Journal of Parkinson's disease · 2020
Changes to Ventilation, Vocalization, and Thermal Nociception in the Pink1-/- Rat Model of Parkinson's Disease.
СтатьяПоддержка NIH: внешняя программаНазвание и аннотация: Перевод пока не подготовлен
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Johnson Rebecca A, Kelm-Nelson Cynthia A, Ciucci Michelle R
Аннотация
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.
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.