Exercise improves cognitive dysfunction and neuroinflammation in mice through Histone H3 lactylation in microglia

Background Exercise is postulated to be a promising non-pharmacological intervention for the improvement of neurodegenerative disease pathology. However, the mechanism of beneficial effects of exercise on the brain remains to be further explored. In this study, we investigated the effect of an exerc...

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Vydáno v:Immunity & ageing Ročník 20; číslo 1; s. 1 - 17
Hlavní autoři: Han, Hao, Zhao, Yawei, Du, Junda, Wang, Sushan, Yang, Xuehan, Li, Weijie, Song, Jiayi, Zhang, Siwei, Zhang, Ziyi, Tan, Yongfei, Hatch, Grant M., Zhang, Ming, Chen, Li
Médium: Journal Article
Jazyk:angličtina
Vydáno: London BioMed Central 17.11.2023
BioMed Central Ltd
Springer Nature B.V
BMC
Témata:
Aging
Aluminum chloride
Alzheimer's disease
Alzheimers disease
Antibodies
Biomedical and Life Sciences
Biomedicine
Clinical Nutrition
Cognitive ability
Cytokines
Dementia
Disease
Exercise
Fitness training programs
Genes
Genotype & phenotype
Geriatrics/Gerontology
Histone H3
Histones
Immunology
Inflammation
Lactate
Lactates
Lactic acid
Lactylation
Memory
Metabolites
Microglia
Morphology
Nervous system diseases
Neurodegeneration
Neurodegenerative diseases
Neuroimmunology and Ageing
Neuroinflammation
Non-pharmacological intervention
Phenotypes
Physical training
Physiology
Public Health
Running
Sodium lactate
China
Neuroinflammation
Exercise
Lactate
Alzheimers disease
Lactylation
Microglia
ISSN:1742-4933, 1742-4933
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Shrnutí:Background Exercise is postulated to be a promising non-pharmacological intervention for the improvement of neurodegenerative disease pathology. However, the mechanism of beneficial effects of exercise on the brain remains to be further explored. In this study, we investigated the effect of an exercise-induced metabolite, lactate, on the microglia phenotype and its association with learning and memory. Results Microglia were hyperactivated in the brains of AlCl 3 /D-gal-treated mice, which was associated with cognitive decline. Running exercise ameliorated the hyperactivation and increased the anti-inflammatory/reparative phenotype of microglia and improved cognition. Mice were injected intraperitoneally with sodium lactate (NaLA) had similar beneficial effects as that of exercise training. Exogenous NaLA addition to cultured BV2 cells promoted their transition from a pro-inflammatory to a reparative phenotype. Conclusion The elevated lactate acted as an “accelerator” of the endogenous “lactate timer” in microglia promoting this transition of microglia polarization balance through lactylation. These findings demonstrate that exercise-induced lactate accelerates the phenotypic transition of microglia, which plays a key role in reducing neuroinflammation and improving cognitive function.
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ISSN:1742-4933
1742-4933
DOI:10.1186/s12979-023-00390-4