Radioprotective effect of ursolic acid in radiation-induced impairment of neurogenesis, learning and memory in adolescent BALB/c mouse

The effect of acute irradiation with 5 Gy or fractionated exposure with 0.5 Gy continuously for 10 days (a total dose of 5 Gy) was evaluated in an immature BALB/c mouse model. Radioprotective effect of ursolic acid (at 25 mg/kg/daily administered 1 h after acute or each of fractionated irradiations, and continuously for 30 days) was also investigated. We found that both acute and fractionated irradiation at a total dose of 5 Gy did not induce any mortality within 30 days after exposure to postnatal day 26 (P26) BALB/c mice, but reduced animal weigh gain in the first few weeks. At 90 days after irradiation, the weight of animals with acute irradiation was still significantly lower than the control group; no significant difference though was observed for those fractionatedly exposed mice compared to the control group. Behavioral tests indicated that acute irradiation at 5 Gy induced deficits in learning and memory in the contextual fear conditioning test. The memory for novel object recognition was also impaired. Similar changes were not observed in mice with fractionated irradiation. Immunohistochemical study demonstrated clearly that acute and fractionated irradiations induced impairment of neurogenesis in the subgranular zone (SGZ) of the dentate gyrus although fractionated exposure induced much lesser loss of newly generated neurons. Ursolic acid administered at 25 mg/kg/daily for 30 days after irradiation greatly improved acute irradiation-induced deficits in contextual learning and memory and in novel object recognition memory although it exacerbated radiation-induced reduction of neurogenesis in SGZ.