Abstract
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.
Highlights
The olfactory bulb (OB) is a region of brain that plays a critical role in health and pathological behaviors such as the detection of hazards in the environment, food selection, olfactory memory formation, mating, and maintenance of mood [1,2,3,4]
The up-regulated proteins in the Olfactory bulb (OB) of mice exposed to EE were categorized based on biological processes (BP), molecular functions (MF), and cellular components (CC) (Table 2)
We provided evidences that EE has the protective effects on the OB through setting an optimal status for antioxidant and xenobiotic metabolism
Summary
The olfactory bulb (OB) is a region of brain that plays a critical role in health and pathological behaviors such as the detection of hazards in the environment, food selection, olfactory memory formation, mating, and maintenance of mood [1,2,3,4]. To maintain cellular integrity and homeostasis of the brain from environmental chemicals, it is necessary to have active xenobiotic metabolism during the olfactory transport [6]. Phase III excretes the final modified product out of the cells via various transporters [6]. Metabolizing enzymes such as the cytochrome P450 (CYPs) family, the UDP-glucuronosyltransferases (UGT) family, glutathione-transferases (GST) family and the aldehyde dehydrogenase (ADH) family are involved in the detoxification process [6, 7]. The phase II enzymes such as UGT and GST family plays an important role in determining the rate of xenobiotic metabolism and ROS detoxification [8]
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