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1. Pharmacological restoration of gut barrier function in stressed neonates partially reverses long-term alterations associated with maternal separation

Author

Muriel Darnaudéry, Eric Gaultier, Anna Maria Costa, Amandine M. Minni, Laurent Ferrier, Vassilia Theodorou, Yann Matime, Isabelle Grit, Jean-Christophe Helbling, Amandine Lépinay, Maïwenn Olier, Marie-Pierre Moisan, Camille Monchaux de Oliveira, Sophie Layé, Patricia Parnet, Marion Rincel, Nutrition et Neurobiologie intégrée (NutriNeuro), Université Bordeaux Segalen - Bordeaux 2-Institut National de la Recherche Agronomique (INRA)-Université Sciences et Technologies - Bordeaux 1-Institut Polytechnique de Bordeaux-Ecole nationale supérieure de chimie, biologie et physique, Neuro-Gastroentérologie & Nutrition (ToxAlim-NGN), ToxAlim (ToxAlim), Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Endocrinologie & Toxicologie de la Barrière Intestinale (ToxAlim-ENTeRisk), Physiopathologie des Adaptations Nutritionnelles (PhAN), and Université de Nantes (UN)-Institut National de la Recherche Agronomique (INRA)

Subjects
Male, Time Factors, medicine.medical_treatment, Gut flora, 16S sequencing, chemistry.chemical_compound, 0302 clinical medicine, Pregnancy, Corticosterone, Intestinal Mucosa, Intestinal barrier, Blood-brain barrier, Female urine sniffing test, biology, Tight junction, Depression, Maternal Deprivation, Azepines, Animal models, medicine.anatomical_structure, [SDV.TOX]Life Sciences [q-bio]/Toxicology, Female, medicine.medical_specialty, Myosin light-chain kinase, Intraperitoneal injection, Intestinal permeability, Naphthalenes, Blood–brain barrier, 03 medical and health sciences, Internal medicine, medicine, Animals, Early-life stress, Rats, Wistar, Myosin light chain kinase, Myosin-Light-Chain Kinase, Pharmacology, Dose-Response Relationship, Drug, business.industry, Lachnospiraceae, medicine.disease, biology.organism_classification, Gastrointestinal Microbiome, Rats, 030227 psychiatry, Irritable bowel syndrome, Endocrinology, Animals, Newborn, chemistry, business, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Stress, Psychological, 030217 neurology & neurosurgery
Abstract

International audience; Intestinal permeability plays an important role in gut-brain axis communication. Recent studies indicate that intestinal permeability increases in neonate pups during maternal separation (MS). The present study aims to determine whether pharmacological inhibition of myosin light chain kinase (MLCK), which regulates tight junction contraction and controls intestinal permeability, in stressed neonates, protects against the long-term effects of MS. Male Wistar rats were exposed to MS (3 h per day from post-natal day (PND)2 to PND14) or left undisturbed and received daily intraperitoneal injection of a MLCK inhibitor (ML-7, 5 mg/kg) or vehicle during the same period. At adulthood, emotional behaviors, corticosterone response to stress, and gut microbiota composition were analyzed. ML-7 restored gut barrier function in MS rats specifically during the neonatal period. Remarkably, ML-7 prevented MS-induced sexual reward-seeking impairment and reversed the alteration of corticosterone response to stress at adulthood. The effects of ML-7 were accompanied by the normalization of the abundance of members of Lachnospiraceae, Clostridiales, Desulfovibrio, Bacteroidales, Enterorhabdus, and Bifidobacterium in the feces of MS rats at adulthood. Altogether, our work suggests that improvement of intestinal barrier defects during development may alleviate some of the long-term effects of early-life stress and provides new insight on brain-gut axis communication in a context of stress.

Published
2019
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2. Maternal high-fat diet and early life stress differentially modulate spine density and dendritic morphology in the medial prefrontal cortex of juvenile and adult rats

Author

Yoottana Janthakhin, Muriel Darnaudéry, Sophie Layé, Corinne Joffre, Marion Rincel, Alexandra Séré, Amandine Lépinay, Vassilia Theodorou, Gwenaëlle Soudain, Sophie Yvon, Guillaume Ferreira, Stéphanie Da Silva, Agnès Aubert, Nutrition et Neurobiologie intégrée (NutriNeuro), Université Bordeaux Segalen - Bordeaux 2-Institut National de la Recherche Agronomique (INRA)-Université Sciences et Technologies - Bordeaux 1-Institut Polytechnique de Bordeaux-Ecole nationale supérieure de chimie, biologie et physique, ToxAlim (ToxAlim), Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Neuro-Gastroentérologie & Nutrition (ToxAlim-NGN), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3)

Subjects
0301 basic medicine, Male, Aging, Neurology, [SDV]Life Sciences [q-bio], Cell Count, 0302 clinical medicine, Pregnancy, Lactation, Prefrontal cortex, Maternal-Fetal Exchange, Neurons, Golgi staining, General Neuroscience, maternal separation, medicine.anatomical_structure, Gestation, gut permeability, Female, Anatomy, conditioned odor preference, maternal nutrition, medicine.medical_specialty, Histology, Prefrontal Cortex, Biology, Diet, High-Fat, Permeability, 03 medical and health sciences, Atrophy, Internal medicine, medicine, Juvenile, Animals, Rats, Wistar, [SDV.GEN]Life Sciences [q-bio]/Genetics, Water Deprivation, Extinction (psychology), Dendrites, medicine.disease, Rats, Gastrointestinal Tract, [SDV.GEN.GA]Life Sciences [q-bio]/Genetics/Animal genetics, 030104 developmental biology, Endocrinology, Animals, Newborn, Odorants, Neuroscience, 030217 neurology & neurosurgery, Stress, Psychological
Abstract

International audience; The medial prefrontal cortex (mPFC) is a key area for the regulation of numerous brain functions including stress response and cognitive processes. This brain area is also particularly affected by adversity during early life. Using an animal model in rats, we recently demonstrated that maternal exposure to a high-fat diet (HFD) prevents maternal separation (MS)-induced gene expression alterations in the developing PFC and attenuates several long-term deleterious behavioral effects of MS. In the present study, we ask whether maternal HFD could protect mPFC neurons of pups exposed to early life stress by examining dendritic morphology and spine density in juvenile [postnatal day (PND) 21] and adult rats submitted to MS. Dams were fed either a control or an HFD throughout gestation and lactation, and pups were submitted to MS from PND2 to PND14. We report that maternal HFD prevents MS-induced spine loss at PND21 and dendritic atrophy at adulthood. Furthermore, we show in adult MS rats that PFC-dependent memory extinction deficits are prevented by maternal HFD. Finally, perinatal HFD exposure reverses gut leakiness following stress in pups and seems to exert an anti-stress effect in dams. Overall, our work demonstrates that maternal HFD affects the developing brain and suggests that nutrition, possibly through gut–brain interactions, could modulate mPFC sensitivity to early stress.

Published
2017
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3. Impact of perinatal exposure to high-fat diet and stress on responses to nutritional challenges, food-motivated behaviour and mesolimbic dopamine function

Author

Marion Rincel, Amandine Lépinay, Hortense Fanet, Muriel Darnaudéry, Stéphanie Caillé, Sylvie Vancassel, Martine Cador, Sophie Layé, L Alonso, L Xia, Marina Romaní-Pérez, Nutrition et Neurobiologie intégrée (NutriNeur0), Ecole nationale supérieure de chimie, biologie et physique-Institut Polytechnique de Bordeaux-Université Sciences et Technologies - Bordeaux 1-Institut National de la Recherche Agronomique (INRA)-Université Bordeaux Segalen - Bordeaux 2, Institut de Neurosciences cognitives et intégratives d'Aquitaine (INCIA), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1-SFR Bordeaux Neurosciences-Centre National de la Recherche Scientifique (CNRS), Université de Bordeaux (UB), Nutrition et Neurobiologie intégrée (NutriNeuro), Université Bordeaux Segalen - Bordeaux 2-Institut National de la Recherche Agronomique (INRA)-Université Sciences et Technologies - Bordeaux 1-Institut Polytechnique de Bordeaux-Ecole nationale supérieure de chimie, biologie et physique, European Project: 267196,EC:FP7:PEOPLE,FP7-PEOPLE-2010-COFUND,AGREENSKILLS(2012), Université Bordeaux Segalen - Bordeaux 2-Institut National de la Recherche Agronomique (INRA)-Université Sciences et Technologies - Bordeaux 1 (UB)-Institut Polytechnique de Bordeaux-Ecole nationale supérieure de chimie, biologie et physique, and Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-SFR Bordeaux Neurosciences-Centre National de la Recherche Scientifique (CNRS)

Subjects
0301 basic medicine, Male, Stress prénatal, Maternal Nutritional Physiological Phenomena, Endocrinology, Diabetes and Metabolism, Dopamine, synergy, Medicine (miscellaneous), Régime maternel, human health, 0302 clinical medicine, Pregnancy, 2. Zero hunger, Maternal deprivation, Synergisme, Nutrition and Dietetics, Perinatal Exposure, Maternal Deprivation, digestive, oral, and skin physiology, Santé humaine, Prenatal Exposure Delayed Effects, Female, medicine.symptom, Signal Transduction, medicine.medical_specialty, Mesolimbic dopamine, Diet, High-Fat, 03 medical and health sciences, Internal medicine, medicine, Animals, Obésité, Obesity, Rats, Wistar, Dopamine metabolism, business.industry, High fat diet, Feeding Behavior, medicine.disease, Rats, Disease Models, Animal, 030104 developmental biology, Endocrinology, business, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Weight gain, 030217 neurology & neurosurgery, Stress, Psychological
Abstract

Background/Objectives: Energy-dense food exposure and stress during development have been suggested to contribute to obesity and metabolic disorders later in life. Although these factors are frequently associated, the effects of their combination have not yet been investigated. In this study, using an animal model, we examined the long-term impact of maternal high-fat diet (HFD) and early-life stress (ELS) on energy homoeostasis control and food motivation.Methods: Body weight growth under HFD, adipose tissue, body weight control in response to fasting and refeeding, food-motivated behaviour and mesolimbic dopamine function were examined in adult male offspring exposed to maternal HFD (during gestation and lactation) and/or ELS (maternal separation 3 h per day from postnatal day 2 to 14).Results: Maternal HFD or ELS alone had no significant effect on offspring body weight; however, the combination of these factors exacerbated body weight gain when animals were exposed to HFD after weaning. There are no other significant combinatory effects of these perinatal events. In contrast, independently of the maternal diet, ELS disrupted body weight control during a fasting–refeeding procedure, increased adipose tissue mass and altered lipid metabolism. Finally, maternal HFD and ELS both resulted in exacerbated food-motivated behaviour and blunted dopamine release in the nucleus accumbens during palatable food consumption.Conclusions: We report a synergistic effect of perinatal HFD exposure and stress on the susceptibility to gain weight under HFD. However, ELS has a stronger impact than maternal HFD exposure on energy homoeostasis and food motivation in adult offspring. Altogether, our results suggest a programming effect of stress and nutrition supporting the hypothesis of the developmental origin of health and disease.

Published
2016
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4. Pharmacological inhibition of gut leakiness prevents the long-term effects of early-life stress in rats

Author

Marion Rincel, C. Monchaux De Oliveira, Aloysio Costa, Vassilia Theodorou, Muriel Darnaudéry, Isabelle Grit, Amandine M. Minni, Amandine Lépinay, Y. Maytime, E. Gauthier, Sophie Layé, Laurent Ferrier, Patricia Parnet, Maïwenn Olier, Nutrition et Neurobiologie intégrée (NutriNeuro), Université Bordeaux Segalen - Bordeaux 2-Institut National de la Recherche Agronomique (INRA)-Université Sciences et Technologies - Bordeaux 1-Institut Polytechnique de Bordeaux-Ecole nationale supérieure de chimie, biologie et physique, Neuro-Gastroentérologie & Nutrition (ToxAlim-NGN), ToxAlim (ToxAlim), Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Endocrinologie & Toxicologie de la Barrière Intestinale (ToxAlim-ENTeRisk), Physiopathologie des Adaptations Nutritionnelles (PhAN), and Université de Nantes (UN)-Institut National de la Recherche Agronomique (INRA)

Subjects
Pharmacology, [SDV.GEN]Life Sciences [q-bio]/Genetics, medicine.medical_specialty, business.industry, [SDV]Life Sciences [q-bio], Early life stress, 030227 psychiatry, Term (time), [SDV.GEN.GA]Life Sciences [q-bio]/Genetics/Animal genetics, 03 medical and health sciences, Psychiatry and Mental health, 0302 clinical medicine, Endocrinology, Neurology, [SDV.TOX]Life Sciences [q-bio]/Toxicology, Internal medicine, medicine, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Pharmacology (medical), Neurology (clinical), business, ComputingMilieux_MISCELLANEOUS, 030217 neurology & neurosurgery, Biological Psychiatry
Abstract

International audience

Published
2017
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5. Environnement précoce et vulnérabilité neuropsychiatrique

Author

Marion Rincel, Anne Gabory, Valérie Daugé, Stefania Maccari, Vassilia Theodorou, Muriel Koehl, Muriel Darnaudéry, Amandine Lépinay, Nutrition et Neurobiologie intégrée (NutriNeuro), Université Bordeaux Segalen - Bordeaux 2-Institut National de la Recherche Agronomique (INRA)-Université Sciences et Technologies - Bordeaux 1-Institut Polytechnique de Bordeaux-Ecole nationale supérieure de chimie, biologie et physique, Biologie du Développement et Reproduction (BDR), École nationale vétérinaire d'Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA), Neuro-Gastroentérologie & Nutrition (ToxAlim-NGN), ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA), Neurocentre Magendie, Université de Bordeaux (UB), MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Istituto Neurologico Merditerraneo (NEUROMED, Sapienza University of Rome (DIAG), Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 (UGSF), Institut National de la Recherche Agronomique (INRA)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Nutrition et Neurobiologie intégrée (NutriNeur0), Université Paris-Saclay, INSERM, Neurocentre Magendie, U1215, Physiopathologie de la Plasticité Neuronale, F-33000 Bordeaux, France, Pharmacochimie moléculaire et structurale, Institut des sciences du Médicament -Toxicologie - Chimie - Environnement (IFR71), Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), stress périnatal et maladies neurodégénératives, Université de Lille, Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Bordeaux Segalen - Bordeaux 2-Institut National de la Recherche Agronomique (INRA)-Université Sciences et Technologies - Bordeaux 1 (UB)-Institut Polytechnique de Bordeaux-Ecole nationale supérieure de chimie, biologie et physique, Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Ecole d'Ingénieurs de Purpan (INP - PURPAN), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT), Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale (U1215 Inserm - UB), Université de Bordeaux (UB)-Institut François Magendie-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Recherche pour le Développement (IRD)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Ecole nationale supérieure de chimie, biologie et physique-Institut Polytechnique de Bordeaux-Université Sciences et Technologies - Bordeaux 1-Institut National de la Recherche Agronomique (INRA)-Université Bordeaux Segalen - Bordeaux 2, Biologie du développement et reproduction (BDR), École nationale vétérinaire d'Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS), Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA), Université de Toulouse (UT)-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, and Koehl, Muriel

Subjects
0301 basic medicine, modèle animal, Developmental psychology, stress, 0302 clinical medicine, MESH: Pregnancy, newborn, animal, MESH: Animals, MESH: Epigenesis, Genetic, humans, moulation épigénétique, [SDV.BDD]Life Sciences [q-bio]/Development Biology, ComputingMilieux_MISCELLANEOUS, adult, genetics and molecular biology (all), MESH: Infant, Newborn, MESH: Stress, Psychological, General Medicine, Early life, animals, female, neuropsychiatrie, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], pregnancy, stress psychologique, brain, MESH: Disease Susceptibility, Biology, in utéro, General Biochemistry, Genetics and Molecular Biology, MESH: Prenatal Exposure Delayed Effects, 03 medical and health sciences, MESH: Brain, prenatal exposure delayed effects, biochemistry, MESH: Mental Disorders, Epigenetics, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], medicine (all), psychological stress, disease models, MESH: Humans, epigenesis, MESH: Adult, [SDV.BDLR]Life Sciences [q-bio]/Reproductive Biology, disease susceptibility, infant, mental disorders, 030104 developmental biology, psychological, genetic, MESH: Disease Models, Animal, Paternal care, MESH: Female, 030217 neurology & neurosurgery, disease models, animal, epigenesis, genetic, infant, newborn, stress, psychological, biochemistry, genetics and molecular biology (all)
Abstract

The human newborn is highly dependent on parental care for its survival but also for the healthy development of its brain. A large body of literature demonstrates the impact of early life adversity, even during the prenatal period, on the adult's health. The susceptibility to neuropsychiatric diseases is often potentiated by early stress. If there is an agreement that a critical developmental period exists, the mechanisms underlying the long term effects of early life adversity are still poorly understood. Recent studies in animals highlight the involvement of epigenetic processes in the transmission of such vulnerabilities, notably via modifications in germ cells, which can be transmitted in the next generations., Du fait de son immaturité à la naissance, le nouveau-né est totalement dépendant des soins parentaux pour sa survie et pour son développement cérébral. Des altérations de la qualité de l’environnement précoce, non seulement lors de l’enfance, mais également en période prénatale, ont un impact, à long terme, sur la santé. Récemment, chez l’animal, des travaux ont mis en évidence des modulations épigénétiques après des stress précoces qui pourraient se transmettre sur plusieurs générations, via des modifications dans les cellules germinales.

Published
2016
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6. Perinatal high-fat diet increases hippocampal vulnerability to the adverse effects of subsequent high-fat feeding

Author

Niyazi Acar, Corinne Joffre, Guillaume Ferreira, Nathalie Castanon, Iciar Gárate, Patricia Parnet, Muriel Darnaudéry, Amandine Lépinay, Bénédicte Langelier, Philippe Guesnet, Thomas Larrieu, Lionel Bretillon, Sophie Layé, Nutrition et Neurobiologie intégrée ( NutriNeur0 ), Université Bordeaux Segalen - Bordeaux 2-Institut National de la Recherche Agronomique ( INRA ) -Université Sciences et Technologies - Bordeaux 1-Institut Polytechnique de Bordeaux-Ecole nationale supérieure de chimie, biologie et physique, Centre des Sciences du Goût et de l'Alimentation [Dijon] ( CSGA ), Institut National de la Recherche Agronomique ( INRA ) -Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique ( CNRS ), MICrobiologie de l'ALImentation au Service de la Santé humaine ( MICALIS ), Institut National de la Recherche Agronomique ( INRA ) -AgroParisTech, PG Consulting, UMR 1280 Physiologie des Adaptations Nutritionnelles, Institut National de la Recherche Agronomique ( INRA ) -Université de Nantes ( UN ) -Alimentation Humaine ( ALIM.H ) -Physiologie des Adaptations Nutritionnelles ( PhAN ), Nutrition et Neurobiologie intégrée (NutriNeur0), Ecole nationale supérieure de chimie, biologie et physique-Institut Polytechnique de Bordeaux-Université Sciences et Technologies - Bordeaux 1-Institut National de la Recherche Agronomique (INRA)-Université Bordeaux Segalen - Bordeaux 2, Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN)-Alimentation Humaine (ALIM.H), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Physiologie des Adaptations Nutritionnelles (PhAN), Nutrition et Neurobiologie intégrée (NutriNeuro), Université Bordeaux Segalen - Bordeaux 2-Institut National de la Recherche Agronomique (INRA)-Université Sciences et Technologies - Bordeaux 1-Institut Polytechnique de Bordeaux-Ecole nationale supérieure de chimie, biologie et physique, Physiologie des Adaptations Nutritionnelles (PhAN), and Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN)

Subjects
medicine.medical_specialty, Offspring, hippocampus, Endocrinology, Diabetes and Metabolism, Weaning, Hippocampal formation, Biology, Diet, High-Fat, memory, Endocrinology, Pregnancy, Fatty Acids, Omega-6, Internal medicine, Lactation, [ SDV.MHEP ] Life Sciences [q-bio]/Human health and pathology, Fatty Acids, Omega-3, medicine, Animals, water maze, TaqMan low-density array, Rats, Wistar, Maze Learning, Omega 3 fatty acid, Biological Psychiatry, Spatial Memory, 2. Zero hunger, chemistry.chemical_classification, Perinatal Exposure, Endocrine and Autonomic Systems, omega-6 fatty acid, omega-3 fatty acid, food and beverages, Rats, Psychiatry and Mental health, medicine.anatomical_structure, Animals, Newborn, chemistry, Prenatal Exposure Delayed Effects, [ SDV.NEU ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Omega-6 fatty acid, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], lipids (amino acids, peptides, and proteins), [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Polyunsaturated fatty acid
Abstract

Epidemiological observations report an increase in fat consumption associated with low intake of n-3 relative to n-6 polyunsaturated fatty acids (PUFAs) in women of childbearing age. However, the impact of these maternal feeding habits on cognitive function in the offspring is unknown. This study aims to investigate the impact of early exposure to a high-fat diet (HFD) with an unbalanced n-6/n-3 PUFAs ratio on hippocampal function in adult rats. Furthermore, we explored the effects of perinatal HFD combined with exposure to HFD after weaning. Dams were fed a control diet (C, 12% of energy from lipids, n-6/n-3 PUFAs ratio: 5) or HFD (HF, 39% of energy from lipids, n-6/n-3 PUFAs ratio: 39) throughout gestation and lactation. At weaning, offspring were placed either on control (C-C, HF-C) or high-fat (HF-HF) diets. In adulthood, hippocampus-dependent memory was assessed using the water-maze task and potential hippocampal alterations were determined by studying PUFA levels, gene expression, neurogenesis and astrocyte morphology. Perinatal HFD induced long-lasting metabolic alterations and some changes in gene expression in the hippocampus, but had no effect on memory. In contrast, spatial memory was impaired in animals exposed to HFD during the perinatal period and maintained on this diet. HF-HF rats also exhibited low n-3 and high n-6 PUFA levels, decreased neurogenesis and downregulated expression of several plasticity-related genes in the hippocampus. To determine the contribution of the perinatal diet to the memory deficits reported in HF-HF animals, an additional experiment was conducted in which rats were only exposed to HFD starting at weaning (C-HF). Interestingly, memory performance in this group was similar to controls. Overall, our results suggest that perinatal exposure to HFD with an unbalanced n-6/n-3 ratio sensitizes the offspring to the adverse effects of subsequent high-fat intake on hippocampal function.

Published
2015
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8. E.26 - Maternal High Fat Diet Reverses the Emotional Consequences of Maternal Separation in Offspring, but Increases Its Vulnerability to Diet-Induced Obesity

Author

Muriel Darnaudéry, Martine Cador, Amandine Lépinay, Sophie Layé, and Stéphanie Caillé

Subjects
Pharmacology, Psychiatry and Mental health, medicine.medical_specialty, Endocrinology, Offspring, Internal medicine, Separation (statistics), medicine, Vulnerability, High fat diet, Biology, medicine.disease, Obesity
Published
2013

9. Maternal high-fat diet prevents developmental programming by early-life stress

Author

Pierre Delage, Amandine Lépinay, Muriel Darnaudéry, Sophie Layé, Jean Fioramonti, Marion Rincel, Vassilia Theodorou, Nutrition et Neurobiologie intégrée (NutriNeuro), Université Bordeaux Segalen - Bordeaux 2-Institut National de la Recherche Agronomique (INRA)-Université Sciences et Technologies - Bordeaux 1-Institut Polytechnique de Bordeaux-Ecole nationale supérieure de chimie, biologie et physique, ToxAlim (ToxAlim), Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Neuro-Gastroentérologie & Nutrition (ToxAlim-NGN), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), This work was supported by the University of Bordeaux (BQR, Aide a l'installation nouvelle equipe), INRA (Action Prioritaire Dpt AlimH), Projet inter-regions Aquitaine et Midi-Pyrenees and by the French National Research Agency (IBISS project ANR-12-DSSA-0004). MR and ALL were supported by a stipend of the Ministere de l'Enseignement Superieur et de la Recherche, Nutrition et Neurobiologie intégrée (NutriNeur0), Ecole nationale supérieure de chimie, biologie et physique-Institut Polytechnique de Bordeaux-Université Sciences et Technologies - Bordeaux 1-Institut National de la Recherche Agronomique (INRA)-Université Bordeaux Segalen - Bordeaux 2, Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)

Subjects
0301 basic medicine, [SDV]Life Sciences [q-bio], Anxiety, Overweight, human health, 0302 clinical medicine, Lactation, rat, Maternal Behavior, Maternal deprivation, Maternal Deprivation, critère de stress, santé humaine, 3. Good health, système nerveux central, régime alimentaire, Psychiatry and Mental health, medicine.anatomical_structure, Prenatal Exposure Delayed Effects, Receptor, Serotonin, 5-HT1A, cerveau, Gestation, Female, Original Article, pregnancy, medicine.symptom, Psychology, medicine.medical_specialty, Offspring, Prefrontal Cortex, Diet, High-Fat, grossesse, Life Change Events, 03 medical and health sciences, Cellular and Molecular Neuroscience, comportement maternel, Internal medicine, medicine, Animals, Rats, Wistar, Biological Psychiatry, Brain-derived neurotrophic factor, Pregnancy, Brain-Derived Neurotrophic Factor, Body Weight, central nervous system, medicine.disease, Repressor Proteins, Disease Models, Animal, mothering ability, 030104 developmental biology, Endocrinology, Animals, Newborn, 030217 neurology & neurosurgery
Abstract

Anxiety disorders and depression are well-documented in subjects exposed to adverse childhood events. Recently, maternal obesity and/or maternal consumption of high-fat diets (HFD) have been also proposed as risk factors for offspring mental health. Here using an animal model in rats, we explored the combinatorial effects of a maternal HFD (40% of energy from fat without impact on maternal weight; during gestation and lactation) and maternal separation (MS) in offspring. In the prefrontal cortex (PFC) of pups, MS led to changes in the expression of several genes such as Bdnf (brain derived neurotrophic factor), 5HT-r1a (serotonin receptor 1a) and Rest4 (neuron-restrictive silencer element, repressor element 1, silencing transcription factor (Rest), splicing variant 4). Surprisingly, perinatal HFD strongly attenuated the developmental alterations induced by MS. Furthermore, maternal HFD totally prevented the endophenotypes (anxiety, spatial memory, social behavior, hypothalamic–pituitary–adrenal (HPA) axis response to stress, hippocampal neurogenesis and visceral pain) associated with MS at adulthood. Finally, we also demonstrated that HFD intake reduced anxiety and enhanced maternal care in stressed dams. Overall, our data suggest that a HFD restricted to gestation and lactation, which did not lead to overweight in dams, had limited effects in unstressed offspring, highlighting the role of maternal obesity, rather than fat exposure per se, on brain vulnerability during development.

Published
2016
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11. Early restoration of gut barrier function abrogates the long-term neurobehavioral effects of early-life stress in rats

Author

Laurent Ferrier, Amandine M. Minni, Julie Thomas, Yann Matime, Anna Maria Costa, Eric Gauthier, Vassilia Theodorou, Muriel Darnaudéry, Camille Monchaux de Oliveira, Sophie Layé, Isabelle Grit, Marion Rincel, Patricia Parnet, Amandine Lépinay, Maïwenn Olier, Nutrition et Neurobiologie intégrée (NutriNeuro), Université Bordeaux Segalen - Bordeaux 2-Institut National de la Recherche Agronomique (INRA)-Université Sciences et Technologies - Bordeaux 1-Institut Polytechnique de Bordeaux-Ecole nationale supérieure de chimie, biologie et physique, Neuro-Gastroentérologie & Nutrition (ToxAlim-NGN), ToxAlim (ToxAlim), Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Endocrinologie & Toxicologie de la Barrière Intestinale (ToxAlim-ENTeRisk), Physiopathologie des Adaptations Nutritionnelles (PhAN), Université de Nantes (UN)-Institut National de la Recherche Agronomique (INRA), and University of Zurich [Zurich] (UZH). CHE.

Subjects
Gut barrier, Endocrine and Autonomic Systems, business.industry, Endocrinology, Diabetes and Metabolism, Early life stress, 030227 psychiatry, Developmental psychology, Term (time), 03 medical and health sciences, Psychiatry and Mental health, 0302 clinical medicine, Endocrinology, [SDV.TOX]Life Sciences [q-bio]/Toxicology, Medicine, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], business, Neuroscience, ComputingMilieux_MISCELLANEOUS, 030217 neurology & neurosurgery, Biological Psychiatry, Function (biology)
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