Vaccinia-related kinase 2 plays a critical role in microglia-mediated synapse elimination during neurodevelopment

Abstract

During postnatal neurodevelopment, excessive synapses must be eliminated by microglia to complete the establishment of neural circuits in the brain. The lack of synaptic regulation by microglia has been implicated in neurodevelopmental disorders such as autism, schizophrenia, and intellectual disability. Here we suggest that vaccinia-related kinase 2 (VRK2), which is expressed in microglia, may stimulate synaptic elimination by microglia. In VRK2-deficient mice (VRK2(KO)), reduced numbers of presynaptic puncta within microglia were observed. Moreover, the numbers of presynaptic puncta and synapses were abnormally increased in VRK2(KO) mice by the second postnatal week. These differences did not persist into adulthood. Even though an increase in the number of synapses was normalized, adult VRK2(KO) mice showed behavioral defects in social behaviors, contextual fear memory, and spatial memory.