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Publication : Trem2 expression in microglia is required to maintain normal neuronal bioenergetics during development.

First Author  Tagliatti E Year  2024
Journal  Immunity Volume  57
Issue  1 Pages  86-105.e9
PubMed ID  38159572 Mgi Jnum  J:344293
Mgi Id  MGI:7574081 Doi  10.1016/j.immuni.2023.12.002
Citation  Tagliatti E, et al. (2024) Trem2 expression in microglia is required to maintain normal neuronal bioenergetics during development. Immunity 57(1):86-105.e9
abstractText  Triggering receptor expressed on myeloid cells 2 (Trem2) is a myeloid cell-specific gene expressed in brain microglia, with variants that are associated with neurodegenerative diseases, including Alzheimer's disease. Trem2 is essential for microglia-mediated synaptic refinement, but whether Trem2 contributes to shaping neuronal development remains unclear. Here, we demonstrate that Trem2 plays a key role in controlling the bioenergetic profile of pyramidal neurons during development. In the absence of Trem2, developing neurons in the hippocampal cornus ammonis (CA)1 but not in CA3 subfield displayed compromised energetic metabolism, accompanied by reduced mitochondrial mass and abnormal organelle ultrastructure. This was paralleled by the transcriptional rearrangement of hippocampal pyramidal neurons at birth, with a pervasive alteration of metabolic, oxidative phosphorylation, and mitochondrial gene signatures, accompanied by a delay in the maturation of CA1 neurons. Our results unveil a role of Trem2 in controlling neuronal development by regulating the metabolic fitness of neurons in a region-specific manner.
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