Astroglia and Brain Metabolism

Astroglia and Brain Metabolism

Arne Schousboe, Anne B. Walls, Lasse K. Bak, Helle S. Waagepetersen
ISBN: 9781615047123 | PDF ISBN: 9781615047130
Copyright © 2015 | 64 Pages | Publication Date: July, 2015

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The present outline of astrocytic metabolic pathways involved in glucose and amino acid metabolism provides detailed information about the enzymatic pathways involved, as well as a description of the basic properties of the enzymes including regulatory mechanisms. Hence, the glycolytic pathway and glycogen metabolism are outlined, followed by a detailed account of pyruvate oxidation and its role as a substrate for the tricarboxylic acid (TCA) cycle. Moreover, a detailed description of the main enzymes involved in glutamate metabolism is provided and the role of the glutamate-glutamine cycle is explained. Since this text is primarily covering astrocytic metabolism, an emphasis has been placed on a discussion of the significance of the astrocyte specific enzymes pyruvate carboxylase and glutamine synthetase, which enable these cells to perform a net synthesis of glutamine, the precursor for synthesis of glutamate and y-aminobutyrate (GABA), the main neurotransmitters of the brain. With this, we have underlined the fundamental importance of astrocytic metabolism for neuronal function with a particular emphasis on the fact that, without continuous support from the astrocytic partners in synaptic function, glutamatergic and GABAergic neurotransmission would not be possible. It is thought provoking that these neurotransmission processes, which account for the vast majority of synaptic activity in the brain, have been made totally dependent on astrocytic metabolic support, particularly with regard to replenishment of the respective neurotransmitters.

Table of Contents

Introduction of Glia
Metabolism of Glia
Concluding Remarks
References
Author Biographies

About the Author(s)

Arne Schousboe, Faculty of Health and Medical Sciences, University of Copenhagen
Arne Schousboe obtained a Ph. D. in biochemistry from the University of Copenhagen in 1968 and, after a short period as Assistant Professor at the University of Copenhagen, he completed a post-doc period (January 1972-September 1973) with Dr. Eugene Roberts at the Department of Neuroscience, City of Hope National Medical Center in Los Angeles. He subsequently joined the University of Copenhagen to resume a tenured position as Associate Professor in the Medical Faculty there and in 1978 he got his doctorate in science (D. Sc.) from the University of Copenhagen. In 1990 he moved to the Royal Danish School of Pharmacy as a Full Professor of biochemistry. This institution has subsequently become a part of the Faculty of Health and Medical Sciences at the University of Copenhagen. He served as Department Chair from 2005-2010 and is now a part-time Professor of Neuropharmacology at the Department of Drug Design and Pharmacology at this Faculty. He has been working on astrocyte function, focusing on amino acid neurotransmission, for more than 4o years and is currently engaged in studies of glutamate and GABA homeostasis and metabolism. He has published over 550 papers on these topics. He has served on the editorial boards of numerous neuroscience journals over the years and is currently the Editor-in-Chief of Neurochemical Research and editor of the book series Advances in Neurobiology.

Anne B. Walls, Faculty of Health and Medical Sciences, University of Copenhagen
Anne B. Walls, Ph.D., is a postdoc researcher at the University of Copenhagen. She obtained her M.Sc. in Pharmacy from the Danish University of Pharmaceutical Sciences, Copenhagen, Denmark, in 2006 and her Ph.D. from the Norwegian University of Science and Technology (NTNU), Trondheim, Norway, in 2010. Her interest in brain energy metabolism and the cellular interplay between astrocytes and neurons was founded in her thesis work conducted in the lab of Prof. Helle S. Waagepetersen and Prof. Arne Schousboe, where she studied the functional importance of brain glycogen. This work continued during her Ph.D. studies in the lab of Prof. Ursula Sonnewald and, at the same time, a special interest in the functional and metabolic importance of the inhibitory neurotransmitter GABA in relation to seizure activity was established. In 2010 she obtained an individual postdoc grant from the Danish Medical Research Council to study the importance of glycogen as energy substrate and precursor for GABAergic signaling and, in 2014, she received another individual postdoc grant from The Lundbeck Foundation to investigate the role of the enzyme glutamate dehydrogenase (GDH) for ammonia fixation in the brain during hyperammonemia and hepatic encephalopathy. Since 2013, she has served as an editorial board member for Metabolic Brain Disease and, together with Prof. Arne Schousboe, has been a guest editor on a special issue of Metabolic Brain Disease on Brain Glycogen: Emergency Fuel and Dynamic Function in Neurotransmission, published in February 2015.

Lasse K. Bak, Faculty of Health and Medical Sciences, University of Copenhagen
Lasse K. Bak, Ph.D., is an associate professor at the Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen. His main field of research is the coupling between brain cell signaling events mediated by cAMP and calcium, and the functional and metabolic responses they elicit. He has published more than 50 scientific peer-reviewed papers, reviews, and book chapters.

Helle S. Waagepetersen, Faculty of Health and Medical Sciences, University of Copenhagen
Helle S. Waagepetersen is Full Professor of Cellular Neuropharmacology at the Department of Drug Design and Pharmacology, University of Copenhagen. She has served as Handling Editor of the Journal of Neurochemistry and is a member of several editorial boards. Professor Waagepetersen has received the European Society of Neurochemistry Young Lectureship Award. She has published a total of 120 peer-reviewed papers, reviews, book chapters, and books within the area of brain energy metabolism. Professor Waagepetersen is employing primary mouse cell culture systems of neurons and astrocytes. In addition, brain slices, isolated mitochondria, and cell lines are applied as model systems. An array of 3H, 15N, and 13C isotopes is utilized in the mapping of metabolic pathways and cellular metabolic interactions and trafficking of metabolites in health and disease. HPLC, mass spectrometry, and 13C NMR are key analytical tools combined with biochemical assays, molecular biology, and fluorescence-based assays and imaging techniques.

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