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Nature Reviews. Neuroscience Dec 2021Itch is one of the most primal sensations, being both ubiquitous and important for the well-being of animals. For more than a century, a desire to understand how itch is... (Review)
Review
Itch is one of the most primal sensations, being both ubiquitous and important for the well-being of animals. For more than a century, a desire to understand how itch is encoded by the nervous system has prompted the advancement of many theories. Within the past 15 years, our understanding of the molecular and neural mechanisms of itch has undergone a major transformation, and this remarkable progress continues today without any sign of abating. Here I describe accumulating evidence that indicates that itch is distinguished from pain through the actions of itch-specific neuropeptides that relay itch information to the spinal cord. According to this model, classical neurotransmitters transmit, inhibit and modulate itch information in a context-, space- and time-dependent manner but do not encode itch specificity. Gastrin-releasing peptide (GRP) is proposed to be a key itch-specific neuropeptide, with spinal neurons expressing GRP receptor (GRPR) functioning as a key part of a convergent circuit for the conveyance of peripheral itch information to the brain.
Topics: Animals; Gastrin-Releasing Peptide; Humans; Neurons; Neuropeptides; Pruritus; Spinal Cord
PubMed: 34663954
DOI: 10.1038/s41583-021-00526-9 -
Trends in Neurosciences Dec 2022Neuropeptides produce robust effects on behavior across species, and recent research has benefited from advances in high-resolution techniques to investigate peptidergic... (Review)
Review
Neuropeptides produce robust effects on behavior across species, and recent research has benefited from advances in high-resolution techniques to investigate peptidergic transmission and expression throughout the brain in model systems. Neuropeptides exhibit distinct characteristics which includes their post-translational processing, release from dense core vesicles, and ability to activate G-protein-coupled receptors (GPCRs). These complex properties have driven the need for development of specialized tools that can sense neuropeptide expression, cell activity, and release. Current research has focused on isolating when and how neuropeptide transmission occurs, as well as the conditions in which neuropeptides directly mediate physiological and adaptive behavioral states. Here we describe the current technological landscape in which the field is operating to decode key questions regarding these dynamic neuromodulators.
Topics: Humans; Neuropeptides; Receptors, G-Protein-Coupled
PubMed: 36257845
DOI: 10.1016/j.tins.2022.09.005 -
Cell Aug 1999Neurons containing the neuropeptide orexin (hypocretin) are located exclusively in the lateral hypothalamus and send axons to numerous regions throughout the central... (Comparative Study)
Comparative Study
Neurons containing the neuropeptide orexin (hypocretin) are located exclusively in the lateral hypothalamus and send axons to numerous regions throughout the central nervous system, including the major nuclei implicated in sleep regulation. Here, we report that, by behavioral and electroencephalographic criteria, orexin knockout mice exhibit a phenotype strikingly similar to human narcolepsy patients, as well as canarc-1 mutant dogs, the only known monogenic model of narcolepsy. Moreover, modafinil, an anti-narcoleptic drug with ill-defined mechanisms of action, activates orexin-containing neurons. We propose that orexin regulates sleep/wakefulness states, and that orexin knockout mice are a model of human narcolepsy, a disorder characterized primarily by rapid eye movement (REM) sleep dysregulation.
Topics: Age of Onset; Animals; Benzhydryl Compounds; Carrier Proteins; Disease Models, Animal; Dog Diseases; Dogs; Electroencephalography; Electromyography; Humans; Hypothalamus; Intracellular Signaling Peptides and Proteins; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Modafinil; Narcolepsy; Neurons; Neuropeptides; Orexin Receptors; Orexins; Phenotype; Posture; Protein Precursors; Receptors, G-Protein-Coupled; Receptors, Neuropeptide; Sleep; Sleep, REM; Species Specificity; Stereotyped Behavior
PubMed: 10481909
DOI: 10.1016/s0092-8674(00)81973-x -
Cell Feb 1998The hypothalamus plays a central role in the integrated control of feeding and energy homeostasis. We have identified two novel neuropeptides, both derived from the same...
The hypothalamus plays a central role in the integrated control of feeding and energy homeostasis. We have identified two novel neuropeptides, both derived from the same precursor by proteolytic processing, that bind and activate two closely related (previously) orphan G protein-coupled receptors. These peptides, termed orexin-A and -B, have no significant structural similarities to known families of regulatory peptides. prepro-orexin mRNA and immunoreactive orexin-A are localized in neurons within and around the lateral and posterior hypothalamus in the adult rat brain. When administered centrally to rats, these peptides stimulate food consumption. prepro-orexin mRNA level is up-regulated upon fasting, suggesting a physiological role for the peptides as mediators in the central feedback mechanism that regulates feeding behavior.
Topics: Animals; CHO Cells; Carrier Proteins; Chromatography, High Pressure Liquid; Cricetinae; Fasting; Feeding Behavior; GTP-Binding Proteins; Humans; Hypothalamus; Intracellular Signaling Peptides and Proteins; Kidney; Male; Molecular Sequence Data; Neurons; Neuropeptides; Orexin Receptors; Orexins; Protein Precursors; RNA, Messenger; Rabbits; Rats; Rats, Wistar; Receptors, G-Protein-Coupled; Receptors, Neuropeptide; Sequence Homology, Amino Acid
PubMed: 9491897
DOI: 10.1016/s0092-8674(00)80949-6 -
International Journal of Molecular... Apr 2022Sleep and wakefulness are basic behavioral states that require coordination between several brain regions, and they involve multiple neurochemical systems, including... (Review)
Review
Sleep and wakefulness are basic behavioral states that require coordination between several brain regions, and they involve multiple neurochemical systems, including neuropeptides. Neuropeptides are a group of peptides produced by neurons and neuroendocrine cells of the central nervous system. Like traditional neurotransmitters, neuropeptides can bind to specific surface receptors and subsequently regulate neuronal activities. For example, orexin is a crucial component for the maintenance of wakefulness and the suppression of rapid eye movement (REM) sleep. In addition to orexin, melanin-concentrating hormone, and galanin may promote REM sleep. These results suggest that neuropeptides play an important role in sleep-wake regulation. These neuropeptides can be divided into three categories according to their effects on sleep-wake behaviors in rodents and humans. (i) Galanin, melanin-concentrating hormone, and vasoactive intestinal polypeptide are sleep-promoting peptides. It is also noticeable that vasoactive intestinal polypeptide particularly increases REM sleep. (ii) Orexin and neuropeptide S have been shown to induce wakefulness. (iii) Neuropeptide Y and substance P may have a bidirectional function as they can produce both arousal and sleep-inducing effects. This review will introduce the distribution of various neuropeptides in the brain and summarize the roles of different neuropeptides in sleep-wake regulation. We aim to lay the foundation for future studies to uncover the mechanisms that underlie the initiation, maintenance, and end of sleep-wake states.
Topics: Galanin; Intracellular Signaling Peptides and Proteins; Neuropeptides; Orexins; Sleep; Vasoactive Intestinal Peptide
PubMed: 35562990
DOI: 10.3390/ijms23094599 -
Proceedings of the National Academy of... Aug 2022Human prefrontal cortex (hPFC) is a complex brain region involved in cognitive and emotional processes and several psychiatric disorders. Here, we present an overview of...
Human prefrontal cortex (hPFC) is a complex brain region involved in cognitive and emotional processes and several psychiatric disorders. Here, we present an overview of the distribution of the peptidergic systems in 17 subregions of hPFC and three reference cortices obtained by microdissection and based on RNA sequencing and RNAscope methods integrated with published single-cell transcriptomics data. We detected expression of 60 neuropeptides and 60 neuropeptide receptors in at least one of the hPFC subregions. The results reveal that the peptidergic landscape in PFC consists of closely located and functionally different subregions with unique peptide/transmitter-related profiles. Neuropeptide-rich PFC subregions were identified, encompassing regions from anterior cingulate cortex/orbitofrontal gyrus. Furthermore, marked differences in gene expression exist between different PFC regions (>5-fold; cocaine and amphetamine-regulated transcript peptide) as well as between PFC regions and reference regions, for example, for somatostatin and several receptors. We suggest that the present approach allows definition of, still hypothetical, microcircuits exemplified by glutamatergic neurons expressing a peptide cotransmitter either as an agonist (hypocretin/orexin) or antagonist (galanin). Specific neuropeptide receptors have been identified as possible targets for neuronal afferents and, interestingly, peripheral blood-borne peptide hormones (leptin, adiponectin, gastric inhibitory peptide, glucagon-like peptides, and peptide YY). Together with other recent publications, our results support the view that neuropeptide systems may play an important role in hPFC and underpin the concept that neuropeptide signaling helps stabilize circuit connectivity and fine-tune/modulate PFC functions executed during health and disease.
Topics: Female; Gene Expression Profiling; Humans; Male; Neuropeptides; Prefrontal Cortex; Receptors, Neuropeptide
PubMed: 35947618
DOI: 10.1073/pnas.2123146119 -
Scientific Reports Jun 2022Neuropeptides and neuropeptide receptors are crucial regulators to insect physiological processes. The 21.0 Gb bases were obtained from Illumina sequencing of two...
Neuropeptides and neuropeptide receptors are crucial regulators to insect physiological processes. The 21.0 Gb bases were obtained from Illumina sequencing of two libraries representing the female and male heads of Phauda flammans (Walker) (Lepidoptera: Phaudidae), which is a diurnal defoliator of ficus plants and usually outbreaks in the south and south-east Asia, to identify differentially expressed genes, neuropeptides and neuropeptide receptor whose tissue expressions were also evaluated. In total, 99,386 unigenes were obtained, in which 156 up-regulated and 61 down-regulated genes were detected. Fifteen neuropeptides (i.e., F1b, Ast, NP1, IMF, Y, BbA1, CAP2b, NPLP1, SIF, CCH2, NP28, NP3, PDP3, ARF2 and SNPF) and 66 neuropeptide receptor genes (e.g., A2-1, FRL2, A32-1, A32-2, FRL3, etc.) were identified and well-clustered with other lepidopteron. This is the first sequencing, identification neuropeptides and neuropeptide receptor genes from P. flammans which provides valuable information regarding the molecular basis of P. flammans.
Topics: Animals; Female; Lepidoptera; Male; Neuropeptides; Receptors, Neuropeptide
PubMed: 35701459
DOI: 10.1038/s41598-022-13590-7 -
Current Opinion in Neurobiology Aug 2012Neuropeptides provide functional flexibility to microcircuits, their inputs and effectors by modulating presynaptic and postsynaptic properties and intrinsic currents.... (Review)
Review
Neuropeptides provide functional flexibility to microcircuits, their inputs and effectors by modulating presynaptic and postsynaptic properties and intrinsic currents. Recent studies have relied less on applied neuropeptide and more on their neural release. In rhythmically active microcircuits (central pattern generators, CPGs), recent studies show that neuropeptide modulation can enable particular activity patterns by organizing specific circuit motifs. Neuropeptides can also modify microcircuit output indirectly, by modulating circuit inputs. Recently elucidated consequences of neuropeptide modulation include changes in motor patterns and behavior, stabilization of rhythmic motor patterns and changes in CPG sensitivity to sensory input. One aspect of neuropeptide modulation that remains enigmatic is the presence of multiple peptide family members in the same nervous system and even the same neurons.
Topics: Animals; Aplysia; Central Pattern Generators; Models, Neurological; Nerve Net; Neurons; Neuropeptides
PubMed: 22305485
DOI: 10.1016/j.conb.2012.01.003 -
ACS Chemical Neuroscience Apr 2019Neuropeptides are chemical messengers that act to regulate a number of physiological processes, including feeding, reward, pain, and memory, among others. PEN is one of... (Review)
Review
Neuropeptides are chemical messengers that act to regulate a number of physiological processes, including feeding, reward, pain, and memory, among others. PEN is one of the most abundant hypothalamic neuropeptides; however, until recently, its target receptor remained unknown. In this Review, we summarize recent developments in research focusing on PEN and its receptor GPR83. We describe the studies leading to the deorphanization of GPR83 as the receptor for PEN. We also describe the signaling mediated by the PEN-GPR83 system, as well as the physiological roles in which PEN-GPR83 has been implicated. As studies have suggested a role for the PEN-GPR83 system in food intake and body weight regulation, as well as in drug addiction and reward disorders, a thorough understanding of this novel neuropeptide-receptor system will help identify novel therapeutic targets to treat pathophysiological conditions involving PEN-GPR83.
Topics: Amino Acid Sequence; Animals; Behavior, Addictive; Humans; Hypothalamus; Neuropeptides; Receptors, G-Protein-Coupled; Reward; Signal Transduction
PubMed: 30726666
DOI: 10.1021/acschemneuro.8b00559 -
Pharmacological Reviews Jul 2022The discovery of insulin in the early 1900s ushered in the era of research related to peptides acting as hormones and neuromodulators, among other regulatory roles.... (Review)
Review
The discovery of insulin in the early 1900s ushered in the era of research related to peptides acting as hormones and neuromodulators, among other regulatory roles. These essential gene products are found in all organisms, from the most primitive to the most evolved, and carry important biologic information that coordinates complex physiology and behavior; their misregulation has been implicated in a variety of diseases. The evolutionary origins of at least 30 neuropeptide signaling systems have been traced to the common ancestor of protostomes and deuterostomes. With the use of relevant animal models and modern technologies, we can gain mechanistic insight into orthologous and paralogous endogenous peptides and translate that knowledge into medically relevant insights and new treatments. Groundbreaking advances in medicine and basic science influence how signaling peptides are defined today. The precise mechanistic pathways for over 100 endogenous peptides in mammals are now known and have laid the foundation for multiple drug development pipelines. Peptide biologics have become valuable drugs due to their unique specificity and biologic activity, lack of toxic metabolites, and minimal undesirable interactions. This review outlines modern technologies that enable neuropeptide discovery and characterization, and highlights lessons from nature made possible by neuropeptide research in relevant animal models that is being adopted by the pharmaceutical industry. We conclude with a brief overview of approaches/strategies for effective development of peptides as drugs. SIGNIFICANCE STATEMENT: Neuropeptides, an important class of cell-cell signaling molecules, are involved in maintaining a range of physiological functions. Since the discovery of insulin's activity, over 100 bioactive peptides and peptide analogs have been used as therapeutics. Because these are complex molecules not easily predicted from a genome and their activity can change with subtle chemical modifications, mass spectrometry (MS) has significantly empowered peptide discovery and characterization. This review highlights contributions of MS-based research towards the development of therapeutic peptides.
Topics: Animals; Humans; Insulins; Mammals; Mass Spectrometry; Neuropeptides; Peptides; Power, Psychological
PubMed: 35710134
DOI: 10.1124/pharmrev.121.000423