甲基苯丙胺改变成瘾小鼠突触可塑性基因的甲基化修饰

目的 研究慢性甲基苯丙胺(methamphetamine,MA)成瘾小鼠神经突触可塑性基因的表达变化情况.方法 选用C57BL/6J小鼠,模拟人类药物成瘾模式,分段渐进性腹腔注射给药5 mg/kg、10 mg/kg或者生理盐水.选取小鼠的大脑皮质和海马组织,通过亚硫酸氢盐处理基因组DNA和甲基化特异性PCR(methy...

Methamphetamine Alters Methylation Modifications of Synaptic Plasticity Genes in Addicted Mice

  Objective  To investigate the expression changes of synaptic plasticity genes in chronic methamphetamine （MA） addicted mice.   Methods   C57BL/6J mice were selected to simulate the human drug addiction model, and the drugs were injected intraperitoneally with 5 mg/kg, 10 mg/kg or normal saline. The cerebral cortex and hippocampus of mice were selected, and the gene expression level of synaptic plasticity was detected by bisulfite treated genomic DNA and methylation specific PCR （MethylmionSpecificPCR, MSP）. The sequencing results were compared and DNA methylation was analyzed by BiQ-Analyzer software.   Results  Compared to mice in the saline-treated group, MA addiction group mice showed increased methylation modification of the Egr2 （P = 0.064） gene promoter CpG site and decreased methylation modification of the Eln （P = 0.083） gene promoter in the cerebral cortex; in hippocampal tissue, methylation modification of the Arc （P = 0.025） and Egr2 （P = 0.034） genes was increased, while Eln （P = 0.063） gene methylation modifications were decreased.   Conclusion  Methylation of synaptic plasticity genes may be involved in the formation of MA addiction mechanism.