中国神经再生研究(英文版) ›› 2023, Vol. 18 ›› Issue (8): 1672-1678.doi: 10.4103/1673-5374.363192

• 综述:神经损伤修复保护与再生 • 上一篇    下一篇

来自3xTg-AD小鼠的永生化海马星形胶质细胞,研究疾病相关星形胶质细胞功能障碍的新模型:比较综述

  

  • 出版日期:2023-08-15 发布日期:2023-02-16

Immortalized hippocampal astrocytes from 3xTg-AD mice, a new model to study disease-related astrocytic dysfunction: a comparative review

Laura Tapella1, *, Giulia Dematteis1, Armando A Genazzani1, Massimiliano De Paola2, Dmitry Lim1, *   

  1. 1Department of Pharmaceutical Sciences, Università del Piemonte Orientale “Amedeo Avogadro”, Novara, Italy; 2Department of Neuroscience, Mario Negri Institute for Pharmacological Research IRCCS, Milano, Italy
  • Online:2023-08-15 Published:2023-02-16
  • Contact: Laura Tapella, PhD, laura.tapella@uniupo.it; Dmitry Lim, PhD, dmitry.lim@uniupo.it.
  • Supported by:
    This work was supported by fellowship to a grant from CRT Foundation, No. 1393-2017 (to LT); grants from the Fondazione Cariplo, Nos. 2013-0795 (to AAG), 2014-1094 (to DL); and grants from The Università del Piemonte Orientale, Nos. FAR-2016 (to DL), FAR-2019 (to DL).

摘要: https://orcid.org/0000-0002-8159-1628 (Laura Tapella); https://orcid.org/0000-0002-4316-2654 (Dmitry Lim); https://orcid.org/0000-0003-2818-9039 (Massimiliano De Paola); https://orcid.org/0000-0002-6317-3182 (Giula Dematteis); https://orcid.org/0000-0003-1923-7430 (Armando A Genazzani)

Abstract: Alzheimer’s disease (AD) is characterized by complex etiology, long-lasting pathogenesis, and cell-type-specific alterations. Currently, there is no cure for AD, emphasizing the urgent need for a comprehensive understanding of cell-specific pathology. Astrocytes, principal homeostatic cells of the central nervous system, are key players in the pathogenesis of neurodegenerative diseases, including AD. Cellular models greatly facilitate the investigation of cell-specific pathological alterations and the dissection of molecular mechanisms and pathways. Tumor-derived and immortalized astrocytic cell lines, alongside the emerging technology of adult induced pluripotent stem cells, are widely used to study cellular dysfunction in AD. Surprisingly, no stable cell lines were available from genetic mouse AD models. Recently, we established immortalized hippocampal astroglial cell lines from amyloid-β precursor protein/presenilin-1/Tau triple-transgenic (3xTg)-AD mice (denominated as wild type (WT)- and 3Tg-iAstro cells) using retrovirus-mediated transduction of simian virus 40 large T-antigen and propagation without clonal selection, thereby maintaining natural heterogeneity of primary cultures. Several groups have successfully used 3Tg-iAstro cells for single-cell and omics approaches to study astrocytic AD-related alterations of calcium signaling, mitochondrial dysfunctions, disproteostasis, altered homeostatic and signaling support to neurons, and blood-brain barrier models. Here we provide a comparative overview of the most used models to study astrocytes in vitro, such as primary culture, tumor-derived cell lines, immortalized astroglial cell lines, and induced pluripotent stem cell-derived astrocytes. We conclude that immortalized WT- and 3Tg-iAstro cells provide a non-competitive but complementary, low-cost, easy-to-handle, and versatile cellular model for dissection of astrocyte-specific AD-related alterations and preclinical drug discovery.

Key words: Alzheimer’s disease, astrocytes immortalization, astroglial Alzheimers’s disease model, blood-brain barrier, calcium signaling, central nervous system homeostasis, disproteostasis, endoplasmic reticulum-mitochondria contacts, induced pluripotent stem cell-derived astrocytes, protein synthesis