Department of Clinical Neurosciences, Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, T2N4N4, Canada.
Department of Anatomy and Cell Biology, Schulich School of Medicine and Dentistry, Western University, London, Ontario, N6A5C1, Canada.
Glia. 2018 Feb;66(2):327-347. doi: 10.1002/glia.23245. Epub 2017 Oct 25.
For decades lysophosphatidylcholine (LPC, lysolecithin) has been used to induce demyelination, without a clear understanding of its mechanisms. LPC is an endogenous lysophospholipid so it may cause demyelination in certain diseases. We investigated whether known receptor systems, inflammation or nonspecific lipid disruption mediates LPC-demyelination in mice. We found that LPC nonspecifically disrupted myelin lipids. LPC integrated into cellular membranes and rapidly induced cell membrane permeability; in mice, LPC injury was phenocopied by other lipid disrupting agents. Interestingly, following its injection into white matter, LPC was cleared within 24 hr but by five days there was an elevation of endogenous LPC that was not associated with damage. This elevation of LPC in the absence of injury raises the possibility that the brain has mechanisms to buffer LPC. In support, LPC injury in culture was significantly ameliorated by albumin buffering. These results shed light on the mechanisms of LPC injury and homeostasis.
几十年来，溶血磷脂酰胆碱（LPC，溶血卵磷脂）一直被用于诱导脱髓鞘，但人们对其机制并不清楚。LPC 是一种内源性溶血磷脂，因此它可能在某些疾病中导致脱髓鞘。我们研究了已知的受体系统、炎症或非特异性脂质紊乱是否介导了 LPC 在小鼠中的脱髓鞘作用。我们发现，LPC 非特异性地破坏髓鞘脂质。LPC 整合到细胞膜中，并迅速诱导细胞膜通透性；在小鼠中，其他破坏脂质的药物可模拟 LPC 损伤。有趣的是，LPC 注入白质后，在 24 小时内被清除，但在 5 天时，内源性 LPC 升高，但与损伤无关。在没有损伤的情况下 LPC 的升高，使得大脑具有缓冲 LPC 的机制成为可能。支持这一观点的是，白蛋白缓冲显著改善了 LPC 在培养中的损伤。这些结果为 LPC 损伤和动态平衡的机制提供了线索。
