Xu Hui, You Zhengchen, Wu Zhonghua, Zhou Liang, Shen Jianhong, Gu Zhikai
Department of Neurosurgery, The Sixth People's Hospital of Nantong, Nantong, 226001, Jiangsu, China.
Department of Neurosurgery, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu, China.
Neurochem Res. 2016 Nov;41(11):2868-2879. doi: 10.1007/s11064-016-2002-1. Epub 2016 Jul 16.
WY14643 is a selective agonist of peroxisome proliferator-activated receptor-α (PPAR-α) with neuroprotective and neurotrophic effects. The aim of this study was to evaluate the effects of WY14643 on cognitive impairments induced by scopolamine, a muscarinic acetylcholine receptor antagonist. We conducted different behavior tests including the Y-maze, Morris water maze, and passive avoidance test to measure the cognitive functions of C57BL/6J mice after scopolamine and WY14643 treatment. It was found that WY14643 injection significantly attenuated the scopolamine-induced cognitive impairments in these behavioral tests. Moreover, WY14643 treatment significantly enhanced the expression of brain-derived neurotrophic factor (BDNF) signaling cascade in the hippocampus. The usage of both PPAR-α inhibitor GW6471 and BDNF system inhibitor K252a fully prevented the memory-enhancing effects of WY14643. Therefore, these findings suggest that WY14643 could improve the scopolamine-induced memory impairments, and these effects are mediated by the activation of PPAR-α and BDNF system, thereby exhibiting a cognition-enhancing potential.
WY14643是过氧化物酶体增殖物激活受体-α（PPAR-α）的选择性激动剂，具有神经保护和神经营养作用。本研究旨在评估WY14643对毒蕈碱型乙酰胆碱受体拮抗剂东莨菪碱诱导的认知障碍的影响。我们进行了不同的行为测试，包括Y迷宫、莫里斯水迷宫和被动回避测试，以测量东莨菪碱和WY14643处理后C57BL/6J小鼠的认知功能。发现在这些行为测试中，注射WY14643可显著减轻东莨菪碱诱导的认知障碍。此外，WY14643处理可显著增强海马体中脑源性神经营养因子（BDNF）信号级联的表达。使用PPAR-α抑制剂GW6471和BDNF系统抑制剂K252a均可完全阻断WY14643的记忆增强作用。因此，这些发现表明WY14643可改善东莨菪碱诱导的记忆障碍，且这些作用是通过激活PPAR-α和BDNF系统介导的，从而展现出增强认知的潜力。
