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轨道前皮层中的适应蛋白复合体2预测酒精使用障碍

Patrick J Mulholland^1,2, Stefano Berto³, Phillip A Wilmarth⁴

¹Department of Neuroscience, Medical University of South Carolina, Charleston, SC, 29425, USA. mulholl@musc.edu.

Molecular psychiatry

|September 7, 2023

概括

这项研究揭示了与酒精使用障碍 (AUD) 相关的轨道前皮层 (OFC) 中的关键蛋白质变化. 这些发现确定了特定的蛋白质和大脑机制,可以控制物种间的酒精消费.

科学领域:

神经科学是一个神经科学.
蛋白质组学是指蛋白质组学.
遗传学遗传学是一个

背景情况:

酒精使用障碍 (AUD) 是一种严重的疾病,涉及强迫性饮酒和认知缺陷.
轨道前皮层 (OFC) 在决策和平衡奖励/风险方面发挥着至关重要的作用,在AUD中可能受到损害.
了解OFC的分子变化对于AUD研究至关重要.

研究的目的:

调查与AUD相关的人类OFC中的蛋白质组变化.
确定因过度饮酒而失调的特定蛋白质和通路.
探索控制酒精饮酒行为的跨物种机制.

主要方法:

来自AUD和对照对象的死后OFC样本的蛋白质组分析.
生物信息学和机器学习用于识别差异表达蛋白质和预测标记.
在小鼠中逆转遗传学,以验证已识别的蛋白质在酒精消费中的作用.

主要成果:

鉴定了超过4,500种蛋白质;47种性别特异性蛋白质与细胞外基质和轴突结构有关.
AUD病例显示了参与突触功能,线粒体功能和跨膜运输的蛋白质的差异表达.
机器学习确定了调节失调的先突触和线粒体蛋白质,预测了AUD严重程度;Ap2a1被验证为影响小鼠饮酒量的关键蛋白质.

结论:

过度饮酒会对人类的OFC蛋白质组产生重大影响.
已识别的OFC蛋白和通路为AUD提供了潜在的治疗点.
调节饮酒的皮质机制在各物种中都存在,其中Ap2a1发挥着重要作用.

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