Changes to Ventilation, Vocalization, and Thermal Nociception in the Pink1–/– Rat Model of Parkinson’s Disease

• Published in: Journal of Parkinson's disease Vol. 10; no. 2; pp. 489 - 504
• Main Authors: Johnson, Rebecca A., Kelm-Nelson, Cynthia A., Ciucci, Michelle R.
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 2020; IOS Press BV
• Subjects: Age; Autopsy; Brain stem; Chemoreception; Dopamine; Gait; Genotypes; Hypercapnia; Hypoxia; Information processing; Larynx; Locus coeruleus; Mechanical ventilation; Movement disorders; Neurodegenerative diseases; Pain perception; Parkinson's disease; PTEN-induced putative kinase; Rodents; Sensorimotor system; Sensory integration; Serotonin; Synuclein; Ventilation; Vocalization behavior; Pink1; rat; sensory; ultrasonic vocalization; Parkinson’s disease; ventilation
• ISSN: 1877-7171; 1877-718X
• DOI: 10.3233/JPD-191853

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.