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Neurochemical Research

, Volume 41, Issue 11, pp 2868–2879 | Cite as

WY14643 Attenuates the Scopolamine-Induced Memory Impairments in Mice

  • Hui Xu
  • Zhengchen You
  • Zhonghua Wu
  • Liang Zhou
  • Jianhong Shen
  • Zhikai Gu
Original Paper

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.

Keywords

Brain-derived neurotrophic factor cAMP response element-binding protein Memory Scopolamine WY14643 

Abbreviations

AchE

Acetyl-cholinesterase

AD

Alzheimer’s disease

ANOVA

Analysis of variance

BDNF

Brain derived neurotrophic factor

ChAT

Choline acteyltransferase

CREB

cAMP response element-binding protein

LTP

Long-term potentiation

mAChR

Muscarinic acetylcholine receptor

PPAR-α

Peroxisome proliferator-activated receptor-α

TrkB

Tyrosine kinase B

Notes

Acknowledgments

This work was funded by innovation and demonstration projects of Nantong Social Science and Technology (HS2011024).

Compliance with Ethical Standards

Conflict of Interest

None.

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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  1. 1.Department of NeurosurgeryThe Sixth People’s Hospital of NantongNantongChina
  2. 2.Department of NeurosurgeryAffiliated Hospital of Nantong UniversityNantongChina
  3. 3.Department of Neurosurgery and Brain and Nerve Research LaboratoryThe First Affiliated Hospital of Soochow UniversitySuzhouChina

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