Experience Modulates the Effects of Histone Deacetylase Inhibitors on Gene and Protein Expression in the Hippocampus: Impaired Plasticity in Aging

Overview

Journal J Neurosci

Specialty Neurology

Date 2015 Aug 21

PMID 26290249

Citations 11

Authors

Angila S Sewal

Holger Patzke

Evelyn J Perez

Pul Park

Elin Lehrmann

Yongqing Zhang

Kevin G Becker

Bonnie R Fletcher

Jeffrey M Long

Peter R Rapp

Affiliations

Soon will be listed here.

Abstract

Significance Statement: The possibility that interventions targeting epigenetic regulation could be effective in treating a range of neurodegenerative disorders has attracted considerable interest. Here we demonstrate in the rat hippocampus that ongoing experience powerfully modifies the molecular response to one such intervention, histone deacetylase inhibitor (HDACi) administration. A single learning episode dramatically shifts the gene expression profile induced by acute HDACi treatment, yielding a qualitatively distinct hippocampal transcriptome compared with the influence of behavioral training alone. The downstream synaptic protein response to HDACi administration is similarly experience-dependent, and we report that this plasticity is disrupted in the aged hippocampus. The findings highlight that accommodating the modulatory influence of ongoing experience represents a challenge for therapeutic development in the area of cognitive neuroepigenetics.

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