title: Investigating the effects of noise-induced hearing loss on serotonin transporters in rat brain using 4-[18F]-ADAM/small animal PET.
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-[(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.
authors: Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan; Department of Pharmacy Practice, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
authors: Hsiao-Hsien
authors: HH
authors: Kang
authors: Department of Otorhinolaryngology-Head and Neck Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
authors: Chih-Hung
authors: CH
authors: Wang
authors: Department of Otorhinolaryngology-Head and Neck Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
authors: Hsin-Chien
authors: HC
authors: Chen
authors: Department of Pharmacy Practice, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; School of Pharmacy, National Defense Medical Center, Taipei, Taiwan.
authors: I-Hsun
authors: IH
authors: Li
authors: Department of Nuclear Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
authors: Cheng-Yi
authors: CY
authors: Cheng
authors: National PET/Cyclotron Center, Department of Nuclear Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
authors: Ren-Shyan
authors: RS
authors: Liu
authors: Department of Nuclear Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; Department of Nuclear Medicine, Changhua Christian Hospital, Changhua, Taiwan.
authors: Wen-Sheng
authors: WS
authors: Huang
authors: Department of Nuclear Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
authors: Chyng-Yann
authors: CY
authors: Shiue
authors: Department of Biology and Anatomy, National Defense Medical Center, Taipei, Taiwan. Electronic address: kuohsing91@yahoo.com.tw.
authors: Kuo-Hsing
authors: KH
authors: Ma
mesh_terms: D000818:Animals; D001596:Benzylamines; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D005462:Fluorine Radioisotopes; D006317:Hearing Loss, Noise-Induced / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals; D051381:Rats; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism*
chemical_list: D001596:Benzylamines; D005462:Fluorine Radioisotopes; D019275:Radiopharmaceuticals; D050486:Serotonin Plasma Membrane Transport Proteins