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The Journal of Neuroscience, June 15, 2002, 22(12):4955-4963

Axonally Transported Peripheral Signals Regulate -Internexin Expression in Regenerating Motoneurons

Tanya S. McGraw¹, J. Parker Mickle², Gerry Shaw¹, and Wolfgang J. Streit¹

Departments of ¹ Neuroscience and ² Neurological Surgery, University of Florida College of Medicine and McKnight Brain Institute, Gainesville, Florida 32611

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 -internexin-NF66. It is well established that NF-L, -M, and -H protein and mRNA are downregulated after peripheral nerve injury. We examined -internexin protein expression after three facial nerve lesion paradigms: crush, transection, and resection. -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 -internexin-positive cells. In contrast, -internexin remained elevated 28 d after nerve resection, an injury that hinders regeneration and target reinnervation. In situ hybridization studies showed an increase in -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 -internexin immunoreactivity, supporting the idea that target reinnervation and inhibitory signals from the periphery regulate the expression of -internexin. Blockage of axonal transport through local colchicine application induced strong immunoreactivity in motoneurons. -Internexin expression was also examined after central axotomy of rubrospinal neurons, which constitutively show -internexin immunoreactivity. After rubrospinal tractotomy, -internexin immunoreactivity transiently increased by 7 d after injury but returned to control levels by 14 d. We conclude that -internexin upregulation in injured motoneurons suggests a role for this IF protein in neuronal regeneration.

Key words: axotomy; regeneration; axonal transport; neurofilament proteins; motoneurons; -internexin

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Copyright © 2002 Society for Neuroscience  0270-6474/02/22124955-09$05.00/0

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