TRPV4 channels involvement in Tau-phosphorilation in PC12 cells exposed to cold
Alzheimer's disease (AD) is a neurodegenerative disease and the temperature is described as a risk factor for the development of the disease. There are two histopathological markers of the disease, senile plaques of beta amyloid protein and neurofibrillary tangles (NFTs) of hyperphosphorilated tau protein. Studies indicate that cold temperatures induces an increase in P-tau, favoring the formation of NFTs, but the mechanisms involved in the transduction of the thermal signal to cells are not yet known. Thus, the thermosensitive channels of the TRP family may be the key for this mechanism. TRPV4 channels are widely expressed in the central nervous system with a thermal activation range between 27 and 34ºC, which is also conducive to the cold-induced increase in P-tau, and can be activated in pathological conditions. Therefore, this study was designed to investigate the involvement of TRPV4 channels in the hyperphosphorylation process of tau protein induced by cold in temperature in PC-12 cell culture. For that, cells were submitted to 33 and 37ºC and treated with the TRPV4 agonist, RN1747, and the TRPV4 antagonist HC067047, and their viability and P-tau levels were evaluated. The treatment with RN1747 increased the influx of calcium into the cell, and the adition of HC067047 blocked this effect. Our results demonstrated that under the temperature conditions studied, as well as blocking or activating TRPV4 pharmacologicaly did not affect cell viability, or lead to any significant differences in the protein expression levels of TRPV4 and P-tau, suggesting a cold resistance of the cellular model.