SDF-1 stimulates neurite growth on inhibitory CNS myelin.
Impaired axonal regeneration is a common observation after central nervous system (CNS) injury. The stromal cell-derived factor-1, SDF-1/CXCL12, has previously been shown to promote axonal growth in the presence of potent chemorepellent molecules known to be important in nervous system development. Here, we report that treatment with SDF-1alpha is sufficient to overcome neurite outgrowth inhibition mediated by CNS myelin towards cultured postnatal dorsal root ganglion neurons. While we found both cognate SDF-1 receptors, CXCR4 and CXCR7/RDC1, to be coexpressed on myelin-sensitive dorsal root ganglion neurons, the distinct expression pattern of CXCR4 on growth cones and branching points of neurites suggests a function of this receptor in chemokine-mediated growth promotion and/or arborization. These in vitro findings were further corroborated as local intrathecal infusion of SDF-1 into spinal cord injury following thoracic dorsal hemisection resulted in enhanced sprouting of corticospinal tract axons into white and grey matter. Our findings indicate that SDF-1 receptor activation might constitute a novel therapeutic approach to promote axonal growth in the injured CNS.
Opatz
Jessica
J
Molecular Neurobiology Laboratory, Department of Neurology, Heinrich-Heine-University, Moorenstrasse 5, D-40225 Düsseldorf, Germany.
Küry
Patrick
P
Schiwy
Nora
N
Järve
Anne
A
Estrada
Veronica
V
Brazda
Nicole
N
Bosse
Frank
F
Müller
Hans Werner
HW
D000818:Animals; D018929:Cell Culture Techniques; D002478:Cells, Cultured; D002490:Central Nervous System / Q000378:metabolism*; D054377:Chemokine CXCL12 / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D005260:Female; D005727:Ganglia, Spinal / Q000166:cytology; D009186:Myelin Sheath / Q000378:metabolism*; D009416:Nerve Regeneration / Q000502:physiology; D016501:Neurites / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D011712:Pyramidal Tracts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D054387:Receptors, CXCR / Q000235:genetics / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism; D013116:Spinal Cord / Q000033:anatomy & histology / Q000187:drug effects / Q000601:surgery
C501898:Ackr3 protein, rat; D054377:Chemokine CXCL12; C486264:Cxcr4 protein, rat; D054387:Receptors, CXCR; D019718:Receptors, CXCR4