Characterisation of the Mouse Cerebellar Proteome in the GFAP-IL6 Model of Chronic Neuroinflammation.

Autor: Asgarov R; Pharmacology Unit, School of Medicine, Western Sydney University, Penrith, NSW, Australia., Sen MK; Proteomics and Lipidomics Lab, School of Medicine, Western Sydney University, Penrith, NSW, Australia., Mikhael M; Mass Spectrometry Facility, School of Medicine, Western Sydney University, Penrith, NSW, Australia., Karl T; Behavioural Neuroscience Lab, School of Medicine, Western Sydney University, Penrith, NSW, Australia.; Neuroscience Research Australia (NeuRA), Randwick, NSW, 2031, Australia.; School of Medical Sciences, University of New South Wales, Kensington, NSW, Australia., Gyengesi E; Pharmacology Unit, School of Medicine, Western Sydney University, Penrith, NSW, Australia., Mahns DA; Integrative Physiology Lab, School of Medicine, Western Sydney University, Penrith, NSW, Australia., Malladi CS; Proteomics and Lipidomics Lab, School of Medicine, Western Sydney University, Penrith, NSW, Australia., Münch GW; School of Medicine, Western Sydney University, Locked Bag 1797, Penrith, NSW, 2751, Australia. G.Muench@westernsydney.edu.au.
Jazyk: angličtina
Zdroj: Cerebellum (London, England) [Cerebellum] 2022 Jun; Vol. 21 (3), pp. 404-424. Date of Electronic Publication: 2021 Jul 29.
DOI: 10.1007/s12311-021-01303-1
Abstrakt: GFAP-IL6 transgenic mice are characterised by astroglial and microglial activation predominantly in the cerebellum, hallmarks of many neuroinflammatory conditions. However, information available regarding the proteome profile associated with IL-6 overexpression in the mouse brain is limited. This study investigated the cerebellum proteome using a top-down proteomics approach using 2-dimensional gel electrophoresis followed by liquid chromatography-coupled tandem mass spectrometry and correlated these data with motor deficits using the elevated beam walking and accelerod tests. In a detailed proteomic analysis, a total of 67 differentially expressed proteoforms including 47 cytosolic and 20 membrane-bound proteoforms were identified. Bioinformatics and literature mining analyses revealed that these proteins were associated with three distinct classes: metabolic and neurodegenerative processes as well as protein aggregation. The GFAP-IL6 mice exhibited impaired motor skills in the elevated beam walking test measured by their average scores of 'number of footslips' and 'time to traverse' values. Correlation of the proteoforms' expression levels with the motor test scores showed a significant positive correlation to peroxiredoxin-6 and negative correlation to alpha-internexin and mitochondrial cristae subunit Mic19. These findings suggest that the observed changes in the proteoform levels caused by IL-6 overexpression might contribute to the motor function deficits.
(© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Databáze: MEDLINE
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