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Neutralization of the membrane protein Nogo-A enhances growth and reactive sprouting in established organotypic hippocampal slice cultures


Craveiro, L M; Hakkoum, D; Weinmann, O; Montani, L; Stoppini, L; Schwab, M E (2008). Neutralization of the membrane protein Nogo-A enhances growth and reactive sprouting in established organotypic hippocampal slice cultures. European Journal of Neuroscience, 28(9):1808-1824.

Abstract

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.

Abstract

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.

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25 citations in Web of Science®
26 citations in Scopus®
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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Brain Research Institute
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:2008
Deposited On:15 Dec 2008 11:05
Last Modified:05 Apr 2016 12:40
Publisher:Wiley-Blackwell
ISSN:0953-816X
Publisher DOI:https://doi.org/10.1111/j.1460-9568.2008.06473.x
PubMed ID:18973596

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