Mechanisms of lysophosphatidylcholine ‐induced demyelination: A primary lipid disrupting myelinopathy

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 injected into white matter causes demyelination, but it is also present endogenously in the blood plasma, and it increases during inflammation of the CNS. LPC might, therefore, be an endogenous mediator of demyelination. LPC induces demyelination by integrating into and disrupting cellular membranes, causing cell death and producing a primary myelinopathy with a secondary immune response. LPC damage produced a delayed elevation of e...
Source: Glia - Category: Neurology Authors: Tags: RESEARCH ARTICLE Source Type: research
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