A compensatory subpopulation of motor neurons in a mouse model of amyotrophic lateral sclerosis
Amyotrophic lateral sclerosis is a fatal paralytic disease that targets motor neurons, leading to motor neuron death and widespread denervation atrophy of muscle. Previous electrophysiological data have shown that some motor axon branches attempt to compensate for loss of innervation, resulting in e...
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Published in | Journal of comparative neurology (1911) Vol. 490; no. 3; pp. 209 - 219 |
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Main Authors | , , |
Format | Journal Article |
Language | English |
Published |
Hoboken
Wiley Subscription Services, Inc., A Wiley Company
26.09.2005
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Subjects | |
Online Access | Get full text |
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Summary: | Amyotrophic lateral sclerosis is a fatal paralytic disease that targets motor neurons, leading to motor neuron death and widespread denervation atrophy of muscle. Previous electrophysiological data have shown that some motor axon branches attempt to compensate for loss of innervation, resulting in enlarged axonal arbors. Recent histological assays have shown that during the course of the disease some axonal branches die back. We thus asked whether the two types of behavior, die‐back and compensatory growth, occur in different branches of single neurons or, alternatively, whether entire motor units are of one type or the other. We used high‐resolution in vivo imaging in the G93A SOD1 mouse model, bred to express transgenic yellow fluorescent protein in all or subsets of motor neurons. Time‐lapse imaging showed that degenerative axon branches are easily distinguished from those undergoing compensatory reinnervation, showing fragmentation of terminal branches but sparing of the more proximal axon. Reconstruction of entire motor units showed that some were abnormally large. Surprisingly, these large motor units contained few if any degenerating synapses. Some small motor units, however, no longer possessed any neuromuscular contacts at all, giving the appearance of “winter trees.” Thus, degenerative versus regenerative changes are largely confined to distinct populations of neurons within the same motor pool. Identification of factors that protect “compensatory” motor neurons from degenerative changes may provide new targets for therapeutic intervention. J. Comp. Neurol. 490:209–219, 2005. © 2005 Wiley‐Liss, Inc. |
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Bibliography: | ArticleID:CNE20620 National Institutes of Health - No. NS020364; No. NS034448 ark:/67375/WNG-GQHXC0M8-9 Helen Hay Whitney Postdoctoral Fellowship istex:0F39477B535060539D76F384803A573CDEC5AE15 Project A.L.S. ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0021-9967 1096-9861 |
DOI: | 10.1002/cne.20620 |