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首页> 外文期刊>BMC Genomics >Age-associated bidirectional modulation of gene expression in single identified R15 neuron of Aplysia
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Age-associated bidirectional modulation of gene expression in single identified R15 neuron of Aplysia

机译：年龄相关的海鸟单个R15神经元中基因表达的双向调控

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Background Despite the advances in our understanding of aging-associated behavioral decline, relatively little is known about how aging affects neural circuits that regulate specific behaviors, particularly the expression of genes in specific neural circuits during aging. We have addressed this by exploring a peptidergic neuron R15, an identified neuron of the marine snail Aplysia californica. R15 is implicated in reproduction and osmoregulation and responds to neurotransmitters such as acetylcholine, serotonin and glutamate and is characterized by its action potential bursts. Results We examined changes in gene expression in R15 neurons during aging by microarray analyses of RNAs from two different age groups, mature and old animals. Specifically we find that 1083 ESTs are differentially regulated in mature and old R15 neurons. Bioinformatics analyses of these genes have identified specific biological pathways that are up or downregulated in mature and old neurons. Comparison with human signaling networks using pathway analyses have identified three major networks [(1) cell signaling, cell morphology, and skeletal muscular system development (2) cell death and survival, cellular function maintenance and embryonic development and (3) neurological diseases, developmental and hereditary disorders] altered in old R15 neurons. Furthermore, qPCR analysis of single R15 neurons to quantify expression levels of candidate regulators involved in transcription (CREB1) and translation (S6K) showed that aging is associated with a decrease in expression of these regulators, and similar analysis in three other neurons (L7, L11 and R2) showed that gene expression change during aging could be bidirectional. Conclusions We find that aging is associated with bidirectional changes in gene expression. Detailed bioinformatics analyses and human homolog searches have identified specific biological processes and human-relevant signaling pathways in R15 that are affected during aging. Evaluation of gene expression changes in different neurons suggests specific transcriptomic signature of single neurons during aging.
机译：背景技术尽管我们对衰老相关的行为下降的理解有了进步，但关于衰老如何影响调节特定行为的神经回路（尤其是衰老过程中特定神经回路中基因表达）的知之甚少。我们已经通过探索肽能神经元R15（一种鉴定出的海洋蜗牛Aplysia californica的神经元）解决了这一问题。 R15与生殖和渗透调节有关，对神经递质如乙酰胆碱，5-羟色胺和谷氨酸有反应，其特征是其动作电位突然爆发。结果我们通过微阵列分析来自两个不同年龄组（成熟和成年动物）的RNA，检查了衰老过程中R15神经元基因表达的变化。具体来说，我们发现在成熟和旧的R15神经元中有1083个EST被差异调节。这些基因的生物信息学分析已经确定了在成熟和旧的神经元中上调或下调的特定生物途径。使用途径分析与人类信号传导网络的比较已确定了三个主要网络[（1）细胞信号传导，细胞形态和骨骼肌系统发育（2）细胞死亡和存活，细胞功能维持和胚胎发育，以及（3）神经系统疾病，发育性和遗传性疾病]改变了旧的R15神经元。此外，对单个R15神经元进行qPCR分析以量化参与转录（CREB1）和翻译（S6K）的候选调节子的表达水平，结果表明衰老与这些调节子的表达减少有关，而其他三个神经元（L7， L11和R2）表明衰老过程中的基因表达变化可能是双向的。结论我们发现衰老与基因表达的双向变化有关。详细的生物信息学分析和人类同源物搜索已确定了衰老过程中受影响的R15中特定的生物学过程和人类相关的信号传导途径。对不同神经元中基因表达变化的评估表明，衰老过程中单个神经元具有特定的转录组特征。

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