Department of Pharmacology, Shenyang Pharmaceutical University, 110016, Shenyang, PR China.
Department of Pharmacology, Shenyang Pharmaceutical University, 110016, Shenyang, PR China.
Behav Brain Res. 2013 Jan 1;236(1):270-282. doi: 10.1016/j.bbr.2012.08.052. Epub 2012 Sep 5.
Microglia function as the primary immune effector cells in the brain and play a pivotal role in the neuroinflammatory processes which are critical component of neurodegenerative diseases. Alcohol abuse has been considered as one of the common reasons for neurodegeneration although the causative factors are poorly understood. Here, we investigated whether activated microglia were implicated in neurodegeneration and cognitive dysfunctions in adult rats after intermittent alcohol abuse. Rats were given orally a priming dose of 5 g/kg ethanol and then 3g/kg every 8h for 4 days, followed by a 3-day ethanol-withdrawal period. These 4 days of ethanol treatments were repeated four times intermittently to simulate the binge drinking of human alcoholics. Neurodegeneration and microglial activation were detected by Fluoro-Jade B staining, Golgi staining, immunohistochemistry and ELISA, respectively, while cognitive function was assessed by Morris water maze and novel object recognition. The results showed that microglial activation and inflammatory cytokine expression were obvious in the parietal association cortex, entorhinal cortex and hippocampus accompanied by neurodegeneration following ethanol treatment. Moreover, learning and memory abilities also declined following ethanol treatments. However, the hypertrophied microglia disappeared accompanied by the decrease of inflammatory cytokines levels on day 4, and ramified microglial proliferated significantly on day 14 after ethanol withdrawal, along with a recovery from neuronal damage and cognitive impairment. Thus, the present study indicated that activated microglia might be involved in neurodegeneration and cognitive dysfunctions induced by intermittent ethanol exposure, and neurotrophic microglia appear to have a contribution to the recovery during abstinence.
小胶质细胞作为大脑中的主要免疫效应细胞，在神经炎症过程中发挥关键作用，而神经炎症是神经退行性疾病的重要组成部分。尽管其致病因素尚不清楚，但酗酒已被认为是导致神经退行性变的常见原因之一。在这里，我们研究了在成年大鼠间歇性酒精滥用后，激活的小胶质细胞是否与神经退行性变和认知功能障碍有关。大鼠经口给予 5g/kg 乙醇的启动剂量，然后每 8 小时给予 3g/kg，持续 4 天，随后进行 3 天的乙醇戒断期。这些 4 天的乙醇处理重复 4 次，以模拟人类酗酒者的 binge drinking。通过荧光金染色、高尔基染色、免疫组织化学和 ELISA 分别检测神经退行性变和小胶质细胞激活，通过 Morris 水迷宫和新物体识别评估认知功能。结果显示，乙醇处理后，顶叶联合皮层、内嗅皮层和海马区的小胶质细胞激活和炎症细胞因子表达明显，并伴有神经退行性变。此外，乙醇处理后学习和记忆能力也下降。然而，在乙醇戒断后第 4 天，肥大的小胶质细胞消失，炎症细胞因子水平下降，第 14 天分枝状小胶质细胞明显增殖，神经元损伤和认知障碍得到恢复。因此，本研究表明，激活的小胶质细胞可能参与间歇性乙醇暴露引起的神经退行性变和认知功能障碍，神经营养小胶质细胞可能有助于戒断期间的恢复。
