Reactive astrocyte nomenclature, definitions, and future directions

1. Nat Neurosci. 2021 Mar;24(3):312-325. doi: 10.1038/s41593-020-00783-4. Epub
2021 Feb 15.

Reactive astrocyte nomenclature, definitions, and future directions.

Escartin C(1), Galea E(2)(3), Lakatos A(#)(4)(5), O’Callaghan JP(#)(6), Petzold
GC(#)(7)(8), Serrano-Pozo A(#)(9)(10), Steinhäuser C(#)(11), Volterra A(#)(12),
Carmignoto G(#)(13)(14), Agarwal A(15), Allen NJ(16), Araque A(17), Barbeito
L(18), Barzilai A(19), Bergles DE(20), Bonvento G(21), Butt AM(22), Chen WT(23),
Cohen-Salmon M(24), Cunningham C(25), Deneen B(26), De Strooper B(23)(27),
Díaz-Castro B(28), Farina C(29), Freeman M(30), Gallo V(31), Goldman JE(32),
Goldman SA(33)(34), Götz M(35)(36), Gutiérrez A(37)(38), Haydon PG(39), Heiland
DH(40)(41), Hol EM(42), Holt MG(43), Iino M(44), Kastanenka KV(45), Kettenmann
H(46), Khakh BS(47), Koizumi S(48), Lee CJ(49), Liddelow SA(50), MacVicar
BA(51), Magistretti P(52)(53), Messing A(54), Mishra A(55), Molofsky AV(56),
Murai KK(57), Norris CM(58), Okada S(59), Oliet SHR(60), Oliveira
JF(61)(62)(63), Panatier A(60), Parpura V(64), Pekna M(65), Pekny M(66),
Pellerin L(67), Perea G(68), Pérez-Nievas BG(69), Pfrieger FW(70), Poskanzer
KE(71), Quintana FJ(72), Ransohoff RM(73), Riquelme-Perez M(21), Robel S(74),
Rose CR(75), Rothstein JD(76), Rouach N(77), Rowitch DH(5), Semyanov A(78)(79),
Sirko S(80)(81), Sontheimer H(82), Swanson RA(83), Vitorica J(38)(84), Wanner
IB(85), Wood LB(86), Wu J(87), Zheng B(88), Zimmer ER(89), Zorec R(90)(91),
Sofroniew MV(92), Verkhratsky A(93)(94).

Author information:
(1)Université Paris-Saclay, CEA, CNRS, MIRCen, Laboratoire des Maladies
Neurodégénératives, Fontenay-aux-Roses, France. .
(2)Institut de Neurociències and Departament de Bioquímica i Biologia Molecular,
Unitat de Bioquímica de Medicina, Universitat Autònoma de Barcelona, Barcelona,
Spain. .
(3)ICREA, Barcelona, Spain. .
(4)John van Geest Centre for Brain Repair and Division of Stem Cell
Neurobiology, Department of Clinical Neurosciences, University of Cambridge,
Cambridge, UK.
(5)Wellcome Trust-MRC Cambridge Stem Cell Institute, Cambridge Biomedical
Campus, Cambridge, UK.
(6)Health Effects Laboratory Division, Centers for Disease Control and
Prevention, National Institute for Occupational Safety and Health, Morgantown,
West Virginia, USA.
(7)German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
(8)Division of Vascular Neurology, Department of Neurology, University Hospital
Bonn, Bonn, Germany.
(9)Alzheimer Research Unit, Department of Neurology, Massachusetts General
Hospital, Charlestown, Massachusetts, USA.
(10)Harvard Medical School, Boston, Massachusetts, USA.
(11)Institute of Cellular Neurosciences, Medical Faculty, University of Bonn,
Bonn, Germany.
(12)Department of Fundamental Neuroscience, University of Lausanne, Lausanne,
Switzerland.
(13)Neuroscience Institute, Italian National Research Council (CNR), Padua,
Italy.
(14)Department of Biomedical Sciences, University of Padua, Padua, Italy.
(15)The Chica and Heinz Schaller Research Group, Institute for Anatomy and Cell
Biology, Heidelberg University, Heidelberg, Germany.
(16)Salk Institute for Biological Studies, Molecular Neurobiology Laboratory, La
Jolla, California, USA.
(17)Department of Neuroscience, University of Minnesota, Minneapolis, Minnesota,
USA.
(18)Institut Pasteur de Montevideo, Montevideo, Uruguay.
(19)Department of Neurobiology, George S. Wise, Faculty of Life Sciences and
Sagol School of Neuroscience, Tel Aviv University, Ramat Aviv Tel Aviv, Israel.
(20)The Solomon H. Snyder Department of Neuroscience, Kavli Neuroscience
Discovery Institute, Johns Hopkins University School of Medicine, Baltimore,
Maryland, USA.
(21)Université Paris-Saclay, CEA, CNRS, MIRCen, Laboratoire des Maladies
Neurodégénératives, Fontenay-aux-Roses, France.
(22)School of Pharmacy and Biomedical Science, University of Portsmouth,
Portsmouth, UK.
(23)Center for Brain and Disease Research, VIB and University of Leuven, Leuven,
Belgium.
(24)’Physiology and Physiopathology of the Gliovascular Unit’ Research Group,
Center for Interdisciplinary Research in Biology (CIRB), College de France,
Unité Mixte de Recherche 7241 CNRS, Unité1050 INSERM, PSL Research University,
Paris, France.
(25)Trinity Biomedical Sciences Institute & Trinity College Institute of
Neuroscience, School of Biochemistry & Immunology, Trinity College Dublin,
Dublin, Republic of Ireland.
(26)Center for Cell and Gene Therapy, Department of Neurosurgery, Baylor College
of Medicine, Houston, Texas, USA.
(27)UK Dementia Research Institute at the University College London, London, UK.
(28)UK Dementia Research Institute at the University of Edinburgh, Centre for
Discovery Brain Sciences, Edinburgh, UK.
(29)Institute of Experimental Neurology (INSpe) and Division of Neuroscience,
San Raffaele Scientific Institute, Milan, Italy.
(30)Vollum Institute, OHSU, Portland, Oregon, USA.
(31)Center for Neuroscience Research, Children’s National Research Institute,
Children’s National Hospital, Washington DC, USA.
(32)Department of Pathology & Cell Biology, Columbia University, New York, New
York, USA.
(33)University of Rochester Medical Center, Rochester, New York, USA.
(34)Center for Translational Neuromedicine, University of Copenhagen Faculty of
Health and Medical Science and Rigshospitalet, Kobenhavn N, Denmark.
(35)Physiological Genomics, Biomedical Center, Ludwig-Maximilians-Universitaet &
Institute of Stem Cell Research, Helmholtz Center Munich, Munich, Germany.
(36)Synergy, Excellence Cluster of Systems Neurology, Biomedical Center, Munich,
Germany.
(37)Dpto. Biología Celular, Genética y Fisiología, Instituto de Investigación
Biomédica de Málaga-IBIMA, Facultad de Ciencias, Universidad de Málaga, Málaga,
Spain.
(38)Centro de Investigación Biomédica en Red sobre Enfermedades
Neurodegenerativas (CIBERNED), Madrid, Spain.
(39)Department of Neuroscience, Tufts University School of Medicine, Boston,
Massachusetts, USA.
(40)Microenvironment and Immunology Research Laboratory, Medical Center, Faculty
of Medicine, University of Freiburg, Freiburg, Germany.
(41)Department of Neurosurgery, Medical Center, University of Freiburg, Faculty
of Medicine, Freiburg, Germany.
(42)Department of Translational Neuroscience, University Medical Center Utrecht
Brain Center, Utrecht University, Utrecht, The Netherlands.
(43)Laboratory of Glia Biology, VIB-KU Leuven Center for Brain and Disease
Research, Leuven, Belgium.
(44)Division of Cellular and Molecular Pharmacology, Nihon University School of
Medicine, Tokyo, Japan.
(45)Massachusetts General Hospital, Harvard Medical School, Charlestown,
Massachusetts, USA.
(46)Cellular Neurosciences, Max Delbrück Center for Molecular Medicine in the
Helmholtz Association, Berlin, Germany.
(47)Department of Physiology, David Geffen School of Medicine at UCLA, Los
Angeles, California, USA.
(48)Department of Neuropharmacology, Interdisciplinary Graduate School of
Medicine, University of Yamanashi, Yamanashi, Japan.
(49)Center for Cognition and Sociality, Institute for Basic Science 55, Expo-ro,
Yuseong-gu, Daejeon, Korea.
(50)Neuroscience Institute, Department of Neuroscience and Physiology,
Department of Ophthalmology, NYU School of Medicine, New York, USA.
(51)Djavad Mowafaghian Centre for Brain Health, University of British Columbia,
Vancouver, British Columbia, Canada.
(52)Division of Biological and Environmental Sciences and Engineering, King
Abdullah University of Science and Technology (KAUST), Thuwal, Saudi Arabia.
(53)Centre de Neurosciences Psychiatriques, University of Lausanne and CHUV,
Site de Cery, Prilly-Lausanne, Lausanne, Switzerland.
(54)Waisman Center and School of Veterinary Medicine, University of
Wisconsin-Madison, Madison, Wisconsin, USA.
(55)Department of Neurology Jungers Center for Neurosciences Research and Knight
Cardiovascular Institute, Oregon Health & Science University, Portland, Oregon,
USA.
(56)Departments of Psychiatry/Weill Institute for Neuroscience University of
California, San Francisco, California, USA.
(57)Centre for Research in Neuroscience, Department of Neurology & Neurosurgery,
Brain Repair and Integrative Neuroscience Program, Research Institute of the
McGill University Health Centre, Montreal, Quebec, Canada.
(58)Sanders-Brown Center on Aging, University of Kentucky College of Medicine,
Lexington, Kentucky, USA.
(59)Department of Immunobiology and Neuroscience, Medical Institute of
Bioregulation, Kyushu University, Fukuoka, Japan.
(60)Université de Bordeaux, Inserm, Neurocentre Magendie, U1215, Bordeaux,
France.
(61)Life and Health Sciences Research Institute (ICVS), School of Medicine,
University of Minho, Braga, Portugal.
(62)ICVS/3B’s -PT Government Associate Laboratory, Braga/Guimarães, Portugal.
(63)IPCA-EST-2Ai, Polytechnic Institute of Cávado and Ave, Applied Artificial
Intelligence Laboratory, Campus of IPCA, Barcelos, Portugal.
(64)Department of Neurobiology, The University of Alabama at Birmingham,
Birmingham, Alabama, USA.
(65)Laboratory of Regenerative Neuroimmunology, Center for Brain Repair,
Department of Clinical Neuroscience, Institute of Neuroscience and Physiology,
Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
(66)Laboratory of Astrocyte Biology and CNS Regeneration, Center for Brain
Repair, Department of Clinical Neuroscience, Institute of Neuroscience and
Physiology, Sahlgrenska Academy at the University of Gothenburg, Gothenburg,
Sweden.
(67)INSERM U1082, Université de Poitiers, Poitiers, France.
(68)Department of Functional and Systems Neurobiology, Cajal Institute, CSIC,
Madrid, Spain.
(69)Department of Basic and Clinical Neuroscience, Maurice Wohl Clinical
Neuroscience Institute, Institute of Psychiatry, Psychology and Neuroscience,
King’s College London, London, UK.
(70)Centre National de la Recherche Scientifique, Université de Strasbourg,
Institut des Neurosciences Cellulaires et Intégratives, Strasbourg, France.
(71)Department of Biochemistry & Biophysics, Kavli Institute for Fundamental
Neuroscience, University of California, San Francisco, California, USA.
(72)Ann Romney Center for Neurologic Diseases, Brigham and Women’s Hospital,
Harvard Medical School. Associate Member, The Broad Institute, Boston,
Massachusetts, USA.
(73)Third Rock Ventures, Boston, Massachusetts, USA.
(74)Fralin Biomedical Research Institute at Virginia Tech Carilion, School of
Neuroscience Virginia Tech, Riverside Circle, Roanoke, Virginia, USA.
(75)Institute of Neurobiology, Heinrich Heine University, Düsseldorf, Germany.
(76)Solomon H. Snyder Department of Neuroscience, Johns Hopkins University
School of Medicine, Baltimore, Maryland, USA.
(77)Neuroglial Interactions in Cerebral Physiology and Pathologies, Center for
Interdisciplinary Research in Biology, Collège de France, CNRS UMR 7241, INSERM
U1050, Labex Memolife, PSL Research University Paris, Paris, France.
(78)Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russia.
(79)Sechenov First Moscow State Medical University, Moscow, Russia.
(80)Physiological Genomics, Biomedical Center, LMU Munich, Munich, Germany.
(81)Institute for Stem Cell Research, Helmholtz Zentrum Munich, Neuherberg,
Germany.
(82)Virginia Tech School of Neuroscience and Center for Glial Biology in Health,
Disease and Cancer, Virginia Tech at the Fralin Biomedical Research Institute,
Roanoke, Virginia, USA.
(83)Dept. of Neurology, University of California San Francisco and San Francisco
Veterans Affairs Health Care System, San Francisco, California, USA.
(84)Dept. Bioquímica y Biología Molecular, Instituto de Biomedicina de Sevilla,
Universidad de Sevilla, Hospital Virgen del Rocío/CSIC, Sevilla, Spain.
(85)Semel Institute for Neuroscience & Human Behavior, IDDRC, David Geffen
School of Medicine, UCLA, Los Angeles, California, USA.
(86)George W. Woodruff School of Mechanical Engineering, Wallace H. Coulter
Department of Biomedical Engineering at Georgia Tech and Emory, and Parker H.
Petit Institute for Bioengineering & Bioscience, Georgia Institute of
Technology, Atlanta, Georgia, USA.
(87)The Vivian L. Smith Department of Neurosurgery, Center for Stem Cell and
Regenerative Medicine, MD Anderson Cancer Center UTHealth Graduate School of
Biomedical Sciences, McGovern Medical School, UTHealth, University of Texas
Health Science Center at Houston, Houston, TX, USA.
(88)Department of Neurosciences, UC San Diego School of Medicine, La Jolla; VA
San Diego Research Service, San Diego, CA, USA.
(89)Department of Pharmacology, Universidade Federal do Rio Grande do Sul, Porto
Alegre, RS, Brazil.
(90)Laboratory of Neuroendocrinology, Molecular Cell Physiology, Institute of
Pathophysiology, University of Ljubljana, Faculty of Medicine, Ljubljana,
Slovenia.
(91)Celica Biomedical, 1000, Ljubljana, Slovenia.
(92)Department of Neurobiology, David Geffen School of Medicine, University of
California, Los Angeles, California, USA. .
(93)Faculty of Biology, Medicine and Health, The University of Manchester,
Manchester, UK. .
(94)Achúcarro Basque Center for Neuroscience, IKERBASQUE, Basque Foundation for
Science, Bilbao, Spain. .
(#)Contributed equally

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.

DOI: 10.1038/s41593-020-00783-4
PMCID: PMC8007081
PMID: 33589835 [Indexed for MEDLINE]

Auteurs Bordeaux Neurocampus