Respiratory disturbances in a mouse model of Parkinson's disease

New Findings

What is the central question of this study? Clinical reports have described and suggested respiratory central and peripheral abnormalities in PD patients; however, these reports have never addressed the occurrences of such abnormalities in an animal model before. PD mice has reduced NK1r‐ir in the preBötC and Phox2b‐expressing neurons in the RTN. PD mice has respiratory frequency and HCVR impairments. Lung collagen deposition and ribcage stiffness appear in PD mice.

Abstract

Parkinson's disease (PD) is a neurodegenerative motor disorder characterized by dopaminergic deficits in the brain. PD patients may experience shortness of breath, dyspnea, breathing difficulty 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 injection of 6‐hydroxydopamine (6‐OHDA; 10 μg/μL; 0.5 μL) or vehicle into the striatum. Ventilatory parameters were assessed in the 40 days following PD induction, by whole body plethysmography. In addition, measurements of respiratory input impedance (closed and opened thorax) were performed. 6‐OHDA reduced the number of tyrosine hydroxylase neurons in the SNpc, the density of neurokinin‐1 receptors immunoreactivity in the pre‐Bӧtzinger complex (preBötC) and the number of Phox2b neurons in the retrotrapezoid nucleus (RTN). Physiological experiments revealed decreased resting respiratory frequency (f_R) in PD animals, due to an increase in expiratory time (T_E) and a blunted hypercapnic ventilatory response. Measurements of respiratory input impedance showed that only PD animals with preserved thorax had increased viscance, indicating that the ribcage could present a stiffening 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 neurodegeneration in respiratory brainstem centers and disruption of lung mechanical properties; suggesting that both central and peripheral deficiencies contribute to PD‐related respiratory pathologies.

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