Dynamic regulation of CeA gene expression during acute and protracted abstinence from chronic binge drinking of male and female C57BL/6J mice

IF 2.5 4区 医学 Q3 PHARMACOLOGY & PHARMACY
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Abstract

While there are numerous brain regions that have been shown to play a role in this AUD in humans and animal models, the central nucleus of the amygdala (CeA) has emerged as a critically important locus mediating binge alcohol consumption. In this study, we sought to understand how relative gene expression of key signaling molecules in the CeA changes during different periods of abstinence following bouts of binge drinking. To test this, we performed drinking in the dark (DID) on two separate cohorts of C57BL/6J mice and collected CeA brain tissue at 1 day (acute) and 7 days (protracted) abstinence after DID. We used qRTPCR to evaluate relative gene expression changes of 25 distinct genes of interest related to G protein-coupled receptors (GPCRs), neuropeptides, ion channel subunits, and enzymes that have been previously implicated in AUD. Our findings show that during acute abstinence CeA punches collected from female mice had upregulated relative mRNA expression of the gamma-aminobutyric acid receptor subunit alpha 2 (Gabra2), and the peptidase, angiotensinase c (Prcp). CeA punches from male mice at the same time point in abstinence had upregulated relative mRNA encoding for neuropeptide-related molecules, neuropeptide Y (Npy) and somatostatin (Sst), as well as the neuropeptide Y receptor Y2 (Npyr2), but downregulated Glutamate ionotropic receptor NMDA type subunit 1 (Grin1). After protracted abstinence, CeA punches collected from female mice had increased mRNA expression of corticotropin releasing hormone (Crh) and Npy. CeA punches collected from male mice at the same timepoint had upregulated relative mRNA expression of Npy2r, Npy, and Sst. Our findings support that there are differences in how the CeA of male and female mice respond to binge-alcohol exposure, highlighting the need to understand the implications of such differences in the context of AUD and binge drinking behavior.

雌雄 C57BL/6J 小鼠在急性和长期戒断慢性暴饮过程中 CeA 基因表达的动态调控。
在人类和动物模型中,有许多脑区已被证明在这种AUD中发挥作用,而杏仁核中央核(CeA)已成为介导暴饮暴食的一个极其重要的部位。在本研究中,我们试图了解在暴饮暴食后的不同戒酒期,杏仁核中央核(CeA)中关键信号分子的相对基因表达是如何变化的。为了验证这一点,我们对两组不同的 C57BL/6J 小鼠进行了黑暗饮酒(DID),并收集了 DID 后禁欲 1 天(急性)和 7 天(长期)的 CeA 脑组织。我们使用 qRTPCR 评估了与 G 蛋白偶联受体 (GPCR)、神经肽、离子通道亚基和酶有关的 25 种不同基因的相对表达变化,这些基因以前曾与 AUD 有过关联。我们的研究结果表明,在急性戒断期间,从雌性小鼠身上收集到的CeA打孔处的γ-氨基丁酸受体亚基α2(Gabra2)和肽酶、血管紧张素酶c(Prcp)的相对mRNA表达上调。在禁欲的同一时间点,雄性小鼠的 CeA 冲剂编码神经肽相关分子神经肽 Y(Npy)和体生长抑素(Sst)以及神经肽 Y 受体 Y2(Npyr2)的相对 mRNA 上调,但谷氨酸离子型受体 NMDA 型亚基 1(Grin1)下调。在长期禁欲后,从雌性小鼠身上采集的 CeA 打孔处促肾上腺皮质激素释放激素(Crh)和 Npy 的 mRNA 表达增加。在同一时间点从雄性小鼠身上采集的CeA打孔液中,Npy2r、Npy和Sst的相对mRNA表达量上调。我们的研究结果表明,雄性和雌性小鼠的CeA对暴饮暴食酒精暴露的反应存在差异,这突出表明有必要了解这种差异对AUD和暴饮暴食行为的影响。
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来源期刊
Alcohol
Alcohol 医学-毒理学
CiteScore
4.60
自引率
4.30%
发文量
74
审稿时长
15.6 weeks
期刊介绍: Alcohol is an international, peer-reviewed journal that is devoted to publishing multi-disciplinary biomedical research on all aspects of the actions or effects of alcohol on the nervous system or on other organ systems. Emphasis is given to studies into the causes and consequences of alcohol abuse and alcoholism, and biomedical aspects of diagnosis, etiology, treatment or prevention of alcohol-related health effects. Intended for both research scientists and practicing clinicians, the journal publishes original research on the neurobiological, neurobehavioral, and pathophysiological processes associated with alcohol drinking, alcohol abuse, alcohol-seeking behavior, tolerance, dependence, withdrawal, protracted abstinence, and relapse. In addition, the journal reports studies on the effects alcohol on brain mechanisms of neuroplasticity over the life span, biological factors associated with adolescent alcohol abuse, pharmacotherapeutic strategies in the treatment of alcoholism, biological and biochemical markers of alcohol abuse and alcoholism, pathological effects of uncontrolled drinking, biomedical and molecular factors in the effects on liver, immune system, and other organ systems, and biomedical aspects of fetal alcohol spectrum disorder including mechanisms of damage, diagnosis and early detection, treatment, and prevention. Articles are published from all levels of biomedical inquiry, including the following: molecular and cellular studies of alcohol''s actions in vitro and in vivo; animal model studies of genetic, pharmacological, behavioral, developmental or pathophysiological aspects of alcohol; human studies of genetic, behavioral, cognitive, neuroimaging, or pathological aspects of alcohol drinking; clinical studies of diagnosis (including dual diagnosis), treatment, prevention, and epidemiology. The journal will publish 9 issues per year; the accepted abbreviation for Alcohol for bibliographic citation is Alcohol.
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