Single nucleus transcriptomics of ventral midbrain identifies glial activation associated with chronic opioid use disorder.
Single nucleus transcriptomics of ventral midbrain identifies glial activation associated with chronic opioid use disorder.
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DOI：
10.1038/s41467-023-41455-8
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发表时间：
2023-09-12
影响因子：
16.6
通讯作者：
Akbarian, Schahram
中科院分区：
文献类型：
--
作者：
Wei, Julong;Lambert, Tova Y.;Valada, Aditi;Patel, Nikhil;Walker, Kellie;Lenders, Jayna;Schmidt, Carl J.;Iskhakova, Marina;Alazizi, Adnan;Mair-Meijers, Henriette;Mash, Deborah C.;Luca, Francesca;Pique-Regi, Roger;Bannon, Michael J.;Akbarian, Schahram
中脑腹侧神经元和胶质细胞的动态相互作用介导奖赏和成瘾行为。我们研究了来自95名有阿片类药物滥用史的个体和没有药物暴露的个体的212，713个腹侧中脑单个核的基因表达。长期暴露于阿片类药物与神经胶质和神经元亚型的比例变化无关，但神经胶质转录组发生了广泛的改变，涉及小胶质细胞，少突胶质细胞和星形胶质细胞中9.5 - 6.2%的表达基因。与免疫应答激活相关的基因，包括干扰素、NFkB信号传导和细胞运动途径，被上调，与之形成对比的是腹侧中脑非多巴胺能神经元中突触信号传导和可塑性基因的下调表达。在慢性阿片类药物暴露的背景下，大脑中脑转录组重编程包括325个基因，这些基因先前的全基因组研究与更广泛人群中的物质使用特征风险有关，从而指出了大脑奖励电路基因组组织中的遗传风险架构。暴露于阿片类药物的人类中脑的细胞特征仍未被探索。在这里，作者通过单个核转录组学显示了阿片类暴露个体中神经胶质免疫反应的激活和突触信号的失调
Dynamic interactions of neurons and glia in the ventral midbrain mediate reward and addiction behavior. We studied gene expression in 212,713 ventral midbrain single nuclei from 95 individuals with history of opioid misuse, and individuals without drug exposure. Chronic exposure to opioids was not associated with change in proportions of glial and neuronal subtypes, however glial transcriptomes were broadly altered, involving 9.5 − 6.2% of expressed genes within microglia, oligodendrocytes, and astrocytes. Genes associated with activation of the immune response including interferon, NFkB signaling, and cell motility pathways were upregulated, contrasting with down-regulated expression of synaptic signaling and plasticity genes in ventral midbrain non-dopaminergic neurons. Ventral midbrain transcriptomic reprogramming in the context of chronic opioid exposure included 325 genes that previous genome-wide studies had linked to risk of substance use traits in the broader population, thereby pointing to heritable risk architectures in the genomic organization of the brain’s reward circuitry. The cellular signatures of the opioid exposed human midbrain remain unexplored. Here, authors show by single nuclei transcriptomics activation of the glial immune response and dysregulation of synaptic signaling in opioid exposed individuals
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影响因子：
3.7
作者：
Bannon, Michael J.;Savonen, Candace L.;Schmidt, Carl J.
通讯作者：
Schmidt, Carl J.
影响因子：
6.2
作者：
Bright, JJ;Natarajan, C;Muthian, G
通讯作者：
Muthian, G
影响因子：
4.6
作者：
通讯作者：
--
影响因子：
16.6
作者：
Egervari, Gabor;Akpoyibo, Diana;Hurd, Yasmin L.
通讯作者：
Hurd, Yasmin L.
影响因子：
8.2
作者：
Green, Jacob M.;Sundman, Mark H.;Chou, Ying-Hui
通讯作者：
Chou, Ying-Hui