Targeted Dorsal Dentate Gyrus or Whole Brain Irradiation in Juvenile Mice Differently Affects Spatial Memory and Adult Hippocampal Neurogenesis

Simple Summary The effects of exposure of the juvenile brain to doses of ionizing radiation (IR) <= 2 Gy on cognitive functions in adulthood are not clearly established in humans, and experimental data are scarce. To elucidate how IR can impact the postnatal brain, we evaluated and compared the effect of whole brain (WB) or hippocampal dorsal dentate gyrus (DDG) X-ray exposure (0.25-2 Gy) on spatial memory, three months after irradiation in mice. In our dose-ranging study, spatial memory was not modified after WB exposure, whereas a deficit was highlighted when irradiation beams were focused on the DDG at the dose of 1 Gy, but not for the lowest or highest doses tested. At 1 Gy, DDG irradiation appeared to be more deleterious to spatial memory and also to adult hippocampal neurogenesis than WB irradiation. Alterations in the generation of newborn neuronal cells in the DG may participate in the memory impairment observed after DDG irradiation at this dose. Finally, our work shows that the brain's response to IR is complex and depends on the dose and the irradiated brain volume. The societal interest of this study is notably linked to the advent of computed tomography scans for head exploration in children. The cognitive consequences of postnatal brain exposure to ionizing radiation (IR) at low to moderate doses in the adult are not fully established. Because of the advent of pediatric computed tomography scans used for head exploration, improving our knowledge of these effects represents a major scientific challenge. To evaluate how IR may affect the developing brain, models of either whole brain (WB) or targeted dorsal dentate gyrus (DDG) irradiation in C57Bl/6J ten-day-old male mice were previously developed. Here, using these models, we assessed and compared the effect of IR (doses range: 0.25-2 Gy) on long-term spatial memory in adulthood using a spatial water maze task. We then evaluated the effects of IR exposure on adult hippocampal neurogenesis, a form of plasticity involved in spatial memory. Three months after WB exposure, none of the doses resulted in spatial memory impairment. In contrast, a deficit in memory retrieval was identified after DDG exposure for the dose of 1 Gy only, highlighting a non-monotonic dose-effect relationship in this model. At this dose, a brain irradiated volume effect was also observed when studying adult hippocampal neurogenesis in the two models. In particular, only DDG exposure caused alteration in cell differentiation. The most deleterious effect observed in adult hippocampal neurogenesis after targeted DDG exposure at 1 Gy may contribute to the memory retrieval deficit in this model. Altogether these results highlight the complexity of IR mechanisms in the brain that can lead or not to cognitive disorders and provide new knowledge of interest for the radiation protection of children.

Automated summary

This study compared the effects of different doses of ionizing radiation on spatial memory and adult hippocampal neurogenesis in mice. The results suggest that targeted DDG exposure at a specific dose may impair spatial memory and alter adult hippocampal neurogenesis. The study also highlights the complexity of the brain's response to radiation, which depends on the dose and the irradiated brain volume.