Search

Your search keyword '"Holt, Matthew G."' showing total 6 results
Start Over Author "Holt, Matthew G." Topic brain
6 results on '"Holt, Matthew G."'

1. Reactive astrocyte nomenclature, definitions, and future directions.

Author

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, and Verkhratsky A

Subjects
Animals, Brain Diseases pathology, Brain Injuries pathology, Humans, Spinal Cord Injuries pathology, Aging pathology, Astrocytes pathology, Brain pathology, Spinal Cord pathology
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.

Published
2021
Full Text
View/download PDF

2. Widespread transduction of astrocytes and neurons in the mouse central nervous system after systemic delivery of a self-complementary AAV-PHP.B vector.

Author

Rincon MY, de Vin F, Duqué SI, Fripont S, Castaldo SA, Bouhuijzen-Wenger J, and Holt MG

Subjects
Animals, Brain cytology, Female, Green Fluorescent Proteins genetics, Green Fluorescent Proteins metabolism, Humans, Mice, Inbred C57BL, Promoter Regions, Genetic, Synapsins genetics, Transgenes, Astrocytes metabolism, Brain metabolism, Dependovirus genetics, Genetic Vectors administration & dosage, Neurons metabolism, Transduction, Genetic
Abstract

Until recently, adeno-associated virus 9 (AAV9) was considered the AAV serotype most effective in crossing the blood-brain barrier (BBB) and transducing cells of the central nervous system (CNS), following systemic injection. However, a newly engineered capsid, AAV-PHP.B, is reported to cross the BBB at even higher efficiency. We investigated how much we could boost CNS transgene expression by using AAV-PHP.B carrying a self-complementary (sc) genome. To allow comparison, 6 weeks old C57BL/6 mice received intravenous injections of scAAV2/9-GFP or scAAV2/PHP.B-GFP at equivalent doses. Three weeks postinjection, transgene expression was assessed in brain and spinal cord. We consistently observed more widespread CNS transduction and higher levels of transgene expression when using the scAAV2/PHP.B-GFP vector. In particular, we observed an unprecedented level of astrocyte transduction in the cortex, when using a ubiquitous CBA promoter. In comparison, neuronal transduction was much lower than previously reported. However, strong neuronal expression (including spinal motor neurons) was observed when the human synapsin promoter was used. These findings constitute the first reported use of an AAV-PHP.B capsid, encapsulating a scAAV genome, for gene transfer in adult mice. Our results underscore the potential of this AAV construct as a platform for safer and more efficacious gene therapy vectors for the CNS.

Published
2018
Full Text
View/download PDF

3. An immunoaffinity-based method for isolating ultrapure adult astrocytes based on ATP1B2 targeting by the ACSA-2 antibody.

Author

Batiuk MY, de Vin F, Duqué SI, Li C, Saito T, Saido T, Fiers M, Belgard TG, and Holt MG

Subjects
Animals, Astrocytes pathology, Brain pathology, Brain Injuries pathology, Disease Models, Animal, Female, Male, Mice, Adenosine Triphosphatases biosynthesis, Adenosine Triphosphatases chemistry, Antibodies chemistry, Astrocytes metabolism, Brain metabolism, Brain Injuries metabolism, Cation Transport Proteins biosynthesis, Cation Transport Proteins chemistry, Cell Adhesion Molecules, Neuronal biosynthesis, Cell Adhesion Molecules, Neuronal chemistry, Epitopes biosynthesis, Epitopes chemistry, Gene Expression Regulation
Abstract

Astrocytes are a major cell type in the mammalian CNS. Astrocytes are now known to play a number of essential roles in processes including synapse formation and function, as well as blood-brain barrier formation and control of cerebral blood flow. However, our understanding of the molecular mechanisms underlying astrocyte development and function is still rudimentary. This lack of knowledge is at least partly due to the lack of tools currently available for astrocyte biology. ACSA-2 is a commercially available antibody originally developed for the isolation of astrocytes from young postnatal mouse brain, using magnetic cell-sorting methods, but its utility in isolating cells from adult tissue has not yet been published. Using a modified protocol, we now show that this tool can also be used to isolate ultrapure astrocytes from the adult brain. Furthermore, using a variety of techniques (including single-cell sequencing, overexpression and knockdown assays, immunoblotting, and immunohistochemistry), we identify the ACSA-2 epitope for the first time as ATP1B2 and characterize its distribution in the CNS. Finally, we show that ATP1B2 is stably expressed in multiple models of CNS injury and disease. Hence, we show that the ACSA-2 antibody possesses the potential to be an extremely valuable tool for astrocyte research, allowing the purification and characterization of astrocytes (potentially including injury and disease models) without the need for any specialized and expensive equipment. In fact, our results suggest that ACSA-2 should be a first-choice method for astrocyte isolation and characterization., (© 2017 by The American Society for Biochemistry and Molecular Biology, Inc.)

Published
2017
Full Text
View/download PDF

4. Molecular and cognitive signatures of ageing partially restored through synthetic delivery of IL2 to the brain.

Author

Lemaitre, Pierre, Tareen, Samar HK, Pasciuto, Emanuela, Mascali, Loriana, Martirosyan, Araks, Callaerts‐Vegh, Zsuzsanna, Poovathingal, Suresh, Dooley, James, Holt, Matthew G, Yshii, Lidia, and Liston, Adrian

Abstract

Cognitive decline is a common pathological outcome during aging, with an ill‐defined molecular and cellular basis. In recent years, the concept of inflammaging, defined as a low‐grade inflammation increasing with age, has emerged. Infiltrating T cells accumulate in the brain with age and may contribute to the amplification of inflammatory cascades and disruptions to the neurogenic niche observed with age. Recently, a small resident population of regulatory T cells has been identified in the brain, and the capacity of IL2‐mediated expansion of this population to counter neuroinflammatory disease has been demonstrated. Here, we test a brain‐specific IL2 delivery system for the prevention of neurological decline in aging mice. We identify the molecular hallmarks of aging in the brain glial compartments and identify partial restoration of this signature through IL2 treatment. At a behavioral level, brain IL2 delivery prevented the age‐induced defect in spatial learning, without improving the general decline in motor skill or arousal. These results identify immune modulation as a potential path to preserving cognitive function for healthy aging. Synopsis: Delivery of interleukin 2 into the brain via a blood–brain barrier crossing AAV vector prevents cognitive decline in the aging mice. A gene delivery system uses an AAV‐based viral vector coupled with an astrocyte‐specific promoter to drive the expression of the anti‐inflammatory cytokine interleukin 2 in the brain of aged mice.At a molecular level, brain‐specific expression of IL2 in aged mice partially reverted the transcriptional signature of aged glial cells to the baseline state of young glial cells.At a cognitive level, brain‐specific expression of IL2 in aged mice partially restored the spatial learning decline, without improving the general decline in motor skill or arousal. [ABSTRACT FROM AUTHOR]

Published
2023
Full Text
View/download PDF

5. Reactive astrocyte nomenclature, definitions, and future directions

Author

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

Subjects
Aging, Brain Diseases, Spinal Cord, Astrocytes, Brain Injuries, Animals, Brain, Humans, Spinal Cord Injuries, 3. Good health
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.

6. Reactive astrocyte nomenclature, definitions, and future directions

Author

Arthur M. Butt, Elena Galea, Richard M. Ransohoff, Raymond A. Swanson, Eduardo R. Zimmer, Christopher M. Norris, Gilles Bonvento, Andras Lakatos, Philip G. Haydon, Wei Ting Chen, Christine R. Rose, Alexey Semyanov, Nicola J. Allen, Anna V. Molofsky, Javier Vitorica, Seiji Okada, Alfonso Araque, Antonia Gutierrez, Masamitsu Iino, Alberto Serrano-Pozo, Vittorio Gallo, C. Justin Lee, Magdalena Götz, Baljit S. Khakh, Christian Steinhäuser, Bart De Strooper, Stéphane H. R. Oliet, Andrea Volterra, Swetlana Sirko, Kira E. Poskanzer, Michael V. Sofroniew, Giorgio Carmignoto, Elly M. Hol, Frank W. Pfrieger, Beatriz G. Pérez-Nievas, Ksenia V. Kastanenka, Keith K. Murai, James P. O'Callaghan, Ina B. Wanner, David H. Rowitch, Pierre J. Magistretti, Cinthia Farina, Marcela Pekna, Albee Messing, Jia Qian Wu, Shane A. Liddelow, Dieter Henrik Heiland, Anusha Mishra, Robert Zorec, Levi B. Wood, Marc R. Freeman, Matthew Holt, Luis Barbeito, Gabor C. Petzold, Luc Pellerin, Jeffrey D. Rothstein, Nathalie Rouach, Carole Escartin, Schuichi Koizumi, Gertrudis Perea, Dwight E. Bergles, Miriam Riquelme-Perez, Martine Cohen-Salmon, Stefanie Robel, James E. Goldman, Binhai Zheng, João Filipe Oliveira, Ari Barzilai, Steven A. Goldman, Brian A. MacVicar, Aude Panatier, Helmut Kettenmann, Alexei Verkhratsky, Amit Agarwal, Colm Cunningham, Blanca Diaz-Castro, Francisco J. Quintana, Milos Pekny, Harald Sontheimer, Benjamin Deneen, Vladimir Parpura, Service MIRCEN (MIRCEN), Institut de Biologie François JACOB (JACOB), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Universitat Autònoma de Barcelona (UAB), ICREA Infection Biology Laboratory (Department of Experimental and Health Sciences), Universitat Pompeu Fabra [Barcelona] (UPF), University of Cambridge [UK] (CAM), National Institute for Occupational Safety and Health [Morgantown, WV, USA] (NIOSH), German Research Center for Neurodegenerative Diseases - Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), University Hospital Bonn, Massachusetts General Hospital [Charlestown, MA, États-Unis], University of Bonn, University of Lausanne (UNIL), Italian National Research Council [Padova, Italy], University of Padua [Italy], Heidelberg University, The Salk Institute for Biological Studies, University of Minnesota [MN, USA], Institut Pasteur de Montevideo, Réseau International des Instituts Pasteur (RIIP), Tel Aviv University [Tel Aviv], Johns Hopkins University School of Medicine [Baltimore], University of Portsmouth, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Centre interdisciplinaire de recherche en biologie (CIRB), Labex MemoLife, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Trinity College Dublin, Baylor College of Medicine (BCM), Baylor University, University College of London [London] (UCL), University of Edinburgh, San Raffaele Scientific Institute, Vita-Salute San Raffaele University and Center for Translational Genomics and Bioinformatics, Vollum Institute, Vollum Institute OHSU, National Children's Hospital, Columbia University [New York], University of Rochester Medical Center (URMC), University of Copenhagen = Københavns Universitet (KU), Ludwig Maximilians Universitaet, SYNERGY, Excellence Cluster of Systems Neurology, Ludwig-Maximilians-Universität München (LMU), Universidad de Málaga [Málaga] = University of Málaga [Málaga], Centro de Investigacion Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III [Madrid] (ISC), Tufts University School of Medicine [Boston], University of Freiburg [Freiburg], Utrecht University [Utrecht], VIB-KU Leuven Center for Brain & Disease Research [Leuven, Belgium], Nihon University School of Medicine [Tokyo, Japan], Max Delbrück Center for Molecular Medicine [Berlin] (MDC), Helmholtz-Gemeinschaft = Helmholtz Association, David Geffen School of Medicine [Los Angeles], University of California [Los Angeles] (UCLA), University of California-University of California, Yamanashi University, Institute for Basic Science [Daejeon] (IBS), New York University School of Medicine (NYU), New York University School of Medicine, NYU System (NYU)-NYU System (NYU), University of British Columbia (UBC), King Abdullah University of Science and Technology, University of Wisconsin-Madison, Oregon Health and Science University [Portland] (OHSU), University of California [San Francisco] (UCSF), University of California, McGill University Health Center [Montreal] (MUHC), University of Kentucky, Kyushu University [Fukuoka], Physiopathologie de la Plasticité Neuronale (Neurocentre Magendie - U1215 Inserm), Université de Bordeaux (UB)-Institut François Magendie-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Minho [Braga], ICVS/3B's—PT Government Associate Laboratory [Braga, Portugal], Polytechnic Institute of Cávado and Ave, University of Alabama at Birmingham [ Birmingham] (UAB), University of Gothenburg (GU), Ischémie Reperfusion en Transplantation d’Organes Mécanismes et Innovations Thérapeutiques ( IRTOMIT), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), Cajal Institute, King‘s College London, Institut des Neurosciences Cellulaires et Intégratives (INCI), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Brigham & Women’s Hospital [Boston] (BWH), Harvard Medical School [Boston] (HMS), Third Rock Ventures, Heinrich Heine Universität Düsseldorf = Heinrich Heine University [Düsseldorf], Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry (IBCh RAS), Russian Academy of Sciences [Moscow] (RAS), Sechenov First Moscow State Medical University, Ludwig Maximilian University [Munich] (LMU), Institute for Stem Cell Research [Neuherberg], Helmholtz-Zentrum München (HZM), Universidad de Sevilla, Georgia Institute of Technology [Atlanta], The University of Texas Health Science Center at Houston (UTHealth), UC San Diego School of Medicine, Universidade Federal do Rio Grande do Sul [Porto Alegre] (UFRGS), University of Ljubljana, University of Manchester [Manchester], Ikerbasque - Basque Foundation for Science, Université Paris-Saclay-Institut de Biologie François JACOB (JACOB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), European Project: 722053,EU-GliaPhD - H2020-EU.1.3. H2020-EU.1.3.1., Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie François JACOB (JACOB), Universität Bonn = University of Bonn, Université de Lausanne = University of Lausanne (UNIL), Escartin, Carole [0000-0003-3613-4118], Galea, Elena [0000-0003-4537-9897], Lakatos, András [0000-0002-1301-2292], Petzold, Gabor C [0000-0002-0145-8641], Serrano-Pozo, Alberto [0000-0003-0899-7530], Volterra, Andrea [0000-0003-1069-1602], Araque, Alfonso [0000-0003-3840-1144], Barbeito, Luis [0000-0002-3047-232X], Bonvento, Gilles [0000-0002-2886-4228], Butt, Arthur M [0000-0001-7579-0746], Deneen, Benjamin [0000-0002-6335-1081], Farina, Cinthia [0000-0002-4466-9676], Gallo, Vittorio [0000-0002-2429-0845], Goldman, Steven A [0000-0002-5498-4303], Götz, Magdalena [0000-0003-1551-9203], Gutiérrez, Antonia [0000-0002-6264-6152], Haydon, Philip G [0000-0001-5698-6698], Heiland, Dieter H [0000-0002-9258-3033], Hol, Elly M [0000-0001-5604-2603], Holt, Matthew G [0000-0002-8958-4027], Koizumi, Schuichi [0000-0001-6184-3106], MacVicar, Brian A [0000-0003-4596-4623], Mishra, Anusha [0000-0002-3642-5049], Molofsky, Anna V [0000-0002-4709-2411], Okada, Seiji [0000-0002-5107-8209], Oliveira, João F [0000-0002-1005-2328], Panatier, Aude [0000-0002-6107-4463], Pekna, Marcela [0000-0003-2734-8237], Perea, Gertrudis [0000-0001-5924-9175], Pfrieger, Frank W [0000-0001-7085-1431], Poskanzer, Kira E [0000-0003-4830-8891], Rose, Christine R [0000-0002-9684-3592], Rothstein, Jeffrey D [0000-0003-2001-8470], Rouach, Nathalie [0000-0002-5574-888X], Rowitch, David H [0000-0002-0079-0060], Semyanov, Alexey [0000-0002-6800-0942], Sirko, Swetlana [0000-0001-5950-616X], Sontheimer, Harald [0000-0002-5843-9871], Swanson, Raymond A [0000-0002-3664-5359], Zorec, Robert [0000-0002-7478-3875], Sofroniew, Michael V [0000-0001-6075-0178], Verkhratsky, Alexei [0000-0003-2592-9898], and Apollo - University of Cambridge Repository

Subjects
0301 basic medicine, Aging, [SDV]Life Sciences [q-bio], Disease, pathology [Spinal Cord], Article, 03 medical and health sciences, 0302 clinical medicine, pathology [Aging], Response to injury, pathology [Brain], medicine, Psychology, Animals, Humans, ddc:610, Reactive Astrocyte, ComputingMilieux_MISCELLANEOUS, Spinal Cord Injuries, pathology [Astrocytes], Brain Diseases, Neurology & Neurosurgery, Extramural, business.industry, General Neuroscience, pathology [Brain Injuries], Neurosciences, pathology [Brain Diseases], Brain, 3. Good health, Brain Disorders, 030104 developmental biology, medicine.anatomical_structure, Spinal Cord, Astrocytes, Brain Injuries, Neurological, Cognitive Sciences, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], pathology [Spinal Cord Injuries], business, Neuroscience, 030217 neurology & neurosurgery, Astrocyte, Spinal cord pathology
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., Funding: CNRS, CEA, ANR, and France Alzheimer to CE.; MCINN (PID2019-107633RB-I00) and Generalitat de Catalunya (2017-SGR547, Grup de demències Sant Pau) to E.G. US Centers for Disease Control and Prevention to J. P.O. Alzheimer’s Association (AACF-17-524184) and NIH-NIA (K08AG064039) to A.S.-P. DFG (SPP1757, STE 552/5, STE 552/4), EU (H2020-MSCA-ITN project 722053 EU-GliaPhD) and BMBF (16GW0182 CONNEXIN) to C.S. Swiss National Science Foundation grant 31003A 173124/1; SNSF NCCR ‘Transcure’ (51NF40-160620); Synapsis Foundation Heidi Seiler-Stiftung 2018-PI01 to A.Volterra. NIH-NINDS (NS084030), Dr. Miriam and Sheldon G. Adelson Medical Foundation and Wings for Life to M.V.S. The authors thank T. Yohannan of Alpha Language Services, Barcelona, for expert copy editing.

Published
2021

Catalog

Books, media, physical & digital resources
See catalog results