title: Post-occlusion administration of sodium butyrate attenuates cognitive impairment in a rat model of chronic cerebral hypoperfusion.
abstract: Chronic cerebral hypoperfusion (CCH) has been commonly associated with Alzheimer's disease and other types of dementia, but therapies that can improve cerebral blood flow displayed little effect on impaired cognition. Epigenetic intervention with histone deacetylase inhibitors, such as sodium butyrate (SB), on the other hand has been shown to improve cognition in several animal models of dementia. To investigate the effect of SB on cognitive impairment induced by CCH in rats, adult male SD rats were given intraperitoneal injections of SB at a daily dose of 840mg/kg for 4weeks, from the 29th day after permanent occlusion of bilateral common carotid arteries (2VO). Learning and memory were assessed by Morris water maze and novel object recognition. Following behavioral tests, western blotting of histone acetylation, of transcription factors, of neuronal/synaptic proteins, were performed using rat hippocampus and cortex. The data showed that SB treatment alleviated hippocampal dependent spatial learning disability in 2VO rats, and altered HDAC1/2 mRNA level, histone H4 acetylation and Nrf2 transcriptional activation in rat hippocampus. Accordingly, cognition-protective effect of SB appeared to be partially mediated by enhancing histone acetylation and hence by facilitating the transcription of Nrf2 downstream genes in the hippocampus. Thus, SB might be considered for putative treatment for CCH-related cognitive impairment.
authors.affiliation: Department of Neurology, Zhongnan Hospital, Wuhan University, Donghu Road 169#, Wuhan 430071, China; Hubei Clinical Research Center for Dementia and Cognitive Impairment, Donghu Road 169#, Wuhan 430071, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Neurology, Zhongnan Hospital, Wuhan University, Donghu Road 169#, Wuhan 430071, China; Hubei Clinical Research Center for Dementia and Cognitive Impairment, Donghu Road 169#, Wuhan 430071, China. Electronic address: wdsjkx@163.com.
authors.forename: Jun-Jian
authors.initials: JJ
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Zhongnan Hospital, Wuhan University, Donghu Road 169#, Wuhan 430071, China; Hubei Clinical Research Center for Dementia and Cognitive Impairment, Donghu Road 169#, Wuhan 430071, China.
authors.forename: Xiong
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Neurology, Zhongnan Hospital, Wuhan University, Donghu Road 169#, Wuhan 430071, China; Hubei Clinical Research Center for Dementia and Cognitive Impairment, Donghu Road 169#, Wuhan 430071, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Neurology, Zhongnan Hospital, Wuhan University, Donghu Road 169#, Wuhan 430071, China; Hubei Clinical Research Center for Dementia and Cognitive Impairment, Donghu Road 169#, Wuhan 430071, China.
authors.forename: Xiao-Feng
authors.initials: XF
authors.lastname: Xie
authors.affiliation: Department of Neurology, Zhongnan Hospital, Wuhan University, Donghu Road 169#, Wuhan 430071, China; Hubei Clinical Research Center for Dementia and Cognitive Impairment, Donghu Road 169#, Wuhan 430071, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Hu
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy* / Q000523:psychology*; D020148:Butyric Acid / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D016893:Carotid Stenosis / Q000523:psychology; D003072:Cognition Disorders / Q000188:drug therapy*; D056284:Histone Deacetylase 1 / Q000096:biosynthesis; D056464:Histone Deacetylase 2 / Q000096:biosynthesis; D006657:Histones / Q000378:metabolism; D007274:Injections, Intraperitoneal; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D011597:Psychomotor Performance / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D021641:Recognition, Psychology / Q000187:drug effects
chemical_list: D006657:Histones; D020148:Butyric Acid; C515890:Hdac1 protein, rat; C533426:Hdac2 protein, rat; D056284:Histone Deacetylase 1; D056464:Histone Deacetylase 2
keywords: Chronic cerebral hypoperfusion; Cognitive impairment; Histone acetylation; NF-E2 related factor 2; Sodium butyrate