1 Department and Research Institute of Rehabilitation Medicine, Yonsei University College of Medicine, Seoul, South Korea.
2 Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, South Korea.
Cell Transplant. 2018 May;27(5):831-839. doi: 10.1177/0963689717742662. Epub 2018 Apr 30.
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.
帕金森病（PD）的非运动症状包括嗅觉功能障碍，即嗅觉减退，这是疾病进展的早期标志。代谢功能障碍可导致神经退行性疾病，各种外源性和内源性化合物也参与 PD 的发病机制。尽管最近的一项研究发现，有氧运动可诱导 PD 患者嗅觉功能的保存或改善，但这种作用的确切潜在机制尚不清楚。我们旨在研究丰富环境（EE）对嗅觉功能障碍的影响，特别是通过与解毒酶相关的代谢途径。8 月龄过表达人 A53T α-突触核蛋白（α-syn）的转基因（Tg）PD 小鼠被随机分配到 EE 或标准条件下 2 个月。埋藏食物试验表明，EE 组的嗅觉功能明显优于对照组。逆转录聚合酶链反应（PCR）和实时定量 PCR 显示，解毒酶——细胞色素 P450 家族 1 亚家族 A 成员 2、对氧磷酶 1、醇脱氢酶 1、UDP 葡糖醛酸基转移酶家族 2 成员 A1 复合物基因座、醛氧化酶同源物 2 和醛谷胱甘肽过氧化物酶 6——在 PD 对照组的嗅球（OB）中的表达显著增加，但在 EE 组中这些酶被正常化。OB 的免疫组织化学染色显示，对照组的氧化应激和硝化 α-syn 显著增加，而 EE 组则减少。总之，我们认为暴露于 EE 可降低氧化应激和硝化 α-syn，从而使解毒酶正常化并改善嗅觉功能障碍。
