Estrogen replacement therapy-induced neuroprotection against brain ischemia-reperfusion injury involves the activation of astrocytes via estrogen receptor β

نویسندگان

  • Yulong Ma
  • Hang Guo
  • Lixia Zhang
  • Liang Tao
  • Anqi Yin
  • Zhaoyu Liu
  • Yan Li
  • Hailong Dong
  • Lize Xiong
  • Wugang Hou
چکیده

The incidence of ischemic stroke is significantly increased in postmenopausal women. However, the neuroprotective effects of estrogen replacement therapy (ERT) against stroke remain controversial, and the role of astrocytes in ERT has rarely been explored. In this study, we investigated the effects of estrogen and selective estrogen receptor (ER) agonists on astrocytes activation and neuronal apoptosis in mice under conditions of cell culture oxygen and glucose deprivation and reperfusion (OGD-R), and global cerebral ischemia (GCI). We demonstrated that hippocampal astrocytes primarily express ERβ. In astrocytes, 2.5-20 nM 17β-estradiol (E2) or 10 nM DPN (ERβ agonist) not 10 nM PPT (ERα agonist), significantly increased GFAP expression. And 10 nM E2, DPN or E2+MPP (ERα antagonist), but not PPT or E2+PHTPP (ERβ antagonist), significantly reduced neuronal apoptosis following the subjection of astrocyte and neuronal cocultures to OGD-R. We also found that either 50 μg/kg E2 or 8 mg/kg DPN replacement (3 weeks) significantly increased GFAP expression and reduced GCI-induced neuronal apoptosis in hippocampal CA1 region of ovariectomized mice. These results indicate that estrogen-induced neuroprotection against ischemia-reperfusion injury involves activation of astrocytes via ERβ. Thus, the discovery and design of astrocyte-selective ERβ modulators may offer a new strategy for ERT of ischemic stroke.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

نقش محافظتی استروژن و پروژسترون بر بافت معدی به دنبال ایسکمی- رپرفیوژن معدی در موش‌های صحرایی نر

Background and Objective: Ischemia-reperfusion (I/R) injury repeatedly occurs in situations such as surgery, hemorrhage, burns, trauma, and infection. It has also been found that females were more resistant than males, indicating that female sex hormones have a protective function. The aim of this study was to determine the role of estrogen, progesterone, and their combination in protecting the...

متن کامل

Estrogen provides neuroprotection against brain edema and blood brain barrier disruption through both estrogen receptors α and β following traumatic brain injury

Objective(s):Estrogen (E2) has neuroprotective effects on blood-brain-barrier (BBB) after traumatic brain injury (TBI). In order to investigate the roles of estrogen receptors (ERs) in these effects, ER-α antagonist (MPP) and, ER-β antagonist (PHTPP), or non-selective estrogen receptors antagonist (ICI 182780) were administered. Materials and Methods: Ovariectomized rats were divided into 10 gr...

متن کامل

Differential Neuroprotection of Selective Estrogen Receptor Agonists against Autonomic Dysfunction and Ischemic Cell Death in Permanent versus Reperfusion Injury

In the present study, we tested the hypothesis that selective activation of estrogen receptor subtypes (ERα and ERβ) would be neuroprotective following ischemia and/or ischemia-reperfusion, as well as prevent the associated autonomic dysfunction. The selective ERα agonist, PPT, when administered 30 min prior to occlusion of the middle cerebral artery (pMCAO), resulted in a dose-dependent neurop...

متن کامل

Estrogen and progesterone attenuate glutamate neurotoxicity via regulation of EAAT3 and GLT-1 in a rat model of ischemic stroke

Objective(s): Glutamate is the most widespread neurotransmitter in the central nervous system and has several functions as a neuromodulator in the brain although in pathological conditions like ischemia it is excessively released causing cell death. Under physiological conditions, glutamate is rapidly scavenged from the synaptic cleft by excitatory amino-acid transport...

متن کامل

The Role of Peroxisome Proliferator Activator Receptor Alpha in Cerebral Ischemia-Reperfusion Injury; a Review Study

Peroxisome proliferator-activated receptor alpha (PPAR-α), which belongs to the nuclear receptor family of ligand-activated transcription factors, was first described as gene regulators for metabolic pathways including lipid metabolism, insulin sensitivity, and glucose homeostasis. Were raised. This nuclear receptor is widely expressed in various tissues, providing a wide range of effects to st...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:

دوره 6  شماره 

صفحات  -

تاریخ انتشار 2016