Lifelong absence of microglia alters hippocampal glutamatergic networks but not synapse and spine density
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ABSTRACT: Microglia sculpt developing neural circuits by eliminating excess synapses in a process called synaptic pruning, by removing apoptotic neurons, and by promoting neuronal survival. To elucidate the role of microglia during embryonic and postnatal brain development, we used a mouse model deficient in microglia throughout life by deletion of the fms-intronic regulatory element (FIRE) in the Csf1r locus. Surprisingly, young adult Csf1rΔFIRE/ΔFIRE mice displayed no changes in excitatory and inhibitory synapse number and spine density of CA1 hippocampal neurons compared to Csf1r+/+ littermates. However, CA1 neurons were less excitable, received less CA3 excitatory input and showed altered synaptic properties, but this did not affect novel object recognition. Cytokine profiling indicated an anti-inflammatory state along with increases in ApoE levels and reactive astrocytes containing synaptic markers in Csf1rΔFIRE/ΔFIRE mice. Notably, these changes in Csf1rΔFIRE/ΔFIRE mice closely resemble the effects of acute microglial depletion in adult mice that had undergone normal development. Our findings suggest that microglia are not mandatory for synaptic pruning, as in their absence this can be achieved by other mechanisms.
SUBMITTER: Mr. Michael Surala
PROVIDER: S-SCDT-10_1038-S44319-024-00130-9 | biostudies-other |
REPOSITORIES: biostudies-other
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