Discussion On Mechanism Of Alzheimer-Like Learning And Memory Impairment In Ovariectimized Rats

AIM:We bilaterally ovariectomized(OVX) SD rats to establish animal model of lowestrogen level. To observe the differences of learning and memory capacity、theweight of rats、weight of the uterus and levels of estradiol in blood between the twogroups. To detect the hippocampus tau protein(tau protein phosphorylation level inThr231, Ser396and Ser404sites and tau-1and tau-5antibody content changes) andexpression level of Cdk5and p25, p35, then further discuss the possible mechanism.Thus for application of this animal model providing more detailed evidence of basicresearch, and for seeking treatment of Alzheimer’s disease provide new breakthroughpoint on estrogen way.METHODS:Adult female Sprague-Dawley rats (weight220±30g,3months old) weresupplied by Experimental Animal Central of Tongji Medical College. Rats wereallowed free access to food and water and maintained at constanttemperature(24±2°C), relative humidity(60±5%). All the rats are being in the animalroom to adapt to1week. All the rats were randomly divided into two groups (Shamand OVX) and underwent bilaterally ovariectomized in the OVX. In Sham group, we only cut some adipose tissue by the side of the ovary. In the seventh week afterovariectomy, all the rats would conducte the MORRIS water maze and test thelearning ability, training for7days,6days later, we will test the memory ability onthe two groups, and getting the materials one day after tested. We will test thedifferences of the weight of rats and theirs uterus、the levels of estradiol in bloodbetween the two groups, and will analysis the content of tau protein(tau proteinphosphorylation level in Thr231, Ser396and Ser404sites and tau-1and tau-5antibody content changes) and Cdk5protein expression level in the organization ofhippocampus by Western blot.RESULT:According to the results of the MORRIS water maze, we found that the latency inOVX group was obviously longer than Sham group in the last two days of thelearning ability(p0.05).6days later, we have tested the memory ability on the twogroups, we found that the latency in OVX group was obviously different between the7thin training and the testing in memory ability. We have tested the differences of theweight of rats and theirs uterus、the levels of estradiol in blood between the twogroups. The results showed that the weight of the uterus and levels of estradiol inblood were obviously low in OVX group(p0.05), and the weight of rats were higherin OVX group(p0.05). The immune activity of tau protein phosphorylation level inThr231, Ser396sites and increased significantly in OVX group by Western blotanalysis(p0.05), in the contrast, the content of tau-1decreased in OVX group(p0.05).The p25/Cdk5expression level was significantly higher in OVX group than Shamgroup in the organization of hippocampus.CONCLUSION: We observed that ovariectomy impaired the learning and memory ability in SDrats; Ovariectomy can induce the levels of estradiol in blood decreasing, and than theweight of rats increased significantly, the weight of uterus became low; themechanism of Alzheimer-like learning and memory impairment maybe related withthe activity upregulation of Cdk5, and then lead to tau protein phosphorylation levelincreasely in some sites.