title: Valproate improves memory deficits in an Alzheimer's disease mouse model: investigation of possible mechanisms of action.
abstract: Alzheimer's disease (AD) is a very common progressive neurodegenerative disorder affecting the learning and memory abilities in the brain. Key findings from recent studies of epigenetic mechanisms of memory suggest chromatin remodeling disorders via histone hypoacetylation of the lysine residue contribute to the cognitive impairment in AD. Therefore, the deinhibition of histone acetylation induced by histone deacetylases (HDACs) inhibitors contributes to recovery of learning and memory. We show here that the antiepileptic drug sodium valproate (VPA) potently enhanced long-term recognition memory and spatial learning and memory in AD transgenic mice. Possible mechanisms showed VPA could significantly elevate histone acetylation through HDACs activity inhibition and increase plasticity-associated gene expression within the hippocampi of mice. Our study suggests that VPA, serving as a HDACs inhibitor, can be considered as a potential pharmaceutical agent for the improvement of cognitive function in AD.
authors.affiliation: Comparative Medical Center, Institute of Laboratory Animal Science, Peking Union Medical College (PUMC) and Chinese Academy of Medical Science (CAMS), Beijing, China.
authors.forename: Zhi-Gang
authors.initials: ZG
authors.lastname: Yao
authors.forename: Liang
authors.initials: L
authors.lastname: Liang
authors.forename: Yu
authors.initials: Y
authors.lastname: Liu
authors.forename: Ling
authors.initials: L
authors.lastname: Zhang
authors.forename: Hua
authors.initials: H
authors.lastname: Zhu
authors.forename: Lan
authors.initials: L
authors.lastname: Huang
authors.forename: Chuan
authors.initials: C
authors.lastname: Qin
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000818:Animals; D004195:Disease Models, Animal; D008568:Memory / Q000187:drug effects* / Q000502:physiology; D008569:Memory Disorders / Q000188:drug therapy* / Q000378:metabolism; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D014635:Valproic Acid / Q000494:pharmacology*
chemical_list: D016564:Amyloid beta-Protein Precursor; D014635:Valproic Acid