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1
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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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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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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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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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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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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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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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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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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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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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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Zheng, Yingqiu, Xiao Cong, Huachen Liu, Yixin Wang, Kenneth B. Storey, and Muyan Chen. "Nervous System Development and Neuropeptides Characterization in Embryo and Larva: Insights from a Non-Chordate Deuterostome, the Sea Cucumber Apostichopus japonicus." Biology 11, no. 10 (October 20, 2022): 1538. http://dx.doi.org/10.3390/biology11101538.
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Here, we described the complex nervous system at five early developmental stages (blastula, gastrula, auricularia, doliolaria and pentactula) of a holothurian species with highly economic value, Apostichopus japonicus. The results revealed that the nervous system of embryos and larvae is mainly distributed in the anterior apical region, ciliary bands or rings, and the feeding and attachment organs, and that serotonergic immunoreactivity was not observed until the embryo developed into the late gastrula; these are evolutionarily conserved features of echinoderm, hemichordate and protostome larvae. Furthermore, based on available transcriptome data, we reported the neuropeptide precursors profile at different embryonic and larval developmental stages. This analysis showed that 40 neuropeptide precursors present in adult sea cucumbers were also identified at different developmental stages of embryos and larvae, and only four neuropeptide precursors (SWYG precursor 2, GYWKDLDNYVKAHKT precursor, Neuropeptide precursor 14-like precursor, GLRFAmprecursor-like precursor) predicted in adults were absent in embryos and larvae. Combining the quantitative expression of ten specific neuropeptide precursor genes (NPs) by qRT-PCR, we revealed the potential important roles of neuropeptides in embryo development, feeding and attachment in A. japonicus larvae. In conclusion, this work provides novel perspectives on the diverse physiological functions of neuropeptides and contributes to understanding the evolution of neuropeptidergic systems in echinoderm embryos and larvae.
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Mateos-Hernández, Lourdes, Natália Pipová, Eléonore Allain, Céline Henry, Clotilde Rouxel, Anne-Claire Lagrée, Nadia Haddad, et al. "Enlisting the Ixodes scapularis Embryonic ISE6 Cell Line to Investigate the Neuronal Basis of Tick—Pathogen Interactions." Pathogens 10, no. 1 (January 14, 2021): 70. http://dx.doi.org/10.3390/pathogens10010070.
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Neuropeptides are small signaling molecules expressed in the tick central nervous system, i.e., the synganglion. The neuronal-like Ixodes scapularis embryonic cell line, ISE6, is an effective tool frequently used for examining tick–pathogen interactions. We detected 37 neuropeptide transcripts in the I. scapularis ISE6 cell line using in silico methods, and six of these neuropeptide genes were used for experimental validation. Among these six neuropeptide genes, the tachykinin-related peptide (TRP) of ISE6 cells varied in transcript expression depending on the infection strain of the tick-borne pathogen, Anaplasma phagocytophilum. The immunocytochemistry of TRP revealed cytoplasmic expression in a prominent ISE6 cell subpopulation. The presence of TRP was also confirmed in A. phagocytophilum-infected ISE6 cells. The in situ hybridization and immunohistochemistry of TRP of I. scapularis synganglion revealed expression in distinct neuronal cells. In addition, TRP immunoreaction was detected in axons exiting the synganglion via peripheral nerves as well as in hemal nerve-associated lateral segmental organs. The characterization of a complete Ixodes neuropeptidome in ISE6 cells may serve as an effective in vitro tool to study how tick-borne pathogens interact with synganglion components that are vital to tick physiology. Therefore, our current study is a potential stepping stone for in vivo experiments to further examine the neuronal basis of tick–pathogen interactions.
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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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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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Fehér, Erzsébet. "Neuropeptid Y és P anyag immunreaktív idegrostok és immunkompetens sejtek változása hepatitisben." Orvosi Hetilap 156, no. 47 (November 2015): 1892–97. http://dx.doi.org/10.1556/650.2015.30300.
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Neuropeptide Y and substance P were thought to play a role in the function of immune cells and in amplification or elimination of the inflammatory processes. In hepatitis the number of both neuropeptide Y and substance P immunoreactive nerve fibres are increased, where the increase of neoropeptide Y is significant. A large number of lymphocytes and mast cells are also stained for neuropeptide Y and substance P. Very close associations (less than 1 µm) were observed between neuropeptide Y immunoreactive nerve fibres and immune cells stained also with neuropeptide Y. Some immune cells were also found to be immunoreactive for tumor necrosis factor-α and NF-κB. Some of the SP IR immunocells were also stained for TNF-α and nuclear factor kappaB. Based on these data it is hypothesized that neuropeptid Y and substance P released from nerve fibres and immune cells play a role in inflammation and elimination of inflammation in hepatitis. Orv. Hetil., 2015, 156(47), 1892–1897.
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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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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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Vörös, Imre, Zsófia Onódi, Viktória Éva Tóth, Tamás G. Gergely, Éva Sághy, Anikó Görbe, Ágnes Kemény, et al. "Saxagliptin Cardiotoxicity in Chronic Heart Failure: The Role of DPP4 in the Regulation of Neuropeptide Tone." Biomedicines 10, no. 7 (July 1, 2022): 1573. http://dx.doi.org/10.3390/biomedicines10071573.
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Dipeptidyl-peptidase-4 (DPP4) inhibitors are novel medicines for diabetes. The SAVOR-TIMI-53 clinical trial revealed increased heart-failure-associated hospitalization in saxagliptin-treated patients. Although this side effect could limit therapeutic use, the mechanism of this potential cardiotoxicity is unclear. We aimed to establish a cellular platform to investigate DPP4 inhibition and the role of its neuropeptide substrates substance P (SP) and neuropeptide Y (NPY), and to determine the expression of DDP4 and its neuropeptide substrates in the human heart. Western blot, radio-, enzyme-linked immuno-, and RNA scope assays were performed to investigate the expression of DPP4 and its substrates in human hearts. Calcein-based viability measurements and scratch assays were used to test the potential toxicity of DPP4 inhibitors. Cardiac expression of DPP4 and NPY decreased in heart failure patients. In human hearts, DPP4 mRNA is detectable mainly in cardiomyocytes and endothelium. Treatment with DPP4 inhibitors alone/in combination with neuropeptides did not affect viability but in scratch assays neuropeptides decreased, while saxagliptin co-administration increased fibroblast migration in isolated neonatal rat cardiomyocyte-fibroblast co-culture. Decreased DPP4 activity takes part in the pathophysiology of end-stage heart failure. DPP4 compensates against the elevated sympathetic activity and altered neuropeptide tone. Its inhibition decreases this adaptive mechanism, thereby exacerbating myocardial damage.
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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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Klose, Markus K., Marcel P. Bruchez, David L. Deitcher, and Edwin S. Levitan. "Temporally and spatially partitioned neuropeptide release from individual clock neurons." Proceedings of the National Academy of Sciences 118, no. 17 (April 19, 2021): e2101818118. http://dx.doi.org/10.1073/pnas.2101818118.
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Neuropeptides control rhythmic behaviors, but the timing and location of their release within circuits is unknown. Here, imaging in the brain shows that synaptic neuropeptide release by Drosophila clock neurons is diurnal, peaking at times of day that were not anticipated by prior electrical and Ca2+ data. Furthermore, hours before peak synaptic neuropeptide release, neuropeptide release occurs at the soma, a neuronal compartment that has not been implicated in peptidergic transmission. The timing disparity between release at the soma and terminals results from independent and compartmentalized mechanisms for daily rhythmic release: consistent with conventional electrical activity–triggered synaptic transmission, terminals require Ca2+ influx, while somatic neuropeptide release is triggered by the biochemical signal IP3. Upon disrupting the somatic mechanism, the rhythm of terminal release and locomotor activity period are unaffected, but the number of flies with rhythmic behavior and sleep–wake balance are reduced. These results support the conclusion that somatic neuropeptide release controls specific features of clock neuron–dependent behaviors. Thus, compartment-specific mechanisms within individual clock neurons produce temporally and spatially partitioned neuropeptide release to expand the peptidergic connectome underlying daily rhythmic behaviors.
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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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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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Colmers, William F., and Bouchaïb El Bahh. "Neuropeptide Y and Epilepsy." Epilepsy Currents 3, no. 2 (March 2003): 53–58. http://dx.doi.org/10.1111/j.1535-7597.2003.03208.x.
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It is a central tenet of the epilepsy field that seizures result from the imbalance of excitation over inhibition ( 1 ). The bulk of excitation is mediated by the neurotransmitter glutamate, whereas inhibition results mainly from the actions of γ-aminobutyric acid (GABA). In the neocortex and hippocampus, the intrinsic sources of GABA are the interneurons, which lately have come under intense scrutiny. It has become clear that a large number of distinct types of interneurons can be differentiated in part by the array of neuropeptides they coexpress (cf. 2). Evidence is emerging that the neuropeptide complement of interneurons plays important roles in the way that interneurons regulate excitability. Here we discuss what is known about the relation of one well-characterized neuropeptide, neuropeptide Y (NPY), and epilepsy in experimental animals and humans, and suggest possible roles for the receptors as targets for the control of excessive excitation in epilepsy.
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Ma, Tianlu, Shinya Matsuoka, and Daniela Drummond-Barbosa. "RNAi-based screens uncover a potential new role for the orphan neuropeptide receptor Moody in Drosophila female germline stem cell maintenance." PLOS ONE 15, no. 12 (December 11, 2020): e0243756. http://dx.doi.org/10.1371/journal.pone.0243756.
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Reproduction is highly sensitive to changes in physiology and the external environment. Neuropeptides are evolutionarily conserved signaling molecules that regulate multiple physiological processes. However, the potential reproductive roles of many neuropeptide signaling pathways remain underexplored. Here, we describe the results of RNAi-based screens in Drosophila melanogaster to identify neuropeptides/neuropeptide receptors with potential roles in oogenesis. The screen read-outs were either the number of eggs laid per female per day over time or fluorescence microscopy analysis of dissected ovaries. We found that the orphan neuropeptide receptor encoded by moody (homologous to mammalian melatonin receptors) is likely required in somatic cells for normal egg production and proper germline stem cell maintenance. However, the egg laying screens had low signal-to-noise ratio and did not lead to the identification of additional candidates. Thus, although egg count assays might be useful for large-scale screens to identify oogenesis regulators that result in dramatic changes in oogenesis, more labor-intensive microscopy-based screen are better applicable for identifying new physiological regulators of oogenesis with more subtle phenotypes.
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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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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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Cadena-Caballero, Cristian E., Nestor Munive-Argüelles, Lina M. Vera-Cala, Carlos Barrios-Hernandez, Ruben O. Duarte-Bernal, Viviana L. Ayus-Ortiz, Luis A. Pardo-Díaz, et al. "APGW/AKH Precursor from Rotifer Brachionus plicatilis and the DNA Loss Model Explain Evolutionary Trends of the Neuropeptide LWamide, APGWamide, RPCH, AKH, ACP, CRZ, and GnRH Families." Journal of Molecular Evolution 91, no. 6 (December 2023): 882–96. http://dx.doi.org/10.1007/s00239-023-10146-9.
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AbstractIn the year 2002, DNA loss model (DNA-LM) postulated that neuropeptide genes to emerged through codons loss via the repair of damaged DNA from ancestral gene namely Neuropeptide Precursor Predictive (NPP), which organization correspond two or more neuropeptides precursors evolutive related. The DNA-LM was elaborated according to amino acids homology among LWamide, APGWamide, red pigment-concentrating hormone (RPCH), adipokinetic hormones (AKHs) and in silico APGW/RPCH NPPAPGW/AKH NPP were proposed. With the above principle, it was proposed the evolution of corazonin (CRZ), gonadotropin-releasing hormone (GnRH), AKH, and AKH/CRZ (ACP), but any NPP never was considered. However, the evolutive relation via DNA-LM among these neuropeptides precursors not has been established yet. Therefore, the transcriptomes from crabs Callinectes toxotes and Callinectes arcuatus were used to characterized ACP and partial CRZ precursors, respectively. BLAST alignment with APGW/RPCH NPP and APGW/AKH NPP allow identified similar NPP in the rotifer Brachionus plicatilis and other invertebrates. Moreover, three bioinformatics algorithms and manual verification were used to purify 13,778 sequences, generating a database with 719 neuropeptide precursors. Phylogenetic trees with the DNA-LM parameters showed that some ACP, CRZ, AKH2 and two NPP share nodes with GnRH from vertebrates and some of this neuropeptide had nodes in invertebrates. Whereas the phylogenetic tree with standard parameters do not showed previous node pattern. Robinson-Foulds metric corroborates the differences among phylogenetic trees. Homology relationship showed four putative orthogroups; AKH4, CRZ, and protostomes GnRH had individual group. This is the first demonstration of NPP in species and would explain the evolution neuropeptide families by the DNA-LM.
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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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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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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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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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Sharma, Suresh D., Gayatri Raghuraman, Myeong-Seon Lee, Nanduri R. Prabhakar, and Ganesh K. Kumar. "Intermittent hypoxia activates peptidylglycine α-amidating monooxygenase in rat brain stem via reactive oxygen species-mediated proteolytic processing." Journal of Applied Physiology 106, no. 1 (January 2009): 12–19. http://dx.doi.org/10.1152/japplphysiol.90702.2008.
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Intermittent hypoxia (IH) associated with sleep apneas leads to cardiorespiratory abnormalities that may involve altered neuropeptide signaling. The effects of IH on neuropeptide synthesis have not been investigated. Peptidylglycine α-amidating monooxygenase (PAM; EC 1.14.17.3) catalyzes the α-amidation of neuropeptides, which confers biological activity to a large number of neuropeptides. PAM consists of O2-sensitive peptidylglycine α-hydroxylating monooxygenase (PHM) and peptidyl-α-hydroxyglycine α-amidating lyase (PAL) activities. Here, we examined whether IH alters neuropeptide synthesis by affecting PAM activity and, if so, by what mechanisms. Experiments were performed on the brain stem of adult male rats exposed to IH (5% O2for 15 s followed by 21% O2for 5 min; 8 h/day for up to 10 days) or continuous hypoxia (0.4 atm for 10 days). Analysis of brain stem extracts showed that IH, but not continuous hypoxia, increased PHM, but not PAL, activity of PAM and that the increase of PHM activity was associated with a concomitant elevation in the levels of α-amidated forms of substance P and neuropeptide Y. IH increased the relative abundance of 42- and 35-kDa forms of PHM (∼1.6- and 2.7-fold, respectively), suggesting enhanced proteolytic processing of PHM, which appears to be mediated by an IH-induced increase of endoprotease activity. Kinetic analysis showed that IH increases Vmaxbut has no effect on Km. IH increased generation of reactive oxygen species in the brain stem, and systemic administration of antioxidant prevented IH-evoked increases of PHM activity, proteolytic processing of PHM, endoprotease activity, and elevations in substance P and neuropeptide Y amide levels. Taken together, these results demonstrate that IH activates PHM in rat brain stem via reactive oxygen species-dependent posttranslational proteolytic processing and further suggest that PAM activation may contribute to IH-mediated peptidergic neurotransmission in rat brain stem.
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Nosova, Olga, Igor Bazov, Victor Karpyak, Mathias Hallberg, and Georgy Bakalkin. "Epigenetic and Transcriptional Control of the Opioid Prodynorphine Gene: In-Depth Analysis in the Human Brain." Molecules 26, no. 11 (June 7, 2021): 3458. http://dx.doi.org/10.3390/molecules26113458.
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Neuropeptides serve as neurohormones and local paracrine regulators that control neural networks regulating behavior, endocrine system and sensorimotor functions. Their expression is characterized by exceptionally restricted profiles. Circuit-specific and adaptive expression of neuropeptide genes may be defined by transcriptional and epigenetic mechanisms controlled by cell type and subtype sequence-specific transcription factors, insulators and silencers. The opioid peptide dynorphins play a critical role in neurological and psychiatric disorders, pain processing and stress, while their mutations cause profound neurodegeneration in the human brain. In this review, we focus on the prodynorphin gene as a model for the in-depth epigenetic and transcriptional analysis of expression of the neuropeptide genes. Prodynorphin studies may provide a framework for analysis of mechanisms relevant for regulation of neuropeptide genes in normal and pathological human brain.
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Semmens, Dean C., Olivier Mirabeau, Ismail Moghul, Mahesh R. Pancholi, Yannick Wurm, and Maurice R. Elphick. "Transcriptomic identification of starfish neuropeptide precursors yields new insights into neuropeptide evolution." Open Biology 6, no. 2 (February 2016): 150224. http://dx.doi.org/10.1098/rsob.150224.
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Neuropeptides are evolutionarily ancient mediators of neuronal signalling in nervous systems. With recent advances in genomics/transcriptomics, an increasingly wide range of species has become accessible for molecular analysis. The deuterostomian invertebrates are of particular interest in this regard because they occupy an ‘intermediate' position in animal phylogeny, bridging the gap between the well-studied model protostomian invertebrates (e.g. Drosophila melanogaster , Caenorhabditis elegans ) and the vertebrates. Here we have identified 40 neuropeptide precursors in the starfish Asterias rubens , a deuterostomian invertebrate from the phylum Echinodermata . Importantly, these include kisspeptin-type and melanin-concentrating hormone-type precursors, which are the first to be discovered in a non-chordate species. Starfish tachykinin-type, somatostatin-type, pigment-dispersing factor-type and corticotropin-releasing hormone-type precursors are the first to be discovered in the echinoderm/ambulacrarian clade of the animal kingdom. Other precursors identified include vasopressin/oxytocin-type, gonadotropin-releasing hormone-type, thyrotropin-releasing hormone-type, calcitonin-type, cholecystokinin/gastrin-type, orexin-type, luqin-type, pedal peptide/orcokinin-type, glycoprotein hormone-type, bursicon-type, relaxin-type and insulin-like growth factor-type precursors. This is the most comprehensive identification of neuropeptide precursor proteins in an echinoderm to date, yielding new insights into the evolution of neuropeptide signalling systems. Furthermore, these data provide a basis for experimental analysis of neuropeptide function in the unique context of the decentralized, pentaradial echinoderm bauplan.
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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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Schéle, Erik, Louise Grahnemo, Fredrik Anesten, Anna Hallén, Fredrik Bäckhed, and John-Olov Jansson. "The Gut Microbiota Reduces Leptin Sensitivity and the Expression of the Obesity-Suppressing Neuropeptides Proglucagon (Gcg) and Brain-Derived Neurotrophic Factor (Bdnf) in the Central Nervous System." Endocrinology 154, no. 10 (October 1, 2013): 3643–51. http://dx.doi.org/10.1210/en.2012-2151.
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The gut microbiota contributes to fat mass and the susceptibility to obesity. However, the underlying mechanisms are not completely understood. To investigate whether the gut microbiota affects hypothalamic and brainstem body fat-regulating circuits, we compared gene expression of food intake-regulating neuropeptides between germ-free and conventionally raised (CONV-R) mice. We found that CONV-R mice had decreased expression of the antiobesity neuropeptide glucagon-like peptide-1 (GLP-1) precursor proglucagon (Gcg) in the brainstem. Moreover, in both the hypothalamus and the brainstem, CONV-R mice had decreased expression of the antiobesity neuropeptide brain-derived neurotrophic factor (Bdnf). CONV-R mice had reduced expression of the pro-obesity peptides neuropeptide-Y (Npy) and agouti-related protein (Agrp), and increased expression of the antiobesity peptides proopiomelanocortin (Pomc) and cocaine- and amphetamine-regulated transcript (Cart) in the hypothalamus. The latter changes in neuropeptide expression could be secondary to elevated fat mass in CONV-R mice. Leptin treatment caused less weight reduction and less suppression of orexigenic Npy and Agrp expression in CONV-R mice compared with germ-free mice. The hypothalamic expression of leptin resistance-associated suppressor of cytokine signaling 3 (Socs-3) was increased in CONV-R mice. In conclusion, the gut microbiota reduces the expression of 2 genes coding for body fat-suppressing neuropeptides, Gcg and Bdnf, an alteration that may contribute to fat mass induction by the gut microbiota. Moreover, the presence of body fat-inducing gut microbiota is associated with hypothalamic signs of Socs-3-mediated leptin resistance, which may be linked to failed compensatory body fat reduction.
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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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Wang, Ying, Juanjuan Kang, Ning Li, Yuwei Zhou, Zhongjie Tang, Bifang He, and Jian Huang. "NeuroCS: A Tool to Predict Cleavage Sites of Neuropeptide Precursors." Protein & Peptide Letters 27, no. 4 (March 17, 2020): 337–45. http://dx.doi.org/10.2174/0929866526666191112150636.
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Background: Neuropeptides are a class of bioactive peptides produced from neuropeptide precursors through a series of extremely complex processes, mediating neuronal regulations in many aspects. Accurate identification of cleavage sites of neuropeptide precursors is of great significance for the development of neuroscience and brain science. Objective: With the explosive growth of neuropeptide precursor data, it is pretty much needed to develop bioinformatics methods for predicting neuropeptide precursors’ cleavage sites quickly and efficiently. Method : We started with processing the neuropeptide precursor data from SwissProt and NueoPedia into two sets of data, training dataset and testing dataset. Subsequently, six feature extraction schemes were applied to generate different feature sets and then feature selection methods were used to find the optimal feature subset of each. Thereafter the support vector machine was utilized to build models for different feature types. Finally, the performance of models were evaluated with the independent testing dataset. Results: Six models are built through support vector machine. Among them the enhanced amino acid composition-based model reaches the highest accuracy of 91.60% in the 5-fold cross validation. When evaluated with independent testing dataset, it also showed an excellent performance with a high accuracy of 90.37% and Area under Receiver Operating Characteristic curve up to 0.9576. Conclusion: The performance of the developed model was decent. Moreover, for users’ convenience, an online web server called NeuroCS is built, which is freely available at http://i.uestc.edu.cn/NeuroCS/dist/index.html#/. NeuroCS can be used to predict neuropeptide precursors’ cleavage sites effectively.
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Zhang, Lin, Fang Yang, Jinhong Cai, Chunmei Huang, Zhengkun Wang, and Wanlong Zhu. "The role of photoperiod on the expression of hypothalamic genes regulating appetite in Chevrier’s field mouse (Apodemus chevrieri)." Animal Biology 65, no. 1 (2015): 45–56. http://dx.doi.org/10.1163/15707563-00002460.
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The hypothalamus and leptin play a key role in the regulation of food intake. The present study investigated the effects of 4 weeks of short- or long-photoperiod on serum leptin levels and food intake in relation to mRNA expression levels of neuropeptide Y, agouti-related protein, pro-opiomelanocortin, and cocaine- and amphetamine-regulated transcript in the hypothalamus of Chevrier’s field mouse (Apodemus chevrieri). There was a significant difference in body fat mass, food intake and neuropeptide Y mRNA expression between the two groups, but serum leptin level, agouti-related protein, pro-opiomelanocortin, and cocaine- and amphetamine-regulated transcript mRNA expression in the hypothalamus were not difference between the two groups. The elevation of neuropeptide Y mRNA regulated neuropeptides in the hypothalamus suggests a physiological role of neuroendocrine factors in food intake during the different photoperiod. We conclude that leptin may be involved in energy balance and body mass regulation.
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Bascal, Z. A., A. Montgomery, L. Holden-Dye, R. G. Williams, M. C. Thorndyke, and R. J. Walker. "NADPH diaphorase activity in peptidergic neurones of the parasitic nematode, Ascaris suum." Parasitology 112, no. 1 (January 1996): 125–34. http://dx.doi.org/10.1017/s0031182000065161.
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SUMMARYThe histochemical marker for nitric oxide synthase, NADPH diaphorase, is known to co-localize in mammalian neurones with various classical neurotransmitters and neuropeptides. The nervous system of the parasitic nematode Ascaris suum has previously been shown to contain both NADPH diaphorase activity and neuropeptide immunoreactivity. This study examined the possibility that NADPH diaphorase and neuropeptide immunoreactivity may co-exist in the same neurones. Two antisera were used, one raised to KYSALMFamide, a C-terminal synthetic analogue of SALMFamide 1 (GFNSALMFamide), and another that recognizes calcitonin-gene-related peptide (CGRP). We provide evidence that in a distinct subset of neurones in the ventral, dorsal and lateral ganglia NADPH diaphorase staining and SALMFamide- like immunoreactivity are co-localized, suggesting a possible role for nitric oxide in modulating neuropeptide activity in these regions. CGRP-like immunoreactivity was less widely distributed, and was not consistently co-localized with NADPH diaphorase.
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Bowker, Robert M., Raymond H. Abhold, John P. Caron, Ioana M. Sonea, Kelly B. Vex, and Rebecca Kotyk. "Neuropeptidergic innervation of equine synovial joints." American Journal of Veterinary Research 54, no. 11 (November 1, 1993): 1831–39. http://dx.doi.org/10.2460/ajvr.1993.54.11.1831.
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Summary Immunocytochemical analysis of equine synovial membranes revealed presence of several neuropeptides, including substance P (sp), neurokinin A, and neuropeptide Y, in nerves of the radiocarpal, middle carpal, and metacarpophalangeal (fetlock) joints. Within the subsynovium, these neuropeptides were located perivascularly, whereas in the fronds, only neuropeptide Y was restricted to the vessels of the synovial membrane. Only sp and neurokinin A were found in the intimal layer. The intimal layer of the metacarpophalangeal joint contained more sp-immunoreactive fibers than were observed in the intimal layer of the radiocarpal joint. Substance P also was detected in the synovial fluid from all 3 joints, but mean ± sd concentrations were significantly different only between the middle carpal joint (37.56 ± 5.48 fmol/ml; n = 6) and the metacarpophalangeal joint (55.80 ± 8.33 fmol/ml; n = 5) and between the middle carpal joint and the radiocarpal joint (52.43 ± 14.60 fmol/ml; n = 7).
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KISHIMOTO, Takeshi. "Neuropeptides and neuropeptide receptors in stroked gerbil brain." Okayama Igakkai Zasshi (Journal of Okayama Medical Association) 97, no. 9-10 (1985): 913–25. http://dx.doi.org/10.4044/joma1947.97.9-10_913.
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Feng, Jiao, Sinda Lepetre-Mouelhi, Anne Gautier, Simona Mura, Catherine Cailleau, François Coudore, Michel Hamon, and Patrick Couvreur. "A new painkiller nanomedicine to bypass the blood-brain barrier and the use of morphine." Science Advances 5, no. 2 (February 2019): eaau5148. http://dx.doi.org/10.1126/sciadv.aau5148.
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The clinical use of endogenous neuropeptides has historically been limited due to pharmacokinetic issues, including plasma stability and blood-brain barrier permeability. In this study, we show that the rapidly metabolized Leu-enkephalin (LENK) neuropeptide may become pharmacologically efficient owing to a simple conjugation with the lipid squalene (SQ). The corresponding LENK-SQ bioconjugates were synthesized using different chemical linkers in order to modulate the LENK release after their formulation into nanoparticles. This new SQ-based nanoformulation prevented rapid plasma degradation of LENK and conferred on the released neuropeptide a notable antihyperalgesic effect that lasted longer than after treatment with morphine in a rat model of inflammation (Hargreaves test). The biodistribution study as well as the use of brain-permeant and -impermeant opioid receptor antagonists indicated that LENK-SQ NPs act through peripherally located opioid receptors. This study represents a novel nanomedicine approach, allowing the specific delivery of LENK neuropeptide into inflamed tissues for pain control.
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Ertl, G., B. Bauer, H. H. Becker, and G. Rose. "Effects of neurotensin and neuropeptide Y on coronary circulation and myocardial function in dogs." American Journal of Physiology-Heart and Circulatory Physiology 264, no. 4 (April 1, 1993): H1062—H1068. http://dx.doi.org/10.1152/ajpheart.1993.264.4.h1062.
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This study analyzed the effects of the neuropeptides, neurotensin, and human and porcine analogue, neuropeptide Y, in anesthetized open-chest dogs. The left anterior descending coronary artery was cannulated and perfused at constant pressure via a blood reservoir. Flow to the coronary cannula was measured by an electromagnetic flowmeter, and regional segment lengths were measured by sonomicrometer crystals. Neurotensin injected into the coronary cannula resulted in a dose-dependent increase of coronary flow; neuropeptide Y resulted in a decrease of coronary flow. Because these changes in flow were not explained by systemic hemodynamic effects or alterations in regional myocardial function, they were considered to be coronary dilatation or constriction. Coronary dilatation by neurotensin was not prevented by alpha- or beta-adrenoceptor blockade but was completely abolished by indomethacin or by lowering coronary perfusion pressure to 35 mmHg when depressed systolic segment shortening indicated myocardial ischemia. Coronary constriction by neuropeptides Y persisted at coronary perfusion pressure of 35 mmHg and was only attenuated by indomethacin. We conclude that in contrast to systemic effects, coronary vasodilatation by neurotensin is mediated by a prostanoid product of cyclooxygenase. Preactivation of the prostaglandin system may explain why neurotensin lost its coronary dilator effect during myocardial ischemia. Neuropeptide Y may elicit coronary constriction in addition to mechanic reduction of coronary flow resembling severe coronary stenosis.
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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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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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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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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.