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Surprising New Players in Glia-Neuron Crosstalk Role in CNS Regeneration

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SurprisingNewPlayersinGlia-NeuronCrosstalk:RoleinCNSRegenerationBrettM.Morrison1,*1DepartmentofNeurology,JohnsHopkinsUniversity,Baltimore,MD21205,USA*Correspondence:bmorris7@jhmi.eduhttps://doi.org/10.1016/j.cmet.2020.10.009Glia-neuroninteractionsunderlieanumberofhomeostaticprocessesinthebrain.InthisissueofCellMeta-bolism,Lietal.(2020)demonstratethattheregenerationofcentralnervoussystemaxonsisacceleratedthroughmodulationofneuronalGABA-Breceptoractivitybymetabolicenergyintermediariesreleasedfromglia.Unlikeperipheralnervoussystemaxons,centralnervoussystem(CNS)axonshavelimitedcapacityforregeneration.Poorrecoveryfromspinalcordinjury(SCI)inpatientsisoneexampleofthislimitedregeneration,andSCIisacommonlystudiedparadigmforinvesti-gatingCNSaxonregenerationinexperimentalanimals.FollowingSCI,thespinalcordatthesiteofinjuryde-velopsaglialscar,whichiscomposedoffibroblasts,immunecells,andextra-cellularmatrix(ECM)inthecoreandglia,includingastrocytes,oligodendro-cyteprecursorcells,andmicroglia,inthesurroundingpenumbra(BradburyandBurnside,2019).ThoughoncethoughttobeprimarilyanimpedimenttorecoveryfromSCI,thecomponentsoftheglialscararenowknowntohavebothpositiveandnegativeinfluencesonregeneration.AxonregenerationfollowingSCIisimprovedbyremovalofECMwithchondroitinase(Rosenzweigetal.,2019)ortreatmentwithNOGOan-tibodies(Mohammedetal.,2020),butnotbyablatingorinterferingwiththefunctionofastrocytes(Andersonetal.,2016).Inthepresentpaper(Lietal.,2020),theauthorsstudyanovelpotentialroleforglialcellsinCNSax

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