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

• Published in: Journal of neuroscience research 2015-07, Vol.93 (11), p.1713-1727
• Main Authors: Grant, Laura M., Kelm-Nelson, Cynthia A., Hilby, Breanna L., Blue, Katherine V., Rajamanickam, Eunice S. Paul, Pultorak, Joshua D., Fleming, Shelia M., Ciucci, Michelle R.
• Format: Article
• Language: English
• ISSN: 0360-4012; 1097-4547
• DOI: 10.1002/jnr.23625

Parkinson disease (PD) is a progressive neurodegenerative disease that leads to a wide range of motor and non-motor 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 alpha-synuclein 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. In the present study, we evaluated the effect of loss of function of the PTEN-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 included ultrasonic vocalizations, tongue force, biting, and gross motor performance that were assayed at 2, 4, 6, and 8 months of age. Aggregated alpha-synuclein and tyrosine hydroxylase immunoreactivity were measured at 8 months. We show that compared to wildtype controls PINK1 −/− rats develop (1) early and progressive vocalization and oromotor deficits; (2) reduced tyrosine hydroxylase immunoreactivity in the locus coeruleus that correlates with vocal loudness and tongue force; and (3) alpha-synuclein neuropathology in brain regions important for cranial sensorimotor control. This novel approach of characterizing a PINK1 −/− genetic model of PD provides the foundational work necessary to define behavioral biomarkers for the development of disease-modifying therapeutics for PD patients.