期刊
BEHAVIOURAL BRAIN RESEARCH
卷 379, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.bbr.2019.112319
关键词
Cornel iridoid glycoside; Vascular dementia; Chronic cerebral hypoperfusion; Neurotrophic factor; Glutamate receptor; PI3K/Akt/GSK3 beta/CREB signaling pathway
资金
- National Natural Science Foundation of China [81874351, 81673406, 81703729]
- Beijing Postdoctoral Research Foundation [2018-ZZ112]
- Beijing Natural Science Foundation [7164315]
- Beijing High-level Health and Technical Personal Plan [2011-1-7, 2014-2-014]
Chronic cerebral hypoperfusion is an important risk factor for vascular dementia (VaD) and other brain dysfunctions, for which there are currently no effective medications available. In the present study, we investigated the potential therapeutic effects of cornel iridoid glycoside (CIG) on VaD in rats modeled by permanent bilateral common carotid artery ligation (2-vessel occlusion, 2VO). The object recognition test (ORT) and Morris water maze (MWM) test were conducted to evaluate the learning and memory function. Western blot analysis and immunohistochemical staining were used to detect the expression of related proteins. Results showed that intragastric administration of CIG (30, 60, and 120 mg/kg) for 3 months significantly increased the discrimination index in ORT and decreased the escape latency in MWM test, ameliorating the learning and memory deficit in 2VO rats. Further data indicated that CIG increased the expression of neurotrophic factors (NGF and BDNF) and their receptors (TrkA and TrkB), glutamate receptor subunits (NMDAR1 and GluR2) in the cerebral cortex and hippocampus of 2VO rats. In addition, CIG elevated the expression of PI3K subunits p110 alpha and p85, further upregulated the phosphorylation of Akt, GSK3 beta-ser9 and CREB in the cerebral cortex and hippocampus at 3 months after 2VO surgery. Collectively, CIG treatment improved learning and memory deficit induced by chronic cerebral hypoperfusion via increasing neurotrophic factors thus protecting glutamate receptors and activating PI3K/Akt/GSK3 beta/CREB signaling pathway in rats. These results suggest that CIG may be beneficial to VaD therapy.
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