Department of Otolaryngology, Kansai Medical University, Takii Hospital, 10-15 Fumizono-cho, Moriguchi, Osaka 570-8506, Japan.
Brain Res. 2012 May 15;1454:23-32. doi: 10.1016/j.brainres.2012.03.018. Epub 2012 Mar 14.
Presbycusis is the impairment of auditory function associated with aging, which stems from peripheral cochlear lesions and degeneration of the central auditory process. The effect of age-induced peripheral hearing loss on the central auditory process is not fully understood. C57Bl/6 (C57) mice present accelerated peripheral hearing loss, which is well developed by middle-age and mimics the human presbycusis pattern. The aim of this study was to elucidate the molecular effects of peripheral hearing loss in the inferior colliculus (IC) with age between young and middle-aged C57 mice using cDNA microarray. Glutamate receptor ionotropic NMDA ζ1 (GluN1) exhibited the greatest decrease in the middle-aged group as determined using cDNA microarray and by further assessment using real-time PCR (qPCR). Histological assessment with in situ hybridization of GluN1 showed significantly decreased expression in all IC subdivisions of the middle-aged group. GluN1 is a receptor for excitatory neurotransmission, and significant downregulation of this gene may be subsequent to the decline of afferent input from the cochlea in aging C57 mice. Consequently, using the combination of microarray, qPCR, and in situ hybridization, we showed that the decline of GluN1 in the IC of aging animals might have a key role in the pathogenesis of presbycusis.
老年性聋是与年龄相关的听觉功能障碍，源于耳蜗外周病变和中枢听觉过程的退化。年龄引起的外周听力损失对中枢听觉过程的影响尚不完全清楚。C57Bl/6（C57）小鼠表现出加速的外周听力损失，这种损失在中年时就已很好地发展，并模拟了人类老年性聋的模式。本研究旨在使用 cDNA 微阵列阐明年轻和中年 C57 小鼠之间与年龄相关的下丘脑中的外周听力损失的分子效应。使用 cDNA 微阵列和实时 PCR（qPCR）进一步评估，谷氨酸能离子型 NMDA ζ1（GluN1）表现出最大的减少。用 GluN1 的原位杂交进行组织学评估显示，中年组的所有 IC 细分中表达明显降低。GluN1 是兴奋性神经递质的受体，该基因的显著下调可能是衰老 C57 小鼠耳蜗传入输入下降的后续结果。因此，我们通过微阵列、qPCR 和原位杂交的组合，表明衰老动物 IC 中 GluN1 的下降可能在老年性聋的发病机制中起关键作用。
