Targeting potassium channels in oligodendrocytes to maintain myelin and a healthy brain across the lifespan

少突胶质细胞是大脑和脊髓中形成髓磷脂的特化细胞。髓磷脂是神经轴突周围的绝缘层，对信息的快速传导和神经元的营养支持至关重要。少突胶质细胞/髓磷脂的终身维持对脑功能和神经元完整性至关重要。我们最近发表的证据表明，髓磷脂损失和白质破坏是大脑衰老的主要因素，而大脑衰老是与年龄相关的认知功能下降的关键潜在因素。因此，了解确保少突胶质细胞和髓磷脂终身维持的基本机制对于促进大脑在整个生命周期中的健康至关重要。我们也发表了证据表明，新的内向整流钾通道Kir7.1对少突胶质细胞的完整性至关重要。这进一步推进了我们之前关于少突胶质细胞中其他钾通道的重要性的数据，包括K2P。在这个项目中，学生将在国际公认的钾通道专家团队的指导和培训下，发现调节通道活性的新机制，以促进少突胶质细胞的功能和完整性，使用广泛的遗传和药理学的功能增益和功能丧失方法。本项目将对少突胶质细胞生物学中钾通道的功能及其在维持健康脑功能中的作用产生新的基础知识。

Oligodendrocytes are specialised cells of the brain and spinal cord that form myelin. Myelin is the insulating layer around nerve axons and is essential for rapid conduction of information and for trophic support of neurones. The life-long maintenance of oligodendrocytes/myelin is essential for brain function and neuronal integrity. We have recently published evidence that myelin loss and white matter disruption are major factors in brain ageing, which is a key underlying factor in age-related decline of cognitive function. Hence, understanding the fundamental mechanisms that ensure the life-long maintenance of oligodendrocytes and myelin is essential for promoting a healthy brain across the lifespan. We also have published evidence that the novel inward rectifying potassium channel Kir7.1 is crucial for oligodendrocyte integrity. This advances our previous data on the importance of other potassium channels in oligodendrocytes, including K2P. In this project, the student will be supervised and trained by a team of internationally recognised potassium channel experts to discover novel mechanisms for modulating channel activity to promote oligodendrocyte function and integrity, using a wide range of genetic and pharmacological gain- and loss-of-function approaches. This project will generate new fundamental knowledge on the functions of potassium channels in oligodendrocyte cell biology and their role in maintaining healthy brain function.