Rotenone and paraquat do not directly activate microglia or induce inflammatory cytokine release.
Both epidemiological and pathological data suggest an inflammatory response including microglia activation and neuro-inflammation in the Parkinsonian brain. Treatments with lipopolysaccharide (LPS), rotenone and paraquat have been used as models for Parkinson's disease, as they cause dopaminergic neuron degeneration in culture and in animals. Recent studies have suggested that rotenone and paraquat induce neuro-inflammation, however, it is not known if they can directly activate microglia. Here, we use primary cultured microglia to address this question. Microglia activation was analyzed by morphological changes and release of nitric oxide and inflammatory cytokines. Treatment with LPS was used as a positive control. While LPS induced morphological changes characteristic of microglial activation and release of nitric oxide and inflammatory cytokines, rotenone and paraquat did not. Our results suggest that paraquat and rotenone do not act directly on microglia and that neuro-inflammation and microglial activation in animals treated with these agents are likely non-cell autonomous, and may occur as a result of dopaminergic neuron damage or factors released by neurons and other cells.
Klintworth
Heather
H
Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA 98195-7234, USA.
Garden
Gwenn
G
Xia
Zhengui
Z
D000704:Analysis of Variance; D000818:Animals; D002478:Cells, Cultured; D002491:Central Nervous System Agents / Q000633:toxicity*; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D016207:Cytokines / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D007150:Immunohistochemistry; D008070:Lipopolysaccharides / Q000633:toxicity; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000166:cytology / Q000187:drug effects* / Q000276:immunology*; D009569:Nitric Oxide / Q000378:metabolism; D010269:Paraquat / Q000633:toxicity*; D012402:Rotenone / Q000633:toxicity*; D013997:Time Factors
D002491:Central Nervous System Agents; D016207:Cytokines; D008070:Lipopolysaccharides; D012402:Rotenone; D009569:Nitric Oxide; D010269:Paraquat