Roles of glia-derived cytokines on neuronal degeneration and regeneration
Roles of glia-derived cytokines on neuronal degeneration and regeneration
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DOI：
10.1196/annals.1366.012
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发表时间：
2006-01-01
期刊：
影响因子：
--
通讯作者：
Mizuno, Tetsuya
中科院分区：
文献类型：
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作者：
Suzumura, Akio;Takeuchi, Hideyuki;Mizuno, Tetsuya
在中枢神经系统的各种炎性或退行性疾病中，在退行性神经元周围观察到活化的小胶质细胞和反应性星形胶质细胞的积聚。这些反应性胶质细胞可能发挥神经毒性或神经保护作用。在这项研究中，我们研究了胶质细胞源性细胞因子对神经元变性和再生的影响。用LPS刺激的小胶质细胞和星形胶质细胞的上清液或各种浓度的重组细胞因子刺激富含神经元的培养物。通过MTS试验评价神经毒性。还通过树枝状串珠的频率来评估神经元损伤，发现这是神经元损伤导致细胞死亡的早期特征。通过RT PCR检测细胞因子对星形胶质细胞神经营养因子mRNA表达的影响。LPS刺激的小胶质细胞的上清液诱导神经元细胞死亡。然而，所有的重组细胞因子检查没有诱导细胞死亡，而IFN γ和TNF α诱导树突串珠，神经元损伤的早期特征。IL-1 β和TNF α增强星形胶质细胞产生神经营养因子。这些观察结果表明，胶质细胞衍生的细胞因子可能协同作用，在神经元变性与其他毒性因子产生的活化小胶质细胞，其中一些也可能通过诱导神经营养因子再生。
Accumulation of activated microglia and reactive astrocytes is observed around degenerating neurons in various inflammatory or degenerative disorders in the central nervous system. These reactive glial cells may play either neurotoxic or neuroprotective roles. In this study, we examined the effects of glia-derived cytokines on neuronal degeneration and regeneration. Neuron-rich cultures were stimulated with supernatant of microglia and astrocytes stimulated with LPS, or a various concentrations of recombinant cytokines. Neurotoxicity was evaluated by an MTS assay. Neuronal damage was also evaluated by a frequency of dendritic beading, which was found to be an early feature of neuronal damage toward cell death. Effects of the cytokines on production of neurotrophic factors by astrocytes were also examined by RT PCR for the expression of mRNA. Supernatant of LPS-stimulated microglia induced neuronal cell death. However, all the recombinant cytokines examined did not induce cell death, while IFN gamma and TNF alpha induced dendrite beading, an early feature of neuronal damage. IL-1 beta and TNF alpha enhanced the production of neurotrophic factors by astrocytes. These observations suggest that glial cell-derived cytokines may synergistically function in neuronal degeneration with other toxic factors produced by activated microglia, and that some of them may also function in regeneration by inducing neurotrophic factors.