Antipsychotic clozapine attenuates phencyclidine-induced behavioral deficits through positive modulation of glutathione peroxidase-1 in mice

Abstract

Event Abstract Back to Event Antipsychotic clozapine attenuates phencyclidine-induced behavioral deficits through positive modulation of glutathione peroxidase-1 in mice The-Vinh Tran1*, Eun-Joo Shin1, Ji Hoon Jeong2, Choon-Gon Jang3 and Hyoung-Chun Kim1 1 Kangwon National University, Neuropsychopharmacology and Toxicology Program, College of Pharmacy, Republic of Korea 2 Chung-Ang University, Department of Pharmacology, College of Medicine, Republic of Korea 3 Sungkyunkwan University, Department of Pharmacology, School of Pharmacy, Republic of Korea It is well-known that down-regulation of GSH-dependent system contribute to schizophrenic condition, and that GSH is an essential substrate of glutathione peroxidase (GPx). As GPx-1 out of GPx isozymes has been recognized as a major isozyme, we investigated the role of GPx-1 gene against behavioral deficits induced by phencyclidine (PCP). PCP-induced behavioral effects were more evident in the GPx-1 knockout (KO) than those in wild type (WT) mice, and these behavioral effects were less pronounced in GPx-1 overexpressing transgenic (GPx-1 TG) than those in non-TG mice. PCP treatment significantly reduced GSH level, and enhanced oxidative burdens in the prefrontal cortex (> hippocampus). PCP treatment significantly up-regulated Nrf2 and NF-kappaB activities, and gamma-glutamylcysteine modifier subunit (GCLm) mRNA expression in WT and non-TG mice. However, GPx-1 KO abolished this up-regulation. On the other hands, genetic overexpression of GPx-1 further up-regulated significantly Nrf2-dependent GSH induction, but down-regulated NF-kappaB p65 activity in the presence of PCP. Antipsychotic clozapine (> haloperidol) significantly up-regulated this Nrf2-dependent GSH synthesis in the presence of PCP, but failed to affect NF-kappaB p65 activity. Our results suggest that co-modulations between GPx-1 gene and Nrf2-dependent GSH synthesis are important for ameliorating behavioral deficits induced by PCP in mice. Acknowledgements This study was supported by a grant (14182MFDS979) from the Korea Food and Drug Administration, Republic of Korea. The-Vinh Tran was supported by the BK21 PLUS program, National Research Foundation of Korea, Republic of Korea. Keywords: Gene Expression, antipsychotic, in vivo, modulation, behavioural deficit Conference: 14th Meeting of the Asian-Pacific Society for Neurochemistry, Kuala Lumpur, Malaysia, 27 Aug - 30 Aug, 2016. Presentation Type: Poster Presentation Session Topic: 14th Meeting of the Asian-Pacific Society for Neurochemistry Citation: Tran T, Shin E, Jeong J, Jang C and Kim H (2016). Antipsychotic clozapine attenuates phencyclidine-induced behavioral deficits through positive modulation of glutathione peroxidase-1 in mice. Conference Abstract: 14th Meeting of the Asian-Pacific Society for Neurochemistry. doi: 10.3389/conf.fncel.2016.36.00143 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 04 Aug 2016; Published Online: 11 Aug 2016. * Correspondence: Mr. The-Vinh Tran, Kangwon National University, Neuropsychopharmacology and Toxicology Program, College of Pharmacy, Chunchon, Kangwon-do, Republic of Korea, thevinh@kangwon.ac.kr Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers The-Vinh Tran Eun-Joo Shin Ji Hoon Jeong Choon-Gon Jang Hyoung-Chun Kim Google The-Vinh Tran Eun-Joo Shin Ji Hoon Jeong Choon-Gon Jang Hyoung-Chun Kim Google Scholar The-Vinh Tran Eun-Joo Shin Ji Hoon Jeong Choon-Gon Jang Hyoung-Chun Kim PubMed The-Vinh Tran Eun-Joo Shin Ji Hoon Jeong Choon-Gon Jang Hyoung-Chun Kim Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.