论文部分内容阅读
It is well known that Estrogens play a vital role not only in reproductive system but also in neuroprotective signaling pathway against neurodegenerative disease.The actions are mainly mediated by specific estrogen receptors, ERα and ERβ.ERα36 is a novel variant of ERα, which share a common structural architecture of ERα, and was widely expressed in organs such as breast, bone and liver which respond to membrane-initiated estrogen and anti-estrogen signaling pathways.However, expression file of different subtypes of estrogen receptor (ER) involved in the process is still unknown.Our aim is to investigate the expression of ERα36 in brain and understand the role of ERα36 in estrogen-induced neuroprotection after cerebral ischemia.In this work, the distribution of ERα36 in the cortex and hippocampus of Sprague-Dawley rats was first detected by immunofluorescence.Then, the rats were randomly divided into four groups: sham group, cerebral ischemia group,ovariectomy group and cerebral ischemia after ovariectomy group.The models of cerebral ischemia were made by middle cerebral artery occlusion (MCAO) using an intraluminal filament method.Rats were treated with 4hours of reversible MCAO except for sham group and ovariectomy group.At 20 hours of reperfusion, neurological deficit scores were evaluated and the brain tissue was isolated.Immunofluorescence and Western blot were carried out to exam the expression of ERα36 and the effect of ERα36 in membrane initiated estrogen signal pathway.We found that: (1) ERα36 was widely expressed in the cortex and hippocampus of rat brain;(2) Compared with sham group, declining endogenous estrogen strengthen the damage degree of cerebral ischemia injury and reduced the expression of ERα36 in CA1 of hippocampus;(3) Reducing endogenous estrogen inhibited the activity of MAPK/ERK signal pathway, and also reduced the expression of caveolin-1, which was co-located with ERα36 in hippocampus.The results suggested that ERα36 may mediate the neuroprotective actions of estrogen after stroke though MAPK/ERK signal pathway and provide a theoretical basis to illustrate the mechanism of membrane initiated estrogen signal pathway in central nervous system.