Lactate promotes microglial scar formation and facilitates locomotor function recovery by enhancing histone H4 lysine 12 lactylation after spinal cord injury

Spinal cord injury (SCI) leads to inflammation and scar formation, with microglia playing a role in this process. Lactate levels increase after SCI and can modify proteins, including histones. This study investigates how lactate and a specific histone modification (H4K12la) affect microglia and recovery after SCI. The study found that lactate treatment promoted microglial proliferation, scar formation, axon regeneration, and locomotor function recovery after SCI. This suggests that lactate, through its effects on microglia, can help the spinal cord repair itself. The researchers identified a signaling pathway involving lactate, H4K12la, and PD-1 in microglia. Lactate increases H4K12la, which in turn promotes PD-1 transcription. Blocking PD-1 reversed the beneficial effects of lactate, indicating that this pathway is important for SCI repair.

• 1
  Lactate levels and lactylation are upregulated in the spinal cord, particularly in microglia, after SCI.
• 2
  Exogenous lactate treatment further elevates H4K12la in microglia after SCI, promoting microglial proliferation and scar formation.
• 3
  Lactate-mediated H4K12la elevation promotes PD-1 transcription in microglia, facilitating axon regeneration and locomotor function recovery after SCI.