Parkinson’s disease (PD) features nonmotor symptoms such as olfactory dysfunction referred to as hyposmia, an initial sign of disease progression. Metabolic dysfunction can contribute to neurodegenerative diseases, and various xenobiotics and endogenous compounds are also involved in the pathogenesis of PD. Although aerobic exercise was found to induce preservation or improvement in olfactory function in PD patients in a recent study, the exact underlying mechanism for this effect is not clear. We aimed to investigate the influence of an enriched environment (EE) on olfactory dysfunction especially via metabolic pathways related to detoxification enzymes. Eight-month-old transgenic (Tg) PD mice that overexpress human A53T α-synuclein (α-syn) were randomly allocated to an EE or standard conditions for 2 mo. The buried food test showed that EE group had significantly improved olfactory function compared to the control group. Reverse transcription polymerase chain reaction (PCR) and real-time quantitative PCR showed that expression of the detoxification enzymes––cytochrome P450 family 1 subfamily A member 2, paraoxonase 1, alcohol dehydrogenase 1, UDP glucuronosyltransferase family 2 member A1 complex locus, aldehyde oxidase homolog 2, and aldehyde glutathione peroxidase 6––was significantly increased in the olfactory bulb (OB) of the PD control group, but these enzymes were normalized in the EE group. Immunohistochemical staining of the OB showed that oxidative stress and nitrated α-syn were significantly increased in the control group but decreased in the EE group. In conclusion, we suggest that exposure to an EE decreases both oxidative stress and nitrated α-syn, resulting in normalized detoxification enzymes and amelioration of olfactory dysfunction.
Bibliographical noteFunding Information:
The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This study was supported by grants from the National Research Foundation (NRF-2014R1A2A1A11052042; 2015M3A9B40 67068) and the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI) funded by the Ministry of Health and Welfare (HI16C1012, HI16C1013, and HI16C1176), Republic of South Korea.
© The Author(s) 2018.
All Science Journal Classification (ASJC) codes
- Biomedical Engineering
- Cell Biology