The potential protective effects of cannabinoid receptor agonist WIN55,212-2 on cognitive dysfunction is associated with the suppression of autophagy and inflammation in an experimental model of vascular dementia.

Abstract:

: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-α) and interleukin 1 beta (IL-1β), 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.

journal_name

Psychiatry Res

journal_title

Psychiatry research

authors

Wang DP,Yin H,Kang K,Lin Q,Su SH,Hai J

doi

10.1016/j.psychres.2018.06.012

subject

Has Abstract

pub_date

2018-09-01 00:00:00

pages

281-288

eissn

0165-1781

issn

1872-7123

pii

S0165-1781(17)31479-8

journal_volume

267

pub_type

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