Glutamatergic Regulation of Remyelination After Spinal Cord Injury
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Date
2019-03
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Abstract
Chronic demyelination, resulting in slowed conduction velocity and impaired recovery, is a hallmark of spinal cord injury (SCI), and is partially due to the loss of oligodendrocytes (OLs). OLs are terminally differentiated and cannot self-renew; thus, the endogenous repair that occurs after SCI is largely attributed to the robust proliferation of oligodendrocyte progenitor cells (OPCs) that differentiate into mature OLs. Since OPCs are the primary source of new myelin, it is critical to understand how OPCs are regulated at various times pre and post-injury. Evidence from chemical demyelination studies show glutamate is packaged in vesicular glutamate transporter (Vglut)-positive vesicles and stored along demyelinated axon shafts. Activity-dependent release of glutamate from these axons stimulates OPC migration, differentiation, and ultimately remyelination. Since spinal tracts are mostly glutamatergic, we expect a similar phenomenon to occur after SCI. Here, we tested the hypothesis that Vglut2 accumulates in axons after SCI and predicts OPC-axon contact points. For this, we collected spinal cords from naïve and SCI mice from 7 days to 6 months post-injury (mpi) to examine Vglut2 distribution in axons. This revealed the number of Vglut2+ puncta in spared white matter increased continuously after SCI to a peak 9-fold greater than naïve at 6mpi. The number of Vglut2+ puncta within axons contacted by OPC processes was also quantified. In naïve tissue, ~10% of Vglut2+ puncta were contacted by an OPC process. OPC/Vglut2 contacts increased significantly by 28dpi and rose to a peak at 6mpi when 40% of Vglut2 puncta had an OPC contact. These results suggest axonal glutamate release promotes OPC contacts with axons after SCI and may play a role in remyelination. Overall this work shows for the first time that OPCs contact Vglut2-enriched regions of axons after CNS trauma, and suggests that loss of such contacts may contribute to chronic post-SCI demyelination.
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Poster Division: Biological Sciences: 1st Place (The Ohio State University Edward F. Hayes Graduate Research Forum)
Keywords
Spinal cord injury, demyelination, remyelination, glutamate