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Ablation of reactive astrocytes exacerbates disease pathology in a model of Alzheimer’s disease
File | Description | Size | Format | |
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glia.23759.pdf | Published version | 6.84 MB | Adobe PDF | View/Open |
Title: | Ablation of reactive astrocytes exacerbates disease pathology in a model of Alzheimer’s disease |
Authors: | Katsouri, L Birch, A Renziehausen, A Zach, C Aman, Y Steeds, H Bonsu, A Palmer, E Mirzaei, N Ries, M Sastre, M |
Item Type: | Journal Article |
Abstract: | The role of astrocytes in the progression of Alzheimer’s disease (AD) remains poorly understood. We assessed the consequences of ablating astrocytic proliferation in 9 months old double transgenic APP23/GFAP-TK mice. Treatment of these mice with the antiviral agent ganciclovir conditionally ablates proliferating reactive astrocytes. The loss of proliferating astrocytes resulted in significantly increased levels of monomeric amyloid-β (Aβ) in brain homogenates, associated with reduced enzymatic degradation and clearance mechanisms. In addition, our data revealed exacerbated memory deficits in mice lacking proliferating astrocytes concomitant with decreased levels of synaptic markers and higher expression of pro-inflammatory cytokines. Our data suggest that loss of reactive astrocytes in AD aggravates amyloid pathology and memory loss, possibly via disruption of amyloid clearance and enhanced neuroinflammation. |
Issue Date: | May-2020 |
Date of Acceptance: | 21-Nov-2019 |
URI: | http://hdl.handle.net/10044/1/75381 |
DOI: | 10.1002/glia.23759 |
ISSN: | 0894-1491 |
Publisher: | Wiley |
Start Page: | 1017 |
End Page: | 1030 |
Journal / Book Title: | Glia |
Volume: | 68 |
Issue: | 5 |
Copyright Statement: | © 2019 The Authors. Glia published by Wiley Periodicals, Inc. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
Sponsor/Funder: | Alzheimer's Research UK (ARUK) Alzheimer's Research UK (ARUK) Alzheimer's Research UK (ARUK) |
Funder's Grant Number: | ART/PPG2009B/10 ART-PG2011-12 P52427 |
Keywords: | Science & Technology Life Sciences & Biomedicine Neurosciences Neurosciences & Neurology astrocyte A beta glial fibrillary acidic protein (GFAP) inflammation synapses A-BETA METABOLISM MOUSE MODELS SECRETED PROTEINS GLIA PROLIFERATION EXPRESSION MICE DEGRADATION MECHANISMS CLEARANCE Aβ astrocyte glial fibrillary acidic protein (GFAP) inflammation synapses Neurology & Neurosurgery 1109 Neurosciences |
Publication Status: | Published online |
Online Publication Date: | 2019-12-04 |
Appears in Collections: | Department of Brain Sciences |