Department of Pharmacology, Institute of Biomedical Science, University of São Paulo, São Paulo, SP, Brazil.
Biomedical Engineering Laboratory, University of São Paulo, São Paulo, Brazil.
Exp Physiol. 2019 May;104(5):729-739. doi: 10.1113/EP087507. Epub 2019 Mar 7.
What is the central question of this study? Clinical reports have described and suggested central and peripheral respiratory abnormalities in Parkinson's disease (PD) patients; however, these reports have never addressed the occurrence of these abnormalities in an animal model. What is the main finding and its importance? A mouse model of PD has reduced neurokinin-1 receptor immunoreactivity in the pre-Bӧtzinger complex and Phox2b-expressing neurons in the retrotrapezoid nucleus. The PD mouse has impairments of respiratory frequency and the hypercapnic ventilatory response. Lung collagen deposition and ribcage stiffness appear in PD mice.
Parkinson's disease (PD) is a neurodegenerative motor disorder characterized by dopaminergic deficits in the brain. Parkinson's disease patients may experience shortness of breath, dyspnoea, breathing difficulties and pneumonia, which can be linked as a cause of morbidity and mortality of those patients. The aim of the present study was to clarify whether a mouse model of PD could develop central brainstem and lung respiratory abnormalities. Adult male C57BL/6 mice received bilateral injections of 6-hydroxydopamine (10 μg μl ; 0.5 μl) or vehicle into the striatum. Ventilatory parameters were assessed in the 40 days after induction of PD, by whole-body plethysmography. In addition, measurements of respiratory input impedance (closed and opened thorax) were performed. 6-Hydroxydopamine reduced the number of tyrosine hydroxylase neurons in the substantia nigra pars compacta, the density of neurokinin-1 receptor immunoreactivity in the pre-Bӧtzinger complex and the number of Phox2b neurons in the retrotrapezoid nucleus. Physiological experiments revealed a reduction in resting respiratory frequency in PD animals, owing to an increase in expiratory time and a blunted hypercapnic ventilatory response. Measurements of respiratory input impedance showed that only PD animals with the thorax preserved had increased viscance, indicating that the ribcage could be stiff in this animal model of PD. Consistent with stiffened ribcage mechanics, abnormal collagen deposits in alveolar septa and airways were observed in PD animals. Our data showed that our mouse model of PD presented with neurodegeneration in respiratory brainstem centres and disruption of lung mechanical properties, suggesting that both central and peripheral deficiencies contribute to PD-related respiratory pathologies.
本研究的核心问题是什么？临床报告描述并提示帕金森病（PD）患者存在中枢和外周呼吸异常；然而，这些报告从未涉及过动物模型中这些异常的发生。主要发现及其重要性是什么？PD 模型鼠的 Pre-Bӧtzinger 复合体中神经激肽-1 受体免疫反应性和梯形核中 Phox2b 表达神经元减少。PD 模型鼠的呼吸频率和高碳酸血症通气反应受损。PD 模型鼠出现肺胶原沉积和肋骨刚性增加。
帕金森病（PD）是一种神经退行性运动障碍，其特征是大脑中多巴胺能神经元缺失。帕金森病患者可能会出现呼吸急促、呼吸困难和肺炎，这些可能会导致患者的发病率和死亡率上升。本研究旨在阐明 PD 模型鼠是否会出现中枢脑干和肺部呼吸异常。成年雄性 C57BL/6 小鼠接受双侧纹状体 6-羟多巴胺（10μgμl；0.5μl）或载体注射。在 PD 诱导后 40 天，通过全身 plethysmography 评估通气参数。此外，还进行了呼吸输入阻抗（闭合和开放胸廓）的测量。6-羟多巴胺减少了黑质致密部酪氨酸羟化酶神经元的数量、Pre-Bӧtzinger 复合体中神经激肽-1 受体免疫反应性的密度以及梯形核中 Phox2b 神经元的数量。生理实验显示，PD 动物的静息呼吸频率降低，这是由于呼气时间延长和高碳酸血症通气反应减弱所致。呼吸输入阻抗测量显示，只有胸廓保持完整的 PD 动物才有粘性增加，这表明 PD 动物模型的肋骨可能僵硬。与肋骨僵硬力学一致，PD 动物的肺泡隔和气道中观察到异常胶原沉积。我们的数据表明，我们的 PD 模型鼠存在呼吸脑干中心的神经退行性变和肺部力学特性的破坏，提示中枢和外周缺陷都导致了与 PD 相关的呼吸病理学。
