title: Brain-derived neurotrophic factor promotes vasculature-associated migration of neuronal precursors toward the ischemic striatum.
abstract: 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.
authors: Cellular Neurobiology Unit, Insitut en Santé Mentale de Québec, Quebec City, Canada.
authors: Sofia
authors: S
authors: Grade
authors: Yuan C
authors: YC
authors: Weng
authors: Marina
authors: M
authors: Snapyan
authors: Jasna
authors: J
authors: Kriz
authors: João O
authors: JO
authors: Malva
authors: Armen
authors: A
authors: Saghatelyan
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology; D002545:Brain Ischemia / Q000235:genetics / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D002465:Cell Movement; D005786:Gene Expression Regulation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017072:Neostriatum / Q000098:blood supply* / Q000473:pathology*; D018919:Neovascularization, Physiologic; D058953:Neural Stem Cells / Q000473:pathology; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D020813:Receptor, trkB / Q000235:genetics; D017475:Receptors, Nerve Growth Factor / Q000235:genetics
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D017475:Receptors, Nerve Growth Factor; C517634:Ngfr protein, mouse; D020813:Receptor, trkB
references: J Neurosci. 2006 Jun 14;26(24):6627-36
references: 16775151
references: J Neurosci. 2008 Dec 10;28(50):13368-83
references: 19074010
references: Stem Cells. 2006 Mar;24(3):739-47
references: 16210404
references: J Vis Exp. 2011 Jan 06;(47):
references: 21248698
references: Mol Cell Neurosci. 1998 Jul;11(4):234-45
references: 9675054
references: Eur J Neurosci. 2007 Oct;26(7):1780-90
references: 17883412
references: Proc Natl Acad Sci U S A. 1992 Jan 15;89(2):648-52
references: 1731336
references: J Neurosci Res. 1995 Aug 1;41(5):684-95
references: 7563249
references: J Neurosci. 2007 May 9;27(19):5146-55
references: 17494700
references: J Neurosci Res. 2006 Aug 15;84(3):626-31
references: 16770774
references: J Neurosci. 2001 Oct 1;21(19):7654-63
references: 11567055
references: J Neurosci. 2007 Mar 21;27(12):3157-62
references: 17376977
references: Neuroscience. 1993 Jul;55(1):23-31
references: 8350988
references: J Neurosci. 2004 Mar 3;24(9):2133-42
references: 14999064
references: Neuron. 2002 Jun 13;34(6):945-60
references: 12086642
references: J Neurosci Res. 2009 Jun;87(8):1892-903
references: 19156869
references: Brain Res. 1998 Jun 29;797(2):278-86
references: 9666147
references: Neuron. 2009 Apr 16;62(1):53-71
references: 19376067
references: Mol Cell Neurosci. 2000 Aug;16(2):87-96
references: 10924253
references: J Neuropathol Exp Neurol. 2009 Jan;68(1):83-93
references: 19104443
references: Neuroscience. 1993 Jul;55(2):473-90
references: 8080474
references: J Cereb Blood Flow Metab. 1999 Nov;19(11):1220-8
references: 10566968
references: Mol Cell Neurosci. 2003 Sep;24(1):171-89
references: 14550778
references: J Neurosci. 1999 Mar 1;19(5):1708-16
references: 10024357
references: Glia. 2012 May;60(6):851-66
references: 22354480
references: Exp Neurol. 1997 Nov;148(1):83-91
references: 9398452
references: J Neurosci. 1995 Aug;15(8):5765-78
references: 7643217
references: J Neurosci. 2001 Sep 1;21(17):6718-31
references: 11517261
references: J Neurosci. 2009 Apr 1;29(13):4172-88
references: 19339612
references: Nature. 2003 Nov 6;426(6962):25-6
references: 14603298
references: Dev Psychobiol. 2012 Sep;54(6):578-89
references: 21432850
references: J Cereb Blood Flow Metab. 2004 Apr;24(4):441-8
references: 15087713
references: J Neurosci. 2012 Feb 1;32(5):1687-704
references: 22302810
references: Annu Rev Neurosci. 2003;26:441-83
references: 12626695
references: Development. 2002 Jul;129(13):3147-60
references: 12070090
references: Neuroscience. 2003;120(1):31-40
references: 12849738
references: Exp Neurol. 1998 Dec;154(2):289-301
references: 9878168
references: Exp Neurol. 1995 Nov;136(1):73-88
references: 7589336
references: EMBO J. 1990 Aug;9(8):2459-64
references: 2369898
references: Neuron. 2010 Jul 29;67(2):213-23
references: 20670830
references: J Cell Biol. 2008 Oct 20;183(2):213-21
references: 18852301
references: Stem Cells. 2010 Mar 31;28(3):545-54
references: 20073084
references: Stroke. 2007 Nov;38(11):3032-9
references: 17901386
references: J Neurosci. 2007 May 30;27(22):5976-80
references: 17537968
references: J Comp Neurol. 1999 Apr 28;407(1):77-91
references: 10213189
references: Dev Biol. 2003 Jun 15;258(2):319-33
references: 12798291
references: Neurochem Int. 2011 Jan;58(1):102-11
references: 21074587
references: Brain Res Bull. 1997;42(1):9-21
references: 8978930
references: J Neurosci. 2004 Sep 1;24(35):7623-31
references: 15342728
references: J Comp Neurol. 2009 Sep 10;516(2):94-104
references: 19575445
references: Exp Neurol. 2001 Jun;169(2):351-63
references: 11358448
references: J Neurosci. 2001 Sep 1;21(17):6706-17
references: 11517260
references: J Cereb Blood Flow Metab. 2009 Jul;29(7):1240-50
references: 19436318
references: Glia. 2010 Jan 15;58(2):218-30
references: 19610095
references: Ann Neurol. 2002 Dec;52(6):802-13
references: 12447935
references: Int J Biol Sci. 2009;5(2):118-27
references: 19173033
references: J Neurosci. 2007 Mar 7;27(10):2596-605
references: 17344397
references: Trends Neurosci. 1994 Nov;17(11):490-6
references: 7531892
references: PLoS One. 2009 Dec 01;4(12):e8101
references: 19956568
references: Neuron. 1993 Feb;10(2):151-64
references: 8439408
references: Nat Med. 2002 Sep;8(9):963-70
references: 12161747
references: Development. 2002 Mar;129(6):1435-42
references: 11880352
references: J Neurosci. 2008 Mar 5;28(10):2383-93
references: 18322085
references: J Neurosci. 2006 Dec 13;26(50):13007-16
references: 17167090
references: Stroke. 2007 Jul;38(7):2165-72
references: 17510456