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| Poster #241 Olfactory system alterations in a novel model of dopaminergic loss by 6-OHDA injections in adult zebrafish |
| Erika Calvo-Ochoa, Nathaniel Vorhees, Samantha Groenwold, Lexus Putt, Nereyda Sanchez-Gama, Mackenzie Williams Biology Department and Neuroscience Program, Hope College, Holland, MI, United States |
Parkinson’s Disease (PD) is a neurodegenerative disorder marked by dopaminergic neuronal loss and motor impairment. Olfactory loss affects over 95% of PD patients, often preceding motor deficits. However, the mechanisms linking PD to olfactory dysfunction remain unclear. One hypothesis suggests that dopaminergic loss leading to retrograde degeneration in the olfactory system underlies this phenomenon. To study this we use zebrafish, whose olfactory system is analogous, yet simpler, to those of mammals. We developed a model of dopaminergic loss in the OB by injecting 6-hydroxydopamine (6-OHDA) into the cerebrospinal fluid at the ventricular zone between the OBs and telencephalon. We sought to selectively target dopaminergic neurons in the OB without affecting posterior motor nuclei to preserve locomotion. We used immunohistochemistry to evaluate post-injection structural alterations and degeneration, and behavioral assays to assess olfactory function. Results confirmed significant dopaminergic neuronal loss in the OB, accompanied by morphological changes in olfactory glomeruli. We also observed degeneration of olfactory sensory neurons (OSN) in the olfactory epithelium (OE), suggesting retrograde degeneration. Neuroinflammatory responses, marked by increased astrocyte and leukocyte activity, were prominent in both the OB and OE during the first seven days post-injection. These degenerative changes correlated with selective disturbances in olfactory-mediated responses, indicating functional alterations. We also report a proliferative response in the OB and OE suggesting repair mechanisms launched following dopaminergic loss. This novel zebrafish model provides valuable insights into the relationship between dopaminergic neuronal loss and olfactory dysfunction in PD. |