Overexpression of X-Linked Inhibitor of Apoptotic Protein (XIAP) reduces age-related neuronal degeneration in the mouse cochlea

Q. Ruan; S. Zeng; A. Liu; Z. Chen; Z. Yu; R. Zhang; J. He; M. Bance; G. Robertson; S. Yin; J. Wang

doi:10.1038/gt.2014.77

Overexpression of X-Linked Inhibitor of Apoptotic Protein (XIAP) reduces age-related neuronal degeneration in the mouse cochlea

Q. Ruan, S. Zeng, A. Liu, Z. Chen, Z. Yu, R. Zhang, J. He, M. Bance, G. Robertson, S. Yin, J. Wang

Medicine

Medicine

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Abstract

Previously, we showed that age-related hearing loss (AHL) was delayed in C57BL6 mice overexpressing X-Linked Inhibitor of Apoptotic Protein (XIAP), and the delayed AHL was associated with attenuated hair cell (HC) loss in XIAP-overexpressing mice. Similar to other reports, the HC loss in aged mice was restricted to the basal turn in this previous study, and occurred slightly at the apical end of the cochlea, showing considerably less spread than the frequency region of hearing loss. In the present study, we examined whether and how AHL is related to the degeneration of neuronal innervation of the cochlea and whether the overexpression of XIAP exerts a protective effect against age-related degeneration in both afferent and efferent cochlear neurites. In contrast to HC loss, degeneration of both afferent and efferent neurites spread to the middle turns of the cochlea. Moreover, XIAP-overexpressing mice lost fewer HC afferent dendrites and efferent axons, as well as fewer spiral ganglion neurons between 3 and 14 months of age in comparison with wild-type littermates. The results suggest that age-related degeneration of cochlear neurites may be independent of HC loss. Further, the inhibition of apoptosis by XIAP appears to reduce degeneration of both afferent and efferent cochlear neurites.

Original language	English
Pages (from-to)	967-974
Number of pages	8
Journal	Gene Therapy
Volume	21
Issue number	11
DOIs	https://doi.org/10.1038/gt.2014.77
Publication status	Published - Nov 13 2014

Bibliographical note

Funding Information:
This study was supported by a grant-in-aid for Scientific Research from Shanghai Municipal Health Bureau (No. 2011-4144), the State Key Development Program for Basic Research of China (Grant no. 2011CB504503 and no. 2012CB967903), the National Science Foundation for Distinguished Young Scholars of China (Grant no. 30925035) and the Canadian Institute of Health Research (MOP79452). The English in this document has been checked by at least two professional editors, both native speakers of English. For a certificate, please see: http://www.textcheck.com/ certificate/D1ntYv.

Publisher Copyright:
© 2014 Macmillan Publishers Limited All rights reserved.

ASJC Scopus Subject Areas

Molecular Medicine
Molecular Biology
Genetics

PubMed: MeSH publication types

Journal Article
Research Support, Non-U.S. Gov't

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10.1038/gt.2014.77

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title = "Overexpression of X-Linked Inhibitor of Apoptotic Protein (XIAP) reduces age-related neuronal degeneration in the mouse cochlea",

abstract = "Previously, we showed that age-related hearing loss (AHL) was delayed in C57BL6 mice overexpressing X-Linked Inhibitor of Apoptotic Protein (XIAP), and the delayed AHL was associated with attenuated hair cell (HC) loss in XIAP-overexpressing mice. Similar to other reports, the HC loss in aged mice was restricted to the basal turn in this previous study, and occurred slightly at the apical end of the cochlea, showing considerably less spread than the frequency region of hearing loss. In the present study, we examined whether and how AHL is related to the degeneration of neuronal innervation of the cochlea and whether the overexpression of XIAP exerts a protective effect against age-related degeneration in both afferent and efferent cochlear neurites. In contrast to HC loss, degeneration of both afferent and efferent neurites spread to the middle turns of the cochlea. Moreover, XIAP-overexpressing mice lost fewer HC afferent dendrites and efferent axons, as well as fewer spiral ganglion neurons between 3 and 14 months of age in comparison with wild-type littermates. The results suggest that age-related degeneration of cochlear neurites may be independent of HC loss. Further, the inhibition of apoptosis by XIAP appears to reduce degeneration of both afferent and efferent cochlear neurites.",

author = "Q. Ruan and S. Zeng and A. Liu and Z. Chen and Z. Yu and R. Zhang and J. He and M. Bance and G. Robertson and S. Yin and J. Wang",

note = "Funding Information: This study was supported by a grant-in-aid for Scientific Research from Shanghai Municipal Health Bureau (No. 2011-4144), the State Key Development Program for Basic Research of China (Grant no. 2011CB504503 and no. 2012CB967903), the National Science Foundation for Distinguished Young Scholars of China (Grant no. 30925035) and the Canadian Institute of Health Research (MOP79452). The English in this document has been checked by at least two professional editors, both native speakers of English. For a certificate, please see: http://www.textcheck.com/ certificate/D1ntYv. Publisher Copyright: {\textcopyright} 2014 Macmillan Publishers Limited All rights reserved.",

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AU - Ruan, Q.

AU - Zeng, S.

AU - Liu, A.

AU - Chen, Z.

AU - Yu, Z.

AU - Zhang, R.

AU - He, J.

AU - Bance, M.

AU - Robertson, G.

AU - Yin, S.

AU - Wang, J.

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PY - 2014/11/13

Y1 - 2014/11/13

N2 - Previously, we showed that age-related hearing loss (AHL) was delayed in C57BL6 mice overexpressing X-Linked Inhibitor of Apoptotic Protein (XIAP), and the delayed AHL was associated with attenuated hair cell (HC) loss in XIAP-overexpressing mice. Similar to other reports, the HC loss in aged mice was restricted to the basal turn in this previous study, and occurred slightly at the apical end of the cochlea, showing considerably less spread than the frequency region of hearing loss. In the present study, we examined whether and how AHL is related to the degeneration of neuronal innervation of the cochlea and whether the overexpression of XIAP exerts a protective effect against age-related degeneration in both afferent and efferent cochlear neurites. In contrast to HC loss, degeneration of both afferent and efferent neurites spread to the middle turns of the cochlea. Moreover, XIAP-overexpressing mice lost fewer HC afferent dendrites and efferent axons, as well as fewer spiral ganglion neurons between 3 and 14 months of age in comparison with wild-type littermates. The results suggest that age-related degeneration of cochlear neurites may be independent of HC loss. Further, the inhibition of apoptosis by XIAP appears to reduce degeneration of both afferent and efferent cochlear neurites.

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Overexpression of X-Linked Inhibitor of Apoptotic Protein (XIAP) reduces age-related neuronal degeneration in the mouse cochlea

Abstract

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