Neural stem and progenitor cells (NSPCs) are important for nerve regeneration after spinal cord injury (SCI). Their proliferation, however, is limited. In this study, we investigated the role of Notch1 signaling in NSPC proliferation using adult mouse spinal cord derived NSPCs. We observed that Notch1 promoted proliferation of NSPCs and that Notch1 overexpression led to an expansion of cells in the S-phase and increased cyclin D1 expression. When investigating the functional relationship between Notch1, p-p38 and Pax6, we found that Notch1 suppressed p-p38 while promoting Pax6 expression. Functional inhibition of p38 with SB202190 led to increased Pax6 expression and to proliferation, as determined by BrdU. Furthermore, we confirmed that Pax6 induced proliferation in adult mouse spinal cord derived NSPCs. In conclusion, we demonstrate that Notch1 promotes the proliferation of mouse spinal NSPCs via a p-p38-pax6-cyclin D1 signaling pathway. This pathway constitutes a promising new therapeutic target for SCI treatment.
Keywords: Neural stem and progenitor cells (NSPCs); Notch signaling; Spinal cord injury (SCI).
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