Abstract: ObjectiveTo observe the imitation of menopause and the change of spatial cognition in mice administrated with D-galactose and to evaluate the molecular mechanism of estrogen to protect the function of hippocampal neurons.MethodsAdult female C57BL/6 mice were bilateral ovariectomy (OVX) and subcutaneously treated with D-galactose (100 mg/kg). In estrogen replacement therapy(ERT) mice were i.p. administrated with E2 (50 μg/kg). It took 8 weeks to induce the model and treat with ERT. Morris water maze was used test the function of spatial learning and memory. Estrogen and oxidative stress enzymes were detected by kit. 8-oxo-dG was immunohistochemical stained, and the expression of MTH1 in brain hippocampus was detected by Western blotting.ResultsThe level of E2 in blood in model group was one fifth of that in Sham group(P<0-01), and E2 level obviously increased in ERT group; the escape latency significantly prolonged in model group(P<0-01), and obviously shortened in ERT group(P<0-05). SOD and GSH-Px significantly reduced and MDA obviously increased in model group(P<0-05); and approached normal in ERT group. 8-oxo-dG as a DNA oxidative damage marker was obviously increased in the hippocampus of model group. However, the expression of DNA repair protein MTH1 significantly reduced(P<0-05), and both of them returned to normal in ERT group(P<0-05).ConclusionEstrogen can improve the function of spatial cognition in aging mice model by repairing the DNA damage of hippocampal neurons.

Key words: estrogen, aging, mice, hippocampus, DNA, damage, repair