Abstract
Exposure to pesticides such as rotenone is a risk factor for Parkinson’s disease. Dopaminergic neurons are especially sensitive to the toxicity of compounds that inhibit the mitochondrial respiratory chain such as rotenone and 1-methyl-4-phenylpyridinium (MPP+). However, there is scarce information on their effects on glia. To evaluate whether these neurotoxicants affect the immune response of glia, primary mouse mixed glial and microglial cultures were treated with interleukin (IL) 4 in the absence and presence of MPP+ or rotenone. Using qRTPCR or western blot, we determined the expression of anti-inflammatory markers, the CD200R1 microglial receptor and its ligand CD200, and genes regulating glycolysis and oxidative metabolism. ATP and lactate levels were additionally determined as an index of cell metabolism. Microglial phagocytosis was also evaluated. MPP+ and rotenone clearly abrogated the IL4-induced expression of anti-inflammatory markers in mixed glial cultures. CD200 and CD200R1 expression and microglia phagocytosis were also affected by the neurotoxicants. Changes in the mRNA expression of the molecules regulating glycolysis and oxidative metabolism, as well as in ATP levels and lactate release suggested that metabolic reprogramming in response to MPP+ and rotenone differs between microglial and mixed glial cultures. These findings support the hypothesis that parkinsonian neurotoxicants may impair brain immune response altering glial cell metabolism.
Highlights
Exposure to pesticides such as rotenone is a risk factor for Parkinson’s disease
We previously described that exposure of primary glial cell cultures to the parkinsonian neurotoxicants MPP+ and rotenone disrupted the immune response to a pro-inflammatory stimulus, LPS/IFN-γ, suggesting that changes in glial cell metabolism interfered with proper glial cell function[11]
We determined the mRNA expression of the anti-inflammatory cytokines IL10, TGFβ and IL1ra, as well as of the molecules involved in tissue repair such as ARG1, MR, FIZZ1 and YM1, which are typical markers of an anti-inflammatory response
Summary
Exposure to pesticides such as rotenone is a risk factor for Parkinson’s disease. Dopaminergic neurons are especially sensitive to the toxicity of compounds that inhibit the mitochondrial respiratory chain such as rotenone and 1-methyl-4-phenylpyridinium (MPP+). There is scarce information on their effects on glia To evaluate whether these neurotoxicants affect the immune response of glia, primary mouse mixed glial and microglial cultures were treated with interleukin (IL) 4 in the absence and presence of MPP+ or rotenone. Changes in the mRNA expression of the molecules regulating glycolysis and oxidative metabolism, as well as in ATP levels and lactate release suggested that metabolic reprogramming in response to MPP+ and rotenone differs between microglial and mixed glial cultures. These findings support the hypothesis that parkinsonian neurotoxicants may impair brain immune response altering glial cell metabolism. The extent to which exposure to neurotoxicants affects the neuroimmune response needs to be further studied
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