Zeng Qing, Xiong Qi, Lin Kuan, Liang Zheng, Zhou Mei, Tian Xiang, Xu Congyue, Ru Qin
Wuhan Institutes of Biomedical Sciences, School of Medicine, Jianghan University, Wuhan 430056, China.
Wuhan Institutes of Biomedical Sciences, School of Medicine, Jianghan University, Wuhan 430056, China.
Brain Res Bull. 2022 Jun 15;184:76-87. doi: 10.1016/j.brainresbull.2022.04.002. Epub 2022 Apr 8.
As a psychoactive substance abused worldwide, methamphetamine (METH) abuse leads to multiple neurodegenerative symptoms including memory deficits. Terminalia chebula retzius extracts (TREs) isolated by our lab have great antioxidant activity and its effect on METH-induced memory deficits has not been investigated yet. The present study was designed to investigate the protective effect of TREs on METH induced cell apoptosis in vitro and memory deficits in vivo. The results showed that TREs treatment attenuated free radical release and improved cell survival of primary hippocampal neurons after METH injury. In the Morris water maze task, TREs treatment reversed METH-induced learning and memory deficits in acquisition and retention. Moreover, TREs reduced oxidative stress in the serum and hippocampus of mice. Additionally, extracellular regulated protein kinases (ERK1/2) pathway and the nuclear factor E2-related factor 2 (Nrf2) pathway were inactivated after METH treatment, and were significantly activated after TREs pretreatment. These findings suggest that TREs may exert potent neuroprotective effect via activation of both ERK and Nrf2 pathways, thus providing a basis for its potential use for ameliorating memory deficits induced by METH.
作为一种在全球范围内被滥用的精神活性物质，甲基苯丙胺（METH）滥用会导致多种神经退行性症状，包括记忆缺陷。我们实验室分离出的诃子提取物（TREs）具有很强的抗氧化活性，但其对METH诱导的记忆缺陷的影响尚未得到研究。本研究旨在探讨TREs对METH诱导的体外细胞凋亡和体内记忆缺陷的保护作用。结果表明，TREs处理可减轻自由基释放，并改善METH损伤后原代海马神经元的细胞存活。在莫里斯水迷宫任务中，TREs处理逆转了METH诱导的学习和记忆获取及保持缺陷。此外，TREs降低了小鼠血清和海马中的氧化应激。另外，METH处理后细胞外调节蛋白激酶（ERK1/2）通路和核因子E2相关因子2（Nrf2）通路失活，而TREs预处理后则显著激活。这些发现表明，TREs可能通过激活ERK和Nrf2通路发挥强大的神经保护作用，从而为其潜在用于改善METH诱导的记忆缺陷提供了依据。
