Reactive astrocyte nomenclature, definitions, and future directions.
Carole EscartinElena GaleaAndrás LakatosJames P O'CallaghanGabor C PetzoldAlberto Serrano-PozoChristian SteinhäuserAndrea VolterraGiorgio CarmignotoAmit AgarwalNicola J AllenAlfonso AraqueLuis BarbeitoAri BarzilaiDwight E BerglesGilles BonventoArthur Morgan ButtWei-Ting ChenMartine Cohen-SalmonColm CunninghamBenjamin DeneenBart De StrooperBlanca Díaz-CastroCinthia FarinaMarc FreemanVittorio GalloJames E GoldmanSteven A GoldmanMagdalena GötzAntonia GutierrezPhilip G HaydonDieter Henrik HeilandElly M HolMatthew G HoltMasamitsu IinoKsenia V KastanenkaHelmut KettenmannBaljit S KhakhSchuichi KoizumiC Justin LeeShane A LiddelowBrian A MacVicarPierre MagistrettiAlbee MessingAnusha MishraAnna Victoria MolofskyKeith K MuraiChristopher M NorrisSeiji OkadaStéphane H R OlietJoão Filipe OliveiraAude PanatierVladimir ParpuraMarcela PeknaMilos PeknyLuc PellerinGertrudis PereaBeatriz G Pérez-NievasFrank W PfriegerKira E PoskanzerFrancisco J QuintanaRichard M RansohoffMiriam Riquelme-PerezStefanie RobelChristine R RoseJeffrey D RothsteinNathalie RouachDavid H RowitchAlexey V SemyanovSwetlana SirkoHarald SontheimerRaymond A SwansonJavier VitoricaIna-Beate WannerLevi B WoodJiaqian WuBinhai ZhengEduardo R ZimmerRobert ZorecMichael V SofroniewAlexei VerkhratskyPublished in: Nature neuroscience (2021)
Reactive astrocytes are astrocytes undergoing morphological, molecular, and functional remodeling in response to injury, disease, or infection of the CNS. Although this remodeling was first described over a century ago, uncertainties and controversies remain regarding the contribution of reactive astrocytes to CNS diseases, repair, and aging. It is also unclear whether fixed categories of reactive astrocytes exist and, if so, how to identify them. We point out the shortcomings of binary divisions of reactive astrocytes into good-vs-bad, neurotoxic-vs-neuroprotective or A1-vs-A2. We advocate, instead, that research on reactive astrocytes include assessment of multiple molecular and functional parameters-preferably in vivo-plus multivariate statistics and determination of impact on pathological hallmarks in relevant models. These guidelines may spur the discovery of astrocyte-based biomarkers as well as astrocyte-targeting therapies that abrogate detrimental actions of reactive astrocytes, potentiate their neuro- and glioprotective actions, and restore or augment their homeostatic, modulatory, and defensive functions.