Investigating the effects of noise-induced hearing loss on serotonin transporters in rat brain using 4-[18F]-ADAM/small animal PET

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Abstract

The serotonin transporter (SERT) is an important marker of the status of serotonergic neurons. The main function of SERT is to regulate the serotonin concentration in the synapse. Recent studies have shown that SERT is expressed in the central auditory pathway and may play a role in the auditory process. However, little is known about the effects of noise on the cerebral serotonin system. In this study, we explored the status of brain SERT in a rat model of noise-induced hearing loss using 4-[18F]-ADAM (a SERT imaging agent) and small animal positron emission tomography (PET) imaging. Male Sprague Dawley rats were exposed to an 8 kHz noise at 118 dB sound pressure level for 3.5 h. An auditory brainstem response test and 4-[18F]-ADAM/small animal PET were performed at different time points after noise exposure. The specific uptake ratios (SURs) for 4-[18F]-ADAM were calculated from the PET imaging data in six brain regions. Immunohistochemistry and surface preparation of the cochleae were performed 30 days after noise exposure. Our data clearly showed that the hearing and cochlear outer hair cells of the rats were lost after noise exposure. In the PET study, the SURs of SERT were markedly reduced by 35%–58% in various brain regions one day after noise exposure. The decrement remained on days 8 and 15 and was approximately 26%–48% on day 29. The distribution and intensity of SERT immunostaining in the brain paralleled the PET imaging data. These results suggest that noise-induced hearing loss involves a reduction in SERT expression in various regions of the rat brain and that changes in SERT are detectable by 4-[18F]-ADAM/small animal PET in vivo.

Highlights

▸ Single noise overexposure markedly reduced the expression of SERT in rat brain. ▸ The reduced effect of SERT would last at least four weeks. ▸ We validated this method for evaluating the serotonin system after noise exposure.

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