103. maternal perinatal high-fat diet increases anxiety-like behavior in male offspring

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vaccine experimental inflammation model together with computa- tional modelling of an instrumental learning task performed during fMRI (1). Twenty-two healthy participants were each tested 3-h after blindly administered typhoid vaccine (0.025 mg) and placebo (0.5 ml 0.9% NaCl) injection. Typhoid but not placebo was associated with a threefold increase in plasma IL-6 (t(21) = 5.20, p < 0.001) confirming induction of mild inflammation. Following inflammation partici- pants demonstrated greater avoidance of a punishing cue (loss £1) and significantly reduced selection of a rewarded cue F(21,1) = 6.41, p = 0.019. Computational modelling of individuals’ choices using a Q-learning model (free parameters alpha (learning- rate), beta (choice-randomness) and R (reward value)) demonstrated significant reduction in reward cue value and increase in value of punishment cues following inflammation F(21,1) = 3.63, p < 0.05. fMRI confirmed previous correlations of appetitive and aversive pre- diction error (PE) within ventral striatal (VS) and anterior insula (AI) regions of interest respectively (FWE p < 0.05) across conditions. However, inflammation significantly impaired VS responses to appe- titive PE and enhanced AI responses to aversive PE (FWE p < 0.05) suggesting that inflammation modulates the value of aversive and appetitive cues via actions on VS and AI prediction error signals respectively. (1) Pessiglione et al., 2006. Nature 442, 1042–45. http://dx.doi.org/10.1016/j.bbi.2014.06.121 102. Enriched maternal care decreases opioid self-administration in adulthood and alters neuroimmune signaling in the nucleus accumbens M.J. Lacagnina a , G.M. Houtz a , C. Wells b , S. Slade b , E.D. Levin b , S.D. Bilbo a a Duke University, Department of Psychology and Neuroscience, 210 Research Drive, Durham, NC 27708, USA b Duke University Medical Center, USA Despite decades of progress, the biological mechanisms underly- ing addiction are unknown. Glia, including astrocytes and microglia, profoundly influence neuronal function and may play a critical role in the development of drug addiction. Previously, we have shown that a neonatal handling procedure (which promotes enriched maternal care) reduces glial activation to an acute morphine chal- lenge and prevents reinstatement of morphine conditioned place preference; likewise, similar results were obtained by pharmacolog- ical manipulation of glia within the nucleus accumbens (NAc). Here, we investigated the effects of opioid self-administration on central immune signaling within the NAc and its modulation by early-life experience. Male rat pups were handled (15 min/day) from postnatal day (P) 2 to P20 or left undisturbed. In adulthood, all rats were tested for self-administration of intravenous remifentanil (a short-acting opioid) in daily 1 h sessions for 2 weeks. Brains were then collected to examine persistent alterations in glial activation. Neonatal han- dling reduced acquisition of remifentanil; this effect was specific for opioids, as acquisition of food reward was unaffected. Remifenta- nil self-administration substantially increased glial antigen expres- sion (Iba1 and GFAP) and proinflammatory gene expression in NAc, including the innate immune receptor TLR4. However, only handled rats showed increased expression of the anti-inflammatory cytokine IL-10. These data establish neural–glial interactions in the NAc as an essential component of self-motivated drug acquisition that can be altered by early-life environmental conditions. http://dx.doi.org/10.1016/j.bbi.2014.06.122 103. Maternal perinatal high-fat diet increases anxiety-like behavior in male offspring G. Winther a , S. Lund b , H.K. Müller a , G. Wegener a a Translational Neuropsychiatric Unit, Department of Clinical Medicine, Skovagervej 2, Aarhus University, Riiskov, Aarhus 8240, Denmark b Department of Endocrinology and Internal Medicine, Aarhus University Hospital, 9 Nørrebrogade 44, Bldg. 3.0, 8000 Aarhus C, Denmark Background: Maternal obesity during gestation represents a sig- nificant health risk for the offspring, becoming evident later in life and includes metabolic syndrome, cardiovascular disease and affec- tive disorders. Inflammation has recently been shown to play an important role in the pathophysiology of affective disorders. Sys- temic inflammation is a hallmark consequence of a high-fat diet and maternal obesity may lead to fetal inflammatory responses. Objective: The aim of this study was to investigate the influence of a high-fat diet on the affective-like behavior in the offspring. Meth- ods: Age matched female rats (Sprague Dawley, n = 20) were fed a high-fat diet or a control diet 8 weeks before breeding, and contin- ued on this diet throughout gestation and lactation. Offspring were weaned onto normal diet. Male and female offspring were tested at the age of PND56 in different behavioral settings for anxiety- (Ele- vated plus-maze) and depression-like (Forced swim test) behavior. Insulin sensitivity was evaluated using the oral glucose tolerance test (OGTT). Results: Offspring from high fat fed rats were signifi- cantly heavier than control offspring at weaning. Male offspring exposed to perinatal high-fat showed increased anxiety-like behav- ior. There was no significant difference in the depression-like behav- ior in males or females. Conclusion: The data suggest that dietary environment during development, has behavioral consequences. This effect seems to be specific for anxiety. http://dx.doi.org/10.1016/j.bbi.2014.06.123 104. Overcrowding stress decreases macrophage activity and increases Salmonella Enteritidis invasion in broiler chickens J. Palermo-Neto a , W.M. Quinteiro-Filho a , A. Ribeiro a , V. Ferraz-de-Paula a , E. Baskeville a , M.L. Pinheiro a , A.T. Akamine a , C.S. Astolfi-Ferreira b , A.J. Ferreira b , A.V. Gomes b a Neuroimmunomodulation Research Group, Department of Pathology, School of Veterinary Medicine, University of São Paulo, São Paulo, Brazil b Laboratory of Ornitopathology, School of Veterinary Medicine, University of São Paulo, São Paulo, SP, Brazil Overcrowding stress is a reality in the poultry industry. Chickens exposed to long-term stressful situations present a reduction of wel- fare and immunosuppression. We designed this experiment to ana- lyze the effects of overcrowding stress (16 birds/m 2 ) on performance parameters, serum corticosterone levels, the relative weight of the bursa of Fabricius, plasma IgA and IgG levels, intestinal integrity, macrophage activity and experimental Salmonella Enteritidis inva- sion. The overcrowding stress decreased performance parameters, induced enteritis and decreased macrophage activity and the relative bursa weight in broiler chickens. When the chickens were similarly stressed and infected with Salmonella Enteritidis, there was an increase in feed conversion and a decrease in plasma IgG levels in the stressed and Salmonella-infected birds. Moderate enteritis was observed throughout the duodenum of chickens stressed and infected with Salmonella. Moreover, the overcrowding stress decreased the macrophage phagocytosis intensity and increased Salmonella Enteritidis counts in the livers of birds challenged with e30 Abstracts from the 21st Annual PNIRS Meeting 40 (2014) e1–e52

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Page 1: 103. Maternal perinatal high-fat diet increases anxiety-like behavior in male offspring

vaccine experimental inflammation model together with computa-tional modelling of an instrumental learning task performed duringfMRI (1). Twenty-two healthy participants were each tested 3-h afterblindly administered typhoid vaccine (0.025 mg) and placebo (0.5 ml0.9% NaCl) injection. Typhoid but not placebo was associated with athreefold increase in plasma IL-6 (t(21) = 5.20, p < 0.001) confirminginduction of mild inflammation. Following inflammation partici-pants demonstrated greater avoidance of a punishing cue (loss £1)and significantly reduced selection of a rewarded cueF(21,1) = 6.41, p = 0.019. Computational modelling of individuals’choices using a Q-learning model (free parameters alpha (learning-rate), beta (choice-randomness) and R (reward value)) demonstratedsignificant reduction in reward cue value and increase in value ofpunishment cues following inflammation F(21,1) = 3.63, p < 0.05.fMRI confirmed previous correlations of appetitive and aversive pre-diction error (PE) within ventral striatal (VS) and anterior insula (AI)regions of interest respectively (FWE p < 0.05) across conditions.However, inflammation significantly impaired VS responses to appe-titive PE and enhanced AI responses to aversive PE (FWE p < 0.05)suggesting that inflammation modulates the value of aversive andappetitive cues via actions on VS and AI prediction error signalsrespectively. (1) Pessiglione et al., 2006. Nature 442, 1042–45.

http://dx.doi.org/10.1016/j.bbi.2014.06.121

102. Enriched maternal care decreases opioid self-administrationin adulthood and alters neuroimmune signaling in the nucleusaccumbensM.J. Lacagnina a, G.M. Houtz a, C. Wells b, S. Slade b, E.D. Levin b,S.D. Bilbo a

a Duke University, Department of Psychology and Neuroscience, 210Research Drive, Durham, NC 27708, USAb Duke University Medical Center, USA

Despite decades of progress, the biological mechanisms underly-ing addiction are unknown. Glia, including astrocytes and microglia,profoundly influence neuronal function and may play a critical rolein the development of drug addiction. Previously, we have shownthat a neonatal handling procedure (which promotes enrichedmaternal care) reduces glial activation to an acute morphine chal-lenge and prevents reinstatement of morphine conditioned placepreference; likewise, similar results were obtained by pharmacolog-ical manipulation of glia within the nucleus accumbens (NAc). Here,we investigated the effects of opioid self-administration on centralimmune signaling within the NAc and its modulation by early-lifeexperience. Male rat pups were handled (15 min/day) from postnatalday (P) 2 to P20 or left undisturbed. In adulthood, all rats were testedfor self-administration of intravenous remifentanil (a short-actingopioid) in daily 1 h sessions for 2 weeks. Brains were then collectedto examine persistent alterations in glial activation. Neonatal han-dling reduced acquisition of remifentanil; this effect was specificfor opioids, as acquisition of food reward was unaffected. Remifenta-nil self-administration substantially increased glial antigen expres-sion (Iba1 and GFAP) and proinflammatory gene expression in NAc,including the innate immune receptor TLR4. However, only handledrats showed increased expression of the anti-inflammatory cytokineIL-10. These data establish neural–glial interactions in the NAc as anessential component of self-motivated drug acquisition that can bealtered by early-life environmental conditions.

http://dx.doi.org/10.1016/j.bbi.2014.06.122

103. Maternal perinatal high-fat diet increases anxiety-likebehavior in male offspringG. Winther a, S. Lund b, H.K. Müller a, G. Wegener a

a Translational Neuropsychiatric Unit, Department of Clinical Medicine,Skovagervej 2, Aarhus University, Riiskov, Aarhus 8240, Denmarkb Department of Endocrinology and Internal Medicine, Aarhus UniversityHospital, 9 Nørrebrogade 44, Bldg. 3.0, 8000 Aarhus C, Denmark

Background: Maternal obesity during gestation represents a sig-nificant health risk for the offspring, becoming evident later in lifeand includes metabolic syndrome, cardiovascular disease and affec-tive disorders. Inflammation has recently been shown to play animportant role in the pathophysiology of affective disorders. Sys-temic inflammation is a hallmark consequence of a high-fat dietand maternal obesity may lead to fetal inflammatory responses.Objective: The aim of this study was to investigate the influence ofa high-fat diet on the affective-like behavior in the offspring. Meth-ods: Age matched female rats (Sprague Dawley, n = 20) were fed ahigh-fat diet or a control diet 8 weeks before breeding, and contin-ued on this diet throughout gestation and lactation. Offspring wereweaned onto normal diet. Male and female offspring were testedat the age of PND56 in different behavioral settings for anxiety- (Ele-vated plus-maze) and depression-like (Forced swim test) behavior.Insulin sensitivity was evaluated using the oral glucose tolerancetest (OGTT). Results: Offspring from high fat fed rats were signifi-cantly heavier than control offspring at weaning. Male offspringexposed to perinatal high-fat showed increased anxiety-like behav-ior. There was no significant difference in the depression-like behav-ior in males or females. Conclusion: The data suggest that dietaryenvironment during development, has behavioral consequences.This effect seems to be specific for anxiety.

http://dx.doi.org/10.1016/j.bbi.2014.06.123

104. Overcrowding stress decreases macrophage activity andincreases Salmonella Enteritidis invasion in broiler chickensJ. Palermo-Neto a, W.M. Quinteiro-Filho a, A. Ribeiro a,V. Ferraz-de-Paula a, E. Baskeville a, M.L. Pinheiro a, A.T. Akamine a,C.S. Astolfi-Ferreira b, A.J. Ferreira b, A.V. Gomes b

a Neuroimmunomodulation Research Group, Department of Pathology,School of Veterinary Medicine, University of São Paulo, São Paulo, Brazilb Laboratory of Ornitopathology, School of Veterinary Medicine,University of São Paulo, São Paulo, SP, Brazil

Overcrowding stress is a reality in the poultry industry. Chickensexposed to long-term stressful situations present a reduction of wel-fare and immunosuppression. We designed this experiment to ana-lyze the effects of overcrowding stress (16 birds/m2) on performanceparameters, serum corticosterone levels, the relative weight of thebursa of Fabricius, plasma IgA and IgG levels, intestinal integrity,macrophage activity and experimental Salmonella Enteritidis inva-sion. The overcrowding stress decreased performance parameters,induced enteritis and decreased macrophage activity and the relativebursa weight in broiler chickens. When the chickens were similarlystressed and infected with Salmonella Enteritidis, there was anincrease in feed conversion and a decrease in plasma IgG levels inthe stressed and Salmonella-infected birds. Moderate enteritis wasobserved throughout the duodenum of chickens stressed andinfected with Salmonella. Moreover, the overcrowding stressdecreased the macrophage phagocytosis intensity and increasedSalmonella Enteritidis counts in the livers of birds challenged with

e30 Abstracts from the 21st Annual PNIRS Meeting 40 (2014) e1–e52