Abstract: Objective To detect the expressions of Lingo-1 and myelin associated protein in the white matter and hippocampus of ovariectomized rats after short-term estrogen replacement therapy in order to explore the possible mechanisms for the effects of estrogen on the brain myelin sheaths and cognitive function. Methods 24 middle-aged (9-12 months) female Sprague-Dawley (SD) rats were bilaterally ovariectomized (OVX) and randomly divided into vehicle replacement (OVX+Veh) group and estrogen replacement (OVX+E) group. After one month ERT, The spatial learning and memory ability of all rats were assessed with Morris water maze. Then, 10 rats were randomly selected from each group. The ultrastucture of myelin sheaths in the cerebral white matter and hippocampus were observed using electron microscope transmission, and the protein expression levels of MBP and Lingo-1 were investigated with western blot and immunohistochemical staining. Results The escape latencies of OVX+E rats in navigation test were significantly shorter than that of OVX+Veh rats(P < 0.05). The myelin sheaths in the white matter and hippocampus of OVX+Veh rats showed obviously degeneration. In the OVX+E group, the expression of MBP in the white matter and hippocampus were significantly higher than that of OVX+Veh group(P < 0.05), however, the expression of Lingo-1 were significantly lower than that of OVX+Veh group(P < 0.05). Conclusions 1-month ERT had significant beneficial effects on the spatial learning capacity and myelin sheaths in the white matter and hippocampus. The protective effects may be related to estrogen-induced downregulation of the Lingo-1 expression in the white matter and hippocampus of rats.

Key words: ［Key words］Cerebral white matter, Hippocampus, Middle-aged ovariectomized rats, Estrogen replacement therapy, Myelin sheath, Lingo-1