Abstract:
Aim: We investigated DNA methylation of BDNF in methamphetamine (METH) dependence in humans and an animal model. Materials & methods: BDNF methylation at exon IV was determined by pyrosequencing of blood DNA from METH-dependent and control subjects, and from rat brain following an escalating dose of METH or vehicle. Bdnf expression was determined in rat brain. Results: BDNF methylation was increased in human METH dependence, greatest in subjects with psychosis and in prefrontal cortex of METH-administered rats; rat hippocampus showed reduced Bdnf methylation and increased gene expression. Conclusion: BDNF methylation is abnormal in human METH dependence, especially METH-dependent psychosis, and in METH-administered rats. This may influence BDNF expression and contribute to the neurotoxic effects of METH exposure.
Lay abstract The effects of methamphetamine (METH), an addictive psychostimulant drug, on changes of DNA methylation of an important regulator of neuronal survival, BDNF, were examined in blood of METH-dependent patients and in the brain of METH-administered rats. BDNF methylation was increased in patients and in the prefrontal cortex of METH-administered rats, while rat hippocampus showed a reduction of Bdnf methylation, with an equivalent increase in gene expression. The methylation increases in humans were greatest in those with a METH-induced psychosis. Although a relationship between Bdnf methylation and its expression has not been proven, changes of BDNF DNA methylation are associated with METH dependence, especially METH-dependent psychosis, suggesting that METH neurotoxicity may relate to the effects of changes in BDNF methylation.
摘要:
目的:我们研究了人类和动物模型中甲基苯丙胺(METH)依赖性中BDNF的DNA甲基化。材料和方法:通过对METH依赖性和对照受试者的血液DNA进行焦磷酸测序来确定外显子IV处的BDNF甲基化,以及在不断增加剂量的METH或媒介物后的大鼠大脑中。在大鼠脑中测定Bdnf表达。结果:BDNF甲基化在人类METH依赖中增加,在患有精神病的受试者和使用METH的大鼠的前额叶皮质中最大;大鼠海马显示出Bdnf甲基化减少和基因表达增加。结论:BDNF甲基化在人类METH依赖中存在异常,尤其是METH依赖性精神病,在METH给药的大鼠中。这可能会影响BDNF的表达,并有助于METH暴露的神经毒性作用。
准备摘要甲基苯丙胺(METH)的影响,一种令人上瘾的精神兴奋剂药物,关于神经元存活的重要调节因子DNA甲基化的变化,BDNF,在METH依赖患者的血液和METH给药大鼠的大脑中进行了检查。BDNF甲基化在METH给药大鼠的患者和前额叶皮质中增加,而大鼠海马显示Bdnf甲基化减少,基因表达的等效增加。人类的甲基化增加在METH诱导的精神病患者中最大。尽管Bdnf甲基化与其表达之间的关系尚未得到证实,BDNFDNA甲基化的变化与METH依赖性有关,尤其是METH依赖性精神病,提示METH神经毒性可能与BDNF甲基化变化的影响有关。