Effect Of Estrogen On Cognitive Function In Postmenopausal Woman

Introduce Postmenopausal woman with mild cognitive impairment could develop to Alzheimer's disease. Although the frequency of cognitive impairment is affected by age, sex, gene and other factors, estrogen should play an important role in cognitive impairment. However, not all studies are consistent with beneficial effects of estrogen on cognitive function. Many attentions are focusing on the gene polymorphisms of ERαand BDNF associated with cognitive impairment. In this paper, we firstly detected the effect of estrogen replacement therapy on postmenopausal rats; we also aimed a cohort with cognitive impairment in postmenopausal woman to learn the effect of estrogen on cognitive function and search the way of estrogen replacement therapy to cognitive impairment in the future. Material and Methods 184 SD female rats retired from breeding for two reproductive cycles,15-month-old, and 350-400g weight, were divided into two groups by random assigned method, 92 rats received estrogen replacement therapy and 92 rats in the control group, each group was divided into two phases. Before testing, estradiol benzoate was injected subcutaneouly on the cervical part of rats in estrogen replacement therapy group(25mg/kg/d), as for the control group, the same capacity of normal saline was used. After being injected for 7 days and 30 days, the rats were tested as following:(1) behavior detected by Morris water maze, including running training session, place navigation test, spatial search test and visible platform test. (2) changes of histomorphology in hippocampus. (3) expression of BDNF mRNA and trkB mRNA in hippocampus. (4)expression of BDNF,trkB and proBDNF in hippocampus. From February 1, 2003 to February 1, 2005, 136 postmenopausal women suppressed menstruation for more than one year, were collected from the Department of Neurology, Daping Hospital of the third military medical university in Chongqing, aged from 45 to 79 years, mean age 62.23±10.12 years. 65 postmenopausal women with cognitive impairment and a sample of 71 postmenopausal women without cognitive impairment in control. The diagnosis of cognitive impairment was based on MMSE scores. The serum levels of estrogen were detected and gene polymorphisms of BDNF and ERαwere collected. Result Experimental study (1) Compared with the control group, the rats of estrogen replacement therapy group showed a better search strategy, shorter escape latency(p<0.05), more percentage of swimming pathlength in platform quadrant and more frequency passing through the location of platform(p<0.05). (2) Number of synapse increased and synaptic cleft became narrower in hippocampus of the rats received estrogen replacement therapy group,no changes about cell organ in CA1 of hippocampus. (3) Contrasted to the control group, expression of BDNF mRNA and TrkB mRNA of hippocampus increased in the rats received estrogen replacement therapy group(p<0.05). (4) Expression of BDNF,TrkB and proBDNF protein in hippocampus in the rats received estrogen replacement therapy group increased(p<0.05). Clinic study (1) In the postmenopausal women with cognitive impairment, the serum levels of estrogen was 20.49±8.13pmol/l,and 28.62±20.33pmol/l in the control postmenopausal women(p<0.05). (2) Compared with the control postmenopausal women, the frequency of genotypes of BDNF196AG ,ER αXx and Pp increased in the postmenopausal women with cognitive impairment (p<0.05). Conclusion 1. Spatial memory retention is enhanced and histomorphology of hippocampus in the rats received estrogen replacement therapy group is meliorated from electron microscope,the expression of BDNFmRNA TrkBmRNA BDNF,TrkB and proBDNF increased. Compared with the rats received estrogen replacement therapy for 7days, the rats received estrogen replacement therapy for 30 days had a better result in Morris maze test. 2.It might be a mechanism that increased expression of BDNF and trkB could improve cognitive function in the rats received estrogen replacement therapy group. 3. Cognitive impairment is related with the low serum levels of estrogen inpostmenopausal woman。4.Genotypes of BDNF, ERαXx and Pp are inherited factors related to cognitive impairment in postmenopausal women.