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Endurance and Brain Glycogen: A Clue Toward Understanding Central Fatigue

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Brain Glycogen Metabolism

Part of the book series: Advances in Neurobiology ((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.

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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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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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Authors and Affiliations

  1. Sport Neuroscience Division, Faculty of Health and Sport Sciences, Advanced Research Initiative for Human High Performance (ARIHHP), University of Tsukuba, Ibaraki, Japan

    Takashi Matsui, Mariko Soya & Hideaki Soya

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  1. Takashi Matsui
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  2. Mariko Soya
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  3. Hideaki Soya
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Correspondence to Takashi Matsui or Hideaki Soya .

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Editors and Affiliations

  1. Center for Basic and Translational Neuroscience, University of Copenhagen, Copenhagen, Denmark

    Mauro DiNuzzo

  2. Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

    Arne Schousboe

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Matsui, T., Soya, M., Soya, H. (2019). Endurance and Brain Glycogen: A Clue Toward Understanding Central Fatigue. In: DiNuzzo, M., Schousboe, A. (eds) Brain Glycogen Metabolism. Advances in Neurobiology, vol 23. Springer, Cham. https://doi.org/10.1007/978-3-030-27480-1_11

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