Neuron loss during early adulthood following prenatal low-dose X-irradiation in the mouse brain

Purpose: Apart from subsequent cell death, little is known about long-term effects of a prenatal low-dose X-irradiation (PLDI) on nuclear (n) and mito chondrial (mt) DNA, and whether these effects are connected with reduced ne uron numbers in the adult brain. Materials and methods: Pregnant mice were X-irradiated with 0, 10 or 50 cGy at day 13 (E13) of pregnancy. One day after (E14), or postnatally at day 2 5 (P25) or P180, the brains of the offspring were analysed concerning the e xtent of nDNA repair, mt biogenesis, and the relative content of nDNA singl e strand breaks (SSB). Stereology was applied for evaluating neuronal loss. Results: One day after irradiation no unrepaired SSB were detected. Signifi cant results were mainly obtained for hippocampal pyramidal cells at P180, particularly cell loss following 50 cGy PLDI, increased SSB content and mt biogenesis (0 vs. 10 cGy) but decreased mt biogenesis for 10 vs. 50 cGy. Conclusions: A hypothesis closely related to that regarding molecular event s during aging is presented for explaining this second wave of cel death in adult mice following PLDI as a result of accumulated mDNA damage caused by PLDI. A possible relation to the neurodegenerative hypothesis of schizophr enia is discussed.