[Effects of estrogen replacement therapy on cognitive function of ovariectomized rats].
OBJECTIVE
To investigate the effect of estrogen replacement therapy applied in different periods to ovariectomized rats and to evaluate the cognitive function of the rats.


METHODS
Totally 40 rats were ovariectomized to be postmenopausal models. They were divided into early hormone replacement therapy group (n = 10, managed by estradiol valerate at day 3 after surgery), early control group (n = 10, managed by saline at day 3 after surgery), late hormone replacement therapy (n = 10, managed by estradiol valerate at day 90 after surgery for 30 days) and late control group (n = 10, managed by saline at day 90 after surgery for 30 days). The behavior indicators of the rats were evaluated by Morris watermaze and hippocampal metabolite was detected by proton magnetic resonance spectroscopy, including N-acetylaspartate (NAA), choline containing compounds (Cho), creatine (Cr), myoinositol (mI), NAA/Cr, Cho/Cr and mI/Cr.


RESULTS
(1)Navigation test: escape latency were (43 ± 13) s at the early control group, (28 ± 9) s at the early HRT group, (82 ± 26) s at the late control group and (48 ± 18) s at late HRT group. Swimming distance were (1 404 ± 238) cm at the early control group, (878 ± 354) cm at the early HRT group, (2 411 ± 818) cm at the late control group and (1 310 ± 434) cm at the late HRT group. The escape latency and swimming distance of the early and late HRT groups were significantly shorter than those at the control groups (P < 0.05). (2) Spatial probe test: the swimming time in the target quadrant of rats in the early HRT group (34.0 ± 3.0) s were longer than those in other groups (P < 0.05). (3) Proton magnetic resonance spectroscopy: NAA/Cr were 1.12 ± 0.17 at the early control group, 1.26 ± 0.12 at the early HRT group, 1.57 ± 0.21 at the late control group and 1.38 ± 0.28 at the late HRT group. The late HRT group and the late control group were higher than their early groups (F = 6.05, P = 0.040). There was no significant difference between the HRT groups and the control groups (F = 0.04, P = 0.860). mI/Cr were 0.69 ± 0.04 at the early control group, 0.46 ± 0.12 at the early HRT group, 0.70 ± 0.03 at the late control group and 0.75 ± 0.08 at the late HRT group. There were statistically significant differences of the experimental time between the early and late groups(F = 16.45, P = 0.004). The differences between the early HRT group and the early control group, and the late HRT group and the late control group were significant (F = 6.01, P = 0.040). And there was an interaction with the experimental time and HRT measures (F = 13.79, P = 0.006); early HRT can reduce the average level of mI/Cr. Cho/Cr were 0.95 ± 0.09 at the early control group, 0.80 ± 0.12 at the early HRT group, 0.87 ± 0.09 at the late control group and 0.85 ± 0.12 at the late HRT group. There was no significant difference among those groups (P > 0.05). NAA/mI: there was an interaction with the experimental time and HRT measures (F = 12.95, P = 0.007). Early HRT can elevated levels of NAA/mI, while the late results were reversed.


CONCLUSIONS
Earlier estrogen replacement therapy may play a positive role in improving cognitive function of the ovariectomized rats.
Department of Obstetrics and Gynecology,Zhongda Hospital, Southeast University, Nanjing 210009, China.
Xiaoyan
X
Liu
Department of Obstetrics and Gynecology,Zhongda Hospital, Southeast University, Nanjing 210009, China.
Liping
L
Wang
Department of Obstetrics and Gynecology,Zhongda Hospital, Southeast University, Nanjing 210009, China.
Danhong
D
Peng
Department of Obstetrics and Gynecology,Zhongda Hospital, Southeast University, Nanjing 210009, China.
Yan
Y
Wang
Department of Obstetrics and Gynecology,Zhongda Hospital, Southeast University, Nanjing 210009, China. Email: renmulan@seu.edu.cn.
Mulan
M
Ren
D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D003071:Cognition / Q000187:drug effects / Q000502:physiology*; D003401:Creatine / Q000378:metabolism; D004195:Disease Models, Animal; D004958:Estradiol / Q000008:administration & dosage / Q000031:analogs & derivatives*; D015914:Estrogen Replacement Therapy; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D009682:Magnetic Resonance Spectroscopy; D018782:Maze Learning / Q000187:drug effects*; D008568:Memory / Q000187:drug effects*; D008593:Menopause; D010052:Ovariectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D001224:Aspartic Acid; D004958:Estradiol; C000179:N-acetylaspartate; D003401:Creatine