Class 1 histone deacetylases differentially modulate memory and synaptic genes in a spatial and temporal manner in aged and APP/PS1 mice

Bryan M. McClarty, Guadalupe Rodriguez, Hongxin Dong*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Epigenetics plays a vital role in aging and Alzheimer's disease (AD); however, whether epigenetic alterations during aging can initiate AD and exacerbate AD progression remains unclear. In this study, using 3-, 12- and 18- month-old APP/PS1 mice and age matched WT littermates, we conducted a series of memory tests, measured synapse-related gene expression, class 1 histone deacetylases (HDACs) abundance, and H3K9ac levels at target gene promoters in the hippocampus and prefrontal cortex (PFC). Our results showed impaired recognition and long-term spatial memory in 18-month-old WT mice and impaired recognition, short-term working, and long-term spatial reference memory in 12-and 18- month-old APP/PS1 mice. These memory impairments are associated with changes of synapse-related gene (nr2a, glur1, glur2, psd95) expression, HDAC abundance, and H3K9ac levels; more specifically, increased HDAC2 was associated with synapse-related gene expression changes through modulation of H3K9ac at the gene promoters during aging and AD progression in the hippocampus. Conversely, increased HDAC3 was associated with synapse-related gene expression changes through modulation of H3K9ac at the gene promoters during AD progression in the PFC. These findings suggest memory impairments in aging and AD may associated with a differential HDAC modulation of synapse-related gene expression in the brain.

Original languageEnglish (US)
Article number148951
JournalBrain research
Volume1837
DOIs
StatePublished - Aug 15 2024

Keywords

  • Aging
  • Alzheimer's Disease
  • Epigenetics
  • Histone acetylation
  • Memory

ASJC Scopus subject areas

  • General Neuroscience
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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