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1
Veenstra, Jan A. "Similarities between decapod and insect neuropeptidomes." PeerJ 4 (May 26, 2016): e2043. http://dx.doi.org/10.7717/peerj.2043.
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Background.Neuropeptides are important regulators of physiological processes and behavior. Although they tend to be generally well conserved, recent results using trancriptome sequencing on decapod crustaceans give the impression of significant differences between species, raising the question whether such differences are real or artefacts.Methods.The BLAST+ program was used to find short reads coding neuropeptides and neurohormons in publicly available short read archives. Such reads were then used to find similar reads in the same archives, and the DNA assembly program Trinity was employed to construct contigs encoding the neuropeptide precursors as completely as possible.Results.The seven decapod species analyzed in this fashion, the crabsEriocheir sinensis, Carcinus maenasandScylla paramamosain, the shrimpLitopenaeus vannamei, the lobsterHomarus americanus, the fresh water prawnMacrobrachium rosenbergiiand the crayfishProcambarus clarkiihad remarkably similar neuropeptidomes. Although some neuropeptide precursors could not be assembled, in many cases individual reads pertaining to the missing precursors show unambiguously that these neuropeptides are present in these species. In other cases, the tissues that express those neuropeptides were not used in the construction of the cDNA libraries. One novel neuropeptide was identified: elongated PDH (pigment dispersing hormone), a variation on PDH that has a two-amino-acid insertion in its core sequence. Hyrg is another peptide that is ubiquitously present in decapods and is likely a novel neuropeptide precursor.Discussion.Many insect species have lost one or more neuropeptide genes, but apart from elongated PDH and hyrg all other decapod neuropeptides are present in at least some insect species, and allatotropin is the only insect neuropeptide missing from decapods. This strong similarity between insect and decapod neuropeptidomes makes it possible to predict the receptors for decapod neuropeptides that have been deorphanized in insects. This includes the androgenic insulin-like peptide that seems to be homologous to drosophila insulin-like peptide 8.
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Veenstra, Jan A. "Coleoptera genome and transcriptome sequences reveal numerous differences in neuropeptide signaling between species." PeerJ 7 (June 17, 2019): e7144. http://dx.doi.org/10.7717/peerj.7144.
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Background Insect neuropeptides are interesting for the potential their receptors hold as plausible targets for a novel generation of pesticides. Neuropeptide genes have been identified in a number of different species belonging to a variety of insects. Results suggest significant neuropeptide variation between different orders, but much less is known of neuropeptidome variability within an insect order. I therefore compared the neuropeptidomes of a number of Coleoptera. Methodology Publicly available genome sequences, transcriptomes and the original sequence data in the form of short sequence read archives were analyzed for the presence or absence of genes coding neuropeptides as well as some neuropeptide receptors in seventeen beetle species. Results Significant differences exist between the Coleoptera analyzed here, while many neuropeptides that were previously characterized from Tribolium castaneum appear very similar in all species, some are not and others are lacking in one or more species. On the other hand, leucokinin, which was presumed to be universally absent from Coleoptera, is still present in non-Polyphaga beetles. Conclusion The variability in neuropeptidome composition between species from the same insect order may be as large as the one that exists between species from different orders.
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Pidsudko, Z., J. Kaleczyc, J. Zmudzki, W. Sienkiewicz, M. Zalecki, M. Klimczuk, and K. Wasowicz. "Changes in the tissue concentrations of several neuropeptides in porcine intestines and intestine-innervating ganglia in the course of porcine proliferative enteropathy." Veterinární Medicína 63, No. 5 (May 29, 2018): 210–15. http://dx.doi.org/10.17221/62/2017-vetmed.
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Inflammatory processes are associated with changes in the interplay of different pro- and anti-inflammatory factors, including neuropeptides, in tissue. This study was performed to investigate the influence of proliferative enteropathy on the concentration of several neuropeptides known to be involved in the regulation of the inflammatory process in porcine intestine and intestine-innervating ganglia. The concentration of galanin, vasoactive intestinal polypeptide, somatostatin, neuropeptide Y, substance P and calcitonin gene-related peptide were assayed with ELISA in the coeliac-superior mesenteric ganglion, inferior mesenteric ganglion, selected dorsal root ganglia, ileum and the descending colon in healthy and sick pigs. The concentrations of the studied neuropeptides were higher in sick animals. Statistically significant differences were found for coeliac-superior mesenteric ganglion (galanin, vasoactive intestinal polypeptide, somatostatin and neuropeptide Y), inferior mesenteric ganglion (galanin, somatostatin and neuropeptide Y), dorsal root ganglia (galanin, somatostatin, neuropeptide Y and calcitonin gene-related peptide), ileum (galanin and somatostatin) and the descending colon (galanin, somatostatin and neuropeptide Y). The data clearly show the influence of the inflammatory process on the concentration of some of the studied neuropeptides present in inflamed tissues and ganglia innervating the inflamed gut. These changes must be associated with the role the studied neuropeptides play in the inflammatory process.
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Ryznar, Rebecca, Nathan Andrews, Kyle Emery, Michaela Snow, Mark Payton, Francina Towne, and Dean Gubler. "Specific Salivary Neuropeptides Shift Synchronously during Acute Stress in Fire Recruits." Brain Sciences 14, no. 5 (May 13, 2024): 492. http://dx.doi.org/10.3390/brainsci14050492.
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Once thought of as an immune-privileged site, we now know that the nervous system communicates in a bidirectional manner with the immune system via the neuroimmune axis. Neuropeptides constitute a component of this axis, playing critical roles in the brain and periphery. The function of salivary neuropeptides in the acute stress response is not well understood. The purpose of this study is to investigate salivary neuropeptide levels during acute stress. Salivary samples were collected from fire recruits engaged in a stress training exercise previously shown to induce acute stress, at three separate timepoints during the exercise and levels of oxytocin, neurotensin, Substance P, α-MSH, and β-Endorphin were measured using the Human Neuropeptide 5-Plex Custom Assay Eve Technologies. All neuropeptides increased throughout the acute stress simulation and during the recovery phase. Exploratory factor analysis (EFA) identified one factor contributing to baseline values across five neuropeptides and Pairwise Pearson Correlation Coefficient analysis showed positive correlations >0.9 for almost all neuropeptide combinations at the pre-stress timepoint. Further analysis identified negative and positive correlations between past-life trauma and self-assessed hardiness, respectively. Calculated neuropeptide scores showed an overall positive correlation to self-assessed hardiness. Altogether, our results suggest that salivary neuropeptides increase synchronously during acute stress and higher levels correlate with an increase in self-assessed hardiness. Further study is required to determine if interventions designed to enhance neuropeptide activity can increase stress resilience, especially in high-stress occupations such as firefighting.
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Kaur, Rimanpreet, Naina Arora, Meera G. Nair, and Amit Prasad. "The interplay of helminthic neuropeptides and proteases in parasite survival and host immunomodulation." Biochemical Society Transactions 50, no. 1 (January 25, 2022): 107–18. http://dx.doi.org/10.1042/bst20210405.
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Neuropeptides comprise a diverse and broad group of neurotransmitters in vertebrates and invertebrates, with critical roles in neuronal signal transduction. While their role in controlling learning and memory in the brains of mammals is known, their extra-synaptic function in infection and inflammation with effects on distinct tissues and immune cells is increasingly recognized. Helminth infections especially of the central nervous system (CNS), such as neurocysticercosis, induce neuropeptide production by both host and helminth, but their role in host–parasite interplay or host inflammatory response is unclear. Here, we review the neurobiology of helminths, and discuss recent studies on neuropeptide synthesis and function in the helminth as well as the host CNS and immune system. Neuropeptides are summarized according to structure and function, and we discuss the complex enzyme processing for mature neuropeptides, focusing on helminth enzymes as potential targets for novel anthelminthics. We next describe known immunomodulatory effects of mammalian neuropeptides discovered from mouse infection models and draw functional parallels with helminth neuropeptides. Last, we discuss the anti-microbial properties of neuropeptides, and how they may be involved in host–microbiota changes in helminth infection. Overall, a better understanding of the biology of helminth neuropeptides, and whether they affect infection outcomes could provide diagnostic and therapeutic opportunities for helminth infections.
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Josefsson, Malin, Magnus Becker, Fritz Stroman, Daniel G. Brenner, and Göran Petersson. "Effect of Recombinant Neutral Endopeptidase (EC 3.4.24.11) on Neuropeptide-Mediated Nasal Fluid Secretion and Plasma Exudation in the Rat." American Journal of Rhinology 12, no. 2 (March 1998): 135–42. http://dx.doi.org/10.2500/105065898781390244.
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The nasal mucosa harbors sensory nerves containing neuropeptides such as substance P (SP), which are released by capsaicin. The neuropeptides are degraded by peptidases, e.g., neutral endopeptidase (NEP) that is present in the nasal mucosa. We studied the effect of enzymatically active recombinant NEP (rNEP) on neuropeptide-evoked secretion of nasal fluid and plasma exudation in rats. rNEP administered intranasally (i.n.) reduced the capsaicin-evoked nasal fluid secretion but failed to reduce the secretion evoked by SP (exogenous) under the experimental conditions used. rNEP reduced the increase in nasal plasma exudation evoked by capsaicin (endogenous neuropeptides). Because rNEP reduced neuropeptide-mediated nasal fluid secretion and plasma exudation in the rat, we suggest that peptidase activity in the nasal mucosa will determine the magnitude of the response to locally released neuropeptides.
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Sun, Changsheng, Jiatong Han, Yixin Bai, Zhaowei Zhong, Yingtao Song, and Yu Sun. "Neuropeptides as the Shared Genetic Crosstalks Linking Periodontitis and Major Depression Disorder." Disease Markers 2021 (October 21, 2021): 1–13. http://dx.doi.org/10.1155/2021/3683189.
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Background. The aim of this study was at investigating the association between major depressive disorder (MDD) and periodontitis based on crosstalk genes and neuropeptides. Methods. Datasets for periodontitis (GSE10334, GSE16134, and GSE23586) and MDD (GSE38206 and GSE39653) were downloaded from GEO. Following batch correction, a differential expression analysis was applied (MDD: ∣ log 2 FC ∣ > 0 and periodontitis ∣ log 2 FC ∣ ≥ 0.5 , p < 0.05 ). The neuropeptide data were downloaded from NeuroPep and NeuroPedia. Intersected genes were potential crosstalk genes. The correlation between neuropeptides and crosstalk genes in MDD and periodontitis was analyzed with Pearson correlation coefficient. Subsequently, regression analysis was performed to calculate the differentially regulated link. Cytoscape was used to map the pathways of crosstalk genes and neuropeptides and to construct the protein-protein interaction network. Lasso regression was applied to screen neuropeptides, whereby boxplots were created, and receiver operating curve (ROC) analysis was conducted. Results. The MDD dataset contained 30 case and 33 control samples, and the periodontitis dataset contained 430 case and 139 control samples. 35 crosstalk genes were obtained. A total of 102 neuropeptides were extracted from the database, which were not differentially expressed in MDD and periodontitis and had no intersection with crosstalk genes. Through lasso regression, 9 neuropeptides in MDD and 43 neuropeptides in periodontitis were obtained. Four intersected neuropeptide genes were obtained, i.e., ADM, IGF2, PDYN, and RETN. The results of ROC analysis showed that IGF2 was highly predictive in MDD and periodontitis. ADM was better than the other three genes in predicting MDD disease. A total of 13 crosstalk genes were differentially coexpressed with four neuropeptides, whereby FOSB was highly expressed in MDD and periodontitis. Conclusion. The neuropeptide genes ADM, IGF2, PDYN, and RETN were intersected between periodontitis and MDD, and FOSB was a crosstalk gene related to these neuropeptides on the transcriptomic level. These results are a basis for future research in the field, needing further validation.
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Shen, Yi-Chen, Xiao Sun, Lei Li, Hu-Yunlong Zhang, Zhi-Li Huang, and Yi-Qun Wang. "Roles of Neuropeptides in Sleep–Wake Regulation." International Journal of Molecular Sciences 23, no. 9 (April 21, 2022): 4599. http://dx.doi.org/10.3390/ijms23094599.
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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.
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Wang, Zhengbing, Wenwu Zhou, Muhammad Hameed, Jiali Liu, and Xinnian Zeng. "Characterization and Expression Profiling of Neuropeptides and G-Protein-Coupled Receptors (GPCRs) for Neuropeptides in the Asian Citrus Psyllid, Diaphorina citri (Hemiptera: Psyllidae)." International Journal of Molecular Sciences 19, no. 12 (December 6, 2018): 3912. http://dx.doi.org/10.3390/ijms19123912.
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Neuropeptides are endogenous active substances that widely exist in multicellular biological nerve tissue and participate in the function of the nervous system, and most of them act on neuropeptide receptors. In insects, neuropeptides and their receptors play important roles in controlling a multitude of physiological processes. In this project, we sequenced the transcriptome from twelve tissues of the Asian citrus psyllid, Diaphorina citri Kuwayama. A total of 40 candidate neuropeptide genes and 42 neuropeptide receptor genes were identified. Among the neuropeptide receptor genes, 35 of them belong to the A-family (or rhodopsin-like), four of them belong to the B-family (or secretin-like), and three of them are leucine-rich repeat-containing G-protein-coupled receptors. The expression profile of the 82 genes across developmental stages was determined by qRT-PCR. Our study provides the first investigation on the genes of neuropeptides and their receptors in D. citri, which may play key roles in regulating the physiology and behaviors of D. citri.
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Liu, Yining, and Min Zhao. "Decode the Stable Cell Communications Based on Neuropeptide-Receptors Network in 36746 Tumor Cells." Biomedicines 10, no. 1 (December 22, 2021): 14. http://dx.doi.org/10.3390/biomedicines10010014.
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Background: As chemical signals of hormones, neuropeptides are essential to regulate cell growth by interacting with their receptors to achieve cell communications in cancer tissues. Previously, neuropeptide transcriptome analysis was limited to tissue-based bulk expression levels. The molecular mechanisms of neuropeptides and their receptors at the single-cell level remain unclear. We conducted a systematic single-cell transcriptome data integration analysis to clarify the similarities and variations of neuropeptide-mediated cell communication between various malignancies. Methods: Based on the single-cell expression information in 72 cancer datasets across 24 cancer types, we characterized actively expressed neuropeptides and receptors as having log values of the quantitative transcripts per million ≥ 1. Then, we created the putative cell-to-cell communication network for each dataset by using the known interaction of those actively expressed neuropeptides and receptors. To focus on the stable cell communication events, we identified neuropeptide and downstream receptors whose interactions were detected in more than half of all conceivable cell-cell interactions (square of the total cell population) in a dataset. Results: Focusing on those actively expressed neuropeptides and receptors, we built over 76 million cell-to-cell communications across 70 cancer datasets. Then the stable cell communication analyses were applied to each dataset, and about 14 million stable cell-to-cell communications could be detected based on 16 neuropeptides and 23 receptors. Further functional analysis indicates these 39 genes could regulate blood pressure and are significantly associated with patients’ survival among over ten thousand The Cancer Genome Atlas (TCGA)pan-cancer samples. By zooming in lung cancer-specific clinical features, we discovered the 39 genes appeared to be enriched in the patients with smoking. In skin cancer, they may differ in the patients with the distinct histological subtype and molecular drivers. Conclusions: At the single-cell level, stable cell communications across cancer types demonstrated some common and distinct neuropeptide-receptor patterns, which could be helpful in determining the status of neuropeptide-based cell communication and developing a peptide-based therapy strategy.
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Grimmelikhuijzen, Cornelis J. P., Michael Williamson, and Georg N. Hansen. "Neuropeptides in cnidarians." Canadian Journal of Zoology 80, no. 10 (October 1, 2002): 1690–702. http://dx.doi.org/10.1139/z02-137.
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Cnidarians are the lowest animal group having a nervous system. In the primitive nervous systems of cnidarians, peptides play important roles as neurotransmitters or neurohormones. So far, we have isolated and sequenced about 35 neuropeptides from different cnidarian classes (Hydrozoa, Scyphozoa, Anthozoa). All these neuropeptides have a C-terminal amide group, which protects against C-terminal degradation, but which also is important for receptor recognition. Also the N-termini of the cnidarian neuropeptides often contain different kinds of protecting groups (such as <Glu residues, L-3-phenyllactyl groups, and X-Pro or X-Pro-Pro sequences). Cnidarian neuropeptides are located in neuronal dense-core vesicles and are synthesized as preprohormones, which can contain up to 41 copies of a neuro peptide sequence. From Hydra, six different neuropeptide genes have been cloned so far. Each gene is expressed by a specific population of neurons, but in two instances coexpression of neuropeptide genes has been found. We have also cloned some of the cnidarian prohormone processing enzymes, among them the enzymes necessary for C-terminal amidation. These enzymes are closely related to their mammalian counterparts. All these data show that the primitive nervous systems of cnidarians have already acquired some of the sophisticated principles that we know from higher animals.
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Lestanova, Z., Z. Bacova, and Jan Bakos. "Mechanisms involved in the regulation of neuropeptide-mediated neurite outgrowth: a minireview." Endocrine Regulations 50, no. 2 (April 1, 2016): 72–82. http://dx.doi.org/10.1515/enr-2016-0011.
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AbstractThe present knowledge, regarding the neuronal growth and neurite extension, includes neuropeptide action in the central nervous system. Research reports have brought much information about the multiple intracellular signaling pathways of neuropeptides. However, regardless of the differences in the local responses elicited by neuropeptides, there exist certain functional similarities in the effects of neuropeptides, mediated by their receptors. In the present review, data of the relevant studies, focused on G protein-coupled receptors activated by neuropeptides, are summarized. Particularly, receptors that activate phosphatidylinositol-calcium system and protein kinase C pathways, resulting in the reorganization of the neuronal cytoskeleton and changes in the neuronal morphology, are discussed. Based on our data received, we are showing that oxytocin increases the gene expression of GTPase cell division cycle protein 42 (Cdc42), implicated in many aspects of the neuronal growth and morphology. We are also paying a special attention to neurite extension and retraction in the context of neuropeptide regulation.
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Tu, Shisheng, Rui Xu, Mengen Wang, Xi Xie, Chenchang Bao, and Dongfa Zhu. "Identification and characterization of expression profiles of neuropeptides and their GPCRs in the swimming crab, Portunus trituberculatus." PeerJ 9 (September 15, 2021): e12179. http://dx.doi.org/10.7717/peerj.12179.
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Neuropeptides and their G protein-coupled receptors (GPCRs) regulate multiple physiological processes. Currently, little is known about the identity of native neuropeptides and their receptors in Portunus trituberculatus. This study employed RNA-sequencing and reverse transcription-polymerase chain reaction (RT-PCR) techniques to identify neuropeptides and their receptors that might be involved in regulation of reproductive processes of P. trituberculatus. In the central nervous system transcriptome data, 47 neuropeptide transcripts were identified. In further analyses, the tissue expression profile of 32 putative neuropeptide-encoding transcripts was estimated. Results showed that the 32 transcripts were expressed in the central nervous system and 23 of them were expressed in the ovary. A total of 47 GPCR-encoding transcripts belonging to two classes were identified, including 39 encoding GPCR-A family and eight encoding GPCR-B family. In addition, we assessed the tissue expression profile of 33 GPCRs (27 GPCR-As and six GPCR-Bs) transcripts. These GPCRs were found to be widely expressed in different tissues. Similar to the expression profiles of neuropeptides, 20 of these putative GPCR-encoding transcripts were also detected in the ovary. This is the first study to establish the identify of neuropeptides and their GPCRs in P. trituberculatus, and provide information for further investigations into the effect of neuropeptides on the physiology and behavior of decapod crustaceans.
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Choudhary, Nilesh C. "A SYSTEMIC REVIEW ON NOVEL TECHNIQUES USED IN THE DETERMINATION OF NEUROPEPTIDE THROUGH THE ANALYTICAL TECHNIQUES." Journal of Medical pharmaceutical and allied sciences 10, no. 3 (July 15, 2021): 2794–800. http://dx.doi.org/10.22270/jmpas.v10i3.1062.
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Neuropeptides are a group of signaling molecules which are located in central nervous system. They control essential physiological function in animals like cardiovascular activity, energy, reproduction, growth, homeostasis, behavior, and stress response. Neuropeptides are the endogenous peptides they act as a neurotransmitter, neuromodulator and hormones. The detection process of neuropeptides is challenging due to their cleavage by peptidases and undergoes posttranslational modification. The in vivo isolation of neuropeptides occurs at very small concentrations as a significance of the efforts made to establish new neuropeptide detection techniques. Here, we examine these view points and the related strategies, and new techniques concentrating on advancements that have exhibited potential in propelling the field lately.
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Semmens, Dean C., Isabel Beets, Matthew L. Rowe, Liisa M. Blowes, Paola Oliveri, and Maurice R. Elphick. "Discovery of sea urchin NGFFFamide receptor unites a bilaterian neuropeptide family." Open Biology 5, no. 4 (April 2015): 150030. http://dx.doi.org/10.1098/rsob.150030.
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Neuropeptides are ancient regulators of physiology and behaviour, but reconstruction of neuropeptide evolution is often difficult owing to lack of sequence conservation. Here, we report that the receptor for the neuropeptide NGFFFamide in the sea urchin Strongylocentrotus purpuratus (phylum Echinodermata) is an orthologue of vertebrate neuropeptide-S (NPS) receptors and crustacean cardioactive peptide (CCAP) receptors. Importantly, this has facilitated reconstruction of the evolution of two bilaterian neuropeptide signalling systems. Genes encoding the precursor of a vasopressin/oxytocin-type neuropeptide and its receptor duplicated in a common ancestor of the Bilateria. One copy of the precursor retained ancestral features, as seen in highly conserved vasopressin/oxytocin–neurophysin-type precursors. The other copy diverged, but this took different courses in protostomes and deuterostomes. In protostomes, the occurrence of a disulfide bridge in neuropeptide product(s) of the precursor was retained, as in CCAP, but with loss of the neurophysin domain. In deuterostomes, we see the opposite scenario—the neuropeptides lost the disulfide bridge, and neurophysin was retained (as in the NGFFFamide precursor) but was subsequently lost in vertebrate NPS precursors. Thus, the sea urchin NGFFFamide precursor and receptor are ‘missing links’ in the evolutionary history of neuropeptides that control ecdysis in arthropods (CCAP) and regulate anxiety in humans (NPS).
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Hsu, I.-Uen, Jeremy W. Linsley, Xiaoli Zhang, Jade E. Varineau, Drew A. Berkhoudt, Lilly E. Reid, Miranda C. Lum, et al. "Stac protein regulates release of neuropeptides." Proceedings of the National Academy of Sciences 117, no. 47 (November 9, 2020): 29914–24. http://dx.doi.org/10.1073/pnas.2009224117.
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Neuropeptides are important for regulating numerous neural functions and behaviors. Release of neuropeptides requires long-lasting, high levels of cytosolic Ca2+. However, the molecular regulation of neuropeptide release remains to be clarified. Recently, Stac3 was identified as a key regulator of L-type Ca2+channels (CaChs) and excitation–contraction coupling in vertebrate skeletal muscles. There is a small family ofstacgenes in vertebrates with other members expressed by subsets of neurons in the central nervous system. The function of neural Stac proteins, however, is poorly understood.Drosophila melanogastercontain a singlestacgene,Dstac, which is expressed by muscles and a subset of neurons, including neuropeptide-expressing motor neurons. Here, genetic manipulations, coupled with immunolabeling, Ca2+imaging, electrophysiology, and behavioral analysis, revealed that Dstac regulates L-type CaChs (Dmca1D) inDrosophilamotor neurons and this, in turn, controls the release of neuropeptides.
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Avgan, Nesli, Heidi G. Sutherland, Rod A. Lea, Larisa M. Haupt, David H. K. Shum, and Lyn R. Griffiths. "Association Study of a Comprehensive Panel of Neuropeptide-Related Polymorphisms Suggest Potential Roles in Verbal Learning and Memory." Genes 15, no. 1 (December 24, 2023): 30. http://dx.doi.org/10.3390/genes15010030.
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Neuropeptides are mostly expressed in regions of the brain responsible for learning and memory and are centrally involved in cognitive pathways. The majority of neuropeptide research has been performed in animal models; with acknowledged differences between species, more research into the role of neuropeptides in humans is necessary to understand their contribution to higher cognitive function. In this study, we investigated the influence of genetic polymorphisms in neuropeptide genes on verbal learning and memory. Variants in genes encoding neuropeptides and neuropeptide receptors were tested for association with learning and memory measures using the Hopkins Verbal Learning Test—Revised (HVLT-R) in a healthy cohort of individuals (n = 597). The HVLT-R is a widely used task for verbal learning and memory assessment and provides five sub-scores: recall, delay, learning, retention, and discrimination. To determine the effect of candidate variants on learning and memory performance, genetic association analyses were performed for each HVLT-R sub-score with over 1300 genetic variants from 124 neuropeptide and neuropeptide receptor genes, genotyped on Illumina OmniExpress BeadChip arrays. This targeted analysis revealed numerous suggestive associations between HVLT-R test scores and neuropeptide and neuropeptide receptor gene variants; candidates include the SCG5, IGFR1, GALR1, OXTR, CCK, and VIPR1 genes. Further characterization of these genes and their variants will improve our understanding of the genetic contribution to learning and memory and provide insight into the importance of the neuropeptide network in humans.
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Ramirez, Manuel, Isabel Prieto, Francisco Vives, Marc de Gasparo, and Francisco Alba. "Neuropeptides, Neuropeptidases and Brain Asymmetry." Current Protein & Peptide Science 5, no. 6 (December 1, 2004): 497–506. http://dx.doi.org/10.2174/1389203043379350.
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Shiraishi, Akira, Toshimi Okuda, Natsuko Miyasaka, Tomohiro Osugi, Yasushi Okuno, Jun Inoue, and Honoo Satake. "Repertoires of G protein-coupled receptors for Ciona-specific neuropeptides." Proceedings of the National Academy of Sciences 116, no. 16 (April 1, 2019): 7847–56. http://dx.doi.org/10.1073/pnas.1816640116.
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Neuropeptides play pivotal roles in various biological events in the nervous, neuroendocrine, and endocrine systems, and are correlated with both physiological functions and unique behavioral traits of animals. Elucidation of functional interaction between neuropeptides and receptors is a crucial step for the verification of their biological roles and evolutionary processes. However, most receptors for novel peptides remain to be identified. Here, we show the identification of multiple G protein-coupled receptors (GPCRs) for species-specific neuropeptides of the vertebrate sister group, Ciona intestinalis Type A, by combining machine learning and experimental validation. We developed an original peptide descriptor-incorporated support vector machine and used it to predict 22 neuropeptide–GPCR pairs. Of note, signaling assays of the predicted pairs identified 1 homologous and 11 Ciona-specific neuropeptide–GPCR pairs for a 41% hit rate: the respective GPCRs for Ci-GALP, Ci-NTLP-2, Ci-LF-1, Ci-LF-2, Ci-LF-5, Ci-LF-6, Ci-LF-7, Ci-LF-8, Ci-YFV-1, and Ci-YFV-3. Interestingly, molecular phylogenetic tree analysis revealed that these receptors, excluding the Ci-GALP receptor, were evolutionarily unrelated to any other known peptide GPCRs, confirming that these GPCRs constitute unprecedented neuropeptide receptor clusters. Altogether, these results verified the neuropeptide–GPCR pairs in the protochordate and evolutionary lineages of neuropeptide GPCRs, and pave the way for investigating the endogenous roles of novel neuropeptides in the closest relatives of vertebrates and the evolutionary processes of neuropeptidergic systems throughout chordates. In addition, the present study also indicates the versatility of the machine-learning–assisted strategy for the identification of novel peptide–receptor pairs in various organisms.
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Mochizuki, Takako, Mika Sakamoto, Yasuhiro Tanizawa, Hitomi Seike, Zhen Zhu, Yi Jun Zhou, Keisuke Fukumura, Shinji Nagata, and Yasukazu Nakamura. "Best Practices for Comprehensive Annotation of Neuropeptides of Gryllus bimaculatus." Insects 14, no. 2 (January 25, 2023): 121. http://dx.doi.org/10.3390/insects14020121.
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Genome annotation is critically important data that can support research. Draft genome annotations cover representative genes; however, they often do not include genes that are expressed only in limited tissues and stages, or genes with low expression levels. Neuropeptides are responsible for regulation of various physiological and biological processes. A recent study disclosed the genome draft of the two-spotted cricket Gryllus bimaculatus, which was utilized to understand the intriguing physiology and biology of crickets. Thus far, only two of the nine reported neuropeptides in G. bimaculatus were annotated in the draft genome. Even though de novo assembly using transcriptomic analyses can comprehensively identify neuropeptides, this method does not follow those annotations on the genome locus. In this study, we performed the annotations based on the reference mapping, de novo transcriptome assembly, and manual curation. Consequently, we identified 41 neuropeptides out of 43 neuropeptides, which were reported in the insects. Further, 32 of the identified neuropeptides on the genomic loci in G. bimaculatus were annotated. The present annotation methods can be applicable for the neuropeptide annotation of other insects. Furthermore, the methods will help to generate useful infrastructures for studies relevant to neuropeptides.
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Serafini, Gianluca, Maurizio Pompili, Daniel Lindqvist, Yogesh Dwivedi, and Paolo Girardi. "The Role of Neuropeptides in Suicidal Behavior: A Systematic Review." BioMed Research International 2013 (2013): 1–22. http://dx.doi.org/10.1155/2013/687575.
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There is a growing evidence that neuropeptides may be involved in the pathophysiology of suicidal behavior. A critical review of the literature was conducted to investigate the association between neuropeptides and suicidal behavior. Only articles from peer-reviewed journals were selected for the inclusion in the present review. Twenty-six articles were assessed for eligibility but only 22 studies were included. Most studies have documented an association between suicidality and some neuropeptides such as corticotropin-releasing factor (CRF), VGF, cholecystokinin, substance P, and neuropeptide Y (NPY), which have been demonstrated to act as key neuromodulators of emotional processing. Significant differences in neuropeptides levels have been found in those who have attempted or completed suicide compared with healthy controls or those dying from other causes. Despite cross-sectional associations between neuropeptides levels and suicidal behavior, causality may not be inferred. The implications of the mentioned studies were discussed in this review paper.
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Li, Zi-Hao, Bin Li, Xiao-Yang Zhang, and Jing-Ning Zhu. "Neuropeptides and Their Roles in the Cerebellum." International Journal of Molecular Sciences 25, no. 4 (February 16, 2024): 2332. http://dx.doi.org/10.3390/ijms25042332.
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Although more than 30 different types of neuropeptides have been identified in various cell types and circuits of the cerebellum, their unique functions in the cerebellum remain poorly understood. Given the nature of their diffuse distribution, peptidergic systems are generally assumed to exert a modulatory effect on the cerebellum via adaptively tuning neuronal excitability, synaptic transmission, and synaptic plasticity within cerebellar circuits. Moreover, cerebellar neuropeptides have also been revealed to be involved in the neurogenetic and developmental regulation of the developing cerebellum, including survival, migration, differentiation, and maturation of the Purkinje cells and granule cells in the cerebellar cortex. On the other hand, cerebellar neuropeptides hold a critical position in the pathophysiology and pathogenesis of many cerebellar-related motor and psychiatric disorders, such as cerebellar ataxias and autism. Over the past two decades, a growing body of evidence has indicated neuropeptides as potential therapeutic targets to ameliorate these diseases effectively. Therefore, this review focuses on eight cerebellar neuropeptides that have attracted more attention in recent years and have significant potential for clinical application associated with neurodegenerative and/or neuropsychiatric disorders, including brain-derived neurotrophic factor, corticotropin-releasing factor, angiotensin II, neuropeptide Y, orexin, thyrotropin-releasing hormone, oxytocin, and secretin, which may provide novel insights and a framework for our understanding of cerebellar-related disorders and have implications for novel treatments targeting neuropeptide systems.
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Kong, Xue, Zhen-Xiang Li, Yu-Qing Gao, Fang-Hua Liu, Zhen-Zhen Chen, Hong-Gang Tian, Tong-Xian Liu, Yong-Yu Xu, and Zhi-Wei Kang. "Genome-Wide Identification of Neuropeptides and Their Receptors in an Aphid Endoparasitoid Wasp, Aphidius gifuensi." Insects 12, no. 8 (August 18, 2021): 745. http://dx.doi.org/10.3390/insects12080745.
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In insects, neuropeptides and their receptors not only play a critical role in insect physiology and behavior but also are the potential targets for novel pesticide discoveries. Aphidius gifuensis is one of the most important and widespread aphid parasitoids, and has been successfully used to control aphid. In the present work, we systematically identified neuropeptides and their receptors from the genome and head transcriptome of A. gifuensis. A total of 35 neuropeptide precursors and 49 corresponding receptors were identified. The phylogenetic analyses demonstrated that 35 of these receptors belong to family-A, four belong to family-B, two belong to leucine-rich repeat-containing GPCRs, four belong to receptor guanylyl cyclases, and four belong to receptor tyrosine kinases. Oral ingestion of imidacloprid significantly up-regulated five neuropeptide precursors and four receptors whereas three neuropeptide precursors and eight receptors were significantly down-regulated, which indicated that these neuropeptides and their receptors are potential targets of some commercial insecticides. The RT-qPCR results showed that dopamine receptor 1, dopamine receptor 2, octopamine receptor, allatostatin-A receptor, neuropeptides capa receptor, SIFamide receptor, FMRFamide receptor, tyramine receptor and short neuropeptide F predominantly were expressed in the head whilst the expression of ion transport peptide showed widespread distribution in various tissues. The high expression levels of these genes suggest their important roles in the central nervous system. Taken together, our study provides fundamental information that may further our understanding of neuropeptidergic signaling systems in the regulation of the physiology and behavior of solitary wasps. Furthermore, this information could also aid in the design and discovery of specific and environment-friendly insecticides.
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Chalmers, John, Vimal Kapoor, Eric Mills, Jane Minson, Margaret Morris, Paul Pilowsky, and Malcolm West. "Do pressor neurons in the ventrolateral medulla release amines and neuropeptides?" Canadian Journal of Physiology and Pharmacology 65, no. 8 (August 1, 1987): 1598–604. http://dx.doi.org/10.1139/y87-251.
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Activation of neurons arising in the rostral ventrolateral medulla evokes a pressor response in the rat and the rabbit. This region of the medulla gives rise to bulbospinal neurons containing many different neurotransmitters, including amines such as adrenaline, noradrenaline and serotonin, and neuropeptides such as substance P and neuropeptide Y. Colocalization of amines and neuropeptides has been described in some neurons descending from the rostral ventrolateral medulla. In this paper we discuss the evidence that bulbospinal serotonin-containing neurons (B3) and adrenaline-containing neurons (C1) arising from this part of the medulla exert pressor effects by distinct central pathways and conclude that they do. We also consider the possibility that the pressor effects of activating these two groups of neurons are associated with release of neuropeptides and highlight evidence that substance P is released into the spinal cord by activation of descending serotonin-containing neurons, while neuropeptide Y may be released by activation of bulbospinal adrenaline-containing neurons.
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Bodea, Alina, and Amorin Remus Popa. "Orectic And Anorectic Peptides And Their Implication In Obesity And The Metabolic Syndrome." Romanian Journal of Diabetes Nutrition and Metabolic Diseases 22, no. 2 (June 1, 2015): 187–91. http://dx.doi.org/10.1515/rjdnmd-2015-0023.
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AbstractBackground and aims: Cardiovascular diseases, diabetes mellitus, the metabolic syndrome and obesity are now globally widespread clinical conditions, addressing different ages, lately extending to young and children. The causes are multiple, involving an interaction between individual genetic risk factors and environmental factors. Many studies showed the importance of the hypothalamic neuropeptides and other neuropeptides in the regulation of the balance between food intake and energy consumption. We reviewed 25 recent research studies describing the physiological and physiopathological mechanisms of the orectic and anorectic peptides and their interaction to adjust the balance between food intake and energy expenditure.Conclusions: The hypothalamus, through its nuclei (arcuate and paraventricular) controls the balance between food intake and energy expenditure. The proopiomelanocortin (POMC) / Cocaine and amphetamine-related transcript (CART) neurons represent the anorectic centre. The neurons that release neuropeptide Y (NPY) and agouti-related protein (AgRP) by stimulation form the orectic centre. The neuropeptide Y (NPY) is the main hypothalamic orectic neuropeptide. Its action, besides stimulating the orectic effect, is to modulate the release of other hypothalamic orectic and anorectic neuropeptides. In addition, the energy balance is regulated by adipokines released by the adipose cells, hormones and neurotransmitters, blood glucose level and other metabolites.
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Puri, Sudan, Brendan M. Kenyon, and Pedram Hamrah. "Immunomodulatory Role of Neuropeptides in the Cornea." Biomedicines 10, no. 8 (August 16, 2022): 1985. http://dx.doi.org/10.3390/biomedicines10081985.
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The transparency of the cornea along with its dense sensory innervation and resident leukocyte populations make it an ideal tissue to study interactions between the nervous and immune systems. The cornea is the most densely innervated tissue of the body and possesses both immune and vascular privilege, in part due to its unique repertoire of resident immune cells. Corneal nerves produce various neuropeptides that have a wide range of functions on immune cells. As research in this area expands, further insights are made into the role of neuropeptides and their immunomodulatory functions in the healthy and diseased cornea. Much remains to be known regarding the details of neuropeptide signaling and how it contributes to pathophysiology, which is likely due to complex interactions among neuropeptides, receptor isoform-specific signaling events, and the inflammatory microenvironment in disease. However, progress in this area has led to an increase in studies that have begun modulating neuropeptide activity for the treatment of corneal diseases with promising results, necessitating the need for a comprehensive review of the literature. This review focuses on the role of neuropeptides in maintaining the homeostasis of the ocular surface, alterations in disease settings, and the possible therapeutic potential of targeting these systems.
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Solway, J., and A. R. Leff. "Sensory neuropeptides and airway function." Journal of Applied Physiology 71, no. 6 (December 1, 1991): 2077–87. http://dx.doi.org/10.1152/jappl.1991.71.6.2077.
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Sensory nerves synthesize tachykinins and calcitonin-gene related peptide and package these neuropeptides together in synaptic vesicles. Stimulation of these C-fibers by a range of chemical and physical factors results in afferent neuronal conduction that elicits central parasympathetic reflexes and in antidromic conduction that results in local release of neuropeptides through the axon reflex. In the airways, sensory neuropeptides act on bronchial smooth muscle, the mucosal vasculature, and submucosal glands to promote airflow obstruction, hyperemia, microvascular hyperpermeability, and mucus hypersecretion. In addition, tachykinins potentiate cholinergic neurotransmission. Proinflammatory effects of these peptides also promote the recruitment, adherence, and activation of granulocytes that may further exacerbate neurogenic inflammation (i.e., neuropeptide-induced plasma extravasation and vasodilation). Enzymatic degradation limits the physiological effects of tachykinins but may be impaired by respiratory infection or other factors. Given their sensitivity to noxious compounds and physical stimuli and their potent effects on airway function, it is possible that neuropeptide-containing sensory nerves play an important role in mediating airway responses in human disease. Supporting this view are the striking phenomenological similarities between hyperpnea-induced bronchoconstriction (HIB) in guinea pigs and HIB in patients with exercise-induced asthma. Endogenous tachykinins released from airway sensory nerves mediate HIB in guinea pigs and also cause hyperpnea-induced bronchovascular hyperpermeability in these animals. On the basis of these observations, it is reasonable to speculate that sensory neuropeptides participate in the pathogenesis of hyperpnea-induced airflow obstruction in human asthmatic subjects as well.
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de Wied, D. "Neuropeptides as psychotropic drugs." Acta Neuropsychiatrica 4, no. 1 (March 1992): 1–7. http://dx.doi.org/10.1017/s0924270800034931.
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SummaryNeuropeptides are endogenous substances present in nerve cells and involved in nervous system functions. Neuropeptides are synthetized in large precursor proteins and several are formed in the same precursor. Neuropeptides affect learning and memory processes, social, sexual and maternal behavior, pain and addiction, body temperature, food and water intake e.a. In addition, neuropeptides possess trophic influences on the nervous system, neuroleptic-like andpsychostimulant-like activities. Disturbances in classical neurotransmitter activity as found in Parkinson's disease, psychoses, and dementia, may also be caused by disturbances in neuropeptide activity. In fact, alterations in the concentration of a number of neuropeptides in schizophrenia, depression, and dementia have been found.Much work has been done during the last decade on the influence of neuropeptides in schizophrenia, autism, depression, and in various disorders associated with memory disturbances. These studies concern neuropeptides related to adrenocorticotropic hormone (ACTH) and melanocyte stimulating hormone (MSH), vasopressin- and endorphin-type neuropeptides, thyrotropic releasing hormone (TRH), and the C-terminal part of oxytocin Pro-Leu-Gly-NH2 (PLG). Several of these exert positive effects but in not more than 25% the response is clinically relevant. This may have to do with the severity of the disease and its chronicity. The modest effects may also be caused by the poor bioavailability of peptides and insufficient pharmacotherapeutic experience regarding dose, and duration of treatment.
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Petrescu, Anca D., Su Yeon An, Juliet Venter, Matthew McMillin, and Sharon DeMorrow. "The Role of Hypothalamic Neuropeptides in Regulation of Liver Functions in Health and Disease." Endocrines 4, no. 2 (June 20, 2023): 457–87. http://dx.doi.org/10.3390/endocrines4020034.
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The communication between brain and peripheral tissues is mediated by neuropeptides that coordinate the functions of each organ with the activities of the entire body in specific environmental conditions. Hypothalamic neuropeptides act as neurotransmitters and hormones to regulate the physiology of food intake, digestion, and metabolism, having a direct or indirect impact on the liver. Investigations on liver pathologies found that dysfunctions of neuropeptides and their receptors are associated with liver disorders such as non-alcoholic fatty liver disease, steatohepatitis, cholestasis, cirrhosis, and liver cancer. In this article, we reviewed neuropeptides that regulate energy homeostasis and lipid and glucose metabolism in the liver and are associated with liver injuries. Firstly, peptides involved in regulatory processes in the brain and liver, such as neuropeptide Y, agouti-related protein, and the galanin family, are related to obesity and its comorbidities, including type 2 diabetes and metabolic syndrome, are presented. Secondly, a comprehensive review of neuropeptides such as secretin, vasoactive intestinal peptide, substance P, and somatostatin, which are involved in liver injuries unrelated to obesity; i.e., cholestasis-induced biliary hyperplasia, cirrhosis, hepatocellular carcinoma, and cholangiocarcinoma, is also presented. The cellular and molecular mechanisms underlining liver injuries related to the dysfunction of these neuropeptides and receptors are also described.
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Muschter, Dominique, Anna-Sophie Beiderbeck, Tanja Späth, Christian Kirschneck, Agnes Schröder, and Susanne Grässel. "Sensory Neuropeptides and their Receptors Participate in Mechano-Regulation of Murine Macrophages." International Journal of Molecular Sciences 20, no. 3 (January 24, 2019): 503. http://dx.doi.org/10.3390/ijms20030503.
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This study aimed to analyze if the sensory neuropeptide SP (SP) and the neurokinin receptor 1 (NK1R) are involved in macrophage mechano-transduction, similar to chondrocytes, and if alpha-calcitonin gene-related peptide (αCGRP) and the CGRP receptor (CRLR/Ramp1) show comparable activity. Murine RAW264.7 macrophages were subjected to a cyclic stretch for 1–3 days and 4 h/day. Loading and neuropeptide effects were analyzed for gene and protein expression of neuropeptides and their receptors, adhesion, apoptosis, proliferation and ROS activity. Murine bone marrow-derived macrophages (BMM) were isolated after surgical osteoarthritis (OA) induction and proliferation, apoptosis and osteoclastogenesis were analyzed in response to loading. Loading induced NK1R and CRLR/Ramp1 gene expression and altered protein expression in RAW264.7 macrophages. SP protein and mRNA level decreased after loading whereas αCGRP mRNA expression was stabilized. SP reduced adhesion in loaded RAW264.7 macrophages and both neuropeptides initially increased the ROS activity followed by a time-dependent suppression. OA induction sensitized BMM to caspase 3/7 mediated apoptosis after loading. Both sensory neuropeptides, SP and αCGRP, and their receptors are involved in murine macrophage mechano-transduction affecting neuropeptide impact on adhesion and ROS activity. OA induction altered BMM apoptosis in response to loading indicate that OA-associated biomechanical alterations might affect the macrophage population.
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Martinez, C., M. Delgado, R. P. Gomariz, and D. Ganea. "Vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide-38 inhibit IL-10 production in murine T lymphocytes." Journal of Immunology 156, no. 11 (June 1, 1996): 4128–36. http://dx.doi.org/10.4049/jimmunol.156.11.4128.
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Abstract Vasoactive intestinal peptide (VIP), a neuropeptide present in the peptidergic innervation of lymphoid organs and expressed in thymocytes and peripheral lymphocytes has been previously reported to modulate cytokine expression in T lymphocytes. In this study, we investigated the effects of VIP and of the structurally related neuropeptide PACAP-38 on the expression of IL-10 in murine lymphocyte cultures. Both neuropeptides inhibit IL-10 production by spleen cells or thymocytes activated via the TCR-associated CD3 complex in a similar dose-response manner. The inhibition is specific, presumably mediated through the VIP-R1, and maximum inhibitory levels are achieved within the first 5 to 15 min of exposure to VIP or PACAP-38. CD4+ T cells function as direct cellular targets for the two neuropeptides. The fact that VIP, PACAP-38, and forskolin, all known cAMP inducers, also inhibit IL-10 production, suggests the participation of cAMP in signal transduction. VIP and PACAP-38 regulate transcriptional expression of IL-10, since IL-10 steady state mRNA levels are significantly reduced by treatment with the two neuropeptides. These results expand the range of neuroendocrine-regulated cytokines and support the idea that neuropeptides such as VIP and PACAP, which are released or produced in the local lymphoid microenvironment and specifically modulate the expression of various cytokines, may participate in the intricate cytokine network controlling local immune responses.
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Mo, Chenmi, and Lei Zhang. "Unraveling the Roles of Neuropeptides in the Chemosensation of the Root-Knot Nematode Meloidogyne javanica." International Journal of Molecular Sciences 25, no. 12 (June 7, 2024): 6300. http://dx.doi.org/10.3390/ijms25126300.
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The identification of novel drug targets in plant-parasitic nematodes (PPNs) is imperative due to the loss of traditional nematicides and a lack of replacements. Chemosensation, which is pivotal for PPNs in locating host roots, has become a focus in nematode behavioral research. However, its underlying molecular basis is still indistinct in such a diverse group of PPNs. To characterize genes participating in chemosensation in the Javanese root-knot nematode Meloidogyne javanica, RNA-sequencing of the second-stage juveniles (J2s) treated with tomato root exudate (TRE) for 1 h and 6 h was performed. Genes related to chemosensation in M. javanica mainly responded to TRE treatment at 1 h. Moreover, a gene ontology (GO) analysis underscored the significance of the neuropeptide G protein-coupled receptor signaling pathway. Consequently, the repertoire of putative neuropeptides in M. javanica, including FMRFamide-like peptides (FLPs), insulin-like peptides (ILPs), and neuropeptide-like peptides (NLPs), were outlined based on a homology analysis. The gene Mjflp-14a, harboring two neuropeptides, was significantly up-regulated at 1 h TRE treatment. Through peptide synthesis and J2 treatment, one of the two neuropeptides (MjFLP-14-2) was proven to influence the J2 chemotaxis towards tomato root tips. Overall, our study reinforces the potential of nematode neuropeptides as novel targets and tools for root-knot nematode control.
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Petrella, Carla, Maria Grazia Di Certo, Christian Barbato, Francesca Gabanella, Massimo Ralli, Antonio Greco, Roberta Possenti, and Cinzia Severini. "Neuropeptides in Alzheimer’s Disease: An Update." Current Alzheimer Research 16, no. 6 (July 23, 2019): 544–58. http://dx.doi.org/10.2174/1567205016666190503152555.
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Neuropeptides are small proteins broadly expressed throughout the central nervous system, which act as neurotransmitters, neuromodulators and neuroregulators. Growing evidence has demonstrated the involvement of many neuropeptides in both neurophysiological functions and neuropathological conditions, among which is Alzheimer’s disease (AD). The role exerted by neuropeptides in AD is endorsed by the evidence that they are mainly neuroprotective and widely distributed in brain areas responsible for learning and memory processes. Confirming this point, it has been demonstrated that numerous neuropeptide-containing neurons are pathologically altered in brain areas of both AD patients and AD animal models. Furthermore, the levels of various neuropeptides have been found altered in both Cerebrospinal Fluid (CSF) and blood of AD patients, getting insights into their potential role in the pathophysiology of AD and offering the possibility to identify novel additional biomarkers for this pathology. We summarized the available information about brain distribution, neuroprotective and cognitive functions of some neuropeptides involved in AD. The main focus of the current review was directed towards the description of clinical data reporting alterations in neuropeptides content in both AD patients and AD pre-clinical animal models. In particular, we explored the involvement in the AD of Thyrotropin-Releasing Hormone (TRH), Cocaine- and Amphetamine-Regulated Transcript (CART), Cholecystokinin (CCK), bradykinin and chromogranin/secretogranin family, discussing their potential role as a biomarker or therapeutic target, leaving the dissertation of other neuropeptides to previous reviews.
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Pearce, Eiluned, Rafael Wlodarski, Anna Machin, and Robin I. M. Dunbar. "Variation in the β-endorphin, oxytocin, and dopamine receptor genes is associated with different dimensions of human sociality." Proceedings of the National Academy of Sciences 114, no. 20 (May 1, 2017): 5300–5305. http://dx.doi.org/10.1073/pnas.1700712114.
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There is growing evidence that the number and quality of social relationships have substantial impacts on health, well-being, and longevity, and, at least in animals, on reproductive fitness. Although it is widely recognized that these outcomes are mediated by a number of neuropeptides, the roles these play remain debated. We suggest that an overemphasis on one neuropeptide (oxytocin), combined with a failure to distinguish between different social domains, has obscured the complexity involved. We use variation in 33 SNPs for the receptor genes for six well-known social neuropeptides in relation to three separate domains of sociality (social disposition, dyadic relationships, and social networks) to show that three neuropeptides (β-endorphin, oxytocin, and dopamine) play particularly important roles, with each being associated predominantly with a different social domain. However, endorphins and dopamine have a much wider compass than oxytocin (whose effects are confined to romantic/reproductive relationships and often do not survive control for other neuropeptides). In contrast, vasopressin, serotonin, and testosterone play only limited roles.
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Gao, Zhengyin, Weng I. Lei, and Leo Tsz On Lee. "The Role of Neuropeptide-Stimulated cAMP-EPACs Signalling in Cancer Cells." Molecules 27, no. 1 (January 5, 2022): 311. http://dx.doi.org/10.3390/molecules27010311.
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Neuropeptides are autocrine and paracrine signalling factors and mainly bind to G protein-coupled receptors (GPCRs) to trigger intracellular secondary messenger release including adenosine 3′, 5′-cyclic monophosphate (cAMP), thus modulating cancer progress in different kind of tumours. As one of the downstream effectors of cAMP, exchange proteins directly activated by cAMP (EPACs) play dual roles in cancer proliferation and metastasis. More evidence about the relationship between neuropeptides and EPAC pathways have been proposed for their potential role in cancer development; hence, this review focuses on the role of neuropeptide/GPCR system modulation of cAMP/EPACs pathways in cancers. The correlated downstream pathways between neuropeptides and EPACs in cancer cell proliferation, migration, and metastasis is discussed to glimmer the direction of future research.
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Bakos, Jan, Martina Zatkova, Zuzana Bacova, and Daniela Ostatnikova. "The Role of Hypothalamic Neuropeptides in Neurogenesis and Neuritogenesis." Neural Plasticity 2016 (2016): 1–10. http://dx.doi.org/10.1155/2016/3276383.
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The hypothalamus is a source of neural progenitor cells which give rise to different populations of specialized and differentiated cells during brain development. Newly formed neurons in the hypothalamus can synthesize and release various neuropeptides. Although term neuropeptide recently undergoes redefinition, small-size hypothalamic neuropeptides remain major signaling molecules mediating short- and long-term effects on brain development. They represent important factors in neurite growth and formation of neural circuits. There is evidence suggesting that the newly generated hypothalamic neurons may be involved in regulation of metabolism, energy balance, body weight, and social behavior as well. Here we review recent data on the role of hypothalamic neuropeptides in adult neurogenesis and neuritogenesis with special emphasis on the development of food intake and social behavior related brain circuits.
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Bülbül, Mehmet, and R. Alberto Travagli. "Novel transmitters in brain stem vagal neurocircuitry: new players on the pitch." American Journal of Physiology-Gastrointestinal and Liver Physiology 315, no. 1 (July 1, 2018): G20—G26. http://dx.doi.org/10.1152/ajpgi.00059.2018.
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The last few decades have seen a major increase in the number of neurotransmitters and neuropeptides recognized as playing a role in brain stem neurocircuits, including those involved in homeostatic functions such as stress responsiveness, gastrointestinal motility, feeding, and/or arousal/wakefulness. This minireview will focus on the known physiological role of three of these novel neuropeptides, i.e., apelin, nesfatin-1, and neuropeptide-S, with a special emphasis on their hypothetical roles in vagal signaling related to gastrointestinal motor functions.
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Zandawala, Meet, Ismail Moghul, Luis Alfonso Yañez Guerra, Jérôme Delroisse, Nikara Abylkassimova, Andrew F. Hugall, Timothy D. O'Hara, and Maurice R. Elphick. "Discovery of novel representatives of bilaterian neuropeptide families and reconstruction of neuropeptide precursor evolution in ophiuroid echinoderms." Open Biology 7, no. 9 (September 2017): 170129. http://dx.doi.org/10.1098/rsob.170129.
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Neuropeptides are a diverse class of intercellular signalling molecules that mediate neuronal regulation of many physiological and behavioural processes. Recent advances in genome/transcriptome sequencing are enabling identification of neuropeptide precursor proteins in species from a growing variety of animal taxa, providing new insights into the evolution of neuropeptide signalling. Here, detailed analysis of transcriptome sequence data from three brittle star species, Ophionotus victoriae , Amphiura filiformis and Ophiopsila aranea , has enabled the first comprehensive identification of neuropeptide precursors in the class Ophiuroidea of the phylum Echinodermata. Representatives of over 30 bilaterian neuropeptide precursor families were identified, some of which occur as paralogues. Furthermore, homologues of endothelin/CCHamide, eclosion hormone, neuropeptide-F/Y and nucleobinin/nesfatin were discovered here in a deuterostome/echinoderm for the first time. The majority of ophiuroid neuropeptide precursors contain a single copy of a neuropeptide, but several precursors comprise multiple copies of identical or non-identical, but structurally related, neuropeptides. Here, we performed an unprecedented investigation of the evolution of neuropeptide copy number over a period of approximately 270 Myr by analysing sequence data from over 50 ophiuroid species, with reference to a robust phylogeny. Our analysis indicates that the composition of neuropeptide ‘cocktails’ is functionally important, but with plasticity over long evolutionary time scales.
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Chandrasekharan, Bindu, Behtash Ghazi Nezami, and Shanthi Srinivasan. "Emerging neuropeptide targets in inflammation: NPY and VIP." American Journal of Physiology-Gastrointestinal and Liver Physiology 304, no. 11 (June 1, 2013): G949—G957. http://dx.doi.org/10.1152/ajpgi.00493.2012.
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The enteric nervous system (ENS), referred to as the “second brain,” comprises a vast number of neurons that form an elegant network throughout the gastrointestinal tract. Neuropeptides produced by the ENS play a crucial role in the regulation of inflammatory processes via cross talk with the enteric immune system. In addition, neuropeptides have paracrine effects on epithelial secretion, thus regulating epithelial barrier functions and thereby susceptibility to inflammation. Ultimately the inflammatory response damages the enteric neurons themselves, resulting in deregulations in circuitry and gut motility. In this review, we have emphasized the concept of neurogenic inflammation and the interaction between the enteric immune system and enteric nervous system, focusing on neuropeptide Y (NPY) and vasoactive intestinal peptide (VIP). The alterations in the expression of NPY and VIP in inflammation and their significant roles in immunomodulation are discussed. We highlight the mechanism of action of these neuropeptides on immune cells, focusing on the key receptors as well as the intracellular signaling pathways that are activated to regulate the release of cytokines. In addition, we also examine the direct and indirect mechanisms of neuropeptide regulation of epithelial tight junctions and permeability, which are a crucial determinant of susceptibility to inflammation. Finally, we also discuss the potential of emerging neuropeptide-based therapies that utilize peptide agonists, antagonists, siRNA, oligonucleotides, and lentiviral vectors.
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Cajado-Carvalho, Daniela, Cristiane da Silva, Roberto Kodama, Douglas Mariano, Daniel Pimenta, Bruno Duzzi, Alexandre Kuniyoshi, and Fernanda Portaro. "Purification and Biochemical Characterization of TsMS 3 and TsMS 4: Neuropeptide-Degrading Metallopeptidases in the Tityus serrulatus Venom." Toxins 11, no. 4 (March 31, 2019): 194. http://dx.doi.org/10.3390/toxins11040194.
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Although omics studies have indicated presence of proteases on the Tityus serrulatus venom (TsV), little is known about the function of these molecules. The TsV contains metalloproteases that cleave a series of human neuropeptides, including the dynorphin A (1-13) and the members of neuropeptide Y family. Aiming to isolate the proteases responsible for this activity, the metalloserrulase 3 and 4 (TsMS 3 and TsMS 4) were purified after two chromatographic steps and identified by mass spectrometry analysis. The biochemical parameters (pH, temperature and cation effects) were determined for both proteases, and the catalytic parameters (Km, kcat, cleavage sites) of TsMS 4 over fluorescent substrate were obtained. The metalloserrulases have a high preference for cleaving neuropeptides but presented different primary specificities. For example, the Leu-enkephalin released from dynorphin A (1-13) hydrolysis was exclusively performed by TsMS 3. Neutralization assays using Butantan Institute antivenoms show that both metalloserrulases were well blocked. Although TsMS 3 and TsMS 4 were previously described through cDNA library studies using the venom gland, this is the first time that both these toxins were purified. Thus, this study represents a step further in understanding the mechanism of scorpion venom metalloproteases, which may act as possible neuropeptidases in the envenomation process.
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Lundy, F. T., and G. J. Linden. "Neuropeptides and Neurogenic Mechanisms in Oral and Periodontal Inflammation." Critical Reviews in Oral Biology & Medicine 15, no. 2 (March 2004): 82–98. http://dx.doi.org/10.1177/154411130401500203.
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It is generally accepted that the nervous system contributes to the pathophysiology of peripheral inflammation, and a neurogenic component has been implicated in many inflammatory diseases, including periodontitis. Neurogenic inflammation should be regarded as a protective mechanism, which forms the first line of defense and protects tissue integrity. However, severe or prolonged noxious stimulation may result in the inflammatory response mediating injury rather than facilitating repair. This review focuses on the accumulating evidence suggesting that neuropeptides have a pivotal role in the complex cascade of chemical activity associated with periodontal inflammation. An overview of neuropeptide synthesis and release introduces the role of neuropeptides and their interactions with other inflammatory factors, which ultimately lead to neurogenic inflammation. The biological effects of the neuropeptides substance P (SP), calcitonin gene-related peptide (CGRP), vasoactive intestinal polypeptide (VIP), and neuropeptide Y (NPY) are summarized, and evidence for their involvement in the localized inflammatory lesions which characterize periodontitis is presented. In this context, the role of CGRP in bone metabolism is described in more detail. Recent research highlighting the role of the nervous system in suppressing pain and inflammation is also discussed.
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Taghert, Paul H. "FMRFamide neuropeptides and neuropeptide-associated enzymes inDrosophila." Microscopy Research and Technique 45, no. 2 (April 15, 1999): 80–95. http://dx.doi.org/10.1002/(sici)1097-0029(19990415)45:2<80::aid-jemt3>3.0.co;2-x.
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Li, Honghao, Liangzhen Jiang, Kaixiang Yang, Shulin Shang, Mingxin Li, and Zhibin Lv. "iNP_ESM: Neuropeptide Identification Based on Evolutionary Scale Modeling and Unified Representation Embedding Features." International Journal of Molecular Sciences 25, no. 13 (June 27, 2024): 7049. http://dx.doi.org/10.3390/ijms25137049.
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Neuropeptides are biomolecules with crucial physiological functions. Accurate identification of neuropeptides is essential for understanding nervous system regulatory mechanisms. However, traditional analysis methods are expensive and laborious, and the development of effective machine learning models continues to be a subject of current research. Hence, in this research, we constructed an SVM-based machine learning neuropeptide predictor, iNP_ESM, by integrating protein language models Evolutionary Scale Modeling (ESM) and Unified Representation (UniRep) for the first time. Our model utilized feature fusion and feature selection strategies to improve prediction accuracy during optimization. In addition, we validated the effectiveness of the optimization strategy with UMAP (Uniform Manifold Approximation and Projection) visualization. iNP_ESM outperforms existing models on a variety of machine learning evaluation metrics, with an accuracy of up to 0.937 in cross-validation and 0.928 in independent testing, demonstrating optimal neuropeptide recognition capabilities. We anticipate improved neuropeptide data in the future, and we believe that the iNP_ESM model will have broader applications in the research and clinical treatment of neurological diseases.
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Edvinsson, L., and PJ Goadsby. "Neuropeptides in the Cerebral Circulation: Relevance to Headache." Cephalalgia 15, no. 4 (August 1995): 272–76. http://dx.doi.org/10.1046/j.1468-2982.1995.1504272.x.
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The article briefly describes the innervation of the human cerebral circulation by nerve fibers containing neuropeptide Y (NPY), vasoactive intestinal peptide (VIP), substance P (SP), and calcitonin gent-related peptide (CGRP). The neuropeptides in human cerebral arteries were characterized by radioimmunoassay in combination with HPLC. These neuropeptides mediate contraction (NPY) and dilatation (VIP, SP, CGRP). In conjunction with spontaneous attacks of migraine or cluster headache, release of CGRP is seen. With the associated symptoms of nasal congestion and rhinorrhea, VIP is released. Successful treatment may abort the peptide release in parallel with disappearance of headache.
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Kuspiel, Sven, Dominik Wiemuth, and Stefan Gründer. "The Neuropeptide Nocistatin Is Not a Direct Agonist of Acid-Sensing Ion Channel 1a (ASIC1a)." Biomolecules 11, no. 4 (April 13, 2021): 571. http://dx.doi.org/10.3390/biom11040571.
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Acid-sensing ion channels (ASICs) are ionotropic receptors that are directly activated by protons. Although protons have been shown to act as a neurotransmitter and to activate ASICs during synaptic transmission, it remains a possibility that other ligands directly activate ASICs as well. Neuropeptides are attractive candidates for alternative agonists of ASICs, because related ionotropic receptors are directly activated by neuropeptides and because diverse neuropeptides modulate ASICs. Recently, it has been reported that the neuropeptide nocistatin directly activates ASICs, including ASIC1a. Here we show that nocistatin does not directly activate ASIC1a expressed in Xenopus oocytes or CHO cells. Moreover, we show that nocistatin acidifies the bath solution to an extent that can fully explain the previously reported activation by this highly acidic peptide. In summary, we conclude that nocistatin only indirectly activates ASIC1a via acidification of the bath solution.
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Southey, Bruce R., and Sandra L. Rodriguez-Zas. "Changes in Neuropeptide Prohormone Genes among Cetartiodactyla Livestock and Wild Species Associated with Evolution and Domestication." Veterinary Sciences 9, no. 5 (May 23, 2022): 247. http://dx.doi.org/10.3390/vetsci9050247.
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The impact of evolution and domestication processes on the sequences of neuropeptide prohormone genes that participate in cell–cell signaling influences multiple biological process that involve neuropeptide signaling. This information is important to understand the physiological differences between Cetartiodactyla domesticated species such as cow, pig, and llama and wild species such as hippopotamus, giraffes, and whales. Systematic analysis of changes associated with evolutionary and domestication forces in neuropeptide prohormone protein sequences that are processed into neuropeptides was undertaken. The genomes from 118 Cetartiodactyla genomes representing 22 families were mined for 98 neuropeptide prohormone genes. Compared to other Cetartiodactyla suborders, Ruminantia preserved PYY2 and lost RLN1. Changes in GNRH2, IAPP, INSL6, POMC, PRLH, and TAC4 protein sequences could result in the loss of some bioactive neuropeptides in some families. An evolutionary model suggested that most neuropeptide prohormone genes disfavor sequence changes that incorporate large and hydrophobic amino acids. A compelling finding was that differences between domestic and wild species are associated with the molecular system underlying ‘fight or flight’ responses. Overall, the results demonstrate the importance of simultaneously comparing the neuropeptide prohormone gene complement from close and distant-related species. These findings broaden the foundation for empirical studies about the function of the neuropeptidome associated with health, behavior, and food production.
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DARMER, Dorothea, Frank HAUSER, Hans-Peter NOTHACKER, Thomas C. G. BOSCH, Michael WILLIAMSON, and Cornelis J. P. GRIMMELIKHUIJZEN. "Three different prohormones yield a variety of Hydra-RFamide (Arg-Phe-NH2) neuropeptides in Hydra magnipapillata." Biochemical Journal 332, no. 2 (June 1, 1998): 403–12. http://dx.doi.org/10.1042/bj3320403.
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The freshwater polyp Hydra is the most frequently used model for the study of development in cnidarians. Recently we isolated four novel Arg-Phe-NH2 (RFamide) neuropeptides, the Hydra-RFamides I–IV, from Hydra magnipapillata. Here we describe the molecular cloning of three different preprohormones from H. magnipapillata, each of which gives rise to a variety of RFamide neuropeptides. Preprohormone A contains one copy of unprocessed Hydra-RFamide I (QWLGGRFG), II (QWFNGRFG), III/IV [(KP)HLRGRFG] and two putative neuropeptide sequences (QLMSGRFG and QLMRGRFG). Preprohormone B has the same general organization as preprohormone A, but instead of unprocessed Hydra-RFamide III/IV it contains a slightly different neuropeptide sequence [(KP)HYRGRFG]. Preprohormone C contains one copy of unprocessed Hydra-RFamide I and seven additional putative neuropeptide sequences (with the common N-terminal sequence QWF/LSGRFGL). The two Hydra-RFamide II copies (in preprohormones A and B) are preceded by Thr residues, and the single Hydra-RFamide III/IV copy (in preprohormone A) is preceded by an Asn residue, confirming that cnidarians use unconventional processing signals to generate neuropeptides from their precursor proteins. Southern blot analyses suggest that preprohormones A and B are each coded for by a single gene, whereas one or possibly two closely related genes code for preprohormone C. Northern blot analyses and in situ hybridizations show that the gene coding for preprohormone A is expressed in neurons of both the head and foot regions of Hydra, whereas the genes coding for preprohormones B and C are specifically expressed in neurons of different regions of the head. All of this shows that neuropeptide biosynthesis in the primitive metazoan Hydra is already rather complex.
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Lee, James Siho, Pei-Yin Shih, Oren N. Schaedel, Porfirio Quintero-Cadena, Alicia K. Rogers, and Paul W. Sternberg. "FMRFamide-like peptides expand the behavioral repertoire of a densely connected nervous system." Proceedings of the National Academy of Sciences 114, no. 50 (November 22, 2017): E10726—E10735. http://dx.doi.org/10.1073/pnas.1710374114.
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Animals, including humans, can adapt to environmental stress through phenotypic plasticity. The free-living nematode Caenorhabditis elegans can adapt to harsh environments by undergoing a whole-animal change, involving exiting reproductive development and entering the stress-resistant dauer larval stage. The dauer is a dispersal stage with dauer-specific behaviors for finding and stowing onto carrier animals, but how dauers acquire these behaviors, despite having a physically limited nervous system of 302 neurons, is poorly understood. We compared dauer and reproductive development using whole-animal RNA sequencing at fine time points and at sufficient depth to measure transcriptional changes within single cells. We detected 8,042 genes differentially expressed during dauer and reproductive development and observed striking up-regulation of neuropeptide genes during dauer entry. We knocked down neuropeptide processing using sbt-1 mutants and demonstrate that neuropeptide signaling promotes the decision to enter dauer rather than reproductive development. We also demonstrate that during dauer neuropeptides modulate the dauer-specific nictation behavior (carrier animal-hitchhiking) and are necessary for switching from repulsion to CO2 (a carrier animal cue) in nondauers to CO2 attraction in dauers. We tested individual neuropeptides using CRISPR knockouts and existing strains and demonstrate that the combined effects of flp-10 and flp-17 mimic the effects of sbt-1 on nictation and CO2 attraction. Through meta-analysis, we discovered similar up-regulation of neuropeptides in the dauer-like infective juveniles of diverse parasitic nematodes, suggesting the antiparasitic target potential of SBT-1. Our findings reveal that, under stress, increased neuropeptide signaling in C. elegans enhances their decision-making accuracy and expands their behavioral repertoire.
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Werner, Felix-Martin, and Rafael Coveñas. "Neural Networks in Generalized Epilepsy and Novel Antiepileptic Drugs." Current Pharmaceutical Design 25, no. 4 (June 3, 2019): 396–400. http://dx.doi.org/10.2174/1381612825666190319121505.
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Background:In previous works, alterations of neurotransmitters and neuropeptides in the brain areas involved in generalized epilepsy have been reported.Objective:We reviewed the alterations of these neurotransmitters and neuropeptides in the following brain areas involved in generalized epilepsy: hippocampus, hypothalamus, thalamus and cerebral cortex. In these brain areas, the neural networks are also actualized. The mechanisms of action of newer antiepileptic drugs in the treatment of generalized epilepsy are also discussed.Results:Up-dating the neurotransmitter and neuropeptide alterations, we found that hippocampal GABAergic neurons presynaptically inhibit epileptogenic neurons via GABAB receptors. Epilepsy modulating neuropeptides (galanin, neuropeptide Y, dynorphin) are also involved. GABA deficiency, serotonin hyperactivity, dopamine hyperactivity and glutamate excitotoxicity can enhance ictogenesis: neurons containing these neurotransmitters form the main neural circuit. An increased excitability occurs when the alteration of these neurotransmitters is permanent.Conclusion:In preclinical studies, the GABAB receptor agonist GS 39,783 exerted a good antiepileptic effect. Perampanel, an AMPA receptor antagonist, showed good clinical effects in the treatment of partial-onset seizures and primary generalized tonic-clonic seizures. In this treatment, perampanel can be combined with other antiepileptic drugs. Brivaracetam, which shows a high affinity for the synaptic vesicle 2A, exerted a good efficacy in the treatment of adult focal seizures and secondarily generalized tonic-clonic seizures.
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Guo, Yichen, Yawen Cheng, Jiaqi An, Yi Qi, and Guogang Luo. "Neuropeptide changes in an improved migraine model with repeat stimulations." Translational Neuroscience 12, no. 1 (January 1, 2021): 523–32. http://dx.doi.org/10.1515/tnsci-2020-0201.
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Abstract Migraine is a medical condition with a severe recursive headache. The activation of the trigeminovascular system is an important mechanism. The neuropeptide calcitonin gene-related peptide (CGRP) plays a crucial role in the pathogenesis of migraine. Several other neuropeptides are also involved; however, their roles in migraine remain unclear. In this study, using a rat model of migraine induced by electrical stimulation of the trigeminal ganglia (TG) and an improved version induced with repeated stimulation, we observed the dynamic changes of these peptides in TG and blood. We demonstrated that the expression of CGRP, pituitary adenylate cyclase activating polypeptide (PACAP), neuropeptide Y (NPY), vasoactive intestinal peptide, and nociceptin in TG was significantly elevated and peaked at different time points after a single stimulation. Their levels in the blood plasma were significantly increased at 12 h after stimulation. The peptides were further elevated with repeated stimulation. The improved rat model of migraine with repeated stimulation of TG resulted in a more pronounced elevation of CGRP, PACAP, and NPY. Thus, the dynamic changes in neuropeptides after stimulation suggest that these neuropeptides may play an important role in the pathogenesis of migraine. Additionally, the migraine model with repetitive stimulation would be a novel model for future research.