Affiliations: [a] Department of Surgical Sciences, University of Wisconsin-Madison, Madison, WI, USA
| [b] Division of Otolaryngology, Department of Surgery, University of Wisconsin-Madison, Madison, WI, USA
| [c] Department of Communication Sciences and Disorders, University of Wisconsin-Madison, Madison, WI, USA
| [d] Neuroscience Training Program, University of Wisconsin-Madison, Madison, WI, USA
Correspondence:
[*]
Correspondence to: Michelle R. Ciucci, Scott H. Goodnight Hall, 1975 Willow Drive, University of
Wisconsin-Madison, Madison, WI 53706, USA. Tel.: +1 608 262 6122; Fax: +1 608 262 6356;
E-mail: [email protected].
Abstract: Background:Individuals with Parkinson’s disease (PD) experience significant vocal communication deficits. Findings in the Pink1–/– rat model of early-onset PD suggest that ultrasonic vocal communication is impaired early, progressively worsens prior to nigrostriatal dopamine depletion, and is associated with loss of locus coeruleus neurons, brainstem α-synuclein, and larynx pathology. Individuals with PD also demonstrate ventilatory deficits and altered sensory processing, which may contribute to vocal deficits. Objective:The central hypothesis is that ventilatory and sensory deficits are present in the early disease stages when limb and vocal motor deficits also present. Methods:Pink1–/– rats were compared to wildtype (WT) controls at longitudinal timepoints. Whole-body flow through plethysmography was used to measure ventilation in the following conditions: baseline, hypoxia, and maximal chemoreceptor stimulation. Plantar thermal nociception, and as a follow up to previous work, limb gait and vocalization were analyzed. Serotonin density (5-HT) in the dorsal raphe was quantified post-mortem. Results:Baseline breathing frequencies were consistently higher in Pink1–/– rats at all time points. In hypoxic conditions, there were no significant changes between genotypes. With hypercapnia, Pink1–/– rats had decreased breathing frequencies with age. Thermal withdrawal latencies were significantly faster in Pink1–/– compared with WT rats across time. No differences in 5-HT were found between genotypes. Vocal peak frequency was negatively correlated to tidal volume and minute ventilation in Pink1–/– rats. Conclusion:This work suggests that abnormal nociceptive responses in Pink1–/– rats and ventilatory abnormalities may be associated with abnormal sensorimotor processing to chemosensory stimuli during disease manifestation.
Keywords: Pink1, ventilation, rat, sensory, ultrasonic vocalization, Parkinson’s disease
