| First Author | Sato H | Year | 2016 |
| Journal | Stem Cells | Volume | 34 |
| Issue | 3 | Pages | 685-98 |
| PubMed ID | 26435273 | Mgi Jnum | J:280412 |
| Mgi Id | MGI:6363383 | Doi | 10.1002/stem.2212 |
| Citation | Sato H, et al. (2016) PDGFR-beta Plays a Key Role in the Ectopic Migration of Neuroblasts in Cerebral Stroke. Stem Cells 34(3):685-98 |
| abstractText | The neuroprotective agents and induction of endogenous neurogenesis remain to be the urgent issues to be established for the care of cerebral stroke. Platelet-derived growth factor receptor beta (PDGFR-beta) is mainly expressed in neural stem/progenitor cells (NSPCs), neurons and vascular pericytes of the brain; however, the role in pathological neurogenesis remains elusive. To this end, we examined the role of PDGFR-beta in the migration and proliferation of NSPCs after stroke. A transient middle cerebral-arterial occlusion (MCAO) was introduced into the mice with conditional Pdgfrb-gene inactivation, including N-PRbeta-KO mice where the Pdgfrb-gene was mostly inactivated in the brain except that in vascular pericytes, and E-PRbeta-KO mice with tamoxifen-induced systemic Pdgfrb-gene inactivation. The migration of the DCX(+) neuroblasts from the subventricular zone toward the ischemic core was highly increased in N-PRbeta-KO, but not in E-PRbeta-KO as compared to Pdgfrb-gene preserving control mice. We showed that CXCL12, a potent chemoattractant for CXCR4-expressing NSPCs, was upregulated in the ischemic lesion of N-PRbeta-KO mice. Furthermore, integrin alpha3 intrinsically expressed in NSPCs that critically mediates extracellular matrix-dependent migration, was upregulated in N-PRbeta-KO after MCAO. NSPCs isolated from N-PRbeta-KO rapidly migrated on the surface coated with collagen type IV or fibronectin that are abundant in vascular niche and ischemic core. PDGFR-beta was suggested to be critically involved in pathological neurogenesis through the regulation of lesion-derived chemoattractant as well as intrinsic signal of NSPCs, and we believe that a coordinated regulation of these molecular events may be able to improve neurogenesis in injured brain for further functional recovery. |
