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

Vecchiarelli, H. A.; Bisht, K.; Sharma, K. P.; Weiser Novak, S.; Traetta, M. E.; Garcia-Segura, M. E.; St-Pierre, M.-K.; Savage, J. C.; Willis, C.; Picard, K.; Bordeleau, M.; Vernoux, N.; Khakpour, M.; Garg, R.; Loewen, S. M.; Murray, C. J.; Grinberg, Y. Y.; Faustino, J.; Halvorson, T.; Lau, V.; Pluchino, S.; Vexler, Z. S.; Carson, M. J.; Manor, U.; Peruzzotti-Jametti, L.; Tremblay, M.-E.

doi:10.1101/2024.10.15.618087

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bioRxiv · 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

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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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Vecchiarelli, H. A., Bisht, K., Sharma, K. P., Weiser Novak, S., Traetta, M. E., Garcia-Segura, M. E., St-Pierre, M.-K., Savage, J. C., Willis, C., Picard, K., Bordeleau, M., Vernoux, N., Khakpour, M., Garg, R., Loewen, S. M., Murray, C. J., Grinberg, Y. Y., Faustino, J., Halvorson, T., Lau, V., Pluchino, S., Vexler, Z. S., Carson, M. J., Manor, U., Peruzzotti-Jametti, L., Tremblay, M.-E.. 2024-10-18. Dark Microglia Are Abundant in Normal Postnatal Development, where they Remodel Synapses via Phagocytosis and Trogocytosis, and Are Dependent on TREM2. https://doi.org/10.1101/2024.10.15.618087

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