Age-associated bidirectional modulation of gene expression in single identified R15 neuron of Aplysia.
Age-associated bidirectional modulation of gene expression in single identified R15 neuron of Aplysia.
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DOI：
10.1186/1471-2164-14-880
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发表时间：
2013-12-14
期刊：
影响因子：
4.4
通讯作者：
Puthanveettil SV
中科院分区：
文献类型：
--
作者：
Kadakkuzha BM;Akhmedov K;Capo TR;Carvalloza AC;Fallahi M;Puthanveettil SV
尽管我们对与衰老相关的行为衰退的理解有所进步，但对于衰老如何影响调节特定行为的神经回路，特别是衰老过程中特定神经回路中基因的表达，我们知之甚少。我们已经通过探索一个肽能神经元R15来解决这个问题，R15是加利福尼亚海蜗牛的一个已识别的神经元。R15参与生殖和渗透调节，对神经递质如乙酰胆碱、血清素和谷氨酸有反应，并以其动作电位爆发为特征。我们通过芯片分析两个不同年龄组（成熟动物和老年动物）的rna，研究了衰老过程中R15神经元基因表达的变化。具体来说，我们发现1083 est在成熟和衰老的R15神经元中受到不同的调控。这些基因的生物信息学分析已经确定了在成熟和衰老神经元中上调或下调的特定生物学途径。通过通路分析与人类信号网络的比较，发现了三个主要网络[(1)细胞信号、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；(3)神经疾病、发育和遗传性疾病]在老R15神经元中发生改变。此外，通过对单个R15神经元的qPCR分析，量化了参与转录（CREB1）和翻译（S6K）的候选调节因子的表达水平，结果表明，衰老与这些调节因子的表达减少有关，对另外三个神经元（L7、L11和R2）的类似分析表明，衰老过程中基因表达的变化可能是双向的。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经确定了R15中受衰老影响的特定生物过程和与人类相关的信号通路。对不同神经元基因表达变化的评估表明单个神经元在衰老过程中具有特定的转录组特征。
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. 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. 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.
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影响因子：
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作者：
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通讯作者：
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影响因子：
2.9
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