Wang Feng, Cui Na, Yang Lijun, Shi Lin, Li Qian, Zhang Gengshen, Wu Jianliang, Zheng Jun, Jiao Baohua
Department of Neurosurgery, The Second Hospital of Hebei Medical University, 215 Heping Road, Shijiazhuang, 050000, Hebei, China.
Department of Reproductive Medicine, The Second Hospital of Hebei Medical University, Shijiazhuang, 050000, China.
Cell Mol Neurobiol. 2015 Oct;35(7):1003-15. doi: 10.1007/s10571-015-0195-5. Epub 2015 Apr 22.
Resveratrol is a naturally occurring phytoalexin found in red grapes, and believed to have neuroprotective, anti-oxidant, and anti-inflammatory effects. But little is known about its effect on the neural impairments induced by microglial over-activation, which leads to neuroinflammation and multiple pathophysiological damages. In this study, we aimed to investigate the protective effects of resveratrol on the impairments of neural development by microglial over-activation insult. The results indicated that resveratrol inhibited the lipopolysaccharide (LPS)-dependent release of cytokines from activated microglia and LPS-dependent changes in NF-κB signaling pathway. Conditioned medium (CM) from activated microglia treated by resveratrol directly protected primary cultured hippocampal neurons against LPS-CM-induced neuronal death, and restored the inhibitory effects of LPS-CM on dendrite sprouting and outgrowth. Finally, neurons cultured in CM from LPS-stimulated microglia treated by resveratrol exhibited increased spine density compared to those without resveratrol treatment. Our findings support that resveratrol inhibits microglial over-activation and alleviates neuronal injuries induced by microglial activation. Our study suggests the use of resveratrol as an alternative intervention approach that could prevent further neuronal insults.
白藜芦醇是一种天然存在的植物抗毒素，存在于红葡萄中，被认为具有神经保护、抗氧化和抗炎作用。但关于其对小胶质细胞过度激活所诱导的神经损伤的影响却知之甚少，小胶质细胞过度激活会导致神经炎症和多种病理生理损伤。在本研究中，我们旨在探究白藜芦醇对小胶质细胞过度激活损伤所致神经发育损伤的保护作用。结果表明，白藜芦醇抑制了活化小胶质细胞中脂多糖（LPS）依赖性细胞因子的释放以及LPS依赖性NF-κB信号通路的变化。经白藜芦醇处理的活化小胶质细胞的条件培养基（CM）直接保护原代培养的海马神经元免受LPS-CM诱导的神经元死亡，并恢复了LPS-CM对树突发芽和生长的抑制作用。最后，与未经白藜芦醇处理的神经元相比，在经白藜芦醇处理的LPS刺激的小胶质细胞的CM中培养的神经元表现出更高的棘密度。我们的研究结果支持白藜芦醇可抑制小胶质细胞过度激活并减轻小胶质细胞激活所诱导的神经元损伤。我们的研究表明，使用白藜芦醇作为一种替代干预方法可以预防进一步的神经元损伤。
