Abstract
Aim:
To explore the intracellular mechanisms underlying the survival/differentiation effect of the glial cell line-derived 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 TH-ir 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 2.50±0.25, respectively).
Conclusion:
The PI3-K/Akt pathway mediates the survival/differentiation effect of GDNF on DA cells.
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Project supported by the Education Department Natural Science Research Funds of the Jiangsu Province of China (No 02KJB310211) and the National Natural Science Research Funds of China (No 30570564).
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Wang, Hj., Cao, Jp., Yu, Jk. et al. Role of PI3-K/Akt pathway and its effect on glial cell line-derived neurotrophic factor in midbrain dopamine cells. Acta Pharmacol Sin 28, 166–172 (2007). https://doi.org/10.1111/j.1745-7254.2007.00494.x
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DOI: https://doi.org/10.1111/j.1745-7254.2007.00494.x
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