Frontiers in Molecular Neuroscience (Jul 2020)
Regeneration of Cochlear Synapses by Systemic Administration of a Bisphosphonate
- Richard Seist,
- Richard Seist,
- Richard Seist,
- Mingjie Tong,
- Mingjie Tong,
- Lukas D. Landegger,
- Lukas D. Landegger,
- Lukas D. Landegger,
- Sasa Vasilijic,
- Sasa Vasilijic,
- Hiroshi Hyakusoku,
- Hiroshi Hyakusoku,
- Hiroshi Hyakusoku,
- Sachiyo Katsumi,
- Sachiyo Katsumi,
- Charles E. McKenna,
- Albert S. B. Edge,
- Albert S. B. Edge,
- Albert S. B. Edge,
- Albert S. B. Edge,
- Konstantina M. Stankovic,
- Konstantina M. Stankovic,
- Konstantina M. Stankovic,
- Konstantina M. Stankovic,
- Konstantina M. Stankovic
Affiliations
- Richard Seist
- Eaton-Peabody Laboratories, Department of Otolaryngology – Head and Neck Surgery, Massachusetts Eye and Ear, Boston, MA, United States
- Richard Seist
- Department of Otolaryngology – Head and Neck Surgery, Harvard Medical School, Boston, MA, United States
- Richard Seist
- Department of Otorhinolaryngology-Head and Neck Surgery, Paracelsus Medical University, Salzburg, Austria
- Mingjie Tong
- Eaton-Peabody Laboratories, Department of Otolaryngology – Head and Neck Surgery, Massachusetts Eye and Ear, Boston, MA, United States
- Mingjie Tong
- Department of Otolaryngology – Head and Neck Surgery, Harvard Medical School, Boston, MA, United States
- Lukas D. Landegger
- Eaton-Peabody Laboratories, Department of Otolaryngology – Head and Neck Surgery, Massachusetts Eye and Ear, Boston, MA, United States
- Lukas D. Landegger
- Department of Otolaryngology – Head and Neck Surgery, Harvard Medical School, Boston, MA, United States
- Lukas D. Landegger
- Department of Otorhinolaryngology-Head and Neck Surgery, Medical University of Vienna, Vienna, Austria
- Sasa Vasilijic
- Eaton-Peabody Laboratories, Department of Otolaryngology – Head and Neck Surgery, Massachusetts Eye and Ear, Boston, MA, United States
- Sasa Vasilijic
- Department of Otolaryngology – Head and Neck Surgery, Harvard Medical School, Boston, MA, United States
- Hiroshi Hyakusoku
- Eaton-Peabody Laboratories, Department of Otolaryngology – Head and Neck Surgery, Massachusetts Eye and Ear, Boston, MA, United States
- Hiroshi Hyakusoku
- Department of Otolaryngology – Head and Neck Surgery, Harvard Medical School, Boston, MA, United States
- Hiroshi Hyakusoku
- Department of Otorhinolaryngology, Yokosuka Kyosai Hospital, Kanagawa, Japan
- Sachiyo Katsumi
- Eaton-Peabody Laboratories, Department of Otolaryngology – Head and Neck Surgery, Massachusetts Eye and Ear, Boston, MA, United States
- Sachiyo Katsumi
- Department of Otolaryngology – Head and Neck Surgery, Harvard Medical School, Boston, MA, United States
- Charles E. McKenna
- Department of Chemistry, University of Southern California, Los Angeles, CA, United States
- Albert S. B. Edge
- Eaton-Peabody Laboratories, Department of Otolaryngology – Head and Neck Surgery, Massachusetts Eye and Ear, Boston, MA, United States
- Albert S. B. Edge
- Department of Otolaryngology – Head and Neck Surgery, Harvard Medical School, Boston, MA, United States
- Albert S. B. Edge
- Speech and Hearing Bioscience and Technology Program, Harvard Medical School, Boston, MA, United States
- Albert S. B. Edge
- Harvard Stem Cell Institute, Cambridge, MA, United States
- Konstantina M. Stankovic
- Eaton-Peabody Laboratories, Department of Otolaryngology – Head and Neck Surgery, Massachusetts Eye and Ear, Boston, MA, United States
- Konstantina M. Stankovic
- Department of Otolaryngology – Head and Neck Surgery, Harvard Medical School, Boston, MA, United States
- Konstantina M. Stankovic
- Speech and Hearing Bioscience and Technology Program, Harvard Medical School, Boston, MA, United States
- Konstantina M. Stankovic
- Harvard Stem Cell Institute, Cambridge, MA, United States
- Konstantina M. Stankovic
- Program in Therapeutic Science, Harvard Medical School, Boston, MA, United States
- DOI
- https://doi.org/10.3389/fnmol.2020.00087
- Journal volume & issue
-
Vol. 13
Abstract
Sensorineural hearing loss (SNHL) caused by noise exposure and attendant loss of glutamatergic synapses between cochlear spiral ganglion neurons (SGNs) and hair cells is the most common sensory deficit worldwide. We show here that systemic administration of a bisphosphonate to mice 24 h after synaptopathic noise exposure regenerated synapses between inner hair cells and SGNs and restored cochlear function. We further demonstrate that this effect is mediated by inhibition of the mevalonate pathway. These results are highly significant because they suggest that bisphosphonates could reverse cochlear synaptopathy for the treatment of SNHL.
Keywords
- auditory nerve
- cochlear synaptopathy
- noise-induced hearing loss
- hidden hearing loss
- bisphosphonate
- synapse regeneration
