Histone deacetylase 3 inhibition re-establishes synaptic tagging and capture in aging through the activation of nuclear factor kappa B

Sci Rep. 2015 Nov 18:5:16616. doi: 10.1038/srep16616.

Abstract

Aging is associated with impaired plasticity and memory. Altered epigenetic mechanisms are implicated in the impairment of memory with advanced aging. Histone deacetylase 3 (HDAC3) is an important negative regulator of memory. However, the role of HDAC3 in aged neural networks is not well established. Late long-term potentiation (late-LTP), a cellular correlate of memory and its associative mechanisms such as synaptic tagging and capture (STC) were studied in the CA1 area of hippocampal slices from 82-84 week old rats. Our findings demonstrate that aging is associated with deficits in the magnitude of LTP and impaired STC. Inhibition of HDAC3 augments the late-LTP and re-establishes STC. The augmentation of late-LTP and restoration of STC is mediated by the activation of nuclear factor kappa B (NFκB) pathway. We provide evidence for the promotion of associative plasticity in aged neural networks by HDAC3 inhibition and hence propose HDAC3 and NFκB as the possible therapeutic targets for treating age -related cognitive decline.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / drug effects*
  • Aging / metabolism*
  • Animals
  • Enzyme Activation
  • Hippocampus / drug effects
  • Hippocampus / physiology
  • Histone Deacetylase Inhibitors / pharmacology*
  • Histone Deacetylases / metabolism*
  • Male
  • NF-kappa B / metabolism*
  • Neuronal Plasticity / drug effects
  • Protein Biosynthesis / drug effects
  • Rats
  • Receptors, N-Methyl-D-Aspartate / metabolism
  • Signal Transduction / drug effects
  • Synapses / drug effects*
  • Synapses / metabolism*

Substances

  • Histone Deacetylase Inhibitors
  • NF-kappa B
  • Receptors, N-Methyl-D-Aspartate
  • Histone Deacetylases
  • histone deacetylase 3