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

IF 5.2 2区 医学 Q1 GERIATRICS & GERONTOLOGY
Hao Han, Yawei Zhao, Junda Du, Sushan Wang, Xuehan Yang, Weijie Li, Jiayi Song, Siwei Zhang, Ziyi Zhang, Yongfei Tan, Grant M Hatch, Ming Zhang, Li Chen
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引用次数: 0

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.

运动通过小胶质细胞组蛋白H3乳酸化改善小鼠认知功能障碍和神经炎症。
背景:运动被认为是一种有希望改善神经退行性疾病病理的非药物干预手段。然而,运动对大脑有益作用的机制仍有待进一步探索。在这项研究中,我们研究了运动诱导的代谢物乳酸对小胶质细胞表型的影响及其与学习和记忆的关系。结果:AlCl3/ d -gal处理小鼠脑内小胶质细胞过度活化,与认知能力下降有关。跑步运动改善了小胶质细胞的过度激活,增加了小胶质细胞的抗炎/修复表型,改善了认知能力。小鼠腹腔注射乳酸钠(NaLA)具有与运动训练相似的有益效果。外源性NaLA添加到培养的BV2细胞中,促进了它们从促炎表型向修复表型的转变。结论:乳酸水平升高是小胶质细胞内源性“乳酸计时器”的“加速器”,通过乳酸化促进了小胶质细胞极化平衡的转变。这些结果表明,运动诱导的乳酸加速了小胶质细胞的表型转变,在减少神经炎症和改善认知功能方面起着关键作用。
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来源期刊
Immunity & Ageing
Immunity & Ageing GERIATRICS & GERONTOLOGY-IMMUNOLOGY
CiteScore
10.20
自引率
3.80%
发文量
55
期刊介绍: Immunity & Ageing is a specialist open access journal that was first published in 2004. The journal focuses on the impact of ageing on immune systems, the influence of aged immune systems on organismal well-being and longevity, age-associated diseases with immune etiology, and potential immune interventions to increase health span. All articles published in Immunity & Ageing are indexed in the following databases: Biological Abstracts, BIOSIS, CAS, Citebase, DOAJ, Embase, Google Scholar, Journal Citation Reports/Science Edition, OAIster, PubMed, PubMed Central, Science Citation Index Expanded, SCImago, Scopus, SOCOLAR, and Zetoc.
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