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A Novel Model for Rapid Induction of Apoptosis in Spiral Ganglions of Mice
Author(s) -
Lee Ji Eun,
Nakagawa Takayuki,
Kim Tae Soo,
Iguchi Fukuichiro,
Endo Tsuyoshi,
Dong Youyi,
Yuki Kazuo,
Naito Yasushi,
Lee Sang Heun,
Ito Juichi
Publication year - 2003
Publication title -
the laryngoscope
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.181
H-Index - 148
eISSN - 1531-4995
pISSN - 0023-852X
DOI - 10.1097/00005537-200306000-00015
Subject(s) - spiral ganglion , tunel assay , apoptosis , immunostaining , terminal deoxynucleotidyl transferase , microbiology and biotechnology , programmed cell death , biology , neurofilament , in situ nick end labeling , peripherin , nitrotyrosine , cytochrome c , pathology , mitochondrion , inner ear , immunohistochemistry , anatomy , immunology , medicine , biochemistry , nitric oxide synthase , gene , enzyme
Objectives/Hypothesis The survival of the spiral ganglion (SG) is a critical issue in preservation of hearing. Research on topics related to this issue requires a mouse experimental model because such a model has advantages including use of genetic information and knockout or “knockin” mice. Thus, the aim of the study was to establish a mouse model for induction of apoptosis of SG neurons with a definite time course. Study Design Laboratory study using experimental animals. Methods C57BL/6 mice were used as experimental animals and were subjected to direct application of cisplatin into the inner ear. Terminal deoxynucleotidyl transferase–mediated dUTP nick‐end labeling (TUNEL) assay and immunostaining for Neurofilament 200‐kD (NF) and peripherin were used for analysis of SG degeneration. In addition, generation of peroxynitrite in affected spiral ganglions was examined by immunostaining for nitrotyrosine. Cellular location of activated caspase‐9 and cytochrome‐c in dying SG neurons were examined for analysis of cell death pathway. Results The TUNEL assay and immunohistochemical analysis for NF and peripherin indicated that type I neurons in spiral ganglions were deleted through the apoptotic pathway over time. Spiral ganglion neurons treated with cisplatin exhibited expression of nitrotyrosine, indicating induction of peroxynitrite by cisplatin. In dying SG neurons, expression of activated caspase‐9 and translocation of cytochrome‐c from mitochondria to cytoplasm were observed, indicating the mitochondrial pathway of apoptosis. Conclusion The predictable fashion of induction of apoptosis in SG neurons over a well‐defined time course in the model in the study will aid studies of the molecular mechanism of cell death and elucidation of a strategy for prevention of SG degeneration.