Neutralization of the membrane protein Nogo-A enhances growth and reactive sprouting in established organotypic hippocampal slice cultures.
The reduced ability of central axons to regenerate after injury is significantly influenced by the presence of several molecules that inhibit axonal growth. Nogo-A is one of the most studied and most potent of the myelin-associated growth inhibitory molecules. Its neutralization, as well as interference with its signalling, allows for enhanced axonal sprouting and growth following injury. Using differentiated rat organotypic hippocampal slice cultures treated for 5 days with either of two different function-blocking anti-Nogo-A antibodies, we show an increase in CA3 fibre regeneration after lesion. In intact slices, 5 days of anti-Nogo-A antibody treatment led to increased sprouting of intact CA3 fibres that are positive for neurofilament 68. A transcriptomic approach confirmed the occurrence of a growth response on the molecular level upon Nogo-A neutralization in intact cultures. Our results demonstrate that Nogo-A neutralization for 5 days is sufficient for the induction of growth in mature CNS tissue without the prerequisite of an injury. Nogo-A may therefore act as a tonic growth suppressor/stabilizer in the adult intact hippocampus.
Craveiro
Luis M
LM
Brain Research Institute, University of Zurich, Zurich, Switzerland. craveiro@hifo.unizh.ch
Hakkoum
David
D
Weinmann
Oliver
O
Montani
Laura
L
Stoppini
Luc
L
Schwab
Martin E
ME
D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000494:pharmacology* / Q000627:therapeutic use; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000235:genetics; D020439:Growth Cones / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D006131:Growth Inhibitors / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009185:Myelin Proteins / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism*; D009416:Nerve Regeneration / Q000187:drug effects / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics; D016900:Neurofilament Proteins / Q000378:metabolism; D055495:Neurogenesis / Q000187:drug effects / Q000276:immunology; D009473:Neuronal Plasticity / Q000187:drug effects / Q000276:immunology; D000070798:Nogo Proteins; D020411:Oligonucleotide Array Sequence Analysis; D009924:Organ Culture Techniques; D051381:Rats; D017208:Rats, Wistar; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics / Q000276:immunology
D000906:Antibodies; D015415:Biomarkers; D006131:Growth Inhibitors; D009185:Myelin Proteins; D009419:Nerve Tissue Proteins; D016900:Neurofilament Proteins; D000070798:Nogo Proteins; C000603197:Rtn4 protein, rat; C066858:neurofilament protein NF 68