Title
Mechanisms of lysophosphatidylcholine-induced demyelination: A primary lipid disrupting myelinopathy
Authors
Jason R. Plemel, Department of Clinical Neurosciences, Hotchkiss Brain Institute, University of Calgary
Nathan J. Michaels, Department of Clinical Neurosciences, Hotchkiss Brain Institute, University of Calgary
Nina Weishaupt, Department of Anatomy and Cell Biology, Schulich School of Medicine and Dentistry, Western University
Andrew V. Caprariello, Department of Clinical Neurosciences, Hotchkiss Brain Institute, University of Calgary
Michael B. Keough, Department of Clinical Neurosciences, Hotchkiss Brain Institute, University of Calgary
James A. Rogers, Department of Clinical Neurosciences, Hotchkiss Brain Institute, University of Calgary
Aran Yukseloglu, Department of Clinical Neurosciences, Hotchkiss Brain Institute, University of Calgary
Jaehyun Lim, Department of Clinical Neurosciences, Hotchkiss Brain Institute, University of Calgary
Vikas V. Patel, Department of Anatomy and Cell Biology, Schulich School of Medicine and Dentistry, Western University
Khalil S. Rawji, Department of Clinical Neurosciences, Hotchkiss Brain Institute, University of Calgary
Samuel K. Jensen, Department of Clinical Neurosciences, Hotchkiss Brain Institute, University of Calgary
Wulin Teo, Department of Clinical Neurosciences, Hotchkiss Brain Institute, University of Calgary
Belinda Heyne, Department of Chemistry, Hotchkiss Brain Institute, University of Calgary
Shawn N. Whitehead, Department of Anatomy and Cell Biology, Schulich School of Medicine and Dentistry, Western University, London
Peter K. Stys, Department of Clinical Neurosciences, Hotchkiss Brain Institute, University of Calgary
Wee V. Yong, Department of Clinical Neurosciences, Hotchkiss Brain Institute, University of Calgary
URL with Digital Object Identifier
https://doi.org/10.1002/glia.23245
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.
