Faculty Mentor(s)

Dr. Erika Calvo-Ochoa, Biology

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Parkinson's Disease (PD), a neurodegenerative disorder characterized by dopaminergic neuronal loss and motor impairment, affects roughly 1 in 500 people. Interestingly, olfaction loss is prevalent in over 95% of those with PD. However, the underlying mechanisms of PD and olfactory dysfunction are not well understood. Zebrafish provide an ideal model to study neurodegenerative diseases and regenerative processes as they present neurogenic capability (i.e., generation of new neurons) and a high degree of neuroplasticity. We developed a model to study the association between dopaminergic loss and olfactory dysfunction in zebrafish. To do this, we used adult zebrafish of both sexes and injected 6-hydroxydopamine (6-OHDA) into the cerebrospinal fluid at the ventricular zone. We assessed dopaminergic neuronal loss, markers of inflammation, and motor and olfactory behavior 1 and 3 days post injection (dpi). We predicted that following the injection of 6-OHDA there would be dopaminergic neuronal loss and an increase in neuroinflammation, resulting in olfactory loss. We show that at 1 dpi, the olfactory bulbs present a dramatic increase in the number of apoptotic cells, confirming an effective lesioning method. Our preliminary results convey no significant difference in the amount of dopaminergic (TH, tyrosine hydroxylase +) neurons, although a clear trend exists. This trend continues 3 dpi, however we observed control levels of cell apoptosis 3 dpi. Further, there was a stark increase in the neuroinflammatory response, by means of GFAP staining 1 and 3 dpi. Interestingly, we found that 1 and 3 dpi fish displayed increased swimming distance and speed, suggesting that injections might be altering motor behavior. Surprisingly, even after the disclosed morphological differences in the bulbs, we found no differences in olfactory function. Overall, our results show that we successfully optimized a method for injection of 6-OHDA to target dopaminergic neurons in the olfactory system.


This research was supported by the Kenneth G. Campbell Foundation, an Ed and Ann Anderson Award, a Stewart research fellowship, the Alfred and Dorothy Popma Fund for Biology, and the Hope College Biology Department.

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