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Prenatal Exposure to Methamphetamine: Up-Regulation of Brain Receptor Genes

机译:产前暴露于甲基苯丙胺:脑受体基因的上调。

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Methamphetamine (METH) is a widespread illicit drug. If it is taken by pregnant women, passes through the placenta and just as it affects the mother, it can impair the development of the offspring. The aim of our study was to identify candidates to investigate for changes in the gene expression in the specific regions of the brain associated with METH addiction in rats. We examined the various areas of the central nervous system (striatum, hippocampus, prefrontal cortex) for signs of impairment in postnatal day 80 in experimental rats, whose mothers had been administered METH (5mg/kg/day) during the entire gestation period. Changes in the gene expression were determined by two methods, microarray and real-time PCR. Results of two microarray trials were evaluated by LIMMA analysis. The first microarray trial detected either up-regulated or down-regulated expression of 2189 genes in the striatum; the second microarray trial detected either up-regulated or down-regulated expression of 1344 genes in the hippocampus of prenatally METH exposed rats. We examined the expressions of 10 genes using the real-time PCR method. Differences in gene expression were counted by the Mann–Whitney U test. Significant changes were observed in the cocaine- and amphetamine-regulated transcript prepropeptide, tachykinin receptor 3, dopamine receptor D3 genes expression in the striatum regions, in the glucocorticoid nuclear receptor Nr3c1 gene expression in the prefrontal cortex and in the carboxylesterase 2 gene expression in the hippocampus prenatally METH exposed rats. The microarray method also detected upregulated expression of trace amine-associated receptor 7h gene in the hippocampus of prenatally METH exposed rats. We have identified susceptible genes; candidates for the study of an impairment related to methamphetamine addiction in the specific regions of the brain.
机译:甲基苯丙胺(METH)是一种广泛的非法药物。如果它是由孕妇服用的,则通过胎盘,就像它影响母亲一样,会损害后代的发育。我们研究的目的是确定候选人,以研究与METH成瘾相关的大脑特定区域中基因表达的变化。我们在实验大鼠的出生后第80天检查了中枢神经系统的各个区域(纹状体,海马,前额叶皮层)有无损伤的迹象,这些大鼠的母亲在整个妊娠期都接受了METH(5mg / kg /天)。基因表达的变化通过两种方法确定,即微阵列和实时PCR。通过LIMMA分析评估了两项微阵列试验的结果。第一个微阵列试验检测到纹状体中2189个基因的表达上调或下调。第二项微阵列试验检测了产前METH暴露大鼠海马中1344个基因的表达上调或下调。我们使用实时PCR方法检查了10个基因的表达。基因表达的差异通过Mann-Whitney U检验进行计数。观察到可卡因和苯丙胺调节的转录前原肽,速激肽受体3,多巴胺受体D3基因在纹状体区域,糖皮质激素核受体Nr3c1基因在额叶皮层和羧化酶2基因表达中的变化海马产前METH暴露的大鼠。该芯片方法还检测了产前METH暴露大鼠海马中痕量胺相关受体7h基因的表达上调。我们已经鉴定出易感基因;研究与大脑特定区域中的甲基苯丙胺成瘾有关的损伤的候选药物。

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