14-3-3γ haploinsufficiency leads to altered dopamine pathway and Parkinson’s disease-like motor incoordination in mice

Eunsil Cho, Jinsil Park, Eun Mi Hwang, Hyung Wook Kim, Jae Yong Park

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

The 14-3-3 protein family with seven isoforms found in mammals is widely expressed in the brain and plays various roles in cellular processes. Several studies have reported that 14-3-3γ, one of the 14-3-3 protein isoforms, is associated with neurological and psychiatric disorders, but the role of 14-3-3γ in the pathophysiology of brain diseases is unclear. Although studies have been conducted on the relationship between 14-3-3γ protein and Parkinson’s disease (PD), a common neurodegenerative disorder with severe motor symptoms such as bradykinesia and rigidity, a direct connection remains to be elucidated. We recently showed that adult heterozygous 14-3-3γ knockout mice are hyperactive and exhibit anxiety-like behavior. In this study, we further characterized the molecular and behavioral changes in aged 14-3-3γ heterozygous mice to investigate the role of 14-3-3γ in the brain. We observed decreased dopamine levels and altered dopamine metabolism in the brains of these mice, including changes in the phosphorylation of proteins implicated in PD pathology. Furthermore, we confirmed that they displayed PD symptom-like behavioral deficits, such as impaired motor coordination and decreased ability to the nest-building activity. These findings suggest an association between 14-3-3γ dysfunction and PD pathophysiology.

Original languageEnglish
Article number2
JournalMolecular brain
Volume16
Issue number1
DOIs
Publication statusPublished - 2023 Dec

Bibliographical note

Funding Information:
This work was supported by the National Research Foundation (NRF) of Korea (NRF- 2017R1A2B3012502, 2017M3C7A1079694, and 2017M3A9C4092979 for J-Y Park and NRF-2021R1F1A1059574 for HW Kim).

Publisher Copyright:
© 2023, The Author(s).

Keywords

  • 14-3-3γ
  • Dopamine
  • Motor incoordination
  • Parkinson’s disease

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience

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