BIOCHEMICAL CHANGES COULD UNDERLIE GABAERGIC SYSTEM ALTERATIONS INDUCED BY NEONATAL X-RADIATION EXPOSURE

CACERES, LG; SARACENO, GE; URAN, SL; CAPANI, F; GUELMAN, LR

San Diego, CA

Congreso; 43th Annual Meeting of the Society for Neuroscience (SFN), San Diego, CA, USA; 2013

Society for Neuroscience

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). Previous results found in our laboratory demonstrated that neonatal X irradiation has the ability to induce different alterations at biochemical level in the hippocampus of 30-days-old rats, including an increase in the density of GABAA receptors and an increase in the protein kinase C (PKC) activity. The neurotrophins are a family of neuronal growth factors that include the brain-derived neurotrophic factor (BDNF). BDNF is implicated in the survival and maintenance of neurons and in the modulation of neural transmission at excitatory and inhibitory synapses. Therefore, BDNF could play a key role in the development of the changes induced in the irradiated hippocampal GABAergic system and the corresponding behavioral output. Besides, given that astrocytes are known to take part in the development and function of neuronal circuitry and since neurons can, in turn, release neurotrophins, it could be hypothesized that abnormal BDNF levels released from neurons might affect astrocytes? performance. In consequence, the aim of the present work was to investigate a possible involvement of BDNF and astrocytes in the modulation of the GABAergic system of irradiated hippocampus. Male Wistar rats were irradiated with 5 Gy of X rays in their cephalic ends between 24 and 48 hours after birth. GFAP immunostaining in the CA1 hippocampal area and hippocampal BDNF levels determination through Western blot were performed in 30-days-old rats. Results show a decrease in hippocampal BDNF levels as well as a decrease in the percentage of the reactive area of GFAP positive astrocytes in the striatum radiatum of CA1 of rats irradiated at birth. These results suggest that the decrease in hippocampal BDNF levels, probably mediated by the increase in hippocampal ROS induced by X radiation, could affect the normal development and survival of both neurons and astrocytes. Given that astrocytes depend on BDNF to regulate inhibitory synapsis and the observed decrease in the number of astrocytes do not support the increase in hippocampal GABAA receptors found in irradiated animals, it could be suggested that a compensatory mechanism aimed to recover the inhibitory tone could be triggered, probably mediated by the increased hippocampal PKC activity.