Witt Martin, Bormann Katja, Gudziol Volker, Pehlke Kerstin, Barth Kathrin, Minovi Amir, Hähner Antje, Reichmann Heinz, Hummel Thomas
Department of Anatomy, University of Rostock, Gertrudenstrasse 9, Rostock, Germany.
Mov Disord. 2009 Apr 30;24(6):906-14. doi: 10.1002/mds.22464.
Parkinson's disease (PD) is a neurodegenerative disorder involving several neuronal systems. Impaired olfactory function may constitute one of the earliest symptoms of PD. However, it is still unclear to what degree changes of the olfactory epithelium may contribute to dysosmia and if these changes are different from those of other hyposmic or anosmic patients. This study aimed to investigate the hypothesis that olfactory loss in PD is a consequence of specific PD-related damage of olfactory epithelium. Biopsies of 7 patients diagnosed with PD were taken. Six patients with PD were hyposmic, one anosmic. As non-PD controls served 9 patients with hyposmia, 9 with anosmia, and 7 normosmic individuals. Further, nasal mucosa of 4 postmortem individuals was investigated. Immunohistochemical examinations were performed with antibodies against olfactory marker protein (OMP), protein gene product 9.5 (PGP 9.5), beta-tubulin, (BT), proliferation-associated antigen (Ki 67), the stem cell marker nestin, cytokeratin, p75NGFr, and alpha-synuclein. Most of the biopsy specimens exhibited irregular areas of olfactory-like, dysplastic epithelium positive for either PGP 9.5 or BT, but negative for OMP. No major histochemical differences in either the expression or distribution of these proteins were observed in the olfactory epithelium of patients with PD compared with controls. Reverse transcription PCR (RT-PCR) data indicated mRNA for OMP in almost all subjects, independently of their olfactory performance. These data support the idea that olfactory loss in Parkinson's disease is not a consequence of damage to the olfactory epithelium but rather results from distinct central-nervous abnormalities.
帕金森病（PD）是一种涉及多个神经元系统的神经退行性疾病。嗅觉功能受损可能是PD最早出现的症状之一。然而，目前仍不清楚嗅觉上皮的变化在多大程度上导致嗅觉障碍，以及这些变化是否与其他嗅觉减退或嗅觉丧失患者的变化不同。本研究旨在探讨PD患者嗅觉丧失是嗅觉上皮特异性PD相关损伤所致这一假说。对7例诊断为PD的患者进行了活检。6例PD患者嗅觉减退，1例嗅觉丧失。作为非PD对照的有9例嗅觉减退患者、9例嗅觉丧失患者和7例嗅觉正常个体。此外，还对4例尸检个体的鼻黏膜进行了研究。使用针对嗅觉标记蛋白（OMP）、蛋白基因产物9.5（PGP 9.5）、β-微管蛋白（BT）、增殖相关抗原（Ki 67）、干细胞标记物巢蛋白、细胞角蛋白、p75神经生长因子受体（p75NGFr）和α-突触核蛋白的抗体进行免疫组织化学检查。大多数活检标本显示出不规则区域的类似嗅觉的发育异常上皮，PGP 9.5或BT呈阳性，但OMP呈阴性。与对照组相比，PD患者嗅觉上皮中这些蛋白的表达或分布未观察到明显的组织化学差异。逆转录聚合酶链反应（RT-PCR）数据表明，几乎所有受试者中都有OMP的mRNA，与他们的嗅觉表现无关。这些数据支持了帕金森病患者嗅觉丧失不是嗅觉上皮损伤的结果，而是由明显的中枢神经异常导致的这一观点。
