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Isolation and characterization of neurotoxic astrocytes derived from adult triple transgenic Alzheimer's disease mice


Pablo Diaz-Amarilla

Florencia Arredondo

Rosina Dapueto

Victoria Boix

Diego Carvalho


Elena Vasilskis


Henry Engler

Eduardo Savio


Alzheimer's disease has been considered mostly as a neuronal pathology, although increasing evidence suggests that glial cells might play a key role in the disease onset and progression. In this sense, astrocytes, with their central role in neuronal metabolism and function, are of great interest for increasing our understanding of the disease. Thus, exploring the morphological and functional changes suffered by astrocytes along the course of this disorder has great therapeutic and diagnostic potential. In this work we isolated and cultivated astrocytes from symptomatic 9-10-months-old adult 3xTg-AD mice, with the aim of characterizing their phenotype and exploring their pathogenic potential. These “old” astrocytes occurring in the 3xTg-AD mouse model of Alzheimer's Disease presented high proliferation rate and differential expression of astrocytic markers compared with controls. They were neurotoxic to primary neuronal cultures both, in neuronal-astrocyte co-cultures and when their conditioned media (ACM) was added into neuronal cultures. ACM caused neuronal GSK3β activation, changes in cytochrome c pattern, and increased caspase 3 activity, suggesting intrinsic apoptotic pathway activation. Exposure of neurons to ACM caused different subcellular responses. ACM application to the somato-dendritic domain in compartmentalised microfluidic chambers caused degeneration both locally in soma/dendrites and distally in axons. However, exposure of axons to ACM did not affect somato-dendritic nor axonal integrity. We propose that this newly described old 3xTg-AD neurotoxic astrocytic population can contribute towards the mechanistic understanding of the disease and shed light on new therapeutical opportunities.


Diaz-Amarilla, P., Arredondo, F., Dapueto, R., Boix, V., Carvalho, D., Santi, M. D., …Savio, E. (2022). Isolation and characterization of neurotoxic astrocytes derived from adult triple transgenic Alzheimer's disease mice. Neurochemistry International, 159, Article 105403.

Journal Article Type Article
Acceptance Date Jul 9, 2022
Online Publication Date Aug 1, 2022
Publication Date Oct 1, 2022
Deposit Date Aug 3, 2022
Publicly Available Date Aug 2, 2023
Journal Neurochemistry International
Print ISSN 0197-0186
Electronic ISSN 1872-9754
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 159
Article Number 105403
Keywords Cell Biology; Cellular and Molecular Neuroscience
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