Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Peroxiredoxin 6 Overexpression Induces Anxiolytic and Depression-Like Behaviors by Regulating the Serotonergic Pathway in Mice

  • Gu, Sun Mi (College of Pharmacy and Medical Research Center, Chungbuk National University) ;
  • Yu, Eunhye (College of Pharmacy and Medical Research Center, Chungbuk National University) ;
  • Kim, Young Eun (College of Pharmacy and Medical Research Center, Chungbuk National University) ;
  • Yoon, Seong Shoon (College of Korean Medicine, Daegu Haany University) ;
  • Lee, Dohyun (Laboratory Animal Center, Osong Medical Innovation Foundation) ;
  • Hong, Jin Tae (College of Pharmacy and Medical Research Center, Chungbuk National University) ;
  • Yun, Jaesuk (College of Pharmacy and Medical Research Center, Chungbuk National University)
  • Received : 2021.11.02
  • Accepted : 2022.03.05
  • Published : 2022.07.01
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Abstract

Peroxiredoxin 6 (PRDX6) is a bifunctional protein with both glutathione peroxidase and calcium-independent phospholipase activity. Recently, we reported that PRDX6 plays an important role in dopaminergic neurodegeneration in Parkinson's disease. However, the relationship between PRDX6 function and emotional behavior remains elusive. In the present study, we examined depression- and anxiety-like behaviors in PRDX6-overexpressing transgenic (PRDX6-Tg) mice using the forced swim test, tail suspension test, open field paradigm, and elevated plus-maze. PRDX6-Tg mice exhibited depression-like behaviors and low anxiety. In particular, female PRDX6-Tg mice exhibited anxiolytic behavior in the open field test. Furthermore, the serotonin content in the cortex and 5-hydroxytryptophan-induced head twitch response were both reduced in PRDX6-Tg mice. Interestingly, levels of dopa decarboxylase expression in the cortex were decreased in male PRDX6-Tg mice but not in female mice. Our findings provide novel insights into the role of PRDX6 in 5-HT synthesis and suggest that PRDX6 overexpression can induce depression-like behaviors via downregulation of the serotonergic neuronal system.

Keywords

Acknowledgement

This work was supported by the Ministry of Food and Drug Safety (20182MFDS422, 20182MFDS425), the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (No. MRC, 2017R1A5A2015541), "Regional Innovation Strategy (RIS)" through the NRF funded by the Ministry of Education (2021RIS-001), and Basic Science Research Program through the NRF funded by the Ministry of Education (NRF-2021R1I1A1A01058188).

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