Brain-derived neurotrophic factor promotes vasculature-associated migration of neuronal precursors toward the ischemic striatum
| Autor: | Jasna Kriz, Marina Snapyan, Sofia Grade, Armen Saghatelyan, João O. Malva, Yuan C. Weng |
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| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Male
Mouse Rostral migratory stream lcsh:Medicine Tropomyosin receptor kinase B Cardiovascular Brain Ischemia Mice 0302 clinical medicine Neural Stem Cells Neurotrophic factors Cell Movement Morphogenesis lcsh:Science Neurons 0303 health sciences Multidisciplinary biology Stem Cells Animal Models Neural stem cell Cell biology Stroke Adult Stem Cells medicine.anatomical_structure Medicine Neurotrophin Research Article Neurogenesis Subventricular zone Neovascularization Physiologic Cell Migration Receptors Nerve Growth Factor 03 medical and health sciences Model Organisms Neuroblast Developmental Neuroscience medicine Animals Receptor trkB Biology 030304 developmental biology Brain-derived neurotrophic factor Brain-Derived Neurotrophic Factor lcsh:R Mice Inbred C57BL Neostriatum Gene Expression Regulation nervous system Astrocytes Immunology biology.protein lcsh:Q 030217 neurology & neurosurgery Developmental Biology Neuroscience |
| Zdroj: | PLoS ONE, Vol 8, Iss 1, p e55039 (2013) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | Stroke induces the recruitment of neuronal precursors from the subventricular zone (SVZ) into the ischemic striatum. In injured areas, de-routed neuroblasts use blood vessels as a physical scaffold to their migration, in a process that resembles the constitutive migration seen in the rostral migratory stream (RMS). The molecular mechanism underlying injury-induced vasculature-mediated migration of neuroblasts in the post-stroke striatum remains, however, elusive. Using adult mice we now demonstrate that endothelial cells in the ischemic striatum produce brain-derived neurotrophic factor (BDNF), a neurotrophin that promotes the vasculature-mediated migration of neuronal precursors in the RMS, and that recruited neuroblasts maintain expression of p75NTR, a low-affinity receptor for BDNF. Reactive astrocytes, which are widespread throughout the damaged area, ensheath blood vessels and express TrkB, a high-affinity receptor for BDNF. Despite the absence of BDNF mRNA, we observed strong BDNF immunolabeling in astrocytes, suggesting that these glial cells trap extracellular BDNF. Importantly, this pattern of expression is reminiscent of the adult RMS, where TrkB-expressing astrocytes bind and sequester vasculature-derived BDNF, leading to the entry of migrating cells into the stationary phase. Real-time imaging of cell migration in acute brain slices revealed a direct role for BDNF in promoting the migration of neuroblasts to ischemic areas. We also demonstrated that cells migrating in the ischemic striatum display higher exploratory behavior and longer stationary periods than cells migrating in the RMS. Our findings suggest that the mechanisms involved in the injury-induced vasculature-mediated migration of neuroblasts recapitulate, at least partially, those observed during constitutive migration in the RMS. |
| Databáze: | OpenAIRE |
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