Defense Date
2025
Document Type
Thesis
Degree Name
Master of Science
Department
Biology
First Advisor
Dr. Jason Newton
Second Advisor
Dr. Santiago Lima
Third Advisor
Dr. Jeremy Allegood
Abstract
Disruptions in sphingolipid metabolism are increasingly implicated in neurodegenerative diseases, yet the utility of the sphingolipidome as a biomarker for neuronal health across diverse biological systems remains underexplored. This thesis addresses this gap by systematically evaluating sphingolipid profiles in multiple model organisms and cellular systems, aiming to establish lipidomic signatures that reflect neuronal status and disease susceptibility. In the initial phase, the environmental neurotoxin β-N-methylamino-L-alanine (BMAA) was employed to perturb sphingolipid homeostasis in SH-SY5Y neuroblastoma and HeLa adenocarcinoma cells. Targeted mass spectrometry revealed that BMAA exposure led to the formation of a novel sphingoid base and altered the abundance of key sphingolipid classes, suggesting a direct link between environmental insult and neuronal lipid dysregulation. Building on these findings, comparative sphingolipidomic analyses were performed in yeast, zebrafish embryos, and mouse brain tissue to assess conserved and context-specific metabolic features. Yeast strains exhibited distinct sphingolipid compositions reflecting underlying biosynthetic diversity and membrane organization. In zebrafish embryos, removal of the yolk sac enabled precise delineation of endogenous sphingolipid metabolism, revealing active synthesis and remodeling in the developing nervous system. Mouse brain tissue from a neurodegenerative model displayed hallmark imbalances in sphingolipid classes. Collectively, these results demonstrate that the sphingolipidome sensitively reflects both environmental exposures and intrinsic developmental or genetic factors affecting neuronal health. This work establishes a framework for leveraging model organisms to interrogate sphingolipid metabolism and supports the use of lipidomic profiling as a tool for early detection and mechanistic study of neurodegenerative processes.
Rights
© Taylor Jones
Is Part Of
VCU University Archives
Is Part Of
VCU Theses and Dissertations
Date of Submission
5-8-2025