Histone deacetylase 3 in hippocampus contributes to memory impairment after chronic constriction injury of sciatic nerve in mice. Issue 2 (February 2021)

• Record Type: Journal Article
• Authors: Zhang, Guang-Fen; Zhou, Zhi-Qiang; Guo, Jie; Gu, Han-Wen; Su, Ming-Zhao; Yu, Bao-Cong; Zhou, Feng; Han, Bao-Yu; Jia, Min; Ji, Mu-Huo; Tao, Yuan-Xiang; Zhao, Chun-Jie; Yang, Jian-Jun
• Is Part Of: Pain. Volume 162:Issue 2(2021)
• Publication Date: 2021-02
• Subjects: Neuropathic pain -- Chronic constriction injury -- Memory impairment -- HDAC3 -- Synaptic plasticity -- Hippocampus; Pain -- Periodicals; Douleur -- Périodiques; Anesthésie -- Périodiques; Pain; Electronic journals; Periodicals; Electronic journals; 616.0472
• DOI: 10.1097/j.pain.0000000000002056
• Languages: English
• ISSNs: 0304-3959

Abstract

Abstract : 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. Abstract : Hippocampal histone deacetylase 3 contributes to chronic constriction injury of sciatic nerve-induced memory impairment by impairing synaptic plasticity in mice.