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的绝缘连接，这种绝缘连接是由被称为少突胶质细胞的细胞实现的。成束的这些“有髓鞘”的连接形成了白色物质，这在人类大脑皮层中非常突出。髓鞘的丢失是多种神经病理学的特征，最显著的是多发性硬化症和其他脱髓鞘疾病。然而，髓鞘丢失在脑瘫、中风和创伤性损伤的不良临床结果中也很重要。重要的是，少突胶质细胞不断丢失，并从大脑中的干细胞池中再生，称为少突胶质细胞祖细胞（OPC）。这些再生过程对于髓磷脂的终身维持和损伤后髓磷脂的修复至关重要。修复的失败或损伤导致髓鞘的损失，并可能对脑功能产生破坏性影响。我们已经确定了少突胶质细胞生成所必需的关键因素，称为Kir4.1通道。该项目的目的是确定OPCs中Kir4.1在少突胶质细胞和髓鞘的终身生成和健康大脑的维持中的重要性。这将提供关于控制髓鞘生成的机制的新知识，以及这在病理学中可能如何出错，并可能最终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.