TY - JOUR
T1 - Post-occlusion administration of sodium butyrate attenuates cognitive impairment in a rat model of chronic cerebral hypoperfusion
AU - Liu, Hui
AU - Zhang, Jun Jian
AU - Li, Xiong
AU - Yang, Ying
AU - Xie, Xiao Feng
AU - Hu, Ke
N1 - Funding Information:
The authors thank Prof. Paul G. M. Luiten (Department of Molecular Neurobiology, University of Groningen, the Netherlands) for providing language help. This study was supported by the National Natural Science Foundation of China (Grant numbers: 81000471 , 81171029 ) and the Fundamental Research Fund for the Central Universities of China (Grant number: 201130302020003 ).
Publisher Copyright:
© 2015 Elsevier Inc.
PY - 2015/5/30
Y1 - 2015/5/30
N2 - 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.
AB - 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.
KW - Chronic cerebral hypoperfusion
KW - Cognitive impairment
KW - Histone acetylation
KW - NF-E2 related factor 2
KW - Sodium butyrate
UR - http://www.scopus.com/inward/record.url?scp=84930683260&partnerID=8YFLogxK
U2 - 10.1016/j.pbb.2015.05.012
DO - 10.1016/j.pbb.2015.05.012
M3 - Article
C2 - 26013850
AN - SCOPUS:84930683260
SN - 0091-3057
VL - 135
SP - 53
EP - 59
JO - Pharmacology, Biochemistry and Behavior
JF - Pharmacology, Biochemistry and Behavior
ER -