Reactive astrocyte nomenclature, definitions, and future directions

Nature Neuroscience 2021

Escartin, Carole and Galea, Elena and Lakatos, Andr{\'a}s and O'Callaghan, James P. and Petzold, Gabor C. and Serrano-Pozo, Alberto and Steinh{\"a}user, Christian and Volterra, Andrea and Carmignoto, Giorgio and Agarwal, Amit and Allen, Nicola J. and Araque, Alfonso and Barbeito, Luis and Barzilai, Ari and Bergles, Dwight E. and Bonvento, Gilles and Butt, Arthur M. and Chen, Wei-Ting and Cohen-Salmon, Martine and Cunningham, Colm and Deneen, Benjamin and De Strooper, Bart and D{\'i}az-Castro, Blanca and Farina, Cinthia and Freeman, Marc and Gallo, Vittorio and Goldman, James E. and Goldman, Steven A. and G{\"o}tz, Magdalena and Guti{\'e}rrez, Antonia and Haydon, Philip G. and Heiland, Dieter H. and Hol, Elly M. and Holt, Matthew G. and Iino, Masamitsu and Kastanenka, Ksenia V. and Kettenmann, Helmut and Khakh, Baljit S. and Koizumi, Schuichi and Lee, C. Justin and Liddelow, Shane A. and MacVicar, Brian A. and Magistretti, Pierre and Messing, Albee and Mishra, Anusha and Molofsky, Anna V. and Murai, Keith K. and Norris, Christopher M. and Okada, Seiji and Oliet, St{\'e}phane H. R. and Oliveira, Jo{\~a}o F. and Panatier, Aude and Parpura, Vladimir and Pekna, Marcela and Pekny, Milos and Pellerin, Luc and Perea, Gertrudis and P{\'e}rez-Nievas, Beatriz G. and Pfrieger, Frank W. and Poskanzer, Kira E. and Quintana, Francisco J. and Ransohoff, Richard M. and Riquelme-Perez, Miriam and Robel, Stefanie and Rose, Christine R. and Rothstein, Jeffrey D. and Rouach, Nathalie and Rowitch, David H. and Semyanov, Alexey and Sirko, Swetlana and Sontheimer, Harald and Swanson, Raymond A. and Vitorica, Javier and Wanner, Ina-Beate and Wood, Levi B. and Wu, Jiaqian and Zheng, Binhai and Zimmer, Eduardo R. and Zorec, Robert and Sofroniew, Michael V. and Verkhratsky, Alexei

Abstract

Reactive astrocytes are astrocytes undergoing morphological, molecular, and functional remodeling in response to injury, disease, or infection of the CNS. Although this remodeling was first described over a century ago, uncertainties and controversies remain regarding the contribution of reactive astrocytes to CNS diseases, repair, and aging. It is also unclear whether fixed categories of reactive astrocytes exist and, if so, how to identify them. We point out the shortcomings of binary divisions of reactive astrocytes into good-vs-bad, neurotoxic-vs-neuroprotective or A1-vs-A2. We advocate, instead, that research on reactive astrocytes include assessment of multiple molecular and functional parameters-preferably in vivo-plus multivariate statistics and determination of impact on pathological hallmarks in relevant models. These guidelines may spur the discovery of astrocyte-based biomarkers as well as astrocyte-targeting therapies that abrogate detrimental actions of reactive astrocytes, potentiate their neuro- and glioprotective actions, and restore or augment their homeostatic, modulatory, and defensive functions.

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