| The process of cognitive decline in postmenopausal women is significantly accelerated due to the lack of estrogen.Animal experiments and clinical studies have confirmed that estrogen replacementtherapy(ERT)can improve cognition functionafter menopause in ovariectomized rats andpostmenopausal women,but its mechanism is not clear.One of the important reasons for the decline of cognitive function is the decrease in the conduction velocity of nerve fibers caused by abnormal myelin structure.Stereological studies have found that one month ERT has protective effect on the loss of myelin sheaths in ovariectomized rats.Leucine-rich repeat and Ig domain containing Nogo receptor interacting protein-1(Lingo-1)plays an important role in the inhibition of myelination,which suggests that Lingo-1 may be involved in the process of protective effect of estrogen on cognitive function and myelin sheaths.Objective: To detect the expressions of Lingo-1 protein and myelin associated protein in the cerebral white matter and hippocampus of middle-aged ovariectomized rats after short-term estrogen replacement therapy in order to explore the possible mechanisms for the effects of estrogen on cognitive function and the myelin sheaths in brain.Methods 1.24 middle-aged(9-12 months)female Sprague-Dawley(SD)rats were bilaterally ovariectomized(OVX)and randomly divided into vehicle replacement(OVX+Veh)group(n = 12)and estrogen replacement(OVX+E)group(n =1 2).OVX+E rats were given subcutaneous injection of 17-estradiol at nape of the neck for a period of one month.OVX+Veh rats were given subcutaneous injections of sesame oil at nape of the neck for a period of one month.Then the serum estrogen levels after operation and after ERT were detected.2.After one month ERT,the spatial learning and memory abilities of all rats were assessed with Morris water maze.3.After Morris water maze test,5 rats were randomly selected from each group.The ultrastucture of the myelin sheaths in the cerebral white matter and hippocampus were observed using electron microscope transmission,the expression distributions of Lingo-1 were investigated with immunohistochemical staining.4.Finally,5 rats were randomly selected from each groupand the protein expression levels of MBP and Lingo-1 were investigated with Western blot.Results 1.Compared with the mean serum estradiol level of OVX rats and the OVX+Veh rats,the mean serum estradiol level of OVX+E rats was significantly higher(P<0.05).The mean serum estradiol levels of OVX rats and the OVX+Veh rats were not significantly different(P>0.05).2.For visible-platform task on day 1,there was no significant difference between the escape latency of OVX+Veh rats and OVX+E rats(P>0.05).The escape latencies of OVX+E rats in navigation test from day 2 to 5were significantly shorter than those of OVX+Veh rats(P < 0.05).There was no significant difference between the two groups in swimming speed,target quadrant swimming time and target quadrant swimming distance on day 6(P>0.05).3.The ultrastructure results showed that the myelin sheaths in the white matter and hippocampus of OVX+Veh rats presented obviously degeneration.However,the myelin sheaths in the white matter and hippocampus of OVX+E rats were compact and complete.4.The results of Western blot showed that the expressions of MBP in brain white matter and hippocampus of OVX+E groupwere significantly higher than those of OVX+Veh group(P < 0.05).5.The results of Western blot and immunohistochemical staining showed that the expressions of Lingo-1 inwhite matter and hippocampus of OVX+E groupwere significantly lower than those of OVX+Veh group(P< 0.05).Conclusions:One month ERT had significant beneficial effects on the spatial learning capacity and the 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. |
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