Curriculum Vitae
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Professor Of
CURRICULUM VITAE Name: ALEXEI VERKHRATSKY Date of birth: July 30, 1961 Citizenship: British Title: MD, PhD, Dr. Sci. Department: Professor of Neurophysiology Faculty of Life Sciences, The University of Manchester Michael Smith Building, Oxford Road, Manchester M13 9PT, UK e-mail: [email protected] Current appointments: Professor of Neurophysiology Higher Education and academic degrees: 1993: Doctor of Medical Sciences, Bogomoletz Institute of Physiology, Physiology, "Mechanisms of calcium signal generation in neurones and glial cells". 1983-1986: PhD, Bogomoletz Institute of Physiology: Physiology, "Tetrodotoxin sensitive ionic currents in the membrane of isolated cardiomyocytes" 1977 - 1983: MD, Kiev Medical Institute. Honours: 2003: Elected Member of Academia Europaea 2006 - 2013: Chairman of the Physiology and Medicine Section of the Academia Europaea; Member of the Council 2012: Elected member of Real Academia Nacional de Farmacia, Spain 2012: Research Award of German Purine Club 2012: Elected member of European Dana Alliance for the Brain Initiatives (since 2015 Dana Alliance for Brain Initiatives). 2013: Recipient of Dozor Visiting Scholar award, Ben Gurion University, Beer Sheva, Israel. 2013: Fellow of Japan Society for the Promotion of Science (JSPS). 2013: Elected member of Nationale Akademie der Wissenschaften Leopoldina (The German National Academy of Sciences Leopoldina). 2016 - present: Vice-Presidnet and Chairmen of the Class C (Life Science and Medicine) of the Academia Europaea. 2016: Copernicus Gold -
OMB No. 0925-0046, Biographical Sketch Format Page
BIOGRAPHICAL SKETCH NAME: Nedergaard, Maiken eRA COMMONS USER NAME (credential, e.g., agency login): mnedergaard POSITION TITLE: Professor EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, include postdoctoral training and residency training if applicable. Add/delete rows as necessary.) DEGREE Completion (if Date FIELD OF STUDY INSTITUTION AND LOCATION applicable) MM/YYYY University of Copenhagen M.D. 1983 Medicine University of Copenhagen Ph.D. 1989 Neuroscience A. Personal statement The objective of my work is to understand the biological functions of astrocytes, their ability to interact with other cell types, and to use this knowledge to develop novel therapeutic strategies to treat, or perhaps cure, a variety of neurological diseases. In vivo explorations have radically challenged the classical dogma – that neurons are the sole substrate of higher brain function – and have led to a shift in paradigm by including astrocytes and other glial cells in higher cognitive functions. No current medications used in clinical medicine target glial cells – the most numerous cells in CNS. The premise for my work is that understanding the basic functions of glial cells offers extraordinary opportunities for combating disease. We have recently identified a fundamentally novel pathway for interstitial solute clearance from the brain consisting of a para-arterial cerebrospinal fluid (CSF) influx path and a para-venous interstitial fluid (ISF) clearance route, which are coupled through convective interstitial bulk flow supported by astrocytic AQP4 water channels. We designated it “the glymphatic system” based on its adoption of functions analogous to the peripheral lymphatic system and the dependence of CSF/ISF fluxes on astroglial AQP4. -
Once Considered Mainly 'Brain Glue,' Astrocytes' Power Revealed 4 April 2012
Once considered mainly 'brain glue,' astrocytes' power revealed 4 April 2012 A type of cell plentiful in the brain, long considered levels must come down immediately for the brain to mainly the stuff that holds the brain together and work properly. Scientists have long known that oft-overlooked by scientists more interested in that's a job for astrocytes - sopping up excess flashier cells known as neurons, wields more potassium, ending the nerve pulse, and restoring power in the brain than has been realized, the cells so they can fire again immediately. according to new research published in Science Signaling. In the paper in Science Signaling, Nedergaard's team discovered an expanded role for astrocytes. Neuroscientists at the University of Rochester The team learned that in addition to simply Medical Center report that astrocytes are crucial absorbing excess potassium, astrocytes for creating the proper environment for our brains themselves can cause potassium levels around the to work. The team found that the cells play a key neuron to drop, putting neuronal signaling to a stop. role in reducing or stopping the electrical signals that are considered brain activity, playing an active "Far from only playing a passive role, astrocytes role in determining when cells called neurons fire can initiate the uptake of potassium in a way that and when they don't. affects neuronal activity," said Nedergaard. "It's a simple, yet powerful mechanism for astrocytes to That is a big step forward from what scientists rapidly modulate neuronal activity." have long considered the role of astrocytes - to nurture neurons and keep them healthy. -
University of Copenhagen, Copenhagen, Denmark
Understanding the functions and relationships of the glymphatic system and meningeal lymphatics Louveau, Antoine; Plog, Benjamin A.; Antila, Salli; Alitalo, Kari; Nedergaard, Maiken; Kipnis, Jonathan Published in: The Journal of Clinical Investigation DOI: 10.1172/JCI90603 Publication date: 2017 Document version Publisher's PDF, also known as Version of record Document license: Unspecified Citation for published version (APA): Louveau, A., Plog, B. A., Antila, S., Alitalo, K., Nedergaard, M., & Kipnis, J. (2017). Understanding the functions and relationships of the glymphatic system and meningeal lymphatics. The Journal of Clinical Investigation, 127(9), 3210-3219. https://doi.org/10.1172/JCI90603 Download date: 26. Sep. 2021 Understanding the functions and relationships of the glymphatic system and meningeal lymphatics Antoine Louveau, … , Maiken Nedergaard, Jonathan Kipnis J Clin Invest. 2017;127(9):3210-3219. https://doi.org/10.1172/JCI90603. Review Series Recent discoveries of the glymphatic system and of meningeal lymphatic vessels have generated a lot of excitement, along with some degree of skepticism. Here, we summarize the state of the field and point out the gaps of knowledge that should be filled through further research. We discuss the glymphatic system as a system that allows CNS perfusion by the cerebrospinal fluid (CSF) and interstitial fluid (ISF). We also describe the recently characterized meningeal lymphatic vessels and their role in drainage of the brain ISF, CSF, CNS-derived molecules, and immune cells from the CNS and meninges to the peripheral (CNS-draining) lymph nodes. We speculate on the relationship between the two systems and their malfunction that may underlie some neurological diseases. Although much remains to be investigated, these new discoveries have changed our understanding of mechanisms underlying CNS immune privilege and CNS drainage. -
Astrocytes in Alzheimer's Disease: Pathological Significance
cells Review Astrocytes in Alzheimer’s Disease: Pathological Significance and Molecular Pathways Pranav Preman 1,2,† , Maria Alfonso-Triguero 3,4,†, Elena Alberdi 3,4,5, Alexei Verkhratsky 3,6,7,* and Amaia M. Arranz 3,7,* 1 VIB Center for Brain & Disease Research, 3000 Leuven, Belgium; [email protected] 2 Laboratory for the Research of Neurodegenerative Diseases, Department of Neurosciences, Leuven Brain Institute (LBI), KU Leuven (University of Leuven), 3000 Leuven, Belgium 3 Achucarro Basque Center for Neuroscience, 48940 Leioa, Spain; [email protected] (M.A.-T.); [email protected] (E.A.) 4 Department of Neurosciences, Universidad del País Vasco (UPV/EHU), 48940 Leioa, Spain 5 Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), 48940 Leioa, Spain 6 Faculty of Biology, Medicine and Health, University of Manchester, Manchester M13 9PT, UK 7 Ikerbasque Basque Foundation for Science, 48009 Bilbao, Spain * Correspondence: [email protected] (A.V.); [email protected] (A.M.A.) † These authors contributed equally to this paper. Abstract: Astrocytes perform a wide variety of essential functions defining normal operation of the nervous system and are active contributors to the pathogenesis of neurodegenerative disorders such as Alzheimer’s among others. Recent data provide compelling evidence that distinct astrocyte states are associated with specific stages of Alzheimer´s disease. The advent of transcriptomics technologies enables rapid progress in the characterisation of such pathological astrocyte states. In this review, Citation: Preman, P.; Alfonso-Triguero, M.; Alberdi, E.; we provide an overview of the origin, main functions, molecular and morphological features of Verkhratsky, A.; Arranz, A.M. -
The Brain's Waste-Removal System
Cerebrum August 2018 The Brain’s Waste-Removal System By Helene Benveniste, M.D., Ph.D. Source/Shutterstock Editor’s Note: The brain, like other parts of the body, needs to maintain “homeostasis” (a constant state) to function, and that requires continuous removal of metabolic waste. For decades, the brain’s waste-removal system remained a mystery to scientists. A few years ago, a team of researchers—with the help of our author—finally found the answer. This discovery—dubbed the glymphatic system— will help us understand how toxic waste accumulates in devastating disorders such as Alzheimer’s disease and point to possible strategies to prevent it. In early February 2012, I received a note from Maiken Nedergaard, a renowned neuroscientist at the University of Rochester whom I knew from our time as medical students at the University of 1 Cerebrum August 2018 Copenhagen. She explained that her team had discovered important features of a new system that transports the fluid that surrounds the brain—a substance called cerebrospinal fluid (CSF). The discovery of how this fluid was transported in the brain, she believed, was the key to understanding how waste is cleared from the brain. Nedergaard’s work with the non-neuronal brain cells called “astroglia” had led her to suspect that these cells might play a role in CSF transport and brain cleansing. She was inspired by an older study' which showed that CSF could rapidly penetrate into channels along the brain vasculature, and astroglial cells structurally help create these channels. Now she needed help with visualizing the system in the whole brain to confirm her suspicions. -
Aquaporin-4 Dependent Glymphatic Solute Transport in Rodent Brain
bioRxiv preprint doi: https://doi.org/10.1101/216499; this version posted November 9, 2017. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Aquaporin-4 dependent glymphatic solute transport in rodent brain Humberto Mestre1*, Benjamin T. Kress1*, Wenyan Zou2*, Tinglin Pu2*, Giridhar Murlidharan3*, Ruth M. Castellanos Rivera3*, Matthew J. Simon4*, Martin M. Pike6*, Benjamin A Plog1, Anna L. R. Xavier7, Alexander S. Thrane7,8 Iben Lundgaard9,1, John H. Thomas10, Ming Xiao2,±, Aravind Asokan3, ±, Jeffrey J. Iliff5,11,±, Maiken Nedergaard1, 2, ± 1Center for Translational Neuromedicine, University of Rochester Medical Center, Elmwood Avenue 601, Rochester, NY 14642, USA, 2Jiangsu Province Key Laboratory of Neurodegeneration, Nanjing Medical University, 101 Longmian Avenue, Jiangning District, Nanjing, Jiangsu, 211166, P. R. China, 3Gene Therapy Center, 5123 Thurston Building, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7352, USA, 5Department of Anesthesiology and Perioperative Medicine, 4Oregon Health & Science University 3181 SW Sam Jackson Park Rd. Mail Code L458; Portland, OR 97229, USA, 6Advanced Imaging Research Center, Oregon Health & Science University, Oregon Health & Science University 3181 SW Sam Jackson Park Rd. Mail Code L458; Portland, OR 97229, USA, 6 Center for Translational Neuromedicine, Faculty of Medical and Health Sciences, University of Copenhagen, Denmark, Blegdamsvej 3B, 2200 Copenhagen N, Denmark,7Department of Ophthalmology, Haukeland University Hospital, Jonas Lies Vei 72, 5021 Bergen, Norway 0047 55974100, 8Department of Experimental Medical Science, Wallenberg Centre for Molecular Medicine, Lund University, Sölvegatan 19, 221 84 Lund, Sweden, 9Department of Mechanical Engineering and Department of Physics & Astronomy, University of Rochester, Rochester, NY 14627, USA, 10Knight Cardiovascular Institute, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd. -
Physiology of Neuronalâ
Neurochemistry International 57 (2010) 332–343 Contents lists available at ScienceDirect Neurochemistry International journal homepage: www.elsevier.com/locate/neuint Physiology of neuronal–glial networking Alexei Verkhratsky a,b,* a Faculty of Life Sciences, The University of Manchester, Oxford Road, Manchester, UK b Institute of Experimental Medicine, ASCR, Prague, Czech Republic ARTICLE INFO ABSTRACT Article history: Neuronal–glial networks are the substrate for the brain function. Evolution of the nervous system Received 5 November 2009 resulted in the appearance of highly specialized neuronal web optimized for rapid information transfer. Received in revised form 5 January 2010 This neuronal web is embedded into glial syncytium, thereby creating sophisticated neuronal–glial Accepted 1 February 2010 circuitry were both types of neural cells are working in concert, ensuring amplification of brain Available online 6 February 2010 computational power. In addition neuroglial cells are fundamental for control of brain homeostasis and they represent the intrinsic brain defence system, being thus intimately involved in pathogenesis of Keywords: neurological diseases. Glia ß 2010 Elsevier Ltd. All rights reserved. Astrocytes Glutamate receptors Purinoceptors Neuronal–glial signalling How does the brain work? How did the intellect evolved? Why 1. Neuronal–glial circuits form the nervous system human being is so different from the beast? How do we think? These questions represent the most formidable challenge the 1.1. Neuroglia: the beginning natural sciences ever faced. The evolution of the nervous functions went from single neurones loosely connected into the diffuse The cell, as the basic unit of the life, was initially discovered by nervous system through the first conglomerates of neural cells Robert Hooke (who also contemplated the name) in 1665 (Hooke, assembled into ganglia to the centralized nervous system. -
Chapter 1. History of Astrocytes
CHAPTER 1 History of Astrocytes OUTLINE Overview 2 Camillo Golgi 16 Naming of the “Astrocyte” 18 Neuron Doctrine 2 Santiago Ramón y Cajal and Glial Purkinje and Valentin’s Kugeln 2 Functions 18 Scheiden, Schwann, and Cell Theory 3 Glial Alterations in Neurological Remak’s Remarkable Observation 4 Disease: Early Concepts 21 The Neurohistology of Robert Bentley Todd 5 Wilder Penfield, Pío Del Río-Hortega, Wilhelm His’ Seminal Contributions 7 and Delineation of the Fridtjof Nansen: The Renaissance Man 8 “Third Element” 22 Auguste Forel: Neurohistology, Penfield’s Idea to Go to Spain 24 Myrmecology, and Sexology 8 Types of Neuroglia 26 Rudolph Albert Von Kölliker: Penfield’s Description of Oligodendroglia 27 Neurohistologist and Cajal Champion 10 Coming Together: The Fruit of Penfield’s Waldeyer and the Neuronlehre Spanish Expedition 30 (Neuron Doctrine) 11 Beginning of the Modern Era 33 Conclusion 12 References 34 Development of the Concept of Neuroglia 12 Rudolf Virchow 12 Other Investigators Develop More Detailed Images of Neuroglial Cells 15 Astrocytes and Epilepsy DOI: http://dx.doi.org/10.1016/B978-0-12-802401-0.00001-6 1 © 2016 Elsevier Inc. All rights reserved. 2 1. HIStorY OF AStrocYTES OVERVIEW In this introduction to the history of astrocytes, we wish to accomplish the following goals: (1) contextualize the evolution of the concept of neuroglia within the development of cell theory and the “neuron doctrine”; (2) explain how the concept of neuroglia arose and evolved; (3) provide an interesting overview of some of the investigators involved in defin- ing the cell types in the central nervous system (CNS); (4) select the interaction of Wilder Penfield and Pío del Río-Hortega for a more in-depth historical vignette portraying a critical period during which glial cell types were being identified, described, and separated; and (5) briefly summarize further developments that presaged the modern era of neurogliosci- ence. -
Astrocytes Alive!
ColloquiumColloquium Astrocytes alive! Maiken Nedergaard, M.D., D.M.Sc. Co-Director - Center for Translational Neuromedicine Professor - Center for Translational Neuromedicine Professor - Department of Biomedical Engineering Professor - Department of Neurobiology and Anatomy 3:00 pm, Monday, December 8, 2008 University of Rochester Sloan Auditorium, Goergen Building DMSc Neuroscience University of Copenhagen 1988 MD Medicine University of Copenhagen 1983 Refreshments provided The lecture will describe how advances in optical imaging allow us for the first time to study the function of electrically non-excitable cell types in brain. Astrocytes Alive! Maiken Nedergaard, M.D., D.M.Sc. University of Rochester Medical Center Abstract The lecture will describe how advances in optical imaging allow us for the first time to study the function of electrically non-excitable cell types in brain. Traditionally, neuroscience has used electrophysiology approaches and thereby overlooked astrocytes – the primary non-excitable cell type in brain. Astrocytes are more numerous than neurons in the adult human brain. It is therefore of considerable interest to define their roles in higher brain function and neurological diseases. Biography Current Appointments * Co-Director - Center for Translational Neuromedicine * Professor - Center for Translational Neuromedicine * Professor - Department of Biomedical Engineering * Professor - Department of Neurobiology and Anatomy Education DMSc Neuroscience University of Copenhagen 1988 MD Medicine University of Copenhagen -
Neurotropic Viruses, Astrocytes, and COVID-19
fncel-15-662578 April 3, 2021 Time: 12:32 # 1 REVIEW published: 09 April 2021 doi: 10.3389/fncel.2021.662578 Neurotropic Viruses, Astrocytes, and COVID-19 Petra Tavcarˇ 1, Maja Potokar1,2, Marko Kolenc3, Miša Korva3, Tatjana Avšic-Župancˇ 3, Robert Zorec1,2* and Jernej Jorgacevskiˇ 1,2 1 Laboratory of Neuroendocrinology–Molecular Cell Physiology, Institute of Pathophysiology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia, 2 Celica Biomedical, Ljubljana, Slovenia, 3 Institute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia At the end of 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV- 2) was discovered in China, causing a new coronavirus disease, termed COVID-19 by the WHO on February 11, 2020. At the time of this paper (January 31, 2021), more than 100 million cases have been recorded, which have claimed over 2 million lives worldwide. The most important clinical presentation of COVID-19 is severe pneumonia; however, many patients present various neurological symptoms, ranging from loss of olfaction, nausea, dizziness, and headache to encephalopathy and stroke, with a high prevalence of inflammatory central nervous system (CNS) syndromes. SARS-CoV-2 may Edited by: also target the respiratory center in the brainstem and cause silent hypoxemia. However, Alexei Verkhratsky, the neurotropic mechanism(s) by which SARS-CoV-2 affects the CNS remain(s) unclear. The University of Manchester, United Kingdom In this paper, we first address the involvement of astrocytes in COVID-19 and then Reviewed by: elucidate the present knowledge on SARS-CoV-2 as a neurotropic virus as well as Arthur Morgan Butt, several other neurotropic flaviviruses (with a particular emphasis on the West Nile virus, University of Portsmouth, tick-borne encephalitis virus, and Zika virus) to highlight the neurotropic mechanisms United Kingdom Alexey Semyanov, that target astroglial cells in the CNS. -
Meningeal Lymphangiogenesis and Enhanced Glymphatic Activity in Mice with Chronically Implanted EEG Electrodes
Research Articles: Neurobiology of Disease Meningeal lymphangiogenesis and enhanced glymphatic activity in mice with chronically implanted EEG electrodes https://doi.org/10.1523/JNEUROSCI.2223-19.2020 Cite as: J. Neurosci 2020; 10.1523/JNEUROSCI.2223-19.2020 Received: 14 September 2019 Revised: 27 December 2019 Accepted: 22 January 2020 This Early Release article has been peer-reviewed and accepted, but has not been through the composition and copyediting processes. The final version may differ slightly in style or formatting and will contain links to any extended data. Alerts: Sign up at www.jneurosci.org/alerts to receive customized email alerts when the fully formatted version of this article is published. Copyright © 2020 the authors 1 Title: Meningeal lymphangiogenesis and enhanced glymphatic activity in mice with chronically 2 implanted EEG electrodes 3 Abbr. title: Reactive response to chronic EEG electrodes 4 5 Authors: Natalie L. Hauglund1, Peter Kusk1, Birgitte R. Kornum2, Maiken Nedergaard1,3 6 Affiliations: 1Center for Translational Neuromedicine, Faculty of Health and Medical Sciences, University of 7 Copenhagen, 2200 Copenhagen, Denmark 8 2 Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark 9 3Center for Translational Neuromedicine, University of Rochester Medical Center, Rochester, NY 14642, USA 10 11 Corresponding author: Maiken Nedergaard, [email protected] 12 13 Number of pages: 31 14 Number of figures: 4 15 Number of words for abstract: 198 16 Number of words for introduction: 523 17 Number of words for discussion: 1371 18 19 Conflict of interest: The authors declare no competing financial interests. 20 21 Acknowledgement: The study was supported by the Novo Nordisk Foundation, the Lundbeck Foundation, 22 and the Adelson Medical Research Foundation.