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April 2nd, 2025
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Hope College
neuroscience
biorxiv

Olfactory dysfunction in a novel model of prodromal Parkinson's disease in adult zebrafish

Vorhees, N. W.Open in Google Scholar•Groenwold, S. L.Open in Google Scholar•Williams, M. T.Open in Google Scholar•Putt, L. S.Open in Google Scholar•Sanchez-Gama, N.Open in Google Scholar•Stalions, G. A.Open in Google Scholar•Taylor, G. M.Open in Google Scholar•Van Dort, H. E.Open in Google Scholar•Calvo-Ochoa, E.Open in Google Scholar

Olfactory dysfunction is a clinical marker of prodromal Parkinson\'s disease (PD), a neurodegenerative disorder characterized by severe motor impairments. Although common, the mechanisms linking PD and olfactory dysfunction remain unclear. To explore this relationship, we developed a model of olfactory dysfunction that recapitulates the prodromal stage of PD without affecting motor function. For this, we used zebrafish, an animal model widely used in PD research that shares olfactory system similarities with mammals and that exhibits unique regenerative capabilities. By injecting 6-hydroxydopamine (6-OHDA) into the dorsal telencephalic ventricle, we observed a significant loss of dopaminergic periglomerular neurons in the olfactory bulb (OB) and retrograde degeneration of olfactory sensory neuron (OSN) in the peripheral olfactory epithelium (OE). These alterations led to impaired olfactory responses to the aversive odorant, cadaverine, although olfactory responses to alanine, an attractive odorant, were not impaired. 6-OHDA triggered a neuroinflammatory response, which was reduced by treatment with the anti-inflammatory drug pranlukast. By 7 dpi, we observed remodeling of dopaminergic synapses in the OB and restoration of the OE, along with a resolution of the neuroinflammatory response. By this time, olfactory responses to cadaverine were fully restored, highlighting the remarkable neuroplasticity of the zebrafish olfactory system. This novel model of prodromal PD could offer valuable insights into the early stages and progression of this neurodegenerative disease and increase our understanding of the relationship between dopaminergic loss and olfactory dysfunction.

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