Department of Anatomy & Neurobiology, University of Kentucky, Lexington, KY 40536, USA.
J Neuroimmunol. 2010 Aug 25;225(1-2):43-51. doi: 10.1016/j.jneuroim.2010.04.010. Epub 2010 May 14.
Aberrant microglia activation causes dopaminergic neuronal loss and nitric oxide produced by microglia plays a critical role in dopaminergic neuronal degeneration. However, no study has determined if GDNF protects dopaminergic neurons via inhibiting nitric oxide generation in Parkinson's disease animal model. We report that GDNF not only reduces lipopolysaccharide-induced degeneration of dopaminergic neurons, suppresses microglia activation and nitric oxide generation, but also reverses the inhibition of phosphoinositide 3-kinase (PI3K) in dopaminergic neurons and microglia. It suggests that the neuroprotective effect of GDNF on dopaminergic neurons may be related to its suppression of microglia activation-mediated nitric oxide via releasing the inhibition of PI3K in both neurons and microglia.
异常的小胶质细胞激活导致多巴胺能神经元的丢失，而小胶质细胞产生的一氧化氮在多巴胺能神经元变性中起着关键作用。然而，尚无研究确定 GDNF 是否通过抑制帕金森病动物模型中的一氧化氮生成来保护多巴胺能神经元。我们报告 GDNF 不仅减少脂多糖诱导的多巴胺能神经元变性，抑制小胶质细胞激活和一氧化氮生成，而且还逆转了多巴胺能神经元和小胶质细胞中磷酸肌醇 3-激酶 (PI3K) 的抑制作用。这表明 GDNF 对多巴胺能神经元的神经保护作用可能与其通过在神经元和小胶质细胞中释放对 PI3K 的抑制来抑制小胶质细胞激活介导的一氧化氮有关。
