水杨酸盐对大鼠听觉中枢超微结构影响的初步研究
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摘要
目的腹腔长期注射水杨酸盐后,检测大鼠听皮层和下丘的突触超微结构改变。方法大鼠分为正常对照组、急性注射组、慢性注射组和慢性恢复组共4个组,取材行透射电镜检测听皮层、下丘和小脑的突触超微结构变化,观察各组间的差异。结果与正常对照组比较,慢性注射组出现突触前囊泡增多(t_(下丘)=-4.61,t_(听皮层)=-7.00,P均<0.01)、突触后致密区增厚(t_(下丘)=-4.72,P<0.01;t_(听皮层)=-3.15,P<0.05)、突触曲率上升(t_(下丘)=-2.32,t_(听皮层)=-3.17,P均<0.05)以及突触活性区长度增加(t_(下丘)=-4.89,t_(听皮层)=-3.48,P均<0.01),急性注射组仅出现突触前囊泡的大量释放(t_(下丘)=-10.57,t_(听皮层)=-8.34,t_(小脑)=-9.18,P均<0.01)。慢性恢复组与正常对照组比较未出现显著性差异(P>0.05)。结论慢性腹腔注射水杨酸后,大鼠下丘和听皮层出现突触神经递质释放增多和传递效率上升的改变。在中枢可塑性的调控下,长期应用水杨酸盐使听觉中枢不断发生结构和功能变化。
OBJECTIVE To observe the changes of synaptic ultrastructures in the rat auditory center after long-term salicylate administration and to elucidate the role of neuroplasticity in some areas of the CNS and its involvement in tinnitus. METHODS The rats were divided into 4 groups: the control group,the acute treatment group, the chronic treatment group,and the recovery group. We investigated ultrastructural alterations in the synapses of inferior colliculus(IC),auditory center(AC) and cerebellum(CRB) by transmission electron microscopy. RESULTS There were more synaptic vesicles(t_(IC)=-4.61, t_(AC)=-7.00,P< 0.01),with greater postsynaptic densities(t_(IC)=-4.72, P<0.01;t_(AC)=-3.15,P<0.05),longer synaptic active zone(t_(IC)=-4.89, t_(AC)=-3.48, P<0.01),and increased synaptic interface curvature(t_(IC)=-2.32,t_(AC)=-3.17,P<0.05) in the chronic treatment group, as compared with the control group. There were more synaptic vesicles but no other changes in the acute salicylatetreatment group(t_(IC)=-10.57, t_(AC)=-8.34, t_(CRB)=-9.18, P<0.01).CONCLUSION These findings showed that long-term salicylate administration have induced synaptic ultrastructural changes in the IC and AC because of neuroplasticity. These structural changes may result in increased speed and efficacy of chemical synaptic transmission. Alterations to neuroplasticity of the auditory center pathway may lead to tinnitus.
OBJECTIVE To observe the changes of synaptic ultrastructures in the rat auditory center after long-term salicylate administration and to elucidate the role of neuroplasticity in some areas of the CNS and its involvement in tinnitus. METHODS The rats were divided into 4 groups: the control group,the acute treatment group, the chronic treatment group,and the recovery group. We investigated ultrastructural alterations in the synapses of inferior colliculus(IC),auditory center(AC) and cerebellum(CRB) by transmission electron microscopy. RESULTS There were more synaptic vesicles(t_(IC)=-4.61, t_(AC)=-7.00,P< 0.01),with greater postsynaptic densities(t_(IC)=-4.72, P<0.01;t_(AC)=-3.15,P<0.05),longer synaptic active zone(t_(IC)=-4.89, t_(AC)=-3.48, P<0.01),and increased synaptic interface curvature(t_(IC)=-2.32,t_(AC)=-3.17,P<0.05) in the chronic treatment group, as compared with the control group. There were more synaptic vesicles but no other changes in the acute salicylatetreatment group(t_(IC)=-10.57, t_(AC)=-8.34, t_(CRB)=-9.18, P<0.01).CONCLUSION These findings showed that long-term salicylate administration have induced synaptic ultrastructural changes in the IC and AC because of neuroplasticity. These structural changes may result in increased speed and efficacy of chemical synaptic transmission. Alterations to neuroplasticity of the auditory center pathway may lead to tinnitus.
引文
[1]Hu SS,Mei L,Chen JY,et al.Expression of immediate-early genes in the dorsal cochlear nucleus in salicylate-induced tinnitus.Eur Arch Otorhinolaryngol,2016,273(2):325-332.
[2]Campbell S,Macqueen G.The role of the hippocampus in the pathophysiology of major depression.J Psychiatry Neurosci,2004,29(6):417-426.
[3]Baguley D,McFerran D,Hall D.Tinnitus.Lancet,2013,382(9904):1600-1607.
[4]Langguth B,Kreuzer PM,Kleinjung T,et al.Tinnitus:causes and clinical management.Lancet Neurol,2013,12(9):920-930.
[5]陈观印,冯立宁,刘志,等.低剂量水杨酸钠大鼠耳鸣模型的建立.中国耳鼻咽喉头颈外科,2012,19(2):77-80.
[6]焦粤农,林颖,邵美君,等.正电子发射断层显像与单光子发射断层显像在耳呜诊断中的比较.中国耳鼻咽喉头颈外科,2015,22(4):185-187.
[7]Elgoyhen AB,Langguth B,De Ridder D,et al.Tinnitus:perspectives from human neuroimaging.Nat Rev Neurosci,2015,16(10):632-642.
[8]Hu SS,Mei L,Chen JY,et al.Expression of immediate-early genes in the inferior colliculus and auditory cortex in salicylateinduced tinnitus in rat.Eur J Histochem,2014,58(1):2294.
[9]Brien JA.Ototoxicity associated with salicylates.A brief review.Drug Saf,1993,9(2):143-148.
[10]Cazals Y.Auditory sensori-neural alterations induced by salicylate.Prog Neurobiol,2000,62(6):583-631.
[11]Cazals Y,Horner KC,Huang ZW.Alterations in average spectrum of cochleoneural activity by long-term salicylate treatment in the guinea pig:a plausible index of tinnitus.J Neurophysiol,1998,80(4):2113-2120.
[12]段清川,刘俊秀,方祎,等.利多卡因对大鼠耳鸣模型听皮层抗坏血酸变化的影响.中国耳鼻咽喉头颈外科,2013,20(2):102-104.
[13]Jastreboff PJ,Brennan JF.Evaluating the loudness of phantom auditory perception(tinnitus)in rats.Audiology,1994,33(4):202-217.
[14]Norena AJ,Eggermont JJ.Enriched acoustic environment after noise trauma reduces hearing loss and prevents cortical map reorganization.J Neurosci,2005,25(3):699-705.
[15]Roberts LE,Eggermont JJ,Caspary DM,et al.Ringing ears:the neuroscience of tinnitus.J Neurosci,2010,30(45):14972-14979.
[16]Huang ZW,Luo Y,Wu Z,et al.Paradoxical enhancement of active cochlear mechanics in long-term administration of salicylate.J Neurophysiol,2005,93(4):2053-2061.
[17]Yang K,Huang ZW,Liu ZQ,et al.Long-term administration of salicylate enhances prestin expression in rat cochlea.Int J Audiol,2009,48(1):18-23.
[18]Yang S,Weiner BD,Zhang LS,et al.Homeostatic plasticity drives tinnitus perception in an animal model.Proc Natl Acad Sci USA,2011,108(36):14974-14979.
[19]Ruel J,Chabbert C,Nouvian R,et al.Salicylate enables cochlear arachidonic-acid-sensitive NMDA receptor responses.J Neurosci,2008,28(29):7313-7323.
[20]Eggermont JJ.Tinnitus:neurobiological substrates.Drug Discov Today,2005,10(19):1283-1290.
[2]Campbell S,Macqueen G.The role of the hippocampus in the pathophysiology of major depression.J Psychiatry Neurosci,2004,29(6):417-426.
[3]Baguley D,McFerran D,Hall D.Tinnitus.Lancet,2013,382(9904):1600-1607.
[4]Langguth B,Kreuzer PM,Kleinjung T,et al.Tinnitus:causes and clinical management.Lancet Neurol,2013,12(9):920-930.
[5]陈观印,冯立宁,刘志,等.低剂量水杨酸钠大鼠耳鸣模型的建立.中国耳鼻咽喉头颈外科,2012,19(2):77-80.
[6]焦粤农,林颖,邵美君,等.正电子发射断层显像与单光子发射断层显像在耳呜诊断中的比较.中国耳鼻咽喉头颈外科,2015,22(4):185-187.
[7]Elgoyhen AB,Langguth B,De Ridder D,et al.Tinnitus:perspectives from human neuroimaging.Nat Rev Neurosci,2015,16(10):632-642.
[8]Hu SS,Mei L,Chen JY,et al.Expression of immediate-early genes in the inferior colliculus and auditory cortex in salicylateinduced tinnitus in rat.Eur J Histochem,2014,58(1):2294.
[9]Brien JA.Ototoxicity associated with salicylates.A brief review.Drug Saf,1993,9(2):143-148.
[10]Cazals Y.Auditory sensori-neural alterations induced by salicylate.Prog Neurobiol,2000,62(6):583-631.
[11]Cazals Y,Horner KC,Huang ZW.Alterations in average spectrum of cochleoneural activity by long-term salicylate treatment in the guinea pig:a plausible index of tinnitus.J Neurophysiol,1998,80(4):2113-2120.
[12]段清川,刘俊秀,方祎,等.利多卡因对大鼠耳鸣模型听皮层抗坏血酸变化的影响.中国耳鼻咽喉头颈外科,2013,20(2):102-104.
[13]Jastreboff PJ,Brennan JF.Evaluating the loudness of phantom auditory perception(tinnitus)in rats.Audiology,1994,33(4):202-217.
[14]Norena AJ,Eggermont JJ.Enriched acoustic environment after noise trauma reduces hearing loss and prevents cortical map reorganization.J Neurosci,2005,25(3):699-705.
[15]Roberts LE,Eggermont JJ,Caspary DM,et al.Ringing ears:the neuroscience of tinnitus.J Neurosci,2010,30(45):14972-14979.
[16]Huang ZW,Luo Y,Wu Z,et al.Paradoxical enhancement of active cochlear mechanics in long-term administration of salicylate.J Neurophysiol,2005,93(4):2053-2061.
[17]Yang K,Huang ZW,Liu ZQ,et al.Long-term administration of salicylate enhances prestin expression in rat cochlea.Int J Audiol,2009,48(1):18-23.
[18]Yang S,Weiner BD,Zhang LS,et al.Homeostatic plasticity drives tinnitus perception in an animal model.Proc Natl Acad Sci USA,2011,108(36):14974-14979.
[19]Ruel J,Chabbert C,Nouvian R,et al.Salicylate enables cochlear arachidonic-acid-sensitive NMDA receptor responses.J Neurosci,2008,28(29):7313-7323.
[20]Eggermont JJ.Tinnitus:neurobiological substrates.Drug Discov Today,2005,10(19):1283-1290.