title: Acute axonal degeneration in vivo is attenuated by inhibition of autophagy in a calcium-dependent manner.
abstract: Axonal degeneration is a pathological hallmark of many traumatic and neurodegenerative neurological disorders. Although the underlying mechanisms remain largely unclear, increased autophagy and the influx of extracellular calcium have been implicated in the pathogenesis of axonal degeneration based on in vitro data. Using in vivo imaging of the rat optic nerve after crush lesion we could now show that both mechanisms are linked and play an important role in acute axonal degeneration in vivo. Our data suggest that crush lesion of the optic nerve induces a rapid calcium influx through calcium channels, which results in a secondary induction of autophagy that participates actively in axonal degradation. Therapeutic manipulation of both events could significantly alter the time course of acute axonal degeneration in vivo and may thus represent promising therapeutic targets for the future.
authors.affiliation: Department of Neurology, University Medicine Göttingen, Georg-August-University, Göttingen, Germany.
authors.forename: Jan C
authors.initials: JC
authors.lastname: Koch
authors.forename: Johanna
authors.initials: J
authors.lastname: Knöferle
authors.forename: Lars
authors.initials: L
authors.lastname: Tönges
authors.forename: Thomas
authors.initials: T
authors.lastname: Ostendorf
authors.forename: Mathias
authors.initials: M
authors.lastname: Bähr
authors.forename: Paul
authors.initials: P
authors.lastname: Lingor
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001343:Autophagy / Q000187:drug effects; D001369:Axons / Q000187:drug effects / Q000473:pathology* / Q000648:ultrastructure; D002118:Calcium / Q000378:metabolism*; D006801:Humans; D061986:MCF-7 Cells; D009409:Nerve Crush; D009410:Nerve Degeneration / Q000473:pathology*; D009900:Optic Nerve / Q000473:pathology / Q000648:ultrastructure; D051381:Rats
chemical_list: C025946:3-methyladenine; D000225:Adenine; D002118:Calcium