6533b824fe1ef96bd12809ee

RESEARCH PRODUCT

A novel microglial subset plays a key role in myelinogenesis in developing brain.

Khalad KarramErik BoddekeAri WaismanMartin KruegerJulia BruttgerTrevor OwensAnouk Benmamar-badelAnouk Benmamar-badelAgnieszka WlodarczykInge R. HoltmanNellie Anne MartinBart J. L. EggenReza KhorooshiIsabella KramerJelkje J. De Boer-bergsmaNir Yogev

subject

0301 basic medicineAgingmedicine.medical_treatmentNews & ViewsInsulin-Like Growth Factor IMyelin SheathCell AggregationNeural PlateMicrogliaACTIVATED MICROGLIAGeneral NeuroscienceExperimental autoimmune encephalomyelitisNeurogenesisIGF1BrainGene Expression Regulation DevelopmentalADULT BRAINUp-RegulationALZHEIMERS-DISEASEmedicine.anatomical_structureEXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITISMyelinogenesisGROWTHFemaleMicrogliaCNSEncephalomyelitis Autoimmune ExperimentalNeurogenesisCentral nervous systemCD11cBiologyGeneral Biochemistry Genetics and Molecular BiologyDEPENDENT MANNER03 medical and health sciencesmedicinePOSTNATAL-DEVELOPMENTAnimalsMolecular BiologyNeuroinflammationGeneral Immunology and MicrobiologyCD11cGrowth factorGene Expression ProfilingCENTRAL-NERVOUS-SYSTEMmedicine.diseaseGALECTIN-1CD11c AntigenMice Inbred C57BL030104 developmental biologynervous systemAnimals NewbornImmunologymyelinogenesisNeuroscienceBiomarkers

description

Microglia are resident macrophages of the central nervous system that contribute to homeostasis and neuroinflammation. Although known to play an important role in brain development, their exact function has not been fully described. Here, we show that in contrast to healthy adult and inflammation-activated cells, neonatal microglia show a unique myelinogenic and neurogenic phenotype. A CD11c(+) microglial subset that predominates in primary myelinating areas of the developing brain expresses genes for neuronal and glial survival, migration, and differentiation. These cells are the major source of insulin-like growth factor 1, and its selective depletion from CD11c(+) microglia leads to impairment of primary myelination. CD11c-targeted toxin regimens induced a selective transcriptional response in neonates, distinct from adult microglia. CD11c(+) microglia are also found in clusters of repopulating microglia after experimental ablation and in neuroinflammation in adult mice, but despite some similarities, they do not recapitulate neonatal microglial characteristics. We therefore identify a unique phenotype of neonatal microglia that deliver signals necessary for myelination and neurogenesis.

10.15252/embj.201696056https://pubmed.ncbi.nlm.nih.gov/29101295