# Effect of Exercise on Brain Health: The Potential Role of Lactate as a Myokine

**Authors:** Takeshi Hashimoto, Hayato Tsukamoto, Soichi Ando, Shigehiko Ogoh

PMC · DOI: 10.3390/metabo11120813 · Metabolites · 2021-11-29

## TL;DR

This paper reviews how exercise improves brain health, possibly through lactate acting as a signaling molecule.

## Contribution

The paper proposes lactate as a potential myokine mediating brain health benefits from exercise.

## Key findings

- Exercise improves brain health through mechanisms that include cerebral metabolism.
- Lactate may regulate cerebrovascular and redox states in response to exercise.
- High-intensity interval exercise is highlighted for its potential to boost lactate production for brain benefits.

## Abstract

It has been well established in epidemiological studies and randomized controlled trials that habitual exercise is beneficial for brain health, such as cognition and mental health. Generally, it may be reasonable to say that the physiological benefits of acute exercise can prevent brain disorders in late life if such exercise is habitually/chronically conducted. However, the mechanisms of improvement in brain function via chronic exercise remain incompletely understood because such mechanisms are assumed to be multifactorial, such as the adaptation of repeated acute exercise. This review postulates that cerebral metabolism may be an important physiological factor that determines brain function. Among metabolites, the provision of lactate to meet elevated neural activity and regulate the cerebrovascular system and redox states in response to exercise may be responsible for exercise-enhanced brain health. Here, we summarize the current knowledge regarding the influence of exercise on brain health, particularly cognitive performance, with the underlying mechanisms by means of lactate. Regarding the influence of chronic exercise on brain function, the relevance of exercise intensity and modality, particularly high-intensity interval exercise, is acknowledged to induce “metabolic myokine” (i.e., lactate) for brain health.

## Linked entities

- **Chemicals:** lactate (PubChem CID 61503)

## Full-text entities

- **Genes:** ARC (activity regulated cytoskeleton associated protein) [NCBI Gene 23237] {aka Arg3.1, hArc}, HES5 (hes family bHLH transcription factor 5) [NCBI Gene 388585] {aka bHLHb38}, EGR1 (early growth response 1) [NCBI Gene 1958] {aka AT225, G0S30, KROX-24, NGFI-A, TIS8, ZIF-268}, Vegfa (vascular endothelial growth factor A) [NCBI Gene 22339] {aka L-VEGF, Vegf, Vpf}, Ppargc1a (peroxisome proliferative activated receptor, gamma, coactivator 1 alpha) [NCBI Gene 19017] {aka A830037N07Rik, Gm11133, PGC-1, PPARGC-1-alpha, Pgc-1alpha, Pgc1}, BDNF (brain derived neurotrophic factor) [NCBI Gene 627] {aka ANON2, BULN2}, Fndc5 (fibronectin type III domain containing 5) [NCBI Gene 384061] {aka 1500001L03Rik, PeP, Pxp}, FNDC5 (fibronectin type III domain containing 5) [NCBI Gene 252995] {aka FRCP2, irisin}, S100A10 (S100 calcium binding protein A10) [NCBI Gene 6281] {aka 42C, ANX2L, ANX2LG, CAL1L, CLP11, Ca[1]}, VEGFA (vascular endothelial growth factor A) [NCBI Gene 7422] {aka L-VEGF, MVCD1, VEGF, VPF}, IGF1 (insulin like growth factor 1) [NCBI Gene 3479] {aka IGF, IGF-I, IGFI, MGF}, Sirt1 (sirtuin 1) [NCBI Gene 93759] {aka SIR2L1, Sir2, Sir2a, Sir2alpha}, Igf1 (insulin-like growth factor 1) [NCBI Gene 16000] {aka C730016P09Rik, Igf-1, Igf-I}, FOS (Fos proto-oncogene, AP-1 transcription factor subunit) [NCBI Gene 2353] {aka AP-1, C-FOS, p55}, Bdnf (brain derived neurotrophic factor) [NCBI Gene 12064], Bdnf (brain-derived neurotrophic factor) [NCBI Gene 24225], CTSB (cathepsin B) [NCBI Gene 1508] {aka APPS, CPSB, KWE, RECEUP}, CEBPA (CCAAT enhancer binding protein alpha) [NCBI Gene 1050] {aka C/EBP-alpha, CEBP}, HCAR1 (hydroxycarboxylic acid receptor 1) [NCBI Gene 27198] {aka FKSG80, GPR104, GPR81, HCA1, LACR1, TA-GPCR}
- **Diseases:** neural alterations (MESH:D004408), sarcopenia (MESH:D055948), dementia (MESH:D003704), schizophrenia (MESH:D012559), hyperventilation (MESH:D006985), mental disorders (MESH:D001523), major depressive disorder (MESH:D003865), muscle hypertrophy (MESH:C536106), cerebrovascular dysfunction (MESH:D002561), HIIT (MESH:D000095027), edema (MESH:D004487), metabolic dysfunction (MESH:D008659), hypoxia (MESH:D000860), osteoporosis (MESH:D010024), brain cell (MESH:D001927), Microvasculature (MESH:D000073436), traumatic brain injury (MESH:D000070642), vascular disease (MESH:D014652), obese (MESH:D009765), anhedonia (MESH:D059445), Alzheimer's disease (MESH:D000544), cerebral disease (MESH:D002539), HIIE (MESH:D000092202), hypercapnia (MESH:D006935), depression (MESH:D003866), brain injury (MESH:D001930), neurological disorders (MESH:D009461), Brain Health (OMIM:603663), Cognitive and Mental Alterations (MESH:D003072)
- **Chemicals:** NO (MESH:D009569), sodium lactate (MESH:D019354), pentose phosphate (MESH:D010428), NAD+ (MESH:D009243), glucose (MESH:D005947), catecholamine (MESH:D002395), L-lactate (MESH:D019344), corticosterone (MESH:D003345), beta-hydroxybutyrate (MESH:D020155), pyruvate (MESH:D019289), acetoacetate (MESH:C016635), oxygen (MESH:D010100), ATP (MESH:D000255), PGE2 (MESH:D015232), HIIE (-)
- **Species:** Rattus norvegicus (brown rat, species) [taxon 10116], Homo sapiens (human, species) [taxon 9606], Mus musculus (house mouse, species) [taxon 10090]

## Full text

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## Figures

3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC8709217/full.md

## References

97 references — full list in the complete paper: https://tomesphere.com/paper/PMC8709217/full.md

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Source: https://tomesphere.com/paper/PMC8709217