title: Early and sustained activation of autophagy in degenerating axons after spinal cord injury.
abstract: Axonal degeneration is one of the initial steps in many neurological disorders and has been associated with increased autophagic activity. Although there are increasing data on the regulation of autophagy proteins in the neuronal soma after spinal cord injury (SCI), their characterization in the axon is scarce. Here, we examined the regulation of autophagy during axonal degeneration in a rat model of SCI following a lesion at Th 8. We analyzed the morphological and ultrastructural changes in injured axons by immunohistochemical evaluation of autophagy-related proteins and electron microscopy at different time points following SCI. The expression of ULK1, Atg7 and Atg5 in damaged axons was rapidly upregulated within hours after SCI. The number of axonal LC3-positive autophagosomes was also rapidly increased after SCI and remained at an increased level for up to 6 weeks. Ultrastructural analysis showed early signs of axonal degeneration and increased autophagy. In conclusion, we show that autophagy is increased early and for a sustained period in degenerating axons after SCI and that it might be an important executive step involved in axonal degeneration. Therefore, autophagy may represent a promising target for future therapeutic interventions in the treatment of axonal degeneration in traumatic central nervous system disorders.
authors.affiliation: Department of Neurology, University Medicine Göttingen, Göttingen, Germany.
authors.forename: Vinicius Toledo
authors.initials: VT
authors.lastname: Ribas
authors.forename: Bianca
authors.initials: B
authors.lastname: Schnepf
authors.forename: Malleswari
authors.initials: M
authors.lastname: Challagundla
authors.forename: Jan Christoph
authors.initials: JC
authors.lastname: Koch
authors.forename: Mathias
authors.initials: M
authors.lastname: Bähr
authors.forename: Paul
authors.initials: P
authors.lastname: Lingor
mesh_terms: D000818:Animals; D001343:Autophagy; D000071187:Autophagy-Related Protein 5; D000071193:Autophagy-Related Protein 7; D000071189:Autophagy-Related Protein-1 Homolog; D001369:Axons / Q000378:metabolism* / Q000648:ultrastructure; D005260:Female; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009410:Nerve Degeneration / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013119:Spinal Cord Injuries / Q000378:metabolism* / Q000473:pathology; D044764:Ubiquitin-Activating Enzymes / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D000071187:Autophagy-Related Protein 5; D000071193:Autophagy-Related Protein 7; D000071189:Autophagy-Related Protein-1 Homolog; D047908:Intracellular Signaling Peptides and Proteins; D008869:Microtubule-Associated Proteins; D011506:Proteins; D044764:Ubiquitin-Activating Enzymes; C545865:Atg5 protein, rat; C561242:Atg7 protein, rat; C526109:Anxa3 protein, rat; C586255:ULK1 protein, rat
keywords: Atg5; Atg7; LC3; ULK1; autophagosome; axonal lesion