Global Transcriptome Changes That Accompany Alterations in Serotonin Levels in Caenorhabditis elegans
Global Transcriptome Changes That Accompany Alterations in Serotonin Levels in Caenorhabditis elegans
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DOI：
10.1534/g3.120.401088
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发表时间：
2020-04-01
影响因子：
2.6
通讯作者：
Prahlad, Veena
中科院分区：
文献类型：
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作者：
Cruz-Corchado, Johnny;Ooi, Felicia K.;Prahlad, Veena
5-羟色胺（5-hydroxytryptamine，5-HT），是一种神经递质，调节情绪和社会认知的多个方面。5-HT在正常和异常行为中所起的作用尚未完全了解，但已被认为是由于其作为“防御信号”的共同功能。然而，5-HT水平也系统地影响细胞生理学，调节细胞分裂、迁移、凋亡、线粒体生物发生、细胞代谢和分化。5-HT的这些不同的细胞效应是否也有共同的基础尚不清楚。C.由于缺乏血脑屏障，由神经元合成和释放的5-HT渗透生物体以调节整个身体的神经元和非神经元细胞，因此elegans提供了一种理想的系统来研究5-HT的全身作用。在这里，我们使用RNA-Seq来表征在C. elegans在改变5-HT水平时，并将转录组与已发表的数据集进行比较。我们发现，5-HT的急性增加伴随着基因表达水平的整体下降，参与应激途径的基因的上调，与已发表的具有激活的防御和免疫反应的动物的转录组显著相关的变化，以及磷酸化真核起始因子eIF 2 α水平的增加。在缺乏色氨酸羟化酶（（）II）的5-HT缺陷动物中，基因表达净增加，与发育和染色质相关的基因过度表达。令人惊讶的是，5-HT水平急性增加和5-HT缺乏的动物的转录组与它们具有惊人生理相似性的突变体的转录组不重叠。这些研究是第一个对5-HT水平改变后发生的系统性转录组变化进行编目的研究。他们进一步表明，在C。线虫在改变5-HT水平时基因表达的变化与生理学变化没有直接相关性。
Serotonin (5-hydroxytryptamine, 5-HT), is a phylogenetically ancient molecule best characterized as a neurotransmitter that modulates multiple aspects of mood and social cognition. The roles that 5-HT plays in normal and abnormal behavior are not fully understood but have been posited to be due to its common function as a 'defense signal'. However, 5-HT levels also systemically impact cell physiology, modulating cell division, migration, apoptosis, mitochondrial biogenesis, cellular metabolism and differentiation. Whether these diverse cellular effects of 5-HT also share a common basis is unclear. C. elegans provides an ideal system to interrogate the systemic effects of 5-HT, since lacking a blood-brain barrier, 5-HT synthesized and released by neurons permeates the organism to modulate neuronal as well as non-neuronal cells throughout the body. Here we used RNA-Seq to characterize the systemic changes in gene expression that occur in C. elegans upon altering 5-HT levels, and compared the transcriptomes to published datasets. We find that an acute increase in 5-HT is accompanied by a global decrease in gene expression levels, upregulation of genes involved in stress pathways, changes that significantly correlate with the published transcriptomes of animals that have activated defense and immune responses, and an increase in levels of phosphorylated eukaryotic initiation factor, eIF2 alpha. In 5-HT deficient animals lacking tryptophan hydroxylase ( () II) there is a net increase in gene expression, with an overrepresentation of genes related to development and chromatin. Surprisingly, the transcriptomes of animals with acute increases in 5-HT levels, and 5-HT deficiency do not overlap with transcriptomes of mutants with whom they share striking physiological resemblance. These studies are the first to catalog systemic transcriptome changes that occur upon alterations in 5-HT levels. They further show that in C. elegans changes in gene expression upon altering 5-HT levels, and changes in physiology, are not directly correlated.