Stress dynamically regulates behavior and glutamatergic gene expression in hippocampus by opening a window of epigenetic plasticity
| Autor: | Sonia Piccinin, Robert Nisticò, Benedetta Bigio, Carla Nasca, Sergio Scaccianoce, Bruce S. McEwen, Danielle Zelli |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Male
Glutamic Acid P300-CBP Transcription Factors Anxiety BDNF H3K27 NMDA mGlu2 resilience Receptors Metabotropic Glutamate Receptors N-Methyl-D-Aspartate Synaptic Transmission Epigenesis Genetic Histones Mice Glutamatergic Glutamate homeostasis Animals p300-CBP Transcription Factors Brain-derived neurotrophic factor Multidisciplinary Behavior Animal Depression Brain-Derived Neurotrophic Factor Dentate gyrus Settore BIO/14 Glutamate receptor Long-term potentiation Biological Sciences Mice Mutant Strains Dentate Gyrus NMDA receptor Psychology Neuroscience Stress Psychological |
| Zdroj: | Proceedings of the National Academy of Sciences. 112:14960-14965 |
| ISSN: | 1091-6490 0027-8424 |
| Popis: | Excitatory amino acids play a key role in both adaptive and deleterious effects of stressors on the brain, and dysregulated glutamate homeostasis has been associated with psychiatric and neurological disorders. Here, we elucidate mechanisms of epigenetic plasticity in the hippocampus in the interactions between a history of chronic stress and familiar and novel acute stressors that alter expression of anxiety- and depressive-like behaviors. We demonstrate that acute restraint and acute forced swim stressors induce differential effects on these behaviors in naive mice and in mice with a history of chronic-restraint stress (CRS). They reveal a key role for epigenetic up- and down-regulation of the putative presynaptic type 2 metabotropic glutamate (mGlu2) receptors and the postsynaptic NR1/NMDA receptors in the hippocampus and particularly in the dentate gyrus (DG), a region of active neurogenesis and a target of antidepressant treatment. We show changes in DG long-term potentiation (LTP) that parallel behavioral responses, with habituation to the same acute restraint stressor and sensitization to a novel forced-swim stressor. In WT mice after CRS and in unstressed mice with a BDNF loss-of-function allele (BDNF Val66Met), we show that the epigenetic activator of histone acetylation, P300, plays a pivotal role in the dynamic up- and down-regulation of mGlu2 in hippocampus via histone-3-lysine-27-acetylation (H3K27Ac) when acute stressors are applied. These hippocampal responses reveal a window of epigenetic plasticity that may be useful for treatment of disorders in which glutamatergic transmission is dysregulated. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|