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-GFR alpha 1 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 (GFR alpha 1) or receptor tyrosine kinase mRNA in MPP+ intoxicated neurons was markedly elevated as early as 2h 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.
Zhang
Yongfang
Y
Shanghai Jiaotong University, School of Medicine, 280 South Chongqing Road, Shanghai 200025, China.
Xia
Zongqin
Z
Hu
Yaer
Y
Orsi
Antonia
A
Rees
Daryl
D
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D000818:Animals; D019610:Cytoprotection; D004298:Dopamine / Q000378:metabolism; D015259:Dopamine Agents / Q000494:pharmacology; D005260:Female; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors / Q000235:genetics / Q000378:metabolism; D008636:Mesencephalon / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D013150:Spirostans / Q000494:pharmacology*; D014446:Tyrosine 3-Monooxygenase / Q000032:analysis / Q000378:metabolism
D015259:Dopamine Agents; C494987:GFRA1 protein, human; D051100:Glial Cell Line-Derived Neurotrophic Factor; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; D013150:Spirostans; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; C046297:sarsasapogenin; D014446:Tyrosine 3-Monooxygenase; D020794:Receptor Protein-Tyrosine Kinases; D004298:Dopamine