Department of Pharmaceutical Sciences, Irma Lerma Rangel College of Pharmacy, Texas A&M University, 1010 W Avenue B, Kingsville, TX, 78363, USA.
Sci Rep. 2021 Oct 29;11(1):21335. doi: 10.1038/s41598-021-00836-z.
Substance abuse affects the central nervous system (CNS) and remains a global health problem. Psychostimulants, such as cocaine and methamphetamine (METH), and opioids affect neuronal function and lead to behavioral impairments via epigenetic modification. Epigenetic changes occur via classical pathways, especially the class III histone deacetylase (HDAC)-sirtuin (SIRT) family, that act as cellular sensors to regulate energy homeostasis and coordinate cellular responses to maintain genome integrity. However, SIRT family (1-7)-associated neurodegeneration has not been elucidated in the context of energy metabolism. The present study examined the effects of psychostimulants, such as cocaine and METH, and opioids, such as morphine, on SIRT family (1-7) [class I, II, III and IV] expression and cellular translocation-mediated dysfunction in astrocytes and microglial cells. The "nootropic" drug piracetam played a preventative role against psychostimulant- and opioid-induced SIRT (1-7) expression in astrocytes. These results indicate that cocaine, METH, and morphine affected deacetylation and cellular function, and these changes were prevented by piracetam in astrocytes.
物质滥用会影响中枢神经系统（CNS），仍是一个全球性的健康问题。兴奋剂，如可卡因和甲基苯丙胺（METH），以及阿片类药物会通过表观遗传修饰影响神经元功能，导致行为障碍。表观遗传变化通过经典途径发生，特别是 class III 组蛋白去乙酰化酶（HDAC）-沉默调节蛋白（SIRT）家族，作为细胞传感器调节能量稳态，并协调细胞对维持基因组完整性的反应。然而，SIRT 家族（1-7）与能量代谢相关的神经退行性变尚未阐明。本研究探讨了兴奋剂，如可卡因和 METH，以及阿片类药物，如吗啡，对星形胶质细胞和小胶质细胞中 SIRT 家族（1-7）[class I、II、III 和 IV]表达和细胞易位介导的功能障碍的影响。“益智药”吡拉西坦对兴奋剂和阿片类药物诱导的星形胶质细胞中 SIRT（1-7）表达具有预防作用。这些结果表明，可卡因、METH 和吗啡影响去乙酰化和细胞功能，而吡拉西坦可预防星形胶质细胞中的这些变化。
