Ge Wei, Ren Chao, Xing Lei, Guan Lina, Zhang Caiyi, Sun Xuwen, Wang Guoping, Niu Haichen, Qun Sen
Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University No. 209 Tongshan Road, Xuzhou 221004, Jiangsu Province, China.
Department of Neurology, Affiliated Hospital of Xuzhou Medical University No. 99 West Huaihai Road, Xuzhou 221002, Jiangsu Province, China.
Am J Transl Res. 2021 Mar 15;13(3):1471-1482. eCollection 2021.
Previous studies have indicated that the generation of newborn hippocampal neurons is impaired in the early phase of Alzheimer's disease (AD). A potential therapeutic strategy being pursued for the treatment of AD is increasing the number of newborn neurons in the adult hippocampus. Recent studies have demonstrated that ginkgo biloba extract (EGb 761) plays a neuroprotective role by preventing memory loss in many neurodegenerative diseases. However, the extent of EGb 761's protective role in the AD process is unclear. In this study, different doses of EGb 761 (0, 10, 20, and 30 mg/kg; intraperitoneal injections once every day for four months) were tested on 5×FAD mice. After consecutive 4-month injections, mice were tested in learning memory tasks, Aβ, and neurogenesis in the dentate gyrus (DG) of hippocampus and morphological characteristics of neurons in DG of hippocampus. Results indicated that EGb 761 (20 and 30 mg/kg) ameliorated memory deficits. Further analysis indicated that EGb 761 can reduce the number of Aβ positive signals in 5×FAD mice, increase the number of newborn neurons, and increase dendritic branching and density of dendritic spines in 5×FAD mice compared to nontreated 5×FAD mice. It was concluded that EGb 761 plays a protective role in the memory deficit of 5×FAD mice.
先前的研究表明,在阿尔茨海默病(AD)的早期阶段,新生海马神经元的生成受损。目前正在探索的一种治疗AD的潜在策略是增加成年海马中新生神经元的数量。最近的研究表明,银杏叶提取物(EGb 761)通过预防许多神经退行性疾病中的记忆丧失发挥神经保护作用。然而,EGb 761在AD进程中的保护作用程度尚不清楚。在本研究中,对5×FAD小鼠测试了不同剂量的EGb 761(0、10、20和30mg/kg;每天腹腔注射一次,共四个月)。连续注射4个月后,对小鼠进行学习记忆任务、Aβ以及海马齿状回(DG)中的神经发生和海马DG中神经元的形态特征测试。结果表明,EGb 76(20和30mg/kg)改善了记忆缺陷。进一步分析表明,与未治疗的5×FAD小鼠相比,EGb 761可以减少5×FAD小鼠中Aβ阳性信号的数量,增加新生神经元的数量,并增加5×FAD小鼠的树突分支和树突棘密度。得出的结论是,EGb 761对5×FAD小鼠的记忆缺陷起保护作用。