TY  - JOUR
AU  - Wang Hong-jun
AU  - Cao Jun-ping
AU  - Yu Jing-kao
AU  - Gao Dian-shuai
PY  - 2016
TI  - Role of PI3-K/Akt pathway and its effect on glial cell line-derived neurotrophic factor in midbrain dopamine cells
JF  - Acta Pharmacologica Sinica; Vol 28, No 2 (February 2007): Acta Pharmacologica Sinica
Y2  - 2016
KW  - 
N2  -  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 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 2.50±0.25, respectively).  Conclusion:   The PI3-K/Akt pathway mediates the survival/differentiation effect of GDNF on  DA cells.
UR  - http://www.chinaphar.com/article/view/4156