal cortex and during selective attention to pleasantness compared to intensity in the right putamen, right ACC and bilateral middle insula. Overall, these results indicate that statements regarding food properties can alter the consumption experience through attention-driven effects on the activation of gustatory and reward regions.

    Finally, the general discussion (Chapter 7) describes main finding and conclusions of this thesis. In sum, we showed that food energy content, sugar type, trait reward sensitivity, health interest, food labels and selective attention all modulate taste-related brain activation. In conclusion, these findings indicate that the formation of the final consumption experience is a very multifaceted process that dependents on numerous factors integrated by the brain, of which we are just beginning to grasp its complexity.

    Slaap je beter van warme melk?
    Teerds, Katja - \ 2015
    hersenen - Verzadigingsmechanisme - neurologie - slaap
    Vitamin D-tour : cognition and depression: the role of vitamin D and its interplay with glucose homeostasis
    Brouwer-Brolsma, E.M. - \ 2014
    Wageningen University. Promotor(en): Lisette de Groot; Edith Feskens, co-promotor(en): Teun Schuurman; Wilma Steegenga. - Wageningen : Wageningen University - ISBN 9789462571082 - 215
    vitamine d - depressie - glucose - homeostase - gezondheid - hersenen - vitaminetekorten - vitamin d - depression - glucose - homeostasis - health - brain - vitamin deficiencies

    According to recent estimations approximately 35.6 million people have dementia worldwide. Globally, 350 million people experience one or more depressive episodes during their life. As the therapeutic options for dementia and depression are limited, these conditions form a major challenge for public health and society. More and more researchers have initiated research on potential preventive factors for dementia and depression, including the potential effects of nutritional factors. The aim of this PhD-thesis was to study the role of vitamin D and its potential interplay with glucose homeostasis, in the development of cognitive decline and depression, using epidemiological data as well experimental animal data.

    Chapter 2 recapitulates a debate between vitamin D experts that was organized to make a step towards the harmonization on the formulation of optimal vitamin D intake levels and serum 25(OH)D concentrations across Europe. It was concluded that based on the current evidence-base 25(OH)D concentrations ≥50 nmol/L are sufficient with respect to optimal bone health. For health outcomes beyond bone health evidence was considered insufficient to formulate optimal levels. In order to achieve and maintain a 25(OH)D concentration ≥50 nmol/L, older adults aged ≥65 years were recommended to adhere to a vitamin D intake of 20 μg/day.

    Chapter 3 shows that there is a high prevalence of 25(OH)D inadequacy in a population of Dutch older adults that participated in the B-PROOF study (n=2857), namely 45% had 25(OH)D concentrations <50 nmol/L. Mean vitamin D intake was 4.9±2.9 µg/day and only 20% of the participants reported to use vitamin D containing supplements. Exploration of the determinants of 25(OH)D status showed significant associations between vitamin D ‘raising’ SNPs (n=2530), higher sun exposure (n=1012), vitamin D intake (n=596) and higher 25(OH)D concentrations. Including all the potential relevant predictors in one model explained 35% of the variance in 25(OH)D status (R2=0.35).

    In chapter 4 the associations between 25(OH)D status and global cognitive performance (n=116), depressive symptoms (n=118), and surrogate markers of glucose intolerance (n=593) were evaluated using data of European adults aged 70-75 years. None of the associations reached significance.

    Studying the potential role of vitamin D in domain-specific cognitive performance and depression in 127 Dutch pre-frail and frail older adults aged ≥65 years (chapter 5), showed an association between 25(OH)D concentration and executive functioning, and a tendency towards an association with information processing speed. Stratification for ‘low’ and ‘high’ fasting glucose concentrations did not suggest an interaction between vitamin D and glucose homeostasis in the association with domain-specific cognitive performance. Moreover, adding fasting glucose or insulin did not substantially influence the associations between 25(OH)D status and domain-specific cognitive performance, and hence a mediation effect of glucose homeostasis was considered unlikely.

    We furthermore observed associations of 25(OH)D status with attention and working memory (n=787) (chapter 6), depression (n=2839) (chapter 7) and grey matter volume of the brain (n=217) (chapter 8) in a population community-dwelling Dutch older adults aged ≥65 years. Again, these studies did not provide evidence that the associations were modified or mediated by glucose intolerance. However, it should be emphasized that glucose intolerance in these three chapters was defined sub-optimally, specifically using blood samples that may have been collected in a non-fasting state, or by using self-reported diabetes data. Hence, the mediation and interaction effects should be interpreted cautiously.

    Finally, chapter 9 shows the results of a proof of principle study on the effect of a long-term vitamin D deficiency on cognitive decline and emotional reactivity in old C57BL/6j mice. Modest tendencies were shown for a relation between vitamin D and spatial learning, but these tendencies did not reach significance. Vitamin D deficiency did not affect recognition memory, spatial memory or emotional reactivity. Mice that received a higher dietary fat load, which was given to induce an impaired glucose tolerance, did not respond differently to a vitamin D deficiency than mice that received a low fat diet did.

    Overall, it is concluded that the evidence for an effect of vitamin D on cognitive performance/decline, depression or brain volume is insufficient to formulate disease specific cut-off values for vitamin D intake or 25(OH)D status. However, given the high prevalence of 25(OH)D concentrations <50 nmol/L we do call for a more active promotion of the current vitamin D intake recommendations.

    Therapeutic brain cancer targeting by gene therapy and immunomodulation : a translational study
    Stathopoulos, A. - \ 2012
    Wageningen University. Promotor(en): Virgil Schijns; Huub Savelkoul, co-promotor(en): F.A. Hofman. - S.l. : s.n. - ISBN 9789461733634 - 192
    hersenen - hersenkanker - gentherapie - immunotherapie - immunologie - geneeskunde - brain - brain cancer - gene therapy - immunotherapy - immunology - medicine

    The hypothesis pertinent to this thesis is that glioma tumours can be therapeutically targeted by gene and/or immunotherapy in order to eliminate or delay tumour recurrence leading to significant morbidity and mortality. In our gene therapeutic approach, described in Chapter 2, we observed that chronic expression of the C-terminal fusion of IsK with EGFP (enhanced green fluorescent protein) led to cell death of more than 50% of transfected U87-MG human astrocytoma cells as early as 2 days after transfection. Our results are consistent with activation of apoptotic pathways following IsK-mediated increase in K+ efflux. However, we abandoned the gene therapy approach because of the more attractive immunotherapeutic intervention strategies for of brain tumours, which is currently emerging as a highly potential clinical option as reviewed in Chapter 3. Interestingly, as described in Chapter 4, we found a strong therapeutic antitumour efficacy for the innate immune response modifier Resiquimod, even as a stand-alone treatment, eventually leading to immunological memory against secondary tumour challenges. In parallel, we observed that cyclophosphamide treatment, although effective as chemotherapeutic agent, may be deleterious to maintenance of long-term antitumour immune memory. Our data also demonstrates that immunotherapeutic parenteral treatment of established glioma tumours by Resiquimod, as defined in the protocol, significantly improves anti-brain tumour immunity in a way that leads to immune memory, which is superior to cyclophosphamide treatment alone. Our studies have thereby identified a promising novel antitumour immunotherapy which may lead to clinical benefit. In Chapter 5, we describe our finding that, in multiple rat glioma models, a certain composition of antigens derived from syngeneic tumour cells and their lysates when therapeutically co-administered with allogeneic cells and their lysates is able to confer anti-tumour immune responses and tumour regression. For the syngeneic C6 model in SD rats therapeutic injections of allogeneic cells alone were sufficient to trigger tumour regression. This immunization approach may prove useful as a postsurgery adjuvant therapy in future cancer treatment protocols, or even as a stand-alone therapeutic tumour vaccination. In another syngeneic rat glioma model, described in Chapter 6, we found that for regression of CNS-1 glioma tumours in Lewis rats specific innate immune response stimulating substances were required as immunological adjuvants. In our hands BCG and IL-2, the Toll-Like receptor (TLR) 7/8 activator Resiquimod, and the cytokine granulocyte-macrophage colony stimulating factor (GM-CSF), showed potent activity. Finally, as described in Chapter 7, we demonstrate that our prototype therapeutic vaccine, when co-delivered in a specific regimen together with the cytokine GM-CSF as immunological adjuvant, is able to arrest progression of glioma tumour growth, when therapeutically administered following low-dose cyclophosphamide. GM-CSF is an attractive vaccine adjuvant because of its proven immune modulatory effects and low toxicity profile. The safe pharmacological use of GM-CSF in patients is well-established, which makes it feasible for clinical use. The use of GM-CSF has been included in the first clinical studies that have been approved for an Investigational New Drug application (IND) for Single patient use in the U.S..

    Cortical mechanisms underlying low-level motion processing in the visual system of human and non-human primates
    Bours, R.J.E. - \ 2010
    Wageningen University. Promotor(en): Johan van Leeuwen; R.J.A. Wezel, co-promotor(en): Martin Lankheet. - [S.l.] : S.n. - ISBN 9789085857945 - 158
    ogen - beweging - mens - primaten - hersenen - neurobiologie - neurowetenschap - geest - kenvermogen - eyes - movement - man - primates - mind - neurobiology - neuroscience - cognition
    Report on restraining and neck cutting or stunning and neck cutting in pink veal calves
    Lambooij, B. ; Werf, J.T.N. van der; Reimert, H.G.M. ; Hindle, V.A. - \ 2010
    Lelystad : Wageningen UR Livestock Research (Report / Wageningen UR Livestock Research 398) - 17
    rundveehouderij - vleeskalveren - dierenwelzijn - slacht - bedwelmen - elektrisch verdoven - hartritme - hersenen - cattle husbandry - veal calves - animal welfare - slaughter - stunning - electronarcosis - cardiac rhythm - brain
    Neural and physiological assessment of welfare during restraining and rotation, after neck cutting, neck cutting followed by captive bolt stunning and electrical stunning followed by neck cutting in pink veal calves.
    Very long-chain n-3 polyunsaturated fatty acids: a head start to win some years between the ears?
    Dullemeijer, C. - \ 2009
    Wageningen University. Promotor(en): Frans Kok; R.J. Brummer, co-promotor(en): I.A. Brouwer. - [S.l.] : S.n. - ISBN 9789085853770 - 136
    vetzuren met een lange keten - hersenen - cognitieve ontwikkeling - mentale vaardigheid - visoliën - ouderen - vaatziekten - omega-3 vetzuren - kenvermogen - long chain fatty acids - brain - cognitive development - mental ability - fish oils - elderly - vascular diseases - omega-3 fatty acids - cognition
    Very long-chain n-3 (or omega-3) polyunsaturated fatty acids have attracted considerable public interest during the past few years for their potential beneficial role in cognitive performance. The proposed benefits stretch from advantages in developing brains of infants and children to preventing cognitive decline at old age.
    In this thesis, we first examined the role of very long-chain n-3 PUFA at the beginning of the lifespan. We investigated the effects of dietary very long-chain n-3 PUFA on the fatty acid composition of the several brain lobes in juvenile pigs, and showed that a diet enriched with fish oil resulted in higher proportions of DHA in the frontal, parietal and occipital brain lobes compared with the temporal brain lobe. These findings suggest a region-specific incorporation of DHA in the developing brain, which may guide future research into the mechanism by which very long-chain n-3 PUFA may in involved in brain development and function.
    Subsequently, we investigated the role of very long-chain n-3 PUFA near the end of the lifespan. In a population of older adults, we investigated the association between very long-chain n-3 PUFA and cognitive decline over three years in multiple cognitive domains. We demonstrated that higher plasma proportions of very long-chain n-3 PUFA were associated with less decline in the cognitive domains sensorimotor speed and complex speed, but not in memory, information-processing speed and word fluency, compared with lower plasma proportions of very long-chain n-3 PUFA. These results suggest a beneficial role of very long-chain n-3 PUFA in the speed-related cognitive domains, which justifies future research in this area with sensitive cognitive outcome measurements that provide domain-specific information.
    Finally, we touched upon the role of very long-chain n-3 PUFA in the macrovascular and the microvascular blood supply in the head region. We showed that plasma very long-chain n-3 PUFA were not associated with changes in carotid intima-media thickness and common carotid distension in a healthy older adult population. This may suggest that the role of very long-chain n-3 PUFA in a healthy population extends in particular to the smaller blood vessels. The role of very long-chain n-3 PUFA in the microcirculation of the brain could therefore be an interesting future direction of research. Although we did not directly investigate the role of very long-chain n-3 PUFA in the brain microcirculation, we did investigate whether plasma very long-chain n-3 PUFA were associated with age-related hearing loss over a period of three years in older adults. Since microvascular disease may decrease the blood supply to the highly vascularised cochlea, this may result in age-related hearing loss. We showed that higher plasma proportions of very long-chain n-3 PUFA were indeed associated with less age-related hearing loss compared with lower plasma proportions of very long-chain n-3 PUFA which implies that the hypothesis of improved microcirculation, if proven correct, may have far-reaching consequences.
    In summary, this thesis showed that very long-chain n-3 PUFA have region-specific effects on the developing brain and that higher plasma proportions of very long-chain n-3 PUFA were associated with less decline in the speed-related cognitive domains and less age-related hearing loss. Further research is required to establish the role of very long-chain n-3 PUFA in the developing as well as the aging brain and to investigate the underlying mechanisms.

    “Very long-chain n-3 polyunsaturated fatty acids: a head start to win some years between the ears?” PhD-thesis by Carla Dullemeijer, Top Institute Food and Nutrition and Division of Human Nutrition, Wageningen University, Wageningen, the Netherlands, May 15, 2009
    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 9789058088796 - 176
    ratten - vruchtbaarheid - voortplantingsvermogen - verouderen - hersenen - neurofysiologie - endocrinologie - rats - fertility - reproductive performance - aging - brain - neurophysiology - endocrinology
    It is well known that fertility decreases in female mammals with advancing age. In women this decrease already starts around the age of 30 and shows a large variation between individuals. The aim of this thesis was to elucidate changes in the reproductive system, especially in the brain, that may underlie the early decline in fertility with age. To this end,neuroendocrinologicalstudies were performed in young and middle-aged females of two rat strains known to differ in the onset of infertility: theWistar(WU) and (UxRP)F1strain.

    The results of the present thesis confirm the idea that the attenuation of theluteinizinghormone (LH) surge is one of the first indications of reproductive aging in rats. The LH surge is responsible for ovulation. It is induced by feedback mechanisms of ovarian steroid hormonesestradioland progesterone on the brain (i.e. on the secretion ofgonadotropin-releasing hormone) and pituitary gland (i.e. on the secretion of LH and follicle-stimulating hormone (FSH)) that become operative when the ovarian follicles are matured, and involves estrogen and progesterone receptors in the brain.

    Our results indicate that the attenuation of the LH surge in middle-aged rats likely results from an altered response of the brain toestradioland possibly also progesterone feedback, since we found a dramatic decrease in the number ofestradioland progesterone-containing neurons in several brain areas known to be crucially involved inneuroendocrineregulation of the reproductive axis. In contrast,estradioland progesterone levels were increased ((UxRP)F1) or even unchanged (Wistar) and the pituitary LH response toGnRHas well as the follicular progesterone production during the LH surge appeared to be comparable between young and middle-aged rats. This suggests that pituitary and ovary functions were still intact. Therefore, changes at the level of the brain may be at the start of the decline in fertility with age in rats.

    Interestingly, we found strain differences in the regulation of the reproductive axis. There was, for instance, a difference between F1 andWistarrats in the magnitude of the LH surge (F1>Wistar) and the magnitude of the pituitary LH response toGnRH(F1<Wistar). Also, middle-aged F1 rats appeared to be reproductively aged to a further extend compared toWistarrats, as judged by the number of changes in the reproductive system.

    Although in women ovarian aging appears to be the dominant reason for fertility decline, there is evidence for considerable variation between individuals in the mechanisms underlying reproductive aging. Based on our present findings and literature, we hypothesize that hypothalamic aging may also contribute to the decline in fertility in some women.

    Stress, endogenous opioids and stereotypies in tethered pigs
    Loijens, L.W.S. - \ 2002
    Wageningen University. Promotor(en): V.M. Wiegant; W.G.P. Schouten. - S.l. : S.n. - ISBN 9789058085757 - 126
    varkens - zeugen - stress - stressreactie - tuierhuisvesting - opiumachtige peptiden - hersenen - abnormaal gedrag - hartfrequentie - diergedrag - adaptatie - dierfysiologie - stereotypen - psychologische fysiologie - pigs - sows - stress - stress response - tethered housing - opioid peptides - brain - abnormal behaviour - heart rate - animal behaviour - adaptation - animal physiology - stereotypes - psychological physiology

    Tether housing of female pigs in narrow, individual boxes represents a chronic stressor for the animals. Pigs that are housed tethered often develop behavioural disturbances, such as stereotypies, and changes in physiological regulation. The results of the studies described in the present thesis confirm and extend previous suggestions that there is an association between stereotypies and brain opioid activity. We found a negative correlation between the intensity of stereotypy performance and opioid receptor densities in the hippocampus and the hypothalamus of pigs which had been housed tethered for two months. This correlation seemed to disappear with increasing duration of tether housing, likely as a consequence of the gradual decrease in receptor density that occurred in pigs with low levels of stereotypies. This receptor decrease might reflect glucocorticoid-induced neuronal cell loss, since we also found a negative correlation between he salivary cortisol concentration and the number of neurons in the hippocampus in long-term tether housed pigs. These results accord with the idea that stereotypies represent a strategy to reduce adverse effects of chronic stress.

    The chronic stress of tether housing not only leads to the development of stereotypies, it can also induce changes in physiological responsivity to further stressful stimulation. The mechanisms underlying these changes likely include alterations in endogenous opioid systems. This is indicated by our finding that antagonism of endogenous opioid activity increased the heart rate response of pigs to a stressful challenge after long-term tether housing but not after loose housing. These results provide evidence indicating that long-term tether housing leads to an increased impact of endogenous opioid systems that attenuate physiological responses to additional acute stress.

    Taken together, the present thesis highlights changes in endogenous opioid activity that are induced by chronic stress and appear to prevent or reduce potentially harmful stress effects.

    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

    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.

    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.

    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.

    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.

    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).

    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 theMPOAis 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 theMPOAcould be contributed to a sexual dimorphism in prolactin- inhibiting factor or prolactin-releasing factor activity.

    The data of chapter 7 show that theMPOAis 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 theMPOAmay be considered as an "anti-surge key-control" centre for (Prl) secretion in female rats. Whether theMPOAexerts its control via one final common neural pathway represented by the tuberoinfundibular dopaminergic system, remains to be determined.

    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, theMPOA,which control is sexually differentiated: stimulatory in the male and inhibitory in the female.

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