Role of PI3-K/Akt pathway and its effect on glial cell line-derived neurotrophic factor in midbrain

来源 :中国神经科学学会第四次会员代表大会暨第七届全国学术会议(The 7th Biennial Meeting and the | 被引量 : 0次 | 上传用户:thomson888
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  Aim:To explore the intracellular mechanisms underlying the survival/differentiation effect of the glial cell linederived neurotrophic factor (GDNF) on dopamine (DA) cells.Methods:Midbrain slice culture and primary cell culture were established,and the cultures were divided into 3 groups:control group,GDNF group,and the phosphatidylinositol 3-kinase/Akt (PI3-K/Akt) pathway-inhibited group.Then the expression of tyrosine hydroxylase (TH) was detected by immunostaining as well as Western blotting.Results:GDNF treatment induced an increase in the number of TH-immunoreactive (ir) cells and the neurite number of TH-ir cells,as well as in the level of TH expression in cultures (Number of Thir cells in the slice culture:control group,8.76+0.75; GDNF group,18.63±0.95.Number of TH-ir cells and neurite number of TH-ir cells in cell culture:control group,3.65±0.88 and 2.49±0.42; GDNF group,6.01±0.43 and 4.89±0.46).Meanwhile,the stimulation of cultured cells with GDNF increased the phosphorylation of Akt,which is a downstream effector of PI3-K/ Akt.The effects of GDNF were specifically blocked by the inhibitor of the PI3-K/Akt pathway,wortmannin (Number of TH-ir cells in slice culture:PI3-K/Akt pathway-inhibited group,6.98±0.58.Number of TH-ir cells and neurite number of TH-ir cells in cell culture:PI3-K/Akt pathway-inhibited group,3.79±0.62 and 2.5(h±0.25,respectively).Conclusion:The PI3-K/ Akt pathway mediates the survival/differentiation effect of GDNF on DA cells.
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