Regulation of Ethanol-Related Behavior and Ethanol Metabolism by the Corazonin Neurons and Corazonin Receptor in Drosophila melanogaster

Sha, Kai; Choi, Su-Mi; Im, Jeongdae; Lee, Gyunghee; Loeffler, F. E.; Park, Jae H.

doi:10.1371/journal.pone.0087062

Cited by 39 publications

(39 citation statements)

References 58 publications

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“…It is known that the CrzR in Drosophila is expressed also in neurons of the CNS [35,39], salivary glands and the dorsal vessel, also known as heart (see FlyAtlas) [36]. Nevertheless, we found that CrzR -Gal4>UAS- CrzR -RNAi resulted in a similar increased resistance to paraquat-induced oxidative stress and a decrease in food intake (figure 8) as seen after targeting CrzR -RNAi to the periphery.…”

Section: Resultssupporting

confidence: 59%

“…We used different fat body Gal4 drivers to knockdown the CrzR and tested the flies in a set of assays for effects on metabolism, stress tolerance, gene expression and neuropeptide levels. We found that these drivers also target expression to the salivary glands, a tissue known to express the CrzR [35,36]. Our findings suggest that systemic Crz signalling predominantly to the fat body and salivary glands regulates starvation, desiccation and oxidative stress resistance, as well as food ingestion.…”

Section: Introductionmentioning

confidence: 83%

“…The following Drosophila melanogaster Gal4 lines were used: ppl- Gal4 [40] from M. Pankratz (Bonn, Germany); to-Gal4 [41] provided by B. Dauwalder (Houston, TX, USA); Crz-Gal4 [94], CrzR-Gal4 T11a and CrzR-Gal4 Se [35] were gifts from J.H. Park (Knoxville, TN, USA).…”

Section: Methodsmentioning

confidence: 99%

“…As the DLPs are neurosecretory cells with axon terminations in the corpora cardiaca, anterior aorta and intestine [32–34], it is likely that Crz primarily functions as circulating hormone acting on peripheral tissues. This is supported by detecting expression of the CrzR in the fat body, salivary glands and heart of adult Drosophila [35,36] (see also FlyAtlas, ). Thus, we set out to investigate the role of systemic Crz signalling under normal conditions and during stress in flies.…”

Section: Introductionmentioning

confidence: 98%

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Systemic corazonin signalling modulates stress responses and metabolism inDrosophila

Kubrak¹,

Lushchak²,

Zandawala³

et al. 2016

Open Biol.

127

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Stress triggers cellular and systemic reactions in organisms to restore homeostasis. For instance, metabolic stress, experienced during starvation, elicits a hormonal response that reallocates resources to enable food search and readjustment of physiology. Mammalian gonadotropin-releasing hormone (GnRH) and its insect orthologue, adipokinetic hormone (AKH), are known for their roles in modulating stress-related behaviour. Here we show that corazonin (Crz), a peptide homologous to AKH/GnRH, also alters stress physiology in Drosophila. The Crz receptor (CrzR) is expressed in salivary glands and adipocytes of the liver-like fat body, and CrzR knockdown targeted simultaneously to both these tissues increases the fly's resistance to starvation, desiccation and oxidative stress, reduces feeding, alters expression of transcripts of Drosophila insulin-like peptides (DILPs), and affects gene expression in the fat body. Furthermore, in starved flies, CrzR-knockdown increases circulating and stored carbohydrates. Thus, our findings indicate that elevated systemic Crz signalling during stress coordinates increased food intake and diminished energy stores to regain metabolic homeostasis. Our study suggests that an ancient stress-peptide in Urbilateria evolved to give rise to present-day GnRH, AKH and Crz signalling systems.

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Section: Resultssupporting

confidence: 59%

Section: Introductionmentioning

confidence: 83%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

See 2 more Smart Citations

Systemic corazonin signalling modulates stress responses and metabolism inDrosophila

Kubrak¹,

Lushchak²,

Zandawala³

et al. 2016

Open Biol.

127

View full text Add to dashboard Cite

show abstract

“…The central complex also has been implicated in the development of functional tolerance to ethanol (Rodan et al, 2002; Scholz, 2009; Rodan and Rothenfluh, 2010) with a subset of neurons within the ellipsoid body mediating the effects of alcohol in sedation and the development of rapid tolerance to alcohol (Nässel, 2002; Urizar et al, 2007). Alcohol-induced sedation also involves the neuroendocrine system through neurons in the pars intercerebralis and the pars lateralis (McClure and Heberlein, 2013; Sha et al, 2014), neurosecretory clusters analogous to the mammalian hypothalamus (de Velasco et al, 2007). Peripheral axons of these neurosecretory cells project to a neuroendocrine gland complex, the ring gland, comparable to the hypothalamic-pituitary axis in mammals (reviewed in (Nässel, 2002).…”

Section: Discussionmentioning

confidence: 99%

Circadian Modulation of Alcohol-Induced Sedation and Recovery in Male and Female Drosophila

Nobrega

Lyons

2016

J Biol Rhythms

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Delineating the factors that affect behavioral and neurological responses to alcohol is critical to facilitate measures for preventing or treating alcohol abuse. The high degree of conserved molecular and physiological processes make Drosophila melanogaster a valuable model for investigating circadian interactions with alcohol-induced behaviors and examining sex-specific differences in alcohol sensitivity. We found that wild-type Drosophila exhibit rhythms in alcohol-induced sedation under light-dark and constant dark conditions with considerably greater alcohol exposure necessary to induce sedation during the late (subjective) day and peak sensitivity to alcohol occurring during the late (subjective) night. The circadian clock also modulated the recovery from alcohol-induced sedation with flies regaining motor control significantly faster during the late (subjective) day. As predicted, the circadian rhythms in sedation and recovery were absent in flies with a mutation in the circadian gene period or arrhythmic flies housed in constant light conditions. Flies lacking a functional circadian clock were more sensitive to the effects of alcohol with significantly longer recovery times. Similar to other animals and humans, Drosophila exhibit sex-specific differences in alcohol sensitivity. We investigated whether the circadian clock modulated the rhythms in the Loss-of-Righting Reflex, alcohol-induced sedation, and recovery differently in males and females. We found that both sexes demonstrate circadian rhythms in the Loss-of-Righting Reflex and sedation with the differences in alcohol sensitivity between males and females most pronounced during the late subjective day. Recovery of motor reflexes following alcohol sedation also exhibited circadian modulation in male and female flies, although the circadian clock did not modulate the difference in recovery times between the sexes. These studies provide a framework outlining how the circadian clock modulates alcohol-induced behaviors in Drosophila and identifies sexual dimorphisms in the circadian modulation of alcohol behaviors.

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Functions of corazonin and histamine in light entrainment of the circadian pacemaker in the Madeira cockroach, Rhyparobia maderae

Arendt

Baz

Stengl

2016

J of Comparative Neurology

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The circadian pacemaker of the Madeira cockroach, Rhyparobia (Leucophaea) maderae, is located in the accessory medulla (AME). Ipsi- and contralateral histaminergic compound eyes are required for photic entrainment. Light pulses delay locomotor activity rhythm during the early night and advance it during the late night. Thus, different neuronal pathways might relay either light-dependent delays or advances to the clock. Injections of neuroactive substances combined with running-wheel assays suggested that GABA, pigment-dispersing factor, myoinhibitory peptides (MIPs), and orcokinins (ORCs) were part of both entrainment pathways, whereas allatotropin (AT) only delayed locomotor rhythms at the early night. To characterize photic entrainment further, histamine and corazonin were injected. Histamine injections resulted in light-like phase delays and advances, indicating that the neurotransmitter of the compound eyes participates in both entrainment pathways. Because injections of corazonin only advanced during the late subjective night, it was hypothesized that corazonin is only part of the advance pathway. Multiple-label immunocytochemistry in combination with neurobiotin backfills demonstrated that a single cell expressed corazonin in the optic lobes that belonged to the group of medial AME interneurons. It colocalized GABA and MIP but not AT or ORC immunoreactivity. Corazonin-immunoreactive (-ir) terminals overlapped with projections of putatively light-sensitive interneurons from the ipsi- and contralateral compound eye. Thus, we hypothesize that the corazonin-ir medial neuron integrates ipsi- and contralateral light information as part of the phase-advancing light entrainment pathway to the circadian clock. J. Comp. Neurol. 525:1250-1272, 2017. © 2016 Wiley Periodicals, Inc.

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Regulation of Ethanol-Related Behavior and Ethanol Metabolism by the Corazonin Neurons and Corazonin Receptor in Drosophila melanogaster

Cited by 39 publications

References 58 publications

Systemic corazonin signalling modulates stress responses and metabolism inDrosophila

Systemic corazonin signalling modulates stress responses and metabolism inDrosophila

Circadian Modulation of Alcohol-Induced Sedation and Recovery in Male and Female Drosophila

Functions of corazonin and histamine in light entrainment of the circadian pacemaker in the Madeira cockroach, Rhyparobia maderae

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