Influence of the axotomy to cell body distance in rat rubrospinal and spinal motoneurons: Differential regulation of GAP-43, tubulins, and neurofilament-M

Axotomized motoneurons regenerate their axons regardless of whether axotomy occurs proximally or distally from their cell bodies. In contrast, regeneration of rubrospinal axons into peripheral nerve grafts has been detected after cervical but not after thoracic injury of the rubrospinal tract. By us...

Full description

Saved in:

Bibliographic Details
Published in:	Journal of comparative neurology (1911) Vol. 414; no. 4; pp. 495 - 510
Main Authors:	Fernandes, Karl J.L., Fan, Da-Peng, Tsui, B.J., Cassar, S.L., Tetzlaff, Wolfram
Format:	Journal Article
Language:	English
Published:	New York John Wiley & Sons, Inc 29-11-1999
Subjects:	Animals Anterior Horn Cells - metabolism Anterior Horn Cells - physiopathology axonal regeneration Axotomy cytoskeletal proteins Efferent Pathways - metabolism Efferent Pathways - physiopathology GAP-43 Protein - metabolism Gene Expression Regulation In Situ Hybridization Male Motor Neurons - metabolism Motor Neurons - physiology Nerve Regeneration - physiology Neurofilament Proteins - metabolism Rats Rats, Sprague-Dawley red nucleus Red Nucleus - metabolism Retrograde Degeneration - metabolism Retrograde Degeneration - physiopathology retrograde tracing RNA, Messenger - analysis sciatic nerve Spinal Cord - physiopathology Spinal Cord - surgery spinal cord injury Tubulin - metabolism
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	Axotomized motoneurons regenerate their axons regardless of whether axotomy occurs proximally or distally from their cell bodies. In contrast, regeneration of rubrospinal axons into peripheral nerve grafts has been detected after cervical but not after thoracic injury of the rubrospinal tract. By using in situ hybridization (ISH) combined with reliable retrograde tracing methods, we compared regeneration‐associated gene expression after proximal and distal axotomy in spinal motoneurons versus rubrospinal neurons. Regardless of whether they were axotomized at the iliac crest (proximal) or popliteal fossa (distal), sciatic motoneurons underwent highly pronounced changes in ISH signals for Growth Associated Protein 43 (GAP‐43) (10–20× increase) and neurofilament M (60–85% decrease). In contrast, tubulin ISH signals substantially increased only after proximal axotomy (3–5× increase). To compare these changes in gene expression with those of axotomized rubrospinal neurons, the rubrospinal tract was transected at the cervical (proximal) or thoracic (distal) levels of the spinal cord. Cervically axotomized rubrospinal neurons showed three‐ to fivefold increases in ISH signals for GAP‐43 and tubulins (only transient) and a 75% decrease for neurofilament‐M. In sharp contrast, thoracic axotomy had only marginal effects. After implantation of peripheral nerve transplants into the spinal cord injury sites, retrograde labeling with the sensitive retrograde tracer Fluoro‐Gold identified regenerating rubrospinal neurons only after cervical axotomy. Furthermore, rubrospinal neurons specifically regenerating into the transplants were hypertrophied and expressed high levels of GAP‐43 and tubulins. Taken together, these data support the concept that, even if central nervous system (CNS) axons are presented with a permissive/supportive environment, appropriate cell body responses to injury are a prerequisite for CNS axonal regeneration. J. Comp. Neurol. 414:495–510, 1999. © 1999 Wiley‐Liss, Inc.
Bibliography:	Rick Hansen Man in Motion Foundation istex:3C233D216B79440649166BBB791D3CAA49127FC5 ArticleID:CNE6 Medical Research Council of Canada - No. MT10689 Natural Sciences and Engineering Research Council ark:/67375/WNG-TF5CGF6N-D Canadian NeuroScience Network ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0021-9967 1096-9861
DOI:	10.1002/(SICI)1096-9861(19991129)414:4<495::AID-CNE6>3.0.CO;2-S