老年性聋小鼠内耳突触调控钾通道基因的筛选与鉴定

陈小玲; 唐峰; 贾立峰; 李海; 李静雅; 袁伟

doi:10.16016/j.1000-5404.201912021

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老年性聋小鼠内耳突触调控钾通道基因的筛选与鉴定

基础医学 | 更新时间：2026-01-09

- 老年性聋小鼠内耳突触调控钾通道基因的筛选与鉴定
- Screening and identification of synaptic regulatory genes in the inner ear of mice with presbycusis
- 第三军医大学学报 2020年42卷第8期页码：765-771
- 作者机构：
- 作者简介：
- 基金信息：
  
  国家自然基金面上项目(81873702);国家自然科学基金面上项目(81470694)
- DOI：10.16016/j.1000-5404.201912021
  中图分类号：
- 收稿：2019-12-02，
  
  纸质出版：2020-04-30
- 稿件说明：
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陈小玲, 唐峰, 贾立峰, 等. 老年性聋小鼠内耳突触调控钾通道基因的筛选与鉴定[J]. 第三军医大学学报, 2020,42(8):765-771.

Xiaoling CHEN, Feng TANG, Lifeng JIA, et al. Screening and identification of synaptic regulatory genes in the inner ear of mice with presbycusis[J]. Journal of Third Military Medical University, 2020, 42(8): 765-771.
陈小玲, 唐峰, 贾立峰, 等. 老年性聋小鼠内耳突触调控钾通道基因的筛选与鉴定[J]. 第三军医大学学报, 2020,42(8):765-771. DOI： 10.16016/j.1000-5404.201912021.

Xiaoling CHEN, Feng TANG, Lifeng JIA, et al. Screening and identification of synaptic regulatory genes in the inner ear of mice with presbycusis[J]. Journal of Third Military Medical University, 2020, 42(8): 765-771. DOI： 10.16016/j.1000-5404.201912021.

摘要

Abstract

Objective

To screen synaptic regulatory genes in the inner ear and explore the mechanism of synaptic damage in presbycusis.

Methods

We examined the mRNA expression of the genes in the basilar membrane of the inner ear of adult (4-week-old) mice and aged (40-week-old) mice using transcriptome sequencing. Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment of the differentially expressed genes (DEGs) were analyzed to identify synaptic regulatory DEGs

and the results were verified using real-time quantitative PCR and immunofluorescence staining.

Results

We identified a total of 3 267 DEGs

including 1 521 down-regulated genes and 1 746 up-regulated genes (FC≥1.5

0.05). GO function enrichment analysis showed that the down-regulated DEGs mainly participated in the regulation of voltage-gated cation channel activity a

nd synaptic function

and the up-regulated DEGs were mostly responsible for regulation of immune functions. We screened 64 synaptic regulatory genes

among which 6 down-regulated potassium channel genes (Kcnq2

Kcnk3

Kcnmb4

Kcnk9

Kcnh5

and Kcnc2) had the highest enrichment. qRT-PCR verified the differential expression of the 6 genes in the inner ear of mice at different ages; immunofluorescence assay demonstrated that the expression of KCNQ2 and KCNMB4 were significantly decreased in the inner ear of aged mice.

Conclusion

Among the synaptic regulatory genes screened in mice with presbycusis

6 potassium channel genes show significantly decreased expressions in the inner ear of aged mice

suggesting their important involvement in synaptic changes in presbycusis.

关键词

Keywords

references

TAWFIK K O KLEPPER K SALIBA J Advances in understanding of presbycusis J Neurosci Res 2019 10.1002/jnr.24426 TAWFIK K O, KLEPPER K, SALIBA J, et al . Advances in understanding of presbycusis[J ] . J Neurosci Res, 2019. DOI: 10.1002/jnr.24426.

RIQUELME R CEDIEL R CONTRERAS J A comparative study of age-related hearing loss in wild type and insulin-like growth factor I deficientmice Front Neuroanat 2010 4 27 10.3389/fnana.2010.00027 RIQUELME R, CEDIEL R, CONTRERAS J, et al . A comparative study of age-related hearing loss in wild type and insulin-like growth factor I deficientmice[J ] . Front Neuroanat, 2010, 4: 27. DOI: 10.3389/fnana.2010.00027.

SAFIEDDINE S EL-AMRAOUI A PETIT C The auditory hair cell ribbon synapse: from assembly tofunction Annu Rev Neurosci 2012 35 509 528 10.1146/annurev-neuro-061010-113705 SAFIEDDINE S, EL-AMRAOUI A, PETIT C. The auditory hair cell ribbon synapse: from assembly tofunction[J]. Annu Rev Neurosci, 2012, 35: 509-528. DOI: 10.1146/annurev-neuro-061010-113705.

SERGEYENKO Y LALL K LIBERMAN M C Age-related cochlearsynaptopathy: an early-onset contributor to auditory functional decline J Neurosci 2013 33 34 13686 13694 10.1523/JNEUROSCI.1783-13.2013 SERGEYENKO Y, LALL K, LIBERMAN M C, et al . Age-related cochlearsynaptopathy: an early-onset contributor to auditory functional decline[J ] . J Neurosci, 2013, 33(34): 13686-13694. DOI: 10.1523/JNEUROSCI.1783-13.2013.

MOSER T PREDOEHL F STARR A Review of hair cell synapse defects in sensorineural hearingimpairment Otol Neurotol 2013 34 6 995 1004 10.1097/MAO.0b013e3182814d4a MOSER T, PREDOEHL F, STARR A. Review of hair cell synapse defects in sensorineural hearingimpairment[J]. Otol Neurotol, 2013, 34(6): 995-1004. DOI: 10.1097/MAO.0b013e3182814d4a

LIBERMAN M C KUJAWA S G Cochlear synaptopathy in acquired sensorineural hearing loss: Manifestations and mechanisms Hear Res 2017 349 138 147 10.1016/j.heares.2017.01.003 LIBERMAN M C, KUJAWA S G. Cochlear synaptopathy in acquired sensorineural hearing loss: Manifestations and mechanisms[J]. Hear Res, 2017, 349: 138-147.DOI: 10.1016/j.heares.2017.01.003.

KUJAWA S G LIBERMAN M C Synaptopathy in the noise-exposed and aging cochlea: Primary neural degeneration in acquired sensorineural hearing loss Hear Res 2015 330 Pt B 191 199 10.1016/j.heares.2015.02.009 KUJAWA S G, LIBERMAN M C.Synaptopathy in the noise-exposed and aging cochlea: Primary neural degeneration in acquired sensorineural hearing loss[J]. Hear Res, 2015, 330(Pt B): 191-199. DOI: 10.1016/j.heares.2015.02.009.

WANG Z GERSTEIN M SNYDER M RNA-Seq: a revolutionary tool for transcriptomics Nat Rev Genet 2009 10 1 57 63 10.1038/nrg2484 WANG Z, GERSTEIN M, SNYDER M. RNA-Seq: a revolutionary tool for transcriptomics[J]. Nat Rev Genet, 2009, 10(1): 57-63. DOI: 10.1038/nrg2484.

SCHRAUWEN I HASIN-BRUMSHTEIN Y CORNEVEAUX JJ A comprehensive catalogue of the coding and non-coding transcripts of the human inner ear Hear Res 2016 333 266 274 10.1016/j.heares.2015.08.013 SCHRAUWEN I, HASIN-BRUMSHTEIN Y, CORNEVEAUX JJ, et al . A comprehensive catalogue of the coding and non-coding transcripts of the human inner ear[J ] . Hear Res, 2016, 333: 266-274. DOI: 10.1016/j.heares.2015.08.013.

HAN J H WU H W HU H Y Characterization of the transcriptome of hair cell regeneration in the neonatal mouseutricle Cell Physiol Biochem 2018 51 3 1437 1447 10.1159/000495592 HAN J H, WU H W, HU H Y, et al . Characterization of the transcriptome of hair cell regeneration in the neonatal mouseutricle[J ] . Cell Physiol Biochem, 2018, 51(3): 1437-1447. DOI: 10.1159/000495592.

GUO Y ZHANG P SHENG Q H LncRNA expression in the auditory forebrain during postnatal development Gene 2016 593 1 201 216 10.1016/j.gene.2016.08.027 GUO Y, ZHANG P, SHENG Q H, et al . LncRNA expression in the auditory forebrain during postnatal development[J ] . Gene, 2016, 593(1): 201-216. DOI: 10.1016/j.gene.2016.08.027.

李胜利武坤毅任晓勇年龄相关听力损失DBA/2J小鼠耳蜗毛细胞马达蛋白-prestin表达下调与耳聋的关系中华耳科学杂志 2018 16 4 562 569 10.3969/j.issn.1672-2922.2018.04.025 李胜利, 武坤毅, 任晓勇.年龄相关听力损失DBA/2J小鼠耳蜗毛细胞马达蛋白-prestin表达下调与耳聋的关系[J].中华耳科学杂志, 2018, 16(4): 562-569. DOI: 10.3969/j.issn.1672-2922.2018.04.025.

LI S L WU K Y REN X Y Down-regulated prestin expression in cochlear outer hair cells in DBA/2J mice with age-related hearing loss Chin J Otol 2018 16 4 562 569 10.3969/j.issn.1672-2922.2018.04.025 LI S L, WU K Y, REN X Y. Down-regulated prestin expression in cochlear outer hair cells in DBA/2J mice with age-related hearing loss[J]. Chin J Otol, 2018, 16(4): 562-569.DOI: 10.3969/j.issn.1672-2922.2018.04.025.

OHLEMILLER K K Age-related hearing loss: the status of Schuknecht's typology Curr Opin Otolaryngol Head Neck Surg 2004 12 5 439 443 10.1097/01.moo.0000134450.99615.22 OHLEMILLER K K. Age-related hearing loss: the status of Schuknecht's typology[J]. Curr Opin Otolaryngol Head Neck Surg, 2004, 12(5): 439-443. DOI: 10.1097/01.moo.0000134450.99615.22.

魏薇杨丽辉熊伟老年性聋小鼠耳蜗带状突触损伤特点及机制研究中华耳科学杂志 2019 17 2 198 202 http://d.old.wanfangdata.com.cn/Periodical/zhekxzz201902012 魏薇, 杨丽辉, 熊伟, 等.老年性聋小鼠耳蜗带状突触损伤特点及机制研究[J].中华耳科学杂志, 2019, 17(2): 198-202.

WEI W YANG L H XIONG W Characteristics of cochlear ribbon synapses damage in aging mice and possiblemechanisms Chin J Otol 2019 17 2 198 202 http://d.old.wanfangdata.com.cn/Periodical/zhekxzz201902012 WEI W, YANG L H, XIONG W, et al . Characteristics of cochlear ribbon synapses damage in aging mice and possiblemechanisms[J ] . Chin J Otol, 2019, 17(2): 198-202.

李晓瑞蒋兴旺张延平 C57B L/6J小鼠随年龄增长耳蜗内毛细胞带状突触数量变化的观察听力学及言语疾病杂志 2015 23 2 176 180 10.3969/j.issn.1006-7299.2015.02.014 李晓瑞, 蒋兴旺, 张延平. C57B L/6J小鼠随年龄增长耳蜗内毛细胞带状突触数量变化的观察[J].听力学及言语疾病杂志, 2015, 23(2): 176-180. DOI: 10.3969/j.issn.1006-7299.2015.02.014.

LI X R JIANG X W ZHANG Y P The changes of the number of ribbon synapse in inner hair cells of C57BL/6J mice with age J Audiol Speech Pathol 2015 23 2 176 180 10.3969/j.issn.1006-7299.2015.02.014 LI X R, JIANG X W, ZHANG Y P. The changes of the number of ribbon synapse in inner hair cells of C57BL/6J mice with age[J]. J Audiol Speech Pathol, 2015, 23(2): 176-180. DOI: 10.3969/j.issn.1006-7299.2015.02.014.

NILIUS B FLOCKERZI V Mammalian transient receptor potential (TRP) cation channels.Preface Handb Exp Pharmacol 2014 223 v vi https://www.researchgate.net/publication/266683729_Mammalian_transient_receptor_potential_TRP_cation_channels_Preface NILIUS B, FLOCKERZI V. Mammalian transient receptor potential (TRP) cation channels.Preface[J]. Handb Exp Pharmacol, 2014, 223: v-vi.

STEEL K P KROS C J A genetic approach to understanding auditory function Nat Genet 2001 27 2 143 149 10.1038/84758 STEEL K P, KROS C J. A genetic approach to understanding auditory function[J]. Nat Genet, 2001, 27(2): 143-149. DOI: 10.1038/84758.

CONTINI D PRICE S D ART JJ Accumulation of K + in the synaptic cleft modulates activity by influencing both vestibular hair cell and Calyx afferent in the turtle J Physiol (Lond) 2017 595 3 777 803 10.1113/JP273060 CONTINI D, PRICE S D, ART JJ. Accumulation of K + in the synaptic cleft modulates activity by influencing both vestibular hair cell and Calyx afferent in the turtle[J ] . J Physiol (Lond), 2017, 595(3): 777-803. DOI: 10.1113/JP273060.

WANG JJ LI Y KCNQ potassium channels in sensory system and neural circuits Acta Pharmacol Sin 2016 37 1 25 33 10.1038/aps.2015.131 WANG JJ, LI Y. KCNQ potassium channels in sensory system and neural circuits[J]. Acta Pharmacol Sin, 2016, 37(1): 25-33. DOI: 10.1038/aps.2015.131.

SOH H PARK S RYAN K Deletion of KCNQ2/3 potassium channels from PV+ interneurons leads to homeostatic potentiation of excitatorytransmission Elife 2018 7 e38617 10.7554/eLife.38617 SOH H, PARK S, RYAN K, et al . Deletion of KCNQ2/3 potassium channels from PV+ interneurons leads to homeostatic potentiation of excitatorytransmission[J ] . Elife, 2018, 7: e38617. DOI: 10.7554/eLife.38617.

SUN W LIU J ZHANG C Potassium channel activator attenuates salicylate-induced cochlear hearing loss potentially amelioratingtinnitus Front Neurol 2015 6 77 10.3389/fneur.2015.00077 SUN W, LIU J, ZHANG C, et al . Potassium channel activator attenuates salicylate-induced cochlear hearing loss potentially amelioratingtinnitus[J ] . Front Neurol, 2015, 6: 77. DOI: 10.3389/fneur.2015.00077.

FETTIPLACE R Hair cell transduction, tuning, and synaptic transmission in the mammaliancochlea Compr Physiol 2017 7 4 1197 1227 10.1002/cphy.c160049 FETTIPLACE R. Hair cell transduction, tuning, and synaptic transmission in the mammaliancochlea[J]. Compr Physiol, 2017, 7(4): 1197-1227. DOI: 10.1002/cphy.c160049.

ROBITAILLE R CHARLTON M P Presynaptic calcium signals and transmitter release are modulated by calcium-activated potassiumchannels J Neurosci 1992 12 1 297 305 10.1523/JNEUROSCI.12-01-00297.1992 ROBITAILLE R, CHARLTON M P. Presynaptic calcium signals and transmitter release are modulated by calcium-activated potassiumchannels[J]. J Neurosci, 1992, 12(1): 297-305.

LEE U S CUI J M BK channel activation: structural and functionalinsights Trends Neurosci 2010 33 9 415 423 10.1016/j.tins.2010.06.004 LEE U S, CUI J M. BK channel activation: structural and functionalinsights[J]. Trends Neurosci, 2010, 33(9): 415-423. DOI: 10.1016/j.tins.2010.06.004.

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