Convergent abnormalities in striatal gene networks in human cocaine use disorder and mouse cocaine administration models.
Convergent abnormalities in striatal gene networks in human cocaine use disorder and mouse cocaine administration models.
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DOI：
10.1126/sciadv.add8946
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发表时间：
2023-02-10
期刊：
影响因子：
13.6
通讯作者：
中科院分区：
文献类型：
--
作者：
可卡因使用障碍（CUD）是一种难治性综合征，药物过量死亡率的上升代表了一场重大的公共卫生危机，给患者和社会带来了巨大的个人和经济成本。可卡因使用的急剧增加推动了对这种目前缺乏有效治疗方案的慢性复发性脑部疾病更好的机制洞察的迫切需要。为了研究所涉及的转录组学变化，我们对两个与CUD密切相关的纹状体脑区域进行了RNA测序，这两个区域是CUD患者和匹配对照的纹状体核和尾状核。加权基因共表达分析确定了富含离子型受体的CUD特异性基因网络，并与降低神经炎症有关，与阿片类药物使用障碍中发现的促炎反应形成对比。整合来自小鼠可卡因自我给药模型的综合转录组数据集，揭示了CUD中进化上保守的基因网络，特别是D1中等多刺神经元是可卡因诱导的可塑性的驱动因素。皮质醇使用障碍改变神经炎症和离子型受体的进化保守的纹状体基因网络。
Cocaine use disorder (CUD) is an intractable syndrome, and rising overdose death rates represent a substantial public health crisis that exacts tremendous personal and financial costs on patients and society. Sharp increases in cocaine use drive the urgent need for better mechanistic insight into this chronic relapsing brain disorder that currently lacks effective treatment options. To investigate the transcriptomic changes involved, we conducted RNA sequencing on two striatal brain regions that are heavily implicated in CUD, the nucleus accumbens and caudate nucleus, from men suffering from CUD and matched controls. Weighted gene coexpression analyses identified CUD-specific gene networks enriched in ionotropic receptors and linked to lowered neuroinflammation, contrasting the proinflammatory responses found in opioid use disorder. Integration of comprehensive transcriptomic datasets from mouse cocaine self-administration models revealed evolutionarily conserved gene networks in CUD that implicate especially D1 medium spiny neurons as drivers of cocaine-induced plasticity. Cocaine use disorder alters evolutionarily conserved striatal gene networks of neuroinflammation and ionotropic receptors.
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影响因子：
30.8
作者：
Finucane HK;Bulik-Sullivan B;Gusev A;Trynka G;Reshef Y;Loh PR;Anttila V;Xu H;Zang C;Farh K;Ripke S;Day FR;ReproGen Consortium;Schizophrenia Working Group of the Psychiatric Genomics Consortium;RACI Consortium;Purcell S;Stahl E;Lindstrom S;Perry JR;Okada Y;Raychaudhuri S;Daly MJ;Patterson N;Neale BM;Price AL
通讯作者：
Price AL
影响因子：
11
作者：
Fernàndez-Castillo N;Cabana-Domínguez J;Corominas R;Cormand B
通讯作者：
Cormand B
影响因子：
4.6
作者：
Cahill KM;Huo Z;Tseng GC;Logan RW;Seney ML
通讯作者：
Seney ML
DOI：
10.1111/gbb.12179
发表时间：
2014-11
期刊：
Genes, brain, and behavior
影响因子：
--
作者：
Enoch MA;Rosser AA;Zhou Z;Mash DC;Yuan Q;Goldman D
通讯作者：
Goldman D
影响因子：
56.9
作者：
Fienberg, AA;Hiroi, N;Greengard, P
通讯作者：
Greengard, P