Low dose of carbon ion irradiation induces early delayed cognitive impairments in mice.

Abstract

People often encounter various sources of ionizing radiation, both in modern medicine and under various environmental conditions, such as space travel, nuclear power plants or in conditions of man-made disasters that may lead to long-term cognitive impairment. Whilst the effect of exposure to low and high doses of gamma and X-radiation on the central nervous system (CNS) has been well investigated, the consequences of protons and heavy ions irradiation are quite different and poorly understood. As for the assessment of long-term effects of carbon ions on cognitive abilities and neurodegeneration, very few data appeared in the literature. The main object of the research is to investigate the effects of accelerated carbon ions on the cognitive function. Experiments were performed on male SHK mice at an age of two months. Mice were irradiated with a dose of 0.7Gy of accelerated carbon ions with an energy of 450meV/n in spread-out Bragg peak (SOBP) on a U-70 particle accelerator (Protvino, Russia). Two months after the irradiation, mice were tested for total activity, spatial learning, as well as long- and short-term hippocampus-dependent memory. One month after the evaluation of cognitive activity, histological analysis of dorsal hippocampus was carried out to assess its morphological state and to reveal late neuronal degeneration. It was found that the mice irradiated with accelerated carbon ions develop an altered behavioral pattern characterized by anxiety and a shortage in hippocampal-dependent memory retention, but not in episodic memory. Nissl staining revealed a reduction in the number of cells in the dorsal hippocampus of irradiated mice, with the most pronounced reduction in cell density observed in the dentate gyrus (DG) hilus. Also, the length of the CA3 field of the dorsal hippocampus was significantly reduced, and the number of cells in it was moderately decreased. Experiments with the use of Fluoro-Jade B (FJB) staining revealed no FJB-positive regions in the dorsal hippocampus of irradiated and control animals 3 months after the irradiation. Thus, no morbid cells were detected in irradiated and control groups. The results obtained indicate that total irradiation with a low dose of carbon ions can produce a cognitive deficit in adult mice without evidence of neurodegenerative pathologic changes.