Rotenone induces neuronal death by microglial phagocytosis of neurons

作者: Julius V. Emmrich , Tamara C. Hornik , Jonas J. Neher , Guy C. Brown

DOI: 10.1111/FEBS.12401

关键词: PhagoptosisNecrosisPhagocytosisRotenoneNeurotoxicityCell biologyMicrogliaChemistryMitochondrionProgrammed cell death

摘要: Rotenone, a common pesticide and inhibitor of mitochondrial complex I, induces microglial activation loss dopaminergic neurons in models Parkinson's disease. However, the mechanisms rotenone neurotoxicity are still poorly defined. Here, we used primary neuronal/glial cultures prepared from rat cerebella to investigate contribution microglia neuronal cell death induced by low concentrations rotenone. Rotenone at 2.5 nm over several days without increasing numbers necrotic or apoptotic neurons, loss/death could be prevented selective removal microglia. increased proliferation phagocytic activity, tumour necrosis factor-α release. Rotenone-induced inhibition signalling between with: cyclo(Arg-Gly-Asp-d-Phe-Val) (to block vitronectin receptor); MRS2578 P2Y6 either annexin V an antibody against phosphatidylserine exposed phosphatidylserine, well-characterized 'eat-me' signal). As phagocytosis five different means death, these data indicate that is least partially mediated otherwise viable (phagoptosis). Thus, disease other neurological diseases might blocking signalling.

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