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Updated: Jul 14, 2026
Author Spotlight: Enhancements in Gene Expression Regulation Research
Published on: September 15, 2023
Histone H3 lysine 18 lactylation attenuates neuroinflammation and neurological damage by regulating microglial plxnb2
1Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; Hubei Key Laboratory of Neural Injury and Functional Reconstruction, Huazhong University of Science and Technology, 430030 Wuhan, China.
Abstract:
Microglia are major resident immune cells in the central nervous system and are actively involved in the pathogenesis of ischemic stroke. Histone lactylation confers macrophage homeostatic gene expressions and regulates physiological and immune-related pathological conditions. However, the spatiotemporal expression and functional role of histone lactylation in microglial reprogramming and neurological injuries after ischemic stroke remain elusive. In this study, we observed increased levels of histone lactylation in peri-infarct areas after the middle cerebral artery occlusion-induced focal cerebral ischemia in mice. The enhanced histone lactylation favored an anti-inflammatory micro-environment and provided neuroprotective effects after ischemia, which might be mediated by histone H3 lysine 18 lactylation (H3K18la)-regulated plxnb2 expression in microglia. Microglia-specific inhibition of plxnb2 abrogated the neuroprotective effects of lactate after ischemic stroke. These findings suggest that interventions aimed at the lactate/lactylation(H3K18la)/plxnb2 axis may represent a promising therapeutic strategy for ischemic stroke treatment.
Insights
Histone lactylation in microglia reduces brain damage after ischemic stroke. Targeting this pathway, specifically histone H3 lysine 18 lactylation (H3K18la) and plxnb2, offers a novel therapeutic approach for stroke recovery.
Area of Science:
- Neuroscience
- Immunology
- Biochemistry
Background:
- Microglia are key immune cells in the central nervous system, crucial in ischemic stroke pathogenesis.
- Histone lactylation influences macrophage gene expression and immune responses, but its role in stroke is unclear.
Purpose of the Study:
- To investigate the role and expression of histone lactylation in microglia following ischemic stroke.
- To elucidate the molecular mechanisms underlying histone lactylation's effects on neurological injury.
Main Methods:
- Induction of focal cerebral ischemia using middle cerebral artery occlusion in mice.
- Assessment of histone lactylation levels in peri-infarct areas.
- Microglia-specific inhibition of plxnb2 to evaluate its role in neuroprotection.
Main Results:
- Increased histone lactylation observed in peri-infarct regions post-stroke.
- Enhanced histone lactylation promoted an anti-inflammatory environment and neuroprotection.
- Histone H3 lysine 18 lactylation (H3K18la) mediated plxnb2 expression in microglia, crucial for neuroprotection.
Conclusions:
- Histone lactylation, particularly H3K18la, plays a neuroprotective role in ischemic stroke by modulating microglial activity.
- The lactate/lactylation(H3K18la)/plxnb2 axis represents a potential therapeutic target for treating ischemic stroke.
