Nucleus of the Solitary Tract Serotonin 5-HT2C Receptors Modulate Food Intake

D’Agostino, Giuseppe; Lyons, David; Cristiano, Claudia; Lettieri, M.; Olarte-Sánchez, Cristian M.; Burke, Luke K.; Greenwald-Yarnell, Megan; Cansell, Céline; Doslikova, Barbora; Georgescu, Teodora; Morentin, Pablo Blanco Martínez de; Myers, Martin G.; Rochford, Justin J.; Heisler, Lora K.

doi:10.1016/j.cmet.2018.07.017

Cited by 114 publications

(109 citation statements)

References 42 publications

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“…However, due to its toxic effects on the heart, d-fenfluramine has been withdrawn from the market, and it has been replaced by the 5-HT 2C R agonist lorcaserin [125]. The multiplicity of mechanisms by which 5-HT modulates feeding behavior is attested by the variety of 5-HTRs implicated (5-HT 1A R, 5-HT 1B R, 5-HT 2C R, 5-HT 4 R), and by the diversity of the brain areas involved in this behavior, for example sub-regions of the hypothalamus [126], the ventral tegmental area, or the nucleus of the solitary tract [127,128]. 5-HT would inhibit feeding behavior via reinforcement of satiety signals and the extension of their duration, likely via a diversity of 5-HT receptors.…”

Section: Feedingmentioning

confidence: 99%

Serotonin in Animal Cognition and Behavior

Bacqué-Cazenave

Bharatiya

Barrière

et al. 2020

IJMS

216

111

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Serotonin (5-hydroxytryptamine, 5-HT) is acknowledged as a major neuromodulator of nervous systems in both invertebrates and vertebrates. It has been proposed for several decades that it impacts animal cognition and behavior. In spite of a completely distinct organization of the 5-HT systems across the animal kingdom, several lines of evidence suggest that the influences of 5-HT on behavior and cognition are evolutionary conserved. In this review, we have selected some behaviors classically evoked when addressing the roles of 5-HT on nervous system functions.In particular, we focus on the motor activity, arousal, sleep and circadian rhythm, feeding, social interactions and aggressiveness, anxiety, mood, learning and memory, or impulsive/compulsive dimension and behavioral flexibility. The roles of 5-HT, illustrated in both invertebrates and vertebrates, show that it is more able to potentiate or mitigate the neuronal responses necessary for the fine-tuning of most behaviors, rather than to trigger or halt a specific behavior. 5-HT is, therefore, the prototypical neuromodulator fundamentally involved in the adaptation of all organisms across the animal kingdom.The organization of the 5-HT systems is completely different between species ranging from a limited number of cells in Aplysia or Drosophila (100 5-HT immunoreactive cells) to several thousand neurons in vertebrates. The variety and the heterogeneity of 5-HT neurons have been highlighted in vertebrates [7] as well as in invertebrates [8]. In general, the 5-HT systems in animals comprise 5-HT neurons, which share a particular shape made of thousands of varicosities, leading to the concept of volume transmission [9], and several 5-HT receptors (5-HTRs). In vertebrates, 5-HT neurons are localized in the midbrain raphe nuclei described as the B1-B9 cell groups [1,10]. The raphe pallidus, obscurus, and pontis form a caudal cluster (B1-B5), whereas the dorsal raphe and median raphe form a rostral cluster in the pons (B6-B9) [11]. The caudal raphe group projects to the spinal cord and the rostral group to the forebrain via an extensive and diffuse innervation. The dorsal raphe nucleus contains the highest number of 5-HT neurons and its anatomical sub-regions display some degrees of specific innervation of the forebrain [12][13][14]. The median and dorsal raphe nuclei receive excitatory and inhibitory inputs from most brain areas [15]. In crustaceans or insects, 5-HT neurons are widely present in each of the ventral cord ganglia, display large local ramifications that act in multiple neuropil areas, and some axonal branches form three pairs of rostrocaudal fibers [16][17][18][19]. Presumably, two of those fibers would project anteriorly and one posteriorly to the entire nervous system [20]. 5-HT neurons are often localized close to sensory integration input area in the brain of arthropods and some 5-HT cells in the abdominal ganglia of crayfish nerve cord are sensitive to the mechanical stimulation of abdominal segmental fringe hairs [21]. In cnidarians, 5-HT cells ...

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Section: Feedingmentioning

confidence: 99%

Serotonin in Animal Cognition and Behavior

Bacqué-Cazenave

Bharatiya

Barrière

et al. 2020

IJMS

216

111

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“…In addition to the POMC neurons of the hypothalamus, other POMC neurons expressing 5-HT2CR may contribute to regulate appetite. In this respect, POMC neurons responsive to 5-HT2CR agonist localized to the nucleus of the solitary tract (NTS) control food intake (D'Agostino et al 2018).…”

Section: Pomc Neuron and Signaling In Response To Feeding Insulin Anmentioning

confidence: 99%

The melanocortin pathway and control of appetite-progress and therapeutic implications

Baldini

Phelan

2019

Journal of Endocrinology

185

125

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The initial discovery thatob/obmice become obese because of a recessive mutation of the leptin gene has been crucial to discover the melanocortin pathway to control appetite. In the melanocortin pathway, the fed state is signaled by abundance of circulating hormones such as leptin and insulin, which bind to receptors expressed at the surface of pro-opiomelanocortin (POMC) neurons to promote processing of POMC to the mature hormone α-melanocyte-stimulating hormone (α-MSH). The α-MSH released by POMC neurons then signals to decrease energy intake by binding to melanocortin-4 receptor (MC4R) expressed by MC4R neurons to the paraventricular nucleus (PVN). Conversely, in the ‘starved state’ activity of agouti-related neuropeptide (AgRP) and of neuropeptide Y (NPY)-expressing neurons is increased by decreased levels of circulating leptin and insulin and by the orexigenic hormone ghrelin to promote food intake. This initial understanding of the melanocortin pathway has recently been implemented by the description of the complex neuronal circuit that controls the activity of POMC, AgRP/NPY and MC4R neurons and downstream signaling by these neurons. This review summarizes the progress done on the melanocortin pathway and describes how obesity alters this pathway to disrupt energy homeostasis. We also describe progress on how leptin and insulin receptors signal in POMC neurons, how MC4R signals and how altered expression and traffic of MC4R change the acute signaling and desensitization properties of the receptor. We also describe how the discovery of the melanocortin pathway has led to the use of melanocortin agonists to treat obesity derived from genetic disorders.

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“…The nucleus of the solitary tract represents the main relay station for viscerosensory signals transmitted from the periphery to the brain (D'Agostino et al, ; Emch, Hermann, & Rogers, ; Grill & Hayes, ). Based on ours and other published findings, we suggest that the nucleus of the solitary tract also plays a crucial role in transmitting melanoma‐related signals.…”

Section: Discussionmentioning

confidence: 99%

Changes in gene expression in brain structures related to visceral sensation, autonomic functions, food intake, and cognition in melanoma‐bearing mice

Horváthová

Tillinger

Padová

et al. 2020

Eur J of Neuroscience

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The brain exerts complex effects on the initiation and progression of cancer in the body. However, the influence of cancer localized in peripheral tissues on the brain has been only partially described. Therefore, we investigated gene expression in brain structures that participate in transmitting viscerosensory signals, regulating autonomic functions and food intake, as well as cognition in C57Bl/6J mice with B16-F10 melanoma. In addition, we investigated the relationship between peripheral inflammation and neuroinflammation. We found increased neuronal activity in the nucleus of the solitary tract of tumor-bearing mice, whereas neuronal activity in the A1/C1 catecholaminergic cell group, parabrachial nucleus, lateral hypothalamic area, ventromedial nucleus of the hypothalamus, paraventricular nucleus of the hypothalamus, and hippocampus was decreased. In the majority of investigated brain structures, we found increased gene expression of IL-1β, whereas gene expression of IL-6 and NF-κB was reduced or unchanged compared with controls. Melanomabearing mice also showed increased gene expression of tyrosine hydroxylase in the A1/C1 catecholaminergic cell group, nucleus of the solitary tract, and locus coeruleus, as well as reduced mRNA levels of hypocretin neuropeptide precursor protein in the lateral hypothalamic area, and proopiomelanocortin in the arcuate nucleus.In addition, we found reduced mRNA levels of Bcl-2, brain-derived neurotrophic factor, and doublecortin in the hippocampus. Our data indicate that skin melanoma induces complex changes in the brain, and these changes are most probably caused by cancer-related signals mediated by pro-inflammatory cytokines. K E Y W O R D Scatecholaminergic cell groups, food intake, hippocampus, hypothalamus, inflammation, neurogenesis, spleen

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Nucleus of the Solitary Tract Serotonin 5-HT2C Receptors Modulate Food Intake

Cited by 114 publications

References 42 publications

Serotonin in Animal Cognition and Behavior

Serotonin in Animal Cognition and Behavior

The melanocortin pathway and control of appetite-progress and therapeutic implications

Changes in gene expression in brain structures related to visceral sensation, autonomic functions, food intake, and cognition in melanoma‐bearing mice

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