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          Institute: MPI für Neurobiologie     Collection: Emeriti     Display Documents

ID: 474418.0, MPI für Neurobiologie / Emeriti
Peripheral Facial Nerve Axotomy in Mice Causes Sprouting of Motor Axons Into Perineuronal Central White Matter: Time Course and Molecular Characterization
Authors:Makwana, M.; Werner, A.; Acosta-Saltos, A.; Gonitel, R.; Pararajasingham, A.; Ruff, C.; Rumajogee, P.; Cuthill, D.; Galiano, M.; Bohatschek, M.; Wallace, A. S.; Anderson, P. N.; Mayer, U.; Behrens, A.; Raivich, G.
Date of Publication (YYYY-MM-DD):2010-03-01
Title of Journal:Journal of Comparative Neurology
Journal Abbrev.:J. Comp. Neurol.
Issue / Number:5
Start Page:699
End Page:721
Review Status:Peer-review
Audience:Not Specified
Abstract / Description: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
Free Keywords:growth cones; regeneration; central sprouting; adhesion molecules; transcription factors; inflammation
External Publication Status:published
Document Type:Article
Version Comment:Automatic journal name synchronization
Affiliations:MPI für Neurobiologie/Emeriti /Neuromorphology (Kreutzberg)
External Affiliations:[Makwana, Milan; Acosta-Saltos, Alejandro; Gonitel, Roman; Pararajasingham, Abirami; Ruff, Crystal; Rumajogee, Prakasham; Cuthill, Dan; Galiano, Mathias; Bohatschek, Marion; Wallace, Adam S.; Raivich, Gennadij] UCL, Perinatal Brain Repair Grp, Dept Obstet & Gynaecol, EGA Inst Womens Hlth, London WC1E 6HX, England.; [Werner, Alexander] Aurigon Co, D-82327 Tutzing, Germany.; [Gonitel, Roman] UCL, Inst Child Hlth, Mol Immunol Unit, London WC1E 6HX, England.; [Anderson, Patrick N.; Raivich, Gennadij] UCL, Dept Anat & Dev Biol, London WC1E 6HX, England.; [Mayer, Ulrike] Univ E Anglia, Biomed Res Ctr, Norwich NR4 7, Norfolk, England.; [Behrens, Axel] London Res Inst, Canc Res UK, London WC2A 3PX, England.
Identifiers:ISI:000273620800008 [ID No:1]
ISSN:0021-9967 [ID No:2]
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