Fiche publication
Date publication
avril 2016
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
Auteurs
Membres identifiés du Cancéropôle Est :
Dr LOEFFLER Jean-Philippe
Tous les auteurs :
Neidl R, Schneider A, Bousiges O, Majchrzak M, Barbelivien A, de Vasconcelos AP, Dorgans K, Doussau F, Loeffler JP, Cassel JC, Boutillier AL
Lien Pubmed
Résumé
Aging weakens memory functions. Exposing healthy rodents or pathological rodent models to environmental enrichment (EE) housing improves their cognitive functions by changing neuronal levels of excitation, cellular signaling, and plasticity, notably in the hippocampus. At the molecular level, brain derived-neurotrophic factor (BDNF) represents an important player that supports EE-associated changes. EE facilitation of learning was also shown to correlate with chromatin acetylation in the hippocampus. It is not known, however, whether such mechanisms are still into play during aging. In this study, we exposed a cohort of aged rats (18-month-old) to either a 6 month period of EE or standard housing conditions and investigated chromatin acetylation-associated events [histone acetyltranferase activity, gene expression, and histone 3 (H3) acetylation] and epigenetic modulation of the Bdnf gene under rest conditions and during learning. We show that EE leads to upregulation of acetylation-dependent mechanisms in aged rats, whether at rest or following a learning challenge. We found an increased expression of Bdnf through Exon-I-dependent transcription, associated with an enrichment of acetylated H3 at several sites of Bdnf promoter I, more particularly on a proximal nuclear factor κB (NF-κB) site under learning conditions. We further evidenced p65/NF-κB binding to chromatin at promoters of genes important for plasticity and hippocampus-dependent learning (e.g., Bdnf, CamK2D). Altogether, our findings demonstrate that aged rats respond to a belated period of EE by increasing hippocampal plasticity, together with activating sustained acetylation-associated mechanisms recruiting NF-κB and promoting related gene transcription. These responses are likely to trigger beneficial effects associated with EE during aging.
Mots clés
Acetylation, Aging, physiology, Animals, Brain-Derived Neurotrophic Factor, metabolism, Chromatin, metabolism, Environment, Epigenesis, Genetic, Female, Gene Expression, genetics, Hippocampus, growth & development, Learning, physiology, Maze Learning, physiology, NF-kappa B, metabolism, Neurogenesis, physiology, Neuronal Plasticity, physiology, Rats, Rats, Long-Evans, Spatial Memory, physiology, Synapses, physiology, Transcription Factor RelA, genetics
Référence
J. Neurosci.. 2016 Apr;36(15):4351-61
