Rebecca A Johnson1, Cynthia A Kelm-Nelson2, Michelle R Ciucci2,3,4. 1. Department of Surgical Sciences, University of Wisconsin-Madison, Madison, WI, USA. 2. Division of Otolaryngology, Department of Surgery, University of Wisconsin-Madison, Madison, WI, USA. 3. Department of Communication Sciences and Disorders, University of Wisconsin-Madison, Madison, WI, USA. 4. Neuroscience Training Program, University of Wisconsin-Madison, Madison, WI, USA.
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.
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.
Authors: Joshua D Pultorak; Cynthia A Kelm-Nelson; Lauren R Holt; Katherine V Blue; Michelle R Ciucci; Aaron M Johnson Journal: Soc Neurosci Date: 2015-09-14 Impact factor: 2.083
Authors: Leigh M Seccombe; Hugh L Giddings; Peter G Rogers; Alastair J Corbett; Michael W Hayes; Matthew J Peters; Elizabeth M Veitch Journal: Respir Physiol Neurobiol Date: 2011-09-29 Impact factor: 1.931
Authors: Maryann N Krasko; Jesse D Hoffmeister; Nicole E Schaen-Heacock; Jacob M Welsch; Cynthia A Kelm-Nelson; Michelle R Ciucci Journal: Brain Sci Date: 2021-07-13