Unraveling axonal mechanisms of traumatic brain injury.

Autor: Pozo Devoto VM; Translational Neuroscience and Ageing Program, Centre for Translational Medicine, International Clinical Research Centre, St. Anne's University Hospital, Brno, Czech Republic., Lacovich V; Translational Neuroscience and Ageing Program, Centre for Translational Medicine, International Clinical Research Centre, St. Anne's University Hospital, Brno, Czech Republic., Feole M; Translational Neuroscience and Ageing Program, Centre for Translational Medicine, International Clinical Research Centre, St. Anne's University Hospital, Brno, Czech Republic., Bhat P; Translational Neuroscience and Ageing Program, Centre for Translational Medicine, International Clinical Research Centre, St. Anne's University Hospital, Brno, Czech Republic., Chovan J; Biostatistics Department, International Clinical Research Centre, St. Anne's University Hospital, Brno, Czech Republic., Čarna M; Translational Neuroscience and Ageing Program, Centre for Translational Medicine, International Clinical Research Centre, St. Anne's University Hospital, Brno, Czech Republic., Onyango IG; Translational Neuroscience and Ageing Program, Centre for Translational Medicine, International Clinical Research Centre, St. Anne's University Hospital, Brno, Czech Republic., Dragišić N; Translational Neuroscience and Ageing Program, Centre for Translational Medicine, International Clinical Research Centre, St. Anne's University Hospital, Brno, Czech Republic., Sűsserová M; Translational Neuroscience and Ageing Program, Centre for Translational Medicine, International Clinical Research Centre, St. Anne's University Hospital, Brno, Czech Republic., Barrios-Llerena ME; Proteomics and Mass Spectrometry Core Lab, International Clinical Research Centre, St. Anne's University Hospital, Brno, Czech Republic., Stokin GB; Translational Neuroscience and Ageing Program, Centre for Translational Medicine, International Clinical Research Centre, St. Anne's University Hospital, Brno, Czech Republic. gbstokin@alumni.ucsd.edu.; Division of Neurology, University Medical Centre, Ljubljana, Slovenia. gbstokin@alumni.ucsd.edu.; Department of Neurosciences, Mayo Clinic, Rochester, MN, USA. gbstokin@alumni.ucsd.edu.
Jazyk: angličtina
Zdroj: Acta neuropathologica communications [Acta Neuropathol Commun] 2022 Sep 21; Vol. 10 (1), pp. 140. Date of Electronic Publication: 2022 Sep 21.
DOI: 10.1186/s40478-022-01414-8
Abstrakt: Axonal swellings (AS) are one of the neuropathological hallmark of axonal injury in several disorders from trauma to neurodegeneration. Current evidence proposes a role of perturbed Ca 2+ homeostasis in AS formation, involving impaired axonal transport and focal distension of the axons. Mechanisms of AS formation, in particular moments following injury, however, remain unknown. Here we show that AS form independently from intra-axonal Ca 2+ changes, which are required primarily for the persistence of AS in time. We further show that the majority of axonal proteins undergoing de/phosphorylation immediately following injury belong to the cytoskeleton. This correlates with an increase in the distance of the actin/spectrin periodic rings and with microtubule tracks remodeling within AS. Observed cytoskeletal rearrangements support axonal transport without major interruptions. Our results demonstrate that the earliest axonal response to injury consists in physiological adaptations of axonal structure to preserve function rather than in immediate pathological events signaling axonal destruction.
(© 2022. The Author(s).)
Databáze: MEDLINE
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