Role of glial cell derived neurotrophic factor in the protective effect of smilagenin on rat mesencephalic dopaminergic neurons damaged by MPP

Tyrosine hydroxylase immunohistochemical analysis revealed that in cultured mesencephalic dopaminergic neurons smilagenin (SMI), added prior to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPP+), protected against the drop of neuron number and neurite outgrowth length caused by MPP+. Addition of anti-GDNF and/or anti-GFRα1 functional antibodies to the medium prior to SMI, eliminated mostly, though incompletely, the action of SMI. The expression of glial cell derived neurotrophic factor (GDNF) mRNA, but not GDNF receptor alpha1 (GFRα1) or receptor tyrosine kinase mRNA in MPP+ intoxicated neurons was markedly elevated as early as 2 h after the addition of SMI with a peak at 24–48 h. Therefore, an important route of the protective action of SMI on dopaminergic neurons is to stimulate intrinsic GDNF expression.