title: Evidence for early and progressive ultrasonic vocalization and oromotor deficits in a PINK1 gene knockout rat model of Parkinson's disease.
abstract: 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.
authors.affiliation: Division of Otolaryngology, Department of Surgery, University of Wisconsin-Madison, Madison, Wisconsin.|Department of Communication Sciences and Disorders, University of Wisconsin-Madison, Madison, Wisconsin.
authors.forename: Laura M
authors.initials: LM
authors.lastname: Grant
authors.affiliation: Division of Otolaryngology, Department of Surgery, University of Wisconsin-Madison, Madison, Wisconsin.
authors.forename: Cynthia A
authors.initials: CA
authors.lastname: Kelm-Nelson
authors.affiliation: Department of Communication Sciences and Disorders, University of Wisconsin-Madison, Madison, Wisconsin.
authors.forename: Breanna L
authors.initials: BL
authors.lastname: Hilby
authors.affiliation: Department of Communication Sciences and Disorders, University of Wisconsin-Madison, Madison, Wisconsin.
authors.forename: Katherine V
authors.initials: KV
authors.lastname: Blue
authors.affiliation: Department of Communication Sciences and Disorders, University of Wisconsin-Madison, Madison, Wisconsin.
authors.forename: Eunice S
authors.initials: ES
authors.lastname: Paul Rajamanickam
authors.affiliation: Department of Zoology, University of Wisconsin-Madison, Madison, Wisconsin.
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Pultorak
authors.affiliation: Department of Neurology, University of Cincinnati, Cincinnati, Ohio.
authors.forename: Shelia M
authors.initials: SM
authors.lastname: Fleming
authors.affiliation: Division of Otolaryngology, Department of Surgery, University of Wisconsin-Madison, Madison, Wisconsin.|Department of Communication Sciences and Disorders, University of Wisconsin-Madison, Madison, Wisconsin.|Neuroscience Training Program, University of Wisconsin-Madison, Madison, Wisconsin.
authors.forename: Michelle R
authors.initials: MR
authors.lastname: Ciucci
mesh_terms: D000818:Animals; D001259:Ataxia / Q000235:genetics*; D001921:Brain / Q000473:pathology*; D004195:Disease Models, Animal; D055786:Gene Knockout Techniques; D007150:Immunohistochemistry; D008297:Male; D009043:Motor Activity / Q000235:genetics; D053580:Muscle Strength / Q000235:genetics; D010300:Parkinson Disease / Q000150:complications / Q000235:genetics* / Q000473:pathology; D011494:Protein Kinases / Q000235:genetics*; D051381:Rats; D020318:Rats, Long-Evans; D014059:Tongue / Q000294:innervation; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics / Q000378:metabolism; D014828:Vocalization, Animal / Q000502:physiology*; D051844:alpha-Synuclein / Q000235:genetics / Q000378:metabolism; D000099202:PTEN-Induced Putative Kinase
chemical_list: D011494:Protein Kinases; D014446:Tyrosine 3-Monooxygenase; D051844:alpha-Synuclein; D000099202:PTEN-Induced Putative Kinase
keywords: PINK1; Parkinson's disease; RRID:AB_1977522; RRID:AB_390204; cranial-sensorimotor; ultrasonic vocalization; α-synuclein; rat