Administration of amitriptyline attenuates noise-induced hearing loss via glial cell line-derived neurotrophic factor (GDNF) induction

• Published in: Brain research Vol. 1144; pp. 74 - 81
• Main Authors: Shibata, Seiji Bruce, Osumi, Yasunori, Yagi, Masao, Kanda, Seiji, Kawamoto, Kohei, Kuriyama, Hiromichi, Nishiyama, Toshimasa, Yamashita, Toshio
• Format: Journal Article
• Language: English
• Published: London Elsevier B.V 04.05.2007; Amsterdam Elsevier; New York, NY
• Subjects: Amitriptyline; Amitriptyline - administration & dosage; Analgesics, Non-Narcotic - administration & dosage; Animals; Auditory Threshold - drug effects; Biological and medical sciences; Cochlea protection; Disease Models, Animal; Ear, auditive nerve, cochleovestibular tract, facial nerve: diseases, semeiology; Evoked Potentials, Auditory, Brain Stem - drug effects; Evoked Potentials, Auditory, Brain Stem - physiology; Female; Gene Expression Regulation - drug effects; Gene Expression Regulation - physiology; Gene Expression Regulation - radiation effects; Glial cell line-derived neurotrophic factor; Glial Cell Line-Derived Neurotrophic Factor - metabolism; Guinea Pigs; Hair cell; Hair Cells, Auditory - drug effects; Hair Cells, Auditory - physiology; Hearing Loss, Noise-Induced - drug therapy; Hearing Loss, Noise-Induced - pathology; Hearing Loss, Noise-Induced - physiopathology; Medical sciences; Neurology; Neuropharmacology; Noise-induced hearing loss; Non tumoral diseases; Otorhinolaryngology. Stomatology; Pharmacology. Drug treatments; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; NTF; N-methyl- d-aspartate; NT-3; OHCs; IHCs; PTS; glial cell line-derived neurotrophic factor; mitogen-activated protein kinase; ABR; auditory brainstem response; TTS; fibroblast growth factor; outer hair cells; NTFs; NMDA; brain-derived neurotrophic factor; TGF-beta1; c-Ret; amitriptyline; MAPK-extracellular signal-regulated kinase (ERK) kinase; neurotrophic factor; BDNF; GDNF family receptor α; MAPK; tyrosine kinase receptor; temporary threshold shift; hair cells; FGF-2; inner hair cells; MEK; AT; GDNF; neurotrophic factors; Noise-induced hearing loss; permanent threshold shift; Hair cell; HC; transforming growth factor; neurotrophin-3; GFR-α; Cochlea protection; Amitriptyline; Glial cell line-derived neurotrophic factor; Psychotropic; Noise; Neuroglia; Auditory disorder; Inner ear; Organ of hearing; Guinea pig; Glial cell line derived neurotrophic factor; ENT disease; Antidepressant agent; factor; Glial cell; Induction; Internal ear disease; Rodentia; Glial cell line-derived neurotrophic; Ciliated cell; Hearing loss; Chemotherapy; Vertebrata; Mammalia; Treatment; Cell line; Cochlea
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2007.01.090

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.