PUBLICATION
Olfactory Dysfunction in a Novel Model of Prodromal Parkinson's Disease in Adult Zebrafish
- Authors
- Vorhees, N.W., Groenwold, S.L., Williams, M.T., Putt, L.S., Sanchez-Gama, N., Stalions, G.A., Taylor, G.M., Van Dort, H.E., Calvo-Ochoa, E.
- ID
- ZDB-PUB-250528-24
- Date
- 2025
- Source
- International Journal of Molecular Sciences 26: (Journal)
- Registered Authors
- Calvo-Ochoa, Erika
- Keywords
- Parkinson’s disease, dopaminergic loss, neurogenesis, neuroinflammation, olfactory dysfunction, olfactory system, zebrafish
- MeSH Terms
-
- Olfactory Mucosa/metabolism
- Olfactory Mucosa/pathology
- Dopaminergic Neurons/metabolism
- Dopaminergic Neurons/pathology
- Olfaction Disorders*/etiology
- Olfaction Disorders*/pathology
- Olfaction Disorders*/physiopathology
- Disease Models, Animal
- Olfactory Bulb/metabolism
- Olfactory Bulb/pathology
- Olfactory Bulb/physiopathology
- Parkinson Disease*/metabolism
- Parkinson Disease*/pathology
- Parkinson Disease*/physiopathology
- Animals
- Humans
- Zebrafish
- Oxidopamine/toxicity
- Olfactory Receptor Neurons/metabolism
- Olfactory Receptor Neurons/pathology
- PubMed
- 40429620 Full text @ Int. J. Mol. Sci.
Citation
Vorhees, N.W., Groenwold, S.L., Williams, M.T., Putt, L.S., Sanchez-Gama, N., Stalions, G.A., Taylor, G.M., Van Dort, H.E., Calvo-Ochoa, E. (2025) Olfactory Dysfunction in a Novel Model of Prodromal Parkinson's Disease in Adult Zebrafish. International Journal of Molecular Sciences. 26:.
Abstract
Olfactory dysfunction is a clinical marker of prodromal Parkinson's disease (PD), yet the underlying mechanisms remain unclear. To explore this relationship, we developed a zebrafish model that recapitulates the olfactory impairment observed in prodromal PD without affecting motor function. We used zebrafish due to their olfactory system's similarity to mammals and their unique nervous system regenerative capacity. By injecting 6-hydroxydopamine (6-OHDA) into the dorsal telencephalic ventricle, we observed a significant loss of dopaminergic (DA) periglomerular neurons in the olfactory bulb (OB) and retrograde degeneration of olfactory sensory neurons (OSNs) in the olfactory epithelium (OE). These alterations impaired olfactory responses to cadaverine, an aversive odorant, while responses to alanine remained intact. 6-OHDA also triggered robust neuroinflammatory responses. By 7 days post-injection, dopaminergic synapses in the OB were remodeled, OSNs in the OE appeared recovered, and neuroinflammation subsided, leading to full recovery of olfactory responses to cadaverine. These findings highlight the remarkable neuroplasticity of zebrafish and suggest that this model of olfactory dysfunction associated with dopaminergic loss could provide valuable insights into some features of early PD pathology. Understanding the interplay between dopaminergic loss and olfactory dysfunction in a highly regenerative vertebrate may inform therapeutic strategies for individuals suffering from olfactory loss.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping