Region-specific reduction of parvalbumin neurons and behavioral changes in adult mice following single exposure to cranial irradiation

Purpose: Ionizing irradiation has several long-term effects including progressive cognitive impairment. Cognitive deterioration generally appears to be caused by abnormalities in the hippocampal dentate gyrus, with abnormal function of parvalbumin-expressing interneurons (PV neurons) in the cerebral cortex. PV neurons are vulnerable to oxidative stress, which can be caused by ionizing irradiation. We speculated that selective impairment of specific brain regions due to ionizing irradiation may alter the degree of cognitive impairment. Methods: We irradiated mature mouse brains with 20 Gy-ionizing irradiation. Subsequently, we analyzed behavioral abnormalities and changes in the number of PV neurons. Results: PV neuron density was significantly lower in some cortical regions of irradiated mice than in control mice. Within 1 week of irradiation, both body weight and temperature of irradiated mice decreased. In the forced swim test, irradiated mice spent significantly less time immobile than did control mice. However, irradiated mice did not display any abnormalities in the elevated plus maze test, Y-maze test, tail suspension test, and social interaction test between 3 to 6 days after irradiation. Conclusions: These results suggest that high-dose irradiation is less likely to cause brain dysfunction in the subacute phase. Moreover, the vulnerability of PV neurons appears to be brain-region specific.