Prolonged low-dose neutron irradiation induces late cellular and molecular impairments in the mice hippocampus and causes cognitive deficit.

Abstract

Late effects of prolonged low-dose neutron exposure on the brain function remain poorly studied. We analyzed the content of neural progenitor cells, microglia and astrocytes, the number of PSD-95 puncta, the expression level of pro- and anti-inflammatory cytokines in the hippocampus, and long-term spatial and recognition memory in conventional (CV) and specific pathogen-free (SPF) mice 2 months after prolonged neutron irradiation at doses of 0.05 (1 day) and 0.5 Gy (10 day). Neurogenesis was intact in all mice. The level of PSD-95 was increased only in CV mice irradiated at 0.05 Gy. In CV mice, an increase in the number of microglia was recorded at both doses and astrocytes at 0.05 Gy; in SPF mice, both microglia and astrocytes increased only after irradiation at 0.5 Gy. The expression of TNFα and IL-1β increased in all irradiated mice; the expression of TGFβ decreased in CV mice irradiated at 0.5 Gy. These findings suggest that the severity of neuroinflammation in irradiated CV mice was higher than in SPF mice. Conventional analysis of escape latencies in the Morris water maze (MWM) revealed an intact spatial memory in both groups, while analysis of the swimming strategies demonstrated spatial reference memory deficits in CV mice irradiated at 0.05 Gy and in SPF mice irradiated at 0.5 Gy. Novel object recognition (NOR) assay demonstrated decreased recognition index only in CV mice (both doses). Thus, the housing conditions of animal before expose affect the neuroinflammation level and cognitive impairment late after prolonged low-dose neutron irradiation.