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Mechanisms of lysophosphatidylcholine‐induced demyelination: A primary lipid disrupting myelinopathy
Author(s) -
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
Publication year - 2018
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.23245
Subject(s) - lysophosphatidylcholine , endogeny , myelin , inflammation , homeostasis , biology , clearance , microbiology and biotechnology , lipid signaling , neuroscience , medicine , immunology , endocrinology , biochemistry , central nervous system , membrane , phosphatidylcholine , phospholipid , urology
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.