Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang 110016, PR China.
State Key Laboratory of Biomacromolecules, Insititute of Biophysics, Chinese Academy of Sciences, Beijing 100101, PR China.
Pharmacol Ther. 2014 Dec;144(3):321-37. doi: 10.1016/j.pharmthera.2014.07.002. Epub 2014 Jul 10.
Alcohol abuse can result in significant alterations to the structure of the brain and ultimately to behavioral dysfunctions. Epidemiological studies have shown that alcoholism is closely associated with impaired memory and judgment. However, the degree of deficit (brain injury) depends on factors such as the age of onset, duration of heavy drinking, continuous versus periodic (binge) drinking and the typical amount consumed per session. In recent years, neuroinflammation has been proposed as one of the alcoholism-induced neuropathological mechanisms, since increased levels of microglial markers are observed in the brains of both post-mortem human alcoholics and various alcohol-treated animals, from newborn or adolescent rodents to adult rodents. Many studies have investigated how microglia modulate alcohol-induced behavioral changes such as cognitive deficits, abnormal locomotor activity, motor impairment and mood disturbance. Importantly, we try to characterize and compare the distinct features in different ethanol (EtOH)-induced neurodegenerative disease (NDD) models. Moreover, mounting evidence indicates that in response to certain environmental toxins, microglia can become over-activated under oxidative stress, releasing pro-inflammatory mediators that cause central nervous system (CNS) disease. The molecular mechanisms involve free radical formation and the release of pro-inflammatory cytokines that are detrimental to neighboring neurons and interfere with the molecules regulating cell-cell interactions. The identification and understanding of the cellular and molecular mechanisms of microglial activation are described, as well as multiple downstream targets, in different alcohol-treated animal models. This review might contribute to the development of treatments and/or therapeutic agents that can reduce or eliminate the deleterious effects of alcohol-induced NDD.
酗酒可导致大脑结构发生重大改变，并最终导致行为功能障碍。流行病学研究表明，酗酒与记忆和判断力受损密切相关。然而，这种缺陷的程度（脑损伤）取决于发病年龄、大量饮酒的持续时间、持续饮酒与周期性（狂饮）饮酒以及每次饮酒的典型量等因素。近年来，神经炎症被认为是酒精中毒引起的神经病理学机制之一，因为在尸检酒精中毒者和各种经酒精处理的动物的大脑中都观察到小胶质细胞标志物水平升高，这些动物包括新生或青春期的啮齿动物到成年啮齿动物。许多研究都调查了小胶质细胞如何调节酒精引起的行为变化，如认知缺陷、异常运动活动、运动障碍和情绪障碍。重要的是，我们试图描述和比较不同乙醇（EtOH）诱导的神经退行性疾病（NDD）模型中的不同特征。此外，越来越多的证据表明，在某些环境毒素的作用下，小胶质细胞在氧化应激下可能过度激活，释放促炎介质，导致中枢神经系统（CNS）疾病。分子机制涉及自由基的形成和促炎细胞因子的释放，这些细胞因子对邻近神经元有害，并干扰调节细胞-细胞相互作用的分子。本文描述了不同酒精处理的动物模型中小胶质细胞激活的细胞和分子机制，以及多个下游靶点。这篇综述可能有助于开发能够减轻或消除酒精诱导的 NDD 有害影响的治疗方法和/或治疗剂。
