Mechanisms and genes in human strial presbycusis from animal models.
Mechanisms and genes in human strial presbycusis from animal models.
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DOI：
10.1016/j.brainres.2009.02.079
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发表时间：
2009-06-24
期刊：
影响因子：
2.9
通讯作者：
Ohlemiller KK
中科院分区：
文献类型：
--
作者：
Ohlemiller KK
Schuknecht提出了一种离散形式的老年性耳聋，其中听力损失主要是由耳蜗血管纹变性和耳蜗内电位（EP）下降引起的。这种形式被认为与遗传有关，并且独立于Corti器官或耳蜗神经元的年龄相关病理。虽然人类广泛的trial变性与听力损失相吻合，但EPs从未在人类中测量过，并且与年龄相关的EP减少从未得到证实。目前还没有发现促进老年性痴呆的人类基因，其病理生理学也没有得到很好的理解。有效地应用动物模型来解决这个问题需要模型显示EP下降，最好是遗传上不同的菌株，它们在EP下降模式及其细胞相关方面有所不同。直到最近，只有两种模型，蒙古沙鼠和Tyrp1B-lt小鼠，已知经历与年龄相关的EP减少。对7个近交小鼠品系的详细研究已经发现了3个品系（C57BL/6J, B6）。CAST-Cdh23CAST、CBA/J)的EP基本没有随年龄增长而下降，而4个菌株（C57BL/6-Tyrc-2J、BALB/cJ、CBA/CaJ、NOD.NON-H2nbl/LtJ）的EP下降程度从中度到重度不等。总的来说，动物模型支持关于实验性老年性痴呆的五个基本原则：1)EP从最初的正常水平逐渐下降是一个决定性特征；2)非普适性，并非所有年龄相关性听力损失都伴有EP下降；3)明确的遗传基础；4)环境或随机事件的调制作用；5)独立试验，Corti器官和神经病理学。人类试体老年性痴呆、沙鼠、BALB/cJ和C57BL/6-Tyrc-2J小鼠之间的共同特征进一步表明，这种疾病通常始于试体边缘细胞功能障碍和丧失。相比之下，NOD。NON-H2nbl小鼠可以模拟与试验微血管疾病更密切相关的序列。对这些和其他近交小鼠和大鼠模型的进一步研究应该揭示促进人类EP下降的候选过程和基因。
Schuknecht proposed a discrete form of presbycusis in which hearing loss results principally from degeneration of cochlear stria vascularis and decline of the endocochlear potential (EP). This form was asserted to be genetically linked, and to arise independently from age-related pathology of either the organ of Corti or cochlear neurons. Although extensive strial degeneration in humans coincides with hearing loss, EPs have never been measured in humans, and age-related EP reduction has never been verified. No human genes that promote strial presbycusis have been identified, nor is its pathophysiology well understood. Effective application of animal models to this issue requires models demonstrating EP decline, and preferably, genetically distinct strains that vary in patterns of EP decline and its cellular correlates. Until recently, only two models, Mongolian gerbils and Tyrp1B-lt mice, were known to undergo age-associated EP reduction. Detailed studies of seven inbred mouse strains have now revealed three strains (C57BL/6J, B6.CAST-Cdh23CAST, CBA/J) showing essentially no EP decline with age, and four strains ranging from modest to severe EP reduction (C57BL/6-Tyrc-2J, BALB/cJ, CBA/CaJ, NOD.NON-H2nbl/LtJ). Collectively, animal models support five basic principles regarding a strial form of presbycusis: 1) Progressive EP decline from initially normal levels as a defining characteristic; 2) Non-universality, not all age-associated hearing loss involves EP decline; 3) A clear genetic basis; 4) Modulation by environment or stochastic events; and 5) Independent strial, organ of Corti, and neural pathology. Shared features between human strial presbycusis, gerbils, and BALB/cJ and C57BL/6-Tyrc-2J mice further suggest this condition frequently begins with strial marginal cell dysfunction and loss. By contrast, NOD.NON-H2nbl mice may model a sequence more closely associated with strial microvascular disease. Additional studies of these and other inbred mouse and rat models should reveal candidate processes and genes that promote EP decline in humans.
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影响因子：
2.8
作者：
Lang, H;Schulte, BA;Schmiedt, RA
通讯作者：
Schmiedt, RA
影响因子：
2.8
作者：
CONLEE, JW;GERITY, LC;BENNETT, ML
通讯作者：
BENNETT, ML
DOI：
10.1159/000276381
发表时间：
1993-03-01
期刊：
ORL-JOURNAL FOR OTO-RHINO-LARYNGOLOGY AND ITS RELATED SPECIALTIES
影响因子：
--
作者：
DEFRAISSINETTE, A;FELIX, H;GLEESON, MJ
通讯作者：
GLEESON, MJ
影响因子：
--
作者：
Hayashi, Hideo;Sone, Michihiko;Nakashima, Tsutomu
通讯作者：
Nakashima, Tsutomu
影响因子：
168.9
作者：
Gates, GA;Mills, JH
通讯作者：
Mills, JH