scholarly journals Ghrelin signaling regulates feeding behavior, metabolism, and memory through the vagus nerve

2020 ◽  
Author(s):  
Elizabeth A. Davis ◽  
Hallie S. Wald ◽  
Andrea N. Suarez ◽  
Jasenka Zubcevic ◽  
Clarissa M. Liu ◽  
...  
Keyword(s):  
Feeding Behavior ◽  
Neural Control ◽  
Critical Role ◽  
Afferent Neuron ◽  
Metabolic Disturbances ◽  
Growth Hormone Secretagogue Receptor ◽  
Growth Hormone Secretagogue ◽  
Nodose Ganglia ◽  
Normal Feeding ◽  
Short Hairpin Rnas

ABSTRACTVagal afferent neuron (VAN) signaling sends information from the gut to the brain and is fundamental in the neural control of feeding behavior and metabolism. Recent findings reveal that VAN signaling also plays a critical role in cognitive processes, including hippocampus (HPC)-dependent memory. VANs, located in nodose ganglia, express receptors for various gut-derived endocrine signals, however, the function of these receptors with regards to feeding behavior, metabolism, and memory control is poorly understood. We hypothesized that VAN-mediated processes are influenced by ghrelin, a stomach-derived orexigenic hormone, via communication to its receptor (growth hormone secretagogue receptor [GHSR]) expressed on gut-innervating VANs. To examine this hypothesis, rats received nodose ganglia injections of an adeno-associated virus (AAV) expressing short hairpin RNAs targeting GHSR (or a control AAV) for RNA interference-mediated VAN-specific GHSR knockdown. Results reveal that VAN GHSR knockdown induced various feeding and metabolic disturbances, including increased meal frequency, impaired glucose tolerance, delayed gastric emptying, and increased body weight compared to controls. Additionally, VAN-specific GHSR knockdown impaired HPC-dependent episodic contextual memory and reduced HPC brain-derived neurotrophic factor expression, but did not affect anxiety-like behavior or levels of general activity. A functional role for endogenous VAN GHSR signaling was further confirmed by results revealing that VAN signaling is required for the hyperphagic effects of ghrelin administered at dark onset, and that gut-restricted ghrelin-induced increases in VAN firing rate require intact VAN GHSR expression. Collective results reveal that VAN GHSR signaling is required for both normal feeding and metabolic function as well as HPC-dependent memory.

scholarly journals Selectively increasing GHS-R1a expression in dCA1 excitatory/inhibitory neurons have opposite effects on memory encoding

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Nan Li ◽  
Na Li ◽  
Fenghua Xu ◽  
Ming Yu ◽  
Zichen Qiao ◽  
...  
Keyword(s):  
Pyramidal Neurons ◽  
Memory Performance ◽  
Critical Role ◽  
Inhibitory Neurons ◽  
Long Term Memory ◽  
Growth Hormone Secretagogue Receptor ◽  
Growth Hormone Secretagogue ◽  
Term Memory ◽  
Selective Increase

Abstract Aim Growth hormone secretagogue receptor 1a (GHS-R1a) is widely distributed in brain including the hippocampus. Studies have demonstrated the critical role of hippocampal ghrelin/GHS-R1a signaling in synaptic physiology, memory and cognitive dysfunction associated with Alzheimer’s disease (AD). However, current reports are inconsistent, and the mechanism underlying memory modulation of GHS-R1a signaling is uncertain. In this study, we aim to investigate the direct impact of selective increase of GHS-R1a expression in dCA1 excitatory/inhibitory neurons on learning and memory. Methods Endogenous GHS-R1a distribution in dCA1 excitatory/inhibitory neurons was assessed by fluorescence in situ hybridization. Cre-dependent GHS-R1a overexpression in excitatory or inhibitory neurons was done by stereotaxic injection of aav-hSyn-DIO-hGhsr1a-2A-eGFP virus in dCA1 region of vGlut1-Cre or Dlx5/6-Cre mice respectively. Virus-mediated GHS-R1a upregulation in dCA1 neurons was confirmed by quantitative RT-PCR. Different behavioral paradigms were used to evaluate long-term memory performance. Results GHS-R1a is distributed both in dCA1 excitatory pyramidal neurons (αCaMKII+) and in inhibitory interneurons (GAD67+). Selective increase of GHS-R1a expression in dCA1 pyramidal neurons impaired spatial memory and object-place recognition memory. In contrast, selective increase of GHS-R1a expression in dCA1 interneurons enhanced long-term memory performance. Our findings reveal, for the first time, a neuronal type-specific role that hippocampal GHS-R1a signaling plays in regulating memory. Therefore, manipulating GHS-R1a expression/activity in different subpopulation of neurons may help to clarify current contradictory findings and to elucidate mechanism of memory control by ghrelin/GHS-R1a signaling, under both physiological and pathological conditions such as AD.

scholarly journals Ghrelin receptors in rat and human nodose ganglia: putative role in regulating CB-1 and MCH receptor abundance

2006 ◽  
Vol 290 (6) ◽  
pp. G1289-G1297 ◽  
Author(s):  
Galina Burdyga ◽  
Andrea Varro ◽  
Rod Dimaline ◽  
David G. Thompson ◽  
Graham J. Dockray
Keyword(s):  
Receptor Expression ◽  
Afferent Neurons ◽  
Growth Hormone Secretagogue Receptor ◽  
Growth Hormone Secretagogue ◽  
Ghrelin Receptor ◽  
Nodose Ganglia ◽  
Melanin Concentrating Hormone ◽  
Ghrelin Receptors ◽  
Vagal Afferent ◽  
Immunohistochemical Studies

Intact vagal afferent neurons are required for the satiety effects of the intestinal hormone cholecystokinin (CCK) and the orexigenic effects of the gastric regulatory peptide ghrelin. In this study, we examined the localization of ghrelin receptors in nodose ganglia and their function in regulating the expression of other orexigenic receptors, notably cannabinoid (CB)-1 and melanin-concentrating hormone (MCH)-1 receptors. With the use of RT-PCR, transcripts corresponding to both functional [growth hormone secretagogue receptor (GHS-R)1a] and truncated forms (GHS-R1b) of the ghrelin receptor were detected in rat nodose ganglia. There was no difference in expression between rats fed ad libitum or fasted for up to 48 h. Immunohistochemical studies using antibodies directed at GHS-R1a revealed expression in over 75% of neurons also expressing CCK-1 receptors in the mid- and caudal regions of the ganglion. There was also expression in human nodose ganglia. In fasted rats in which CB-1 and MCH-1 receptor expression was increased, administration of ghrelin prevented the downregulation by refeeding. We conclude that the actions of CCK and ghrelin are mediated by a common population of vagal afferent neurons. Ghrelin may act to limit the action of CCK in depressing expression of CB-1 and MCH-1 receptors and other receptors.

scholarly journals Structure and dynamics of G protein-coupled receptor–bound ghrelin reveal the critical role of the octanoyl chain

2019 ◽  
Vol 116 (35) ◽  
pp. 17525-17530 ◽  
Author(s):  
Guillaume Ferré ◽  
Maxime Louet ◽  
Oliver Saurel ◽  
Bartholomé Delort ◽  
Georges Czaplicki ◽  
...  
Keyword(s):  
G Protein ◽  
Critical Role ◽  
Conformational Space ◽  
Coarse Grained ◽  
Hydrophobic Core ◽  
G Protein Coupled Receptor ◽  
Growth Hormone Secretagogue Receptor ◽  
Growth Hormone Secretagogue ◽  
Structure And Dynamics ◽  
G Protein Coupled

Ghrelin plays a central role in controlling major biological processes. As for other G protein-coupled receptor (GPCR) peptide agonists, the structure and dynamics of ghrelin bound to its receptor remain obscure. Using a combination of solution-state NMR and molecular modeling, we demonstrate that binding to the growth hormone secretagogue receptor is accompanied by a conformational change in ghrelin that structures its central region, involving the formation of a well-defined hydrophobic core. By comparing its acylated and nonacylated forms, we conclude that the ghrelin octanoyl chain is essential to form the hydrophobic core and promote access of ghrelin to the receptor ligand-binding pocket. The combination of coarse-grained molecular dynamics studies and NMR should prove useful in improving our mechanistic understanding of the complex conformational space explored by a natural peptide agonist when binding to its GPCR. Such information should also facilitate the design of new ghrelin receptor-selective drugs.

scholarly journals Functional interaction between Ghrelin and GLP-1 regulates feeding through the vagal afferent system

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Weidong Zhang ◽  
T. M. Zaved Waise ◽  
Koji Toshinai ◽  
Wakaba Tsuchimochi ◽  
Farhana Naznin ◽  
...  
Keyword(s):  
Vagal Afferents ◽  
Growth Hormone Secretagogue Receptor ◽  
Growth Hormone Secretagogue ◽  
Electrophysiological Properties ◽  
Feeding Regulation ◽  
Nodose Ganglia ◽  
Patch Clamp Experiment ◽  
Fine Control ◽  
Vagal Afferent ◽  
Glucagon Like Peptide 1

Abstract The gastrointestinal tract transmits feeding-regulatory signals to the brain via neuronal and hormonal pathways. Here we studied the interaction between the orexigenic gastric peptide, ghrelin, and the anorectic intestinal peptide, glucagon-like peptide 1 (GLP-1), in terms of feeding regulation via the vagal afferents. GLP-1 preadministration 30 min before ghrelin administration to rats and mice abolished ghrelin-induced food intake, while ghrelin preadministration abolished the anorectic effect of GLP-1. Ghrelin preadministration suppressed GLP-1-induced Fos expression in the nodose ganglia (NG). Electrophysiological assessment confirmed that the initially administered peptide abolished the vagal afferent electrical alteration induced by the subsequently administered peptide. Both the growth hormone secretagogue receptor (GHSR) and the GLP-1 receptor (GLP-1R) are co-localised in a major proportion of NG neurons that innervate the stomach. In these Ghsr+Glp1r+ neurons, ghrelin preadministration abolished the GLP-1-induced calcium response. Ghrelin generated a hyperpolarising current and GLP-1 generated a depolarising current in isolated NG neurons in a patch-clamp experiment. Ghrelin and GLP-1 potently influenced each other in terms of vagally mediated feeding regulation. This peptidergic interaction allows for fine control of the electrophysiological properties of NG neurons.

scholarly journals Cannabinoid-Induced Conditioned Place Preference, Intravenous Self-Administration, and Behavioral Stimulation Influenced by Ghrelin Receptor Antagonism in Rats

2021 ◽  
Vol 22 (5) ◽  
pp. 2397
Author(s):  
Chrysostomos Charalambous ◽  
Tereza Havlickova ◽  
Marek Lapka ◽  
Nina Puskina ◽  
Romana Šlamberová ◽  
...  
Keyword(s):  
Conditioned Place Preference ◽  
Fixed Ratio ◽  
Place Preference ◽  
Self Administration ◽  
Growth Hormone Secretagogue Receptor ◽  
Growth Hormone Secretagogue ◽  
Ghrelin Receptor ◽  
Addiction Therapy ◽  
Significant Efficacy ◽  
Lever Pressing

Cannabis/cannabinoids are widely used for recreational and therapy purposes, but their risks are largely disregarded. However, cannabinoid-associated use disorders and dependence are alarmingly increasing and an effective treatment is lacking. Recently, the growth hormone secretagogue receptor (GHSR1A) antagonism was proposed as a promising mechanism for drug addiction therapy. However, the role of GHS-R1A and its endogenous ligand ghrelin in cannabinoid abuse remains unclear. Therefore, the aim of our study was to investigate whether the GHS-R1A antagonist JMV2959 could reduce the tetrahydrocannabinol (THC)-induced conditioned place preference (CPP) and behavioral stimulation, the WIN55,212-2 intravenous self-administration (IVSA), and the tendency to relapse. Following an ongoing WIN55,212-2 self-administration, JMV2959 3 mg/kg was administered intraperitoneally 20 min before three consequent daily 120-min IVSA sessions under a fixed ratio FR1, which significantly reduced the number of the active lever-pressing, the number of infusions, and the cannabinoid intake. Pretreatment with JMV2959 suggested reduction of the WIN55,212-2-seeking/relapse-like behavior tested in rats on the twelfth day of the forced abstinence period. On the contrary, pretreatment with ghrelin significantly increased the cannabinoid IVSA as well as enhanced the relapse-like behavior. Co-administration of ghrelin with JMV2959 abolished/reduced the significant efficacy of the GHS-R1A antagonist in the cannabinoid IVSA. Pretreatment with JMV2959 significantly and dose-dependently reduced the manifestation of THC-induced CPP. The THC-CPP development was reduced after the simultaneous administration of JMV2959 with THC during conditioning. JMV2959 also significantly reduced the THC-induced behavioral stimulation in the LABORAS cage. Our findings suggest that GHS-R1A importantly participates in the rewarding/reinforcing effects of cannabinoids.

scholarly journals Growth hormone secretagogue receptor in dopamine neurons controls appetitive and consummatory behaviors towards high-fat diet in ad-libitum fed mice

2020 ◽  
Vol 119 ◽  
pp. 104718
Author(s):  
María Paula Cornejo ◽  
Franco Barrile ◽  
Daniela Cassano ◽  
Julieta Paola Aguggia ◽  
Guadalupe García Romero ◽  
...  
Keyword(s):  
Growth Hormone ◽  
High Fat Diet ◽  
Dopamine Neurons ◽  
High Fat ◽  
Growth Hormone Secretagogue Receptor ◽  
Growth Hormone Secretagogue ◽  
Ad Libitum

Novel Isoxazole Carboxamides as Growth Hormone Secretagogue Receptor (GHS-R) Antagonists.

ChemInform ◽  
2005 ◽  
Vol 36 (4) ◽  
Author(s):  
Bo Liu ◽  
Gang Liu ◽  
Zhili Xin ◽  
Michael D. Serby ◽  
Hongyu Zhao ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Growth Hormone Secretagogue Receptor ◽  
Growth Hormone Secretagogue

Physiological Response of Juvenile Coho Salmon (Oncorhynchus kisutch) and Rainbow Trout (Salmo gairdneri) to Handling and Crowding Stress in Intensive Fish Culture

1976 ◽  
Vol 33 (12) ◽  
pp. 2699-2702 ◽  
Author(s):  
Gary A. Wedemeyer
Keyword(s):  
Rainbow Trout ◽  
Feeding Behavior ◽  
Coho Salmon ◽  
Physiological Stress ◽  
Oncorhynchus Kisutch ◽  
Fish Distribution ◽  
Salmo Gairdneri ◽  
Crowding Stress ◽  
Normal Feeding ◽  
Intensive Fish Culture

Moving 4–5-in. coho salmon (Oncorhynchus kisutch) held in soft (20 ppm CaCO3) water from the relatively light loading density of 0.5 lb/ft3 to 1, 2, or 4 lb/ft3 (density index, DI = 0.1, 0.2, 0.4, 0.8) caused significant stress as indicated by loss of feeding behavior, but only minimal physiological disturbances, as indicated by lack of hyperglycemia or hypochloremia. However, moving them to 6 or 12 lb/ft3 (DI = 1.2, 2.4) caused significant physiological stress which required at least a week for recovery. Smolting coho salmon were physiologically stressed by population densities of 1 lb/ft3 or more and a subclinical corynebacterial kidney infection was activated. Rainbow trout (Salmo gairdneri) (4–5 in.) were physiologically stressed when moved and held at 1 lb/ft3 or more but retained normal feeding behavior. This indicates that handling and crowding stress will be minimized in softwater areas if densities in fish distribution trucks or in ponds or raceways during disease treatments are held to 0.1–0.5 lb/gal.

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