Prosaposin-derived peptide alleviates ischaemia-induced hearing loss

• Published in: Acta oto-laryngologica Vol. 133; no. 5; pp. 462 - 468
• Main Authors: Terashita, Takehiro, Saito, Shouichiro, Nabeka, Hiroaki, Hato, Naohito, Wakisaka, Hiroyuki, Shimokawa, Tetsuya, Kobayashi, Naoto, Gyo, Kiyofumi, Matsuda, Seiji
• Format: Journal Article
• Language: English
• Published: England Informa Healthcare 01-05-2013; Taylor & Francis
• Subjects: Animals; Apoptosis; bcl-2; Cochlea - blood supply; Disease Models, Animal; Evoked Potentials, Auditory, Brain Stem; Gerbillinae; Hearing Loss - drug therapy; Hearing Loss - etiology; Ischemia - complications; loss of inner hair cells; Organ of Corti - metabolism; Proto-Oncogene Proteins c-bcl-2 - metabolism; Saposins - chemical synthesis; Saposins - therapeutic use; transient cochlear ischaemia
• ISSN: 0001-6489; 1651-2251
• DOI: 10.3109/00016489.2012.750430

Abstract
Conclusion: An 18-mer peptide derived from the neurotrophic region of prosaposin (PS-pep) prevents hearing loss and cochlear damage due to transient cochlear ischaemia by activating an anti-apoptotic pathway. PS-pep is a potent candidate molecule for alleviating ischaemia-induced hearing loss. Objective: PS-pep was investigated for its protective effects against ischaemia-induced hearing loss and cochlear damage. Methods: Ischaemia was induced in both cochleae in Mongolian gerbils by pulling the ligatures around both vertebral arteries in an anterior direction using 5 g weights for 15 min. PS-pep was synthesized artificially and administered subcutaneously four times after the induction of transient cochlear ischaemia. Results: An increase in the auditory brainstem response threshold was alleviated in animals treated with 2.0 mg/kg PS-pep. Histological examinations conducted on day 7 showed that the loss of inner hair cells (IHCs) was more prominent than that of outer hair cells. Higher doses of PS-pep significantly alleviated IHC loss. An increase in the anti-apoptotic factor bcl-2 was also noted in the IHCs treated with PS-pep.