The Effect of Environmental Enrichment on Glutathione-Mediated Xenobiotic Metabolism and Antioxidation in Normal Adult Mice

Olfactory bulb (OB) plays an important role in protecting against harmful substances via the secretion of antioxidant and detoxifying enzymes. Environmental enrichment (EE) is a common rehabilitation method and known to have beneficial effects in the central nervous system. However, the effects of E...

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Main Authors: Jung Hwa Seo, Soonil Pyo, Yoon-Kyum Shin, Bae-Geun Nam, Jeong Won Kang, Kwang Pyo Kim, Hoo Young Lee, Sung-Rae Cho
Format: Article
Language:English
Published: Frontiers Media S.A. 2018-07-01
Series:Frontiers in Neurology
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fneur.2018.00425/full
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author Jung Hwa Seo
Jung Hwa Seo
Soonil Pyo
Soonil Pyo
Yoon-Kyum Shin
Yoon-Kyum Shin
Bae-Geun Nam
Bae-Geun Nam
Jeong Won Kang
Jeong Won Kang
Kwang Pyo Kim
Hoo Young Lee
Hoo Young Lee
Hoo Young Lee
Sung-Rae Cho
Sung-Rae Cho
Sung-Rae Cho
Sung-Rae Cho
Sung-Rae Cho
Sung-Rae Cho
author_facet Jung Hwa Seo
Jung Hwa Seo
Soonil Pyo
Soonil Pyo
Yoon-Kyum Shin
Yoon-Kyum Shin
Bae-Geun Nam
Bae-Geun Nam
Jeong Won Kang
Jeong Won Kang
Kwang Pyo Kim
Hoo Young Lee
Hoo Young Lee
Hoo Young Lee
Sung-Rae Cho
Sung-Rae Cho
Sung-Rae Cho
Sung-Rae Cho
Sung-Rae Cho
Sung-Rae Cho
author_sort Jung Hwa Seo
collection DOAJ
description Olfactory bulb (OB) plays an important role in protecting against harmful substances via the secretion of antioxidant and detoxifying enzymes. Environmental enrichment (EE) is a common rehabilitation method and known to have beneficial effects in the central nervous system. However, the effects of EE in the OB still remain unclear. At 6 weeks of age, CD-1® (ICR) mice were assigned to standard cages or EE cages. After 2 months, we performed proteomic analysis. Forty-four up-regulated proteins were identified in EE mice compared to the control mice. Gene Ontology analysis and Kyoto Encyclopedia of Genes and Genomes Pathway demonstrated that the upregulated proteins were mainly involved in metabolic pathways against xenobiotics. Among those upregulated proteins, 9 proteins, which participate in phase I or II of the xenobiotic metabolizing process and are known to be responsible for ROS detoxification, were validated by qRT-PCR. To explore the effect of ROS detoxification mediated by EE, glutathione activity was measured by an ELISA assay. The ratio of reduced glutathione to oxidized glutathione was significantly increased in EE mice. Based on a linear regression analysis, GSTM2 and UGT2A1 were found to be the most influential genes in ROS detoxification. For further analysis of neuroprotection, the level of iNOS and the ratio of Bax to Bcl-2 were significantly decreased in EE mice. While TUNEL+ cells were significantly decreased, Ki67+ cells were significantly increased in EE mice, implicating that EE creates an optimal state for xenobiotic metabolism and antioxidant activity. Taken together, our results suggested that EE protects olfactory layers via the upregulation of glutathione-related antioxidant and xenobiotic metabolizing enzymes, eventually lowering ROS-mediated inflammation and apoptosis and increasing neurogenesis. This study may provide an opportunity for a better understanding of the beneficial effects of EE in the OB.
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spelling doaj.art-97b09b8525c84f509dca7b1d8972c6a72022-12-22T01:14:25ZengFrontiers Media S.A.Frontiers in Neurology1664-22952018-07-01910.3389/fneur.2018.00425336327The Effect of Environmental Enrichment on Glutathione-Mediated Xenobiotic Metabolism and Antioxidation in Normal Adult MiceJung Hwa Seo0Jung Hwa Seo1Soonil Pyo2Soonil Pyo3Yoon-Kyum Shin4Yoon-Kyum Shin5Bae-Geun Nam6Bae-Geun Nam7Jeong Won Kang8Jeong Won Kang9Kwang Pyo Kim10Hoo Young Lee11Hoo Young Lee12Hoo Young Lee13Sung-Rae Cho14Sung-Rae Cho15Sung-Rae Cho16Sung-Rae Cho17Sung-Rae Cho18Sung-Rae Cho19Department and Research Institute of Rehabilitation Medicine, Yonsei University College of Medicine, Seoul, South KoreaBrain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, South KoreaDepartment and Research Institute of Rehabilitation Medicine, Yonsei University College of Medicine, Seoul, South KoreaBrain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, South KoreaDepartment and Research Institute of Rehabilitation Medicine, Yonsei University College of Medicine, Seoul, South KoreaBrain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, South KoreaDepartment and Research Institute of Rehabilitation Medicine, Yonsei University College of Medicine, Seoul, South KoreaGraduate Program of NanoScience and Technology, Yonsei University, Seoul, South KoreaDepartment of Applied Chemistry, Kyung Hee University, Yongin, South KoreaPrecision Medicine Branch, Research Institute, National Cancer Center, Goyang, South KoreaDepartment of Applied Chemistry, Kyung Hee University, Yongin, South KoreaDepartment of Medicine, The Graduate School of Yonsei University, Seoul, South KoreaTBI Rehabilitation Center, National Traffic Injury Rehabilitation Hospital, Yangpyeong, South KoreaDepartment of Rehabilitation Medicine, School of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, South KoreaDepartment and Research Institute of Rehabilitation Medicine, Yonsei University College of Medicine, Seoul, South KoreaBrain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, South KoreaGraduate Program of NanoScience and Technology, Yonsei University, Seoul, South KoreaDepartment of Medicine, The Graduate School of Yonsei University, Seoul, South KoreaYonsei Stem Cell Research Center, Avison Biomedical Research Center, Seoul, South Korea0Rehabilitation Institute of Neuromuscular Disease, Yonsei University College of Medicine, Seoul, South KoreaOlfactory bulb (OB) plays an important role in protecting against harmful substances via the secretion of antioxidant and detoxifying enzymes. Environmental enrichment (EE) is a common rehabilitation method and known to have beneficial effects in the central nervous system. However, the effects of EE in the OB still remain unclear. At 6 weeks of age, CD-1® (ICR) mice were assigned to standard cages or EE cages. After 2 months, we performed proteomic analysis. Forty-four up-regulated proteins were identified in EE mice compared to the control mice. Gene Ontology analysis and Kyoto Encyclopedia of Genes and Genomes Pathway demonstrated that the upregulated proteins were mainly involved in metabolic pathways against xenobiotics. Among those upregulated proteins, 9 proteins, which participate in phase I or II of the xenobiotic metabolizing process and are known to be responsible for ROS detoxification, were validated by qRT-PCR. To explore the effect of ROS detoxification mediated by EE, glutathione activity was measured by an ELISA assay. The ratio of reduced glutathione to oxidized glutathione was significantly increased in EE mice. Based on a linear regression analysis, GSTM2 and UGT2A1 were found to be the most influential genes in ROS detoxification. For further analysis of neuroprotection, the level of iNOS and the ratio of Bax to Bcl-2 were significantly decreased in EE mice. While TUNEL+ cells were significantly decreased, Ki67+ cells were significantly increased in EE mice, implicating that EE creates an optimal state for xenobiotic metabolism and antioxidant activity. Taken together, our results suggested that EE protects olfactory layers via the upregulation of glutathione-related antioxidant and xenobiotic metabolizing enzymes, eventually lowering ROS-mediated inflammation and apoptosis and increasing neurogenesis. This study may provide an opportunity for a better understanding of the beneficial effects of EE in the OB.https://www.frontiersin.org/article/10.3389/fneur.2018.00425/fullenvironmental enrichmentolfactory bulbmetabolizing enzymesantioxidantdetoxificationglutathione
spellingShingle Jung Hwa Seo
Jung Hwa Seo
Soonil Pyo
Soonil Pyo
Yoon-Kyum Shin
Yoon-Kyum Shin
Bae-Geun Nam
Bae-Geun Nam
Jeong Won Kang
Jeong Won Kang
Kwang Pyo Kim
Hoo Young Lee
Hoo Young Lee
Hoo Young Lee
Sung-Rae Cho
Sung-Rae Cho
Sung-Rae Cho
Sung-Rae Cho
Sung-Rae Cho
Sung-Rae Cho
The Effect of Environmental Enrichment on Glutathione-Mediated Xenobiotic Metabolism and Antioxidation in Normal Adult Mice
Frontiers in Neurology
environmental enrichment
olfactory bulb
metabolizing enzymes
antioxidant
detoxification
glutathione
title The Effect of Environmental Enrichment on Glutathione-Mediated Xenobiotic Metabolism and Antioxidation in Normal Adult Mice
title_full The Effect of Environmental Enrichment on Glutathione-Mediated Xenobiotic Metabolism and Antioxidation in Normal Adult Mice
title_fullStr The Effect of Environmental Enrichment on Glutathione-Mediated Xenobiotic Metabolism and Antioxidation in Normal Adult Mice
title_full_unstemmed The Effect of Environmental Enrichment on Glutathione-Mediated Xenobiotic Metabolism and Antioxidation in Normal Adult Mice
title_short The Effect of Environmental Enrichment on Glutathione-Mediated Xenobiotic Metabolism and Antioxidation in Normal Adult Mice
title_sort effect of environmental enrichment on glutathione mediated xenobiotic metabolism and antioxidation in normal adult mice
topic environmental enrichment
olfactory bulb
metabolizing enzymes
antioxidant
detoxification
glutathione
url https://www.frontiersin.org/article/10.3389/fneur.2018.00425/full
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