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 5Gy or fractionated exposure with 0.5Gy continuously for 10days (a total dose of 5Gy) was evaluated in an immature BALB/c mouse model. Radioprotective effect of ursolic acid (at 25mg/kg/daily administered 1h after acute or each of fractionated irradiations, and continuously for 30days) was also investigated. We found that both acute and fractionated irradiation at a total dose of 5Gy did not induce any mortality within 30days after exposure to postnatal day 26 (P26) BALB/c mice, but reduced animal weigh gain in the first few weeks. At 90days 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 5Gy 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 25mg/kg/daily for 30days 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.
Radiation Physiology Laboratory, Singapore Nuclear Research and Safety initiative, National University of Singapore, 1 CREATE Way #04-01, CREATE Tower, 138602, Singapore. Electronic address: snrtfr@nus.edu.sg.
Feng Ru
FR
Tang
Defence Medical and Environmental Research Institute, DSO National Laboratories, 11 Stockport Road, 11760, Singapore.
Weng Keong
WK
Loke
Neuroscience Phenotyping Core, Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, 117456, Singapore.
Peiyan
P
Wong
Temasek Laboratories, National University of Singapore, 5A, Engineering Drive 1, 117411, Singapore.
Boo Cheong
BC
Khoo
D000818:Animals; D000831:Animals, Newborn; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D003213:Conditioning, Psychological / Q000187:drug effects / Q000528:radiation effects; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use*; D004195:Disease Models, Animal; D000089622:Doublecortin Domain Proteins; D005239:Fear / Q000187:drug effects / Q000528:radiation effects; D019417:Hindlimb Suspension; D006624:Hippocampus / Q000187:drug effects / Q000528:radiation effects; D019394:Ki-67 Antigen / Q000378:metabolism; D007859:Learning Disabilities / Q000188:drug therapy* / Q000209:etiology*; D008124:Locomotion / Q000187:drug effects / Q000528:radiation effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D055495:Neurogenesis / Q000187:drug effects*; D009479:Neuropeptides / Q000378:metabolism; D011833:Radiation Injuries, Experimental / Q000150:complications* / Q000188:drug therapy; D021641:Recognition, Psychology / Q000528:radiation effects; D013550:Swimming / Q000523:psychology; D014315:Triterpenes / Q000627:therapeutic use*; D000097245:Ursolic Acid
D051792:Basic Helix-Loop-Helix Proteins; D016861:Cyclooxygenase Inhibitors; D000089622:Doublecortin Domain Proteins; D019394:Ki-67 Antigen; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D014315:Triterpenes; D000097245:Ursolic Acid; C093564:Neurogenic differentiation factor 1
Cognition; Irradiation; Neurogenesis; Radioprotection; Ursolic acid