Neonatal exposure to low-dose X-ray causes behavioral defects and abnormal hippocampal development in mice

Development of the hippocampus is critical for its normal maturation. However, there is no systematic study on the effects of low-dose (≤2 Gy) neonatal X-ray exposure on different cells at different developmental stages of the mouse hippocampus. The present study demonstrated that irradiation with 2 Gy at postnatal day (PD) 3 in mice induced anxiety and impairment of spatial learning and memory in adult mice. Neuroinflammatory cells were observed in the dentate gyrus (DG) and CA3 areas of the hippocampus at PD3 + 1. X-ray irradiation impaired neuronal complexity and neurogenesis. However, the number of astrocytes and microglia in the hippocampus was increased the first day after irradiation, and then decreased 21 days later. The protein expression levels of NF-κB, C/EBP homologous protein (CHOP), and γH₂ A histone family member X (γH₂ AX) increased from 7 to 21 days after irradiation, or till 90 days after irradiation for IL-1β, whereas those of hippocampal sirtuin1 (SIRT1) decreased after 21 days of irradiation at PD3. These results suggest that neonatal X-ray irradiation-induced neuroinflammation impaired neuroplasticity and neurogenesis in the hippocampus, leading to the anxiety and spatial memory disorder during adulthood. The mechanisms involved in the induction of developmental neurotoxicity following low-dose irradiation may involve the inflammation-mediated signaling pathway IL-1β/ SIRT1/CHOP.