| BackgroudMore than 80% of dementia is Alzheimer's disease (AD) type, which affects 2-3 times more women than men. AD is associated with severe cognition impairment. Several epidemiological and clinical evidences have suggested that estrogen replacement therapy (ERT) after menopause may reduce the risk of developing AD, improve cognition of AD patients and relieve postmenopausal symptoms, such as depression, anxiety, insomnia. However, some other clinical trials have shown postmenopausal estrogen therapy may have no related to the prevalence of AD and not improve cognition of AD women. Therefore, the role of estrogen (E) on the cognitive function of postmenopausal women still remains controversial, and the mechanism needs further study.It has been suggested that types of estrogen, as well as dosage, cyclical regiments may directly influence the effect of ERT on postmenopausal cognition. Premarin, purified from pregnant horse, is one of the most common use conjugated equine estrogens in previous researches. Up to date, more and more novel estrogen reagents are available, such as 17 P -estradiol, phytoestrogen. Progynova is a pure valerate estradiol reagent, purified from natural plants. In present study, we will detect the effect of two different estrogen reagents on brain cognitive regions- hippocampus and cortex.Estrogen exerts its effects by binding to the intracellular estrogen receptor (ER) distributes in estrogen-responsive tissues. For a long period, there was a single ER, until a novel ER subtype was cloned from rat prostate in 1996. The novel ER was named as ER 3, differed from the classic ER- ER a . Although both ER subtypes act as transcription factors and modulate targetgenes, several studies have shown die two subtypes have different structures, tissue distribution and specific affinity to ligands, which help in part to provide insight into the possible different biological roles of the ERs. ER a and ER 3 were demonstrated to express both in hippocampus and cortex, however, exogenous estrogen may influence ERs expression in the above two brain regions, which directly affects the effect of ERT on postmenopausal cognition. But few studies reported it.Depositions of amyloid protein precursor (APP) and its metabolic product- P amyloid protein (A P ) in central nervous system (CNS) are considered to be a distinctive pathological change of AD. Although the whole metabolism proceeding of APP in CNS still remains elusive, it has been shown to involve in death and apoptosis of neurons, hi vitro studies indicated E increased APP secrete soluble product and inhibited the accumulation of A P in CNS. E also attenuates neuron apoptosis induced by APP and and the neurotoxicity of APP. It implies estrogen plays a role in regulating APP metabolism, which may be one of the mechanisms that E protects cognition, but few in vivo studies have reported the correlation.Part I Effect of estrogen on ER a and ER 3 expression in cortex and hippocampus of female SD rats Objective to study ER a and ER & expression in hippocampus and cortex of female SD rat following ovariectomy, and compare the effects of two different estrogen reagents on ER a and ER P expression. Methods 20 adult female SD rats were divided into 4 groups: intact (control), ovariectomized (OVX), OVX + Premarin (Premarin), OVX + Progynova (Progynova). Tissues of control group were collected without interferes. The other 3 groups were ovariectomied 48 days before estrogen treatment. Two experiments groups were orally injected with Premarin or Progynova for 12 days, at same time, the OVX group were orally injected with saline sodium as control. Tissue samples were collected, and reverse transcription polymerase chain reaction (RT-PCR) and Streptavidin peroxidase conjugated (SP) immunohistochemistry assay were employed to detect the distributions of ERa and ER0 in the two brain regions. ERs mRNA and protein levels were compared by relative quantitative analysis. Results 1. Compared with control group, both ER a and ER P mRNA and protein levels decre... |
