Abstract
AbstractMultiple Sclerosis is an autoimmune demyelination disorder with unknown etiology. Despite the myelin damage, the roles of myelinating oligodendrocytes in driving disease progression remain unknown. We hypothesize that disrupting vesicular transport in oligodendrocytes during adolescence will disrupt myelin integrity and causes neuroinflammation. By creating a mouse model of SNAP-23 conditional knockout in mature oligodendrocytes, we showed that impairment in vesicular trafficking in oligodendrocytes causes demyelination. Neuroinflammation with infiltration of peripheral immune T cells into the central nervous system was observed accompanied by demyelination. Mechanistically, SNAP-23 removal in oligodendrocytes caused abnormal axon-myelin structures and impaired myelin protein trafficking, both can contribute to autoimmune activation and demyelination. With our novel animal model, we propose that oligodendrocyte injury is an endogenous early event in triggering Multiple Sclerosis.One-Sentence SummaryImpaired vesicular transport in oligodendrocytes in adults caused demyelination and inflammation driving Multiple Sclerosis
Publisher
Cold Spring Harbor Laboratory