Changes in nitric oxide synthase and PKC activities in neonatal ionizing radiation cerebellum.. Partial neuroprotection by a treatment with 17-â-estradiol.

MARÍA ZORRILLA ZUBILETE; DAFNE MAGALÍ SILBERMAN; LAURA RUTH GUELMAN; HUGO RÍOS; ANA MARÍA GENARO; LUIS MARÍA ZIEHER

, Innsbruck, Austria

Congreso; 20th Biennal Meeting International Society for Neurochemistry,; 2005

International Society for Neurochemistry

Exposure to ionizing radiation during neonatal period can generate plastic changes, mainly in highly immature organs, such as cerebellum (CE).  PKC regulates a variety of intracellular and extracelullar signals in the developing brain suggesting that might be target of radiation damage.  Estrogens promote growth, cellular survival and also prevent axonal pruning. Modulation of nitric oxide synthase (NOS) activity by PKC was just investigated in irradiated rat cerebellum.  The aim of the present work was to evaluate motor, structural and biochemical changes induced by neonatal ionizing radiation and to find drugs which could improve changes observed in this neonatal model. Our results show motor alterations in irradiated animals ( I ) respect to control animals (C) in test of footprint [Control (C) = 0.39 ± 0.06 vs. I=0.86 ± 0.07 cm.], changes in the citoarchitecture of irradiated cerebellum and an increase in the activity of PKC (C=103 ± 15; I=305 ±10 pmol/min/g).  The activity of constitutive NOS (C=1234 ± 9.68; I=433 ± 4.32 pmol/citrul/g) was diminished 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-estradiol restore some of those alterations; the motor syndrome was restored (I+17-estradiol =0.42. ± 0.02 cm) and cytoarchitecture of irradiated and treated cerebellum resembled the control tissue. These findings show  that 17-beta-estradiol exerts a partial neuroprotector effect suggesting that it could be used like adjuvant in neuroprotectant therapies.