title: Glial cell line-derived neurotrophic factor protects midbrain dopaminergic neurons against lipopolysaccharide neurotoxicity.
abstract: 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.
authors.affiliation: Department of Anatomy & Neurobiology, University of Kentucky, Lexington, KY 40536, USA. bin.xing@UTSouthwestern.edu
authors.forename: Bin
authors.initials: B
authors.lastname: Xing
authors.forename: Tao
authors.initials: T
authors.lastname: Xin
authors.forename: Lingling
authors.initials: L
authors.lastname: Zhao
authors.forename: Randy L
authors.initials: RL
authors.lastname: Hunter
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
authors.forename: Guoying
authors.initials: G
authors.lastname: Bing
mesh_terms: 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
chemical_list: 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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