小柯机器人

美国约翰霍普金斯大学医学院Apuã C. M. Paquola，Daniel R. Weinberger和Jennifer A. Erwin共同合作近期取得重要工作进展，他们研究发现精神分裂症患者尾状核转录组的分析突出了抗精神病药物和新风险基因的作用。该项研究成果2022年11月1日在线发表于《自然—神经科学》杂志上。

研究人员对443名个体（245名神经正常个体，154名精神分裂症患者和44名双相情感障碍患者）死后纹状体尾状核的精神分裂症的遗传和转录情况进行了全面分析，其中210名来自非洲，233名来自欧洲血统。综合表达数量性状位点分析、孟德尔随机化与最新精神分裂症全基因组关联研究、全转录组关联研究和差异表达分析，研究人员确定了许多与精神分裂症风险相关的基因，其中可能包括多巴胺D2受体短异构体。他们发现抗精神病药物对尾状核基因表达有广泛的影响。

研究人员构建了尾状核基因表达网络，强调了涉及精神分裂症风险的相互作用。这些分析为精神分裂症的研究提供了基础，并能帮助深入了解风险机制和潜在的治疗靶点。

据了解，大多数对精神分裂症患者大脑中基因表达的研究都集中在皮层区域，但皮层下的核团，如纹状体，与该疾病有突出的关系。目前的抗精神病药物针对纹状体密集的多巴胺能神经分布。

附：英文原文

Title: Analysis of the caudate nucleus transcriptome in individuals with schizophrenia highlights effects of antipsychotics and new risk genes

Author: Benjamin, Kynon J. M., Chen, Qiang, Jaffe, Andrew E., Stolz, Joshua M., Collado-Torres, Leonardo, Huuki-Myers, Louise A., Burke, Emily E., Arora, Ria, Feltrin, Arthur S., Barbosa, Andr Rocha, Radulescu, Eugenia, Pergola, Giulio, Shin, Joo Heon, Ulrich, William S., Deep-Soboslay, Amy, Tao, Ran, Hyde, Thomas M., Kleinman, Joel E., Erwin, Jennifer A., Weinberger, Daniel R., Paquola, Apu C. M.

Issue&Volume: 2022-11-01

Abstract: Most studies of gene expression in the brains of individuals with schizophrenia have focused on cortical regions, but subcortical nuclei such as the striatum are prominently implicated in the disease, and current antipsychotic drugs target the striatum’s dense dopaminergic innervation. Here, we performed a comprehensive analysis of the genetic and transcriptional landscape of schizophrenia in the postmortem caudate nucleus of the striatum of 443 individuals (245 neurotypical individuals, 154 individuals with schizophrenia and 44 individuals with bipolar disorder), 210 from African and 233 from European ancestries. Integrating expression quantitative trait loci analysis, Mendelian randomization with the latest schizophrenia genome-wide association study, transcriptome-wide association study and differential expression analysis, we identified many genes associated with schizophrenia risk, including potentially the dopamine D2 receptor short isoform. We found that antipsychotic medication has an extensive influence on caudate gene expression. We constructed caudate nucleus gene expression networks that highlight interactions involving schizophrenia risk. These analyses provide a resource for the study of schizophrenia and insights into risk mechanisms and potential therapeutic targets.

DOI: 10.1038/s41593-022-01182-7

Source: https://www.nature.com/articles/s41593-022-01182-7

Nature Neuroscience：《自然—神经科学》，创刊于1998年。隶属于施普林格·自然出版集团，最新IF：28.771
官方网址：https://www.nature.com/neuro/
投稿链接：https://mts-nn.nature.com/cgi-bin/main.plex