Prosaposin-derived peptide alleviates ischaemia-induced hearing loss

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.

Keywords::

• Apoptosis
• bcl-2
• loss of inner hair cells
• transient cochlear ischaemia

Acknowledgment

This study was supported in part by a research grant to S.M. (no. 19659380) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.