title: Rosiglitazone protects dopaminergic neurons against lipopolysaccharide-induced neurotoxicity through inhibition of microglia activation.
abstract: Recent evidence has suggested that microglia activation plays an important role in the pathogenesis of Parkinson's disease (PD). Activated microglia secrete various proinflammatory cytokines and neurotoxic mediators, which may contribute to the development of PD. Thus, the inhibition of microglia activation may have a therapeutic benefit in the treatment of PD. In the present study, using mesencephalic neuron-microglia mixed culture and microglia-enriched culture, we investigated whether rosiglitazone (RGZ), a member of peroxisome proliferator-activated receptor gamma (PPARγ) agonists, could inhibit microglia activation. Our results showed that RGZ significantly inhibited lipopolysaccharide (LPS)-induced microglia activation and the production of tumor necrosis factor-alpha (TNF-α), nitric oxide (NO), and superoxide. We further investigated the intracellular signaling pathways regulating the production of TNF-α and NO in LPS-activated microglia. The results showed that RGZ inhibited the phosphorylation and nuclear translocation of the p65 subunit of NF-κB, and the phosphorylation of p38 mitogen-activated protein kinase (p38MAPK). Taken together, our results suggested that the therapeutic effects of RGZ were partially mediated by modulating microglia activation.
authors.affiliation: Department of Anatomy, Shandong University School of Medicine, 44 Wenhua Xilu, Jinan, Shandong, PR China.
authors.forename: Xiuquan
authors.initials: X
authors.lastname: He
authors.forename: Lei
authors.initials: L
authors.lastname: Feng
authors.forename: Haiwei
authors.initials: H
authors.lastname: Meng
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Wang
authors.forename: Shuwei
authors.initials: S
authors.lastname: Liu
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D002452:Cell Count; D002478:Cells, Cultured; D018920:Coculture Techniques; D059290:Dopaminergic Neurons / Q000187:drug effects*; D004622:Embryo, Mammalian; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000633:toxicity*; D008636:Mesencephalon / Q000166:cytology; D017628:Microglia / Q000187:drug effects / Q000502:physiology*; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide; D011247:Pregnancy; D021381:Protein Transport / Q000187:drug effects; D051381:Rats; D000077154:Rosiglitazone; D013482:Superoxide Dismutase; D045162:Thiazolidinediones / Q000494:pharmacology*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D007004:Hypoglycemic Agents; D008070:Lipopolysaccharides; D016328:NF-kappa B; D045162:Thiazolidinediones; D014409:Tumor Necrosis Factor-alpha; D000077154:Rosiglitazone; D009569:Nitric Oxide; D014446:Tyrosine 3-Monooxygenase; D013482:Superoxide Dismutase