Project summary
Swallowing problems in Parkinson’s disease (PD) affect 90% of patients, with significant
consequences for quality of life and morbidity, and are resistant to current dopamine
deficiency targeting treatments for movement impairments caused by PD (Coelho et al., 2010;
Plowman-Prine et al., 2009). The treatment resistant nature of swallowing problems
implicates neurological damage outside the substantia nigra and striatum. Most cases of PD
result in part from exposure to toxic substances, resulting in widespread brain pathologies (de
Lau & Breteler, 2006). PD affects multiple components of feeding and their coordination,
which are controlled by different parts of the brain (Kwon &Lee, 2019). The overall goal of this
project is to identify treatment resistant components of feeding and their neuropathological
correlates in PD. The central hypothesis is that specific components of the feeding process are
differentially impaired by neurodegeneration inside and outside the substantia nigra resulting
in an overall treatment resistant phenotype. Three related specific aims will test this
hypothesis. Specific aims 1 will compare behavioral, biomechanical, and neuromuscular
differences in chew-swallow-breathe coordination in a generalized model of PD, the rat
rotenone injection model (Cannon et al., 2009) versus a 6-OHDA induced targeted
nigrostriatal lesion model (Russell et al., 2013) to identify feeding dysfunction not related to
nigrostriatal deficits. Specific aim two will examine how differences in behavioral and
sensorimotor complexity between solid food eating and liquid drinking affect severity of
behavioral, biomechanical, and neuromuscular oropharyngeal discoordination in a rotenone
injection rat model of PD. Specific aim 3 will test the behavioral, biomechanical, and
neuromuscular impact of levodopa-induced rescue of chewing function (Karlsson et al., 1992)
on feeding coordination in a rotenone injection rat model of PD to identify pathophysiological
mechanisms of dysphagia that are resistant to treatments targeting dopamine deficiency. The
approach is innovative in combining complimentary lesion models, behavioral models, and
neuropharmacological approaches, with a detailed analysis of feeding to find the
pathophysiological basis of dysphagia treatment resistance in PD. The approach is significant
in targeting the underlying mechanism of treatment resistance in a common, understudied
symptom of PD. The neuromuscular, neuropathological, and biomechanical findings of this
from this work will lead to further research into the neurological basis of treatment resistance
of dysphagia in PD, with the ultimate goal of developing targeted therapeutic interventions.
