Oh Soo-Jin, Lee C Justin
Center for Neuroscience, Korea Institute of Science and Technology (KIST), Seoul 02792, Korea.
Convergence Research Center for Diagnosis, Treatment and Care System of Dementia, Korea Institute of Science and Technology (KIST), Seoul 02792, Korea.
Exp Neurobiol. 2017 Jun;26(3):113-121. doi: 10.5607/en.2017.26.3.113. Epub 2017 Jun 14.
Bestrophin-1 (Best1) is a calcium-activated anion channel identified from retinal pigment epithelium where human mutations are associated with Best's macular degeneration. Best1 is known to be expressed in a variety of tissues including the brain, and is thought to be involved in many physiological processes. This review focuses on the current state of knowledge on aspects of expression and function of Best1 in the brain. Best1 protein is observed in cortical and hippocampal astrocytes, in cerebellar Bergmann glia and lamellar astrocytes, in thalamic reticular neurons, in meninges and in the epithelial cells of the choroid plexus. The most prominent feature of Best1 is its significant permeability to glutamate and GABA in addition to chloride ions because glutamate and GABA are important transmitters in the brain. Under physiological conditions, both Best1-mediated glutamate release and tonic GABA release from astrocytes modulate neuronal excitability, synaptic transmission and synaptic plasticity. Under pathological conditions such as neuroinflammation and neurodegeneration, reactive astrocytes phenotypically switch from GABA-negative to GABA-producing and redistribute Best1 from the perisynaptic microdomains to the soma and processes to tonically release GABA via Best1. This implicates that tonic GABA release from reactive astrocyte via redistributed Best1 is a common phenomenon that occur in various pathological conditions with astrogliosis such as traumatic brain injury, neuroinflammation, neurodegeneration, and hypoxic and ischemic insults. These properties of Best1, including the permeation and release of glutamate and GABA and its redistribution in reactive astrocytes, promise us exciting discoveries of novel brain functions to be uncovered in the future.
Bestrophin-1（Best1）是一种从视网膜色素上皮细胞中鉴定出的钙激活阴离子通道，人类该基因的突变与Best氏黄斑变性相关。已知Best1在包括大脑在内的多种组织中表达，并被认为参与许多生理过程。本综述聚焦于Best1在大脑中表达和功能方面的当前知识状态。在皮质和海马星形胶质细胞、小脑伯格曼胶质细胞和层状星形胶质细胞、丘脑网状神经元、脑膜以及脉络丛上皮细胞中均观察到Best1蛋白。Best1最显著的特征是除了对氯离子有显著通透性外，对谷氨酸和γ-氨基丁酸（GABA）也有显著通透性，因为谷氨酸和GABA是大脑中的重要神经递质。在生理条件下，Best1介导的星形胶质细胞谷氨酸释放和GABA的持续性释放均可调节神经元兴奋性、突触传递和突触可塑性。在诸如神经炎症和神经退行性变等病理条件下，反应性星形胶质细胞的表型从GABA阴性转变为产生GABA，并将Best1从突触周围微区重新分布到胞体和突起，以通过Best1持续性释放GABA。这意味着反应性星形胶质细胞通过重新分布的Best1持续性释放GABA是一种常见现象，发生在各种伴有星形胶质细胞增生的病理条件下，如创伤性脑损伤、神经炎症、神经退行性变以及缺氧和缺血性损伤。Best1的这些特性，包括谷氨酸和GABA的通透与释放及其在反应性星形胶质细胞中的重新分布，有望在未来为我们带来关于新的脑功能的令人兴奋的发现。
