Different mating contexts lead to extensive rewiring of female brain coexpression networks in the guppy
Bloch, Natasha I. ; Corral-López, Alberto ; Buechel, Séverine D. ; Kotrschal, Alexander ; Kolm, Niclas ; Mank, Judith E. - \ 2020
Genes, Brain and Behavior (2020). - ISSN 1601-1848
brain - decision-making - differential network analysis - gene networks - guppy - mating behavior - neurogenomics - sensory processing - social behavior - transcriptome
Understanding the basis of behavior requires dissecting the complex waves of gene expression that underlie how the brain processes stimuli and produces an appropriate response. In order to determine the dynamic nature of the neurogenomic network underlying mate choice, we use transcriptome sequencing to capture the female neurogenomic response in two brain regions involved in sensory processing and decision-making under different mating and social contexts. We use differential coexpression (DC) analysis to evaluate how gene networks in the brain are rewired when a female evaluates attractive and nonattractive males, greatly extending current single-gene approaches to assess changes in the broader gene regulatory network. We find the brain experiences a remarkable amount of network rewiring in the different mating and social contexts we tested. Further analysis indicates the network differences across contexts are associated with behaviorally relevant functions and pathways, particularly learning, memory and other cognitive functions. Finally, we identify the loci that display social context-dependent connections, revealing the basis of how relevant neurological and metabolic pathways are differentially recruited in distinct social contexts. More broadly, our findings contribute to our understanding of the genetics of mating and social behavior by identifying gene drivers behind behavioral neural processes, illustrating the utility of DC analysis in neurosciences and behavior.
The Importance of Maternal Folate Status for Brain Development and Function of Offspring
Naninck, Eva F.G. ; Stijger, Pascalle C. ; Brouwer-Brolsma, Elske M. - \ 2019
Advances in Nutrition 10 (2019)3. - ISSN 2161-8313 - p. 502 - 519.
brain - cognition - developmental - folate - folic acid - maternal - neuropsychological - prenatal
The importance of an adequate periconceptional maternal folate status to prevent fetal neural tube defects has been well demonstrated and resulted in the recommendation for women to use folic acid supplements during the periconception period. The importance of maternal folate status for offspring neurodevelopment and brain health is less well described. We reviewed the current evidence linking maternal folate status before conception and during pregnancy with neurodevelopment and cognition of the offspring. We discuss both animal and human studies. Preclinical research revealed the importance of maternal folate status for several key processes required for normal neurodevelopment and brain functioning in the offspring, including DNA synthesis, regulation of gene expression, synthesis of phospholipids and neurotransmitters, and maintenance of healthy plasma homocysteine concentrations. Human observational studies are inconclusive; about half have shown a positive association between maternal folate status and cognitive performance of offspring. Whereas some studies suggest a positive association between maternal folate intake and cognition of offspring during childhood, data from interventional studies are too limited to conclude that there is a direct effect. Future preclinical studies are needed to help us characterize the behavioral effects, understand the underlying mechanisms, and to establish an optimal dosage and time window of folate supplementation. Moreover, more conclusive data from well-designed human observational studies and randomized controlled trials are needed to determine whether current recommendations for folic acid supplementation during pregnancy cover the needs for normal cognitive development in the offspring.
Supplementary Material for: Nasonia Parasitic Wasps Escape from Haller's Rule by Diphasic, Partially Isometric Brain-Body Size Scaling and Selective Neuropil Adaptations
Groothuis, J. ; Smid, H.M. - \ 2017
Haller's rule - brain - insect - Nasonia vitripennis - parasitic wasp - confocal laser scanning microscopy - plasticity - neuropil - mushroom body
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.
A maternal Western diet during gestation and lactation modifies offspring’s microbiota activity, blood lipid levels, cognitive responses, and hippocampal neurogenesis in Yucatan pigs
Val-Laillet, David ; Besson, M. ; Guérin, S. ; Coquery, N. ; Randuineau, G. ; Kanzari, A. ; Quesnel, H. ; Bonhomme, N. ; Bolhuis, J.E. ; Kemp, B. ; Blat, S. ; Huërou-Luron, I. Le; Clouard, C.M. - \ 2017
FASEB Journal 31 (2017)5. - ISSN 0892-6638 - p. 2037 - 2049.
early nutrition - development - eating behavior - metabolism - brain
A suboptimal early nutritional environment (i.e., excess of energy, sugar, and fat intake) can increase susceptibility to diseases and neurocognitive disorders. The purpose of this study was to investigate in nonobese Yucatan minipigs (Sus scrofa) the impact of maternal diet [standard (SD) vs. Western (WD) diet] during gestation and 25 d of lactation on milk composition, blood metabolism, and microbiota activity of sows (n = 17) and their piglets (n = 65), and on spatial cognition (n = 51), hippocampal plasticity (n = 17), and food preferences/motivation (n = 51) in the progeny. Milk dry matter and lipid content, as well as plasma total cholesterol and free fatty acid (FFA) concentrations (P < 0.05) were higher in WD than in SD sows. Microbiota activity decreased in both WD sows and 100-d-old piglets (P < 0.05 or P < 0.10, depending on short-chain FAs [SCFAs]). At weaning [postnatal day (PND) 25], WD piglets had increased blood triglyceride and FFA levels (P < 0.01). Both SD and WD piglets consumed more of a known SD than an unknown high-fat/-sucrose (HFS) diet (P < 0.0001), but were quicker to obtain HFS rewards compared with SD rewards (P < 0.01). WD piglets had higher working memory (P = 0.015) and reference memory (P < 0.001) scores, which may reflect better cognitive abilities in the task context and a higher motivation for the food rewards. WD piglets had a smaller hippocampal granular cell layer (P = 0.03) and decreased neurogenesis (P < 0.005), but increased cell proliferation (P < 0.001). A maternal WD during gestation and lactation, even in the absence of obesity, has significant consequences for piglets’ blood lipid levels, microbiota activity, gut–brain axis, and neurocognitive abilities after weaning.—Val-Laillet, D., Besson, M., Guérin, S., Coquery, N., Randuineau, G., Kanzari, A., Quesnel, H., Bonhomme, N., Bolhuis, J. E., Kemp, B., Blat, S., Le Huërou-Luron, I., Clouard, C. A maternal Western diet during gestation and lactation modifies offspring’s microbiota activity, blood lipid levels, cognitive responses, and hippocampal neurogenesis in Yucatan pigs.
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.
Dietary Linoleic and a-Linolenic Acid Affect Anxiety-Related Responses and Exploratory Activity in Growing Pigs
Clouard, C.M. ; Gerrits, W.J.J. ; Kerkhof, I. van; Smink, W. ; Bolhuis, J.E. - \ 2015
The Journal of Nutrition 145 (2015)2. - ISSN 0022-3166 - p. 358 - 364.
polyunsaturated fatty-acids - docosahexaenoic acid - inflammatory processes - open-field - behavior - brain - rats - mice - deficiency - piglets
Background: Growing evidence suggests that the dietary ratio of linoleic acid (LA) to a-linolenic acid (ALA), the precursors of arachidonic acid (AA) and docosahexaenoic acid (DHA), respectively, may affect behavior in mammals. Objective: This study aimed at evaluating the impact of dietary LA and ALA intake on behaviors of growing pigs, a pertinent model for human nutrition. Methods: At 7 wk of age, 32 pigs were allocated to 4 dietary treatments varying in daily intake of LA (1.3 and 2.6 g · kg body weight-0.75 · d-1 for low- and high-LA groups, respectively) and ALA (0.15 and 1.5 g · kg body weight-0.75 · d-1 for low- and high-ALA groups, respectively) for 4 wk. Between days 12 and 18, general behavior in the home pen was observed and pigs were subjected to an open field and novel object test. At 11 wk of age, brain fatty acid composition was analyzed. Results: Compared with high LA intake, low LA intake increased the time spent on exploration, particularly nosing in the home pen (P <0.05) and the open field (P <0.05), and tended to reduce the time spent lying with eyes open in the home pen (P = 0.09). Time spent lying with eyes open also tended to be affected by LA × ALA interaction (P = 0.08). A high-LA/high-ALA intake (ratio of 2; P <0.05) and a low-LA/high-ALA intake (ratio of 1; P = 0.06) decreased the latency to approach the novel object compared with a low-LA/low-ALA intake (ratio of 9). DHA in the frontal cortex was positively correlated with exploratory behaviors in the home pen (rs = 0.56, P <0.01), whereas AA was negatively correlated with time spent lying with eyes closed (rs = –0.48, P <0.01). Conclusions: Low LA intake and a low dietary LA:ALA ratio increased exploration and decreased anxiety-related behaviors in pigs. It is suggested that changes in brain DHA and AA induced by dietary LA and ALA intake mediate these behavioral changes.
Do you like what you see? The role of first fixation and total fixation duration in consumer choice
Laan, L.N. van der; Hooge, I.T.C. ; Ridder, D.T.D. de; Viergever, M.A. ; Smeets, P.A.M. - \ 2015
Food Quality and Preference 39 (2015)2015. - ISSN 0950-3293 - p. 46 - 55.
gaze bias - visual-attention - decision-making - eyetracking data - eye-movements - food - preference - system - brain - vmpfc
Although there has been recent growing interest in the associations between measures of visual attention and consumer choice, there is still uncertainty about the role of the first fixation in consumer choice and the factors that drive total fixation duration. The study aimed (1) to investigate the influence of the first fixation on consumer choice, and (2) to disentangle two factors driving total fixation duration, namely preference formation (the process of establishing a preference for one of the items of the choice set) and the decision goal (task instruction). Participants chose between two products while their eye movements were measured. To investigate the influence of first fixation location on choice, first fixation location was manipulated in half of the trials. To disentangle effects of preference formation and the decision goal, participants selected either the product they wanted, or the product they did not want. Our findings showed that manipulating the first fixation towards an alternative did not influence its likelihood of being chosen. Although total fixation duration was mainly determined by the decision goal, it was also influenced by preference formation. The results provide important implications for the interpretation of eye tracking results and in-store marketing.
Evaluation of two commercial, rapid, ELISA kits testing or scrapie in retro-pharyngeal lymph nodes in sheep
Kittelberger, R. ; McIntuyre, L. ; Watts, S. ; MacDiarmid, S. ; Hannah, M.J. ; Jenner, J. ; Bueno, R. ; Swainsbury, R. ; Langeveld, J.P.M. ; Keulen, L.J.M. van; Zijderveld, F.G. van; Wemheuer, W.M. ; Richt, J.A. ; Sorenson, S.J. ; Pigott, C.J. ; O'Keefe, J.S. - \ 2014
New Zealand Veterinary Journal 62 (2014)6. - ISSN 0048-0169 - p. 343 - 350.
natural scrapie - prion protein - immunohistochemical detection - new-zealand - prp - accumulation - diagnosis - genotypes - tissues - brain
AIMS: To estimate the number of cases of scrapie that would occur in sheep of different prion protein (PrP) genotypes if scrapie was to become established in New Zealand, and to compare the performance of two commercially available, rapid ELISA kits using ovine retro-pharyngeal lymph nodes (RLN) from non-infected and infected sheep of different PrP genotypes. METHODS: Using published data on the distribution of PrP genotypes within the New Zealand sheep flock and the prevalence of cases of scrapie in these genotypes in the United Kingdom, the annual expected number of cases of scrapie per genotype was estimated, should scrapie become established in New Zealand, assuming a total population of 28 million sheep. A non-infected panel of RLN was collected from 737 sheep from New Zealand that had been culled, found in extremis or died. Brain stem samples were also collected from 131 of these sheep. A second panel of infected samples comprised 218 and 117 RLN from confirmed scrapie cases that had originated in Europe and the United States of America, respectively. All samples were screened using two commercial, rapid, transmissible spongiform encephalopathy ELISA kits: Bio-Rad TeSeE ELISA (ELISA-BR), and IDEXX HerdChek BSE-Scrapie AG Test (ELISA-ID). RESULTS: If scrapie became established in New Zealand, an estimated 596 cases would occur per year; of these 234 (39%) and 271 (46%) would be in sheep carrying ARQ/ARQ and ARQ/VRQ PrP genotypes, respectively. For the non-infected samples from New Zealand the diagnostic specificity of both ELISA kits was 100%. When considering all infected samples, the diagnostic sensitivity was 70.4 (95% CI=65.3-75.3)% for ELISA-BR and 91.6 (95% CI=88.2-94.4)% for ELISA-ID. For the ARQ/ARQ genotype (n=195), sensitivity was 66.2% for ELISA-BR and 90.8% for ELISA-ID, and for the ARQ/VRQ genotype (n=107), sensitivity was 81.3% for ELISA-BR and 98.1% for ELISA-ID. CONCLUSIONS: In this study, the ELISA-ID kit demonstrated a higher diagnostic sensitivity for detecting scrapie in samples of RLN from sheep carrying scrapie-susceptible PrP genotypes than the ELISA-BR kit at comparable diagnostic specificity.
Hypothalamic vasotocin and tyrosine hydroxylase levels following maternal care and selection for low mortality in laying hens
Hewlett, S.E. ; Zeinstra, E.C. ; Eerdenburg, Frank J.C.M. ; Rodenburg, T.B. ; Kooten, P.J.S. van; Staay, F.J. van der; Nordquist, R.E. - \ 2014
BMC Veterinary Research 10 (2014). - ISSN 1746-6148 - 10 p.
feather pecking behavior - gallus-domesticus - dopamine neurons - social-behavior - hpa axis - stress - brain - chicken - system - area
BACKGROUND: Feather pecking and cannibalism are major concerns in poultry farming, both in terms of animal welfare and farm economics. Genetic selection and introduction of (aspects of) maternal care have been suggested as potential interventions to reduce feather pecking in laying hens. Altered brain development has been proposed to reflect welfare states in animals, and can provide more insight into the underlying processes involved in feather pecking. Both vasotocin (the avian homologue of vasopressin) and dopaminergic neural circuitry have roles in control of social behaviors as well as in the stress response, and may be linked to feather pecking. Thus, the hypothalamus of adult laying hens selected for low early mortality (LML), which show low feather pecking, was examined and compared with a control line of adult laying hens selected for production characteristics only (CL). The effect of foster hen rearing on the two genetic lines and their hypothalamic morphology was also investigated. RESULTS: We demonstrated an increase in the number of neurons positive for the rate-limiting enzyme in dopamine production, tyrosine hydroxylase, in the periventricular area of the hypothalamus in the LML hens compared to CL hens. Hen-reared chicks showed more vasotocin -positive neurons in the medial pre-optic area compared to the hens raised without a hen. No correlations were found between behavior in an open field at 5-6 weeks of age, and the histology of the same hens at adulthood. CONCLUSION: The hypothalamic dopaminergic and vasotinergic systems are altered in hens following genetic selection or maternal care, indicating a potential role for these systems in feather pecking. Keywords: Hypothalamus, Vasotocin, Vasopressin, Tyrosine hydroxylase, Dopamine, Welfare, Laying hen
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.
Food preference and intake in response to ambient odours in overweight and normal-weight females
Zoon, H.F.A. ; He, W. ; Wijk, R.A. de; Graaf, C. de; Boesveldt, S. - \ 2014
Physiology and Behavior 133 (2014). - ISSN 0031-9384 - p. 190 - 196.
cephalic phase responses - cue exposure - unrestrained eaters - eating behavior - external cues - appetite - humans - perception - obesity - brain
In our food abundant environment, food cues play an important role in the regulation of energy intake. Odours can be considered as external cues that can signal energy content in the anticipatory phase of eating. This study aims to determine whether exposure to olfactory cues associated with energy dense foods leads to increased food intake and greater preference for energy-dense foods. In addition, we assessed whether BMI and hunger state modulated this effect. Twenty-five overweight (mean BMI: 31.3 kg/m2, S.E.: 0.6) and 25 normal-weight (mean BMI: 21.9 kg/m2, S.E.: 0.4) females, matched on age and restraint score, participated. In 6 separate sessions they were exposed to odours of three different categories (signalling non-food, high-energy food and low-energy food) in two motivational states (hungry and satiated). After 10 min of exposure food preference was assessed with a computerized two-item forced choice task and after 20 min a Bogus Taste Test was used to determine energy intake (kcal and g). In a hungry state, the participants ate more (p <.001) and preferred high-energy products significantly more often (p <.001) when compared to the satiated state. A trend finding for the interaction between hunger and BMI suggested that the food preference of overweight participants was less affected by their internal state (p = .068). Neither energy intake (kcal: p = .553; g: p = .683) nor food preference (p = .280) was influenced by ambient exposure to odours signalling different categories. Future studies need to explore whether food odours can indeed induce overeating. More insight is needed regarding the possible influence of context (e.g. short exposure duration, large variety of food) and personality traits (e.g. restraint, impulsive) on odour-induced overeating.
No role for vitamin D or a moderate fat diet in aging induced cognitive decline and emotional reactivity in C57BL/6 mice
Brouwer, E.M. ; Schuurman, T. ; Groot, C.P.G.M. de; Feskens, E.J.M. ; Lute, C. ; Naninck, E.F.G. ; Arndt, S.S. ; Staay, F.J. van der; Bravenboer, N. ; Korosi, A. ; Steegenga, W.T. - \ 2014
Behavioural Brain Research 267 (2014). - ISSN 0166-4328 - p. 133 - 143.
serum 25-hydroxyvitamin d - d supplementation - d deficiency - depressive symptoms - alzheimers-disease - insulin-resistance - older women - pre-post - brain - association
Background Epidemiological studies have shown associations between vitamin D, mental health and glucose homeostasis in the elderly. Causal evidence, however, is still lacking. Objective The objective of this study was to investigate the importance of vitamin D in the prevention of emotional disturbances and cognitive decline in aging C57BL/6 mice, with pre-diabetes type II as potential effect modifier. Methods Mice were exposed to one of four diets from 10 months till 24 months of age: low fat vitamin D adequate (LFD), LF vitamin D deficient (LF), moderate fat vitamin D adequate (MFD), and MF vitamin D deficient (MF). The MFD/MF diet was applied to induce a condition resembling pre-diabetes type II. Behavior was assessed twice in the same group of mice at 6–8 and at 22–23 months of age using the Open Field Test (OFT), Elevated Plus Maze (EPM), Object Recognition Test (ORT) and the Morris Water Maze (MWM). Results We successfully induced vitamin D deficiency in the LF/MF mice. Moreover, fasting glucose and fasting insulin levels were significantly higher in MFD/MF mice than in LFD/LF mice. A significant aging effect was observed for most behavioral parameters. A MF(D) diet was shown to delay or prevent the age-related increase in emotional reactivity in the EPM. No effect of vitamin D or vitamin D*fat on behavioral outcomes was measured. Conclusion Aging significantly affected emotional reactivity and cognitive performance. Although other studies have shown effects of vitamin D on emotional reactivity and cognitive performance in mice, these findings could not be confirmed in aged C57BL/6 mice in this study.
Altered gut microbiota and activity in a murine model of autism spectrum disorders
Theije, C.G. de; Wopereis, H.J. ; Ramadan, M. ; Eijndthoven, T. van; Lambert, J. ; Knol, J. ; Garssen, J. ; Kraneveld, A.D. ; Oozeer, R. - \ 2014
Brain, Behavior, and Immunity 37 (2014). - ISSN 0889-1591 - p. 197 - 206.
valproic acid - intestinal microbiota - maternal separation - host interactions - propionic-acid - onset autism - children - brain - microflora - exposure
Autism spectrum disorder (ASD) is a heterogeneous group of complex neurodevelopmental disorders with evidence of genetic predisposition. Intestinal disturbances are reported in ASD patients and compositional changes in gut microbiota are described. However, the role of microbiota in brain disorders is poorly documented. Here, we used a murine model of ASD to investigate the relation between gut microbiota and autism-like behaviour. Using next generation sequencing technology, microbiota composition was investigated in mice in utero exposed to valproic acid (VPA). Moreover, levels of short chain fatty acids (SCFA) and lactic acid in caecal content were determined. Our data demonstrate a transgenerational impact of in utero VPA exposure on gut microbiota in the offspring. Prenatal VPA exposure affected operational taxonomic units (OTUs) assigned to genera within the main phyla of Bacteroidetes and Firmicutes and the order of Desulfovibrionales, corroborating human ASD studies. In addition, OTUs assigned to genera of Alistipes, Enterorhabdus, Mollicutes and Erysipelotrichalis were especially associated with male VPA-exposed offspring. The microbial differences of VPA in utero-exposed males deviated from those observed in females and was (i) positively associated with increased levels of caecal butyrate as well as ileal neutrophil infiltration and (ii) inversely associated with intestinal levels of serotonin and social behaviour scores. These findings show that autism-like behaviour and its intestinal phenotype is associated with altered microbial colonization and activity in a murine model for ASD, with preponderance in male offspring. These results open new avenues in the scientific trajectory of managing neurodevelopmental disorders by gut microbiome modulation
Chronic Allopurinol Treatment during the Last Trimester of Pregnancy in Sows: Effects on Low and Normal Birth Weight Offspring
Gieling, E.T. ; Antonides, A. ; Fink-Gremmels, J. ; Haar, K. ter; Kuller, W.I. ; Meijer, E. ; Nordquist, R.E. ; Stouten, J.M. ; Zeinstra, E. ; Staay, F.J. van der - \ 2014
PLoS ONE 9 (2014)1. - ISSN 1932-6203 - 15 p.
intrauterine growth-restriction - for-gestational-age - children born - placental insufficiency - attentional problems - newborn piglets - spleen weight - brain - memory - stress
Low-birth-weight (LBW) children are born with several risk factors for disease, morbidity and neonatal mortality, even if carried to term. Placental insufficiency leading to hypoxemia and reduced nutritional supply is the main cause for LBW. Brain damage and poor neurological outcome can be the consequence. LBW after being carried to term gives better chances for survival, but these children are still at risk for poor health and the development of cognitive impairments. Preventive therapies are not yet available. We studied the risk/efficacy of chronic prenatal treatment with the anti-oxidative drug allopurinol, as putative preventive treatment in piglets. LBW piglets served as a natural model for LBW. A cognitive holeboard test was applied to study the learning and memory abilities of these allopurinol treated piglets after weaning. Preliminary analysis of the plasma concentrations in sows and their piglets suggested that a daily dose of 15 mg.kg-1 resulted in effective plasma concentration of allopurinol in piglets. No adverse effects of chronic allopurinol treatment were found on farrowing, birth weight, open field behavior, learning abilities, relative brain, hippocampus and spleen weights. LBW piglets showed increased anxiety levels in an open field test, but cognitive performance was not affected by allopurinol treatment. LBW animals treated with allopurinol showed the largest postnatal compensatory body weight gain. In contrast to a previous study, no differences in learning abilities were found between LBW and normal-birth-weight piglets. This discrepancy might be attributable to experimental differences. Our results indicate that chronic prenatal allopurinol treatment during the third trimester of pregnancy is safe, as no adverse side effects were observed. Compensatory weight gain of treated piglets is a positive indication for the chronic prenatal use of allopurinol in these animals. Further studies are needed to assess the possible preventive effects of allopurinol on brain functions in LBW piglets.
Immune dysregulation in autism spectrum disorder
Briceno Noriega, D. ; Savelkoul, H.F.J. - \ 2014
European Journal of Pediatrics 173 (2014)1. - ISSN 0340-6199 - p. 33 - 43.
pervasive developmental disorders - vitamin-d - risk-factors - antibrain antibodies - maternal infection - proximal 15q - twin pairs - brain - children - pregnancy
Autism spectrum disorder (ASD) is a common and severe neuro-developmental disorder in early childhood which is defined by social and communication deficits and repetitive and stereotypic behaviours. The aetiology of ASD remains poorly understood. Susceptibility to development of ASD has significant environmental components, in addition to the profound genetic heritability. Few genes have been associated to the risk for ASD development. There is substantial evidence implicating chronic neurological inflammation and immune dysregulation leading to upregulation of inflammatory cytokines in the ASD brain, probably due to altered blood–brain barrier function. The immune system is characterized by excessive and skewed cytokine responses, modulated T cell reactivity, decreased regulation and production of immunosuppressive cytokines, modified NK function and increased autoantibody production. Conclusion: The perinatal environment generates vulnerability to chronic neuro-inflammation in the brain associated with profound modulation and dysregulation in the immune system leading to the rapid development of ASD in genetically susceptible children.
The endocannabinoid system and emotional processing: A pharmacological fMRI study with Delta 9-tetrahydrocannabinol
Bossong, M.G. ; Hell, H.H. van; Jager, G. ; Kahn, R.S. ; Ramsey, N.F. ; Jansma, J.M. - \ 2013
European Neuropsychopharmacology 23 (2013)12. - ISSN 0924-977X - p. 1687 - 1697.
cb1 cannabinoid receptors - happy facial expressions - healthy-volunteers - antagonist rimonabant - major depression - memory function - functional mri - amygdala - brain - involvement
Various psychiatric disorders such as major depression are associated with abnormalities in emotional processing. Evidence indicating involvement of the endocannabinoid system in emotional processing, and thus potentially in related abnormalities, is increasing. In the present study, we examined the role of the endocannabinoid system in processing of stimuli with a positive and negative emotional content in healthy volunteers. A pharmacological functional magnetic resonance imaging (fMRI) study was conducted with a placebo-controlled, cross-over design, investigating effects of the endocannabinoid agonist Delta 9-tetrahydrocannabinol (THC) on brain function related to emotional processing in 11 healthy subjects. Performance and brain activity during matching of stimuli with a negative ('fearful faces') or a positive content ('happy faces') were assessed after placebo and THC administration. After THC administration, performance accuracy was decreased for stimuli with a negative but not for stimuli with a positive emotional content. Our task activated a network of brain regions including amygdala, orbital frontal gyrus, hippocampus, parietal gyrus, prefrontal cortex, and regions in the occipital cortex. THC interacted with emotional content, as activity in this network was reduced for negative content, while activity for positive content was increased. These results indicate that THC administration reduces the negative bias in emotional processing. This adds human evidence to support the hypothesis that the endocannabinoid system is involved in modulation of emotional processing. Our findings also suggest a possible role for the endocannabinoid system in abnormal emotional processing, and may thus be relevant for psychiatric disorders such as major depression. (C) 2013 Elsevier B.V. and ECNP. All rights reserved.
Effect of Replacing Sugar with Non-Caloric Sweeteners in Beverages on the Reward Value after Repeated Exposure
Griffioen-Roose, S. ; Smeets, P.A.M. ; Weijzen, P.L.G. ; Rijn, I. van; Bosch, I. van den; Graaf, C. de - \ 2013
PLoS ONE 8 (2013)11. - ISSN 1932-6203
body-weight - artificial sweetener - energy density - food-intake - satiety - brain - choice - flavor - adults - taste
Background: The reward value of food is partly dependent on learned associations. It is not yet known whether replacing sugar with non-caloric sweeteners in food is affecting long-term acceptance. Objective: To determine the effect of replacing sugar with non-caloric sweeteners in a nutrient-empty drink (soft drink) versus nutrient-rich drink (yoghurt drink) on reward value after repeated exposure. Design: We used a randomized crossover design whereby forty subjects (15 men, 25 women) with a mean +/- SD age of 21 +/- 2 y and BMI of 21.5 +/- 1.7 kg/m(2) consumed a fixed portion of a non-caloric sweetened (NS) and sugar sweetened (SS) versions of either a soft drink or a yoghurt drink (counterbalanced) for breakfast which were distinguishable by means of colored labels. Each version of a drink was offered 10 times in semi-random order. Before and after conditioning the reward value of the drinks was assessed using behavioral tasks on wanting, liking, and expected satiety. In a subgroup (n=18) fMRI was performed to assess brain reward responses to the drinks. Results: Outcomes of both the behavioral tasks and fMRI showed that conditioning did not affect the reward value of the NS and SS versions of the drinks significantly. Overall, subjects preferred the yoghurt drinks to the soft drinks and the ss drinks to the NS drinks. In addition, they expected the yoghurt drinks to be more satiating, they reduced hunger more, and delayed the first eating episode more. Conditioning did not influence these effects. Conclusion: Our study showed that repeated consumption of a non-caloric sweetened beverage, instead of a sugar sweetened version, appears not to result in changes in the reward value. It cannot be ruled out that learned associations between sensory attributes and food satiating capacity which developed preceding the conditioning period, during lifetime, affected the reward value of the drinks.
Prioritization of candidate genes for cattle reproductive traits, based on protein-protein interactions, gene expression, and text-mining
Hulsegge, B. ; Woelders, H. ; Smits, M.A. ; Schokker, D. ; Jiang, L. ; Sorensen, P. - \ 2013
Physiological genomics 45 (2013)10. - ISSN 1094-8341 - p. 400 - 406.
dairy-cows - quantitative measure - interaction networks - estrous behavior - disease genes - identification - patterns - amygdala - brain - bioinformatics
Reproduction is of significant economic importance in dairy cattle. Improved understanding of mechanisms that control estrous behavior and other reproduction traits could help in developing strategies to improve and/or monitor these traits. The objective of this study was to predict and rank genes and processes in brain areas and pituitary involved in reproductive traits in cattle using information derived from three different data sources: gene expression, protein-protein interactions, and literature. We identified 59, 89, 53, 23, and 71 genes in bovine amygdala, dorsal hypothalamus, hippocampus, pituitary, and ventral hypothalamus, respectively, potentially involved in processes underlying estrus and estrous behavior. Functional annotation of the candidate genes points to a number of tissue-specific processes of which the “neurotransmitter/ion channel/synapse” process in the amygdala, “steroid hormone receptor activity/ion binding” in the pituitary, “extracellular region” in the ventral hypothalamus, and “positive regulation of transcription/metabolic process” in the dorsal hypothalamus are most prominent. The regulation of the functional processes in the various tissues operate at different biological levels, including transcriptional, posttranscriptional, extracellular, and intercellular signaling levels.