Astrocyte-derived growth factors and estrogen neuroprotection: role of transforming growth factor-α in estrogen-induced upregulation of glutamate transporters in astrocytes.
Astrocyte-derived growth factors and estrogen neuroprotection: role of transforming growth factor-α in estrogen-induced upregulation of glutamate transporters in astrocytes.
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DOI：
10.1016/j.mce.2014.01.010
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发表时间：
2014-05-25
影响因子：
4.1
通讯作者：
Lee, Eunsook
中科院分区：
文献类型：
--
作者：
Karki, Pratap;Smith, Keisha;Johnson, James, Jr.;Lee, Eunsook
过去十年的广泛研究彻底改变了我们对星形胶质细胞在大脑中的作用的理解，从仅仅支持细胞到在各种生理功能中发挥积极作用，包括通过与神经元的串扰进行突触传递以及通过释放神经营养因子来保护神经。尤其是，大量研究报道，星形胶质细胞在不同的临床和实验神经元损伤模型中介导17-雌二醇(17β-estadiol，E_2)和选择性雌激素受体调节剂(SERM)的神经保护作用。星形胶质细胞含有两个主要的谷氨酸转运体，谷氨酸转运体(GLAST)和谷氨酸转运体-1(GLT-1)，它们在防止兴奋性神经细胞死亡方面发挥关键作用，这一过程与大多数神经退行性疾病有关。研究表明，雌二醇可以增加星形胶质细胞GLAST和GLT-1mRNA和蛋白的表达以及谷氨酸的摄取。转化生长因子α(转化生长因子α)等生长因子似乎介导了E2诱导的这些转运蛋白的增强。这些发现表明，E2对兴奋性毒性神经元损伤具有神经保护作用，至少部分是通过提高星形胶质细胞谷氨酸转运体的水平和功能来实现的。因此，本综述将讨论星形胶质细胞介导的E2神经保护机制，重点是谷氨酸转运体。
Extensive studies from the past decade have completely revolutionized our understanding about the role of astrocytes in the brain from merely supportive cells to an active role in various physiological functions including synaptic transmission via cross-talk with neurons and neuroprotection via releasing neurotrophic factors. Particularly, numerous studies have reported that astrocytes mediate the neuroprotective effects of 17β-estradiol (E2) and selective estrogen receptor modulators (SERMs) in various clinical and experimental models of neuronal injury. Astrocytes contain two main glutamate transporters, glutamate aspartate transporter (GLAST) and glutamate transporter-1 (GLT-1), that play a key role in preventing excitotoxic neuronal death, a process associated with most neurodegenerative diseases. E2 has shown to increase expression of both GLAST and GLT-1 mRNA and protein and glutamate uptake in astrocytes. Growth factors such as transforming growth factor α (TGF-α) appear to mediate E2-induced enhancement of these transporters. These findings suggest that E2 exerts neuroprotection against excitotoxic neuronal injuries, at least in part, by enhancing astrocytic glutamate transporter levels and function. Therefore, the present review will discuss proposed mechanisms involved in astrocyte-mediated E2 neuroprotection, with a focus on glutamate transporters.
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