WY14643 Attenuates the Scopolamine-Induced Memory Impairments in Mice

• DOI: 10.1007/s11064-016-2002-1
• Publication Date: 2016-07-16T01:17:41Z
• Authors: Hui Xu; Zhengchen You; Zhonghua Wu; Liang Zhou; Jianhong Shen; Zhikai Gu
• Keywords: Male; Memory Disorders; 0303 health sciences; Brain-Derived Neurotrophic Factor; Hippocampus; 3. Good health; Mice, Inbred C57BL; Disease Models, Animal; 03 medical and health sciences; Cognition; Neuroprotective Agents; Pyrimidines; Memory; Avoidance Learning; Animals; Maze Learning; Signal Transduction

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.