Journal article
Global Transcriptome Changes That Accompany Alterations in Serotonin Levels in Caenorhabditis elegans
G3 (Bethesda, Md.), Vol.10(4), pp.1225-1246
04/09/2020
DOI: 10.1534/g3.120.401088
PMCID: PMC7144078
PMID: 31996358
Abstract
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.
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
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, eIF2α. In 5-HT deficient animals lacking tryptophan hydroxylase (
) 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
changes in gene expression upon altering 5-HT levels, and changes in physiology, are not directly correlated.
Details
- Title: Subtitle
- Global Transcriptome Changes That Accompany Alterations in Serotonin Levels in Caenorhabditis elegans
- Creators
- Johnny Cruz-Corchado - Department of Biology, Aging Mind and Brain Initiative, Iowa Neuroscience Institute, 143 Biology Building, Iowa City, IA 52242-1324Felicia K Ooi - Department of Biology, Aging Mind and Brain Initiative, Iowa Neuroscience Institute, 143 Biology Building, Iowa City, IA 52242-1324Srijit Das - Department of Biology, Aging Mind and Brain Initiative, Iowa Neuroscience Institute, 143 Biology Building, Iowa City, IA 52242-1324Veena Prahlad - Department of Biology, Aging Mind and Brain Initiative, Iowa Neuroscience Institute, 143 Biology Building, Iowa City, IA 52242-1324 veena-prahlad@uiowa.edu
- Resource Type
- Journal article
- Publication Details
- G3 (Bethesda, Md.), Vol.10(4), pp.1225-1246
- DOI
- 10.1534/g3.120.401088
- PMID
- 31996358
- PMCID
- PMC7144078
- NLM abbreviation
- G3 (Bethesda)
- ISSN
- 2160-1836
- eISSN
- 2160-1836
- Publisher
- United States
- Grant note
- R01 AG050653 / NIA NIH HHS
- Language
- English
- Date published
- 04/09/2020
- Academic Unit
- Microbiology and Immunology; Iowa Neuroscience Institute; Biology
- Record Identifier
- 9984070545202771
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