Increasing local levels of neuregulin (glial growth factor-2) by direct infusion into areas of demyelination does not alter remyelination in the rat CNS.

Abstract

Glial growth factor-2 (GGF-2) is a neuronally derived isoform of neuregulin shown in vitro to promote proliferation and survival of oligodendrocytes, the myelinating cells of the CNS. Enhanced remyelination has been demonstrated in vivo following systemic delivery of human recombinant GGF-2 (rhGGF-2) in experimental autoimmune encephalomyelitis (EAE). However, it is uncertain whether this is the result of direct effects of rhGGF-2 on cells of the oligodendrocyte lineage or due to modulation of the immune or inflammatory response. If this enhanced remyelination was due to direct effects of rhGGF-2 on cells of the oligodendrocyte lineage then one would expect rhGGF-2 to induce a similar proremyelinating response in nonimmune, gliotoxin models of demyelination. Using a gliotoxin model of demyelination we were therefore able to ascertain the in vivo effect of rhGGF-2 following local CNS delivery in a model that is not confounded by the concurrent presence of an immune-mediated process. No significant alteration in the rate or character of remyelination was evident following local delivery as compared to controls, and indeed nor following systemic delivery in the gliotoxin model. The results of this study therefore indicate that both direct infusion and systemic delivery of rhGGF-2 do not alter remyelination in a nonimmune, gliotoxin model of demyelination. This suggests that the proremyelinating effects of systemically delivered rhGGF-2 in EAE are unlikely to be due to direct effects on the oligodendrocyte lineage, but may be mediated by rhGGF-2 inducing an environment more favourable to remyelination, possibly through modulation of the immune response.

• Authors: Jacques Penderis, Rachel H Woodruff, Andras Lakatos, Wen-Wu Li, Mark D Dunning, Chao Zhao, Mark Marchionni, Robin J M Franklin
• Journal: The European journal of neuroscience (Eur J Neurosci) Vol. 18 Issue 8 Pg. 2253-64 (Oct 2003) ISSN: 0953-816X [Print] France
• PMID: 14622186 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Enzyme Inhibitors
• Indoles
• Nerve Tissue Proteins
• Neuregulin-1
• Nrg1 protein, rat
• RNA, Messenger
• DAPI
• Receptor, ErbB-2
• Receptor, ErbB-3
• Ethidium
• Bromodeoxyuridine

Topics

• Animals
• Bromodeoxyuridine (metabolism)
• Cell Count
• Cell Division
• Cells, Cultured
• Central Nervous System (drug effects, pathology)
• Demyelinating Diseases (chemically induced, pathology)
• Dose-Response Relationship, Drug
• Drug Administration Routes (veterinary)
• Enzyme Inhibitors (toxicity)
• Ethidium (toxicity)
• Female
• Immunohistochemistry (methods)
• In Vitro Techniques
• Indoles (metabolism)
• Myelin Sheath (drug effects)
• Nerve Tissue Proteins
• Neuregulin-1 (administration & dosage)
• Oligodendroglia (drug effects, metabolism)
• RNA, Messenger
• Rats
• Rats, Sprague-Dawley
• Receptor, ErbB-2 (metabolism)
• Receptor, ErbB-3 (metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• Schwann Cells
• Time Factors