Understanding non-motor symptoms of Parkinson’s disease is important in order to unravel the underlying molecular mechanisms of the disease. Olfactory dysfunction is an early stage, non-motor symptom which occurs in 95% of Parkinson’s disease patients. Mitochondrial dysfunction is a key feature in Parkinson’s disease and importantly contributes to the selective loss of dopaminergic neurons the substantia nigra pars compacta. The olfactory bulb, the first olfactory processing station, also contains dopaminergic neurons, which modulate odor information and thereby enable odor detection as well as odor discrimination. MitoPark mice are a genetic model for Parkinson’s disease with severe mitochondrial dysfunction, reproducing the differential vulnerability of dopaminergic neurons in the midbrain. These animals were used to investigate the impact of mitochondrial dysfunction on olfactory-related behavior and olfactory bulb dopaminergic neuron survival. Odor detection was severely impaired in MitoPark mice. Interestingly, only the small anaxonic dopaminergic subpopulation, which is continuously replenished by neurogenesis, was moderately reduced in number, much less compared with dopaminergic neurons in the midbrain. As a potential compensatory response, an enhanced mobilization of progenitor cells was found in the subventricular zone. These results reveal a high robustness of dopaminergic neurons located in the olfactory bulb towards mitochondrial impairment, in striking contrast to their midbrain counterparts.

了解帕金森氏病的非运动性症状很重要，以阐明该病的潜在分子机制。嗅觉功能障碍是一种早期的非运动性症状，发生在95％的帕金森氏病患者中。线粒体功能障碍是帕金森氏病的一个关键特征，并且对黑质致密性多巴胺能神经元的选择性丧失起重要作用。。嗅球是第一个嗅觉处理站，它还包含多巴胺能神经元，该神经元可调节气味信息，从而实现气味检测和气味识别。MitoPark小鼠是患有严重线粒体功能障碍的帕金森氏病的遗传模型，在中脑中产生多巴胺能神经元的差异性脆弱性。这些动物被用来调查线粒体功能障碍对嗅觉相关行为和嗅球多巴胺能神经元存活的影响。MitoPark小鼠的气味检测严重受损。有趣的是，只有少量的无神经元多巴胺能亚群（通过神经发生不断补充）的数量有所减少，与中脑的多巴胺能神经元相比要少得多。作为一种潜在的补偿性对策，在脑室下区域发现增强了祖细胞的动员。这些结果表明，嗅球中的多巴胺能神经元对线粒体损伤具有很高的鲁棒性，与中脑类似物形成鲜明对比。