title: Capsaicin ameliorates stress-induced Alzheimer's disease-like pathological and cognitive impairments in rats.
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.
authors: Department of Pathophysiology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China.
authors: Xia
authors: X
authors: Jiang
authors: Lin-Wei
authors: LW
authors: Jia
authors: Xiao-Hong
authors: XH
authors: Li
authors: Xiang-Shu
authors: XS
authors: Cheng
authors: Jia-Zhao
authors: JZ
authors: Xie
authors: Zhi-Wei
authors: ZW
authors: Ma
authors: Wei-Jie
authors: WJ
authors: Xu
authors: Yue
authors: Y
authors: Liu
authors: Yun
authors: Y
authors: Yao
authors: Lai-Ling
authors: LL
authors: Du
authors: Xin-Wen
authors: XW
authors: Zhou
mesh_terms: D000544:Alzheimer Disease / Q000473:pathology / Q000517:prevention & control* / Q000523:psychology; D000818:Animals; D002211:Capsaicin / Q000494:pharmacology / Q000627:therapeutic use*; D003072:Cognition Disorders / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D049229:Dendritic Spines / Q000187:drug effects / Q000473:pathology; D004195:Disease Models, Animal; D008297:Male; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013315:Stress, Psychological / Q000188:drug therapy* / Q000473:pathology / Q000523:psychology
chemical_list: D002211:Capsaicin