Inhibition of Histone Deacetylase 3 Restores Amyloid-β Oligomer-Induced Plasticity Deficit in Hippocampal CA1 Pyramidal Neurons

J Alzheimers Dis. 2016;51(3):783-91. doi: 10.3233/JAD-150838.


Neurodegenerative diseases such as Alzheimer's disease (AD) are associated with alterations in epigenetic factors leading to cognitive decline. Histone deacetylase 3 (HDAC3) is a known critical epigenetic negative regulator of learning and memory. In this study, attenuation of long-term potentiation by amyloid-β oligomer, and its reversal by specific HDAC3 inhibitor RGFP966, was performed in rat CA1 pyramidal neurons using whole cell voltage-clamp and field recording techniques. Our findings provide the first evidence that amyloid-β oligomer-induced synaptic plasticity impairment can be prevented by inhibition of HDAC3 enzyme both at the single neuron as well as in a population of neurons, thus identifying HDAC3 as a potential target for ameliorating AD related plasticity impairments.

Keywords: Amyloid-β oligomer; HDAC3; RGFP966; epigenetics; long-term potentiation; synaptic plasticity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acrylamides / pharmacology
  • Alzheimer Disease / drug therapy
  • Alzheimer Disease / enzymology
  • Amyloid beta-Peptides / toxicity*
  • Animals
  • Excitatory Postsynaptic Potentials / drug effects
  • Excitatory Postsynaptic Potentials / physiology
  • Hippocampus / drug effects*
  • Hippocampus / enzymology
  • Histone Deacetylase Inhibitors / pharmacology*
  • Histone Deacetylases / metabolism*
  • Long-Term Potentiation / drug effects*
  • Long-Term Potentiation / physiology
  • Male
  • Patch-Clamp Techniques
  • Peptide Fragments / toxicity*
  • Phenylenediamines / pharmacology
  • Pyramidal Cells / drug effects*
  • Pyramidal Cells / enzymology
  • Rats, Wistar
  • Tissue Culture Techniques


  • Acrylamides
  • Amyloid beta-Peptides
  • Histone Deacetylase Inhibitors
  • Peptide Fragments
  • Phenylenediamines
  • RGFP966
  • amyloid beta-protein (1-42)
  • Histone Deacetylases
  • histone deacetylase 3