The Nogo-Nogo Receptor Pathway Limits a Spectrum of Adult CNS Axonal Growth

The hypothesis that Nogo-A (Reticulon 4A) and Nogo-66 receptor (NgR1) limit adult CNS axonal growth after injury is supported by both in vitro experiments and in vivo pharmacological studies. However, genetic assessment of the role of Nogo-A in corticospinal tract (CST) axons after spinal cord dorsa...

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Bibliographic Details
Published in:The Journal of neuroscience 2006-11, Vol.26 (47), p.12242-12250
Main Authors: Cafferty, William B. J, Strittmatter, Stephen M
Format: Article
Language:English
Subjects:
Analysis of Variance
Animals
Axons - physiology
Behavior, Animal
Calcitonin Gene-Related Peptide - metabolism
Central Nervous System - cytology
Functional Laterality
Glial Fibrillary Acidic Protein - metabolism
Mice
Mice, Inbred C57BL
Mice, Knockout
Myelin Basic Protein - metabolism
Myelin Proteins - metabolism
Nogo Proteins
Protein Kinase C - metabolism
Psychomotor Performance - physiology
Pyramidal Tracts - injuries
Pyramidal Tracts - metabolism
Pyramidal Tracts - physiology
Receptors, Peptide - deficiency
Receptors, Peptide - metabolism
Signal Transduction - physiology
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Summary:The hypothesis that Nogo-A (Reticulon 4A) and Nogo-66 receptor (NgR1) limit adult CNS axonal growth after injury is supported by both in vitro experiments and in vivo pharmacological studies. However, genetic assessment of the role of Nogo-A in corticospinal tract (CST) axons after spinal cord dorsal hemisection has yielded conflicting results. CST regeneration is detected in homozygous nogo-ab(trap/trap) mice, but not in nogo-ab(atg/atg) mice. CST regeneration is also present after pharmacological NgR blockade, but not in ngr1(-/-) mice. To assess the nogo-ab(atg) and ngr1-null alleles for other axon growth phenotypes, we created unilateral pyramidotomies and monitored the uninjured CST. There is robust pyramidotomy-induced growth of nogo-ab(atg/atg) and ngr1(-/-) CST axons into denervated cervical gray matter. This fiber growth correlates with recovery of fine motor skill in the affected forelimb. Thus nogo-ab and ngr1 play a modulated role in limiting CNS axonal growth across a spectrum of different tracts in various lesion models.
ISSN:0270-6474
1529-2401
DOI:10.1523/JNEUROSCI.3827-06.2006