Evidence for early and progressive ultrasonic vocalization and oromotor deficits in a PINK1 gene knockout rat model of Parkinson's disease

Parkinson's disease (PD) is a progressive neurodegenerative disease that leads to a wide range of motor and nonmotor deficits. Specifically, voice and swallow deficits manifest early, are devastating to quality of life, and are difficult to treat with standard medical therapies. The pathologica...

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Bibliographic Details
Published in:Journal of neuroscience research 2015-11, Vol.93 (11), p.1713-1727
Main Authors: Grant, Laura M., Kelm-Nelson, Cynthia A., Hilby, Breanna L., Blue, Katherine V., Paul Rajamanickam, Eunice S., Pultorak, Joshua D., Fleming, Shelia M., Ciucci, Michelle R.
Format: Article
Language:English
Subjects:
alpha-Synuclein - genetics
alpha-Synuclein - metabolism
Animals
Ataxia - genetics
Brain - pathology
cranial-sensorimotor
Disease Models, Animal
Gene Knockout Techniques
Immunohistochemistry
Male
Motor Activity - genetics
Muscle Strength - genetics
Parkinson Disease - complications
Parkinson Disease - genetics
Parkinson Disease - pathology
Parkinson's disease
PINK1
Protein Kinases - genetics
rat
Rats
Rats, Long-Evans
RRID:AB_1977522
RRID:AB_390204
Tongue - innervation
Tyrosine 3-Monooxygenase - genetics
Tyrosine 3-Monooxygenase - metabolism
ultrasonic vocalization
Vocalization, Animal - physiology
α-synuclein
α‐synuclein
rat
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Summary:Parkinson's disease (PD) is a progressive neurodegenerative disease that leads to a wide range of motor and nonmotor deficits. Specifically, voice and swallow deficits manifest early, are devastating to quality of life, and are difficult to treat with standard medical therapies. The pathological hallmarks of PD include accumulation of the presynaptic protein α‐synuclein (αSyn) as well as degeneration of substantia nigra dopaminergic neurons. However, there is no clear understanding of how or when this pathology contributes to voice and swallow dysfunction in PD. The present study evaluates the effect of loss of function of the phosphatase and tensin homolog‐induced putative kinase 1 gene in rats (PINK1–/–), a model of autosomal recessive PD in humans, on vocalization, oromotor and limb function, and neurodegenerative pathologies. Behavioral measures include ultrasonic vocalizations, tongue force, biting, and gross motor performance that are assayed at 2, 4, 6, and 8 months of age. Aggregated αSyn and tyrosine hydroxylase immunoreactivity (TH‐ir) were measured at 8 months. We show that, compared with wild‐type controls, PINK1–/– rats develop 1) early and progressive vocalization and oromotor deficits, 2) reduced TH‐ir in the locus coeruleus that correlates with vocal loudness and tongue force, and 3) αSyn neuropathology in brain regions important for cranial sensorimotor control. This novel approach of characterizing a PINK1–/– genetic model of PD provides the foundational work required to define behavioral biomarkers for the development of disease‐modifying therapeutics for PD patients. © 2015 Wiley Periodicals, Inc. Parkinson disease (PD) is a progressive neurodegenerative disease that leads to a wide range of deficits, including voice and swallow deficits. We show that PINK1 ‐/‐ rats develop vocalization and oromotor deficits as well as neuropathology in brain regions important for cranial sensorimotor control.
ISSN:0360-4012
1097-4547
DOI:10.1002/jnr.23625