Proteolysis of submembrane cytoskeletal proteins ankyrin-G and αII-spectrin following diffuse brain injury: a role in white matter vulnerability at Nodes of Ranvier.
A high membrane-to-cytoplasm ratio makes axons particularly vulnerable to traumatic injury. Posttraumatic shifts in ionic homeostasis promote spectrin cleavage, disrupt ankyrin linkages and destabilize axolemmal proteins. This study contrasted ankyrin-G and αII-spectrin degradation in cortex and corpus callosum following diffuse axonal injury produced by fluid percussion insult. Ankyrin-G lysis occurred preferentially in white matter, with acute elevation of all fragments and long-term reduction of a low kD form. Calpain-generated αII-spectrin fragments increased in both regions. Caspase-3 lysis of αII-spectrin showed a small, acute rise in cortex but was absent in callosum. White matter displayed nodal damage, with horseradish peroxidase permeability into the submyelin space. Ankyrin-G-binding protein neurofascin and spectrin-binding protein ankyrin-B showed acute alterations in expression. These results support ankyrin-G vulnerability in white matter following trauma and suggest that ankyrin-G and αII-spectrin proteolysis disrupts Node of Ranvier integrity. The time course of such changes were comparable to previously observed functional deficits in callosal fibers.
Reeves
Thomas M
TM
Department of Anatomy and Neurobiology, School of Medicine, Virginia Commonwealth University Medical Center, Richmond, VA, USA. tmreeves@vcu.edu
Greer
John E
JE
Vanderveer
Andrew S
AS
Phillips
Linda L
LL
D000704:Analysis of Variance; D000818:Animals; D017487:Ankyrins / Q000378:metabolism*; D001812:Blood-Brain Barrier; D001930:Brain Injuries / Q000378:metabolism / Q000473:pathology*; D002540:Cerebral Cortex / Q000378:metabolism; D003337:Corpus Callosum / Q000378:metabolism; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000502:physiology*; D006735:Horseradish Peroxidase / Q000378:metabolism; D008297:Male; D008840:Microfilament Proteins / Q000378:metabolism*; D009413:Nerve Fibers, Myelinated / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D011901:Ranvier's Nodes / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D033921:Vesicular Transport Proteins / Q000378:metabolism*
D017487:Ankyrins; D008840:Microfilament Proteins; C422208:Sptan1 protein, rat; D033921:Vesicular Transport Proteins; D006735:Horseradish Peroxidase