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

Juhyun Lee, Seunghyun Lee, Young Jae Ryu, Dohyun Lee, Sangjune Kim, Ji Young Seo, Eunji Oh, Sun Ha Paek, Seung U. Kim, Chang Man Ha, Se Young Choi, Kyong Tai Kim

Research output: Contribution to journalArticleResearchpeer-review

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 (VRK2KO), reduced numbers of presynaptic puncta within microglia were observed. Moreover, the numbers of presynaptic puncta and synapses were abnormally increased in VRK2KO 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 VRK2KO mice showed behavioral defects in social behaviors, contextual fear memory, and spatial memory.

Original languageEnglish
Pages (from-to)1667-1679
Number of pages13
JournalGLIA
Volume67
Issue number9
DOIs
StatePublished - 1 Sep 2019

Fingerprint

Vaccinia
Microglia
Synapses
Phosphotransferases
Social Behavior
Autistic Disorder
Intellectual Disability
Fear
Schizophrenia
Brain

Keywords

  • VRK2
  • microglia
  • neurodevelopment
  • synapse elimination

Cite this

Lee, J., Lee, S., Ryu, Y. J., Lee, D., Kim, S., Seo, J. Y., ... Kim, K. T. (2019). Vaccinia-related kinase 2 plays a critical role in microglia-mediated synapse elimination during neurodevelopment. GLIA, 67(9), 1667-1679. https://doi.org/10.1002/glia.23638
Lee, Juhyun ; Lee, Seunghyun ; Ryu, Young Jae ; Lee, Dohyun ; Kim, Sangjune ; Seo, Ji Young ; Oh, Eunji ; Paek, Sun Ha ; Kim, Seung U. ; Ha, Chang Man ; Choi, Se Young ; Kim, Kyong Tai. / Vaccinia-related kinase 2 plays a critical role in microglia-mediated synapse elimination during neurodevelopment. In: GLIA. 2019 ; Vol. 67, No. 9. pp. 1667-1679.
@article{0de5ec2e7d424762a95ac241574a1bc3,
title = "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 (VRK2KO), reduced numbers of presynaptic puncta within microglia were observed. Moreover, the numbers of presynaptic puncta and synapses were abnormally increased in VRK2KO 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 VRK2KO mice showed behavioral defects in social behaviors, contextual fear memory, and spatial memory.",
keywords = "VRK2, microglia, neurodevelopment, synapse elimination",
author = "Juhyun Lee and Seunghyun Lee and Ryu, {Young Jae} and Dohyun Lee and Sangjune Kim and Seo, {Ji Young} and Eunji Oh and Paek, {Sun Ha} and Kim, {Seung U.} and Ha, {Chang Man} and Choi, {Se Young} and Kim, {Kyong Tai}",
year = "2019",
month = "9",
day = "1",
doi = "10.1002/glia.23638",
language = "English",
volume = "67",
pages = "1667--1679",
journal = "GLIA",
issn = "0894-1491",
publisher = "John Wiley and Sons Inc.",
number = "9",

}

Lee, J, Lee, S, Ryu, YJ, Lee, D, Kim, S, Seo, JY, Oh, E, Paek, SH, Kim, SU, Ha, CM, Choi, SY & Kim, KT 2019, 'Vaccinia-related kinase 2 plays a critical role in microglia-mediated synapse elimination during neurodevelopment', GLIA, vol. 67, no. 9, pp. 1667-1679. https://doi.org/10.1002/glia.23638

Vaccinia-related kinase 2 plays a critical role in microglia-mediated synapse elimination during neurodevelopment. / Lee, Juhyun; Lee, Seunghyun; Ryu, Young Jae; Lee, Dohyun; Kim, Sangjune; Seo, Ji Young; Oh, Eunji; Paek, Sun Ha; Kim, Seung U.; Ha, Chang Man; Choi, Se Young; Kim, Kyong Tai.

In: GLIA, Vol. 67, No. 9, 01.09.2019, p. 1667-1679.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Vaccinia-related kinase 2 plays a critical role in microglia-mediated synapse elimination during neurodevelopment

AU - Lee, Juhyun

AU - Lee, Seunghyun

AU - Ryu, Young Jae

AU - Lee, Dohyun

AU - Kim, Sangjune

AU - Seo, Ji Young

AU - Oh, Eunji

AU - Paek, Sun Ha

AU - Kim, Seung U.

AU - Ha, Chang Man

AU - Choi, Se Young

AU - Kim, Kyong Tai

PY - 2019/9/1

Y1 - 2019/9/1

N2 - 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 (VRK2KO), reduced numbers of presynaptic puncta within microglia were observed. Moreover, the numbers of presynaptic puncta and synapses were abnormally increased in VRK2KO 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 VRK2KO mice showed behavioral defects in social behaviors, contextual fear memory, and spatial memory.

AB - 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 (VRK2KO), reduced numbers of presynaptic puncta within microglia were observed. Moreover, the numbers of presynaptic puncta and synapses were abnormally increased in VRK2KO 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 VRK2KO mice showed behavioral defects in social behaviors, contextual fear memory, and spatial memory.

KW - VRK2

KW - microglia

KW - neurodevelopment

KW - synapse elimination

UR - http://www.scopus.com/inward/record.url?scp=85065313872&partnerID=8YFLogxK

U2 - 10.1002/glia.23638

DO - 10.1002/glia.23638

M3 - Article

VL - 67

SP - 1667

EP - 1679

JO - GLIA

JF - GLIA

SN - 0894-1491

IS - 9

ER -