Histone deacetylase 3 in hippocampus contributes to memory impairment after chronic constriction injury of sciatic nerve in mice

Guang Fen Zhang, Zhi Qiang Zhou, Jie Guo, Han Wen Gu, Ming Zhao Su, Bao Cong Yu, Feng Zhou, Bao Yu Han, Min Jia, Mu Huo Ji, Yuan Xiang Tao, Chun Jie Zhao, Jian Jun Yang

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

Chronic neuropathic pain is frequently accompanied by memory impairment, yet the underlying mechanisms remain unclear. Here, we showed that mice displayed memory impairment starting at 14 days and lasting for at least 21 days after chronic constriction injury (CCI) of unilateral sciatic nerve in mice. Systemic administration of the pan histone deacetylase (HDAC) inhibitor sodium butyrate attenuated this memory impairment. More specifically, we found that hippocampus HDAC3 was involved in this process because the levels of its mRNA and protein increased significantly in the hippocampus at 14 and 21 days after CCI, but not sham surgery. Systemic administration of the selective HDAC3 antagonist RGFP966 attenuated CCI-induced memory impairment, improved hippocampal long-term potentiation impairment, and rescued reductions of dendritic spine density and synaptic plasticity-associated protein in the hippocampus. In addition, HDAC3 overexpression in the hippocampus led to memory impairment without affecting basal nociceptive responses in naive mice. Our findings suggest that HDAC3 contributes to memory impairment after CCI by impairing synaptic plasticity in hippocampus. Histone deacetylase 3 might serve as a potential molecular target for therapeutic treatment of memory impairment under neuropathic pain conditions.

Original languageEnglish (US)
Pages (from-to)382-395
Number of pages14
JournalPain
Volume162
Issue number2
DOIs
StatePublished - Feb 1 2021

All Science Journal Classification (ASJC) codes

  • Clinical Neurology
  • Neurology
  • Anesthesiology and Pain Medicine

Keywords

  • Chronic constriction injury
  • HDAC3
  • Hippocampus
  • Memory impairment
  • Neuropathic pain
  • Synaptic plasticity

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