Pharmacological inhibition of Notch signaling in the mature guinea pig cochlea

Ryusuke Hori; Takayuki Nakagawa; Tatsunori Sakamoto; Yoshinori Matsuoka; Shinji Takebayashi; Juichi Ito

doi:10.1097/WNR.0b013e3282f213e0

Pharmacological inhibition of Notch signaling in the mature guinea pig cochlea

Ryusuke Hori, Takayuki Nakagawa, Tatsunori Sakamoto, Yoshinori Matsuoka, Shinji Takebayashi, Juichi Ito

Research output: Contribution to journal › Article › peer-review

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Abstract

Recent studies using explant cultures have demonstrated that pharmacological inhibition of Notch signaling by γ-secretase inhibitors generates supernumerary hair cells in embryonic or neonatal cochleae. The aim of this study was to examine the effects of such pharmacological inhibition on mature auditory epithelia in vivo. Normal adult guinea pig auditory epithelia exhibited weak or no immunoreactivity for Notch1 and Jagged1, whereas ototoxic treatment caused the upregulation of these molecules in damaged auditory epithelia. Local application of a γ-secretase inhibitor in damaged cochleae generated ectopic hair cells in mature auditory epithelia. These findings indicate that pharmacological inhibition of Notch signaling is a possible strategy for hair cell regeneration in adult auditory epithelia.

Original language	English
Pages (from-to)	1911-1914
Number of pages	4
Journal	Neuroreport
Volume	18
Issue number	18
DOIs	https://doi.org/10.1097/WNR.0b013e3282f213e0
Publication status	Published - 12-2007
Externally published	Yes

All Science Journal Classification (ASJC) codes

General Neuroscience

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abstract = "Recent studies using explant cultures have demonstrated that pharmacological inhibition of Notch signaling by γ-secretase inhibitors generates supernumerary hair cells in embryonic or neonatal cochleae. The aim of this study was to examine the effects of such pharmacological inhibition on mature auditory epithelia in vivo. Normal adult guinea pig auditory epithelia exhibited weak or no immunoreactivity for Notch1 and Jagged1, whereas ototoxic treatment caused the upregulation of these molecules in damaged auditory epithelia. Local application of a γ-secretase inhibitor in damaged cochleae generated ectopic hair cells in mature auditory epithelia. These findings indicate that pharmacological inhibition of Notch signaling is a possible strategy for hair cell regeneration in adult auditory epithelia.",

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AU - Sakamoto, Tatsunori

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AU - Takebayashi, Shinji

AU - Ito, Juichi

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AB - Recent studies using explant cultures have demonstrated that pharmacological inhibition of Notch signaling by γ-secretase inhibitors generates supernumerary hair cells in embryonic or neonatal cochleae. The aim of this study was to examine the effects of such pharmacological inhibition on mature auditory epithelia in vivo. Normal adult guinea pig auditory epithelia exhibited weak or no immunoreactivity for Notch1 and Jagged1, whereas ototoxic treatment caused the upregulation of these molecules in damaged auditory epithelia. Local application of a γ-secretase inhibitor in damaged cochleae generated ectopic hair cells in mature auditory epithelia. These findings indicate that pharmacological inhibition of Notch signaling is a possible strategy for hair cell regeneration in adult auditory epithelia.

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Pharmacological inhibition of Notch signaling in the mature guinea pig cochlea

Abstract

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