Glial metabolic rewiring promotes axon regeneration and functional recovery in the central nervous system

The mature central nervous system (CNS) struggles to regenerate axons after injury due to an inhibitory environment created by reactive glial cells. This study demonstrates that this inhibitory environment is reversible and depends on the metabolic status of glial cells. By manipulating glial cells in Drosophila, researchers found that increasing glycolysis can promote axon regeneration. This process is facilitated by metabolites produced by glia, specifically L-lactate and L-2-hydroxyglutarate (L-2HG). The local application of L-lactate to injured spinal cords in adult mice promoted corticospinal tract axon regeneration, which led to behavioral recovery, indicating a potential therapeutic strategy for CNS injuries.

• 1
  Activation of PI3K and EGFR pathways in glial cells significantly enhances axon regeneration in the CNS of Drosophila.
• 2
  Glial metabolic rewiring, specifically increased glycolysis, is sufficient to promote axon regeneration, with L-lactate and L-2HG acting as key mediators.
• 3
  L-lactate and L-2HG act on neuronal metabotropic GABAB receptors, leading to increased cAMP signaling, which is crucial for neuronal regrowth and functional recovery.