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Endurance and Brain Glycogen: A Clue Toward Understanding Central Fatigue

Chapter
First Online:
Part of the Advances in Neurobiology book series (NEUROBIOL, volume 23)

Abstract

Brain glycogen stored in astrocytes produces lactate as a neuronal energy source transported by monocarboxylate transporters (MCTs) to maintain neuronal functions, such as hippocampus-regulated memory formation. Although exercise activates brain neurons, the role of astrocytic glycogen in the brain during exercise remains unknown. Since muscle glycogen fuels active muscles during exercise, we hypothesized that astrocytic glycogen plays an energetic role in the brain during exercise to maintain endurance capacity through lactate transport. To explore this hypothesis, we have used a rat model of prolonged exercise, microwave irradiation for the accurate detection of brain glycogen, capillary electrophoresis-mass spectrometry-based metabolomics, and inhibitors of glycogenolysis (1,4-dideoxy-1,4-imino-d-arabinitol; DAB) and lactate transport (α-cyano-4-hydroxycinnamate; 4-CIN). During prolonged exhaustive exercise, muscle glycogen was depleted and brain glycogen decreased when associated with decreased blood glucose levels and increased serotonergic activity known as central fatigue factors, suggesting brain glycogen decrease as an integrative factor for central fatigue. Prolonged exhaustive exercise also increased MCT2 protein in the brain, which takes up lactate in neurons, just as muscle MCTs are increased. Metabolomics revealed that brain but not muscle adenosine triphosphate (ATP) was maintained with lactate and other glycogenolytic and glycolytic sources. Intracerebroventricular (icv) injection of DAB suppressed brain lactate production and decreased hippocampal ATP levels at exhaustion. An icv injection of 4-CIN also decreased hippocampal ATP, resulting in lower endurance capacity. Our findings provide direct evidence that astrocytic glycogen-derived lactate fuels the brain to maintain endurance capacity during exhaustive exercise. Brain ATP levels maintained by glycogen might serve as a possible defense mechanism for neurons in the exhausted state.

Keywords

Endurance exercise Central fatigue Brain glycogen Lactate Metabolomics 

Abbreviations

4-CIN

α-Cyano-4-hydroxycinnamate

5-HIAA

5-Hydroxyindoleacetic acid

5-HT

5-Hydroxytryptamine (serotonin)

AAA

Aromatic amino acid

AMP

Adenosine monophosphate

ATP

Adenosine triphosphate

BCAA

Branched-chain amino acid

DAB

1,4-Dideoxy-1,4-imino-d-arabinitol

F1-6P

Fructose-1, 6-bisphosphate

fMRI

Functional magnetic resonance imaging

GLUT

Glucose transporter

icv

Intracerebroventricular

IMP

Inosine monophosphate

MCT

Monocarboxylate transporter

MHPG

Methoxyhydroxyphenylglycol

MI

Microwave irradiation

NA

Noradrenaline

PCr

Phosphocreatine

TCA

Tricarboxylic acid

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Notes

Acknowledgements

This research was supported in part by special funds for Education and Research from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) granted to the Human High Performance (HHP) Research Project; the Team “Nippon” Multi-Support project; grants from the Japan Society for the Promotion of Science (JSPS) to the Global Initiative for Sports Neuroscience (GISN): For Development of Exercise Prescription Enhancing Cognitive Functions; and JSPS Grants-in-Aid for Scientific Research A, Challenging Exploratory Research, JSPS Fellow (Superlative Post-Doc), and Young Scientist A.

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© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Sport Neuroscience Division, Faculty of Health and Sport SciencesAdvanced Research Initiative for Human High Performance (ARIHHP), University of TsukubaIbarakiJapan

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