Thallium-201 Imaging in Intact Olfactory Sensory Neurons with Reduced Pre-Synaptic Inhibition In Vivo

Hideaki Shiga,Kazuma Ogawa,Sadaharu Miyazono,Masami Kumai,Kohshin Washiyama,Tomohiro Noguchi,Hiroshi Wakabayashi,Junichi Taki,Seigo Kinuya,Tomo Hiromasa,Takaki Miwa

doi:10.1007/s12035-020-02078-y

Abstract

In this study, we determined whether the 201Tl (thallium-201)-based olfactory imaging is affected if olfactory sensory neurons received reduced pre-synaptic inhibition signals from dopaminergic interneurons in the olfactory bulb in vivo. The thallium-201 migration rate to the olfactory bulb and the number of action potentials of olfactory sensory neurons were assessed 3 h following left side nasal administration of rotenone, a mitochondrial respiratory chain complex I inhibitor that decreases the number of dopaminergic interneurons without damaging the olfactory sensory neurons in the olfactory bulb, in mice (6–7 animals per group). The migration rate of thallium-201 to the olfactory bulb was significantly increased following intranasal administration of thallium-201 and rotenone (10 μg rotenone, p = 0.0012; 20 μg rotenone, p = 0.0012), compared with that in control mice. The number of action potentials was significantly reduced in the olfactory sensory neurons in the rotenone treated side of 20 μg rotenone-treated mice, compared with that in control mice (p = 0.0029). The migration rate of thallium-201 to the olfactory bulb assessed with SPECT-CT was significantly increased in rats 24 h after the left intranasal administration of thallium-201 and 100 μg rotenone, compared with that in control rats (p = 0.008, 5 rats per group). Our results suggest that thallium-201 migration to the olfactory bulb is increased in intact olfactory sensory neurons with reduced pre-synaptic inhibition from dopaminergic interneurons in olfactory bulb glomeruli.

Highlights

Detecting the mechanisms underpinning olfactory dysfunction is challenging, owing to the difficulty in directly viewing the connectivity of peripheral olfactory nerves using current magnetic resonance imaging (MRI)
The thallium-201 migration rate to the olfactory bulb, as assessed with SPECT-CT, was significantly increased in normal rats 24 h following intranasal administration of 201Tl and 100 μg rotenone, compared with the rate following treatment with 201Tl and vehicle control (1% DMSO in phosphate-buffered saline (PBS)) (Fig. 5a, Mann-Whitney test, p = 0.008, 5 rats per group)
We aimed to determine whether thallium-201 migration to the olfactory bulb is affected by pre-synaptic inhibition of olfactory sensory neurons from the dopaminergic interneurons in the olfactory bulb in vivo

Summary

Introduction

Detecting the mechanisms underpinning olfactory dysfunction is challenging, owing to the difficulty in directly viewing the connectivity of peripheral olfactory nerves using current magnetic resonance imaging (MRI). Thallium-201-based olfactory imaging is referred to as olfactory scintigraphy. The radioisotope thallium-201 is transported within olfactory neural tracts after nasal administration in rodents [3]. This transport is significantly decreased by transecting olfactory nerve fibers and correlates with odor detection ability in mice [4, 5]. Thallium can readily substitute potassium at the sodium/potassium (Na+/K+)-membrane adenosine triphosphatase (ATPase) activation sites [6]. Nasally administered thallium-201 may be transported into olfactory nerve cells as a substitute for potassium

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Conclusion