Effects of Estrogen Deficiency on Learning and Memory and Cell Proliferation and Maturation in Hippocampus of Dementia Mice
Luo Min1,2, Zhao Yueyang1, Du Yexiang1, Li Yanzhen1, He Guiqiong1,3, Wang Kejian1,3*
To investigate the effects of different estrogen deficiency time on learning, memory and hippocampal cell proliferation, maturation in APP/PS1 double transgenic mice, exploring its possible mechanisms, 3-month-old APP/PS1 double transgenic AD female mice underwent bilateral ovariectomy (AD-OVX), shamoperated AD mice (AD-Sham) and wild-type mice (WT) of the same age were used as controls. 1 week ovariectomy (simulating early menopause) and 3 months (simulating mid-late menopause) respectively, Morris water maze showed that in APP/PS1 double transgenic AD mice, 1 week after OVX, there was no significant difference in escape latency, escape length and passing times between AD-OVX group and AD-Sham group (P>0.05); However, after OVX 3 months, the time and escape length of the AD-OVX group were significantly prolonged P<0.05), and the passing times were also decreased (P<0.05). uterine weight, EDU, immunofluorescence, Western blot were used to reflect estrogen levels, cell proliferation status, senile plaques, NeuN protein and aromatase levels in the brain of APP/PS1 double transgenic mice respectively. In APP/PS1 double transgenic AD mice, 1 week after OVX, circulating estrogen level was no obvious change. No senile plaques were found in the brain of mice. The number of neonatal positive cells in the hippocampus of mice and the expression of NeuN were increased in reactivity (P<0.05). At this time, the expression of aromatase was also increased (P<0.05). However, after OVX 3 months, the circulating estrogen level was significantly decreased (P<0.05). The senile plaques in the brain were increased significantly (P<0.05). The number of neonatal positive cells and the expression of NeuN in the hippocampus of mice were significantly decreased (P<0.05). At this time, the level of aromatase was decreased significantly (P<0.05). This results indicate that the early estrogen deficiency increases the proliferation and maturation of hippocampus cells in dementia mice reactively, and has no effect on learning and memory in mice. However, with the prolongation of estrogen deficiency, learning and memory impairment and proliferation and maturation cells in hippocampus are reduced in dementia mice. This effect may be closely related to changes in aromatase levels in the brain.
CN
EN