Xingnaojing ameliorates synaptic plasticity and memory deficits in an Aβ1-42 induced mouse model of Alzheimer's disease

Yi Liu; Siyi Xu; Huijie Bian; Yi Qian; Huiya Li; Shu Shu; Jiang Chen; Xiang Cao; Yue Gu; Jiali Jin; Xi Zhang; Yun Xu; Xiaolei Zhu

doi:10.1016/j.jphs.2020.05.002

Xingnaojing ameliorates synaptic plasticity and memory deficits in an Aβ_1-42 induced mouse model of Alzheimer's disease

J Pharmacol Sci. 2020 Aug;143(4):245-254. doi: 10.1016/j.jphs.2020.05.002. Epub 2020 May 14.

Authors

Yi Liu¹, Siyi Xu², Huijie Bian³, Yi Qian¹, Huiya Li¹, Shu Shu¹, Jiang Chen¹, Xiang Cao¹, Yue Gu¹, Jiali Jin¹, Xi Zhang¹, Yun Xu⁴, Xiaolei Zhu⁵

Affiliations

¹ Department of Neurology, Drum Tower Hospital, Medical School and The State Key Laboratory of Pharmaceutical Biotechnology, Institute of Brain Science, Nanjing University, Nanjing, China; Jiangsu Key Laboratory for Molecular Medicine, Medical School of Nanjing University, Nanjing, China.
² Department of Neurology, Drum Tower Hospital, Medical School and The State Key Laboratory of Pharmaceutical Biotechnology, Institute of Brain Science, Nanjing University, Nanjing, China; Department of Neurology, Drum Tower Hospital of Nanjing Medical University, Nanjing, China; Jiangsu Key Laboratory for Molecular Medicine, Medical School of Nanjing University, Nanjing, China.
³ Department of Neurology, Drum Tower Hospital, Medical School and The State Key Laboratory of Pharmaceutical Biotechnology, Institute of Brain Science, Nanjing University, Nanjing, China; Department of Neurology, Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China; Jiangsu Key Laboratory for Molecular Medicine, Medical School of Nanjing University, Nanjing, China.
⁴ Department of Neurology, Drum Tower Hospital, Medical School and The State Key Laboratory of Pharmaceutical Biotechnology, Institute of Brain Science, Nanjing University, Nanjing, China; Department of Neurology, Drum Tower Hospital of Nanjing Medical University, Nanjing, China; Department of Neurology, Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China; Jiangsu Key Laboratory for Molecular Medicine, Medical School of Nanjing University, Nanjing, China. Electronic address: xuyun20042001@aliyun.com.
⁵ Department of Neurology, Drum Tower Hospital, Medical School and The State Key Laboratory of Pharmaceutical Biotechnology, Institute of Brain Science, Nanjing University, Nanjing, China; Department of Neurology, Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China; Jiangsu Key Laboratory for Molecular Medicine, Medical School of Nanjing University, Nanjing, China. Electronic address: zhuquelee@126.com.

PMID: 32482409
DOI: 10.1016/j.jphs.2020.05.002

Abstract

The accumulation of insoluble amyloid β (Aβ) peptides is one of the pathological changes in Alzheimer's disease (AD), which induced synaptic plasticity impairment and excitatory amino acid toxicity associated with decreased memory function. Xingnaojing (XNJ), a well-known prescription in traditional Chinese medicine, has been used for the treatment of stroke for many years in China. In this study, we aim to investigate the therapeutic effects of XNJ in a hippocampus of Aβ_1-42 induced mouse model of AD which showed significant memory loss and impaired synaptic morphology and function. Treatment of XNJ could attenuate spatial and working memory dysfunction, increase dendritic spine density and improve long-term potential (LTP) induction. In addition, XNJ treatment significantly increased the level of N-methyl-d-aspartate receptors (NMDARs) and inhibit the NMDA/α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) ratio in AD mice. XNJ treatment also activated the AKT/mechanistic target of rapamycin (mTOR) pathway, while inhibition of the mTOR pathway by rapamycin could reverse the protective effects of XNJ treatment. In conclusion, XNJ protected against synaptic plasticity and memory impairment in AD mice via the activation of AKT/mTOR signaling pathway, suggesting XNJ as an alternative treatment for AD.

Keywords: Alzheimer's disease; Amyloid-β; NMDAR; Synaptic plasticity; Xingnaojing.

MeSH terms

Alzheimer Disease / drug therapy*
Alzheimer Disease / metabolism
Alzheimer Disease / physiopathology*
Amyloid beta-Peptides / metabolism*
Animals
Brain / metabolism*
Brain / physiopathology*
Disease Models, Animal
Drugs, Chinese Herbal / pharmacology*
Drugs, Chinese Herbal / therapeutic use*
Male
Memory Disorders / drug therapy*
Mice, Inbred C57BL
Neuronal Plasticity / drug effects*
Peptide Fragments / metabolism*

Substances

Amyloid beta-Peptides
Drugs, Chinese Herbal
Peptide Fragments
amyloid beta-protein (1-42)
xingnao jieyu