Age-related changes in GABAA receptor subunit composition and function in rat auditory system
Age-related changes in GABAA receptor subunit composition and function in rat auditory system
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DOI：
10.1016/s0306-4522(99)00121-9
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发表时间：
1999-01-01
期刊：
影响因子：
3.3
通讯作者：
Naritoku, DK
中科院分区：
文献类型：
--
作者：
Caspary, DM;Holder, TM;Naritoku, DK
年龄相关性听力损失（老年性耳聋）导致的区分语言和噪音的能力下降可能反映了中枢神经系统听觉信息处理受损。老年性耳聋的部分原因可能是抑制性神经递质GABA的功能丧失。本研究评估了青成年、中年和老年大鼠下丘GABA(A)受体的年龄相关变化：(i)受体亚基组成和（ii）受体功能。Western blotting检测Fischer 344和Fischer 344/Brown-Norway F1杂交大鼠下丘制备物中选定GABA(A)受体亚基的蛋白水平。在这两种菌株中，老龄组的γ(1)亚基蛋白显著升高，α(1)亚基蛋白显著降低。为了检验这种假定的年龄相关亚基变化的功能后果，我们测量了外源性GABA将氯离子输送/转运到Fischer 344下丘微囊制剂中的能力。在老龄动物下丘制备的样品中，gaba介导的氯化物内流显著增加。结合先前的研究，这些结果强烈提示GABA(A)受体组成的年龄相关变化。这些变化可能反映了面对突触前GABA释放的显著丧失时抑制功能的代偿性上调。这些发现提供了一个在衰老过程中可能发生的可塑性神经递质受体变化的例子。(c) 1999年ibro。Elsevier Science Ltd.出版。
A decline in the ability to discriminate speech from noise due to age-related hearing loss (presbycusis) may reflect impaired auditory information processing within the central nervous system. Presbycusis may result, in part, from functional loss of the inhibitory neurotransmitter GABA. The present study assessed age-related changes of the GABA(A) receptor in the inferior colliculus of young-adult, middle-aged, and aged rats related to: (i) receptor subunit composition and (ii) receptor function. Western blotting was used to measure protein levels of selected GABA(A), receptor subunits in preparations obtained from the inferior colliculus of Fischer 344 and Fischer 344/Brown-Norway F1 hybrid rats. In both strains, the aged group exhibited significant increases in gamma(1) subunit protein and a decrease in alpha(1) subunit protein. To examine the functional consequence of this putative age-related subunit change, we measured the ability of exogenous GABA to flux/translocate chloride ions into microsac preparations derived from Fischer 344 inferior colliculus. GABA-mediated chloride influx was significantly increased in samples prepared from the inferior colliculus of aged animals.Together with previous studies, these results strongly suggest an age-related change in GABA(A) receptor composition. These changes may reflect a compensatory up-regulation of inhibitory function in the face of significant loss of presynaptic GABA release. These findings provide one example of plastic neurotransmitter receptor changes which can occur during the ageing process. (C) 1999 IBRO. Published by Elsevier Science Ltd.