DRG2 deficient mice exhibit impaired motor behaviors with reduced striatal dopamine release

Hye Ryeong Lim, Mai Tram Vo, Dong Jun Kim, Unn Hwa Lee, Jong Hyuk Yoon, Hyung Jun Kim, Jeongah Kim, Sang Ryong Kim, Jun Yeon Lee, Chae Ha Yang, Hee Young Kim, June Seek Choi, Kijeong Kim, Esther Yang, Hyun Kim, Seongsoo Lee, Byung Ju Lee, Kyungjin Kim, Jeong Woo Park, Chang Man Ha

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Developmentally regulated GTP-binding protein 2 (DRG2) was first identified in the central nervous system of mice. However, the physiological function of DRG2 in the brain remains largely unknown. Here, we demonstrated that knocking out DRG2 impairs the function of dopamine neurons in mice. DRG2 was strongly expressed in the neurons of the dopaminergic system such as those in the striatum (Str), ventral tegmental area (VTA), and substantia nigra (SN), and on neuronal cell bodies in high-density regions such as the hippocampus (HIP), cerebellum, and cerebral cortex in the mouse brain. DRG2 knockout (KO) mice displayed defects in motor function in motor coordination and rotarod tests and increased anxiety. However, unexpectedly, DRG2 depletion did not affect the dopamine (DA) neuron population in the SN, Str, or VTA region or dopamine synthesis in the Str region. We further demonstrated that dopamine release was significantly diminished in the Str region of DRG2 KO mice and that treatment of DRG2 KO mice with l-3,4-dihydroxyphenylalanine (L-DOPA), a dopamine precursor, rescued the behavioral motor deficiency in DRG2 KO mice as observed with the rotarod test. This is the first report to identify DRG2 as a key regulator of dopamine release from dopamine neurons in the mouse brain.

Original languageEnglish
Article number60
JournalInternational journal of molecular sciences
Volume21
Issue number1
DOIs
Publication statusPublished - 2020 Jan 1

Keywords

  • Developmentally regulated GTP-binding protein 2 (DRG2)
  • Dopamine release
  • Dopaminergic neurons
  • Motor coordination
  • Motor deficiency
  • Striatum

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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  • Cite this

    Lim, H. R., Vo, M. T., Kim, D. J., Lee, U. H., Yoon, J. H., Kim, H. J., Kim, J., Kim, S. R., Lee, J. Y., Yang, C. H., Kim, H. Y., Choi, J. S., Kim, K., Yang, E., Kim, H., Lee, S., Lee, B. J., Kim, K., Park, J. W., & Ha, C. M. (2020). DRG2 deficient mice exhibit impaired motor behaviors with reduced striatal dopamine release. International journal of molecular sciences, 21(1), [60]. https://doi.org/10.3390/ijms21010060