ARG1-expressing microglia show a distinct molecular signature and modulate postnatal development and function of the mouse brain
Nature Neuroscience · 32 authors, 17 centres
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This preclinical study identifies a specialized subtype of mouse brain microglia expressing the enzyme ARG1. The study uses a conditional knockout model to show that loss of microglial Arg1 impairs specific aspects of brain development and cognitive function in female mice.
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RNA-seq analysis revealed that ARG1-expressing microglia have a unique molecular signature compared to other microglia. The study reports that female mice lacking microglial Arg1 showed significant impairments in long-term memory and deficits in hippocampal long-term potentiation (LTP), a key cellular mechanism for learning and memory. Morphological analysis also indicated impaired maturation of dendritic spines in the hippocampus. In contrast, motor behavior was unaffected. The findings suggest that ARG1-expressing microglia play a developmentally regulated role in shaping neuronal circuits involved in cognition. The study is limited to mice, and the authors note that while human ARG1 deficiency is linked to neurological problems, whether this is specifically due to microglial dysfunction requires further investigation.
