title: Temporal profiles of cytoskeletal protein loss following traumatic axonal injury in mice.
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 alpha-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.
authors.affiliation: Department of Neurosurgery, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Gulyeter
authors.initials: G
authors.lastname: Serbest
authors.forename: Matthew F
authors.initials: MF
authors.lastname: Burkhardt
authors.forename: Robert
authors.initials: R
authors.lastname: Siman
authors.forename: Ramesh
authors.initials: R
authors.lastname: Raghupathi
authors.forename: Kathryn E
authors.initials: KE
authors.lastname: Saatman
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism* / Q000473:pathology*; D015153:Blotting, Western; D002154:Calpain / Q000502:physiology; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016900:Neurofilament Proteins / Q000378:metabolism; D020221:Optic Nerve Injuries / Q000378:metabolism* / Q000473:pathology*; D013997:Time Factors; D014404:Tubulin / Q000378:metabolism
chemical_list: D003598:Cytoskeletal Proteins; D016900:Neurofilament Proteins; D014404:Tubulin; C066858:neurofilament protein NF 68; D002154:Calpain