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

Article type: Research Article

Authors: Jiang, Xia^{a; b; c; 1} | Jia, Lin-Wei^{a; 1} | Li, Xiao-Hong^{a; b} | Cheng, Xiang-Shu^{a; b} | Xie, Jia-Zhao^{a; b} | Ma, Zhi-Wei^{a; b} | Xu, Wei-Jie^a | Liu, Yue^a | Yao, Yun^{a; b} | Du, Lai-Ling^{a; b} | Zhou, Xin-Wen^{a; b; *}

Affiliations: [a] Department of Pathophysiology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China | [b] Key Laboratory of Neurological Diseases of Education Ministry of China, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China | [c] Department of Pathology, Hubei University of Chinese Medicine, Wuhan, P.R. China

Correspondence: [*] Correspondence to: Dr. Xin-Wen Zhou, Department of Pathophysiology, Key Laboratory of Neurological Diseases of Education Ministry of China, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, P.R. China. Tel.: +86 27 83692625; Fax: +86 27 83693883; E-mail: zhouxinwen@mail.hust.edu.cn.

Note: [1] These authors contributed equally to this work.

Abstract: 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.

Keywords: Alzheimer's disease, capsaicin, dendritic arborization, spatial memory, tau hyperphosphorylation

DOI: 10.3233/JAD-121837

Journal: Journal of Alzheimer's Disease, vol. 35, no. 1, pp. 91-105, 2013