Neuroinflammatory pathways in binge alcohol-induced neuronal degeneration: oxidative stress cascade involving aquaporin, brain edema, and phospholipase A2 activation.
Neuroinflammatory pathways in binge alcohol-induced neuronal degeneration: oxidative stress cascade involving aquaporin, brain edema, and phospholipase A2 activation.
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DOI：
10.1007/s12640-011-9276-5
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发表时间：
2012-01
影响因子：
3.7
通讯作者：
Neafsey EJ
中科院分区：
文献类型：
--
作者：
Collins MA;Neafsey EJ
在成年大鼠模型中，慢性酗酒暴露导致皮质和海马神经元变性，兴奋性毒性受体拮抗剂不能减轻这种变性，但抗氧化剂可以防止这种变性。神经炎症（神经胶质-神经元）信号通路被认为是氧化应激和脑损伤的基础。基于我们的实验结果以及对胶质细胞水通道的促神经炎潜力的了解，我们提出水通道蛋白-4的诱导可以是酒精神经毒性作用的关键起始因子，通过煽动基于细胞水肿的神经炎症级联反应，涉及磷脂酶A2活性增加，多不饱和脂肪酸释放/膜耗竭，促生存信号传导减少和氧化应激。一个可测试的方案，这一途径，结合最近的研究结果，酒精脑的文献表明神经免疫激活的作用（上调NF-κ B，促炎细胞因子和Toll样受体）。我们提出的论点，这种神经免疫激活可能与水通道蛋白4和神经胶质细胞肿胀增加，甚至依赖于。
Chronic binge alcohol exposure in adult rat models causes neuronal degeneration in the cortex and hippocampus that is not reduced by excitotoxic receptor antagonists, but is prevented by antioxidants. Neuroinflammatory (glial-neuronal) signaling pathways are believed to underlie the oxidative stress and brain damage. Based on our experimental results as well as increased knowledge about the pro-neuroinflammatory potential of glial water channels, we propose that induction of aquaporin-4 can be a critical initiating factor in alcohol’s neurotoxic effects, via the instigation of cellular edema-based neuroinflammatory cascades involving increased phospholipase A2 activities, polyunsaturated fatty acid release/membrane depletion, decreased prosurvival signaling, and oxidative stress. A testable scheme for this pathway is presented that incorporates recent findings in the alcohol-brain literature indicating a role for neuroimmune activation (upregulation of NF-kappaB, proinflammatory cytokines and toll-like receptors). We present the argument that such neuroimmune activation could be associated with or even dependent on increased aquaporin-4 and glial swelling as well.