title: Long-lasting sprouting and gene expression changes induced by the monoclonal antibody IN-1 in the adult spinal cord.
abstract: Lesion-induced plasticity of the rat corticospinal tract (CST) decreases postnatally, simultaneously with myelin appearance. In adult rats, compensatory sprouting can be induced by the monoclonal antibody (mAb) IN-1 raised against the growth inhibitory protein Nogo-A. In this study, we examined separately the fate of sensory and motor corticospinal fibers after mAb IN-1 application. Intact adult rats treated with the IN-1 antibody exhibited an increase of aberrant CST projections, i.e., sensory fibers projecting into the ventral horn and motor fibers projecting dorsally. Unilateral lesion of the CST [pyramidotomy (PTX)] in the presence of mAb IN-1 triggered a progressive reorganization of the sprouting of the remaining CST across the midline, with sensory fibers projecting gradually into the denervated dorsal horn and motor fibers projecting into the denervated ventral horn. In unilaterally denervated spinal cords, aberrant sprouts were only transient and disappeared by 6 weeks, whereas midline crossing fibers ending in the appropriate target region were stabilized and persisted over the entire study period. Within the spinal cord, IN-1 antibody treatment was associated with upregulation of growth factors (BDNF, VEGF), growth-related proteins (actin, myosin, GAP-43), and transcription factors (STATs), whereas pyramidotomy induced an enhanced expression of guidance molecules (semaphorins and slits) as well as neurotrophic factors (BDNF, IGFs, BMPs). These gene expression changes may contribute to attraction, guidance, and stabilization of sprouting CST fibers.
authors.affiliation: Brain Research Institute, Department of Biology, University of Zürich, ETH Zürich, 8057 Zürich, Switzerland. florence.bareyre@access.unizh.ch
authors.forename: Florence M
authors.initials: FM
authors.lastname: Bareyre
authors.forename: Brigitte
authors.initials: B
authors.lastname: Haudenschild
authors.forename: Martin E
authors.initials: ME
authors.lastname: Schwab
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D001369:Axons / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D003714:Denervation; D015870:Gene Expression / Q000187:drug effects*; D020869:Gene Expression Profiling; D008297:Male; D009046:Motor Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009185:Myelin Proteins / Q000037:antagonists & inhibitors; D009333:Neck; D009412:Nerve Fibers / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D009416:Nerve Regeneration / Q000187:drug effects* / Q000502:physiology; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D009475:Neurons, Afferent / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D000070798:Nogo Proteins; D020411:Oligonucleotide Array Sequence Analysis; D011712:Pyramidal Tracts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D012313:RNA / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D013997:Time Factors
chemical_list: D000911:Antibodies, Monoclonal; D009185:Myelin Proteins; D000070798:Nogo Proteins; C000603197:Rtn4 protein, rat; D012313:RNA