Browse > Article
http://dx.doi.org/10.4062/biomolther.2021.169

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)
Publication Information
Biomolecules & Therapeutics / v.30, no.4, 2022 , pp. 334-339 More about this Journal
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;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Stockmeier, C. A. (2003) Involvement of serotonin in depression: evidence from postmortem and imaging studies of serotonin receptors and the serotonin transporter. J. Psychiatr. Res. 37, 357-373.   DOI
2 Oliviero, G., Munawar, N., Watson, A., Streubel, G., Manning, G., Bardwell, V., Bracken, A. P. and Cagney, G. (2015) The variant Polycomb Repressor Complex 1 component PCGF1 interacts with a pluripotency sub-network that includes DPPA4, a regulator of embryogenesis. Sci. Rep. 5, 18388.   DOI
3 Porsolt, R. D., Le Pichon, M. and Jalfre, M. (1977) Depression: a new animal model sensitive to antidepressant treatments. Nature 266, 730-732.   DOI
4 Rosenzweig-Lipson, S. (2011) New horizons for selective 5-HT2C receptor ligands in psychiatric/neurological disorders. Neuropsychopharmacology 36, 363-364.   DOI
5 Vaccarino, V., Brennan, M. L., Miller, A. H., Bremner, J. D., Ritchie, J. C., Lindau, F., Veledar, E., Su, S., Murrah, N. V., Jones, L., Jawed, F., Dai, J., Goldberg, J. and Hazen, S. L. (2008) Association of major depressive disorder with serum myeloperoxidase and other markers of inflammation: a twin study. Biol. Psychiatry 64, 476-483.   DOI
6 Yun, H. M., Choi, D. Y., Oh, K. W. and Hong, J. T. (2015) PRDX6 exacerbates dopaminergic neurodegeneration in a MPTP mouse model of Parkinson's disease. Mol. Neurobiol. 52, 422-431.   DOI
7 Cryan, J. F., Mombereau, C. and Vassout, A. (2005) The tail suspension test as a model for assessing antidepressant activity: review of pharmacological and genetic studies in mice. Neurosci. Biobehav. Rev. 29, 571-625.   DOI
8 Birzniece, V., Johansson, I. M., Wang, M. D., Backstrom, T. and Olsson, T. (2002) Ovarian hormone effects on 5-hydroxytryptamine (2A) and 5-hydroxytryptamine (2C) receptor mRNA expression in the ventral hippocampus and frontal cortex of female rats. Neurosci. Lett. 319, 157-161.   DOI
9 Canal, C. E. and Morgan, D. (2012) Head-twitch response in rodents induced by the hallucinogen 2,5-dimethoxy-4-iodoamphetamine: a comprehensive history, a re-evaluation of mechanisms, and its utility as a model. Drug Test. Anal. 4, 556-576.   DOI
10 Colpaert, F. C. and Janssen, P. A. (1983) The head-twitch response to intraperitoneal injection of 5-hydroxytryptophan in the rat: antagonist effects of purported 5-hydroxytryptamine antagonists and of pirenperone, an LSD antagonist. Neuropharmacology 22, 993-1000.   DOI
11 Hillhouse, T. M. and Porter, J. H. (2015) A brief history of the development of antidepressant drugs: from monoamines to glutamate. Exp. Clin. Psychopharmacol. 23, 1-21.   DOI
12 Mchedlidze, O., Dzadzamia, S., Butskhrikidze, M., Tsomaia, V. and Nachkebia, N. (2011) Changes of locomotor, exploratory and emotional behavior in animal model of depression induced by deficiency of brain monoamine content. Georgian Med. News 198, 76-82.
13 Mouri, A., Sasaki, A., Watanabe, K., Sogawa, C., Kitayama, S., Mamiya, T., Miyamoto, Y., Yamada, K., Noda, Y. and Nabeshima, T. (2012) MAGE-D1 regulates expression of depression-like behavior through serotonin transporter ubiquitylation. J. Neurosci. 32, 4562-4580.   DOI
14 Canal, C. E., Olaghere Da Silva, U. B., Gresch, P. J., Watt, E. E., Sanders-Bush, E. and Airey, D. C. (2010) The serotonin 2C receptor potently modulates the head-twitch response in mice induced by a phenethylamine hallucinogen. Psychopharmacology (Berl.) 209, 163-174.   DOI
15 Owens, M. J. and Nemeroff, C. B. (1994) Role of serotonin in the pathophysiology of depression: focus on the serotonin transporter. Clin. Chem. 40, 288-295.   DOI
16 Schreiber, R., Brocco, M., Audinot, V., Gobert, A., Veiga, S. and Millan, M. J. (1995) (1-(2,5-dimethoxy-4 iodophenyl)-2-aminopropane)-induced head-twitches in the rat are mediated by 5-hydroxytryptamine (5-HT) 2A receptors: modulation by novel 5-HT2A/2C antagonists, D1 antagonists and 5-HT1A agonists. J. Pharmacol. Exp. Ther. 273, 101-112.
17 Lister, R. G. (1987) The use of a plus-maze to measure anxiety in the mouse. Psychopharmacology (Berl.) 92, 180-185.   DOI
18 Ng, J., Heales, S. J. and Kurian, M. A. (2014) Clinical features and pharmacotherapy of childhood monoamine neurotransmitter disorders. Paediatr. Drugs 16, 275-291.   DOI
19 Tomida, S., Mamiya, T., Sakamaki, H., Miura, M., Aosaki, T., Masuda, M., Niwa, M., Kameyama, T., Kobayashi, J., Iwaki, Y., Imai, S., Ishikawa, A., Abe, K., Yoshimura, T., Nabeshima, T. and Ebihara, S. (2009) Usp46 is a quantitative trait gene regulating mouse immobile behavior in the tail suspension and forced swimming tests. Nat. Genet. 41, 688-695.   DOI
20 Can, A., Dao, D. T., Arad, M., Terrillion, C. E., Piantadosi, S. C. and Gould, T. D. (2012) The mouse forced swim test. J. Vis. Exp. (59), e3638.
21 Chae, H. Z., Robison, K., Poole, L. B., Church, G., Storz, G. and Rhee, S. G. (1994) Cloning and sequencing of thiol-specific antioxidant from mammalian brain: alkyl hydroperoxide reductase and thiol-specific antioxidant define a large family of antioxidant enzymes. Proc. Natl. Acad. Sci. U.S.A. 91, 7017-7021.   DOI
22 Corne, S. J., Pickering, R. W. and Warner, B. T. (1963) A method for assessing the effects of drugs on the central actions of 5-hydroxytryptamine. Br. J. Pharmacol. Chemother. 20, 106-120.   DOI
23 Kasahara, T., Kubota, M., Miyauchi, T., Noda, Y., Mouri, A., Nabeshima, T. and Kato, T. (2006) Mice with neuron-specific accumulation of mitochondrial DNA mutations show mood disorder-like phenotypes. Mol. Psychiatry 11, 577-593.   DOI
24 Lopatina, O., Yoshihara, T., Nishimura, T., Zhong, J., Akther, S., Fakhrul, A. A., Liang, M., Higashida, C., Sumi, K., Furuhara, K., Inahata, Y., Huang, J. J., Koizumi, K., Yokoyama, S., Tsuji, T., Petugina, Y., Sumarokov, A., Salmina, A. B., Hashida, K., Kitao, Y., Hori, O., Asano, M., Kitamura, Y., Kozaka, T., Shiba, K., Zhong, F., Xie, M. J., Sato, M., Ishihara, K. and Higashida, H. (2014) Anxiety- and depression-like behavior in mice lacking the CD157/BST1 gene, a risk factor for Parkinson's disease. Front. Behav. Neurosci. 8, 133.   DOI
25 Manevich, Y., Feinstein, S. I. and Fisher, A. B. (2004) Activation of the antioxidant enzyme 1-CYS peroxiredoxin requires glutathionylation mediated by heterodimerization with pi GST. Proc. Natl. Acad. Sci. U.S.A. 101, 3780-3785.   DOI
26 Darmani, N. A. (1996) Differential potentiation of L-tryptophan-induced head-twitch response in mice by cocaine and sertraline. Life Sci. 59, 1109-1119.   DOI
27 Fisher, A. B., Dodia, C., Manevich, Y., Chen, J. W. and Feinstein, S. I. (1999) Phospholipid hydroperoxides are substrates for non-selenium glutathione peroxidase. J. Biol. Chem. 274, 21326-21334.   DOI
28 Jacobsen, J. P., Medvedev, I. O. and Caron, M. G. (2012) The 5-HT deficiency theory of depression: perspectives from a naturalistic 5-HT deficiency model, the tryptophan hydroxylase 2Arg439His knockin mouse. Philos. Trans. R. Soc. Lond. B Biol. Sci. 367, 2444-2459.   DOI
29 Nabeshima, T., Hiramatsu, M., Niwa, K., Fuji, K. and Kameyama, T. (1992) Effect of naftidrofuryl oxalate on 5-HT2 receptors in mouse brain: evaluation based on quantitative autoradiography and headtwitch response. Eur. J. Pharmacol. 223, 109-115.   DOI
30 Millevoi, S., Thion, L., Joseph, G., Vossen, C., Ghisolfi-Nieto, L. and Erard, M. (2001) Atypical binding of the neuronal POU protein NOct3 to noncanonical DNA targets. Implications for heterodimerization with HNF-3 beta. Eur. J. Biochem. 268, 781-791.   DOI
31 Murai, R., Noda, Y., Matsui, K., Kamei, H., Mouri, A., Matsuba, K., Nitta, A., Furukawa, H. and Nabeshima, T. (2007) Hypofunctional glutamatergic neurotransmission in the prefrontal cortex is involved in the emotional deficit induced by repeated treatment with phencyclidine in mice: implications for abnormalities of glutamate release and NMDA-CaMKII signaling. Behav. Brain Res. 180, 152-160.   DOI
32 Zou, J., Weng, R. H., Chen, Z. Y., Wei, X. B., Wang, R., Chen, D., Xia, Y. and Wang, Q. (2016) Position emission tomography/single-photon emission tomography neuroimaging for detection of premotor Parkinson's disease. CNS Neurosci. Ther. 22, 167-177.   DOI
33 Miyamoto, Y., Yamada, K., Noda, Y., Mori, H., Mishina, M. and Nabeshima, T. (2002) Lower sensitivity to stress and altered monoaminergic neuronal function in mice lacking the NMDA receptor epsilon 4 subunit. J. Neurosci. 22, 2335-2342.   DOI
34 Siu, W. K. (2015) Genetics of monoamine neurotransmitter disorders. Transl. Pediatr. 4, 175-180.
35 Steru, L., Chermat, R., Thierry, B. and Simon, P. (1985) The tail suspension test: a new method for screening antidepressants in mice. Psychopharmacology (Berl.) 85, 367-370.   DOI
36 Balasinor, N. H., D'souza, R., Nanaware, P., Idicula-Thomas, S., Kedia-Mokashi, N., He, Z. and Dym, M. (2010) Effect of high intratesticular estrogen on global gene expression and testicular cell number in rats. Reprod. Biol. Endocrinol. 8, 72.   DOI
37 Buonora, J. E., Mousseau, M., Jacobowitz, D. M., Lazarus, R. C., Yarnell, A. M., Olsen, C. H., Pollard, H. B., Diaz-Arrastia, R., Latour, L. and Mueller, G. P. (2015) Autoimmune profiling reveals peroxiredoxin 6 as a candidate traumatic brain injury biomarker. J. Neurotrauma 32, 1805-1814.   DOI
38 Nic Dhonnchadha, B. A., Bourin, M. and Hascoet, M. (2003) Anxiolyticlike effects of 5-HT2 ligands on three mouse models of anxiety. Behav. Brain Res. 140, 203-214.   DOI
39 Crawley, J. N. (1999) Behavioral phenotyping of transgenic and knockout mice: experimental design and evaluation of general health, sensory functions, motor abilities, and specific behavioral tests. Brain Res. 835, 18-26.   DOI