Novel insights into neuron-glia communication: the case of neuroinflammation triggered by Maneb

BENZI JUNCOS, O.N.; CONDE, M.; ALZA, N.P.; SALVADOR, G.

Congreso; FALAN Congress 2022; 2022

First, we characterized the redox status of neurons exposed to Maneb. We determined that the increase in reactive oxygen species triggered by the pesticide was associated with a downregulation of antioxidant defenses (hemeoxigenase-1, glutathione cysteine ligase and superoxide dismutase). The oxidative injury triggered by Maneb was accompanied by a different profile in AA and DHA content in neurons and astrocytes. Increased neuronal DHA levels were associated with exacerbated cell death observed in the presence of Maneb and the FPR2/ALX antagonist, QuinC7. Astrocyte-derived secretome was able to prevent Maneb-triggered neuronal death and also to revert the deleterious effect of FPR2/ALX blockage. In line with this, astrocytes showed decreased AA and DHA levels, which were coincident with their secretome-mediated neuroprotective role. Pharmacological inhibition of key enzymes (cyclooxygenase-2, lipoxygenase-15, cytochrome P450) responsible for the production of inflammation/resolution related lipid mediators demonstrated that the spatial (neurons or astrocytes) activation of these pathways was involved in the cellular response to Maneb- induced toxicity.