This study was performed to compare the fractionated irradiation with the chronic d-galactose/NaNO(2) administration as models for hippocampal neurogenesis suppression. Eight-week-old C57BL/6 mice were exposed to γ-rays at 0.5 Gy semiweekly for 10 weeks or injected with d-galactose/NaNO(2) mixture (1250 mg/kg of d-galactose and 90 mg/kg of NaNO(2), i.p) 5 times per week for 10 weeks. To evaluate the suppression of hippocampal neurogenesis, we examined the numbers of the doublecortin (DCX; an immature progenitor cell marker) and Ki-67 (a proliferating cell marker) expressing cells by immunohistochemistry in the dentate gyrus (DG) region of the hippocampus in each treated group in comparison with those of age-matched control and 24-month-old mice as the positive control. The number of DCX-positive cells in the DG area was significantly decreased in both the irradiation and d-galactose/NaNO(2) groups (96% and 50%) compared with the control. Also Ki-67-positive cells were significantly decreased in both groups (91% and 41%) compared with the control. Especially, both DCX and Ki-67-positive cells of irradiation group was much more significantly changed than those of the d-galactose/NaNO(2) group. The positive control group of 24-momth-old mice showed dramatic decreases as similar irradiation group in DCX (99%) and Ki-67 (98%) - positive cells compared to the control group. In conclusion, this fractionated irradiation was a more effective method for depleting hippocampal neurogenesis than chronic d-galactose/NaNO(2) exposure.
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