ORCID Profile
0000-0001-6739-6394
Current Organisation
National Research University Higher School of Economics
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Publisher: Springer Science and Business Media LLC
Date: 29-07-2022
DOI: 10.1007/S12311-021-01303-1
Abstract: 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.
Publisher: Wiley
Date: 04-2020
Publisher: Frontiers Media SA
Date: 03-04-2019
Publisher: Elsevier BV
Date: 10-2015
Publisher: Springer Science and Business Media LLC
Date: 11-02-2020
DOI: 10.1038/S41598-020-58838-2
Abstract: Chronic glial activation is characterized by increased numbers of activated glial cells, secreting free radicals and cytotoxic cytokines, subsequently causing neuronal damage. In order to investigate the anti-inflammatory activity of Longvida ® Optimised Curcumin (LC), we fed 500 ppm of LC to 2-month-old wild type and GFAP-IL6 mice for 6 months. LC feeding led to a significant reduction in the number of Iba-1 + microglia by 26% in the hippoc us and by 48% in the cerebellum, GFAP + astrocytes by 30%, and TSPO + cells by 24% in the hippoc us and by 31% in the cerebellum of the GFAP-IL6 mice. The morphology of the cells was assessed and LC significantly decreased the dendritic length of microglia and the convex area, convex perimeter, dendritic length, nodes and number of processes of astrocytes in the hippoc us while decreasing the soma area and perimeter in the cerebellum, in LC-fed GFAP-IL6 mice. In addition, LC feeding increased pre- and postsynaptic protein levels and improved balance measured by Rotarod. Together, these data suggest that LC is able to attenuate the inflammatory pathology and ameliorate neurodegeneration and motor deficits in GFAP-IL6 mice. For patients with neuro-inflammatory disorders, LC might potentially reverse the detrimental effects of chronic glial activation.
Publisher: Springer Science and Business Media LLC
Date: 28-09-2014
DOI: 10.1038/NM.3672
Location: No location found
Location: Russian Federation
No related grants have been discovered for Rustam Asgarov.