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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
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 calcito...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Wiley Subscription Services, Inc., A Wiley Company
2010
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4491910/ https://www.ncbi.nlm.nih.gov/pubmed/20034058 http://dx.doi.org/10.1002/cne.22240 |
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author | Makwana, Milan Werner, Alexander Acosta-Saltos, Alejandro Gonitel, Roman Pararajasingham, Abirami Ruff, Crystal Rumajogee, Prakasham Cuthill, Dan Galiano, Mathias Bohatschek, Marion Wallace, Adam S Anderson, Patrick N Mayer, Ulrike Behrens, Axel Raivich, Gennadij |
author_facet | Makwana, Milan Werner, Alexander Acosta-Saltos, Alejandro Gonitel, Roman Pararajasingham, Abirami Ruff, Crystal Rumajogee, Prakasham Cuthill, Dan Galiano, Mathias Bohatschek, Marion Wallace, Adam S Anderson, Patrick N Mayer, Ulrike Behrens, Axel Raivich, Gennadij |
author_sort | Makwana, Milan |
collection | PubMed |
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 beta1, 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. © 2009 Wiley-Liss, Inc. |
format | Online Article Text |
id | pubmed-4491910 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | Wiley Subscription Services, Inc., A Wiley Company |
record_format | MEDLINE/PubMed |
spelling | pubmed-44919102015-07-06 Peripheral Facial Nerve Axotomy in Mice Causes Sprouting of Motor Axons Into Perineuronal Central White Matter: Time Course and Molecular Characterization Makwana, Milan Werner, Alexander Acosta-Saltos, Alejandro Gonitel, Roman Pararajasingham, Abirami Ruff, Crystal Rumajogee, Prakasham Cuthill, Dan Galiano, Mathias Bohatschek, Marion Wallace, Adam S Anderson, Patrick N Mayer, Ulrike Behrens, Axel Raivich, Gennadij J Comp Neurol Research Articles 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 beta1, 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. © 2009 Wiley-Liss, Inc. Wiley Subscription Services, Inc., A Wiley Company 2010-03-01 2009-10-13 /pmc/articles/PMC4491910/ /pubmed/20034058 http://dx.doi.org/10.1002/cne.22240 Text en Copyright © 2009 Wiley-Liss, Inc. |
spellingShingle | Research Articles Makwana, Milan Werner, Alexander Acosta-Saltos, Alejandro Gonitel, Roman Pararajasingham, Abirami Ruff, Crystal Rumajogee, Prakasham Cuthill, Dan Galiano, Mathias Bohatschek, Marion Wallace, Adam S Anderson, Patrick N Mayer, Ulrike Behrens, Axel Raivich, Gennadij Peripheral Facial Nerve Axotomy in Mice Causes Sprouting of Motor Axons Into Perineuronal Central White Matter: Time Course and Molecular Characterization |
title | Peripheral Facial Nerve Axotomy in Mice Causes Sprouting of Motor Axons Into Perineuronal Central White Matter: Time Course and Molecular Characterization |
title_full | Peripheral Facial Nerve Axotomy in Mice Causes Sprouting of Motor Axons Into Perineuronal Central White Matter: Time Course and Molecular Characterization |
title_fullStr | Peripheral Facial Nerve Axotomy in Mice Causes Sprouting of Motor Axons Into Perineuronal Central White Matter: Time Course and Molecular Characterization |
title_full_unstemmed | Peripheral Facial Nerve Axotomy in Mice Causes Sprouting of Motor Axons Into Perineuronal Central White Matter: Time Course and Molecular Characterization |
title_short | Peripheral Facial Nerve Axotomy in Mice Causes Sprouting of Motor Axons Into Perineuronal Central White Matter: Time Course and Molecular Characterization |
title_sort | peripheral facial nerve axotomy in mice causes sprouting of motor axons into perineuronal central white matter: time course and molecular characterization |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4491910/ https://www.ncbi.nlm.nih.gov/pubmed/20034058 http://dx.doi.org/10.1002/cne.22240 |
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