Neuron loss during early adulthood following prenatal low-dose X-irradiation in the mouse brain.
OBJECTIVE
Apart from subsequent cell death, little is known about long-term effects of a prenatal low-dose X-irradiation (PLDI) on nuclear (n) and mitochondrial (mt) DNA, and whether these effects are connected with reduced neuron numbers in the adult brain.


METHODS
Pregnant mice were X-irradiated with 0, 10 or 50cGy at day 13 (E13) of pregnancy. One day after (E14), or postnatally at day 25 (P25) or P180, the brains of the offspring were analysed concerning the extent of nDNA repair, mt biogenesis, and the relative content of nDNA single strand breaks (SSB). Stereology was applied for evaluating neuronal loss.


RESULTS
One day after irradiation no unrepaired SSB were detected. Significant 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. 10cGy) but decreased mt biogenesis for 10 vs. 50 cGy.


CONCLUSIONS
A hypothesis closely related to that regarding molecular events during aging is presented for explaining this second wave of cell death in adult mice following PLDI as a result of accumulated mtDNA damage caused by PLDI. A possible relation to the neurodegenerative hypothesis of schizophrenia is discussed.
Korr
H
H
RWTH University of Aachen, Department of Anatomy and Cell Biology, Pauwelsstrasse/Wendlingweg 2, D-52057 Aachen, Germany. hkorr@post.klinikum.rwth-aachen.de
Thorsten Rohde
H
H
Benders
J
J
Dafotakis
M
M
Grolms
N
N
Schmitz
C
C
D000818:Animals; D001921:Brain / Q000196:embryology / Q000378:metabolism / Q000502:physiology / Q000528:radiation effects*; D002540:Cerebral Cortex / Q000378:metabolism / Q000502:physiology / Q000528:radiation effects; D004247:DNA / Q000378:metabolism / Q000528:radiation effects; D004260:DNA Repair; D004272:DNA, Mitochondrial / Q000096:biosynthesis / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006624:Hippocampus / Q000378:metabolism / Q000502:physiology / Q000528:radiation effects; D051379:Mice; D009474:Neurons / Q000378:metabolism / Q000473:pathology / Q000502:physiology / Q000528:radiation effects*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D017966:Pyramidal Cells / Q000378:metabolism / Q000502:physiology / Q000528:radiation effects
D004272:DNA, Mitochondrial; D004247:DNA