Biomolecules & Therapeutics  https://doi.org/10.4062/biomolther.2021.169
Peroxiredoxin 6 Overexpression Induces Anxiolytic and Depression-Like Behaviors by Regulating the Serotonergic Pathway in Mice
Sun Mi Gu1,†, Eunhye Yu1,†, Young Eun Kim1, Seong Shoon Yoon2, Dohyun Lee3, Jin Tae Hong1,* and Jaesuk Yun1,*
1College of Pharmacy and Medical Research Center, Chungbuk National University, Cheongju 28160,
2College of Korean Medicine, Daegu Haany University, Daegu 42158,
3Laboratory Animal Center, Osong Medical Innovation Foundation, Cheongju 28160, Republic of Korea
*E-mail: jinthong@chungbuk.ac.kr (Hong JT), jyun@chungbuk.ac.kr (Yun J)
Tel: +82-43-261-2813 (Hong JT), +82-43-261-2827 (Yun J)
Fax: +82-43-268-2732 (Hong JT), +82-43-268-2732 (Yun J)
The first two authors contributed equally to this work.
Received: November 2, 2021; Revised: February 9, 2022; Accepted: March 5, 2022; Published online: March 31, 2022.
© The Korean Society of Applied Pharmacology. All rights reserved.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
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: Peroxiredoxin 6, Depression, Anxiety, L-amino acid decarboxylase, Serotonin


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