| Summary: | 碩士 === 國防醫學院 === 生物及解剖學研究所 === 101 === In recent years, the treatment of noise-induced hearing loss is an important issue in clinical medicine. Excessive noise may induce the impairment of central auditory system. Hearing loss patients under this circumstance may have some psychiatric diseases, such as depression and anxiety. Previous studies showed that depression and anxiety may have abnormal levels of serotonin and serotonin transporters. Serotonin transporter (SERT) is a protein located presynaptically in serotonergic neurons and regulates the serotonin concentration in synaptic cleft. Recent studies found that serotonin transporters also exist in some auditory pathways, such as cochlear neuclei inferior collicular and auditory cortex. The purpose of this study was to investigate the effect of citalopram and resveratrol against noise-induced serotonergic abnormality in rat brain.
In this study, male Sprague Dawley rats were exposed to the noise at intensity of 116 dB SPL and frequency at 8 kHz. The citalopram (20mg/kg) and resveratrol (30mg/kg) was injected intraperitoneally before noise exposure and once per day for 4 successive days. The 4-[18F]-ADAM /micro-Positron Emission Tomography (micro-PET) and Auditory Brainstem Response test (ABR test) were performed at 1 day, 1 week, and 4 week after noise exposure. Finally, the result of immunohistochemistry (IHC) staining were compared to in vivo nenuroimage findings in hearing loss model.
The results of specific uptake ratios (SURs) showed that noise-induced hearing loss could cause the reduction of 4-[18F]-ADAM uptake in various brain regions after noise exposure 1 day and 1 week. In contrast, the SURs of 4-[18F]-ADAM in the rats with citalopram or resveratrol treatment were significantly higher than those of without drug-treated rats. The immunohistochemistry data showed that the density of serotonin transporters positive fiber had no significantly difference in four groups after noise exposure 4 weeks. As for the result of ABR test, the threshold of hearing loss group was higher than that of normal group, and there is no significantly difference among the drug-treated groups and without drug-treated group.
These results suggested that the citalopram and resveratrol may provide neuroprotective effects against noise-induced serotonergic damages, but these two drugs had no effects on protecting hearing after noise exposure. The 4-[18F]-ADAM coupled with small animal PET may be available to monitor the status of SERT in the therapeutic progress.
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