The Investigation Of Neuron Apoptosis Mediated By ERα On Cognitive Dysfunction In Aged Mice Induced By Repeated Abortion In Adult And Menopausal Depression

The ageing of population is not only one of the main trends of social population development, but also an important social problem for every country in the world. With the proportion of old people continue to increase in countries, researches focusing on health of elder adults attract more and more attentions. The incidence of depression, cognitive dysfunction and premature ovary failure is also increasing. Depression and cognitive dysfunction of patients with women than men, and the incidence of depression and cognitive dysfunction of women are two to three times that of men, Estrogen plays an important role in the women’s health. In adolescence, menstrual cycle, pregnancy and menopause the estrogen of women changes regularity and irregularity. Another research reports that ER alpha plays important role in depression and cognitive dysfunction. In order to study the role of estrogen receptor in elderly health, we use the menopausal depression, drug abortion and low birth weight three kinds of animal models and observe the change of the emotional, cognitive and the reproductive health, and to investigate the role of ERa in the motivation and cognition.1 ER a involved in menopausal depression induce by unpredictable chronic mild stressThe level of estrogen in the menopause transition had irregular changes and the estrogen level is lower after menopause. The menopause model was established through ovariectomy of female rats, then giving unpredictable chronic mild stress. We found that vertical and horizontal movement of rats significantly reduce, sugar water intake rate significantly reduced. TUNEL staining results show that cell apoptosis significantly increased in the DG area. Immunohistochemical study results show that the expression of GAL and ER alpha is increasing in the hippocampus CA1 area.T he expression level of galanin R2 and galanin R3 mRNA in the hypothalamus is significantly increased. After covering E2, vertical and horizontal movement of rats were significantly increased, the sugar water intake rate significantly increased. The expression of GAL and ER alpha decreased in hippocampal CA1 area. The expression level of galanin R2 and galanin R3 mRNA in the hypothalamus area is significantly reduced. The above results show that the climacteric rats after stress can result in climacteric depression, its mechanism may be related to the changes of expression of ER alpha and GAL and its receptors in the hippocampus and hypothalamus.2 Effect of neuron apoptosis mediated by ER a on cognitive dysfunction in aged mice induced by repeated abortion in adultAbortion causes the sudden changes of estrogen in women. We used the model of repeated medical termination of pregnancy in BALB/c mice by using cavity injection of RU486 at the dose of 2 mg/kg, the results show that repeated abortion in childbearing age period in mice can lead to body weight, activities and cognitive decline in old age. The expression of ERa decreased a mean 60%-80% in hippocampus and hypothalamus in aging mice. The mice given ER alpha antagonists MPP, leading to weight loss, estrus cycle disorders, and cognitive decline. When incubation with MPP for 24h, the vitality of SY5Y nerve cells is decreased and the rate of apoptotic is increased. The results showed that ER alpha play an important role in cognitive ability in elderly mice caused by repeated abortion in childbearing age period.3 The low birth weight induced reproductive endocrine disorders in adult and old age miceAdverse intrauterine environment can lead to dysplasia and low birth weight, further affecting the growth and reproductive health. The brain can affect the whole reproductive endocrine axis. In the study,we used an inbred BALB/c mouse model of naturally occurs low birth weight and studied the growth and reproductive endocrine function. The results showed that the weight of low birth weight mice in developing, adulthood and old age is lower than the normal control group. Compared with control group, the rate of pregnancy failure of low birth weight mice increased significantly. The hormone levels obviously change in reproductive endocrine axis, the levels of E2 and GnRH in the serum of female mice in old age. Morphological of the uterus changes, and the contraction of the uterus is significant, the uterus cross-sectional area is significantly lower. In hypothalamus the expression of ER alpha and ER beta increases, the expression of P66 decreased and the expression of 4-HDE increased. The above results show that the level of E2 and its receptor changes in old age of low birth weight mice, resulting in reproductive endocrine disorders.In summary, ovarian stress in castration rats induced menopausal depression. ERa expression increased and cell apoptosis increased in the hypothalamus and the hippocampus. Repeated abortion in adult mice can lead to depression and cognitive decline in agng. ERa expression decreased in the hypothalamus and the hippocampus, and ER β had no change. The vitality of SY5Y nerve cells decreased and the rate of apoptotic increased when incubation with MPP. In addition, the pregnancy rate of low birth weight mice decreased significantly in adult and the irregular oestrous cycle time occurred earlier in old age. The expression of ER alpha and ER beta increased in hypothalamus, oxidative stress levels increased in aging in low birth weight. Therefore, ER alpha plays a role in regulating the changes of the elderly emotional, cognitive and the reproductive health.