Pharmacological inhibition of Notch signaling in the mature guinea pig cochlea

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 aud...

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Veröffentlicht in:	Neuroreport 2007-12, Vol.18 (18), p.1911-1914
Hauptverfasser:	Hori, Ryusuke, Nakagawa, Takayuki, Sakamoto, Tatsunori, Matsuoka, Yoshinori, Takebayashi, Shinji, Ito, Juichi
Format:	Artikel
Sprache:	eng
Schlagworte:	Amyloid Precursor Protein Secretases - antagonists & inhibitors Amyloid Precursor Protein Secretases - metabolism Animals Biological and medical sciences Calcium-Binding Proteins - metabolism Cochlea - drug effects Cochlea - metabolism Cochlea - physiopathology Dipeptides - pharmacology Ear and associated structures. Auditory pathways and centers. Hearing. Vocal organ. Phonation. Sound production. Echolocation Ear, auditive nerve, cochleovestibular tract, facial nerve: diseases, semeiology Enzyme Inhibitors - pharmacology Fundamental and applied biological sciences. Psychology Guinea Pigs Hair Cells, Auditory - drug effects Hair Cells, Auditory - metabolism Hearing Loss, Sensorineural - metabolism Hearing Loss, Sensorineural - physiopathology Intercellular Signaling Peptides and Proteins - metabolism Kanamycin Medical sciences Membrane Proteins - metabolism Nerve Degeneration - chemically induced Nerve Degeneration - metabolism Nerve Degeneration - physiopathology Neuronal Plasticity - physiology Neurotoxins Non tumoral diseases Otorhinolaryngology. Stomatology Receptors, Notch - antagonists & inhibitors Receptors, Notch - metabolism Serrate-Jagged Proteins Signal Transduction - drug effects Signal Transduction - physiology Vertebrates: nervous system and sense organs
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Zusammenfassung:	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.
ISSN:	0959-4965 1473-558X
DOI:	10.1097/WNR.0b013e3282f213e0