Department of Basic Medical Sciences, Physiology Group, Faculty of Medicine and Health Sciences, Ghent University, De Pintelaan 185, Block B, 9000, Ghent, Belgium.
ICIRB, CNRS UMR7241/INSERM U1050, Collège de France, Paris Cedex 05, France.
Neurochem Res. 2017 Sep;42(9):2519-2536. doi: 10.1007/s11064-017-2313-x. Epub 2017 Jun 20.
Neuronal survival, electrical signaling and synaptic activity require a well-balanced micro-environment in the central nervous system. This is achieved by the blood-brain barrier (BBB), an endothelial barrier situated in the brain capillaries, that controls near-to-all passage in and out of the brain. The endothelial barrier function is highly dependent on signaling interactions with surrounding glial, neuronal and vascular cells, together forming the neuro-glio-vascular unit. Within this functional unit, connexin (Cx) channels are of utmost importance for intercellular communication between the different cellular compartments. Connexins are best known as the building blocks of gap junction (GJ) channels that enable direct cell-cell transfer of metabolic, biochemical and electric signals. In addition, beyond their role in direct intercellular communication, Cxs also form unapposed, non-junctional hemichannels in the plasma membrane that allow the passage of several paracrine messengers, complementing direct GJ communication. Within the NGVU, Cxs are expressed in vascular endothelial cells, including those that form the BBB, and are eminent in astrocytes, especially at their endfoot processes that wrap around cerebral vessels. However, despite the density of Cx channels at this so-called gliovascular interface, it remains unclear as to how Cx-based signaling between astrocytes and BBB endothelial cells may converge control over BBB permeability in health and disease. In this review we describe available evidence that supports a role for astroglial as well as endothelial Cxs in the regulation of BBB permeability during development as well as in disease states.
神经元存活、电信号传递和突触活动需要中枢神经系统中有一个良好平衡的微环境。血脑屏障 (BBB) 实现了这一点，它是位于脑毛细血管中的内皮屏障，可以控制进出大脑的几乎所有物质的传递。内皮屏障功能高度依赖于与周围胶质细胞、神经元和血管细胞的信号相互作用，共同形成神经胶质血管单元。在这个功能单元中，连接蛋白 (Cx) 通道对于不同细胞区室之间的细胞间通讯至关重要。连接蛋白作为间隙连接 (GJ) 通道的构建块而广为人知，可实现代谢物、生化和电信号的直接细胞间传递。此外，除了在直接细胞间通讯中的作用外，Cx 还在质膜中形成非偶联的非连接性半通道，允许几种旁分泌信使通过，补充直接 GJ 通讯。在 NGVU 中，Cx 表达于血管内皮细胞，包括形成 BBB 的细胞，并且在星形胶质细胞中表达丰富，尤其是在围绕脑血管的终足过程中。然而，尽管在这个所谓的神经血管界面处 Cx 通道的密度很高，但尚不清楚星形胶质细胞和 BBB 内皮细胞之间基于 Cx 的信号如何汇聚以控制 BBB 在健康和疾病中的通透性。在这篇综述中，我们描述了现有的证据，这些证据支持星形胶质细胞和内皮细胞 Cx 在 BBB 通透性的调节中发挥作用，无论是在发育过程中还是在疾病状态下。
