Central and Peripheral Respiratory Disturbances in a Mice Model of Parkinson's Disease

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 and breathing difficulty. Breathing abnormalities have been recognized as a cause of morbidity and mortality of PD patients. It is well known that PD patients have a predisposition to develop pneumonia, embolism and allergic reactions compared to general population. However, it's not clear if an animal model of PD could develop lung properties changes. The aim of the present study is to confirm the role of neurodegenerative processes in brainstem regions involved in breathing control and to investigate lung properties in a mouse model of PD. Experiments were performed in adult male C57BL/6 mice (20–25 g, N = 14). The animals received bilateral injection of 6‐hydroxydopamine hydrochloride (6‐OHDA; 10 μg/μL; 0.5 μL) or vehicle into the striatum. The ventilatory parameters were assessed by whole body plethysmograph and measurements of respiratory mechanics by a mouse ventilator (flexiVent) 40 days after PD induction. 6‐OHDA reduced the number of tyrosine hydroxilase (TH+) neurons in the SNpc 40 days after the toxin injection. No changes in TH+ were observed in C1 and Locus coeruleus regions in PD mice. We also noticed a reduction in the immunoreactivity of neurokinin‐1 receptors (NK1R) in the pre‐Bötzinger complex (preBötC) and in the number of Phox2b neurons in the retrotrapezoid nucleus (RTN). Physiological experiments were conducted in the same animals. Resting respiratory frequency (fR) in PD animals was reduced (156.3 ± 3.4 vs. control: 176.1 ± 3.5 breaths/min) leading to an increase of expiratory time (TE) (0.36 ± 0.02 vs. control: 0.28 ± 0.03 ms). In respect to mechanical properties, PD animals with preserved thorax elicited an increase in airway resistance (0.33 ± 0.02 vs. control: 0.27 ± 0.01 cmH2O.s/ml) and elastance (31.3 ± 2.1 vs. control: 25.3 ± 0.6 cmH2O/ml, p<0.019). However, after open the thorax, PD animals did not show changes in airway resistance, but still have an increase in elastance (30.8 ± 2.1 vs. control: 24.0 ± 1.4 cmH2O/ml, p<0.017), indicating that the ribcage could be stiffened in PD. PD animals presented collagen deposition in alveolar septa (18.3 ± 1.5 vs. control: 12.5 ± 1.4 %). Our data showed that PD animals presented neurodegeneration in respiratory brainstem areas and a disruption of lung properties, suggesting that central and peripheral deficiencies can contribute to the respiratory changes observed in this model.Support or Funding InformationFAPESP, CNPq, CAPES/PROEXThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.