Capsaicin Ameliorates Stress-Induced Alzheimer's Disease-Like Pathological and Cognitive Impairments in Rats

作者：Xia Jiang, Linwei Jia, Xiaohong Li, Xiangshu Cheng, Jiazhao Xie, Zhiwei Ma, Weijie Xu, Yue Liu, Yun Yao, Lailing Du, Xinwen Zhou · 发表于：Journal of Alzheimer s Disease · 年份：2013 · DOI：10.3233/jad-121837 · 被引用次数：70 · 研究领域：Ion Channels and Receptors、Biochemical effects in animals、Circadian rhythm and melatonin

Hyperphosphorylated tau aggregated into neurofibrillary tangles is a hallmark lesion of Alzheimer's disease (AD) and is linked to synaptic and cognitive impairments. In animal models, cold water stress (CWS) can cause cognitive disorder and tau hyperphosphorylation. Capsaicin (CAP), a specific TRPV1 agonist, is neuroprotective against stress-induced impairment, but the detailed mechanisms are still elusive. Here, we investigated whether CAP mitigates CWS-induced cognitive and AD-like pathological alterations in rats. The animals were administered CAP (10 mg/kg in 0.2 ml, 0.1% ethanol) or a control (0.2 ml normal saline, 0.1% ethanol) by intragastric infusion 1 h before CWS treatment. Our results showed that CAP significantly attenuated CWS-induced spatial memory impairment and suppression of PP-DG long-term potentiation; CAP abolished CWS-induced dendritic regression and enhanced several memory-associated proteins decreased by CWS, such as synapsin I and PSD93; CAP also prevented CWS-induced tau hyperphosphorylation by abolishing inhibition of protein phosphatase 2A. Taken together, this study demonstrated that activation of TRPV1 can mitigate CWS-induced AD-like neuropathological alterations and cognitive impairment and may be a promising target for therapeutic intervention in AD.