Imperial College London
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ProfessorMagdalenaSastre

Faculty of Medicine, Department of Brain Sciences

Professor in Molecular Neuroscience
 
 
 
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Contact

 

+44 (0)20 7594 6673m.sastre

 
 
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Location

 

406Burlington DanesHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Davis:2020:10.1002/alz.047419,
author = {Davis, N and Mota, BC and Stead, L and Palmer, EOC and Lombardero, L and RodriguezPuertas, R and de, Paola V and Barnes, SJ and Sastre, M},
doi = {10.1002/alz.047419},
journal = {Alzheimer's & Dementia},
title = {Ablation of astrocytes affects Aβ degradation, microglia activation and synaptic connectivity in an <i>ex vivo</i> model of Alzheimer’s disease},
url = {http://dx.doi.org/10.1002/alz.047419},
volume = {16},
year = {2020}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - <jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Astrocytes provide vital support to neurons in normal and pathological conditions. In Alzheimer's disease (AD) brains, reactive astrocytes have been found surrounding amyloid plaques, forming an astrocytic scar. However, their role and potential mechanisms through which they affect neuroinflammation, amyloid pathology and synaptic density in AD remain unclear.</jats:p></jats:sec><jats:sec><jats:title>Method</jats:title><jats:p>To explore the role of astrocytes on amyloid pathology and neuroinflammatory markers, we pharmacologically ablated astrocytes in organotypic brain culture slices (OBCSs) generated from the 5XFAD mouse model of amyloidosis with selective astrocytic toxin Lalphaaminoadipate (LAAA). To examine the effects on synaptic circuitry, we measured dendritic spine number and size in OBCSs from Thy1GFP transgenic mice incubated with synthetic amyloidbeta (Aβ)42, or double transgenics Thy1GFP/5XFAD mice treated with LAAA or vehicle for 24h.</jats:p></jats:sec><jats:sec><jats:title>Result</jats:title><jats:p>Treatment of OBCSs with LAAA resulted in an increased expression of proinflammatory cytokines, such as TNFα in conditioned media, without changes in microglial density. In addition, pharmacological ablation of astrocytes led to an increase in Aβ levels in homogenates of OBCS from 5XFAD mice compared with vehicle controls, associated with reduced expression of Neprilysin and Apolipoprotein E, which are involved in Aβ clearance. In addition, OBSCs from wildtype mice treated with LAAA and synthetic amyloid presented 56% higher levels of Aβ in culture media compared to sections treated with Aβ alone, concomitant with reduced expression of the Aβ degrading enzyme IDE in culture medium, suggesting that astrocytes contribut
AU  - Davis,N
AU  - Mota,BC
AU  - Stead,L
AU  - Palmer,EOC
AU  - Lombardero,L
AU  - RodriguezPuertas,R
AU  - de,Paola V
AU  - Barnes,SJ
AU  - Sastre,M
DO  - 10.1002/alz.047419
PY  - 2020///
SN  - 1552-5260
TI  - Ablation of astrocytes affects Aβ degradation, microglia activation and synaptic connectivity in an <i>ex vivo</i> model of Alzheimer’s disease
T2  - Alzheimer's & Dementia
UR  - http://dx.doi.org/10.1002/alz.047419
VL  - 16
ER  -
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