title: WY14643 Attenuates the Scopolamine-Induced Memory Impairments in Mice.
abstract: 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.
authors.affiliation: Department of Neurosurgery, The Sixth People's Hospital of Nantong, Nantong, 226001, Jiangsu, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Xu
authors.affiliation: Department of Neurosurgery, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu, China.
authors.forename: Zhengchen
authors.initials: Z
authors.lastname: You
authors.affiliation: Department of Neurosurgery, The Sixth People's Hospital of Nantong, Nantong, 226001, Jiangsu, China.
authors.forename: Zhonghua
authors.initials: Z
authors.lastname: Wu
authors.affiliation: Department of Neurosurgery and Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, 215006, Jiangsu, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Department of Neurosurgery, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu, China. jianhongshennt@gmail.com.
authors.forename: Jianhong
authors.initials: J
authors.lastname: Shen
authors.affiliation: Department of Neurosurgery, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu, China. ntguzhikai@126.com.
authors.forename: Zhikai
authors.initials: Z
authors.lastname: Gu
mesh_terms: D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D003071:Cognition / Q000187:drug effects*; D004195:Disease Models, Animal; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects*; D008569:Memory Disorders / Q000139:chemically induced / Q000188:drug therapy*; D008810:Mice, Inbred C57BL; D018696:Neuroprotective Agents / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D018696:Neuroprotective Agents; D011743:Pyrimidines; C006253:pirinixic acid
keywords: Brain-derived neurotrophic factor; Memory; Scopolamine; WY14643; cAMP response element-binding protein