Low‐dose rapamycin‐induced autophagy in cochlear outer sulcus cells

• Main Authors: Chika Saegusa, Makoto Hosoya, Takanori Nishiyama, Tsubasa Saeki, Chisato Fujimoto, Hideyuki Okano, Masato Fujioka, Kaoru Ogawa
• Format: Article
• Language: English
• Published: Wiley 2020-06-01
• Series: Laryngoscope Investigative Otolaryngology
• Subjects: autophagy; hearing loss; inner ear; outer sulcus cell; rapamycin
• Online Access: https://doi.org/10.1002/lio2.392

Abstract Objectives Autophagy is an intracellular housekeeping process that degrades cytoplasmic organelles, damaged molecules, and abnormal proteins or pathogens and is essential for normal hearing. Recent studies revealed the essential roles of autophagy in hearing and balance. The aim of this study was to evaluate the activation state of rapamycin‐induced autophagy in cochlear outer sulcus cells (OSCs). Methods We used autophagy reporter transgenic mice expressing the green fluorescent protein‐microtubule‐associated protein light chain 3 (GFP‐LC3) fusion protein and counted GFP‐LC3 puncta in cochlear OSCs to evaluate the activation state of autophagy after oral administration of rapamycin. Results We observed basal level GFP‐LC3 expression and an increase in the number of GFP‐LC3 puncta in cochlear OSCs by oral administration of rapamycin. This increase was detected when the daily rapamycin intake was as low as 0.025 mg/kg, and it was dose dependent. The increased number of puncta was more at the basal turn than the apical turn. Conclusion Oral intake of low‐dose rapamycin activates autophagy in cochlear OSCs. Level of evidence NA.