7,8,3'-Trihydroxyflavone, a potent small molecule TrkB receptor agonist, protects spiral ganglion neurons from degeneration both in vitro and in vivo.

Biochemical and Biophysical Research Communications
Qing YuXi Lin

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.

References

Mar 22, 1996·Neuroreport·B MalgrangeG Moonen
Jul 1, 1997·International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience·J M MillerR A Altschuler
Jul 24, 2001·Amyotrophic Lateral Sclerosis and Other Motor Neuron Disorders : Official Publication of the World Federation of Neurology, Research Group on Motor Neuron Diseases·G OchsK V Toyka
Oct 1, 1992·The European Journal of Neuroscience·Patrik ErnforsHåkan Persson
Apr 12, 2005·Neuron·Xi ChenDavid D Ginty
Sep 10, 2005·Otology & Neurotology : Official Publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology·Sarah L McGuinness, Robert K Shepherd
Jan 18, 2007·Proceedings of the National Academy of Sciences of the United States of America·Shoeb AhmadXi Lin
May 13, 2009·Biochemical and Biophysical Research Communications·Yunfeng WangXi Lin
May 28, 2009·Nature Neuroscience·John V Brigande, Stefan Heller
Feb 6, 2010·Proceedings of the National Academy of Sciences of the United States of America·Dennis C ChoiKerry J Ressler
Feb 6, 2010·Proceedings of the National Academy of Sciences of the United States of America·Sung-Wuk JangKeqiang Ye
Sep 9, 2011·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Aurélie BlugeotChrystel Becker
Sep 9, 2011·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Latha Devi, Masuo Ohno
Dec 24, 2011·Journal of Applied Physiology·Rebecca A JohnsonQiang Chang

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Citations

Aug 9, 2013·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Qing YuXi Lin
Jul 3, 2016·Medical Science Monitor : International Medical Journal of Experimental and Clinical Research·Haohong Shi, Xingjing Luo
Dec 30, 2020·JCI Insight·Katharine A FernandezAlbert Sb Edge

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