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[Preprint]. 2024 Oct 18:2024.10.15.618087. [Version 1] doi: 10.1101/2024.10.15.618087

Dark Microglia Are Abundant in Normal Postnatal Development, where they Remodel Synapses via Phagocytosis and Trogocytosis, and Are Dependent on TREM2

Haley A Vecchiarelli, Kanchan Bisht, Kaushik Sharma, Sammy Weiser Novak, Marianela E Traetta, Monica Emili Garcia-Segura, Marie-Kim St-Pierre, Julie C Savage, Cory Willis, Katherine Picard, Maude Bordeleau, Nathalie Vernoux, Mohammadparsa Khakpour, Rishika Garg, Sophia M Loewen, Colin J Murray, Yelena Y Grinberg, Joel Faustino, Torin Halvorson, Victor Lau, Stefano Pluchino, Zinaida S Vexler, Monica J Carson, Uri Manor, Luca Peruzzotti-Jametti, Marie-Ève Tremblay
PMCID: PMC11507757  PMID: 39463930

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.

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