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  Peripheral facial nerve axotomy in mice causes sprouting of motor axons into perineuronal central white matter: Time course and molecular characterization

Makwana, M., Werner, A., Acosta-Saltos, A., Gonitel, R., Pararajasingham, A., Ruff, C., et al. (2010). Peripheral facial nerve axotomy in mice causes sprouting of motor axons into perineuronal central white matter: Time course and molecular characterization. The Journal of Comparative Neurology, 518(5), 699-721. doi:10.1002/cne.22240.

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Makwana, M., Author
Werner, A.1, Author           
Acosta-Saltos, A., Author
Gonitel, R., Author
Pararajasingham, A., Author
Ruff, C., Author
Rumajogee, P., Author
Cuthill, D., Author
Galiano, M.1, Author           
Bohatschek, M.2, Author           
Wallace, A. S., Author
Anderson, P. N., Author
Mayer, U., Author
Behrens, A., Author
Raivich, G.1, Author           
Affiliations:
1Emeritus Group: Neuromorphology / Kreutzberg, MPI of Neurobiology, Max Planck Society, ou_1113551              
2University College London, United Kingdom, ou_persistent22              

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Free keywords: growth cones; regeneration; central sprouting; adhesion molecules; transcription factors; inflammation
 Abstract: Generation of new axonal sprouts plays an important role in neural repair In the current study, we examined the appearance, composition and effects of gene deletions on intrabrainstem sprouts following peripheral facial nerve axotomy Axotomy was followed by the appearance of galanin(+) and calcitonin gene-related peptide (CGRP)(+) sprouts peaking at day 14, matching both large, neuropeptide(+) subpopulations of axotomized facial motoneurons, but with CGRP(+) sprouts considerably rarer. Strong immunoreactivity for vesicular acetylcholine transporter (VAChT) and retrogradely transported MiniRuby following its application on freshly cut proximal facial nerve stump confirmed their axotomized motoneuron origin; the sprouts expressed CD44 and alpha7beta1 integrin adhesion molecules and grew apparently unhindered along neighboring central white matter tracts. Quantification of the galanin(+) sprouts revealed a stronger response following cut compared with crush (day 7-14) as well as enhanced sprouting after recut (day 8 + 6 vs 14; 14 + 8 vs. 22), arguing against delayed appearance of sprouting being the result of the initial phase of reinnervation. Sprouting was strongly diminished in brain Jun-deficient mice but enhanced in alpha7 null animals that showed apparently compensatory up-regulation in beta 1, suggesting important regulatory roles for transcription factors and the sprout-associated adhesion molecules. Analysis of inflammatory stimuli revealed a 50% reduction 12-48 hours following systemic endotoxin associated with neural inflammation and a tendency toward more sprouts in TNFR1/2 null mutants (P = 10%) with a reduced inflammatory response, indicating detrimental effects of excessive inflammation. Moreover, the study points to the usefulness of the facial axotomy model in exploring physiological and molecular stimuli regulating central sprouting. J. Comp. Neurol. 518:699-721, 2010. (C) 2009 Wiley-Liss, Inc

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Language(s): eng - English
 Dates: 2010-03-01
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: eDoc: 474418
ISI: 000273620800008
DOI: 10.1002/cne.22240
 Degree: -

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Title: The Journal of Comparative Neurology
Source Genre: Journal
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Publ. Info: Hoboken, N.J. : John Wiley & Sons
Pages: - Volume / Issue: 518 (5) Sequence Number: - Start / End Page: 699 - 721 Identifier: ISSN: 1550-7130
CoNE: https://pure.mpg.de/cone/journals/resource/111088197763336