Targeting prefrontal cortex GABAergic microcircuits for the treatment of alcohol use disorder.
Targeting prefrontal cortex GABAergic microcircuits for the treatment of alcohol use disorder.
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DOI：
10.3389/fnsyn.2022.936911
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发表时间：
2022
影响因子：
3.7
通讯作者：
Joffe, Max E. E.
中科院分区：
文献类型：
--
作者：
Fish, Kenneth N. N.;Joffe, Max E. E.
关键词：
开发酒精使用障碍（AUD）的新疗法对于改善患者的治疗效果和减轻与该疾病相关的痛苦至关重要。更好地了解酒精改变大脑功能的分子和神经回路机制将有助于合理开发新的有效治疗方法。临床研究一致表明前额皮质 (PFC) 功能与 AUD 症状相关。人群水平分析已将 PFC 结构和功能与酗酒和/或 AUD 诊断联系起来。因此，针对特定的 PFC 细胞类型和神经回路有望开发新的治疗方法。在这里，我们概述了 PFC 内抑制性神经元亚型的形式和功能的巨大多样性，并描述了它们的治疗潜力。然后我们总结了 AUD 群体遗传学研究、临床神经生理学发现和转化神经科学发现。这项研究总体表明，通过 PFC 抑制性微电路快速传输的变化是乙醇神经生物学效应的核心组成部分，也是 AUD 的核心症状。最后，我们认为，迫切需要将性别作为生物变量和人类死后脑组织进行检查，以最大限度地努力将研究结果转化为新的临床治疗方法。
Developing novel treatments for alcohol use disorders (AUDs) is of paramount importance for improving patient outcomes and alleviating the suffering related to the disease. A better understanding of the molecular and neurocircuit mechanisms through which alcohol alters brain function will be instrumental in the rational development of new efficacious treatments. Clinical studies have consistently associated the prefrontal cortex (PFC) function with symptoms of AUDs. Population-level analyses have linked the PFC structure and function with heavy drinking and/or AUD diagnosis. Thus, targeting specific PFC cell types and neural circuits holds promise for the development of new treatments. Here, we overview the tremendous diversity in the form and function of inhibitory neuron subtypes within PFC and describe their therapeutic potential. We then summarize AUD population genetics studies, clinical neurophysiology findings, and translational neuroscience discoveries. This study collectively suggests that changes in fast transmission through PFC inhibitory microcircuits are a central component of the neurobiological effects of ethanol and the core symptoms of AUDs. Finally, we submit that there is a significant and timely need to examine sex as a biological variable and human postmortem brain tissue to maximize the efforts in translating findings to new clinical treatments.
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