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The degree of astrocyte activation in multiple system atrophy is inversely proportional to the distance to α-synuclein inclusions
Citation
Radford, R and Rcom-H'cheo-Gauthier, A and Wong, MB and Eaton, ED and Quilty, M and Blizzard, C and Norazit, A and Meedeniya, A and Vickers, JC and Gai, WP and Guillemin, GJ and West, AK and Dickson, TC and Chung, R and Pountney, DL, The degree of astrocyte activation in multiple system atrophy is inversely proportional to the distance to α-synuclein inclusions, Molecular and Cellular Neuroscience, 65 pp. 68-81. ISSN 1044-7431 (2015) [Refereed Article]
Copyright Statement
Copyright 2015 Elsevier
DOI: doi:10.1016/j.mcn.2015.02.015
Abstract
Multiple system atrophy (MSA) exhibits widespread astrogliosis together with α-synuclein (α-syn) glial cytoplasmic inclusions (GCIs) in mature oligodendrocytes. We quantified astrocyte activation by morphometric analysis of MSA cases, and investigated the correlation to GCI proximity. Using Imaris software, we obtained "skinned" three-dimensional models of GFAP-positive astrocytes in MSA and control tissue (n = 75) from confocal z-stacks and measured the astrocyte process length and thickness and radial distance to the GCI. Astrocytes proximal to GCI-containing oligodendrocytes (r < 25μm) had significantly (p, 0.05) longer and thicker processes characteristic of activation than distal astrocytes (r > 25μm), with a reciprocal linear correlation (m, 90μm2) between mean process length and radial distance to the nearest GCI (R2, 0.7). In primary cell culture studies, α-syn addition caused ERK-dependent activation of rat astrocytes and perinuclear α-syn inclusions in mature (MOSP-positive) rat oligodendrocytes. Activated astrocytes were also observed in close proximity to α-syn deposits in a unilateral rotenone-lesion mouse model. Moreover, unilateral injection of MSA tissue-derived α-syn into the mouse medial forebrain bundle resulted in widespread neuroinflammation in the α-syn-injected, but not sham-injected hemisphere. Taken together, our data suggests that the action of localized concentrations of α-syn may underlie both astrocyte and oligodendrocyte MSA pathological features.
Item Details
| Item Type: | Refereed Article |
|---|---|
| Keywords: | alpha-synuclein, multiple system atrophy, neuroinflammation, progressive supranuclear palsy, quantitative morphometry |
| Research Division: | Medical and Health Sciences |
| Research Group: | Neurosciences |
| Research Field: | Neurology and Neuromuscular Diseases |
| Objective Division: | Health |
| Objective Group: | Clinical Health (Organs, Diseases and Abnormal Conditions) |
| Objective Field: | Nervous System and Disorders |
| Author: | Eaton, ED (Dr Emma Eaton) |
| Author: | Quilty, M (Miss Marian Quilty) |
| Author: | Blizzard, C (Dr Catherine Blizzard) |
| Author: | Vickers, JC (Professor James Vickers) |
| Author: | West, AK (Professor Adrian West) |
| Author: | Dickson, TC (Professor Tracey Dickson) |
| ID Code: | 99270 |
| Year Published: | 2015 |
| Web of Science® Times Cited: | 15 |
| Deposited By: | Menzies Institute for Medical Research |
| Deposited On: | 2015-03-18 |
| Last Modified: | 2017-11-06 |
| Downloads: | 0 |
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