Axonally transported peripheral signals regulate alpha-internexin expression in regenerating motoneurons.
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.
McGraw
Tanya S
TS
Department of Neuroscience, University of Florida College of Medicine and McKnight Brain Institute, Gainesville, Florida 32611, USA.
Mickle
J Parker
JP
Shaw
Gerry
G
Streit
Wolfgang J
WJ
D000818:Animals; D001370:Axonal Transport; D001522:Behavior, Animal; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D002818:Cordotomy; D005154:Facial Nerve / Q000601:surgery; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007381:Intermediate Filament Proteins / Q000096:biosynthesis* / Q000235:genetics; D008297:Male; D009046:Motor Neurons / Q000378:metabolism* / Q000502:physiology*; D009409:Nerve Crush; D009416:Nerve Regeneration; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D015533:Transcriptional Activation
D002352:Carrier Proteins; D007381:Intermediate Filament Proteins; D012333:RNA, Messenger; C046643:alpha-internexin