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首页> 外文期刊>The European Journal of Neuroscience >Glial mechanisms underlying substance use disorders
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Glial mechanisms underlying substance use disorders

机译：隐形物质使用障碍的胶质机制

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Addiction is a devastating disorder that produces persistent maladaptive changes to the central nervous system, including glial cells. Although there is an extensive body of literature examining the neuronal mechanisms of substance use disorders, effective therapies remain elusive. Glia, particularly microglia and astrocytes, have an emerging and meaningful role in a variety of processes beyond inflammation and immune surveillance, and may represent a promising therapeutic target. Indeed, glia actively modulate neurotransmission, synaptic connectivity and neural circuit function, and are critically poised to contribute to addictive-like brain states and behaviors. In this review, we argue that glia influence the cellular, molecular, and synaptic changes that occur in neurons following drug exposure, and that this cellular relationship is critically modified following drug exposure. We discuss direct actions of abused drugs on glial function through immune receptors, such as Toll-like receptor 4, as well as other mechanisms. We highlight how drugs of abuse affect glia-neural communication, and the profound effects that glial-derived factors have on neuronal excitability, structure, and function. Recent research demonstrates that glia have brain region-specific functions, and glia in different brain regions have distinct contributions to drug-associated behaviors. We will also evaluate the evidence demonstrating that glial activation is essential for drug reward and drug-induced dopamine release, and highlight clinical evidence showing that glial mechanisms contribute to drug abuse liability. In this review, we synthesize the extensive evidence that glia have a unique, pivotal, and underappreciated role in the development and maintenance of addiction.
机译：成瘾是一种毁灭性的疾病，可产生对中枢神经系统的持续存在的不良变化，包括胶质细胞。虽然存在广泛的文献，但研究了物质使用障碍的神经元机制，但有效的疗法仍然难以捉摸。 Glia，特别是小胶质细胞和星形胶质细胞，在超出炎症和免疫监测的各种过程中具有新出现和有意义​​的作用，并且可以代表有前途的治疗目标。实际上，胶胶积极调节神经传递，突触连接和神经电路功能，并批判性地有助于令人上瘾的脑状态和行为。在本综述中，我们认为胶质胶质胶质胶质在药物暴露后的神经元中发生的细胞，分子和突触变化，并且这种细胞关系在药物暴露后受到重症修饰。我们通过免疫受体讨论滥用药物对胶质功能的直接作用，例如Toll样受体4以及其他机制。我们强调了滥用药物如何影响胶虫 - 神经通信，以及神经胶质导出因子对神经元兴奋性，结构和功能的深刻影响。最近的研究表明，Glia具有脑区域特异性功能，不同脑区的胶质胶片对药物相关行为具有明显的贡献。我们还将评估证明胶质激活的证据对于药物奖励和药物诱导的多巴胺释放至关重要，并突出显示临床证据，表明胶质机制有助于滥用药物滥用责任。在这篇综述中，我们综合了广泛的证据，即胶质胶片在成瘾的开发和维护方面具有独特，关键和低估的作用。

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