Critical function of Kir4.1 for the life-long generation of oligodendrocytes and myelin

大脑的巨大计算能力依赖于神经细胞与髓鞘之间的隔离，这种连接被称为少突胶质细胞。这些“有髓”连接的束形成了白质，在人类大脑皮层中非常突出。髓鞘丢失是多种神经病理的一个特征，最明显的是多发性硬化症和其他脱髓鞘疾病。然而，髓鞘丢失也是脑性瘫痪、中风和创伤性损伤临床结果不佳的重要原因。重要的是，少突胶质细胞不断地丢失，并从大脑中的干细胞池中再生，这些干细胞被称为少突胶质前体细胞(OPC)。这些再生过程对于髓鞘的终生维持和损伤后的修复是必不可少的。修复的失败或损害会导致髓鞘的丢失，并可能对大脑功能产生毁灭性的影响。我们已经确定了一个对少突胶质细胞生成至关重要的关键因素，称为Kir4.1通道。这个项目的目的是确定Kir4.1在OPC中在终生生成少突胶质细胞和髓鞘以及维持健康大脑中的重要性。这将为控制髓鞘生成的机制以及这种机制如何在病理上出错提供新的知识，并最终可能导致识别新的细胞靶点，以保护健康的大脑。

The massive computing power of the brain depends on the insulation of nerve cell connections with myelin sheaths, by cells known as oligodendrocytes. Bundles of these 'myelinated' connections form the white matter that is very prominent in the human cortex. The loss of myelin is a feature of multiple neuropathologies, most notably Multiple Sclerosis and other demyelinating diseases. However, myelin loss is also important in the poor clinical outcomes of cerebral palsy, stroke, and traumatic injury. Importantly, oligodendrocytes are continuously being lost and regenerated from a pool of stem cells in the brain, called oligodendrocyte progenitor cells (OPCs). These regenerative processes are essential for the life-long maintenance of myelin and for repair of myelin following damage. The failure or impairment of repair results in the loss of myelin and can have devastating effects on brain function. We have identified a key factor that is essential for oligodendrocyte generation, known as Kir4.1 channels. The aim of this project is to determine the importance of Kir4.1 in OPCs in the life-long generation of oligodendrocytes and myelin and maintenance of a healthy brain. This will provide new knowledge on the mechanisms controlling the generation of myelin and how this may go wrong in pathology and may ultimately lead to the identification of new cellular targets for protecting the healthy brain.