Research Projects

Parkinson’s Disease (PD) is a progressive neurodegenerative disorder primarily known for its motor symptoms due to dopaminergic neuron loss in the substantia nigra. However, non-motor manifestations, especially cardiovascular dysregulation, are increasingly recognized as early indicators and major contributors to morbidity in PD patients. Clinical studies reveal cardiac sympathetic denervation and autonomic imbalance, yet the underlying mechanisms and cardiac consequences remain poorly understood in preclinical models. There is a critical gap in our knowledge regarding how neurodegeneration in PD leads to systemic cardiac pathology, and how brain-heart molecular interactions evolve during disease progression. The central hypothesis of this study is that chemically induced PD leads to progressive cardiac dysfunction through neural denervation, cellular remodeling, and activation of shared stress-responsive molecular pathways in the brain and heart. To test this hypothesis, we will use the rotenone-induced PD rat model, a well-established paradigm that replicates dopaminergic neurodegeneration and autonomic dysfunction. We propose that understanding these alterations at the single-cell level will reveal novel signatures of neurocardiac pathology, which may serve as early biomarkers or therapeutic targets. The study is structured around three interrelated objectives: Objective 1 involves the induction of PD in rats through chronic rotenone administration. Neurobehavioral assessments, including motor function tests, will be used to confirm disease establishment. Concurrently, we will perform cardiac functional evaluation using histopathological assessments (TTC staining for infarction, fibrosis quantification, and immunohistochemistry for neural markers) to capture the onset and severity of cardiac pathology. Objective 2 aims to assess cardiac autonomic denervation and structural remodeling in PD. Immunostaining for tyrosine hydroxylase (TH) will be used to evaluate sympathetic innervation and choline acetyltransferase (ChAT) for parasympathetic fibers, while collagen staining and fibrotic gene expression will determine extracellular matrix remodeling. These analyses will establish a link between neurodegeneration and cardiac remodeling and help identify anatomical substrates of dysfunction. Objective 3 will employ single-cell RNA sequencing (scRNA-seq) of heart and brain tissues to delineate cell-type-specific transcriptomic changes during PD progression. This approach will reveal critical pathways involved in inflammation, mitochondrial dysfunction, neuroinflammation, fibrosis, and cellular stress. The proposed research will generate the first integrated map of functional, structural, and molecular cardiac changes in a rodent model of PD. The single-cell transcriptomic datasets generated will serve as a resource for identifying potential biomarkers or therapeutic targets relevant to both neurological and cardiovascular systems.