College of Pharmacy, Keimyung University, Daegu 42601, Korea.
Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 08826, Korea.
Int J Mol Sci. 2020 Nov 23;21(22):8856. doi: 10.3390/ijms21228856.
Methamphetamine (MA) use disorder is a chronic neuropsychiatric disease characterized by recurrent binge episodes, intervals of abstinence, and relapses to MA use. Therefore, identification of the key genes and pathways involved is important for improving the diagnosis and treatment of this disorder. In this study, high-throughput RNA sequencing was performed to find the key genes and examine the comparability of gene expression between whisker follicles and the striatum of rats following MA self-administration. A total of 253 and 87 differentially expressed genes (DEGs) were identified in whisker follicles and the striatum, respectively. Multivariate and network analyses were performed on these DEGs to find hub genes and key pathways within the constructed network. A total of 129 and 49 genes were finally selected from the DEG sets of whisker follicles and of the striatum. Statistically significant DEGs were found to belong to the classes of genes involved in nicotine addiction, cocaine addiction, and amphetamine addiction in the striatum as well as in Parkinson's, Huntington's, and Alzheimer's diseases in whisker follicles. Of note, several genes and pathways including retrograde endocannabinoid signaling and the synaptic vesicle cycle pathway were common between the two tissues. Therefore, this study provides the first data on gene expression levels in whisker follicles and in the striatum in relation to MA reward and thereby may accelerate the research on the whisker follicle as an alternative source of biomarkers for the diagnosis of MA use disorder.
甲基苯丙胺（MA）使用障碍是一种慢性神经精神疾病，其特征是反复发作的狂欢发作、禁欲期和复吸 MA 滥用。因此，鉴定涉及的关键基因和途径对于改善这种疾病的诊断和治疗非常重要。在这项研究中，进行了高通量 RNA 测序，以发现关键基因，并检查 MA 自我给药后大鼠胡须毛囊和纹状体之间的基因表达的可比性。在胡须毛囊和纹状体中分别鉴定出 253 和 87 个差异表达基因（DEG）。对这些 DEG 进行多变量和网络分析，以找到构建网络内的枢纽基因和关键途径。最后，从胡须毛囊和纹状体的 DEG 集中分别选择了 129 和 49 个基因。统计上显著的 DEG 被发现属于纹状体中涉及尼古丁成瘾、可卡因成瘾和安非他命成瘾的基因类别，以及胡须毛囊中帕金森病、亨廷顿病和阿尔茨海默病的基因类别。值得注意的是，包括逆行内源性大麻素信号和突触小泡循环途径在内的几个基因和途径在这两种组织中是共同的。因此，本研究首次提供了与 MA 奖励相关的胡须毛囊和纹状体中基因表达水平的数据，从而可能加速对胡须毛囊作为 MA 使用障碍诊断的生物标志物替代来源的研究。
