Temporal profiles of cytoskeletal protein loss following traumatic axonal injury in mice

Gulyeter Serbest, Matthew F. Burkhardt, Robert Siman, Ramesh Raghupathi, Kathryn E. Saatman

Research output: Contribution to journalArticlepeer-review

69 Scopus citations

Abstract

To examine the time course and relative extent of proteolysis of neurofilament and tubulin proteins after traumatic axonal injury (TAI), anesthetized mice were subjected to optic nerve stretch injury. Immunohistochemistry confirmed neurofilament accumulation within axonal swellings at 4, 24, and 72 h postinjury (n = 4 injured and 2 sham per time point). Immunoblotting of optic nerve homogenates (n = 5 injured and 1 sham at 0.5, 4, 24 or 72 h) revealed calpain-mediated spectrin proteolytic fragments after injury. Protein levels for NF68 progressively decreased from 0.5 h to 24 h postinjury, while NF200 and α-tubulin levels decreased acutely (0.5-4 h), with a secondary decline at 72 h postinjury. These data demonstrate that diffusely distributed TAI is associated not only with a localized accumulation of neurofilament proteins, but also significant decreases in total cytoskeletal protein levels which may be mediated, in part, by calpains. Protection of the axonal cytoskeleton represents a potential therapeutic target for axonal damage associated with injury or neurodegenerative diseases.

Original languageEnglish
Pages (from-to)2006-2014
Number of pages9
JournalNeurochemical Research
Volume32
Issue number12
DOIs
StatePublished - Dec 2007

Bibliographical note

Funding Information:
Acknowledgments This study was supported, in part, by NIH P50-NS08803, R01-NS45131, R01-NS41561 and T32-NS043126. We would like to thank Dr. Juan Wang for assistance with immunoblotting and Heather N. Foozer for assistance with manuscript preparation.

Keywords

  • Calpain
  • Cytoskeleton
  • Neurofilament
  • Optic nerve
  • Spectrin
  • Tubulin
  • White matter

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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