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
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
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大麻素受体激动剂 WIN55,212-2 对认知功能障碍的潜在保护作用与血管性痴呆实验模型中自噬和炎症的抑制有关
DOI：
10.1016/j.psychres.2018.06.012
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发表时间：
2018-09
期刊：
影响因子：
--
通讯作者：
Hai Jian
中科院分区：
文献类型：
--
作者：
Wang Da-Peng;Yin Hang;Kang Kai;Lin Qi;Su Shao-Hua;Hai Jian
血管性痴呆(VaD)是以慢性脑缺血和进行性记忆减退为特征的疾病，在老年人中发病率较高。然而，目前尚无有效的治疗方法，其发病机制尚不清楚。本研究探讨了合成大麻素受体激动剂WIN55,212-2(WIN)对VaD的影响及其分子机制。采用双血管结扎(2VO)法建立VaD模型。空间参照学习采用Morris水迷宫，再认记忆采用新型物体再认测验。免疫组织化学和Western印迹法检测自噬相关蛋白[微管相关蛋白1轻链3(LC-3)和Beclin-1]。Western印迹法检测caspase-3的表达。采用逆转录-聚合酶链式反应和免疫印迹法检测炎症因子肿瘤坏死因子-α(TN-α)和白介素1-β(IL-1β)。VAD可增加LC-3、Beclin-1和炎症因子的水平，而Win慢性治疗可逆转这些升高。温阳还能降低CAPase-3的表达，改善VaD大鼠的学习记忆障碍。提示WIN对VaD大鼠认知功能障碍具有神经保护作用，其机制可能与抑制过度自噬和炎症有关。
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.
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DOI：
10.1016/j.biopha.2017.05.021
发表时间：
2017-07
期刊：
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
影响因子：
--
作者：
Dapeng Wang;Ke-jia Liu;Graham Kasper;Qi Lin;J. Hai
通讯作者：
Dapeng Wang;Ke-jia Liu;Graham Kasper;Qi Lin;J. Hai
WIN55,212-2 保护大鼠永久性局灶性脑缺血后中风半影区的少突胶质细胞前体细胞
影响因子：
8.2
作者：
Sun, Jing;Fang, Yin-quan;Liao, Hong
通讯作者：
Liao, Hong
影响因子：
3.7
作者：
Escamilla-Ramirez, Angel;Garcia, Esperanza;Santamaria, Abel
通讯作者：
Santamaria, Abel
大麻素 1 受体肽配体加压素、(m) RVD-加压素 (α) 和 (m)VD-加压素 (α) 对正常年轻人和 A beta 中新物体和物体位置识别任务中记忆的影响 (1-42)
影响因子：
2.7
作者：
Zhang Rui-san;He Zhen;Jin Wei-dong;Wang Rui;Zhang Rui-san;Wang R
通讯作者：
Wang R
影响因子：
8.2
作者：
Patel S;Hill MN;Cheer JF;Wotjak CT;Holmes A
通讯作者：
Holmes A