title: Aspirin protects dopaminergic neurons against lipopolysaccharide-induced neurotoxicity in primary midbrain cultures.
abstract: Aspirin (ASA) is one of the most widely used nonsteroidal anti-inflammatory drugs. ASA has primarily been used to treat headaches, rheumatic pain, and inflammation, but its therapeutic effects have recently been demonstrated on a range of disorders, including those of the central nervous system. In this study, we investigated whether ASA is neuroprotective in inflammation-mediated neurodegenerative diseases. Pretreatment with ASA reduced the lipopolysaccharide (LPS)-induced degeneration of dopaminergic (DA) neurons in mesencephalic neuron-glia cultures in a dose-dependent manner. The neuroprotective effect of ASA was attributed to the inhibition of microglial activation because of its observed inhibitory effects on LPS-stimulated nitric oxide, tumor necrosis factor-α, and superoxide production by microglial cells. Moreover, ASA increased the production of the anti-inflammatory cytokines transforming growth factor beta-1 and interleukin-10 in neuron-glia cultures after stimulation with LPS. Mechanistic studies revealed that the neuroprotective effects of ASA were mediated through the inhibition of nicotinamide adenine dinucleotide phosphate oxidase (PHOX), a key enzyme for superoxide production in microglia. These results suggest that ASA protects DA neurodegeneration by inhibiting the microglial-mediated oxidative stress/inflammatory response and by regulating the production of anti-inflammatory cytokines.
authors.affiliation: Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China, 1277 Jiefang Avenue, Wuhan, Hubei, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.forename: Heng
authors.initials: H
authors.lastname: Zhai
authors.forename: Luqi
authors.initials: L
authors.lastname: Huang
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.forename: Yan
authors.initials: Y
authors.lastname: Xu
authors.forename: Xian
authors.initials: X
authors.lastname: Qiao
authors.forename: Shenggang
authors.initials: S
authors.lastname: Sun
authors.forename: Yan
authors.initials: Y
authors.lastname: Wu
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001241:Aspirin / Q000494:pharmacology*; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018920:Coculture Techniques; D059290:Dopaminergic Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D004660:Encephalitis / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000633:toxicity; D008636:Mesencephalon / Q000166:cytology*; D017628:Microglia / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009247:NADH, NADPH Oxidoreductases / Q000037:antagonists & inhibitors / Q000378:metabolism; D000074624:NADPH Oxidase 1; D019636:Neurodegenerative Diseases / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D061251:Primary Cell Culture; D051381:Rats; D013481:Superoxides / Q000378:metabolism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D008070:Lipopolysaccharides; D018696:Neuroprotective Agents; D013481:Superoxides; D009569:Nitric Oxide; D009247:NADH, NADPH Oxidoreductases; D000074624:NADPH Oxidase 1; D001241:Aspirin