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The stress-induced transcription factor NR4A1 adjusts mitochondrial function and synapse number in prefrontal cortex

dc.rights.licenseopenen_US
dc.contributor.authorJEANNETEAU, Freddy
dc.contributor.authorBARRERE, Christian
dc.contributor.authorVOS, Mariska
dc.contributor.authorDE VRIES, Carlie J.M.
dc.contributor.authorROUILLARD, Claude
dc.contributor.authorLEVESQUE, Daniel
dc.contributor.authorDROMARD, Yann
hal.structure.identifierNutrition et Neurobiologie intégrée [NutriNeuro]
dc.contributor.authorMOISAN, Marie Pierre
IDREF: 060242264
dc.contributor.authorDURIC, Vanja
dc.contributor.authorFRANKLIN, Tina C.
dc.contributor.authorDUMAN, Ronald S.
dc.contributor.authorLEWIS, David A.
dc.contributor.authorGINSBERG, Stephen D.
dc.contributor.authorARANGO-LIEVANO, Margarita
dc.date.accessioned2021-09-28T10:11:52Z
dc.date.available2021-09-28T10:11:52Z
dc.date.issued2018-02-07
dc.identifier.issn0270-6474en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/112463
dc.description.abstractEnThe energetic costs of behavioral chronic stress are unlikely to be sustainable without neuronal plasticity. Mitochondria have the capacity to handle synaptic activity up to a limit before energetic depletion occurs. Protective mechanisms driven by the induction of neuronal genes likely evolved to buffer the consequences of chronic stress on excitatory neurons in prefrontal cortex (PFC), as this circuitry is vulnerable to excitotoxic insults. Little is known about the genes involved in mitochondrial adaptation to the buildup of chronic stress. Using combinations of genetic manipulations and stress for analyzing structural, transcriptional, mitochondrial, and behavioral outcomes, we characterized NR4A1 as a stress-inducible modifier of mitochondrial energetic competence and dendritic spine number in PFC. NR4A1 acted as a transcription factor for changing the expression of target genes previously involved in mitochondrial uncoupling, AMP-activated protein kinase activation, and synaptic growth. Maintenance of NR4A1 activity by chronic stress played a critical role in the regressive synaptic organization in PFC of mouse models of stress (male only). Knockdown, dominant-negative approach, and knockout of Nr4a1 in mice and rats (male only) protected pyramidal neurons against the adverse effects of chronic stress. In human PFC tissues of men and women, high levels of the transcriptionally active NR4A1 correlated with measures of synaptic loss and cognitive impairment. In the context of chronic stress, prolonged expression and activity of NR4A1 may lead to responses of mitochondria and synaptic connectivity that do not match environmental demand, resulting in circuit malfunction between PFC and other brain regions, constituting a pathological feature across disorders.
dc.language.isoENen_US
dc.subject.enDendritic spines
dc.subject.enMitochondria
dc.subject.enPrefrontal cortex
dc.subject.enPyramidal neurons
dc.subject.enStress
dc.title.enThe stress-induced transcription factor NR4A1 adjusts mitochondrial function and synapse number in prefrontal cortex
dc.typeArticle de revueen_US
dc.identifier.doi10.1523/JNEUROSCI.2793-17.2017en_US
dc.subject.halSciences du Vivant [q-bio]/Neurosciences [q-bio.NC]en_US
dc.identifier.pubmed29295823en_US
bordeaux.journalJournal of Neuroscienceen_US
bordeaux.page1335-1350en_US
bordeaux.volume38en_US
bordeaux.hal.laboratoriesNutriNeurO (Laboratoire de Nutrition et Neurobiologie Intégrée) - UMR 1286en_US
bordeaux.issue6en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.institutionINRAEen_US
bordeaux.teamNutrition, mémoire et glucocorticoïdesen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
bordeaux.identifier.funderIDInstitut National de la Santé et de la Recherche Médicaleen_US
bordeaux.identifier.funderIDFP7 People: Marie-Curie Actionsen_US
bordeaux.identifier.funderIDFondation pour la Recherche Médicaleen_US
hal.exportfalse
dc.rights.ccPas de Licence CCen_US
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