Influence of psychostimulants and opioids on epigenetic modification of class III histone deacetylase (HDAC)-sirtuins in glial cells.

Influence of psychostimulants and opioids on epigenetic modification of class III histone deacetylase (HDAC)-sirtuins in glial cells.
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精神兴奋剂和阿片类药物对神经胶质细胞中III类组蛋白去乙酰化酶(HDAC)-sirtuins的表观遗传修饰的影响。

DOI:
10.1038/s41598-021-00836-z
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发表时间:
2021-10-29
期刊:
影响因子:
4.6
通讯作者:
Samikkannu T
Samikkannu T
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Sivalingam K;Doke M;Khan MA;Samikkannu T

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药物滥用会影响中枢神经系统(CNS),并且仍然是一个全球健康问题。可卡因和甲基苯丙胺 (METH) 等精神兴奋剂以及阿片类药物会影响神经元功能,并通过表观遗传修饰导致行为障碍。表观遗传变化通过经典途径发生,尤其是 III 类组蛋白脱乙酰酶 (HDAC)-sirtuin (SIRT) 家族,它们充当细胞传感器来调节能量稳态并协调细胞反应以维持基因组完整性。然而,SIRT 家族 (1-7) 相关的神经变性尚未在能量代谢的背景下得到阐明。本研究探讨了精神兴奋剂(例如可卡因和冰毒)和阿片类药物(例如吗啡)对星形胶质细胞和小胶质细胞中 SIRT 家族 (1-7) [I、II、III 和 IV 类] 表达以及细胞易位介导的功能障碍的影响。 “促智”药物吡拉西坦对精神兴奋剂和阿片类药物诱导的星形胶质细胞 SIRT (1-7) 表达起到预防作用。这些结果表明,可卡因、冰毒和吗啡会影响星形胶质细胞中的脱乙酰化和细胞功能,而吡拉西坦可以阻止这些变化。
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.
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