RESUMO
In this study, we show that one single dose of gamma-irradiation at birth induces an inhibition of the cerebellar calcium dependent nitric oxide synthase (NOS) activity, probably correlated to the motor abnormalities and the disarrangement in the cerebellar cytoarchitecture observed in adult rats. This decrease in calcium dependent NOS activity could be associated with an increased protein kinase C (PKC) activity. PKC inhibition partially restores calcium dependent NOS activity, indicating that PKC activity could be negatively modulating the catalytic activity of calcium dependent NOS. These findings suggest that a decrease in nitric oxide (NO) production and the related increase in PKC activity could be intracellular events that participate in the onset of motor and cerebellar abnormalities induced by postnatal gamma-irradiation at early stages of life.
Assuntos
Cerebelo/enzimologia , Cerebelo/efeitos da radiação , Raios gama , Óxido Nítrico Sintase/efeitos da radiação , Proteína Quinase C/efeitos da radiação , Lesões Experimentais por Radiação/enzimologia , Análise de Variância , Animais , Animais Recém-Nascidos , Calbindinas , Cálcio/metabolismo , Cerebelo/patologia , Feminino , Marcha/efeitos da radiação , Masculino , Neurônios/enzimologia , Neurônios/patologia , Neurônios/efeitos da radiação , Ratos , Ratos Wistar , Proteína G de Ligação ao Cálcio S100/efeitos da radiação , Transdução de Sinais/efeitos da radiação , Fatores de TempoRESUMO
Neonatal X-irradiation induces permanent abnormalities in cerebellar cortex cytoarchitecture and neurochemistry, as well as impairment in motor gait. The aim of the present work was to examine the potential protective properties of WR-2721 (Amifostine, Ethyol), a free radical scavenger, against the above mentioned alterations by using a previously described neuroprotection assessment protocol. Pre-irradiation treatment with amifostine was effective in partially preventing the cerebellar morphological damage and the motor gait impairment induced by ionizing radiation. No changes in cerebellar noradrenaline (NA) levels were detected in amifostine-treated irradiated animals. These results suggest that it is possible to counteract radiation-induced damage in the cerebella and motor gait of neonatal rats through oxygen free radical scavenger administration prior to irradiation. The presence of the agent before the injury occurs, favors the efficacy of amifostine neuroprotective activity. Clinical implications of this model are related to the daily exposure of many people to different sources of radiation (accidental, diagnostical or therapeutical).