Neuromedins U and S involvement in the regulation of the hypothalamo–pituitary–adrenal axis

Malendowicz, Ludwik K.; Ziółkowska, Agnieszka; Ruciński, Marcin

doi:10.3389/fendo.2012.00156

Cited by 23 publications

(17 citation statements)

References 105 publications

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“…The second, centrally expressed NMU receptor, NMUR2, is necessary for the effect of NMU on food intake and physical activity (Zeng et al, 2006; Peier et al, 2009). In this context, NMU is well established as a factor in regulation of the hypothalamo-pituitary axis (Wren et al, 2002; Malendowicz et al, 2012) and has a range of effects in the hypothalamus, the most important being the release of corticotropin-releasing hormone (CRH) (Hanada et al, 2001, 2003). We show that a subset of hugin-producing neurons targets the pars intercerebralis, the Drosophila homolog of the hypothalamus, in a similar fashion: neuroendocrine target cells in the pars intercerebralis produce a range of peptides, including diuretic hormone 44 which belongs to the insect CRH-like peptide family (Cabrero et al, 2002) (Figure 10).…”

Section: Discussionmentioning

confidence: 99%

“…In parallel to the synaptic connectivity, mNSCs also express the G-protein-coupled receptor PK2-R1, a hugin receptor, rendering them likely targets of both fast synaptic transmission and neuromodulatory effects from hugin neurons. These mNSCs produce diuretic hormone 44 (DH44, a CRH-like peptide) and Drosophila insulin-like peptides, both of which have mammalian homologs that are likewise downstream of NMU (Wren et al, 2002; Malendowicz et al, 2012). Endocrine function is essential to ensure homeostasis of the organism and coordinate fundamental behaviors, such as feeding, mating and reproduction, and acts as integrator of external and internal sensory cues (Swanson, 2000).…”

Section: Introductionmentioning

confidence: 99%

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Synaptic transmission parallels neuromodulation in a central food-intake circuit

Schlegel

Texada

Miroschnikow

et al. 2016

eLife

136

158

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NeuromedinU is a potent regulator of food intake and activity in mammals. In Drosophila, neurons producing the homologous neuropeptide hugin regulate feeding and locomotion in a similar manner. Here, we use EM-based reconstruction to generate the entire connectome of hugin-producing neurons in the Drosophila larval CNS. We demonstrate that hugin neurons use synaptic transmission in addition to peptidergic neuromodulation and identify acetylcholine as a key transmitter. Hugin neuropeptide and acetylcholine are both necessary for the regulatory effect on feeding. We further show that subtypes of hugin neurons connect chemosensory to endocrine system by combinations of synaptic and peptide-receptor connections. Targets include endocrine neurons producing DH44, a CRH-like peptide, and insulin-like peptides. Homologs of these peptides are likewise downstream of neuromedinU, revealing striking parallels in flies and mammals. We propose that hugin neurons are part of an ancient physiological control system that has been conserved at functional and molecular level.DOI: http://dx.doi.org/10.7554/eLife.16799.001

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Synaptic transmission parallels neuromodulation in a central food-intake circuit

Schlegel

Texada

Miroschnikow

et al. 2016

eLife

136

158

View full text Add to dashboard Cite

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“…In mammals, the anorexigenic actions of NMU and NMS are mediated by the activation of CRH neurons (reviewed by Malendowicz et al (2012)). Administration of NMU could not suppress food intake or increase oxygen consumption and body temperature in CRH-knockout mice (Hanada et al 2003).…”

Section: Discussionmentioning

confidence: 99%

Distinct functions of neuromedin u and neuromedin s in orange-spotted grouper

Xiao

Liu

et al. 2015

Journal of Molecular Endocrinology

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Neuromedin U (NMU) and neuromedin S (NMS) play inhibitory roles in the regulation of food intake and energy homeostasis in mammals. However, their functions are not clearly established in teleost fish. In the present study, nmu and nms homologs were identified in several fish species. Subsequently, their cDNA sequences were cloned from the orange-spotted grouper (Epinephelus coioides). Sequence analysis showed that the orangespotted grouper Nmu proprotein contains a 21-amino acid mature Nmu peptide (Nmu-21). The Nms proprotein lost the typical mature Nms peptide, but it retains a putative 34-amino acid peptide (Nmsrp). In situ hybridization revealed that nmu-and nms-expressing cells are mainly localized in the hypothalamic regions associated with appetite regulation. Food deprivation decreased the hypothalamic nmu mRNA levels but induced an increase of nms mRNA levels. Periprandial expression analysis showed that hypothalamic expression of nmu increased significantly at 3 h post-feeding, while nms expression was elevated at the normal feeding time. I.p. injection of synthetic Nmu-21 peptide suppressed the hypothalamic neuropeptide y (npy) expression, while Nmsrp administration significantly increased the expression of npy and orexin in orange-spotted grouper. Furthermore, the mRNA levels of LH beta subunit (lhb) and gh in the pituitary were significantly down-regulated after Nmu-21 peptide administration, while Nmsrp was able to significantly stimulate the expression of FSH beta subunit (fshb), prolactin (prl), and somatolaction (sl). Our results indicate that nmu and nms possess distinct neuroendocrine functions and pituitary functions in the orange spotted grouper.

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“…The C-terminal heptapeptide and critical residues are indicated by the shaded box and asterisks. Amino acids are color coded by type (after Malendowicz et al, 2012): blue=basic, red=acidic, green=non-polar, light green=polar. (B–F) Endogenous expression of nmu in the hypothalamus (single arrow), brainstem (double arrow), and spinal cord (arrowhead) of 24–120 hpf zebrafish.…”

Section: Figurementioning

confidence: 99%

A Zebrafish Genetic Screen Identifies Neuromedin U as a Regulator of Sleep/Wake States

Chiu

Rihel

Lee

et al. 2016

Neuron

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Summary Neuromodulation of arousal states ensures that an animal appropriately responds to its environment and engages in behaviors necessary for survival. However, the molecular and circuit properties underlying neuromodulation of arousal states such as sleep and wakefulness remain unclear. To tackle this challenge in a systematic and unbiased manner, we performed a genetic overexpression screen to identify genes that affect larval zebrafish arousal. We found that the neuropeptide neuromedin U (Nmu) promotes hyperactivity and inhibits sleep in zebrafish larvae, whereas nmu mutant animals are hypoactive. We show that Nmu-induced arousal requires Nmu receptor 2 and signaling via corticotrophin-releasing hormone (Crh) receptor 1. In contrast to previously proposed models, we find that Nmu does not promote arousal via the hypothalamic-pituitary-adrenal axis, but rather likely acts via brainstem crh-expressing neurons. These results reveal an unexpected functional and anatomical interface between the Nmu system and brainstem arousal systems that represents a novel wake-promoting pathway.

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Neuromedins U and S involvement in the regulation of the hypothalamo–pituitary–adrenal axis

Cited by 23 publications

References 105 publications

Synaptic transmission parallels neuromodulation in a central food-intake circuit

Synaptic transmission parallels neuromodulation in a central food-intake circuit

Distinct functions of neuromedin u and neuromedin s in orange-spotted grouper

A Zebrafish Genetic Screen Identifies Neuromedin U as a Regulator of Sleep/Wake States

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