An opioid-like system regulating feeding behavior in C. elegans

Cheong, Mi Cheong; Artyukhin, Alexander B.; You, Young-Jai; Avery, Leon

doi:10.7554/elife.06683

Cited by 45 publications

(59 citation statements)

References 76 publications

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“…Additional similarities include neuroendocrine pathways such as insulin and steroid hormone signaling as well as neuromodulators, for example, serotonin and dopamine, and feeding regulatory neuropeptides such as oxytocin and opioid-like peptides [4,5,9]. As in mammals, the nervous system of C. elegans integrates both external and internal cues to modulate behavior but also peripheral physiology via hormone secretion [5,10,11].…”

Section: Overview Of C Elegans Energy Balance Pathwaysmentioning

confidence: 99%

“…If C. elegans have been cultivated on one species of bacteria, then transferred to another their pharyngeal pumping rate is depressed which appears to involve a type of conditioning of sensory neurons to the odors and taste of different foods [54]. A large array of neuropeptide and biogenic amine neuromodulators regulate pharyngeal pumping in the presence and absence of food [5,9,53]. …”

Section: Intersection Of Metabolic and Food Sensory Pathways With Feementioning

confidence: 99%

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Investigating Connections between Metabolism, Longevity, and Behavior in Caenorhabditis elegans

Lemieux

Ashrafi

2016

Trends in Endocrinology & Metabolism

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An overview of C. elegans as an experimental organism for studying energy balance is presented. Some of the unresolved questions that complicate the interpretation of lipid measurements from C. elegans are highlighted. We review studies that show both lipid synthesis and breakdown pathways are activated and needed for the longevity of hermaphrodites that lack their germ lines. These findings illustrate the heterogeneity of triglyceride rich lipid particles in C. elegans and reveal specific lipid signals that promote longevity. Finally, we provide a brief overview of feeding behavioral responses of C. elegans to varying nutritional conditions and highlight an unanticipated metabolic pathway that allows for the incorporation of experience in feeding behavior.

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Section: Overview Of C Elegans Energy Balance Pathwaysmentioning

confidence: 99%

Section: Intersection Of Metabolic and Food Sensory Pathways With Feementioning

confidence: 99%

Investigating Connections between Metabolism, Longevity, and Behavior in Caenorhabditis elegans

Lemieux

Ashrafi

2016

Trends in Endocrinology & Metabolism

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“…For the most part, it has been possible to achieve consistent results between the two approaches, generating strong confidence in the results, although there have been occasional puzzling exceptions (Cheong et al, 2015: PMID 25898004). Overall, the data matching neuropeptides to their cognate receptors remains sparse and we have a long way to go to fully match up these signaling molecules.…”

Section: Neurotransmitters and Receptors That Signal Through Hetermentioning

confidence: 92%

“…However, based on sequence similarity as well as additional functional data, some worm receptors have been described as models for specific mammalian receptors. Thus C. elegans NPR-1 is similar to the mammalian neuropeptide Y receptor (de Bono and Bargmann, 1998: PMID 9741632), C. elegans PDFR-1 is similar to the Drosophila pigment dispersing factor receptor and mammalian vasoactive peptide and calcitonin receptors (Janssen et al, 2008: PMID 18390545), and C. elegans NPR-17 is similar to mammalian opioid receptors (Cheong et al, 2015: PMID 25898004).…”

Section: Neurotransmitters and Receptors That Signal Through Hetermentioning

confidence: 99%

Neurotransmitter signaling through heterotrimeric G proteins: insights from studies in C. elegans

Koelle

2018

WormBook

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Neurotransmitters signal via G protein coupled receptors (GPCRs) to modulate activity of neurons and muscles. C. elegans has ~150 G protein coupled neuropeptide receptor homologs and 28 additional GPCRs for small-molecule neurotransmitters. Genetic studies in C. elegans demonstrate that neurotransmitters diffuse far from their release sites to activate GPCRs on distant cells. Individual receptor types are expressed on limited numbers of cells and thus can provide very specific regulation of an individual neural circuit and behavior. G protein coupled neurotransmitter receptors signal principally via the three types of heterotrimeric G proteins defined by the G alpha subunits Gαo, Gαq, and Gαs. Each of these G alpha proteins is found in all neurons plus some muscles. Gαo and Gαq signaling inhibit and activate neurotransmitter release, respectively. Gαs signaling, like Gαq signaling, promotes neurotransmitter release. Many details of the signaling mechanisms downstream of Gαq and Gαs have been delineated and are consistent with those of their mammalian orthologs. The details of the signaling mechanism downstream of Gαo remain a mystery. Forward genetic screens in C. elegans have identified new molecular components of neural G protein signaling mechanisms, including Regulators of G protein Signaling (RGS proteins) that inhibit signaling, a new Gαq effector (the Trio RhoGEF domain), and the RIC-8 protein that is required for neuronal Gα signaling. A model is presented in which G proteins sum up the variety of neuromodulator signals that impinge on a neuron to calculate its appropriate output level.

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“…88 Such differences in molecular systems and pharmacology between C. elegans and vertebrates could be viewed as a limitation of the model and indeed could limit its application for certain drug classes. However, as previously discussed, C. elegans do respond to many of the common drugs of abuse (e.g., EtOH and the psychomotor stimulants) and the recent discovery of a class of opioid receptors in C. elegans 89 may provide a new avenue for drug-abuse modeling and treatment screening in C. elegans .…”

Section: Leveraging C Elegans For Model Development and Drug Discmentioning

confidence: 92%

Caenorhabditis elegans as a Model to Study the Molecular and Genetic Mechanisms of Drug Addiction

Engleman

Katner

Neal-Beliveau

2016

Progress in Molecular Biology and Translational Science

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Drug addiction takes a massive toll on society. Novel animal models are needed to test new treatments and understand the basic mechanisms underlying addiction. Rodent models have identified the neurocircuitry involved in addictive behavior and indicate that rodents possess some of the same neurobiologic mechanisms that mediate addiction in humans. Recent studies indicate that addiction is mechanistically and phylogenetically ancient and many mechanisms that underlie human addiction are also present in invertebrates. The nematode Caenorhabditis elegans has conserved neurobiologic systems with powerful molecular and genetic tools and a rapid rate of development that enables cost-effective translational discovery. Emerging evidence suggests that C. elegans is an excellent model to identify molecular mechanisms that mediate drug-induced behavior and potential targets for medications development for various addictive compounds. C. elegans emit many behaviors that can be easily quantitated including some that involve interactions with the environment. Ethanol (EtOH) is the best-studied drug-of-abuse in C. elegans and at least 50 different genes/targets have been identified as mediating EtOH’s effects and polymorphisms in some orthologs in humans are associated with alcohol use disorders. C. elegans has also been shown to display dopamine and cholinergic system–dependent attraction to nicotine and demonstrate preference for cues previously associated with nicotine. Cocaine and methamphetamine have been found to produce dopamine-dependent reward-like behaviors in C. elegans. These behavioral tests in combination with genetic/molecular manipulations have led to the identification of dozens of target genes/systems in C. elegans that mediate drug effects. The one target/gene identified as essential for drug-induced behavioral responses across all drugs of abuse was the cat-2 gene coding for tyrosine hydroxylase, which is consistent with the role of dopamine neurotransmission in human addiction. Overall, C. elegans can be used to model aspects of drug addiction and identify systems and molecular mechanisms that mediate drug effects. The findings are surprisingly consistent with analogous findings in higher-level organisms. Further, model refinement is warranted to improve model validity and increase utility for medications development.

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An opioid-like system regulating feeding behavior in C. elegans

Cited by 45 publications

References 76 publications

Investigating Connections between Metabolism, Longevity, and Behavior in Caenorhabditis elegans

Investigating Connections between Metabolism, Longevity, and Behavior in Caenorhabditis elegans

Neurotransmitter signaling through heterotrimeric G proteins: insights from studies in C. elegans

Caenorhabditis elegans as a Model to Study the Molecular and Genetic Mechanisms of Drug Addiction

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