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20(S)-protopanaxadiol and oleanolic acid ameliorate cognitive deficits in APP/PS1 transgenic mice by enhancing hippocampal neurogenesis

Journal of Ginseng Research 2021년 45권 2호 p.325 ~ 333
Lin Kaili, 방창석, Liu Bin, Zhang Zhang, Zhang Zhu, Zhu Peili, Wang Ying, Deng Qiudi, Yung Ken Kin-Lam, Zhang Shiqing,
소속 상세정보
 ( Lin Kaili ) - Guangzhou Medical University School of Public Health
방창석 ( Bang Chang-Seok ) - Hong Kong Baptist University Faculty of Science Department of Biology
 ( Liu Bin ) - Guangzhou Medical University Second Affiliated Hospital Guangzhou Institute of Cardiovascular Disease
 ( Zhang Zhang ) - Hong Kong Baptist University Faculty of Science Department of Biology
 ( Zhang Zhu ) - Hong Kong Baptist University Faculty of Science Department of Biology
 ( Zhu Peili ) - Hong Kong Baptist University Faculty of Science Department of Biology
 ( Wang Ying ) - Hong Kong Baptist University Faculty of Science Department of Biology
 ( Deng Qiudi ) - Guangzhou Medical University GMU-GIBH Joint School of Life Sciences
 ( Yung Ken Kin-Lam ) - Hong Kong Baptist University Faculty of Science Department of Biology
 ( Zhang Shiqing ) - Hong Kong Baptist University Faculty of Science Department of Biology

Abstract


Background: Alzheimer's disease (AD) is one of the most prevalent neurodegenerative disorders. Enhancing hippocampal neurogenesis by promoting proliferation and differentiation of neural stem cells (NSCs) is a promising therapeutic strategy for AD. 20(S)-protopanaxadiol (PPD) and oleanolic acid (OA) are small, bioactive compounds found in ginseng that can promote NSC proliferation and neural differentiation in vitro. However, it is currently unknown whether PPD or OA can attenuate cognitive deficits by enhancing hippocampal neurogenesis in vivo in a transgenic APP/PS1 AD mouse model. Here, we administered PPD or OA to APP/PS1 mice and monitored the effects on cognition and hippocampal neurogenesis.

Methods: We used the Morris water maze, Y maze, and open field tests to compare the cognitive capacities of treated and untreated APP/PS1 mice. We investigated hippocampal neurogenesis using Nissl staining and BrdU/NeuN double labeling. NSC proliferation was quantified by Sox2 labeling of the hippocampal dentate gyrus. We used western blotting to determine the effects of PPD and OA on Wnt/GSK3β/β-catenin pathway activation in the hippocampus.

Results: Both PPD and OA significantly ameliorated the cognitive impairments observed in untreated APP/PS1 mice. Furthermore, PPD and OA significantly promoted hippocampal neurogenesis and NSC proliferation. At the mechanistic level, PPD and OA treatments resulted in Wnt/GSK-3β/β-catenin pathway activation in the hippocampus.

Conclusion: PPD and OA ameliorate cognitive deficits in APP/PS1 mice by enhancing hippocampal neurogenesis, achieved by stimulating the Wnt/GSK-3β/β-catenin pathway. As such, PPD and OA are promising novel therapeutic agents for the treatment of AD and other neurodegenerative diseases.

키워드

Alzheimer's disease; 20(S)-protopanaxadiol; oleanolic acid; cognitive deficits; hippocampal neurogenesis

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