Brain Glycogen Metabolism

440 Pages·2019·13.818 MB·English

by  Mauro DiNuzzo, Arne Schousboe

Advances in Neurobiology 23
Mauro DiNuzzo
Arne Schousboe E ditors
Brain
Glycogen
Metabolism
Advances in Neurobiology
Volume 23
Series Editor
Arne Schousboe
More information about this series at http://www.springer.com/series/8787
Mauro DiNuzzo • Arne Schousboe
Editors
Brain Glycogen Metabolism
Editors
Mauro DiNuzzo Arne Schousboe
Center for Basic and Translational Faculty of Health and Medical Sciences
Neuroscience University of Copenhagen
University of Copenhagen Copenhagen, Denmark
Copenhagen, Denmark
ISSN 2190-5215 ISSN 2190-5223 (electronic)
Advances in Neurobiology
ISBN 978-3-030-27479-5 ISBN 978-3-030-27480-1 (eBook)
https://doi.org/10.1007/978-3-030-27480-1
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Preface
Glycogen is the sole carbohydrate reserve of the brain. Glycogen granules are
located in astrocytic processes surrounding neuronal elements, where they can be
readily mobilized at times of increased energy need (e.g., during sensory stimula-
tion) or energy failure (e.g., when blood glucose supply is inadequate). Remarkably,
the long-held concept that brain glycogen serves solely as an emergency depot has
been recently displaced by numerous, unequivocal, and fundamental observations
that related its utilization to the support of cognitive functions. Any interference
with brain glycogen metabolism affects neurophysiology at multiple hierarchical
scales, including cellular (e.g., astrocyte-neuron interactions), network (e.g., neuro-
nal excitability), and system (e.g., learning and memory) levels. Not surprisingly,
specific forms of glycogen storage disease are associated with mental retardation,
and glycogen has been implicated in aging and several pathological conditions,
such as epilepsy, diabetes, and dementia. Glycogen turnover is under dynamic con-
trol by neurotransmitters, neuromodulators, and extracellular potassium, or put sim-
ply, brain activity.
It goes without saying that this seemed to us a particularly good time to have a
book about brain glycogen. While many books have been published about energy
metabolism in the central nervous system, none has focused specifically on brain
glycogen. Cerebral glycogen metabolism is only briefly touched upon in many neu-
roscience books, and, with the exception of a couple of special issues, there is a
substantial lack of journal titles centered on brain glycogen. It is our opinion that
brain glycogen research is more than mature to have a dedicated book. Our idea of
such a book has been that of providing an unbiased state-of-the-art summary about
the current knowledge of brain glycogen metabolism. The underlying principal aim
has been to allow the reader appreciating how the relatively small cerebral glycogen
content is so crucial for normal brain function, thereby, fundamentally revisiting the
vestigial nature commonly associated with the polysaccharide in the brain. As such,
the book fills a gap in current literature. Leading international experts have contrib-
uted up-to-date accounts of cerebral glycogen metabolism, covering the most
important progresses obtained in the last 25 years. Our intent has been to be as
inclusive as possible, especially for the topics that are still without any apparent
v
vi Preface
consensus. Indeed, while there is no doubt that glycogen is essential to brain func-
tion, there are ongoing debates about the relevant biochemical mechanisms. Thus,
opposite views normally found as sealed-off compartments in scientific publica-
tions finally could coexist in one place. The book chapters accordingly discuss dif-
ferent potential fates for glycogen-derived metabolites and related metabolic
pathways that might be implicated in supporting the energetics of neurons and glial
cells. Some chapters review the metabolic and functional features of brain glycogen
as well as of the brain-specific enzyme isoforms that synthetize and degrade the
polysaccharide, which are exquisitely sensitive to small and physiological energy
fluctuations. Other chapters cover the localization of glycogen in different brain
structures and the relevant metabolic aspects in either white or gray matter. Several
chapters describe how physiological and pathological conditions affect glycogen
metabolism in the brain. The book also includes historical perspectives that outline
how brain glycogen has progressively gained attention as an essential player in cere-
bral energy metabolism. We believe that the material contained in the book consti-
tutes a good reference about brain glycogen metabolism, which holds a great
potential for stimulating further research.
We express our sincere gratitude to all the authors of the book, and we are more
than confident that many others will join us, including undergraduate and graduate
students as well as researchers and professionals working with or interested in brain
glycogen metabolism. All these people will benefit from having the current knowl-
edge of the field at hand. We also thank Springer Science for the continuous support
and helpful insights throughout all the stages of putting this work together. Finally,
we wish to acknowledge the invited researchers who could not participate to the
present endeavor, as many among them have had a pivotal role in developing new
ideas and performing critical experiments that advanced the field of brain glycogen
metabolism. We hope to have given their work the appropriate credit within the vari-
ous chapters of the book. One of these researchers is our friend Leif Hertz (1930–
2018), to whose memory this book is dedicated.
Copenhagen, Denmark Mauro DiNuzzo
Arne Schousboe
Contents
Major Advances in Brain Glycogen Research: Understanding
of the Roles of Glycogen Have Evolved from Emergency Fuel Reserve
to Dynamic, Regulated Participant in Diverse Brain Functions . . . . . . . . 1
Gerald A. Dienel and Gerald M. Carlson
Brain Glycogen Structure and Its Associated Proteins:
Past, Present and Future . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
M. Kathryn Brewer and Matthew S. Gentry
Structure and Regulation of Glycogen Synthase in the Brain . . . . . . . . . . 83
Bartholomew A. Pederson
The Structure and the Regulation of Glycogen
Phosphorylases in Brain . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 125
Cécile Mathieu, Jean-Marie Dupret, and Fernando Rodrigues-Lima
Regional Distribution of Glycogen in the Mouse
Brain Visualized by Immunohistochemistry . . . . . . . . . . . . . . . . . . . . . . . . 147
Yuki Oe, Sonam Akther, and Hajime Hirase
Technical and Comparative Aspects of Brain Glycogen Metabolism . . . . 169
Long Wu, Nicholas J. M. Butler, and Raymond A. Swanson
Metabolism of Glycogen in Brain White Matter . . . . . . . . . . . . . . . . . . . . . 187
Angus M. Brown, Laura R. Rich, and Bruce R. Ransom
Glycogenolysis in Cerebral Cortex During Sensory Stimulation,
Acute Hypoglycemia, and Exercise: Impact on Astrocytic
Energetics, Aerobic Glycolysis, and Astrocyte-Neuron Interactions . . . . . 209
Gerald A. Dienel and Douglas L. Rothman
vii
viii Contents
State-Dependent Changes in Brain Glycogen Metabolism . . . . . . . . . . . . . 269
Mauro DiNuzzo, Anne B. Walls, Gülin Öz, Elizabeth R. Seaquist,
Helle S. Waagepetersen, Lasse K. Bak, Maiken Nedergaard,
and Arne Schousboe
Glycogen in Astrocytes and Neurons: Physiological
and Pathological Aspects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 311
Jordi Duran, Agnès Gruart, Juan Carlos López-Ramos,
José M. Delgado- García, and Joan J. Guinovart
Endurance and Brain Glycogen: A Clue Toward Understanding
Central Fatigue . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 331
Takashi Matsui, Mariko Soya, and Hideaki Soya
Role of Brain Glycogen During Ischemia, Aging and Cell-to-Cell
Interactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 347
Chinthasagar Bastian, John Quinn, Christine Doherty, Caroline Franke,
Anna Faris, Sylvain Brunet, and Selva Baltan
Dysregulation of Glycogen Metabolism with Concomitant
Spatial Memory Dysfunction in Type 2 Diabetes:
Potential Beneficial Effects of Chronic Exercise . . . . . . . . . . . . . . . . . . . . . 363
Mariko Soya, Subrina Jesmin, Takeru Shima, Takashi Matsui,
and Hideaki Soya
Development of a Model to Test Whether Glycogenolysis
Can Support Astrocytic Energy Demands of Na+, K+-ATPase
and Glutamate- Glutamine Cycling, Sparing an Equivalent
Amount of Glucose for Neurons . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 385
Douglas L. Rothman and Gerald A. Dienel
Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 435
Major Advances in Brain Glycogen
Research: Understanding of the Roles
of Glycogen Have Evolved
from Emergency Fuel Reserve to Dynamic,
Regulated Participant in Diverse Brain
Functions
Gerald A. Dienel and Gerald M. Carlson
Abstract Brain glycogen is extremely difficult to study because it is very labile to
physiological status and postmortem autolysis, and glycogen degradative enzymes
are rapidly activated by metabolites and signaling molecules. Glycogen is predomi-
nantly located within astrocytes in adult brain, and abnormal glycogen metabolism
in neurons has lethal consequences. Diverse distribution of glycogen among subcel-
lular compartments suggests local regulation and different functional roles, and
recent studies have revealed critically important roles for glycogen in normal brain
function and Lafora disease. This brief overview highlights some of the major
advances in elucidation of glycogen’s roles in astrocytic functions and neurotrans-
mission and the severe consequences of aberrant neuronal glycogen metabolism.
Keywords Astrocyte · Brain · Glycogen · Glycogen debranching enzyme ·
Glycogen granule · Glycogen phosphorylase · Phosphorylase kinase · Lafora
disease (Lafora progressive myoclonic epilepsy, MELF) · Neuron ·
Neurotransmission
G. A. Dienel (*)
Department of Neurology, University of Arkansas for Medical Sciences,
Little Rock, AR, USA
Department of Cell Biology and Physiology, University of New Mexico,
Albuquerque, NM, USA
e-mail: [email protected]
G. M. Carlson
Department of Biochemistry and Molecular Biology, University of Kansas Medical Center,
Kansas City, KS, USA
e-mail: [email protected]
© Springer Nature Switzerland AG 2019 1
M. DiNuzzo, A. Schousboe (eds.), Brain Glycogen Metabolism, Advances in
Neurobiology 23, https://doi.org/10.1007/978-3-030-27480-1_1
2 G. A. Dienel and G. M. Carlson
Abbreviations
cAMP cyclic AMP
CMR Cerebral metabolic rate for glucose
glc
CMR Cerebral metabolic rate for oxygen
O2
Glc Glucose
Glc-6-P Glucose-6-phosphate
KO Knockout
1 Introduction
Studies on glycogen metabolism in liver, where it contributes to maintenance of
blood glucose, and in muscle, where it supplies energy to sustain contraction, have
a long and illustrious history, and many luminaries of science have worked on this
polyglucan. Glycogen was discovered in the nineteenth century (1857) by the great
physiologist Claude Bernard, who for decades investigated mammalian sugar
metabolism (Young 1957). The following year, August Kekulé, a key figure in
developing a structural theory of organic chemistry, accurately determined glyco-
gen’s empirical formula to be CH O (Young 1957), consistent with a polymer of
6 10 5
glucose linked via glycosidic bonds. In the twentieth century, work on glycogen
metabolism continued, and directly resulted in six Nobel Prizes. At the level of
enzymes that act directly on glycogen, Carl and Gerty Cori were awarded (1947) the
honor for their work on glycogen phosphorylase, whereas Luis Leloir received the
award (1970) for his studies on glycogen synthase. For regulatory aspects of the
cascade activation of glycogenolysis, Earl Sutherland was honored (1971) for iden-
tifying cAMP as the second messenger linking epinephrine to the activation of gly-
cogen phosphorylase. Finally, their discovery of the stimulation of the catalytic
activity of glycogen phosphorylase and phosphorylase kinase through post-
translational phosphorylation resulted in the award being presented (1992) to
Edmond Fischer and Edwin Krebs. Studies of glycogen metabolism in the twenty
first century have been steadily expanding, however, from muscle and liver into the
brain, where glycogen seems to play different and sometimes surprising roles.
As an important energy reserve in brain, glycogen is predominantly localized in
astrocytes, with very small amounts in neurons. Regulation of astrocytic glycoge-
nolysis by neurotransmitters integrates astrocytic metabolism with neuronal signal-
ing, and dysregulation of glycogen turnover causes severe epilepsy and, ultimately,
death of patients with Lafora disease. Glycogen fuels K+ uptake into cultured astro-
cytes in the presence of adequate levels of glucose, revealing a role in the energetics
of control of the extracellular ionic milieu during neurotransmission. Astrocytic gly-
cogen mobilization during brain activation can also spare blood-borne glucose for
use by neurons as energy demand is increased. Glycogenolysis is required for learn-
ing and memory consolidation, but the mechanisms remain to be established.
Putative functions (that are not mutually exclusive) include fuel for astrocytes,