Hypervulnerability of the adolescent prefrontal cortex to nutritional stress via reelin deficiency.
Identifieur interne : 000A57 ( Main/Exploration ); précédent : 000A56; suivant : 000A58Hypervulnerability of the adolescent prefrontal cortex to nutritional stress via reelin deficiency.
Auteurs : M A Labouesse [Suisse] ; O. Lassalle [France] ; J. Richetto [Suisse] ; J. Iafrati [France] ; U. Weber-Stadlbauer [Suisse] ; T. Notter [Suisse] ; T. Gschwind [Suisse] ; L. Pujadas [Espagne] ; E. Soriano [Espagne] ; A C Reichelt [Australie] ; C. Labouesse [Suisse] ; W. Langhans [Suisse] ; P. Chavis [France] ; U. Meyer [Suisse]Source :
- Molecular psychiatry [ 1476-5578 ] ; 2017.
Descripteurs français
- KwdFr :
- Alimentation riche en graisse (effets indésirables), Animaux, Cortex préfrontal (croissance et développement), Cortex préfrontal (métabolisme), Malnutrition (métabolisme), Molécules d'adhérence cellulaire neuronale (métabolisme), Mâle, Plasticité neuronale, Protéines de la matrice extracellulaire (métabolisme), Protéines de tissu nerveux (métabolisme), Récepteurs du N-méthyl-D-aspartate (métabolisme), Serine endopeptidases (métabolisme), Souris, Souris de lignée C57BL, Souris transgéniques, Synapses (métabolisme).
- MESH :
- croissance et développement : Cortex préfrontal.
- effets indésirables : Alimentation riche en graisse.
- métabolisme : Cortex préfrontal, Malnutrition, Molécules d'adhérence cellulaire neuronale, Protéines de la matrice extracellulaire, Protéines de tissu nerveux, Récepteurs du N-méthyl-D-aspartate, Serine endopeptidases, Synapses.
- Animaux, Mâle, Plasticité neuronale, Souris, Souris de lignée C57BL, Souris transgéniques.
English descriptors
- KwdEn :
- Animals, Cell Adhesion Molecules, Neuronal (metabolism), Diet, High-Fat (adverse effects), Extracellular Matrix Proteins (metabolism), Male, Malnutrition (metabolism), Mice, Mice, Inbred C57BL, Mice, Transgenic, Nerve Tissue Proteins (metabolism), Neuronal Plasticity, Prefrontal Cortex (growth & development), Prefrontal Cortex (metabolism), Receptors, N-Methyl-D-Aspartate (metabolism), Serine Endopeptidases (metabolism), Synapses (metabolism).
- MESH :
- chemical , metabolism : Cell Adhesion Molecules, Neuronal, Extracellular Matrix Proteins, Nerve Tissue Proteins, Receptors, N-Methyl-D-Aspartate, Serine Endopeptidases.
- adverse effects : Diet, High-Fat.
- growth & development : Prefrontal Cortex.
- metabolism : Malnutrition, Prefrontal Cortex, Synapses.
- Animals, Male, Mice, Mice, Inbred C57BL, Mice, Transgenic, Neuronal Plasticity.
Abstract
Overconsumption of high-fat diets (HFDs) can critically affect synaptic and cognitive functions within telencephalic structures such as the medial prefrontal cortex (mPFC). The underlying mechanisms, however, remain largely unknown. Here we show that adolescence is a sensitive period for the emergence of prefrontal cognitive deficits in response to HFD. We establish that the synaptic modulator reelin (RELN) is a critical mediator of this vulnerability because (1) periadolescent HFD (pHFD) selectively downregulates prefrontal RELN(+) cells and (2) augmenting mPFC RELN levels using transgenesis or prefrontal pharmacology prevents the pHFD-induced prefrontal cognitive deficits. We further identify N-methyl-d-aspartate-dependent long-term depression (NMDA-LTD) at prefrontal excitatory synapses as a synaptic signature of this association because pHFD abolishes NMDA-LTD, a function that is restored by RELN overexpression. We believe this study provides the first mechanistic insight into the vulnerability of the adolescent mPFC towards nutritional stress, such as HFDs. Our findings have primary relevance to obese individuals who are at an increased risk of developing neurological cognitive comorbidities, and may extend to multiple neuropsychiatric and neurological disorders in which RELN deficiency is a common feature.
DOI: 10.1038/mp.2016.193
PubMed: 27843148
Affiliations:
- Australie, Espagne, France, Suisse
- Canton de Vaud, Canton de Zurich, Catalogne, Provence-Alpes-Côte d'Azur
- Barcelone, Lausanne, Marseille, Zurich
- Université d'Aix-Marseille, Université de Zurich
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Le document en format XML
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Lassalle</name><affiliation wicri:level="4"><nlm:affiliation>INSERM, INMED UMR S 901, Aix-Marseille Université, Marseille, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>INSERM, INMED UMR S 901, Aix-Marseille Université, Marseille</wicri:regionArea><placeName><region type="region">Provence-Alpes-Côte d'Azur</region><region type="old region">Provence-Alpes-Côte d'Azur</region><settlement type="city">Marseille</settlement><settlement type="city">Marseille</settlement></placeName><orgName type="university">Université d'Aix-Marseille</orgName></affiliation></author><author><name sortKey="Richetto, J" sort="Richetto, J" uniqKey="Richetto J" first="J" last="Richetto">J. Richetto</name><affiliation wicri:level="1"><nlm:affiliation>Institute of Pharmacology and Toxicology, University of Zurich-Vetsuisse, Zurich, Switzerland.</nlm:affiliation><country xml:lang="fr">Suisse</country><wicri:regionArea>Institute of Pharmacology and Toxicology, University of Zurich-Vetsuisse, Zurich</wicri:regionArea><wicri:noRegion>Zurich</wicri:noRegion></affiliation></author><author><name sortKey="Iafrati, J" sort="Iafrati, J" uniqKey="Iafrati J" first="J" last="Iafrati">J. Iafrati</name><affiliation wicri:level="4"><nlm:affiliation>INSERM, INMED UMR S 901, Aix-Marseille Université, Marseille, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>INSERM, INMED UMR S 901, Aix-Marseille Université, Marseille</wicri:regionArea><placeName><region type="region">Provence-Alpes-Côte d'Azur</region><region type="old region">Provence-Alpes-Côte d'Azur</region><settlement type="city">Marseille</settlement><settlement type="city">Marseille</settlement></placeName><orgName type="university">Université d'Aix-Marseille</orgName></affiliation></author><author><name sortKey="Weber Stadlbauer, U" sort="Weber Stadlbauer, U" uniqKey="Weber Stadlbauer U" first="U" last="Weber-Stadlbauer">U. Weber-Stadlbauer</name><affiliation wicri:level="1"><nlm:affiliation>Physiology and Behavior Laboratory, ETH Zurich, Schwerzenbach, Switzerland.</nlm:affiliation><country xml:lang="fr">Suisse</country><wicri:regionArea>Physiology and Behavior Laboratory, ETH Zurich, Schwerzenbach</wicri:regionArea><wicri:noRegion>Schwerzenbach</wicri:noRegion></affiliation></author><author><name sortKey="Notter, T" sort="Notter, T" uniqKey="Notter T" first="T" last="Notter">T. Notter</name><affiliation wicri:level="1"><nlm:affiliation>Institute of Pharmacology and Toxicology, University of Zurich-Vetsuisse, Zurich, Switzerland.</nlm:affiliation><country xml:lang="fr">Suisse</country><wicri:regionArea>Institute of Pharmacology and Toxicology, University of Zurich-Vetsuisse, Zurich</wicri:regionArea><wicri:noRegion>Zurich</wicri:noRegion></affiliation></author><author><name sortKey="Gschwind, T" sort="Gschwind, T" uniqKey="Gschwind T" first="T" last="Gschwind">T. Gschwind</name><affiliation wicri:level="4"><nlm:affiliation>Institute of Pharmacology and Toxicology, University of Zurich, Zurich, Switzerland.</nlm:affiliation><country xml:lang="fr">Suisse</country><wicri:regionArea>Institute of Pharmacology and Toxicology, University of Zurich, Zurich</wicri:regionArea><orgName type="university">Université de Zurich</orgName><placeName><settlement type="city">Zurich</settlement><region nuts="3" type="region">Canton de Zurich</region></placeName></affiliation></author><author><name sortKey="Pujadas, L" sort="Pujadas, L" uniqKey="Pujadas L" first="L" last="Pujadas">L. Pujadas</name><affiliation wicri:level="3"><nlm:affiliation>Department of Cell Biology, Physiology and Immunology, University of Barcelona, Barcelona, Spain.</nlm:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Department of Cell Biology, Physiology and Immunology, University of Barcelona, Barcelona</wicri:regionArea><placeName><settlement type="city">Barcelone</settlement><region nuts="2" type="region">Catalogne</region></placeName></affiliation></author><author><name sortKey="Soriano, E" sort="Soriano, E" uniqKey="Soriano E" first="E" last="Soriano">E. Soriano</name><affiliation wicri:level="3"><nlm:affiliation>Department of Cell Biology, Physiology and Immunology, University of Barcelona, Barcelona, Spain.</nlm:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Department of Cell Biology, Physiology and Immunology, University of Barcelona, Barcelona</wicri:regionArea><placeName><settlement type="city">Barcelone</settlement><region nuts="2" type="region">Catalogne</region></placeName></affiliation></author><author><name sortKey="Reichelt, A C" sort="Reichelt, A C" uniqKey="Reichelt A" first="A C" last="Reichelt">A C Reichelt</name><affiliation wicri:level="1"><nlm:affiliation>School of Health and Biomedical Sciences, RMIT, Melbourne, VIC, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>School of Health and Biomedical Sciences, RMIT, Melbourne, VIC</wicri:regionArea><wicri:noRegion>VIC</wicri:noRegion></affiliation></author><author><name sortKey="Labouesse, C" sort="Labouesse, C" uniqKey="Labouesse C" first="C" last="Labouesse">C. Labouesse</name><affiliation wicri:level="3"><nlm:affiliation>Laboratory of Cell Biophysics, Ecole Polytechnique Federale de Lausanne, Lausanne, Switzerland.</nlm:affiliation><country xml:lang="fr">Suisse</country><wicri:regionArea>Laboratory of Cell Biophysics, Ecole Polytechnique Federale de Lausanne, Lausanne</wicri:regionArea><placeName><settlement type="city">Lausanne</settlement><region nuts="3" type="region">Canton de Vaud</region></placeName></affiliation></author><author><name sortKey="Langhans, W" sort="Langhans, W" uniqKey="Langhans W" first="W" last="Langhans">W. Langhans</name><affiliation wicri:level="1"><nlm:affiliation>Physiology and Behavior Laboratory, ETH Zurich, Schwerzenbach, Switzerland.</nlm:affiliation><country xml:lang="fr">Suisse</country><wicri:regionArea>Physiology and Behavior Laboratory, ETH Zurich, Schwerzenbach</wicri:regionArea><wicri:noRegion>Schwerzenbach</wicri:noRegion></affiliation></author><author><name sortKey="Chavis, P" sort="Chavis, P" uniqKey="Chavis P" first="P" last="Chavis">P. Chavis</name><affiliation wicri:level="4"><nlm:affiliation>INSERM, INMED UMR S 901, Aix-Marseille Université, Marseille, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>INSERM, INMED UMR S 901, Aix-Marseille Université, Marseille</wicri:regionArea><placeName><region type="region">Provence-Alpes-Côte d'Azur</region><region type="old region">Provence-Alpes-Côte d'Azur</region><settlement type="city">Marseille</settlement><settlement type="city">Marseille</settlement></placeName><orgName type="university">Université d'Aix-Marseille</orgName></affiliation></author><author><name sortKey="Meyer, U" sort="Meyer, U" uniqKey="Meyer U" first="U" last="Meyer">U. Meyer</name><affiliation wicri:level="1"><nlm:affiliation>Physiology and Behavior Laboratory, ETH Zurich, Schwerzenbach, Switzerland.</nlm:affiliation><country xml:lang="fr">Suisse</country><wicri:regionArea>Physiology and Behavior Laboratory, ETH Zurich, Schwerzenbach</wicri:regionArea><wicri:noRegion>Schwerzenbach</wicri:noRegion></affiliation></author></analytic><series><title level="j">Molecular psychiatry</title><idno type="eISSN">1476-5578</idno><imprint><date when="2017" type="published">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Cell Adhesion Molecules, Neuronal (metabolism)</term><term>Diet, High-Fat (adverse effects)</term><term>Extracellular Matrix Proteins (metabolism)</term><term>Male</term><term>Malnutrition (metabolism)</term><term>Mice</term><term>Mice, Inbred C57BL</term><term>Mice, Transgenic</term><term>Nerve Tissue Proteins (metabolism)</term><term>Neuronal Plasticity</term><term>Prefrontal Cortex (growth & development)</term><term>Prefrontal Cortex (metabolism)</term><term>Receptors, N-Methyl-D-Aspartate (metabolism)</term><term>Serine Endopeptidases (metabolism)</term><term>Synapses (metabolism)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Alimentation riche en graisse (effets indésirables)</term><term>Animaux</term><term>Cortex préfrontal (croissance et développement)</term><term>Cortex préfrontal (métabolisme)</term><term>Malnutrition (métabolisme)</term><term>Molécules d'adhérence cellulaire neuronale (métabolisme)</term><term>Mâle</term><term>Plasticité neuronale</term><term>Protéines de la matrice extracellulaire (métabolisme)</term><term>Protéines de tissu nerveux (métabolisme)</term><term>Récepteurs du N-méthyl-D-aspartate (métabolisme)</term><term>Serine endopeptidases (métabolisme)</term><term>Souris</term><term>Souris de lignée C57BL</term><term>Souris transgéniques</term><term>Synapses (métabolisme)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Cell Adhesion Molecules, Neuronal</term><term>Extracellular Matrix Proteins</term><term>Nerve Tissue Proteins</term><term>Receptors, N-Methyl-D-Aspartate</term><term>Serine Endopeptidases</term></keywords><keywords scheme="MESH" qualifier="adverse effects" xml:lang="en"><term>Diet, High-Fat</term></keywords><keywords scheme="MESH" qualifier="croissance et développement" xml:lang="fr"><term>Cortex préfrontal</term></keywords><keywords scheme="MESH" qualifier="effets indésirables" xml:lang="fr"><term>Alimentation riche en graisse</term></keywords><keywords scheme="MESH" qualifier="growth & development" xml:lang="en"><term>Prefrontal Cortex</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Malnutrition</term><term>Prefrontal Cortex</term><term>Synapses</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Cortex préfrontal</term><term>Malnutrition</term><term>Molécules d'adhérence cellulaire neuronale</term><term>Protéines de la matrice extracellulaire</term><term>Protéines de tissu nerveux</term><term>Récepteurs du N-méthyl-D-aspartate</term><term>Serine endopeptidases</term><term>Synapses</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Male</term><term>Mice</term><term>Mice, Inbred C57BL</term><term>Mice, Transgenic</term><term>Neuronal Plasticity</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Mâle</term><term>Plasticité neuronale</term><term>Souris</term><term>Souris de lignée C57BL</term><term>Souris transgéniques</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Overconsumption of high-fat diets (HFDs) can critically affect synaptic and cognitive functions within telencephalic structures such as the medial prefrontal cortex (mPFC). The underlying mechanisms, however, remain largely unknown. Here we show that adolescence is a sensitive period for the emergence of prefrontal cognitive deficits in response to HFD. We establish that the synaptic modulator reelin (RELN) is a critical mediator of this vulnerability because (1) periadolescent HFD (pHFD) selectively downregulates prefrontal RELN(+) cells and (2) augmenting mPFC RELN levels using transgenesis or prefrontal pharmacology prevents the pHFD-induced prefrontal cognitive deficits. We further identify N-methyl-d-aspartate-dependent long-term depression (NMDA-LTD) at prefrontal excitatory synapses as a synaptic signature of this association because pHFD abolishes NMDA-LTD, a function that is restored by RELN overexpression. We believe this study provides the first mechanistic insight into the vulnerability of the adolescent mPFC towards nutritional stress, such as HFDs. Our findings have primary relevance to obese individuals who are at an increased risk of developing neurological cognitive comorbidities, and may extend to multiple neuropsychiatric and neurological disorders in which RELN deficiency is a common feature.</div></front></TEI><affiliations><list><country><li>Australie</li><li>Espagne</li><li>France</li><li>Suisse</li></country><region><li>Canton de Vaud</li><li>Canton de Zurich</li><li>Catalogne</li><li>Provence-Alpes-Côte d'Azur</li></region><settlement><li>Barcelone</li><li>Lausanne</li><li>Marseille</li><li>Zurich</li></settlement><orgName><li>Université d'Aix-Marseille</li><li>Université de Zurich</li></orgName></list><tree><country name="Suisse"><noRegion><name sortKey="Labouesse, M A" sort="Labouesse, M A" uniqKey="Labouesse M" first="M A" last="Labouesse">M A Labouesse</name></noRegion><name sortKey="Gschwind, T" sort="Gschwind, T" uniqKey="Gschwind T" first="T" last="Gschwind">T. Gschwind</name><name sortKey="Labouesse, C" sort="Labouesse, C" uniqKey="Labouesse C" first="C" last="Labouesse">C. Labouesse</name><name sortKey="Langhans, W" sort="Langhans, W" uniqKey="Langhans W" first="W" last="Langhans">W. Langhans</name><name sortKey="Meyer, U" sort="Meyer, U" uniqKey="Meyer U" first="U" last="Meyer">U. Meyer</name><name sortKey="Notter, T" sort="Notter, T" uniqKey="Notter T" first="T" last="Notter">T. Notter</name><name sortKey="Richetto, J" sort="Richetto, J" uniqKey="Richetto J" first="J" last="Richetto">J. Richetto</name><name sortKey="Weber Stadlbauer, U" sort="Weber Stadlbauer, U" uniqKey="Weber Stadlbauer U" first="U" last="Weber-Stadlbauer">U. Weber-Stadlbauer</name></country><country name="France"><region name="Provence-Alpes-Côte d'Azur"><name sortKey="Lassalle, O" sort="Lassalle, O" uniqKey="Lassalle O" first="O" last="Lassalle">O. Lassalle</name></region><name sortKey="Chavis, P" sort="Chavis, P" uniqKey="Chavis P" first="P" last="Chavis">P. Chavis</name><name sortKey="Iafrati, J" sort="Iafrati, J" uniqKey="Iafrati J" first="J" last="Iafrati">J. Iafrati</name></country><country name="Espagne"><region name="Catalogne"><name sortKey="Pujadas, L" sort="Pujadas, L" uniqKey="Pujadas L" first="L" last="Pujadas">L. Pujadas</name></region><name sortKey="Soriano, E" sort="Soriano, E" uniqKey="Soriano E" first="E" last="Soriano">E. Soriano</name></country><country name="Australie"><noRegion><name sortKey="Reichelt, A C" sort="Reichelt, A C" uniqKey="Reichelt A" first="A C" last="Reichelt">A C Reichelt</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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