The Role of Indirect PAR1 Activation in Tissue Repair after SCI
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Series/Report no.:2014 Richard J. and Martha D. Denman Undergraduate Research Forum. 19th
PAR1 (Protease-Activated Receptor 1) is a G protein-coupled receptor present on many different CNS (Central Nervous System) cell types. When cleaved by serine proteases, PAR1 initiates several signaling cascades associated with tissue repair. After spinal cord injury (SCI), PAR1 is upregulated within the damaged tissue. We hypothesized that PAR1 activation would promote the proliferation of oligodendrocyte progenitor cells (OPC’s), which are known to play a role in repair after SCI. Indeed, activation of PAR1 within the spinal cord via microinjection of a PAR1 agonist promoted an increase in OPC proliferation, accompanied by an acculumation of microglia surrounding the microinjection site. However, when pure OPC cultures were treated with the same agonist, PAR1 activation had no effect. This suggests that other cells in the in vivo microenvironment may indirectly promote the OPC response. Our goal is to determine if the activation of PAR1 on microglia or astrocytes promotes proliferation of OPC’s in vitro. OPC’s will be co-cultured with microglia and astrocytes, followed by activation of glial cells by PAR1 agonist. Through quantificaiton of these mixed glial cultures, we hope to determine if there is indeed a relationship between PAR1 activated microglia/astrocytes and the proliferation of these progenitor cells. This data may help elucidate the role of PAR1 in the regeneration of damaged spinal tissue and therefore repair after SCI.
Health Professions - Laboratory/Cellular: 2nd Place (The Ohio State University Denman Undergraduate Research Forum)
Academic Major: Neuroscience