The loss of estrogen efficacy against cerebral ischemia in aged postmenopausal female mice

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• 作者：Min Cai ; Yu-Long Ma ; Pei Qin ; Yan Li ; Li-Xia Zhang ; Huang Nie ; Zhengwu Peng ; Hui Dong ; Hai-Long Dong ; Wu-Gang Hou ; Li-Ze Xiong
• 关键词：CNS ; central nervous system ; CHIP ; C terminus of heat shock cognate protein 70 (Hsc70)-interacting protein ; E2 ; 17尾-estradiol ; ER ; estrogen receptor ; GCI ; global cerebral ischemia ; HRT ; hormone replacement therapy ; LTED ; long-term 17尾-estradiol deprivation ; MCAO ; transient middle cerebral artery occlusion ; OVX ; ovariectomized ; rCBF ; regional cerebral blood flow ; TTC ; 2 ; 3 ; 5-triphenyltetrazolium chloride
• 刊名：Neuroscience Letters
• 出版年：13 January, 2014
• 年：2014
• 卷：558
• 期：Complete
• 页码：115-119
• 全文大小：969 K

文摘

Estrogen has been shown to have neuroprotective effects in numerous experimental studies involving young and adult animals. However, several clinical trials have found that in aged postmenopausal women who received estrogen replacement therapy, there did not appear to be a reduction in the incidence of stroke. The aim of this study was to investigate the effects of physiological dosages of estrogen on aged female mice subjected to ischemia-reperfusion injury. Adult ovariectomized (OVX) female mice and 22-month-old female mice received daily subcutaneous injections of 100 渭g/kg or 300 渭g/kg 17尾-estradiol (E2) at the back of the neck for four weeks, and the expression levels of estrogen receptor (ER) 伪 and 尾 in the cerebral cortex were determined using real-time PCR and Western blotting analyses. To mimic ischemic stroke, the mice received middle cerebral artery occlusion (MCAO) treatment for 1 h followed by a 24-h reperfusion period. The mice were then subjected to neurological deficit testing and infarct volume evaluation. The aged mice showed higher neurological deficit scores and larger infarct volumes compared with the adult mice. Both the lower and higher physiological dosages of E2 significantly improved the neurological test scores and decreased the infarct volume in the adult mice; however, E2 showed no neuroprotective effects in the aged mice. Furthermore, the protein expression of ER伪 and ER尾 in the cerebral cortex was significantly decreased in the aged mice compared with the adult mice, and this decrease was not rescued by E2 treatment. These results indicate that the down-regulation of ER伪 and ER尾 in the cerebral cortex may contribute to the loss of estrogen efficacy against ischemic injury in aged females and may point to new therapies for ischemic stroke in aged postmenopausal women.