Hippocampal pharmacological and morphological changes could underlie associative memory alterations in rats irradiated at birth

CACERES LG; CID, M; SARACENO, GE; ROMERO JI; URAN SL; CAPANI F; SALVATIERRA, NA; GUELMAN LR

Buenos Aires

Congreso; 5th Special Conference of the International Society for Neurochemistry; 2012

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 alterations in the associative memory of 30-days-old rats. This change seems to be triggered by the decrease in anxiety levels observed in irradiated rats and the increase in hippocampal protein kinase C (PKC) activity. It would be suggested that PKC could be a key mediator capable of modifying the hippocampal morphological and/or pharmacological features that could underlie the observed behavioural changes. Since PKC is thought to modulate GABAA receptors and since the GABAergic system would be involved in a variety of anxiety abnormalities, the aim of the present work was to investigate if radiation-induced alterations would be mediated by abnormalities in the GABAergic system. Moreover, as PKC can also intervene in the regulation of the density of dendritic spines, morphological assessment of the hippocampal CA1 region was also evaluated. Male Wistar rats were irradiated with 5 Gy of X rays in their cephalic ends between 24 and 48 hours after birth. GABAA receptor binding assay was performed in 15 and 30-days-old rats. Morphological assessment of mushroom dendritic spines was performed in hippocampus (Hip) of 30-days-old rats. Results show an increase in the number of mushroom dendritic spines Faloidine (+) in the CA1 region of the Hip of irradiated rats. Moreover, an increased GABAA receptor density was observed only in the synaptosomes of irradiated Hip of 30-days-old rats. Taking together, these results suggest that the morphological and pharmacological changes could underlie, at least in part, the behavioural changes observed in the irradiated rats, which could also be modulated by PKC.