Age-related gene expression change of GABAergic system in visual cortex of rhesus macaque
Age-related gene expression change of GABAergic system in visual cortex of rhesus macaque
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DOI：
10.1016/j.gene.2016.05.010
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发表时间：
2016-09-30
期刊：
影响因子：
3.5
通讯作者：
Su, Bing
中科院分区：
文献类型：
--
作者：
Liao, Chenghong;Han, Qian;Su, Bing
视觉功能退化是衰老过程中的常见现象，可能是由受损的中枢视觉通路的变化介导的。用GABA或其激动剂治疗可以恢复衰老猕猴初级视觉皮层中视觉神经元的能力。然而，关于非人类灵长类动物的 GABA 能系统变化与视觉功能老化退化之间的关系，人们知之甚少。采用定量PCR方法，测量了不同年龄组初级视觉皮层（Brodmann's 17）中24个GABA相关基因的表达变化。在本研究中，分别通过实时RT-PCR和Western blot检测谷氨酸脱羧酶(GAD65)的mRNA和蛋白。结果显示，老年猴体内的 GAD65 信息水平没有显着改变，但蛋白质显着减少。由于GAD65在GABA合成中发挥重要作用，GAD65蛋白的下调可能是导致老年猕猴初级视觉皮层中GABA减少的关键因素。此外，即使经过Banjamini校正进行多重比较，衰老过程中14个GABA受体基因中有7个上调，1个GABA受体基因显着减少（P < 0.05）。这些结果表明，GAD65 蛋白的失调可能导致一些与年龄相关的神经视觉功能障碍，并且大多数 GABA 受体基因对健康老年猴皮层中 GABA 释放减少产生明显的补偿作用。 (C) 2016 Elsevier B.V. 保留所有权利。
Degradation of visual function is a common phenomenon during aging and likely mediated by change in the impaired central visual pathway. Treatment with GABA or its agonist could recover the ability of visual neurons in the primary visual cortex of senescent macaques. However, little is known about how GABAergic system change is related to the aged degradation of visual function in nonhuman primate. With the use of quantitative PCR method, we measured the expression change of 24 GABA related genes in the primary visual cortex (Brodmann's 17) of different age groups. In this study, both of mRNA and protein of glutamic acid decarboxylase (GAD65) were measured by real-time RT-PCR and Western blot, respectively. Results revealed that the level of GAD65 message was not significantly altered, but the proteins were significantly decreased in the aged monkey. As GAD65 plays an important role in GABA synthesis, the down-regulation of GAD65 protein was likely the key factor leading to the observed GABA reduction in the primary visual cortex of the aged macaques. In addition, 7 of 14 GABA receptor genes were up-regulated and one GABA receptor gene was significantly reduced during aging process even after Banjamini correction for multiple comparisons (P < 0.05). These results suggested that the dysregulation of GAD65 protein might contribute to some age-related neural visual dysfunctions and most of GABA receptor genes induce a clear indication of compensatory effect for the reduced GABA release in the healthy aged monkey cortex. (C) 2016 Elsevier B.V. All rights reserved.