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Li, F., Sami, A., Noristani, H.N., Slattery, K., Qiu, J., Groves, T., Wang, S., Veerasammy, K., Chen, Y.X., Morales, J., Haynes, P., Sehgal, A., He, Y., Li, S., Song, Y. (2020). Glial Metabolic Rewiring Promotes Axon Regeneration and Functional Recovery in the Central Nervous System.  Cell Metab. 32(5): 767--785.e7.
FlyBase ID
FBrf0247146
Publication Type
Research paper
Abstract

Axons in the mature central nervous system (CNS) fail to regenerate after axotomy, partly due to the inhibitory environment constituted by reactive glial cells producing astrocytic scars, chondroitin sulfate proteoglycans, and myelin debris. We investigated this inhibitory milieu, showing that it is reversible and depends on glial metabolic status. We show that glia can be reprogrammed to promote morphological and functional regeneration after CNS injury in Drosophila via increased glycolysis. This enhancement is mediated by the glia derived metabolites: L-lactate and L-2-hydroxyglutarate (L-2HG). Genetically/pharmacologically increasing or reducing their bioactivity promoted or impeded CNS axon regeneration. L-lactate and L-2HG from glia acted on neuronal metabotropic GABAB receptors to boost cAMP signaling. Local application of L-lactate to injured spinal cord promoted corticospinal tract axon regeneration, leading to behavioral recovery in adult mice. Our findings revealed a metabolic switch to circumvent the inhibition of glia while amplifying their beneficial effects for treating CNS injuries.

PubMed ID
PubMed Central ID
PMC7642184 (PMC) (EuropePMC)
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Secondary IDs
    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Cell Metab.
    Title
    Cell Metabolism
    Publication Year
    2005-
    ISBN/ISSN
    1550-4131
    Data From Reference
    Alleles (68)
    Genes (45)
    Natural transposons (1)
    Insertions (2)
    Experimental Tools (2)
    Transgenic Constructs (56)