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成年大鼠孕期暴露于酒精后,其大脑中自愿酒精摄入量及突触核蛋白mRNA编码的性别差异

Sex-Related Differences in Voluntary Alcohol Intake and mRNA Coding for Synucleins in the Brain of Adult Rats Prenatally Exposed to Alcohol.

作者信息

Kokhan Viktor S, Chaprov Kirill, Ninkina Natalia N, Anokhin Petr K, Pakhlova Ekaterina P, Sarycheva Natalia Y, Shamakina Inna Y

机构信息

V.P. Serbsky Federal Medical Research Centre for Psychiatry and Narcology, 119034 Moscow, Russia.

Institute of Physiologically Active Compounds RAS, 142432 Chernogolovka, Russia.

出版信息

Biomedicines. 2022 Sep 2;10(9):2163. doi: 10.3390/biomedicines10092163.

Abstract

Maternal alcohol consumption is one of the strong predictive factors of alcohol use and consequent abuse; however, investigations of sex differences in response to prenatal alcohol exposure (PAE) are limited. Here we compared the effects of PAE throughout gestation on alcohol preference, state anxiety and mRNA expression of presynaptic proteins α-, β- and γ-synucleins in the brain of adult (PND60) male and female Wistar rats. Total RNA was isolated from the hippocampus, midbrain and hypothalamus and mRNA levels were assessed with quantitative RT-PCR. Compared with naïve males, naïve female rats consumed more alcohol in "free choice" paradigm (10% ethanol vs. water). At the same time, PAE produced significant increase in alcohol consumption and preference in males but not in females compared to male and female naïve groups, correspondingly. We found significantly lower α-synuclein mRNA levels in the hippocampus and midbrain of females compared to males and significant decrease in α-synuclein mRNA in these brain areas in PAE males, but not in females compared to the same sex controls. These findings indicate that the impact of PAE on transcriptional regulation of synucleins may be sex-dependent, and in males' disruption in α-synuclein mRNA expression may contribute to increased vulnerability to alcohol-associated behavior.

摘要

母亲饮酒是酒精使用及后续滥用的重要预测因素之一;然而,关于产前酒精暴露(PAE)反应中性别差异的研究却很有限。在此,我们比较了整个孕期PAE对成年(出生后第60天)雄性和雌性Wistar大鼠大脑中酒精偏好、状态焦虑以及突触前蛋白α-、β-和γ-突触核蛋白mRNA表达的影响。从海马体、中脑和下丘脑分离出总RNA,并用定量逆转录聚合酶链反应评估mRNA水平。与未接触酒精的雄性相比,未接触酒精的雌性大鼠在“自由选择”模式下(10%乙醇与水)饮用了更多酒精。同时,与相应的未接触酒精的雄性和雌性组相比,PAE使雄性大鼠的酒精摄入量和偏好显著增加,而雌性大鼠则没有。我们发现,与雄性相比,雌性大鼠海马体和中脑中α-突触核蛋白mRNA水平显著较低,并且与同性对照相比,PAE雄性大鼠这些脑区中α-突触核蛋白mRNA显著减少,而雌性大鼠没有。这些发现表明,PAE对突触核蛋白转录调控的影响可能具有性别依赖性,并且在雄性中,α-突触核蛋白mRNA表达的破坏可能导致对酒精相关行为的易感性增加。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a7bc/9496239/e5e82bc39383/biomedicines-10-02163-g001.jpg

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