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Differential gene expression and stereological analyses of the cerebellum following methamphetamine exposure

机译：甲基苯丙胺暴露后脑细胞的差异基因表达及天体学分析

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Abstract Methamphetamine (METH) is a highly addictive psychostimulant that profoundly aimed at monoaminergic systems in the brain. Despite the leading role of cerebellum in sensorimotor control as well as augmented locomotor activity under the influence of METH, there are few studies examining the effect of METH administration on gene expression profiling and structural consequences in the cerebellar region. Thus, we sought to explore the effects of METH on the cerebellum, from gene expression changes to structural alterations. In this respect, we investigated genome‐wide mRNA expression using high throughput RNA‐seq technology and confirmatory quantitative real‐time PCR, accompanied by stereological analysis of cerebellar layers along with identification of reactive astrogliosis by glial fibrillary acidic protein and behavioral assessment following METH exposure. According to our RNA‐seq data, 473 unique differentially expressed genes (DEG) were detected upon METH injections in which a large number of these genes engage basically in biological regulations and metabolic processes, chiefly located in nucleus and membrane. In addition, pathway analysis of METH‐induced DEG revealed several enriched signaling cascades related largely to immune response, neurotransmission, cell growth, and death. Further, METH induced a significant reduction in volumes of cerebellar layers (molecular, granular, and Purkinje) and a decrease in the white matter volume along with a rise in astrogliosis as well as increased locomotor activity. In conclusion, considering gene expression changes combined with structural alterations of the cerebellum in response to METH, these data suggest METH‐induced neurotoxicity in the cerebellar region.
机译：摘要甲基苯丙胺（甲基）是一种令人上瘾的精神疗法，对大脑中的单氨酰胺能系统造成深远。尽管小脑在感觉电流控制中的主要作用以及在甲基甲基的影响下产生了增强的运动活动，但仍有少量研究甲基胺对小脑区域中基因表达分析和结构后果的影响。因此，从基因表达变化到结构改变，我们试图探索甲基甲基甲基的影响。在这方面，我们使用高通量RNA-SEQ技术和验证定量实时PCR研究了基因组 - 宽的mRNA表达，并伴随着小脑层的立体学分析以及通过胶质纤维酸性蛋白质的活性星力术和行为评估培养。根据我们的RNA-SEQ数据，在甲基注射时检测到473个独特的差异表达基因（DEG），其中大量这些基因在生物法规和代谢过程中，主要位于核和膜中。此外，甲基诱导的DEG的途径分析揭示了几种富含免疫应答，神经递血，细胞生长和死亡的富集的信号级联。此外，甲基诱导大脑层（分子，颗粒状和Purkinje）的显着降低，以及白质量的降低以及星间隙的升高以及增加的运动活性。总之，考虑到基因表达与小脑的结构改变结合含量甲基，这些数据表明细胞区域中的甲基诱导的神经毒性。

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