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

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Date
2023-11-17
Authors
Han, Hao
Zhao, Yawei
Du, Junda
Wang, Sushan
Yang, Xuehan
Li, Weijie
Song, Jiayi
Zhang, Siwei
Zhang, Ziyi
Tan, Yongfei
Journal Title
Journal ISSN
Volume Title
Publisher
BMC
Abstract

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 AlCl3/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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Keywords
exercise, lactate, lactylation, microglia, neuroinflammation, Alzheimer's disease
Citation
Immunity & Ageing. 2023 Nov 17;20(1):63