Mechanisms of lysophosphatidylcholine‐induced demyelination: A primary lipid disrupting myelinopathy. Issue 2 (25th October 2017)

• Record Type: Journal Article
• Authors: Plemel, Jason R.; Michaels, Nathan J.; Weishaupt, Nina; Caprariello, Andrew V.; Keough, Michael B.; Rogers, James A.; Yukseloglu, Aran; Lim, Jaehyun; Patel, Vikas V.; Rawji, Khalil S.; Jensen, Samuel K.; Teo, Wulin; Heyne, Belinda; Whitehead, Shawn N.; Stys, Peter K.; Yong, V. Wee
• Is Part Of: Glia. Volume 66:Issue 2(2018)
• Page Start: 327
• Page End: 347
• Publication Date: 2017-10-25
• Subjects: demyelination -- lysolecithin -- multiple sclerosis -- myelin -- oligodendrocyte; Neuroglia -- Periodicals; Neurology -- Periodicals; 611.0188
• DOI: 10.1002/glia.23245
• Languages: English
• ISSNs: 0894-1491

Abstract

Abstract: 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. Main Points: LPC integrates into cellular membranes causing cell death and demyelination due to its lipid‐disrupting properties.