Glial cell line-derived neurotrophic factor protects midbrain dopaminergic neurons against lipopolysaccharide neurotoxicity.
Aberrant microglia activation causes dopaminergic neuronal loss and nitric oxide produced by microglia plays a critical role in dopaminergic neuronal degeneration. However, no study has determined if GDNF protects dopaminergic neurons via inhibiting nitric oxide generation in Parkinson's disease animal model. We report that GDNF not only reduces lipopolysaccharide-induced degeneration of dopaminergic neurons, suppresses microglia activation and nitric oxide generation, but also reverses the inhibition of phosphoinositide 3-kinase (PI3K) in dopaminergic neurons and microglia. It suggests that the neuroprotective effect of GDNF on dopaminergic neurons may be related to its suppression of microglia activation-mediated nitric oxide via releasing the inhibition of PI3K in both neurons and microglia.
Xing
Bin
B
Department of Anatomy & Neurobiology, University of Kentucky, Lexington, KY 40536, USA. bin.xing@UTSouthwestern.edu
Xin
Tao
T
Zhao
Lingling
L
Hunter
Randy L
RL
Chen
Yan
Y
Bing
Guoying
G
D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004622:Embryo, Mammalian; D051098:Glial Cell Line-Derived Neurotrophic Factors / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000633:toxicity*; D008636:Mesencephalon / Q000166:cytology*; D017628:Microglia / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects*; D009569:Nitric Oxide / Q000378:metabolism; D009924:Organ Culture Techniques; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D051098:Glial Cell Line-Derived Neurotrophic Factors; D008070:Lipopolysaccharides; D009569:Nitric Oxide; D014446:Tyrosine 3-Monooxygenase; D019869:Phosphatidylinositol 3-Kinases; D004298:Dopamine
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