Sodium butyrate improves memory function in an Alzheimer's disease mouse model when administered at an advanced stage of disease progression

J Alzheimers Dis. 2011;26(1):187-97. doi: 10.3233/JAD-2011-110080.


Dysregulation of histone acetylation has been implicated in the onset of age-associated memory impairment and the pathogenesis of neurodegenerative diseases. Elevation of histone acetylation via administration of histone deacetylase (HDAC) inhibitors is currently being pursued as a novel therapeutic avenue to treat memory impairment linked to Alzheimer's disease (AD). Here we show that severe amyloid pathology correlates with a pronounced dysregulation of histone acetylation in the forebrain of APPPS1-21 mice. Importantly, prolonged treatment with the pan-HDAC inhibitor sodium butyrate improved associative memory in APPPS1-21 mice even when administered at a very advanced stage of pathology. The recovery of memory function correlated with elevated hippocampal histone acetylation and increased expression of genes implicated in associative learning. These data advance our understanding of the potential applicability of HDAC inhibitors for the treatment of AD and suggest that HDAC inhibitors may have beneficial effects even when administered long after the onset of disease-associated symptoms.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation / drug effects
  • Alzheimer Disease / complications
  • Alzheimer Disease / genetics
  • Alzheimer Disease / pathology
  • Amyloid beta-Protein Precursor / genetics
  • Analysis of Variance
  • Animals
  • Avoidance Learning / drug effects
  • Brain / drug effects
  • Brain / metabolism
  • Butyrates / therapeutic use*
  • Disease Models, Animal
  • Electroshock / adverse effects
  • Exploratory Behavior / drug effects
  • Freezing Reaction, Cataleptic / drug effects
  • Gene Expression Regulation / drug effects*
  • Gene Expression Regulation / genetics
  • Histone Acetyltransferases / metabolism
  • Histones / metabolism
  • Locomotion / drug effects
  • Locomotion / genetics
  • Memory Disorders / drug therapy*
  • Memory Disorders / etiology
  • Mice
  • Mice, Transgenic
  • Microscopy, Confocal
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Presenilin-1 / genetics


  • Amyloid beta-Protein Precursor
  • Butyrates
  • Histones
  • Nerve Tissue Proteins
  • Presenilin-1
  • Histone Acetyltransferases