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作为老年性聋模型的Fischer 344大鼠。

The Fischer 344 rat as a model of presbycusis.

作者信息

Syka Josef

机构信息

Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, 142 20 Prague, Czech Republic.

出版信息

Hear Res. 2010 Jun 1;264(1-2):70-8. doi: 10.1016/j.heares.2009.11.003. Epub 2009 Nov 10.

Abstract

Due to the rising number of the aged human population all over the world, presbycusis is a phenomenon that deserves the increasing attention of the medical community as regards to prevention and treatment. This requires finding appropriate animal models for human presbycusis that will be useful in future experiments. Among the available rat strains, the Fischer 344 (F344) strain promises to serve as a model producing prompt and profound presbycusis. Hearing thresholds begin to increase in this strain during the first year of life; toward the end of the second year, the thresholds are very high. The threshold shifts progress independently in both ears. The rapid deterioration of distortion product otoacoustic emissions, with the majority of outer hair cells (OHC) being present and morphologically intact, is apparently produced by the disruption of prestin. The age-related changes within inner ear function are accompanied by deterioration of acoustical signal processing within central auditory system, mainly due to impaired GABA inhibition. The loss of GABA inhibition in old animals is expressed primarily in the inferior colliculus but is also present in the cochlear nuclei and the auditory cortex. Sound-evoked behavioral reactions are also impaired in old F344 rats. Taken together, the described characteristics of the aging F344 rat auditory system supports the idea that this strain may serve as a suitable model for studying the mechanisms of presbycusis, its prevention and treatment.

摘要

由于全球老年人口数量不断增加,老年性聋作为一种现象,在预防和治疗方面值得医学界日益关注。这就需要找到适合人类老年性聋的动物模型,以便在未来的实验中发挥作用。在现有的大鼠品系中,Fischer 344(F344)品系有望成为一种能迅速产生严重老年性聋的模型。在该品系大鼠出生后的第一年,听力阈值就开始升高;到第二年末,阈值变得非常高。双耳的阈值变化是独立进行的。畸变产物耳声发射迅速恶化,此时大多数外毛细胞(OHC)仍然存在且形态完整,这显然是由预应力蛋白的破坏所导致的。内耳功能的年龄相关变化伴随着中枢听觉系统内声学信号处理能力的下降,主要原因是γ-氨基丁酸(GABA)抑制作用受损。老年动物中GABA抑制作用的丧失主要表现在下丘,但在耳蜗核和听觉皮层也存在。在老年F344大鼠中,声音诱发的行为反应也受到损害。综上所述,衰老的F344大鼠听觉系统的上述特征支持了这样一种观点,即该品系可能是研究老年性聋的机制、预防和治疗的合适模型。

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