J Neuro Res. 2019;97:923–932. wileyonlinelibrary.com/journal/jnr
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923 © 2019 Wiley Periodicals, Inc.
1 | INTRODUCTION
The mammalian brain consumes a significant portion of the total
body energy. In humans, while occupying a mere 2% of the body
mass, the brain consumes up to 20% of the total body energy (Clarke
& Sokoloff, 1999). Evidently, it is of prime importance to secure a
stable supply of energy substrate to the brain. Glucose is the prime
energy substrate in the brain and is constantly supplied by the blood.
Hypo‐ or hyper‐glycemia results in malfunctioning of the brain and
leads to loss of consciousness, as seen in diabetes mellitus. After
taken up from the blood to a cell, glucose is converted to pyruvate
for further energy metabolism.
In mammalian cells, glucose can also be stored as glycogen, a
highly branched polysaccharide that is readily broken down into
glucose phosphate to meet metabolic demands. The functional role
of cellular glycogen storage as an intermediate energy reservoir
is well‐established in peripheral organs. For instance, in the liver,
monosaccharides are supplied by the blood from the small intestine
and eventually stored into glycogen. Hepatic glycogen serves as a
buffer to sustain healthy levels of blood glucose (e.g., 90–130 mg/dl
in humans). Excess glucose is stored in hepatocytes as glycogen, and
glycogenolysis occurs to secrete glucose to the blood upon events of
low blood glucose level. These operations are mediated by the pan‐
creas through insulin and glucagon signaling, respectively. In skeletal
muscles, glycogen is mobilized as an initial phosphocreatine pool is
depleted upon events of prolonged muscle contraction. Interestingly,
while the liver and muscles are the two major sources of glycogen
storage representing approximately 100 g (5%–6% of the organs
fresh weight) and 400–500 g (1%–2% of muscle mass) of glycogen,
Received: 17 November 2018
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Revised: 4 January 2019
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Accepted: 7 January 2019
DOI: 10.1002/jnr.24386
MINIREVIEW
Glycogen distribution in mouse hippocampus
Hajime Hirase
1,2,3
* | Sonam Akther
1,2
* | Xiaowen Wang
1
| Yuki Oe
1
*HH and SA contributed equally to this article.
1
RIKEN Center for Brain Science, Wako,
Japan
2
Saitama University Brain Science Institute,
Saitama, Japan
3
Center for Translational Neuromedicine,
Faculty of Medical and Health
Sciences, University of Copenhagen,
Copenhagen, Denmark
Correspondence
Hajime Hirase and Yuki Oe, RIKEN Center
for Brain Science, Wako, Saitama, Japan.
Emails: hajime.hirase@riken.jp; yuki.oe@
riken.jp
Funding information
Japan Society for the Promotion of
Science, Grant/Award Number: KAKENHI
16H01888, 16K10738, and 18H05150;
Human Frontier Science Program, Grant/
Award Number: RGP0036/2014; Lundbeck
Foundation Visiting Professorship ‐
Lundbeck Foundation
Correction added on February 12, 2019,
after first online publication: Funding
information text have been changed from
‘Lundbeck Foundation Professorship
‐ Lundbeck Foundation’ to ‘Lundbeck
Foundation Visiting Professorship ‐
Lundbeck Foundation’.
Abstract
The hippocampus is a limbic structure involved in the consolidation of episodic mem‐
ory. In the recent decade, glycogenolysis in the rodent hippocampus has been shown
critical for synaptic plasticity and memory formation. Astrocytes are the primary
cells that store glycogen which is subject to degradation in hypoglycemic conditions.
Focused microwave application to the brain halts metabolic activities, and therefore
preserves brain glycogen. Immunohistochemistry against glycogen on focused mi‐
crowave‐assisted brain samples is suitable for both macroscopic and microscopic in‐
vestigation of glycogen distribution. Glycogen immunohistochemistry in the
hippocampus showed a characteristic punctate signal pattern that depended on hip‐
pocampal layers. In particular, the hilus is the most glycogen‐rich subregion of the
hippocampus. Moreover, large glycogen puncta (>0.5 µm in diameter) observed in
neuropil areas are organized in a patchy pattern consisting of puncta‐rich and ‐poor
astrocytes. These observations are discussed with respect to distinct hippocampal
neural activity states observed in live animals.
KEYWORDS
astrocytes, glycogen, hippocampus, neuromodulators, potassium