Cypermethrin Induces the Activation of Rat Primary Microglia and Expression of Inflammatory Proteins

Cypermethrin activates microglia, which is found to be decisive in neurodegeneration in the experimental rats. While the involvement of microglial activation in toxicant-induced neurodegeneration is reported, the effect of low concentration of cypermethrin on the expression of inflammatory proteins from the rat primary microglia is not yet properly understood. The study intended to delineate the effect of low concentration of cypermethrin on the expression and release of proteins from the microglia. Rat primary microglial cells were treated with cypermethrin to check the expression of inflammatory proteins. Cypermethrin-treated microglia conditioned media and cells were collected to measure the expression and release of inflammatory proteins. Cypermethrin augmented the protein kinase C-delta (PKC-delta), inducible nitric oxide synthase (iNOS), phosphorylated mitogen-activated protein kinase (MAPK) p38 and p42/44, matrix metalloproteinase (MMP)-3, and MMP-9 levels in the cell lysate and tumour necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) levels in the microglia conditioned media. Pre-treatment with minocycline, a microglial activation inhibitor or rottlerin, a PKC-delta inhibitor, notably reduced the release of TNF-alpha in the conditioned media and expression of iNOS protein in the microglia. Minocycline reduced the expression of PKC-delta, phosphorylated p38 and p42/44 MAPKs, MMP-3, and MMP-9 proteins in the microglia. While cypermethrin-treated conditioned media induced the toxicity in the rat primary neurons, minocycline or rottlerin reduced the cypermethrin treated microglia conditioned media-induced toxicity. The outcomes of the present study suggest that cypermethrin activates microglia and releases TNF-alpha and IL-1 beta as well as up-regulates the expression of PKC-delta, iNOS, phosphorylated p38 and p42/44 MAPKs, MMP-3, and MMP-9 proteins, which could contribute to neurodegeneration.

Automated summary

The study revealed that cypermethrin activation of microglia leads to an increase in the release and expression of inflammatory proteins, potentially contributing to neurodegeneration. Additionally, treatments with inhibitors such as minocycline and rottlerin reduced the toxicity induced by cypermethrin-treated microglia conditioned media on rat primary neurons.