Axonally transported peripheral signals regulate alpha-internexin expression in regenerating motoneurons.
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| Abstract |
The class IV neuronal intermediate filament (IF) family proteins includes the neurofilament (NF) triplet proteins NF-L, NF-M, and NF-H and also the more recently characterized alpha-internexin-NF66. It is well established that NF-L, -M, and -H protein and mRNA are downregulated after peripheral nerve injury. We examined alpha-internexin protein expression after three facial nerve lesion paradigms: crush, transection, and resection. Alpha-internexin immunoreactivity was absent in the perikarya of uninjured facial motoneurons but increased dramatically in all three injury paradigms, with maximum immunoreactivity observed at 7 d after injury. Twenty-eight days after nerve crush or transection, there was a dramatic decrease in the number of alpha-internexin-positive cells. In contrast, alpha-internexin remained elevated 28 d after nerve resection, an injury that hinders regeneration and target reinnervation. In situ hybridization studies showed an increase in alpha-internexin mRNA expression in the facial nucleus at 7 and 14 d after injury. Retrograde transport of fluorogold from the whisker pads to the facial nucleus was seen only in motoneurons that lacked alpha-internexin immunoreactivity, supporting the idea that target reinnervation and inhibitory signals from the periphery regulate the expression of alpha-internexin. Blockage of axonal transport through local colchicine application induced strong immunoreactivity in motoneurons. Alpha-internexin expression was also examined after central axotomy of rubrospinal neurons, which constitutively show alpha-internexin immunoreactivity. After rubrospinal tractotomy, alpha-internexin immunoreactivity transiently increased by 7 d after injury but returned to control levels by 14 d. We conclude that alpha-internexin upregulation in injured motoneurons suggests a role for this IF protein in neuronal regeneration.
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| Authors | Tanya S McGraw, J Parker Mickle, Gerry Shaw, Wolfgang J Streit |
| Journal | The Journal of neuroscience : the official journal of the Society for Neuroscience (J Neurosci) Vol. 22 Issue 12 Pg. 4955-63 (Jun 15 2002) ISSN: 1529-2401 [Electronic] United States |
| PMID | 12077192 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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