Effects of Ethanol on Immune Response in the Brain: Region-Specific Changes in Adolescent Versus Adult Mice
Effects of Ethanol on Immune Response in the Brain: Region-Specific Changes in Adolescent Versus Adult Mice
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DOI：
10.1111/acer.12244
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发表时间：
2014-02-01
影响因子：
3.2
通讯作者：
Drew, Paul D.
中科院分区：
文献类型：
--
作者：
Kane, Cynthia J. M.;Phelan, Kevin D.;Drew, Paul D.
背景酒精的使用贯穿整个生命周期，从青春期开始一直持续到成年。乙醇 (EtOH) 诱导的病理学随年龄而变化，包括神经发生、神经变性和神经胶质细胞激活的变化。乙醇诱导的神经胶质活化和免疫活性变化被认为有助于乙醇诱导的神经病理学。最近的研究表明神经胶质源性神经免疫分子在酒精滥用和成瘾中发挥着新的作用。方法对青少年和成年C57BL/6小鼠进行6g/kg EtOH灌胃处理10天，并在处理后1天收获组织。我们比较了 EtOH 对海马、小脑和大脑皮层趋化因子和细胞因子表达以及星形胶质细胞胶质原纤维酸性蛋白 (GFAP) 免疫染色和形态的影响。结果与对照组相比，EtOH 增加了成年小鼠所有 3 个区域中趋化因子 CCL2/MCP-1 的 mRNA 水平。细胞因子白介素 6 (IL-6) 仅在成人小脑中选择性增加。乙醇不会影响成年动物这些脑区中细胞因子肿瘤坏死因子-α (TNF-) 的 mRNA 水平。有趣的是，青春期小鼠海马体、小脑或皮质中的 CCL2、IL-6 和 TNF-mRNA 水平并未增加。成年和青少年小鼠的 EtOH 治疗导致 GFAP 免疫染色增加。结论总的来说，这些数据表明对神经炎症和成瘾相关分子以及星形胶质细胞表型的 EtOH 调节存在年龄和区域特异性敏感性。这些研究可能对不同酒精引起的神经病理学和整个生命周期的酒精成瘾具有重要意义。
BackgroundAlcohol use occurs across the life span beginning in adolescence and continuing through adulthood. Ethanol (EtOH)-induced pathology varies with age and includes changes in neurogenesis, neurodegeneration, and glial cell activation. EtOH-induced changes in glial activation and immune activity are believed to contribute to EtOH-induced neuropathology. Recent studies indicate an emerging role of glial-derived neuroimmune molecules in alcohol abuse and addiction.MethodsAdolescent and adult C57BL/6 mice were treated via gavage with 6g/kg EtOH for 10days, and tissue was harvested 1day post treatment. We compared the effects of EtOH on chemokine and cytokine expression and astrocyte glial fibrillary acidic protein (GFAP) immunostaining and morphology in the hippocampus, cerebellum, and cerebral cortex.ResultsEtOH increased mRNA levels of the chemokine CCL2/MCP-1 in all 3 regions of adult mice relative to controls. The cytokine interleukin-6 (IL-6) was selectively increased only in the adult cerebellum. EtOH did not affect mRNA levels of the cytokine tumor necrosis factor-alpha (TNF-) in any of these brain regions in adult animals. Interestingly, CCL2, IL-6, and TNF- mRNA levels were not increased in the hippocampus, cerebellum, or cortex of adolescent mice. EtOH treatment of adult and adolescent mice resulted in increased GFAP immunostaining.ConclusionsCollectively, these data indicate an age- and region-specific susceptibility to EtOH regulation of neuroinflammatory and addiction-related molecules as well as astrocyte phenotype. These studies may have important implications concerning differential alcohol-induced neuropathology and alcohol addiction across the life span.