Meuth Sven G, Kanyshkov Tatjana, Melzer Nico, Bittner Stefan, Kieseier Bernd C, Budde Thomas, Wiendl Heinz
Department of Neurology, University of Würzburg, Josef-Schneider-Strafe 11, 97080 Würzburg, Germany.
Neurosci Lett. 2008 Dec 3;446(2-3):133-8. doi: 10.1016/j.neulet.2008.09.038.
Multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis (EAE) are characterized by T cell-mediated autoimmune inflammation of the central nervous system (CNS) leading to oligodendrocyte loss and demyelination accompanied by neuronal cell death. Neuronal TWIK-related acid-sensitive potassium (TASK) channels allow the regulated efflux of potassium ions. These channels might either protect neurons in the inflamed CNS by modulating electrical excitability or even contribute to inflammatory neurodegeneration mediating intracellular potassium depletion. Using a combination of in-situ-hybridisation and immunofluorescence staining, we found increased neuronal expression of TASK1 and TASK3 channels in the optic nerve and decreased expression in the spinal cord and thalamus of rats undergoing MOG-induced EAE. Inflammatory plaques of human MS patients displayed profoundly lowered expression of both TASK isoforms. Thus, regulated expression of TASK channels might contribute to a molecular switch between death and survival of neurons in autoimmune CNS inflammation.
多发性硬化症（MS）及其动物模型实验性自身免疫性脑脊髓炎（EAE）的特征是中枢神经系统（CNS）由T细胞介导的自身免疫性炎症，导致少突胶质细胞丢失和脱髓鞘，并伴有神经元细胞死亡。神经元的TWIK相关酸敏感钾（TASK）通道允许钾离子的调节性外流。这些通道可能通过调节电兴奋性来保护炎症中枢神经系统中的神经元，甚至可能通过介导细胞内钾耗竭而导致炎症性神经变性。通过原位杂交和免疫荧光染色相结合的方法，我们发现在经髓鞘少突胶质细胞糖蛋白（MOG）诱导的EAE大鼠的视神经中，TASK1和TASK3通道的神经元表达增加，而在脊髓和丘脑中表达降低。人类MS患者的炎性斑块显示这两种TASK亚型的表达均显著降低。因此，TASK通道的调节性表达可能有助于自身免疫性中枢神经系统炎症中神经元死亡与存活之间的分子转换。
