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Annual Review of Medicine 2009Serotonin is perhaps best known as a neurotransmitter that modulates neural activity and a wide range of neuropsychological processes, and drugs that target serotonin... (Review)
Review
Serotonin is perhaps best known as a neurotransmitter that modulates neural activity and a wide range of neuropsychological processes, and drugs that target serotonin receptors are used widely in psychiatry and neurology. However, most serotonin is found outside the central nervous system, and virtually all of the 15 serotonin receptors are expressed outside as well as within the brain. Serotonin regulates numerous biological processes including cardiovascular function, bowel motility, ejaculatory latency, and bladder control. Additionally, new work suggests that serotonin may regulate some processes, including platelet aggregation, by receptor-independent, transglutaminase-dependent covalent linkage to cellular proteins. We review this new "expanded serotonin biology" and discuss how drugs targeting specific serotonin receptors are beginning to help treat a wide range of diseases.
Topics: Animals; Humans; Serotonin
PubMed: 19630576
DOI: 10.1146/annurev.med.60.042307.110802 -
Obesity Reviews : An Official Journal... Jul 2021The role of serotonin in food intake has been studied for decades. Food intake is mainly regulated by two brain circuitries: (i) the homeostatic circuitry, which matches... (Review)
Review
The role of serotonin in food intake has been studied for decades. Food intake is mainly regulated by two brain circuitries: (i) the homeostatic circuitry, which matches energy intake to energy expenditure, and (ii) the hedonic circuitry, which is involved in rewarding and motivational aspects of energy consumption. In the homeostatic circuitry, serotonergic signaling contributes to the integration of metabolic signals that convey the body's energy status and facilitates the ability to suppress food intake when homeostatic needs have been met. In the hedonic circuitry, serotonergic signaling may reduce reward-related, motivational food consumption. In contrast, peripherally acting serotonin promotes energy absorption and storage. Disturbed serotonergic signaling is associated with obesity, emphasizing the importance to understand the role of serotonergic signaling in food intake. However, unraveling the serotonin-mediated regulation of food intake is complex, as the effects of serotonergic signaling in different brain regions depend on the regional expression of serotonin receptor subtypes and downstream effects via connections to other brain regions. We therefore provide an overview of the effects of serotonergic signaling in brain regions of the homeostatic and hedonic regulatory systems on food intake. Furthermore, we discuss the disturbances in serotonergic signaling in obesity and its potential therapeutic implications.
Topics: Eating; Energy Metabolism; Humans; Obesity; Reward; Serotonin
PubMed: 33559362
DOI: 10.1111/obr.13210 -
Endocrine Reviews Aug 2019Serotonin is a phylogenetically ancient biogenic amine that has played an integral role in maintaining energy homeostasis for billions of years. In mammals, serotonin... (Review)
Review
Serotonin is a phylogenetically ancient biogenic amine that has played an integral role in maintaining energy homeostasis for billions of years. In mammals, serotonin produced within the central nervous system regulates behavior, suppresses appetite, and promotes energy expenditure by increasing sympathetic drive to brown adipose tissue. In addition to these central circuits, emerging evidence also suggests an important role for peripheral serotonin as a factor that enhances nutrient absorption and storage. Specifically, glucose and fatty acids stimulate the release of serotonin from the duodenum, promoting gut peristalsis and nutrient absorption. Serotonin also enters the bloodstream and interacts with multiple organs, priming the body for energy storage by promoting insulin secretion and de novo lipogenesis in the liver and white adipose tissue, while reducing lipolysis and the metabolic activity of brown and beige adipose tissue. Collectively, peripheral serotonin acts as an endocrine factor to promote the efficient storage of energy by upregulating lipid anabolism. Pharmacological inhibition of serotonin synthesis or signaling in key metabolic tissues are potential drug targets for obesity, type 2 diabetes, and nonalcoholic fatty liver disease (NAFLD).
Topics: Adipose Tissue, Brown; Adipose Tissue, White; Animals; Energy Metabolism; Humans; Lipid Metabolism; Serotonin; Signal Transduction
PubMed: 30901029
DOI: 10.1210/er.2018-00283 -
Canadian Medical Association Journal Apr 1970
Review
Topics: Animals; Brain; Chlorine; Humans; Hydroxyindoleacetic Acid; Phenylalanine; Rats; Reserpine; Serotonin; Serotonin Antagonists; Tryptophan
PubMed: 4910705
DOI: No ID Found -
Journal of Clinical Sleep Medicine :... Feb 2017Melatonin is an important neurohormone, which mediates circadian rhythms and the sleep cycle. As such, it is a popular and readily available supplement for the treatment...
STUDY OBJECTIVES
Melatonin is an important neurohormone, which mediates circadian rhythms and the sleep cycle. As such, it is a popular and readily available supplement for the treatment and prevention of sleep-related disorders including insomnia and jet lag. This study quantified melatonin in 30 commercial supplements, comprising different brands and forms and screened supplements for the presence of serotonin.
METHODS
A total of 31 supplements were analyzed by ultraperformance liquid chromatography with electrochemical detection for quantification of melatonin and serotonin. Presence of serotonin was confirmed through analysis by ultraperformance liquid chromatography with mass spectrometry detection.
RESULTS
Melatonin content was found to range from -83% to +478% of the labelled content. Additionally, lot-to-lot variable within a particular product varied by as much as 465%. This variability did not appear to be correlated with manufacturer or product type. Furthermore, serotonin (5-hydroxytryptamine), a related indoleamine and controlled substance used in the treatment of several neurological disorders, was identified in eight of the supplements at levels of 1 to 75 μg.
CONCLUSIONS
Melatonin content did not meet label within a 10% margin of the label claim in more than 71% of supplements and an additional 26% were found to contain serotonin. It is important that clinicians and patients have confidence in the quality of supplements used in the treatment of sleep disorders. To address this, manufacturers require increased controls to ensure melatonin supplements meet both their label claim, and also are free from contaminants, such as serotonin.
COMMENTARY
A commentary on this article appears in this issue on page 163.
Topics: Biological Products; Chromatography, Liquid; Dietary Supplements; Electrochemical Techniques; Mass Spectrometry; Melatonin; Serotonin
PubMed: 27855744
DOI: 10.5664/jcsm.6462 -
Journal of Neurophysiology Jun 2020The serotonergic system has been widely studied across animal taxa and different functional networks. This modulatory system is therefore well positioned to compare the... (Comparative Study)
Comparative Study Review
The serotonergic system has been widely studied across animal taxa and different functional networks. This modulatory system is therefore well positioned to compare the consequences of neuromodulation for sensory processing across species and modalities at multiple levels of sensory organization. Serotonergic neurons that innervate sensory networks often bidirectionally exchange information with these networks but also receive input representative of motor events or motivational state. This convergence of information supports serotonin's capacity for contextualizing sensory information according to the animal's physiological state and external events. At the level of sensory circuitry, serotonin can have variable effects due to differential projections across specific sensory subregions, as well as differential serotonin receptor type expression within those subregions. Functionally, this infrastructure may gate or filter sensory inputs to emphasize specific stimulus features or select among different streams of information. The near-ubiquitous presence of serotonin and other neuromodulators within sensory regions, coupled with their strong effects on stimulus representation, suggests that these signaling pathways should be considered integral components of sensory systems.
Topics: Animals; Auditory Perception; Nerve Net; Olfactory Perception; Receptors, Serotonin; Serotonergic Neurons; Serotonin; Signal Transduction
PubMed: 32401124
DOI: 10.1152/jn.00034.2020 -
BMB Reports Oct 2023Serotonin receptors, also known as 5-HT receptors, belong to the G protein-coupled receptors (GPCRs) superfamily. They mediate the effects of serotonin, a... (Review)
Review
Serotonin receptors, also known as 5-HT receptors, belong to the G protein-coupled receptors (GPCRs) superfamily. They mediate the effects of serotonin, a neurotransmitter that plays a key role in a wide range of functions including mood regulation, cognition and appetite. The functions of serotonin are mediated by a family of 5-HT receptors including 12 GPCRs belonging to six major families: 5-HT, 5-HT, 5-HT, 5-HT, 5-HT and 5-HT. Despite their distinct characteristics and functions, these receptors' subtypes share common structural features and signaling mechanisms. Understanding the structure, functions and pharmacology of the serotonin receptor family is essential for unraveling the complexities of serotonin signaling and developing targeted therapeutics for neuropsychiatric disorders. However, developing drugs that selectively target specific receptor subtypes is challenging due to the structural similarities in their orthosteric binding sites. This review focuses on the recent advancements in the structural studies of 5-HT receptors, highlighting the key structural features of each subtype and shedding light on their potential as targets for mental health and neurological disorders (such as depression, anxiety, schizophrenia, and migraine) drugs. [BMB Reports 2023; 56(10): 527-536].
Topics: Serotonin; Receptors, Serotonin; Binding Sites
PubMed: 37817438
DOI: 10.5483/BMBRep.2023-0147 -
Current Neuropharmacology 2019A burgeoning literature documents the confluence of ovarian steroids and central serotonergic systems in the injunction of epileptic seizures and epileptogenesis.... (Review)
Review
A burgeoning literature documents the confluence of ovarian steroids and central serotonergic systems in the injunction of epileptic seizures and epileptogenesis. Estrogen administration in animals reduces neuronal death from seizures by up-regulation of the prosurvival molecule i.e. Bcl-2, anti-oxidant potential and protection of NPY interneurons. Serotonin modulates epileptiform activity in either direction i.e administration of 5-HT agonists or reuptake inhibitors leads to the activation of 5-HT3 and 5-HT1A receptors tending to impede focal and generalized seizures, while depletion of brain 5-HT along with the destruction of serotonergic terminals leads to expanded neuronal excitability hence abatement of seizure threshold in experimental animal models. Serotonergic neurotransmission is influenced by the organizational activity of steroid hormones in the growing brain and the actuation effects of steroids which come in adulthood. It is further established that ovarian steroids bring induction of dendritic spine proliferation on serotonin neurons thus thawing a profound effect on serotonergic transmission. This review features 5-HT1A and 5-HT3 receptors as potential targets for ameliorating seizure-induced neurodegeneration and recurrent hypersynchronous neuronal activity. Indeed 5-HT3 receptors mediate cross-talk between estrogenic and serotonergic pathways, and could be well exploited for combinatorial drug therapy against epileptogenesis.
Topics: Animals; Epilepsy; Estrogens; Humans; Receptors, Serotonin; Seizures; Serotonin
PubMed: 29956631
DOI: 10.2174/1570159X16666180628164432 -
International Journal of Molecular... Apr 2022Serotonin (5-HT) is an attractive neurotransmitter system, in terms of physiology, physiopathology, and medicines [...].
Serotonin (5-HT) is an attractive neurotransmitter system, in terms of physiology, physiopathology, and medicines [...].
Topics: Nervous System; Neurotransmitter Agents; Serotonin
PubMed: 35563104
DOI: 10.3390/ijms23094712 -
Annals of the New York Academy of... Sep 2013Neuroscientists are now discovering how hormones and brain chemicals shape social behavior, opening potential avenues for pharmacological manipulation of ethical values.... (Review)
Review
Neuroscientists are now discovering how hormones and brain chemicals shape social behavior, opening potential avenues for pharmacological manipulation of ethical values. Here, we review recent studies showing how altering brain chemistry can alter moral judgment and behavior, focusing in particular on the neuromodulator serotonin and its role in shaping values related to harm and fairness. We synthesize previous findings and consider the potential mechanisms through which serotonin could increase the aversion to harming others. We present a process model whereby serotonin influences social behavior by shifting social preferences in the positive direction, enhancing the value people place on others' outcomes. This model may explain previous findings relating serotonin function to prosocial behavior, and makes new predictions regarding how serotonin may influence the neural computation of value in social contexts.
Topics: Humans; Judgment; Morals; Serotonin; Social Behavior
PubMed: 25627116
DOI: 10.1111/nyas.12229