2026 Undergraduate Research Showcase
Brain-on-a-Dish Model Reveals Early Axonal Dysfunction in Parkinson’s Disease Using Human iPSC-Derived Dopaminergic Organoids
Document Type
Student Presentation
Presentation Date
4-24-2026
Faculty Sponsor
Dr. Nilufar Ali
Abstract
Idaho also has one of the highest age-adjusted Parkinson’s disease (PD)–related mortality rates in the United States (9.0 per 100,000), underscoring an urgent need for early biomarkers and disease-modifying interventions. A defining but underappreciated feature of PD is that 50–70% of dopaminergic (DA) neuronal soma loss and near-complete degeneration of DA axons in the nigrostriatal pathway occur prior to clinical symptom onset. Despite this, the mechanisms driving early axonal vulnerability remain poorly defined.
To model axon-specific vulnerability in a human-relevant system, we differentiated control human induced pluripotent stem cells (iPSCs) into midbrain DA neurons and three-dimensional DAergic organoids, establishing robust platforms for axon outgrowth, branching, and sprouting. Under basal conditions, DA neurons and organoids formed organized axonal networks with active sprouting, polarized mitochondrial transport, and stable spontaneous firing measured by multielectrode array recordings and normal oxygen consumption. In contrast, PD-like stressors induced early axonal phenotypes, including impaired axon extension, altered sprouting, disrupted mitochondrial distribution, and reduced firing rates and network synchrony, despite preserved neuronal viability. Live-cell imaging revealed stress-dependent reductions in mitochondrial membrane potential and axonal transport, linking metabolic compromise to functional network deficits.
This study establishes a platform to define early-stage relevant axonal dysfunction in PD. Future studies will integrate patient-derived biospecimens and clinical phenotyping to enable biomarker discovery and therapeutic screening. Together, this approach advances translational readiness, strengthens clinical–basic integration in Idaho, and supports development of early intervention strategies for PD.
Recommended Citation
Baldridge, Joshua; Arif, Shehbeel; Laskar, Masihhur; Pu, Xinzhu; Woodbury, Luke; Oxford, Julie; and Ali, Nilufar, "Brain-on-a-Dish Model Reveals Early Axonal Dysfunction in Parkinson’s Disease Using Human iPSC-Derived Dopaminergic Organoids" (2026). 2026 Undergraduate Research Showcase. 14.
https://scholarworks.boisestate.edu/under_showcase_2026/14