TY - JOUR
T1 - Prenatal protracted gamma irradiation at very low dose rate over several days induces severe neuronal loss in rat hippocampus and cerebellum
AU - de Saint-Georges, Louis
A2 - Jacquet, Paul
N1 - Score = 10
PY - 2005/1/1
Y1 - 2005/1/1
N2 - In general, prenatal irradiation causes various damages to the developing brain. However, little is known about the consequences of very low dose rate prenatal protracted irradiation over several days on neuron numbers in the offspring brain, and on volumes of the corresponding brain regions. Pregnant Wistar rats were exposed either to a protracted gamma irradiation from embryonic day (E) 13 to E16 (0.7 mGy/min; approximately 3 Gy in total) or were sham-irradiated. Thirty months old male and female offspring were then analyzed for alterations in hippocampal and cerebellar morphology. Using design-based stereology and the analysis of sets of sections systematically and randomly sampled to span the entire brain region of interest, a statistically significant decrease in number of hippocampal pyramidal and granule cells as well as of cerebellar Purkinje and granule cells (approximately 50%) was found in male and female irradiated offspring. The volumes of these brain regions were similarly altered. The analysis of only a “representative” section per animal yielded mostly non-significant trends. Evaluation of neuron densities showed no differences between prenatally irradiated and sham-irradiated offspring. Thus, very low dose rate prenatal protracted gamma irradiation did not result in the same morphologic alterations in the offspring brain as previously observed after prenatal short-term irradiation with comparable doses but at high dose rate. Rather, it had dramatic effects on number of cells whose progenitors underwent division during the selected period of irradiation. This suggests that the vulnerable period for these cells closely overlaps with the phase of division of their progenitors. However, irradiation also affected cells whose progenitors underwent division after the selected period of irradiation. In this case neuron loss was probably a secondary effect due mainly to the absence of trophic support from postsynaptic targets.
AB - In general, prenatal irradiation causes various damages to the developing brain. However, little is known about the consequences of very low dose rate prenatal protracted irradiation over several days on neuron numbers in the offspring brain, and on volumes of the corresponding brain regions. Pregnant Wistar rats were exposed either to a protracted gamma irradiation from embryonic day (E) 13 to E16 (0.7 mGy/min; approximately 3 Gy in total) or were sham-irradiated. Thirty months old male and female offspring were then analyzed for alterations in hippocampal and cerebellar morphology. Using design-based stereology and the analysis of sets of sections systematically and randomly sampled to span the entire brain region of interest, a statistically significant decrease in number of hippocampal pyramidal and granule cells as well as of cerebellar Purkinje and granule cells (approximately 50%) was found in male and female irradiated offspring. The volumes of these brain regions were similarly altered. The analysis of only a “representative” section per animal yielded mostly non-significant trends. Evaluation of neuron densities showed no differences between prenatally irradiated and sham-irradiated offspring. Thus, very low dose rate prenatal protracted gamma irradiation did not result in the same morphologic alterations in the offspring brain as previously observed after prenatal short-term irradiation with comparable doses but at high dose rate. Rather, it had dramatic effects on number of cells whose progenitors underwent division during the selected period of irradiation. This suggests that the vulnerable period for these cells closely overlaps with the phase of division of their progenitors. However, irradiation also affected cells whose progenitors underwent division after the selected period of irradiation. In this case neuron loss was probably a secondary effect due mainly to the absence of trophic support from postsynaptic targets.
KW - Development
KW - Prenatal low-dose irradiation
KW - Stereology
KW - Brain
UR - http://ecm.sckcen.be/OTCS/llisapi.dll/open/ezp_27307
UR - http://knowledgecentre.sckcen.be/so2/bibref/3442
M3 - Article
SN - 0306-4522
VL - 130
SP - 935
EP - 948
JO - Neuroscience
JF - Neuroscience
IS - 4
ER -