Targeted cell-specific deletion of Kir4.1 channels to determine their functions in oligodendrocytes

少突胶质细胞是大脑和脊髓中形成髓鞘的特殊细胞。髓鞘是神经轴突周围的绝缘层，对信息的快速传递是必不可少的。因此，少突胶质细胞的正常功能对终生健康至关重要。大脑中的大多数少突胶质细胞是在出生前后和发育的第一年产生的。然而，少突胶质细胞继续在成人大脑中生成，这对于取代在正常衰老过程中丢失的细胞非常重要。值得注意的是，在老化的大脑中产生的少突胶质细胞可能不足以进行修复过程，这在与年龄相关的白质完整性和认知功能的丧失中是重要的。老化大脑中白质缺陷背后的机制尚未解决。现在，我们已经确定了一种特殊的细胞膜离子通道，称为Kir4.1，它对少突胶质细胞的功能至关重要。我们建议确定Kir4.1在发育和老化的大脑中调节少突胶质细胞生成的机制。这项工作符合BBSRC老龄化研究(终身健康和福祉)的研究优先事项，并将为解决BSRC核心生物科学和专题战略优先事项作出重大贡献。

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. As such, the normal functioning of oligodendrocytes is essential for Lifelong Health and Wellbeing. Most oligodendrocytes in the brain are generated around birth and during the first years of development. However, oligodendrocytes continue to be generated in the adult brain and this is important for replacing cells that are lost during normal ageing. Notably, generation of oligodendrocytes in the ageing brain can be inadequate for reparative processes, and this is important in age-related loss of white matter integrity and cognitive function. The mechanisms underlying white matter defects in the ageing brain are unresolved. Now, we have identified a specific cell membrane ion channel called Kir4.1 that is crucial for oligodendrocyte function. We propose to determine the mechanisms by which Kir4.1 regulates the generation of oligodendrocytes in the developing and ageing brain. This work meets the BBSRC Research Priority of Ageing Research (Lifelong Health and Wellbeing), and will make a significant contribution to addressing BBSRC core bioscience and thematic strategic priorities.