Children's Hospital of Nanjing Medical University, China.
Key Lab of Modern Toxicology (NJMU), Ministry of Education; Department of Toxicology, School of Public Health, Nanjing Medical University, China.
J Toxicol Sci. 2019;44(7):493-503. doi: 10.2131/jts.44.493.
Methamphetamine (METH) is a potent and highly addictive central nervous system stimulant. The association between METH exposure and Alzheimer's disease (AD) has gained more attention, but, the mechanisms behind METH-induced neuron-related adverse outcomes remain poorly understood. With the western blot assay, our results revealed that METH exposure significantly increased the expression of AD-associated pathological proteins, including the amyloid precursor protein (APP) and the phosphorylated tau protein (p-tau). Meanwhile, the insulin signaling was disturbed after the administration of METH, since the key insulin signaling proteins, such as p-AKT, p-GSK3α, p-GSK3β and p-ERK, were reduced. Additionally, the linking between the pathological proteins and the insulin signaling mediated by METH in the present work was verified by the treatment with the insulin signaling enhancer rosiglitazone, which was shown to improve the insulin signaling and decrease APP and p-tau expression. Thus, targeting insulin signaling may provide novel insights into potential therapeutic intervention for METH-mediated AD-like neurodegeneration.
甲基苯丙胺（METH）是一种强效且高度成瘾的中枢神经系统兴奋剂。METH 暴露与阿尔茨海默病（AD）之间的关联引起了更多关注，但 METH 诱导的神经元相关不良后果的机制仍知之甚少。通过 Western blot 检测，我们的结果表明，METH 暴露显著增加了 AD 相关病理蛋白的表达，包括淀粉样前体蛋白（APP）和磷酸化 tau 蛋白（p-tau）。同时，METH 给药后胰岛素信号受到干扰，因为关键的胰岛素信号蛋白，如 p-AKT、p-GSK3α、p-GSK3β 和 p-ERK，减少了。此外，通过用胰岛素信号增强剂罗格列酮处理，验证了本工作中由 METH 介导的病理蛋白与胰岛素信号之间的联系，结果表明罗格列酮能改善胰岛素信号并降低 APP 和 p-tau 的表达。因此，针对胰岛素信号可能为 METH 介导的 AD 样神经退行性变的潜在治疗干预提供新的见解。
