Genistein protects dopaminergic neurons by inhibiting microglial activation.
Inflammation participates in the pathogenesis and progression of Parkinson's disease, in which microglia play a key role. Inhibition of microglia activation has been shown to attenuate inflammation-mediated dopaminergic neurodegeneration. In this study, we found that genistein, the primary soybean isoflavone, concentration-dependently attenuated the lipopolysaccharide-induced decrease in dopamine uptake and loss of tyrosine hydroxylase-immunoreactive neurons in rat mesencephalic neuron-glia cultures. Genistein also inhibited lipopolysaccharide-induced microglia activation and production of tumor necrosis factor-alpha, nitric oxide and superoxide in mesencephalic neuron-glia cultures and microglia-enriched cultures. Our results indicate that genistein may protect dopaminergic neurons from lipopolysaccharide-induced injury and its effective inhibition of microglia activation may be one of the mechanisms.
Wang
Xijin
X
Department of Neurology & Institute of Neurology, Ruijin Hospital, Shanghai Second Medical University, Shanghai 200025, China.
Chen
Shengdi
S
Ma
Guozhao
G
Ye
Min
M
Lu
Guoqiang
G
D000818:Animals; D039481:CD11b Antigen / Q000378:metabolism; D002478:Cells, Cultured; D018920:Coculture Techniques; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004622:Embryo, Mammalian; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019833:Genistein / Q000494:pharmacology*; D007150:Immunohistochemistry / Q000379:methods; D008070:Lipopolysaccharides / Q000494:pharmacology; D008636:Mesencephalon / Q000166:cytology*; D017628:Microglia / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D014316:Tritium / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D039481:CD11b Antigen; D004791:Enzyme Inhibitors; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D014316:Tritium; D019833:Genistein; D004298:Dopamine