RESUMO
This study investigated the protective effects of dextromethorphan (DXM) on noise-induced hearing loss (NIHL) in rats. This study aimed to improve the auditory threshold and to understand the protective effects of DXM against N-methyl-d-aspartate (NMDA)-induced neurite degeneration of serotonergic neurons. The animals were exposed to 8-kHz narrowband noise at a 118-dB sound pressure level for 3.5â¯h. The hearing thresholds were determined by measuring the auditory brainstem response to click stimuli. Serotonin transporter (SERT) expression was determined through micro-positron emission tomography (PET) using N,N-dimethyl-2-(2-amino-4-18F-fluorophenylthio)benzylamine (4-[18F]-ADAM). We also investigated the effects of DXM on NMDA-induced morphological changes in the primary cultures of rat serotonergic neurons. NIHL significantly improved after prophylactic treatment with DXM (pâ¯<â¯.05). SERT density in DXM-treated rats was significantly higher than that in non-DXM-treated rats. Because prophylactic medication restored the NMDA-inhibited neurite length of serotonergic neurons and presented SERT density, DXM could be a potential agent in alleviating NIHL.
Assuntos
Benzilaminas/farmacologia , Encéfalo/efeitos dos fármacos , Dextrometorfano/farmacologia , Perda Auditiva/tratamento farmacológico , Perda Auditiva/metabolismo , Proteínas de Ligação a RNA/metabolismo , Compostos Radiofarmacêuticos/farmacologia , Animais , Encéfalo/metabolismo , Tronco Encefálico/efeitos dos fármacos , Tronco Encefálico/metabolismo , Modelos Animais de Doenças , Potenciais Evocados Auditivos do Tronco Encefálico/efeitos dos fármacos , Masculino , N-Metilaspartato/farmacologia , Tomografia por Emissão de Pósitrons/métodos , Ratos , Ratos Sprague-Dawley , Neurônios Serotoninérgicos/efeitos dos fármacos , Neurônios Serotoninérgicos/metabolismo , Proteínas da Membrana Plasmática de Transporte de Serotonina/metabolismoRESUMO
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-[(18)F]-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 3.5h. An auditory brainstem response test and 4-[(18)F]-ADAM/small animal PET were performed at different time points after noise exposure. The specific uptake ratios (SURs) for 4-[(18)F]-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-[(18)F]-ADAM/small animal PET in vivo.