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| Poster #Olfactory Receptor N Non-invasive method to measure olfaction and smell disorders using flourescene agent targeting NaV1.7 |
| Dauren Adilbay 1,2,3, Junior Gonzales1, Marianna Zazhytska4, Paula Demetrio de Souza Franca1,5, Raik Artschwager1, Snehal Patel2, Albana Kodra4,6, Jonathan Overdevest7, Chun Yen Chow8,9, Glenn King8,9, Sanjay Jain10,11, Alvaro Ordonez10,11, Laurence Carroll10,11, Stavros Lomvardas4, Thomas Reiner1,12, Naga Vara Kishore Pillarsetty1,12 1Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, United States 2Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, United States 3Department of Otolaryngology - Head and Neck Surgery, Medical University of South Carolina, Charleston, SC, United States 4Mortimer B. Zuckerman Mind, Brain and Behavior Institute, Columbia University, , New York, NY, United States 5Department of Otorhinolaryngology and Head and Neck Surgery, Federal University of São Paul, Sao Paulo, --, Brazil 6Department of Genetics and Development, Columbia University Irving Medical Center, Vagelos College of Physicians and Surgeons, Columbia University,, New York, NY, United States 7Department of Otolaryngology-Head and Neck Surgery, Columbia University Irving Medical Center, Vagelos College of Physicians and Surgeons, Columbia University, , New York, NY, United States 8Institute for Molecular Bioscience, University of Queensland, St. Lucia, --, Australia 9Australian Research Council Centre of Excellence for Innovations in Peptide and Protein Science, University of Queensland,, St. Lucia, --, Australia 10Center for Infection and Inflammation Imaging Research, Johns Hopkins University School of Medicine,, Baltimore, MD, United States 11Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, United States 12Department of Radiology, Weill Cornell Medicine, New York, NY, United States |
Objective: Currently there are no objective methods to measure loss of olfaction. Voltage gated sodium channel 1.7 (NaV1.7) is the predominant sodium channel in olfactory sensory neurons (OSN) that plays major role in olfaction. Tsp1a is a natural peptide derived from spider toxin that targets NaV1.7 with high selectivity. In this study, we examined whether NaV1.7 expression is associated with olfaction and whether signal from fluorescently labeled Tsp1a could function as a readout for olfactory function. Methods: Athymic nude mice were intravenously (i.v.) injected with Tsp1a-IR800 and epifluorescence images were acquired using an IVIS Spectrum animal imaging system and average radiant efficiency in the region of the olfactory epithelium/bulb (ROEB) was measured. Methimazole was used to chemically ablate the olfactory epithelium in mice. Buried food test as performed to measure time to find food and correlate with fluorescence signal. Immunoshistochemistry (IHC), Single cell RNA sequencing(scRNA-seq) and bulk RNA-seq was performed on olfactory epithelium of SARS-CoV-2 infected mice and hamsters and human cadavers. Results: The area of ROEB was clearly visible in epifluorescence in vivo images of mice and significant reduction in signal was observed after olfactory ablation. Inverse correlation between the time to find buried food and radiant efficiency. Mice after olfactory ablation as well as SARS-CoV-2 infection had significantly lower expression of NaV1.7. RNA-seq from hamsters ROEB tissues and humans OSN cells revealed significantly lower level of SCN1A gene RNA expression post SARS-CoV-2 infection. Conclusion: We demonstrate fluorescent imaging of mouse epithelium is possible, suggesting that labeled Tsp1a tracers may serve as an objective diagnostic tool for loss of smell. |