Centre for Brain Research and Department of Anatomy with Medical Imaging, University of Auckland, Auckland, New Zealand.
Waikato Mass Spectrometry Facility, University of Waikato, Hamilton, New Zealand.
Sci Rep. 2017 Sep 5;7(1):10454. doi: 10.1038/s41598-017-10659-6.
In Parkinson's disease (PD), the olfactory bulb is typically the first region in the body to accumulate alpha-synuclein aggregates. This pathology is linked to decreased olfactory ability, which becomes apparent before any motor symptoms occur, and may be due to a local metal imbalance. Metal concentrations were investigated in post-mortem olfactory bulbs and tracts from 17 human subjects. Iron (p < 0.05) and sodium (p < 0.01) concentrations were elevated in the PD olfactory bulb. Combining laser ablation inductively coupled plasma mass spectrometry and immunohistochemistry, iron and copper were evident at very low levels in regions of alpha-synuclein aggregation. Zinc was high in these regions, and free zinc was detected in Lewy bodies, mitochondria, and lipofuscin of cells in the anterior olfactory nucleus. Increased iron and sodium in the human PD olfactory bulb may relate to the loss of olfactory function. In contrast, colocalization of free zinc and alpha-synuclein in the anterior olfactory nucleus implicate zinc in PD pathogenesis.
在帕金森病（PD）中，嗅球通常是体内第一个积累α-突触核蛋白聚集物的区域。这种病理学与嗅觉能力下降有关，这种下降在出现任何运动症状之前就已经很明显，可能是由于局部金属失衡引起的。研究人员调查了 17 名人类尸体的嗅球和嗅束中的金属浓度。PD 嗅球中的铁（p<0.05）和钠（p<0.01）浓度升高。结合激光烧蚀电感耦合等离子体质谱和免疫组织化学，在α-突触核蛋白聚集区域可以检测到铁和铜的极低水平。这些区域的锌含量很高，Lewy 体、线粒体和嗅前核细胞中的脂褐素中检测到游离锌。人类 PD 嗅球中的铁和钠增加可能与嗅觉功能丧失有关。相比之下，游离锌和α-突触核蛋白在前嗅核中的共定位表明锌在 PD 发病机制中起作用。
