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

Juhyun Lee1, Seunghyun Lee2, Young-Jae Ryu3

  • 1Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang, Republic of Korea.

Glia
|May 4, 2019
PubMed

Insights

Microglia regulate brain development by eliminating synapses. Vaccinia-related kinase 2 (VRK2) deficiency in mice impairs this process, leading to synaptic and behavioral deficits, potentially linking VRK2 to neurodevelopmental disorders.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Developmental Biology

Background:

  • Microglia are crucial for eliminating excess synapses during postnatal neurodevelopment.
  • Dysfunctional microglial synaptic pruning is linked to neurodevelopmental disorders like autism and schizophrenia.

Purpose of the Study:

  • To investigate the role of vaccinia-related kinase 2 (VRK2) in microglial synaptic elimination.
  • To determine the impact of VRK2 deficiency on neural circuit formation and associated behaviors.

Main Methods:

  • Utilized VRK2-deficient (VRK2KO) mice to study synaptic pruning.
  • Quantified presynaptic puncta within microglia and overall synapse numbers.
  • Assessed behavioral phenotypes in adult VRK2KO mice.

Main Results:

  • VRK2KO mice exhibited reduced presynaptic puncta within microglia.
  • An abnormal increase in presynaptic puncta and synapses was observed in VRK2KO mice during the second postnatal week.
  • While synapse numbers normalized by adulthood, VRK2KO mice displayed deficits in social, contextual fear, and spatial memory.

Conclusions:

  • VRK2 plays a role in microglial-mediated synaptic elimination during early neurodevelopment.
  • VRK2 deficiency leads to transient synaptic abnormalities and persistent behavioral deficits.
  • VRK2 may be a potential therapeutic target for neurodevelopmental disorders involving synaptic dysregulation.
Keywords:
VRK2microglianeurodevelopmentsynapse elimination

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