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. 2023 Aug;73(7-8):487-515.
doi: 10.1007/s12031-023-02105-2. Epub 2023 Jun 15.

Transcriptomic Analyses of Neurotoxic Astrocytes Derived from Adult Triple Transgenic Alzheimer's Disease Mice

Diego Carvalho  1 , Pablo Diaz-Amarilla  2 , Rosina Dapueto  2 , María Daniela Santi  2   3 , Pablo Duarte  2 , Eduardo Savio  2 , Henry Engler  2   4 , Juan A Abin-Carriquiry  5   6 , Florencia Arredondo  7   8
Affiliations

Transcriptomic Analyses of Neurotoxic Astrocytes Derived from Adult Triple Transgenic Alzheimer's Disease Mice

Diego Carvalho et al. J Mol Neurosci. 2023 Aug.

Abstract

Neurodegenerative diseases such as Alzheimer's disease have been classically studied from a purely neuronocentric point of view. More recent evidences support the notion that other cell populations are involved in disease progression. In this sense, the possible pathogenic role of glial cells like astrocytes is increasingly being recognized. Once faced with tissue damage signals and other stimuli present in disease environments, astrocytes suffer many morphological and functional changes, a process referred as reactive astrogliosis. Studies from murine models and humans suggest that these complex and heterogeneous responses could manifest as disease-specific astrocyte phenotypes. Clear understanding of disease-associated astrocytes is a necessary step to fully disclose neurodegenerative processes, aiding in the design of new therapeutic and diagnostic strategies. In this work, we present the transcriptomics characterization of neurotoxic astrocytic cultures isolated from adult symptomatic animals of the triple transgenic mouse model of Alzheimer's disease (3xTg-AD). According to the observed profile, 3xTg-AD neurotoxic astrocytes show various reactivity features including alteration of the extracellular matrix and release of pro-inflammatory and proliferative factors that could result in harmful effects to neurons. Moreover, these alterations could be a consequence of stress responses at the endoplasmic reticulum and mitochondria as well as of concomitant metabolic adaptations. Present results support the hypothesis that adaptive changes of astrocytic function induced by a stressed microenvironment could later promote harmful astrocyte phenotypes and further accelerate or induce neurodegenerative processes.

Keywords: Adult 3xTg-AD mice; Alzheimer’s disease; Astrocytes; Neurodegeneration; Transcriptomics.

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References

    1. Acín-Pérez R, Fernández-Silva P, Peleato ML, Pérez-Martos A, Enriquez JA (2008) Respiratory active mitochondrial supercomplexes. Mol Cell 32:529–539. https://doi.org/10.1016/J.MOLCEL.2008.10.021 - DOI - PubMed
    1. Acosta C, Anderson HD, Anderson CM (2017) Astrocyte dysfunction in Alzheimer disease. J Neurosci Res 95:2430–2447. https://doi.org/10.1002/JNR.24075 - DOI - PubMed
    1. Adhami F, Yu D, Yin W, Schloemer A, Burns KA, Liao G, Degen JL, Chen J, Kuan C-Y (2008) Deleterious effects of plasminogen activators in neonatal cerebral hypoxia-ischemia. Am J Pathol 172:1704–1716. https://doi.org/10.2353/AJPATH.2008.070979 - DOI - PubMed - PMC
    1. Adlimoghaddam A, Snow WM, Stortz G, Perez C, Djordjevic J, Goertzen AL, Ko JH, Albensi BC (2019) Regional hypometabolism in the 3xTg mouse model of Alzheimer’s disease. Neurobiol Dis 127:264–277. https://doi.org/10.1016/J.NBD.2019.03.008 - DOI - PubMed
    1. Al-Dalahmah O, Sosunov AA, Shaik A, Ofori K, Liu Y, Vonsattel JP, Adorjan I, Menon V, Goldman JE (2020) Single-nucleus RNA-seq identifies Huntington disease astrocyte states. Acta Neuropathol Commun 8:1–21. https://doi.org/10.1186/s40478-020-0880-6 - DOI

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