CONICET | Buscador de Institutos y Recursos Humanos

Ionizing radiation is a physical agent extensively used to kill tumor cells during human cancer therapy. Unfortunately, normal brain can undergo undesirable tissue injury during the treatment of cerebral tumors. Damage on target nervous structures includes the induction of oxidative stress, a common mechanism observed in animal models of neurodegenerative diseases and neurotoxicity, which would be mainly mediated by reactive oxygen species (ROS).. The elevated vulnerability of the immature brain, together with the limited availability of therapeutic tools that can attenuate Central Nervous System damage, supports the search and development of new preventive and therapeutic strategies. Previous results found in our laboratory demonstrated that 17-ß-estradiol (βE) was able to prevent hippocampal-related behavioral and biochemical changes induced by neonatal ionizing radiation. In addition, an isomer poorly active on the estrogen receptor, 17-α-estradiol, was also able to counteract these changes, supporting the hypothesis that an antioxidant mechanism could underlie the neuroprotective ability, although it would not be discarded that βE could exert its neuroprotective role by acting through estrogen receptors (ER) activation. Interestingly, a subtype of ER, the ERαseems to be implicated in a variety of cellular events associated with neuroprotection against different neuronal insults. , Since another subtype of ER, the ERβ, is thought to be involved in processes of brain development and the regulation of anxiety processes, the impact of an injury induced at early developmental stages would interfere with the physiological activity of this receptor. Therefore, the aim of the present work was to investigate the participation of each ER in the prevention of X radiation-induced changes. Male Wistar rats were irradiated with 5 Gy of X rays between 24 and 48 hours after birth. A subset of rats was subcutaneously administered with successive injections of the ERα selective agonist propylpyrazole-triol (PPT) or the ERβ selective agonist diarylpropionitrile (DPN) prior and after irradiation. At 30 days of age, rats were subjected to behavioral tasks to evaluate habituation memory and anxiety levels. Hippocampal ROS levels were also assessed. Results show that both DPN and PPT were able to counteract radiation-induced changes in habituation memory and the increase in ROS observed in the irradiated rats, but only DPN was able to restore anxiety levels to control values. These data suggest that ERα and ERβ would be involved in the mechanism of estrogen neuroprotection. Therefore, it would be hypothesized that multiple mechanisms, both receptor-dependent and independent, might act in concert to achieve the prevention of the X radiation effects.