The effect of environmental enrichment on glutathione-mediated xenobiotic metabolism and antioxidation in normal adult mice

Jung Hwa Seo, Soonil Pyo, Yoon Kyum Shin, Bae Geun Nam, Jeong Won Kang, Kwang Pyo Kim, Hoo Young Lee, Sung Rae Cho

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5 Citations (Scopus)


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.

Original languageEnglish
Article number425
JournalFrontiers in Neurology
Issue numberJUL
Publication statusPublished - 2018 Jul 4

Bibliographical note

Funding Information:
This study was supported by grants from the National Research Foundation (NRF-5-2017-A0154-00395), the Ministry of Science and Technology, Republic of Korea, the Korean Health Technology R&D Project (HI16C1012), Ministry of Health & Welfare, Republic of Korea

Publisher Copyright:
© 2018 Seo, Pyo, Shin, Nam, Kang, Kim, Lee and Cho.

All Science Journal Classification (ASJC) codes

  • Neurology
  • Clinical Neurology


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