Impaired Breathing During Exposure to Hypoxia and Carotid Body Dysfunction in an Animal Model of Parkinson's Disease

Background: Parkinson's disease (PD) manifestations involve respiratory dysfunction and motor disability. Previous research on PD has mainly focused on central dopamine (DA) deficits and their effect on ventilation. Objectives: The purpose of the study was to analyze the function of carotid bodies (CB), sensors of blood O₂, by studying the hypoxic ventilatory response (HVR) and measuring biogenic amine content in the CB of a 6-hydroxydopamine (6-OHDA) induced PD model. We also investigated the effects of supplementation with the DA biosynthesis precursor L-DOPA on HVR and central DA depletion on hypoxic phrenic (PHR) and hypoglossal (HG) nerve activity. Methods: After 6-OHDA intrastriatal injection, awake Wistar rats were tested in a plethysmographic chamber to study the HVR (8% O₂) before and after L-DOPA treatment. Registration of PHR and HG under acute hypoxia (8% O₂) was performed in anesthetized rats. Results: The 6-OHDA rats showed reduced normoxic ventilation and HVR, eliminated by L-DOPA treatment. Increased HG activity during hypoxia in the form of increased amplitude and pre-inspiratory amplitude was observed. In addition to decreased striatal levels of DA, serotonin (5-HT) and noradrenaline (NA), reduced NA (42%) and 5-HT (52%) were found in CB of 6-OHDA rats. The open-field test showed a decrease in motor activity 2 weeks after the lesion. Conclusions: Our results showed NA and 5-HT deficits in CB in the PD model, which may be responsible for impaired HVR. L-DOPA treatment, replenishing DA deficiency in the striatum, stimulated HVR. Increased pre-inspiratory HG activity indicates modifications to the central mechanisms controlling their activity.