Abstract
While MPP+ may not directly activate microglia, the initial neuronal damage inflicted by the toxin may trigger microglia, possibly leading to synergistic pro-apoptotic interaction between neuro-inflammation and toxin-induced neurotoxicity, which may further aggravate neurodegeneration. However, what molecular targets are synergistically up or downregulated during this interaction is not well understood. Here, we addressed this by co-culturing fully differentiated human SH-SY5Y cells treated with parkinsonian toxin 1-Methyl-4-phenylpyridinium (MPP+), with endotoxin-activated microglial cell line EOC 20 to determine how this interaction affects pro-apoptotic (p38, JNK, and bax:bcl2 ratios) and pro-survival (NF-κB, MEK1) signaling at both mRNA and protein levels. Concurrent MPP+ and endotoxin-treatment aggravated a decrease in SH-SY5Y cell viability and caused strong synergistic increases in the bax:bcl2 ratio, but also NF-κB and JNK signaling. These effects were attenuated by microglia inhibitor minocycline. Altogether, these data provide further molecular insights into the important role or even conditional requirement of microglia activation in the progressive neurodegenerative nature of PD.