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Psychiatry Res. 2018 Sep;267:281-288. doi: 10.1016/j.psychres.2018.06.012. Epub 2018 Jun 14.

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.

Author information

1
Department of Neurosurgery, Tong Ji Hospital, Tong Ji University School of Medicine, Shanghai 200065, China.
2
Department of Neurosurgery, Zao Zhuang Municipal Hospital, Zaozhuang, Shandong 277000, China.
3
Department of Research and Surveillance Evaluation, Shanghai Center for Health Promotion, Shanghai 200040, China.
4
Department of Pharmacy, Institutes of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
5
Department of Neurosurgery, Tong Ji Hospital, Tong Ji University School of Medicine, Shanghai 200065, China. Electronic address: sushaoshu@zoho.com.cn.
6
Department of Neurosurgery, Tong Ji Hospital, Tong Ji University School of Medicine, Shanghai 200065, China. Electronic address: haijiandoct@zoho.com.cn.

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.

KEYWORDS:

Autophagy; Cannabinoid receptor; Cognition; Inflammation; Vascular dementia

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