噪声暴露对大鼠听皮层兴奋性及GABA和NMDA受体表达的影响
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摘要
目的观察噪声暴露对大鼠听皮层兴奋性以及听皮层γ-氨基丁酸(γ-amino butyric acid,GABA)和N-甲基-天冬氨酸(N-methyl-D-aspartic acid,NMDA)受体表达的影响。方法将14只SD大鼠随机分为噪声暴露高剂量组(3只)、中剂量组(4只)、低剂量组(4只)和正常对照组(3只),高、中、低剂量噪声暴露组大鼠分别于125dB SPL白噪声暴露2小时、120dB SPL白噪声暴露1小时和90dB SPL白噪声暴露1小时,正常对照组不给予噪声暴露;在噪声暴露前、暴露后1小时、1天、3天、1周、2周行听性脑干反应(ABR)和声诱发听皮层放电率检测;运用蛋白免疫印迹技术检测听皮层兴奋性增强的大鼠以及对照组大鼠听皮层组织中GABA和NMDA两种受体亚型(GABAA、GABAB和NR2A、NR2B)的蛋白表达水平。结果所有噪声暴露组大鼠在暴露后1小时各频率ABR反应阈较暴露前显著提高,脱离噪声环境2周后,低、中剂量噪声暴露组各频率ABR反应阈恢复至暴露前水平,高剂量噪声暴露组ABR阈移未恢复。与暴露前相比,低剂量噪声暴露后大鼠听皮层放电率在各时间点未升高;中剂量噪声暴露后1小时听皮层放电率升高,2周后降低至暴露前水平;高剂量组噪声暴露后听皮层放电率在各时间点均降低。与对照组相比,噪声暴露后听皮层放电率升高的大鼠听皮层GABAA、GABAB、NR2A、NR2B受体表达水平均降低。结论 120dB SPL噪声暴露1小时可导致大鼠听皮层兴奋性增强,这可能与听皮层通过减少GABA抑制作用增强听觉中枢兴奋性来补偿外周听觉系统信号输入的减少有关。
Objective To investigate the effects of noise exposure on auditory cortex excitability and expressions ofγ-amino butyric acid(GABA)and N-methyl-D-aspartic acid(NMDA)in rats.Methods 14 spraguedawley rats were used in the study.3 of them were exposed to white noise at 125 dB SPL for 2 has high-noise level group,while another 4 at 120 dB SPL for 1 has medium level group,4 rats at 90 dB SPL for 1 has low noise level,and the left 3 rats without noise exposed as as normal group.The auditory brainstem response(ABR)and auditory cortex firing rate were detected before and 1 hour,1 day,3 days,1 week and 2 weeks after noise exposure.The expression of GABA and NMDA receptor subunits in auditory cortex were examined by western blotting.Results The ABR thresholds were significantly increased 1 hafter exposure in all the noise-exposed groups.2 weeks after noise exposure,the ABR threshold shifts diminished boch in the low and medium noise level groups,but remained still in high noise level group.Auditory cortex firing rate in lowl noise evel group did not change at all time points,after noise exposure,but it increased 1 hour after noise expose in the medium level groups and returned to normal 2 weeks later.It decreased at all the time points after noise exposure in high level group.Compared to the control group,expressions of GABAA,GABAB NR2 Aand NR2 Breceptor in the auditory cortex were all reduced in all the noise exposure groups.Conclusion Exposure to white noise at 120 dB SPL for 1 hresults in increased auditory cortical excitability in rats,which may be related with enhancement of auditory cortical excitability to compensate the reduction in peripheral inputs by reducing cortical GABA inhibition.
Objective To investigate the effects of noise exposure on auditory cortex excitability and expressions ofγ-amino butyric acid(GABA)and N-methyl-D-aspartic acid(NMDA)in rats.Methods 14 spraguedawley rats were used in the study.3 of them were exposed to white noise at 125 dB SPL for 2 has high-noise level group,while another 4 at 120 dB SPL for 1 has medium level group,4 rats at 90 dB SPL for 1 has low noise level,and the left 3 rats without noise exposed as as normal group.The auditory brainstem response(ABR)and auditory cortex firing rate were detected before and 1 hour,1 day,3 days,1 week and 2 weeks after noise exposure.The expression of GABA and NMDA receptor subunits in auditory cortex were examined by western blotting.Results The ABR thresholds were significantly increased 1 hafter exposure in all the noise-exposed groups.2 weeks after noise exposure,the ABR threshold shifts diminished boch in the low and medium noise level groups,but remained still in high noise level group.Auditory cortex firing rate in lowl noise evel group did not change at all time points,after noise exposure,but it increased 1 hour after noise expose in the medium level groups and returned to normal 2 weeks later.It decreased at all the time points after noise exposure in high level group.Compared to the control group,expressions of GABAA,GABAB NR2 Aand NR2 Breceptor in the auditory cortex were all reduced in all the noise exposure groups.Conclusion Exposure to white noise at 120 dB SPL for 1 hresults in increased auditory cortical excitability in rats,which may be related with enhancement of auditory cortical excitability to compensate the reduction in peripheral inputs by reducing cortical GABA inhibition.
引文
1代洪,陶泽璋.噪声性损害对听觉中枢影响的研究进展[J].听力学及言语疾病杂志,2008,16:526.
2 Kaltenbach JA.Tinnitus:models and mechanisms.[J].Hear Res,2011,276:52.
3 Vogler DP,Robertson D,Mulders WH.Hyperactivity in the ventral cochlear nucleus after cochlear trauma.[J].Journal of Neuroscience,2011,31:6639.
4 邹巧治,商秀丽.GABA受体在听觉系统中的作用及研究现状[J].医学临床研究,2010,27:545.
5 Paoletti P,Neyton J.NMDA receptor subunits:function and pharmacology.[J].Current Opinion in Pharmacology,2006,7:39.
6 Kotak VC,Takesian AE,Sanes DH.Hearing loss prevents the maturation of GABA ergic transmission in the auditory cortex[J].Cerebral Cortex,2008,18:2098.
7 颜微微,李明,杨光.耳鸣大鼠NMDA受体亚型1、2A、2B的表达研究[J].中华耳科学杂志,2009,7:216.
8 Ouda L,Druga R,Syka J.Distribution of SMI-32-immunoreactive neurons in the central auditory system of the rat.[J].Brain Structure&Function,2012,217:19.
9 张永海,隋建峰,刘国龙,等.大鼠初级听皮层神经元兴奋性频率反应域的特征[J].第三军医大学学报,2007,29:576.
10 王顶,柳柯,张悦,等.120dB白噪声对C57BL/6J小鼠听力损失的观察研究[J].中华耳科学杂志,2017,15:217.
11 刘芳利,罗彬,孙敬武,等.噪声暴露对大鼠ABR反应阈及听皮层谷氨酸脱羧酶67表达的影响[J].听力学及言语疾病杂志,2014,22:268.
12 Lobarinas E,Spankovich C,Prell CGL.Evidence of“hidden hearing loss”following noise exposures that produce robust TTS and ABR wave-I amplitude reductions[J].Hearing Research,2016,349:155.
13 Nordmann AS,Bohne BA,Harding GW.Histopathological differences between temporary and permanent threshold shift1[J].Hearing Research,2000,139:13.
14 石闯,柳柯,杨仕明,等.宽频带白噪声适度暴露对小鼠听力损害的实验研究[J].中华耳科学杂志,2014,12:307.
15 Basta D,Tzschentke B,Ernst A.Noise-induced cell death in the mouse medial geniculate body and primary auditory cortex[J].Neuroscience Letters,2005,381:199.
16 Su YT,Meng XX,Zhang X,et al.Doxepin mitigates noise induced neuronal damage in primary auditory cortex of mice via suppression of acid sphingomyelinase/ceramide pathway[J].Anatomical Record-advances in Integrative Anatomy&Evolutionary Biology,2017,300:2220.
17 Kujawa SG,Liberman MC.Adding insult to injury:cochlear nerve degeneration after"temporary"noise-induced hearing loss[J].Journal of Neuroscience,2009,29:14077.
18 Rüttiger L,Singer W,Panfordwalsh R,et al.The reduced cochlear output and the failure to adapt the central auditory response causes tinnitus in noise exposed rats[J].Plos One,2013,8:e57247.
19 Scholl B,Wehr M.Disruption of balanced cortical excitation and inhibition by acoustic trauma[J].Journal of Neurophysiology,2008,100:646.
20 Wei S,Deng A,Jayaram A,et al.Noise exposure enhances auditory cortex responses related to hyperacusis behavior.[J].Brain Research,2012,1485:108.
21 李孛,冯艳梅,殷善开.听觉受损后听觉中枢GABA通路的物质改变[J].听力学及言语疾病杂志,2014,22:317.
2 Kaltenbach JA.Tinnitus:models and mechanisms.[J].Hear Res,2011,276:52.
3 Vogler DP,Robertson D,Mulders WH.Hyperactivity in the ventral cochlear nucleus after cochlear trauma.[J].Journal of Neuroscience,2011,31:6639.
4 邹巧治,商秀丽.GABA受体在听觉系统中的作用及研究现状[J].医学临床研究,2010,27:545.
5 Paoletti P,Neyton J.NMDA receptor subunits:function and pharmacology.[J].Current Opinion in Pharmacology,2006,7:39.
6 Kotak VC,Takesian AE,Sanes DH.Hearing loss prevents the maturation of GABA ergic transmission in the auditory cortex[J].Cerebral Cortex,2008,18:2098.
7 颜微微,李明,杨光.耳鸣大鼠NMDA受体亚型1、2A、2B的表达研究[J].中华耳科学杂志,2009,7:216.
8 Ouda L,Druga R,Syka J.Distribution of SMI-32-immunoreactive neurons in the central auditory system of the rat.[J].Brain Structure&Function,2012,217:19.
9 张永海,隋建峰,刘国龙,等.大鼠初级听皮层神经元兴奋性频率反应域的特征[J].第三军医大学学报,2007,29:576.
10 王顶,柳柯,张悦,等.120dB白噪声对C57BL/6J小鼠听力损失的观察研究[J].中华耳科学杂志,2017,15:217.
11 刘芳利,罗彬,孙敬武,等.噪声暴露对大鼠ABR反应阈及听皮层谷氨酸脱羧酶67表达的影响[J].听力学及言语疾病杂志,2014,22:268.
12 Lobarinas E,Spankovich C,Prell CGL.Evidence of“hidden hearing loss”following noise exposures that produce robust TTS and ABR wave-I amplitude reductions[J].Hearing Research,2016,349:155.
13 Nordmann AS,Bohne BA,Harding GW.Histopathological differences between temporary and permanent threshold shift1[J].Hearing Research,2000,139:13.
14 石闯,柳柯,杨仕明,等.宽频带白噪声适度暴露对小鼠听力损害的实验研究[J].中华耳科学杂志,2014,12:307.
15 Basta D,Tzschentke B,Ernst A.Noise-induced cell death in the mouse medial geniculate body and primary auditory cortex[J].Neuroscience Letters,2005,381:199.
16 Su YT,Meng XX,Zhang X,et al.Doxepin mitigates noise induced neuronal damage in primary auditory cortex of mice via suppression of acid sphingomyelinase/ceramide pathway[J].Anatomical Record-advances in Integrative Anatomy&Evolutionary Biology,2017,300:2220.
17 Kujawa SG,Liberman MC.Adding insult to injury:cochlear nerve degeneration after"temporary"noise-induced hearing loss[J].Journal of Neuroscience,2009,29:14077.
18 Rüttiger L,Singer W,Panfordwalsh R,et al.The reduced cochlear output and the failure to adapt the central auditory response causes tinnitus in noise exposed rats[J].Plos One,2013,8:e57247.
19 Scholl B,Wehr M.Disruption of balanced cortical excitation and inhibition by acoustic trauma[J].Journal of Neurophysiology,2008,100:646.
20 Wei S,Deng A,Jayaram A,et al.Noise exposure enhances auditory cortex responses related to hyperacusis behavior.[J].Brain Research,2012,1485:108.
21 李孛,冯艳梅,殷善开.听觉受损后听觉中枢GABA通路的物质改变[J].听力学及言语疾病杂志,2014,22:317.