A novel microglial subset plays a key role in myelinogenesis in developing brain.
Agnieszka WlodarczykInge R HoltmanMartin KruegerNir YogevJulia BruttgerReza KhorooshiAnouk Benmamar-BadelJelkje J de Boer-BergsmaNellie A MartinKhalad KarramIsabella KramerErik Wgm BoddekeEsther Von StebutBart Jl EggenTrevor OwensPublished in: The EMBO journal (2017)
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.
Keyphrases
- inflammatory response
- neuropathic pain
- lipopolysaccharide induced
- lps induced
- cerebral ischemia
- spinal cord injury
- spinal cord
- induced apoptosis
- resting state
- oxidative stress
- white matter
- traumatic brain injury
- escherichia coli
- functional connectivity
- gene expression
- magnetic resonance
- metabolic syndrome
- genome wide
- type diabetes
- childhood cancer
- computed tomography
- magnetic resonance imaging
- cognitive impairment
- young adults
- preterm infants
- adipose tissue
- endoplasmic reticulum stress
- transcription factor
- insulin resistance
- subarachnoid hemorrhage
- endothelial cells
- cancer therapy
- low birth weight
- quality improvement
- pi k akt
- stress induced
- genome wide analysis