Decreased Weight, DNA, RNA and Protein Content of the Brain after Neutron Irradiation of the 18-day Mouse Embryo

Abstract

Pregnant mice were irradiated with 0.5 Gy fission neutrons on the eighteenth day of their gestation. The average litter size at birth was unchanged but mortality increased 5-6 fold in the first 3 days. The irradiated mice were the same weight as control mice at birth but showed a progressively increasing weight deficiency up to at least 36 days as compared to controls. Brain weight was 37, 45 and 25 per cent less in 2-, 3- and 52-week old irradiated animals, respectively, and the ratio of brain weight to body weight was 25, 27 and 13 per cent less. The concentrations of DNA, RNA and protein (mg/g wet tissue) were the same in irradiated and control mice in both brain and liver at all three ages. Total DNA, RNA and protein contents of whole brain after irradiation were 56-75 per cent of the control levels. No definite decrease was observed in liver. Histological study at 6 hours after irradiation showed nuclear pyknosis in the central nervous system from definite to very severe according to the part examined. It is concluded that damage to the central nervous system of the 18-day mouse foetus after neutron irradiation is mainly due to killing and/or inhibition of the differentiation of neuroblasts.

Brain Slices from Glutaminase-Deficient Mice Metabolize Less Glutamine: A Cellular Metabolomic Study with Carbon 13 NMR

“…However, there was not a good correlation between the reduction of the glutaminase activity and that of glutamine utilization, which was decreased by only 21.4%. It is noteworthy that, taking a dry weight/protein ratio equal to 1.3 (Antal et al, 1984), in both control and glutaminase-deficient mice, flux through glutaminase represented only 0.7% and 1.1% (with 5 mmol/L [3-13 C]glutamine) and 0.3% and 0.4% (with 1 mmol/L [3-13 C]glutamine) of the corresponding maximal glutaminase activity measured in brain homogenates of these mice (Gaisler-Salomon et al, 2009). Thus, despite this, our study shows that a reduction of the maximal activity of glutaminase in the brain is accompanied by a reduction of flux through glutaminase.…”

Postnatal Changes in Mice Exposed In Utero to Fast Neutrons

“…Several studies have demonstrated that prenatal exposure to low-LET radiation induced abnormalities of the developing brain such as cerebral hypoplasia [5][6][7] and neuronal cell death 8,9 , and deceleration of neuronal migration 10,11 in rodents. As for neutrons, Vogel and his colleagues examined the changes of brain in mice prenatally exposed to 0.5 Gy of fission neutrons [12][13][14] , and showed that the body weight and the brain weight decreased induced in the irradiated mice 12,13 . Regarding the mechanism, they showed that the damage to the brain of the fetus after neutron irradiation was mainly due to killing and /or inhibition of the differentiation of neuroblasts 13 , and inhibition of protein synthesis was also observed in the irradiated brain 14 .…”

“…As for neutrons, Vogel and his colleagues examined the changes of brain in mice prenatally exposed to 0.5 Gy of fission neutrons [12][13][14] , and showed that the body weight and the brain weight decreased induced in the irradiated mice 12,13 . Regarding the mechanism, they showed that the damage to the brain of the fetus after neutron irradiation was mainly due to killing and /or inhibition of the differentiation of neuroblasts 13 , and inhibition of protein synthesis was also observed in the irradiated brain 14 . Although, their studies revealed the important mechanisms concerned in the abnormalities of developing brain induced by prenatal irradiation with neutrons, the dose-response relationships and mechanisms of the biological effects of prenatal exposure to neutrons in comparison with those of low-LET radiation have not yet been clarified.…”

“…5 G y o f f i s s i o n n e u t r o n s w i t h contamination of 0.18 Gy of gamma-rays at E17, and showed remarkable decreases of the brain weight and the body weight in the irradiated mice, however the postnatal histopathological changes of the affected brains were not been determined. Antal et al 13 focused on the early events in the cerebrum of the fetuses, and they hypothesized that pycnotic nuclei, inhibition of mitosis in neuroblasts, and cell death observed in the brains 6 hours after irradiation were the major changes in prenatal irradiation-induced cerebral hypoplasia in mice. Inouye et al 10 presented that the inhibition of neuronal migration during the brain development by low-dose of low-LET radiation participated in cerebral hypoplasia induced in mice.…”

“…The histopathological differences from those reports may be related to the strain difference or type of radiation. Vogel et al 12 and Antal et al 13 examined the abnormalities of brain development in BDF1 mice i r r a d i a t e d w i t h 0 . 5 G y o f f i s s i o n n e u t r o n s w i t h contamination of 0.18 Gy of gamma-rays at E17, and showed remarkable decreases of the brain weight and the body weight in the irradiated mice, however the postnatal histopathological changes of the affected brains were not been determined.…”