期刊
PSYCHIATRY RESEARCH
卷 267, 期 -, 页码 281-288出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.psychres.2018.06.012
关键词
Autophagy; Cannabinoid receptor; Cognition; Inflammation; Vascular dementia
类别
资金
- National Nature Science Foundation of China [81771410, 81271212, 81601146]
- Priority of Shanghai key discipline of medicine [2017ZZ02020]
Vascular dementia (VaD) is characteristic of chronic brain ischemia and progressive memory decline, which has a high incidence in the elderly. However, there are no effective treatments for VaD, and the underlying mechanism of its pathogenesis remains unclear. This study investigated the effects of a synthetic cannabinoid receptor agonist WIN55,212-2 (WIN) on VaD, and molecular mechanisms of the effects. VaD model was induced by 2-vessel occlusion (2VO). Spatial reference learning was evaluated by the Morris water maze, and recognition memory was assessed using the novel object recognition test. Autophagy-related proteins [microtubule-associated protein 1 light chain 3 (LC-3) and Beclin-1] were examined by immunohistochemistry and Western blot. Caspase-3 was detected by Western blot. Inflammatory factors, tumor necrosis factor alpha (TNF-alpha) and interleukin 1 beta (IL-1 beta), were estimated by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot. VaD increased the levels of LC-3, Beclin-1, and inflammatory factors, which were reversed by chronic treatment with WIN. WIN decreased the expression of Capase-3, and improved the learning and memory impairment of VaD rats. These data indicate that WIN exerts a neuroprotective effect on the cognitive deficits of VaD rats, which may be associated with the suppression of excessive autophagy and inflammation.
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