Post-occlusion administration of sodium butyrate attenuates cognitive impairment in a rat model of chronic cerebral hypoperfusion

Hui Liu, Jun Jian Zhang, Xiong Li, Ying Yang, Xiao Feng Xie, Ke Hu

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

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 840 mg/kg for 4 weeks, 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.

Original languageEnglish
Pages (from-to)53-59
Number of pages7
JournalPharmacology Biochemistry and Behavior
Volume135
DOIs
StatePublished - May 30 2015
Externally publishedYes

Keywords

  • Chronic cerebral hypoperfusion
  • Cognitive impairment
  • Histone acetylation
  • NF-E2 related factor 2
  • Sodium butyrate

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