Increased transcription of TSPO, HDAC2, and HDAC6 in the amygdala of males with alcohol use disorder.
Increased transcription of TSPO, HDAC2, and HDAC6 in the amygdala of males with alcohol use disorder.
复制标题
酒精使用障碍男性杏仁核中TSPO、HDAC2和HDAC6转录增加。
DOI：
10.1002/brb3.1961
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发表时间：
2021-03
影响因子：
3.1
通讯作者：
Volkow ND
中科院分区：
文献类型：
--
作者：
De Carvalho LM;Wiers CE;Sun H;Wang GJ;Volkow ND
反复暴露于高剂量的酒精会触发神经炎症过程，导致酒精使用障碍（AUD）的渴望和情绪功能障碍。转运蛋白（TSPO）的上调被认为是神经炎症的生物标志物，TSPO配体已被用作神经炎症的神经成像生物标志物。表观遗传机制也涉及对酒精的神经炎症反应，并且已经报道了暴露于慢性酒精的动物的大脑中HDAC2和HDAC6的表达升高。本研究在与AUD相关的四个脑区中检查了TSPO、HDAC 2和HDAC 6在人死后脑组织中的转录调节，所述人死后脑组织来自先前诊断为AUD的男性（n = 11），与年龄匹配的非依赖性男性（n = 13）相比：前额叶皮质（PFC）、丘脑核（NAc）、海马（HPP）和杏仁核（AMY）。与对照组相比，AUD中AMY和PFC中的转运蛋白mRNA水平以及AMY中的HDAC2和HDAC6 mRNA水平上调。在AMY中，TSPO mRNA水平与HDAC 2和HDAC 6 mRNA水平呈正相关，表明HDAC 2和HDAC 6可能在该脑区调节TSPO。相反，在NAc和HPP中，TSPO、HDAC 2和HDAC 6没有组间差异。我们的研究是第一个发现上调的TSPO mRNA水平AMY和PFC在死后的大脑从AUD一致的神经炎症，并在杏仁核，他们牵连的HDAC2和HDAC6的TSPO的表观遗传调节。第一项研究，以确定TSPO mRNA水平在死后AUD脑。与对照组相比，AUD患者杏仁核中TSPO、HDAC2和HDAC6 mRNA水平上调，前额叶皮质中TSPO上调。杏仁核中TSPO、HDAC2和HDAC6 mRNA水平之间的正相关性。
Repeated exposure to high doses of alcohol triggers neuroinflammatory processes that contribute to craving and mood dysfunction in alcohol use disorder (AUD). The upregulation of the translocator protein (TSPO) is considered a biomarker of neuroinflammation, and TSPO ligands have been used as neuroimaging biomarkers of neuroinflammation. Epigenetic mechanisms are also implicated in neuroinflammatory responses to alcohol, and elevated expression of HDAC2 and HDAC6 has been reported in the brain of animals exposed to chronic alcohol. The present study examined the transcriptional regulation of TSPO, HDAC2, and HDAC6 in human postmortem brain tissue from males previously diagnosed with AUD (n = 11) compared to age‐matched nondependent males (n = 13) in four brain regions relevant to AUD: prefrontal cortex (PFC), nucleus accumbens (NAc), hippocampus (HPP), and amygdala (AMY). Translocator protein mRNA levels in AMY and PFC and HDAC2 and HDAC6 mRNA levels in AMY were upregulated in AUD compared to controls. In AMY, TSPO mRNA levels were positively associated with HDAC2 and HDAC6 mRNA levels, suggesting a possible regulation of TSPO by HDAC2 and HDAC6 in this brain region. In contrast, there were no group differences for TSPO, HDAC2, and HDAC6 in NAc and HPP. Our study is the first to find upregulated TSPO mRNA levels in AMY and PFC in postmortem brains from AUD consistent with neuroinflammation, and in the amygdala, they implicate epigenetic regulation of TSPO by HDAC2 and HDAC6. First study to identify TSPO mRNA levels in the postmortem AUD brain. Upregulation of TSPO, HDAC2, and HDAC6 mRNA levels in the amygdala, and upregulation of TSPO in the prefrontal cortex in AUD compared to controls. Positive association between the TSPO, HDAC2, and HDAC6 mRNA levels in amygdala.
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在酒精依赖性中，流动蛋白的体内成像，即活化的小胶质细胞的标志。
影响因子：
11
作者：
Hillmer AT;Sandiego CM;Hannestad J;Angarita GA;Kumar A;McGovern EM;Huang Y;O'Connor KC;Carson RE;O'Malley SS;Cosgrove KP
通讯作者：
Cosgrove KP
DOI：
10.3109/00048678009159381
发表时间：
1980-01-01
影响因子：
4.6
作者：
LAMBIE, DG;JOHNSON, RH;WHITESIDE, EA
通讯作者：
WHITESIDE, EA
影响因子：
4.5
作者：
Lin, Ran;Rittenhouse, Danielle;Wallace, Douglas C.
通讯作者：
Wallace, Douglas C.
影响因子：
6.4
作者：
Gui, Yaxing;Marks, Jordan D.;Serrano-Pozo, Alberto
通讯作者：
Serrano-Pozo, Alberto
影响因子：
4.2
作者：
Kannan, Vishnu;Brouwer, Nieske;Boddeke, Hendrikus W. G. M.
通讯作者：
Boddeke, Hendrikus W. G. M.