PMID- 22575512
OWN - NLM
STAT- MEDLINE
DCOM- 20120831
LR  - 20211021
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Print)
IS  - 0006-291X (Linking)
VI  - 422
IP  - 3
DP  - 2012 Jun 8
TI  - 7,8,3'-Trihydroxyflavone, a potent small molecule TrkB receptor agonist, protects 
      spiral ganglion neurons from degeneration both in vitro and in vivo.
PG  - 387-92
LID - 10.1016/j.bbrc.2012.04.154 [doi]
AB  - 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.
CI  - Copyright (c) 2012 Elsevier Inc. All rights reserved.
FAU - Yu, Qing
AU  - Yu Q
AD  - Department of Otolaryngology Head & Neck Surgery, Beijing Tongren Hospital 
      Capital Medical University, #1 Dong Jiao Min Xiang Street, Beijing 100730, China.
FAU - Chang, Qing
AU  - Chang Q
FAU - Liu, Xia
AU  - Liu X
FAU - Gong, Shusheng
AU  - Gong S
FAU - Ye, Keqiang
AU  - Ye K
FAU - Lin, Xi
AU  - Lin X
LA  - eng
GR  - R33 DC010476/DC/NIDCD NIH HHS/United States
GR  - 4R33DC010476/DC/NIDCD NIH HHS/United States
GR  - R01 DC010204/DC/NIDCD NIH HHS/United States
GR  - R01DC010204/DC/NIDCD NIH HHS/United States
GR  - R01 DC006483/DC/NIDCD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20120507
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (7,8,3'-trihydroxyflavone)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Flavones)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Neurotrophin 3)
RN  - EC 2.7.10.1 (Receptor, trkB)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/physiology
MH  - Cell Survival
MH  - *Cytoprotection
MH  - Flavones/*pharmacology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Nerve Degeneration/pathology/*prevention & control
MH  - Neurons/*drug effects/pathology
MH  - Neuroprotective Agents/*pharmacology
MH  - Neurotrophin 3/physiology
MH  - Receptor, trkB/*agonists
MH  - Spiral Ganglion/*drug effects/pathology
PMC - PMC3388121
MID - NIHMS381094
COIS- Disclosure Statement Authors declare no conflict of interest in this study.
EDAT- 2012/05/12 06:00
MHDA- 2012/09/01 06:00
PMCR- 2013/06/08
CRDT- 2012/05/12 06:00
PHST- 2012/04/18 00:00 [received]
PHST- 2012/04/30 00:00 [accepted]
PHST- 2012/05/12 06:00 [entrez]
PHST- 2012/05/12 06:00 [pubmed]
PHST- 2012/09/01 06:00 [medline]
PHST- 2013/06/08 00:00 [pmc-release]
AID - S0006-291X(12)00843-1 [pii]
AID - 10.1016/j.bbrc.2012.04.154 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2012 Jun 8;422(3):387-92. doi: 
      10.1016/j.bbrc.2012.04.154. Epub 2012 May 7.