Neuroimmune basis of alcoholic brain damage.
Neuroimmune basis of alcoholic brain damage.
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DOI：
10.1016/b978-0-12-801284-0.00010-5
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发表时间：
2014
影响因子：
--
通讯作者：
Vetreno RP
中科院分区：
文献类型：
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作者：
Crews FT;Vetreno RP
酒精引起的脑损伤很可能是与酒精依赖相关的功能障碍的糟糕决定的原因之一。人类酗酒者的大脑体积在全球范围内丧失，最严重的是额叶皮质。狂饮诱导的神经免疫基因通过增加氧化应激，特别是NADPH氧化酶诱导的氧化应激，增加神经退行性变。此外，HMGB1-TLR4和先天免疫的NF-κB靶基因增加，导致对乙醇和其他释放HMGB1或直接刺激TLR受体和/或NMDARs的药物的持久和敏化的神经免疫反应。神经免疫信号和谷氨酸兴奋毒性与酒精性神经变性有关。青少年酒精滥用模型会导致显著的额叶皮质退化，并显示出最严重的海马神经发生丧失。青春期是酒精引起的神经退行性变和脑结构、基因表达和成年表型成熟的高危时期。综上所述，这些发现支持这样的假设，即青春期是大脑神经免疫基因表达持续和长期增加的风险时期，这些基因表达促进了酒精消费、神经免疫基因诱导和神经变性的持续和长期增加，我们发现这些都与酒精使用障碍有关。
Alcohol-induced brain damage likely contributes to the dysfunctional poor decisions associated with alcohol dependence. Human alcoholics have a global loss of brain volume that is most severe in the frontal cortex. Neuroimmune gene induction by binge drinking increases neurodegeneration through increased oxidative stress, particularly NADPH oxidase-induced oxidative stress. In addition, HMGB1-TLR4 and innate immune NF-κB target genes are increased leading to persistent and sensitized neuroimmune responses to ethanol and other agents that release HMGB1 or directly stimulate TLR receptors and/or NMDA receptors. Neuroimmune signaling and glutamate excitotoxicity are linked to alcoholic neurodegeneration. Models of adolescent alcohol abuse lead to significant frontal cortical degeneration and show the most severe loss of hippocampal neurogenesis. Adolescence is a period of high risk for ethanol-induced neurodegeneration and alterations in brain structure, gene expression, and maturation of adult phenotypes. Together, these findings support the hypothesis that adolescence is a period of risk for persistent and long-lasting increases in brain neuroimmune gene expression that promote persistent and long-term increases in alcohol consumption, neuroimmune gene induction, and neurodegeneration that we find associated with alcohol use disorders.