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.
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.
J Pharmacol Sci. 2020 Aug;143(4):245-254. doi: 10.1016/j.jphs.2020.05.002. Epub 2020 May 14.
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 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.
淀粉样β（Aβ）肽的积累是阿尔茨海默病（AD）的病理变化之一，它导致突触可塑性损伤和兴奋性氨基酸毒性，与记忆功能下降有关。醒脑静（XNJ）是一种在中国应用于治疗中风多年的中药名方。在这项研究中，我们旨在研究 XNJ 对 Aβ诱导的 AD 小鼠模型的治疗作用，该模型表现出明显的记忆丧失和突触形态和功能受损。XNJ 治疗可减轻空间和工作记忆功能障碍，增加树突棘密度并改善长时程增强（LTP）诱导。此外，XNJ 治疗还显著增加了 N-甲基-D-天冬氨酸受体（NMDARs）的水平，并抑制了 AD 小鼠中 NMDA/α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）的比值。XNJ 治疗还激活了 AKT/雷帕霉素的哺乳动物靶点（mTOR）通路，而 rapamycin 抑制 mTOR 通路可逆转 XNJ 治疗的保护作用。总之，XNJ 通过激活 AKT/mTOR 信号通路来保护 AD 小鼠的突触可塑性和记忆损伤，提示 XNJ 可作为 AD 的替代治疗方法。
