Reactive astrocyte nomenclature, definitions, and future directions

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

doi:10.1038/s41593-020-00783-4

Reactive astrocyte nomenclature, definitions, and future directions

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

^*Corresponding author for this work

Department of Neurobiology

Research output: Contribution to journal › Review article › peer-review

1434 Scopus citations

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.

Original language	English
Pages (from-to)	312-325
Number of pages	14
Journal	Nature Neuroscience
Volume	24
Issue number	3
DOIs	https://doi.org/10.1038/s41593-020-00783-4
State	Published - Mar 2021

Funding

Funders	Funder number
Centers for Disease Control and Prevention
Centre National de la Recherche Scientifique
Commissariat à l'Énergie Atomique et aux Énergies Alternatives
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung	31003A 173124/1, 160620, 173124
National Institute of Mental Health	R01MH104701
Synapsis Foundation Heidi Seiler-Stiftung	2018-PI01
SNSF NCCR	51NF40-160620
Alzheimer's Association	AACF-17-524184
National Institute on Aging	R56AG060974, RF1AG061774, R01AG056998, R01AG066171, K08AG064039
Japan Society for the Promotion of Science	19H04746
Deutsche Forschungsgemeinschaft	722053 EU-GliaPhD, STE 552/5, STE 552/4, SPP1757
National Institute of Neurological Disorders and Stroke	R01NS036692, R01NS105807, R01NS102807, R01NS084030
Generalitat de Catalunya	2017-SGR547
Bundesministerium für Bildung und Forschung	16GW0182, 16GW0182 CONNEXIN
Horizon 2020 Framework Programme	722053

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10.1038/s41593-020-00783-4

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Escartin, C., Galea, E., Lakatos, A., O’Callaghan, J. P., Petzold, G. C., Serrano-Pozo, A., Steinhäuser, C., Volterra, A., Carmignoto, G., Agarwal, A., Allen, N. J., Araque, A., Barbeito, L., Barzilai, A., Bergles, D. E., Bonvento, G., Butt, A. M., Chen, W. T., Cohen-Salmon, M., ... Verkhratsky, A. (2021). Reactive astrocyte nomenclature, definitions, and future directions. Nature Neuroscience, 24(3), 312-325. https://doi.org/10.1038/s41593-020-00783-4

@article{de22d2c4a5754a27b8f15a698ce3f8a1,

title = "Reactive astrocyte nomenclature, definitions, and future directions",

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.",

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

note = "Publisher Copyright: {\textcopyright} 2021, Springer Nature America, Inc.",

year = "2021",

month = mar,

doi = "10.1038/s41593-020-00783-4",

language = "אנגלית",

volume = "24",

pages = "312--325",

journal = "Nature Neuroscience",

issn = "1097-6256",

publisher = "Nature Research",

number = "3",

}

Escartin, C, Galea, E, Lakatos, A, O’Callaghan, JP, Petzold, GC, Serrano-Pozo, A, Steinhäuser, C, Volterra, A, Carmignoto, G, Agarwal, A, Allen, NJ, Araque, A, Barbeito, L, Barzilai, A, Bergles, DE, Bonvento, G, Butt, AM, Chen, WT, Cohen-Salmon, M, Cunningham, C, Deneen, B, De Strooper, B, Díaz-Castro, B, Farina, C, Freeman, M, Gallo, V, Goldman, JE, Goldman, SA, Götz, M, Gutiérrez, A, Haydon, PG, Heiland, DH, Hol, EM, Holt, MG, Iino, M, Kastanenka, KV, Kettenmann, H, Khakh, BS, Koizumi, S, Lee, CJ, Liddelow, SA, MacVicar, BA, Magistretti, P, Messing, A, Mishra, A, Molofsky, AV, Murai, KK, Norris, CM, Okada, S, Oliet, SHR, Oliveira, JF, Panatier, A, Parpura, V, Pekna, M, Pekny, M, Pellerin, L, Perea, G, Pérez-Nievas, BG, Pfrieger, FW, Poskanzer, KE, Quintana, FJ, Ransohoff, RM, Riquelme-Perez, M, Robel, S, Rose, CR, Rothstein, JD, Rouach, N, Rowitch, DH, Semyanov, A, Sirko, S, Sontheimer, H, Swanson, RA, Vitorica, J, Wanner, IB, Wood, LB, Wu, J, Zheng, B, Zimmer, ER, Zorec, R, Sofroniew, MV & Verkhratsky, A 2021, 'Reactive astrocyte nomenclature, definitions, and future directions', Nature Neuroscience, vol. 24, no. 3, pp. 312-325. https://doi.org/10.1038/s41593-020-00783-4

TY - JOUR

T1 - Reactive astrocyte nomenclature, definitions, and future directions

AU - Escartin, Carole

AU - Galea, Elena

AU - Lakatos, András

AU - O’Callaghan, James P.

AU - Petzold, Gabor C.

AU - Serrano-Pozo, Alberto

AU - Steinhäuser, Christian

AU - Volterra, Andrea

AU - Carmignoto, Giorgio

AU - Agarwal, Amit

AU - Allen, Nicola J.

AU - Araque, Alfonso

AU - Barbeito, Luis

AU - Barzilai, Ari

AU - Bergles, Dwight E.

AU - Bonvento, Gilles

AU - Butt, Arthur M.

AU - Chen, Wei Ting

AU - Cohen-Salmon, Martine

AU - Cunningham, Colm

AU - Deneen, Benjamin

AU - De Strooper, Bart

AU - Díaz-Castro, Blanca

AU - Farina, Cinthia

AU - Freeman, Marc

AU - Gallo, Vittorio

AU - Goldman, James E.

AU - Goldman, Steven A.

AU - Götz, Magdalena

AU - Gutiérrez, Antonia

AU - Haydon, Philip G.

AU - Heiland, Dieter H.

AU - Hol, Elly M.

AU - Holt, Matthew G.

AU - Iino, Masamitsu

AU - Kastanenka, Ksenia V.

AU - Kettenmann, Helmut

AU - Khakh, Baljit S.

AU - Koizumi, Schuichi

AU - Lee, C. Justin

AU - Liddelow, Shane A.

AU - MacVicar, Brian A.

AU - Magistretti, Pierre

AU - Messing, Albee

AU - Mishra, Anusha

AU - Molofsky, Anna V.

AU - Murai, Keith K.

AU - Norris, Christopher M.

AU - Okada, Seiji

AU - Oliet, Stéphane H.R.

AU - Oliveira, João F.

AU - Panatier, Aude

AU - Parpura, Vladimir

AU - Pekna, Marcela

AU - Pekny, Milos

AU - Pellerin, Luc

AU - Perea, Gertrudis

AU - Pérez-Nievas, Beatriz G.

AU - Pfrieger, Frank W.

AU - Poskanzer, Kira E.

AU - Quintana, Francisco J.

AU - Ransohoff, Richard M.

AU - Riquelme-Perez, Miriam

AU - Robel, Stefanie

AU - Rose, Christine R.

AU - Rothstein, Jeffrey D.

AU - Rouach, Nathalie

AU - Rowitch, David H.

AU - Semyanov, Alexey

AU - Sirko, Swetlana

AU - Sontheimer, Harald

AU - Swanson, Raymond A.

AU - Vitorica, Javier

AU - Wanner, Ina Beate

AU - Wood, Levi B.

AU - Wu, Jiaqian

AU - Zheng, Binhai

AU - Zimmer, Eduardo R.

AU - Zorec, Robert

AU - Sofroniew, Michael V.

AU - Verkhratsky, Alexei

PY - 2021/3

Y1 - 2021/3

N2 - 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.

AB - 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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DO - 10.1038/s41593-020-00783-4

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C2 - 33589835

AN - SCOPUS:85100133612

SN - 1097-6256

VL - 24

SP - 312

EP - 325

JO - Nature Neuroscience

JF - Nature Neuroscience

IS - 3

ER -

Reactive astrocyte nomenclature, definitions, and future directions

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