title: 7,8,3'-Trihydroxyflavone, a potent small molecule TrkB receptor agonist, protects spiral ganglion neurons from degeneration both in vitro and in vivo.
abstract: Most sensorineural hearing loss cases occur as a result of hair cell loss, which results in secondary degeneration of spiral ganglion neurons (SGNs). Substantial loss of SGNs reduces the benefit of cochlear implants, which rely on SGNs for transmitting signals to the central auditory centers. Brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) play essential roles in cochlear development and are required for SGN survival. Here we report that 7,8,3'-trihydroxyflavone (7,8,3'-THF), which is a small molecule agonist of tyrosine receptor kinase B (TrkB), promoted SGN survival with high potency both in vitro and in vivo. The compound protected the SGNs in a TrkB-dependent manner, as its effects on SGNs disappeared when the TrkB was blocked. Application of 7,8,3'-THF in the bulla of conditional connexin26 (cCx26)-null mice dramatically rescued SGNs in the applied ear compared to untreated control cochlea in the same animal. Our findings suggest that 7,8,3'-THF is a promising therapeutic agent protecting the SGNs from degeneration both in vitro and in vivo.
authors.affiliation: Department of Otolaryngology Head & Neck Surgery, Beijing Tongren Hospital Capital Medical University, #1 Dong Jiao Min Xiang Street, Beijing 100730, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Yu
authors.forename: Qing
authors.initials: Q
authors.lastname: Chang
authors.forename: Xia
authors.initials: X
authors.lastname: Liu
authors.forename: Shusheng
authors.initials: S
authors.lastname: Gong
authors.forename: Keqiang
authors.initials: K
authors.lastname: Ye
authors.forename: Xi
authors.initials: X
authors.lastname: Lin
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000502:physiology; D002470:Cell Survival; D019610:Cytoprotection; D047309:Flavones / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009410:Nerve Degeneration / Q000473:pathology / Q000517:prevention & control*; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D020933:Neurotrophin 3 / Q000502:physiology; D020813:Receptor, trkB / Q000819:agonists*; D013136:Spiral Ganglion / Q000187:drug effects* / Q000473:pathology
chemical_list: C574665:7,8,3'-trihydroxyflavone; D019208:Brain-Derived Neurotrophic Factor; D047309:Flavones; D018696:Neuroprotective Agents; D020933:Neurotrophin 3; D020813:Receptor, trkB