title: Administration of amitriptyline attenuates noise-induced hearing loss via glial cell line-derived neurotrophic factor (GDNF) induction.
abstract: Antidepressant treatments have been described to induce neurotrophic factors (NTFs) and reverse the cell loss observed in rodent stress models. Amitriptyline (AT), a tricyclic antidepressant agent, has been reported in recent studies to induce glial cell line-derived neurotrophic factor (GDNF) synthesis and release in rat C6 glioblastoma cells. GDNF has shown protection against acoustic trauma in previous studies. Therefore, we investigated whether AT could induce GDNF synthesis in the cochlea and attenuate cochlea damage against acoustic trauma. We used Hartley guinea pigs and injected AT (30 mg/kg) or saline into the peritoneum. Subjects were exposed to 117 dB SPL octave band noise centered at 4 kHz for 24 h. Noise-induced hearing loss (NIHL) was assessed with auditory brain stem response (ABR) at 4, 8 and 16 kHz measured prior to the injection, 3 days and 7 days after noise exposure. For histological assessment, we observed the sensory epithelium using a surface preparation technique and assessed the quantitative hair cell (HC) damage. We evaluated GDNF synthesis with or without intense noise exposure at 3, 12 and 24 h after the administration of AT in the cochlea using Western blot analysis. GDNF expression was shown 3 h and 12 h after the injection without noise, whereas with noise the GDNF expression lasted for 24 h. The AT-administrated group showed significantly reduced ABR threshold shift and less HC damage than the saline-administrated group. These findings suggest that the administration of AT-induced GDNF levels in the cochlea and attenuated cochlea damage from NIHL.
authors.affiliation: Department of Otolaryngology, Kansai Medical University Takii Hospital, 10-15 Fumizonocho Moriguchi-shi, Osaka 570-8507, Japan. shibatas@takii.kmu.ac.jp
authors.forename: Seiji Bruce
authors.initials: SB
authors.lastname: Shibata
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Osumi
authors.forename: Masao
authors.initials: M
authors.lastname: Yagi
authors.forename: Seiji
authors.initials: S
authors.lastname: Kanda
authors.forename: Kohei
authors.initials: K
authors.lastname: Kawamoto
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Kuriyama
authors.forename: Toshimasa
authors.initials: T
authors.lastname: Nishiyama
authors.forename: Toshio
authors.initials: T
authors.lastname: Yamashita
mesh_terms: D000639:Amitriptyline / Q000008:administration & dosage*; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage*; D000818:Animals; D001309:Auditory Threshold / Q000187:drug effects; D004195:Disease Models, Animal; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects / Q000502:physiology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000502:physiology / Q000528:radiation effects; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000378:metabolism*; D006168:Guinea Pigs; D006198:Hair Cells, Auditory / Q000187:drug effects / Q000502:physiology; D006317:Hearing Loss, Noise-Induced / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology
chemical_list: D018712:Analgesics, Non-Narcotic; D051100:Glial Cell Line-Derived Neurotrophic Factor; D000639:Amitriptyline