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Noninvasive Diagnostic Method to Objectively Measure Olfaction and Diagnose Smell Disorders by a Molecularly Targeted Fluorescence Imaging Agent
The Journal of Nuclear Medicine ( IF 9.1 ) Pub Date : 2024-08-01 , DOI: 10.2967/jnumed.123.266123
Dauren Adilbay 1, 2 , Junior Gonzales 1 , Marianna Zazhytska 3 , Paula Demetrio de Souza Franca 1, 4 , Sheryl Roberts 1 , Tara D Viray 1 , Raik Artschwager 1 , Snehal Patel 2 , Albana Kodra 3, 5 , Jonathan B Overdevest 6 , Chun Yuen Chow 7, 8 , Glenn F King 7, 8 , Sanjay K Jain 9, 10, 11 , Alvaro A Ordonez 9, 10 , Laurence S Carroll 9, 11 , Stavros Lomvardas 3 , Thomas Reiner 12, 13 , Nagavarakishore Pillarsetty 12, 13
Affiliation  

Despite the recent advances in understanding the mechanisms of olfaction, no tools are currently available to noninvasively identify loss of smell. Because of the substantial increase in patients presenting with coronavirus disease 2019–related loss of smell, the pandemic has highlighted the urgent need to develop quantitative methods. Methods: Our group investigated the use of a novel fluorescent probe named Tsp1a-IR800P as a tool to diagnose loss of smell. Tsp1a-IR800P targets sodium channel 1.7, which plays a critical role in olfaction by aiding the signal propagation to the olfactory bulb. Results: Intuitively, we have identified that conditions leading to loss of smell, including chronic inflammation and coronavirus disease 2019, correlate with the downregulation of sodium channel 1.7 expression in the olfactory epithelium, both at the transcript and at the protein levels. We demonstrated that lower Tsp1a-IR800P fluorescence emissions significantly correlate with loss of smell in live animals—thus representing a potential tool for its semiquantitative assessment. Currently available methods rely on delayed subjective behavioral studies. Conclusion: This method could aid in significantly improving preclinical and clinical studies by providing a way to objectively diagnose loss of smell and therefore aid the development of therapeutic interventions.



中文翻译:


通过分子靶向荧光成像剂客观测量嗅觉和诊断嗅觉障碍的无创诊断方法



尽管最近在理解嗅觉机制方面取得了进展,但目前还没有可用的工具来非侵入性地识别嗅觉丧失。由于患有 2019 年冠状病毒病相关嗅觉丧失的患者大幅增加,这场大流行凸显了开发定量方法的迫切需要。方法:我们小组研究了使用一种名为 Tsp1a-IR800 P的新型荧光探针作为诊断嗅觉丧失的工具。 Tsp1a-IR800 P靶向钠通道 1.7,钠通道通过帮助信号传播到嗅球而在嗅觉中发挥关键作用。结果:直观上,我们发现导致嗅觉丧失的病症,包括慢性炎症和 2019 年冠状病毒病,与嗅觉上皮中钠通道 1.7 表达的下调相关,无论是在转录本还是蛋白质水平。我们证明,较低的 Tsp1a-IR800 P荧光发射与活体动物的嗅觉丧失显着相关,因此代表了半定量评估的潜在工具。目前可用的方法依赖于延迟的主观行为研究。结论:该方法通过提供一种客观诊断嗅觉丧失的方法,可以帮助显着改善临床前和临床研究,从而有助于治疗干预措施的发展。

更新日期:2024-08-02
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