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

作　　者：Laura Tapella Giulia Dematteis Armando A Genazzani Massimiliano De Paola Dmitry Lim 

机构地区：[1]Department of Pharmaceutical Sciences,Universitàdel Piemonte Orientale“Amedeo Avogadro”,Novara,Italy [2]Department of Neuroscience,Mario Negri Institute for Pharmacological Research IRCCS,Milano,Italy

出　　处：《Neural Regeneration Research》2023年第8期1672-1678,共7页中国神经再生研究（英文版）

基　　金：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);grants from The Universitàdel Piemonte Orientale,Nos.FAR-2016(to DL),FAR-2019(to DL)。

摘　　要：Alzheimer's disease(AD)is characterized by complex etiology,long-lasting pathogenesis,and celltype-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-βprecursor 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 noncompetitive but complementary,low-cost,easy-to-handle,and versatile cellular model for dissection of astrocyte-specific AD-related alterations and preclinical drug discovery.

关 键 词：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 

分 类 号：R285.5[医药卫生—中药学]