Brain-derived neurotrophic factor promotes vasculature-associated migration of neuronal precursors toward the ischemic striatum

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 migrato...

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Bibliographic Details
Published in:	PloS one Vol. 8; no. 1; p. e55039
Main Authors:	Grade, Sofia, Weng, Yuan C, Snapyan, Marina, Kriz, Jasna, Malva, João O, Saghatelyan, Armen
Format:	Journal Article
Language:	English
Published:	United States Public Library of Science 29-01-2013 Public Library of Science (PLoS)
Subjects:	Affinity Analgesics Animals Astrocytes Astrocytes - metabolism Astrocytes - pathology Biology Blood Blood vessels Brain Brain Ischemia - genetics Brain Ischemia - metabolism Brain Ischemia - pathology Brain Ischemia - physiopathology Brain slice preparation Brain-derived neurotrophic factor Brain-Derived Neurotrophic Factor - genetics Brain-Derived Neurotrophic Factor - metabolism Carotid arteries Cell migration Cell Movement Endothelial cells Exploratory behavior Gene Expression Regulation Glial cells Injuries Ischemia Kinases Male Medicine Mice Mice, Inbred C57BL mRNA Neostriatum Neostriatum - blood supply Neostriatum - pathology Neovascularization, Physiologic Neural stem cells Neural Stem Cells - pathology Neurobiology Neuroblasts Neurogenesis Neuroimaging Neurons Neurons - metabolism Neurons - pathology Neurosciences Precursors Receptor, trkB - genetics Receptors, Nerve Growth Factor - genetics Rodents Stationary phase Stroke Subventricular zone TrkB receptors Veins & arteries Canada Quebec City Quebec Canada
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Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Competing Interests: The authors have declared that no competing interests exist. Conceived and designed the experiments: AS JOM. Performed the experiments: SG YCW MS JK AS. Analyzed the data: SG JOM MS AS. Wrote the paper: SG JOM AS.
ISSN:	1932-6203 1932-6203
DOI:	10.1371/journal.pone.0055039