Behavioral Performance and Microglial Status in Mice After Moderate Dose of Proton Irradiation

Abstract

Abstract The cognitive impairment is a remote effect of gamma radiation treatment of malignancies. The major part of the studies on the effect of proton irradiation (a promising alternative in the treatment of radioresistant tumors and tumors located close to critical organs) on the cognitive abilities of laboratory animals and their relation to morphological changes in the brain is rather contradictory. The aim of this study was to investigate cognitive functions and the dynamics of changes in morphological parameters of hippocampal microglial cells after proton irradiation. Two months after the cranial irradiation, 8–9-week-old male SHK mice were tested for total activity, spatial learning, as well as long- and short-term hippocampus-dependent memory. To estimate the morphological parameters of microglia, the brain slices of control and irradiated animals each with different time after proton irradiation (24 h, 7 days, 1 month) were stained for microglial marker Iba-1. No changes in behavior or deficits in short-term and long-term hippocampus-dependent memory were found, but the impairment of episodic memory was observed. A change in the morphology of hippocampal microglial cells, which is characteristic of the transition of cells to an activated state, was detected. Radiation-induced oxidative stress into the brain tissue of mice one day after exposure resulted in a slight decrease in cell density, which was restored to the control level by 30 days after exposure, probably due to the activation of proliferation. The results obtained may be promising with regard to the future use of using high doses of protons per fraction in the irradiation of tumors.