CHANGES IN NITRIC OXIDE SYNTHASE AND PKC ACTIVITIES IN NEONATAL IONIZING RADIATION CEREBELLUM. PARTIAL NEUROPROTECTION BY A TREATMENT WITH 17-BETA-ESTRADIOL

ZORRILLA ZUBILETE, M.A; SILBERMAN, D.M; GUELMAN, L.R; RIOS, H; GENARO, A.M; ZIEHER, L.M.

Insbruck, Austria

Congreso; ISN and ESN 20th Biennial Meeting; 2005

International Society of Neurochemistry and European Society of Neurochemistry

Exposure to ionizing radiation during neonatal period can generateplastic changes, mainly in highly immature organs, such as cerebellum(CE). PKC regulates a variety of intracellular and extracelullar signals inthe developing brain suggesting that might be target of radiationdamage. Estrogens promote growth, cellular survival and also preventaxonal pruning. Modulation of nitric oxide synthase (NOS) activity byPKC was just investigated in irradiated rat cerebellum. The aim of thepresent work was to evaluate motor, structural and biochemical changesinduced by neonatal ionizing radiation and to find drugs which couldimprove changes observed in this neonatal model. Our results show motoralterations in irradiated animals ( I ) respect to control animals (C) in testof footprint [Control (C) = 0.39 ± 0.06 vs. I=0.86 ± 0.07 cm.], changes inthe citoarchitecture of irradiated cerebellum and an increase in the activityof PKC (C=103 ± 15; I=305 ±10 pmol/min/g). The activity ofconstitutive NOS (C=1234 ± 9.68; I=433 ± 4.32 pmol/citrul/g) wasdiminished and the activity of iNOS, in the long term, was increased(C=29.8 ± 1.9 vs. I=2824.1 ± 99.1). Pre-treatment with 17-estradiolrestore some of those alterations; the motor syndrome was restored (I+17-estradiol =0.42. ± 0.02 cm) and cytoarchitecture of irradiated and treatedcerebellum resembled the control tissue. These findings show that 17-beta-estradiol exerts a partial neuroprotector effect suggesting that itcould be used like adjuvant in neuroprotectant therapies.