Modifications in hippocampal environment could underlie behavioral changes observed in 30-days-old rats irradiated at birth

CACERES, LG; CID, MP; URAN, SL; ZORRILLA ZUBILETE, MA; SALVATIERRA NA; GUELMAN, LR

Congreso; 24th ISN-ASN Biennial Meeting; 2013

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. Therefore, the study of radiation effects on the Central Nervous System becomes clinically relevant. Previous results found in our laboratory demonstrated that neonatal X irradiation has the ability to induce behavioural and biochemical alterations. Now, we are interested in studying the mechanisms that underlie the changes in associative memory observed in 30-days-old rats irradiated at birth and their relationship with the alterations in the anxiety state. Since it is known that neurotrophins could be involved in the modulation of memory and anxiety processes, the aim of the present work was to investigate the basal state of neurotrophins in irradiated animals as well as the possible contribution of the hippocampal GABAergic system and oxidative stress in the setting of the environment in which the behavioral changes occur. Male Wistar rats were irradiated with 5 Gy of X rays in their cephalic ends between 24 and 48 hours after birth. GABAA receptor density, ROS levels and levels of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) were determined in the hippocampus (HC) of 15 and 30-days-old rats. Results show an increased GABAA receptor density in irradiated HC of 30-days-old rats as well as an increase in oxidative stress, without changes at 15 days. The levels of both neurotrophins remained unchanged at 15-days-old rats whereas only BNDF levels were significantly decreased in 30-days-old rats HC. These data suggest that an increase in GABAA receptor density could have a causal relationship with the decrease in anxiety observed in irradiated rats and probably might underlie associative memory changes. On the other hand, the decreased BDNF levels could be triggered by radiation-induced oxidative stress. Together, it would be suggested that within a limited developmental window (15 and 30 days post-injury) a biochemical compensation of radiation-induced changes may take place, since decreased BDNF levels could determine a stimulation of GABAergic neurotransmission that could underlie the behavioral changes, supporting an anxiogenic role for BDNF.