Late-Life Environmental Enrichment Induces Acetylation Events and Nuclear Factor κB-Dependent Regulations in the Hippocampus of Aged Rats Showing Improved Plasticity and Learning
Autor: | Jean-Christophe Cassel, Romain Neidl, Kevin Dorgans, Anne Pereira de Vasconcelos, Anne Schneider, Jean-Philippe Loeffler, Olivier Bousiges, Alexandra Barbelivien, Anne-Laurence Boutillier, Monique Majchrzak, Frédéric Doussau |
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Přispěvatelé: | Laboratoire de neurosciences cognitives et adaptatives (LNCA), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Institut de recherches sur la catalyse et l'environnement de Lyon (IRCELYON), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Institut des Neurosciences Cellulaires et Intégratives (INCI), Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique (CNRS), Mécanismes Centraux et Périphériques de la Neurodégénérescence, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS) |
Jazyk: | angličtina |
Rok vydání: | 2016 |
Předmět: |
0301 basic medicine
Aging Neurogenesis Gene Expression Environment Hippocampus Epigenesis Genetic 03 medical and health sciences 0302 clinical medicine Neuroplasticity Animals Learning Rats Long-Evans Epigenetics Maze Learning ComputingMilieux_MISCELLANEOUS Spatial Memory Brain-derived neurotrophic factor Environmental enrichment Neuronal Plasticity biology General Neuroscience Brain-Derived Neurotrophic Factor NF-kappa B Transcription Factor RelA Acetylation Articles Chromatin Rats 030104 developmental biology Histone Synapses biology.protein [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] Female Neuroscience Chromatin immunoprecipitation 030217 neurology & neurosurgery |
Zdroj: | Journal of Neuroscience Journal of Neuroscience, Society for Neuroscience, 2016, 36 (15), pp.4351-4361. ⟨10.1523/JNEUROSCI.3239-15.2016⟩ |
ISSN: | 0270-6474 1529-2401 |
Popis: | 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 theBdnfgene 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 ofBdnfthroughExon-I-dependent transcription, associated with an enrichment of acetylated H3 at several sites ofBdnfpromoter 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.SIGNIFICANCE STATEMENTAging weakens memory functions. Optimizing the neuronal circuitry required for normal brain function can be achieved by increasing sensory, motor, and cognitive stimuli resulting from interactions with the environment (behavioral therapy). This can be experimentally modeled by exposing rodents to environmental enrichment (EE), as with large cages, numerous and varied toys, and interaction with other rodents. However, EE effects in aged rodents has been poorly studied, and it is not known whether beneficial mechanisms evidenced in the young adults can still be recruited during aging. Our study shows that aged rats respond to a belated period of EE by activating specific epigenetic and transcriptional signaling that promotes gene expression likely to facilitate plasticity and learning behaviors. |
Databáze: | OpenAIRE |
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