National Institute of Medicinal Materials.
National Geriatric Hospital.
Biol Pharm Bull. 2019;42(8):1384-1393. doi: 10.1248/bpb.b19-00288.
We previously demonstrated that Bacopa monnier (L.) WETTST. extract (BME) ameliorated cognitive dysfunction in animal models of dementia by enhancing synaptic plasticity-related signaling in the hippocampus and protecting cholinergic neurons in the medial septum. To further clarify the pharmacological features and availability of BME as a novel anti-dementia agent, we investigated whether BME affects neuronal repair using a mouse model of trimethyltin (TMT)-induced neuronal loss/self-repair in the hippocampus. Mice pretreated with TMT (2.8 mg/kg, intraperitoneally (i.p.)) on day 0 were given BME (50 mg/kg, per os (p.o.)) once daily for 15-30 d. Cognitive performance of the animals was elucidated twice by the object location test and modified Y maze test on days 17-20 (Phase I) and days 32-35 (Phase II) or by the passive avoidance test on Phase II. TMT impaired hippocampus-dependent spatial working memory and amygdala-dependent fear-motivated memory. The administration of BME significantly prevented TMT-induced cognitive deficits. The protective effects of BME on the spatial memory deficits were confirmed by Nissl staining of hippocampal tissues and propidium iodide staining of organotypic hippocampal slice cultures. Immunohistochemical studies conducted on days 17 and 32 revealed that thirty days of treatment with BME increased the number of 5-bromo-2'-deoxyuridine (BrdU)-immunopositive cells in the dentate gyrus region of TMT-treated mice, whereas fifteen days of treatment with BME had no effect. These results suggest that BME ameliorates TMT-induced cognition dysfunction mainly via protecting the hippocampal neurons from TMT-induced hippocampal lesions and partly via promoting neuroregeneration in the dentate gyrus regions.
我们之前的研究表明，益智草（Bacopa monnier （L.） Wettst.）提取物（BME）通过增强海马突触可塑性相关信号，保护中隔胆碱能神经元，改善痴呆动物模型的认知功能障碍。为了进一步阐明 BME 作为一种新型抗痴呆药物的药理学特征和可用性，我们研究了 BME 是否会影响使用三甲基锡（TMT）诱导的海马神经元丢失/自我修复的小鼠模型中的神经元修复。第 0 天，用 TMT（2.8mg/kg，腹腔内（i.p.））预处理小鼠，随后每天用 BME（50mg/kg，口服（p.o.））处理 15-30 天。在第 17-20 天（第 I 阶段）和第 32-35 天（第 II 阶段）通过物体位置测试和改良 Y 迷宫测试两次阐明动物的认知性能，或者在第 II 阶段通过被动回避测试阐明。TMT 损害了海马依赖性空间工作记忆和杏仁核依赖性恐惧动机记忆。BME 的给药显著预防了 TMT 诱导的认知缺陷。通过对海马组织进行尼氏染色和对器官型海马切片培养物进行碘化丙啶染色，证实了 BME 对空间记忆缺陷的保护作用。在第 17 天和第 32 天进行的免疫组织化学研究表明，30 天的 BME 治疗增加了 TMT 处理小鼠齿状回区 5-溴-2'-脱氧尿苷（BrdU）阳性细胞的数量，而 15 天的 BME 治疗则没有影响。这些结果表明，BME 通过保护海马神经元免受 TMT 诱导的海马损伤，部分通过促进齿状回区域的神经再生，改善 TMT 诱导的认知功能障碍。
