Department of Biomedicine & Health Sciences, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea.
Department of Physiology, College of Medicine, Kyung Hee University, Seoul 02435, Korea.
Int J Mol Sci. 2020 Jul 11;21(14):4901. doi: 10.3390/ijms21144901.
Trimethyltin (TMT) is a potent neurotoxin affecting various regions of the central nervous system, including the neocortex, the cerebellum, and the hippocampus. Phosphatidylserine (PS) is a membrane phospholipid, which is vital to brain cells. We analyzed the neuroprotective effects of soybean-derived phosphatidylserine (Bean-PS) on cognitive function, changes in the central cholinergic systems, and neural activity in TMT-induced memory deficits in a rat model.
The rats were randomly divided into an untreated normal group, a TMT group (injected with TMT + vehicle), and a group injected with TMT + Bean-PS. The rats were treated with 10% hexane (TMT group) or TMT + Bean-PS (50 mg·kg, oral administration (p.o.)) daily for 21 days, following a single injection of TMT (8.0 mg/kg, intraperitoneally (i.p.)). The cognitive function of Bean-PS was assessed using the Morris water maze (MWM) test and a passive avoidance task (PAT). The expression of acetylcholine transferase (ChAT) and acetylcholinesterase (AchE) in the hippocampus was assessed via immunohistochemistry. A positron emission tomography (PET) scan was used to measure the glucose uptake in the rat brain.
Treatment with Bean-PS enhanced memory function in the Morris water maze (MWM) test. Consistent with the behavioral results, treatment with Bean-PS diminished the damage to cholinergic cells in the hippocampus, in contrast to those of the TMT group. The TMT+Bean-PS group showed elevated glucose uptake in the frontal lobe of the rat brain.
These results demonstrate that Bean-PS protects against TMT-induced learning and memory impairment. As such, Bean-PS represents a potential treatment for neurodegenerative disorders, such as Alzheimer's disease.
三甲基锡（TMT）是一种强效神经毒素，影响中枢神经系统的多个区域，包括大脑皮层、小脑和海马体。磷脂酰丝氨酸（PS）是一种膜磷脂，对脑细胞至关重要。我们分析了大豆来源的磷脂酰丝氨酸（Bean-PS）对 TMT 诱导的记忆缺陷大鼠模型中认知功能、中枢胆碱能系统变化和神经活性的神经保护作用。
大鼠随机分为未处理的正常组、TMT 组（注射 TMT+载体）和 TMT+Bean-PS 组。大鼠每天接受 10%己烷（TMT 组）或 TMT+Bean-PS（50mg·kg，口服（p.o.））治疗 21 天，随后单次注射 TMT（8.0mg/kg，腹腔内（i.p.））。使用 Morris 水迷宫（MWM）测试和被动回避任务（PAT）评估 Bean-PS 的认知功能。通过免疫组织化学评估海马乙酰胆碱转移酶（ChAT）和乙酰胆碱酯酶（AchE）的表达。使用正电子发射断层扫描（PET）测量大鼠脑内的葡萄糖摄取。
Bean-PS 治疗增强了 Morris 水迷宫（MWM）测试中的记忆功能。与行为结果一致，Bean-PS 治疗减轻了海马胆碱能细胞的损伤，与 TMT 组相比。TMT+Bean-PS 组大鼠大脑额叶的葡萄糖摄取增加。
这些结果表明，Bean-PS 可预防 TMT 诱导的学习和记忆障碍。因此，Bean-PS 可能是阿尔茨海默病等神经退行性疾病的潜在治疗方法。
