Dark Microglia Are Abundant in Normal Postnatal Development, where they Remodel Synapses via Phagocytosis and Trogocytosis, and Are Dependent on TREM2
Authors:
- Haley Alleson VecchiarelliHVHaley Alleson Vecchiarelli
- Kanchan BishtKBKanchan Bisht
- Kaushik P SharmaKSKaushik P Sharma
- Sammy Weiser NovakSNSammy Weiser Novak
- Marianela E. TraettaMTMarianela E. Traetta
- Monica Emili Garcia-SeguraMGMonica Emili Garcia-Segura
- Marie-Kim St-PierreMSMarie-Kim St-Pierre
- Julie C. SavageJSJulie C. Savage
- Cory WillisCWCory Willis
- Katherine PicardKPKatherine Picard
- Nathalie VernouxNVNathalie Vernoux
Preprint
Abstract
This study examined dark microglia—a state linked to central nervous system pathology and neurodegeneration—during postnatal development in the mouse ventral hippocampus, finding that dark microglia interact with blood vessels and synapses and perform trogocytosis of pre-synaptic axon terminals. Furthermore, we found that dark microglia in development notably expressed C-type lectin domain family 7 member A (CLEC7a), lipoprotein lipase (LPL) and triggering receptor expressed on myeloid cells 2 (TREM2) and required TREM2, differently from other microglia, suggesting a link between their role in remodeling during development and central nervous system pathology. Together, these results point towards a previously under-appreciated role for dark microglia in synaptic pruning and plasticity during normal postnatal development.Keywords
This publication has 28 references indexed in Scilit:
- Microglia states and nomenclature: A field at its crossroadsNeuron, 2022
- Microglial functional alteration and increased diversity in the challenged brain: Insights into novel targets for interventionBrain, Behavior, & Immunity - Health, 2021
- Developmental Heterogeneity of Microglia and Brain Myeloid Cells Revealed by Deep Single-Cell RNA SequencingNeuron, 2019
- The TREM2-APOE Pathway Drives the Transcriptional Phenotype of Dysfunctional Microglia in Neurodegenerative DiseasesImmunity, 2017
- A Unique Microglia Type Associated with Restricting Development of Alzheimer’s DiseaseCell, 2017
- Dark microglia: A new phenotype predominantly associated with pathological statesGlia, 2016
- New insights on the role of microglia in synaptic pruning in health and diseaseCurrent Opinion in Neurobiology, 2016
- Cholinergic innervation and thalamic input in rat nucleus accumbensJournal of Chemical Neuroanatomy, 2009
- Evidence for synaptic stripping by cortical microgliaGlia, 2006
- Displacement of synaptic terminals from regenerating motoneurons by microglial cellsCell and tissue research, 1968