可卡因成瘾中的DISC1信号传导：迈向共病的分子机制
DISC1 signaling in cocaine addiction: Towards molecular mechanisms of co-morbidity.
作者信息
Gancarz Amy, Jouroukhin Yan, Saito Atsushi, Shevelkin Alexey, Mueller Lauren E, Kamiya Atsushi, Dietz David M, Pletnikov Mikhail V
机构信息
The State University of New York at Buffalo, Buffalo, NY, USA.
Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, USA.
出版信息
Neurosci Res. 2016 Apr;105:70-4. doi: 10.1016/j.neures.2015.09.001. Epub 2015 Sep 15.
Substance abuse and other psychiatric diseases may share molecular pathology. In order to test this hypothesis, we examined the role of Disrupted In Schizophrenia 1 (DISC1), a psychiatric risk factor, in cocaine self-administration (SA). Cocaine SA significantly increased expression of DISC1 in the nucleus accumbens (NAc); while knockdown of DISC1 in NAc significantly increased cocaine SA and decreased phosphorylation of GSK-3β at Ser9 compared to scrambled shRNA. Our study provides the first mechanistic evidence of a critical role of DISC1 in drug-induced behavioral neuroadaptations and sheds more light at the shared molecular pathology of drug abuse and other major psychiatric disorders.
药物滥用和其他精神疾病可能具有共同的分子病理学机制。为了验证这一假说，我们研究了精神分裂症相关1基因（DISC1）这一精神疾病风险因素在可卡因自我给药（SA）中的作用。可卡因自我给药显著增加了伏隔核（NAc）中DISC1的表达；而与乱序短发夹RNA相比，伏隔核中DISC1基因敲低显著增加了可卡因自我给药，并降低了糖原合成酶激酶3β（GSK-3β）在丝氨酸9位点的磷酸化水平。我们的研究首次提供了DISC1在药物诱导的行为神经适应性变化中起关键作用的机制证据，并为药物滥用和其他主要精神疾病的共同分子病理学机制提供了更多线索。
Zotero 插件