PARTICIPATION OF PKC IN THE BEHAVIORAL CHANGES INDUCED BY X-RADIATION. NEUROPROTECTIVE ROLE OF 17-beta-ESTRADIOL

CACERES, LG; ZORRILLA ZUBILETE, MA; URAN, SL; GUELMAN, LR

San Diego, California, USA

Congreso; . 40th Annual Meeting of the Society for Neuroscience (SFN); 2010

Society for Neuroscience (SFN)

Developing Central Nervous System (CNS) is vulnerable to radiation-induced reactive oxygen species. The consequent oxidative stress has been shown to produce changes at different levels in the hippocampus (Hip), involving the participation of different molecular targets. We have found that irradiated rats (Rx) have better associative memory, showing enhanced performance in the inhibitory avoidance test (IA). There are many molecular targets that could be involved in this behavioral change, including protein kinase C (PKC), a well known kinase related with memory and learning processes as well as anxiety mechanisms. On the other hand, 17-beta-estradiol (betaE) could be used as a neuroprotector, since it was able to counteract some changes induced by oxidative stress.The aim of the present work was to evaluate the participation of PKC in the behavioral changes induced by X radiation and the ability of betaE, a potential neuroprotector, to counteract these effects.Neonatal male Wistar rats were X-irradiated (5 Gy) in their cephalic ends between 24 and 48h of postnatal life and a group of these animals (E2) was treated with betaE (5 ìg/g). Elevated Plus Maze (EPM) and IA tasks as well as the levels of PKC (total activity and protein quantity of â1 isoform) in Hip were assessed in 30-days-old rats.The improvement in the performance of Rx group in the IA test failed to be reversed by betaE. However, betaE was able to counteract the decrease in anxiety observed in the EPM in the Rx group. The PKC activity increased in the Rx group remained increased in the E2 group, although a decrease in the PKC translocation to the membrane was observed in the latter. On the other hand, protein quantification of the PKC beta1 isoform showed an increase in the Rx group that was normalized after betaE treatment.These results suggest that PKC have an important role in the changes induced by X-rays on the Hip. As PKC participates in memory processes, it might be suggested that the better performance in the IA observed in the Rx group as well as in the modification in the anxiety levels can be attributed to changes in PKC activity, being the PKC beta1 one of the isoforms that would account for this increase. On the other hand, the present work demonstrated that betaE was able to counteract, at least in part, radiation-induced changes, probably acting on molecular targets like PKC. Although the increase in total activity could not be normalized, the decrease in membrane translocation could be seen as an attempt to compensate for the abnormally high activity levels