Date of Defense

7-21-2026

Date of Graduation

6-2026

Department

Biological Sciences

First Advisor

John Spitsbergen

Second Advisor

Sangwoo Lee

Abstract

Heart disease is the number one leading cause of death; about 1 in every five deaths is due to heart disease. “Heart disease” is a catch-all phrase that encompasses a variety of conditions that affect the heart’s structure and function. Many of these symptoms can be attributed to dysfunction within the parasympathetic, sympathetic, and sensory nervous systems. Neurotrophic factors like GDNF (Glial cell line-derived neurotrophic factor), BDNF (Brain-derived neurotrophic factor), and NGF (Nerve growth factor) promotes neuronal survival, and regeneration of the nerve fibers of the heart, especially sensory and autonomic nerve fibers. Studies have suggested that increased expression of GDNF promotes sympathetic nerve fiber growth in the heart. This study aims to evaluate both autonomic systems and sensory systems and their presence when GDNF is neutralized. The expected result of this thesis is to see if there is reduced morphology in sympathetic and sensory fibers in 4-week old anti-GDNF rats relative to the 4-week old non-injected rats. The predicted outcome is to see less innervation in the anti-GDNF-treated rats.

This hypothesis will be tested by injecting 4-week-old rats with anti-GDNF, with the experimental group receiving a one dose and another experimental group receiving a second dose over a course of five days. Animals roughly 4 weeks of age received a single injection of anti-GDNF with a dosage of 0.5 μl of stock/10g rat weight. The anti-GDNF was a 500ug/500ul solution and was diluted 1:100. The control group received an injection of 0.9% Sterile saline made with NaCl and DI water and a syringe filter. Slides were imaged by a confocal microscope, and pictures were captured for further analysis.

The preliminary observations suggest that inhibition of GDNF reduced sympathetic and sensory nerve fiber fluorescence intensity on the images in the rat heart, which visually appears to reduce from the control to the double dose animals. Qualitative assessment indicates a reduced fluorescent intensity of sensory, sympathetic, and parasympathetic nerve fibers, but statistical analysis has not been done to confirm the qualitative results. The current results are not enough to confirm the hypothesis, which states that the expected result of this thesis is to see if there is reduced morphology in sympathetic and sensory fibers in the anti-GDNF rats at the age of four weeks relative to the non-injected rats. The significance of the findings is a visual decrease in morphology and density from the control to the double-dosed rats. Overall, this study highlights the potential role of GDNF in regulating cardiac autonomic innervation and establishes a foundation for future quantitative analyses to determine how GDNF inhibition affects sympathetic nerve remodeling. Finally, future studies should include larger sample sizes and longer observation periods to improve the reliability of the findings and provide a better understanding of the long-term effects of GDNF inhibition on cardiac sensory and autonomic innervation.

Access Setting

Honors Thesis-Open Access

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