Search Results (22)

Gut microbiota have a significant impact neurotransmitters, short-chain fatty acids (SCFAs), immune signaling molecules, and gut hormones. These signaling molecules interact with receptors on the gut wall, immune cells, or the enteric nervous system (ENS), and reach the central nervous system (CNS) via the Vagus nerve (VN). SCFAs interact with G protein-coupled receptors (GPCRs), Toll-like receptors (TLRs), and proliferator-activated receptors (PPARs), influencing inflammatory reactions, gut motility, nutrient absorption, hormone secretion, neurochemical signaling, and brain functions. Olfactory receptor OR51E1 influences blood pressure, vascular reactivity, and arterial stiffness. Activation of the brainstem nucleus tractus solitarius (NTS) by glucagon-like peptide 1 (GLP-1) influences mood, cognition, and gastrointestinal motility. Prolactin-releasing peptide (PrRP) binds to its receptor (PrRPR), suppressing food intake, and regulating stress, cardiovascular reactions, and circadian rhythms. In-depth studies on how gut microbiota control cognitive behavior, mood, and neuropsychiatric disorders are lacking. G protein receptor 119 (GPR119) suppresses appetite and may find an application in the treatment of type 2 diabetes and obesity. The binding of butyrate to nuclear factor kappa B (NF-κB) and proliferator-activated receptor γ (PPARγ) regulates the production of pro-and anti-inflammatory cytokines. This suppresses protein CD36, preventing the uptake of oxidized low-density lipoprotein (ox-LDL) and cardiovascular diseases (CVDs). This review focuses on a few prominent health conditions related to CVDs, i.e., metabolic syndrome (MetS), cancer, and brain functions. Information in this review is based on animal and preclinical studies published in repositories such as PubMed, the National Institutes of Health (NIH), NIH PubChem, ScienceDirect, MDPI, Frontiers, Cell Press, and the CAS Content Collection. Full article

Maternal behavior encompasses a range of biologically driven responses whose expression and duration vary across species. Maternal responses rely on robust adaptive changes in the female brain, enabling mothers to engage in caregiving, nourishing, and offspring protection. Morphological and functional changes in the maternal brain enhance sensitivity to offspring cues, eliciting maternal behaviors, rewarding responses, and social processing stimuli essential for parenting. Maternal behavior comprises a range of biological responses that extend beyond basic actions, reflecting a complex, evolutionarily shaped neurobiological adaptation. These behaviors can be broadly categorized into direct behaviors, which are explicitly aimed at the care of the offspring, and indirect behaviors that, overall, ensure the protection, nourishment, and survival of the newborn. The secretion of main neuropeptide hormones, such as oxytocin (OT), prolactin (PRL), and placental lactogens (PLs), during the peripartum period, is relevant for inducing and regulating maternal responses to offspring cues, including suckling behavior. Although PRL is primarily associated with reproductive and parental functions in vertebrates, it also modulates distinct neural functions during pregnancy that extend from lactogenesis to adult neurogenesis, neuroprotection, and neuroplasticity, all of which contribute to preparing the maternal brain for motherhood and parenting interactions. Parvocellular OT-containing neurons in the paraventricular nucleus (PVN) and in the anterior hypothalamic nucleus (AHN) project axon collaterals to the medial preoptic area, which, in turn, projects to the nucleus accumbens (NACC) and lateral habenula (lHb) via the retrorubral field (RRF) and the ventral tegmental area (VTA), which mediate the motivational aspects of maternal responses to offspring cues. The reshaping process of the brain and neural networks implicated in motherhood depends on several factors, such as up- and downregulation of neuronal gene expression of bioactive peptide hormones (i.e., OT, PRL, TIP-39, galanin, spexin, pituitary adenylate cyclase-activating polypeptide (PACAP), corticotropin-releasing hormone (CRH), peptide receptors, and transcription factors (i.e., c-fos and pSTAT)) in target neurons in hypothalamic nuclei, mesolimbic areas, the hippocampus, and the brainstem, which, overall, regulate the expression of maternal behavior to offspring cues, as shown in postpartum female rodents. In this review, we describe the modulatory neuropeptides, the neural networks underlying peptide transmission systems, and cell signaling involved in parenthood. We highlight the dysregulation of neuropeptide hormones and their receptors in the central nervous system in relation to psychiatric disorders. Full article

Prolactin-releasing peptide (PrRP) has a regulatory role in both acute and chronic stress, suggesting its potential contribution to stress-related disorders such as depression. However, not all individuals with depression respond equally to stressors. We aimed to determine whether the PrRP system could underlie stress coping, an important aspect of depression. The forced swim test was used both as a stressor and as a method to assess coping strategy. Based on immobility time, active coping and passive coping subgroups were identified, and 10 brain regions were studied using qPCR to measure the mRNA expression levels of PrRP and its receptors (specific: GPR10; non-specific: NPFFR2). Passive coping animals spent more time in an immobile posture and exhibited altered mRNA expression levels in the medullary A1 region, the habenula, and the arcuate nucleus than control or active coping rats. Additionally, we identified corticotropin-releasing hormone and vesicular glutamate transporter 2 positive neurons in the A1 medullary region that contained Prrp, suggesting a modulatory role of PrRP in these excitatory neurons involved in stress regulation. Our findings reinforce the hypothesis that PrRP plays a role in stress coping, a process closely linked to depression. However its effect is brain region-specific. Full article

Off-season breeding is a method of encouraging animals through manual intervention to reproduce during the non-breeding season. The egg-laying period of the Zhedong white goose usually starts from September and ends in April of the following year. During the summer months from May to August, with long daylight hours and high temperatures, the white geese rest and do not lay eggs. This study explored the effects of off-season breeding on egg production performance, serum biochemical indicators, and hormone secretion in Zhedong white goose. The experiment was divided into normal breeding and off-seasonal breeding. The results suggested that the peak laying period lasted 3 months, and egg production was 15.62% higher than that in the control group in the off-season breeding group. The off-season breeding group had a 4.13% higher egg fertilization rate in November (laying period) than the control group, and the hatching rate of hatched eggs and fertilized eggs in the peak laying period was 2.77% and 2.3% higher, respectively, than the control group. The experimental group showed significantly higher serum P, ALB (albumin), TG (triglyceride), and TC (total cholesterol) levels; serum AST (glutamic oxalacetic transaminase) activity; and CREA (creatinine) and BUN (blood urea nitrogen) levels than the control group at different time points. The serum LH (luteinizing hormone), FSH (follicle-stimulating hormone), P4 (progesterone), and E2 (estradiol) levels were significantly higher in the off-season breeding group than in the control group. The serum T3 (triiodothyronine) and T4 (Tetraiodothyronine) levels were significantly higher in the off-season breeding group than in the control group at different points in the breeding cycle. The control group showed a significantly higher gene expression of GnRH (gonadotropin releasing hormone) in the hypothalamus; GnRH, FSH, and LH in the pituitary; and GnRH in the ovary and significantly lower gene expression of VIP (vasoactine intestinal peptide) and PRL (prolactin) in the pituitary than the off-season breeding group. Thus, the off-season breeding of Zhedong white geese may prolong the peak laying period and improve egg production performance, thus enhancing the economic benefits of goose breeding. Full article

This review provides a comprehensive analysis of the pelvic plexus and its regulation across various mammalian species, including rats, cats, dogs, and pigs. The pelvic and hypogastric nerves play crucial roles in regulating pelvic functions such as micturition, defecation, and erection. The anatomical organization of these nerves varies, forming either well-defined ganglia or complex plexuses. Despite these variations, the neurons within these structures are consistently regulated by key neurotransmitters, norepinephrine and acetylcholine. These neurons also possess receptors for testosterone and prolactin, particularly in rats, indicating the significant role of these hormones in neuronal function and development. Moreover, neuropeptides such as vasoactive intestinal peptide (VIP), substance P, neuropeptide Y (NPY), somatostatin (SOM), galanin (GAL), and calcitonin gene-related peptide (CGRP) are co-released with neurotransmitters to modulate pelvic functions. This review highlights the complex interplay between neurotransmitters, neuropeptides, and hormones in regulating pelvic physiology and emphasizes the importance of hormonal regulation in maintaining the functionality and health of the pelvic plexus across different species. Full article

The RFamide peptide family is a group of proteins that share a common C-terminal arginine–phenylalanine–amide motif. To date, the family comprises five groups in mammals: neuropeptide FF, LPXRFamides/RFamide-related peptides, prolactin releasing peptide, QRFP, and kisspeptins. Different RFamide peptides have their own cognate receptors and are produced by different cell populations, although they all can also bind to neuropeptide FF receptors with different affinities. RFamide peptides function in the brain as neuropeptides regulating key aspects of homeostasis such as energy balance, reproduction, and cardiovascular function. Furthermore, they are involved in the organization of the stress response including modulation of pain. Considering the interaction between stress and various parameters of homeostasis, the role of RFamide peptides may be critical in the development of stress-related neuropathologies. This review will therefore focus on the role of RFamide peptides as possible key hubs in stress and stress-related psychopathologies. The neurotransmitter coexpression profile of RFamide-producing cells is also discussed, highlighting its potential functional significance. The development of novel pharmaceutical agents for the treatment of stress-related disorders is an ongoing need. Thus, the importance of RFamide research is underlined by the emergence of peptidergic and G-protein coupled receptor-based therapeutic targets in the pharmaceutical industry. Full article

Tuberoinfundibular dopamine (TIDA) neurons have cell bodies located in the arcuate nucleus of the mediobasal hypothalamus. They project to the external zone of the median eminence, and the dopamine (DA) released there is carried by the hypophysial portal vasculature to the anterior pituitary. The DA then activates D2 receptors to inhibit prolactin (PRL) secretion from lactotrophs. The TIDA neuronal population is the principal regulatory factor controlling PRL secretion. The neuroendocrine role subserved by TIDA neurons sets them apart from other dopaminergic populations like the nigrostriatal and mesolimbic DA neurons. TIDA neurons exhibit intrinsic oscillatory fluctuations in their membrane potential that give rise to phasic firing and bursting activity. TIDA neuronal activity is sexually differentiated and modulated by gonadal hormones and PRL, as well as an array of small molecule and peptide neurotransmitters. This review covers these characteristics. Full article

In recent years, new DNA methylation variants have been reported in genes biologically relevant to Alzheimer’s disease (AD) in human brain tissue. However, this AD-specific epigenetic information remains brain-locked and unreachable during patients’ lifetimes. In a previous methylome performed in the hippocampus of 26 AD patients and 12 controls, we found higher methylation levels in AD patients in the promoter region of PRLHR, a gene involved in energy balance regulation. Our aim was to further characterize PRLHR’s role in AD and to evaluate if the liquid biopsy technique would provide life access to this brain information in a non-invasive way. First, we extended the methylation mapping of PRLHR and validated previous methylome results via bisulfite cloning sequencing. Next, we observed a positive correlation between PRLHR methylation levels and AD-related neuropathological changes and a decreased expression of PRLHR in AD hippocampus. Then, we managed to replicate the hippocampal methylation differences in plasma cfDNA from an additional cohort of 35 AD patients and 35 controls. The isolation of cfDNA from the plasma of AD patients may constitute a source of potential epigenetic biomarkers to aid AD clinical management. Full article

Multiple studies have reported new or exacerbated persistent or resistant hypertension in patients previously infected with COVID-19. We used literature-based discovery to identify and prioritize multi-scalar explanatory biology that relates resistant hypertension to COVID-19. Cross-domain text mining of 33+ million PubMed articles within a comprehensive knowledge graph was performed using SemNet 2.0. Unsupervised rank aggregation determined which concepts were most relevant utilizing the normalized HeteSim score. A series of simulations identified concepts directly related to COVID-19 and resistant hypertension or connected via one of three renin–angiotensin–aldosterone system hub nodes (mineralocorticoid receptor, epithelial sodium channel, angiotensin I receptor). The top-ranking concepts relating COVID-19 to resistant hypertension included: cGMP-dependent protein kinase II, MAP3K1, haspin, ral guanine nucleotide exchange factor, N-(3-Oxododecanoyl)-L-homoserine lactone, aspartic endopeptidases, metabotropic glutamate receptors, choline-phosphate cytidylyltransferase, protein tyrosine phosphatase, tat genes, MAP3K10, uridine kinase, dicer enzyme, CMD1B, USP17L2, FLNA, exportin 5, somatotropin releasing hormone, beta-melanocyte stimulating hormone, pegylated leptin, beta-lipoprotein, corticotropin, growth hormone-releasing peptide 2, pro-opiomelanocortin, alpha-melanocyte stimulating hormone, prolactin, thyroid hormone, poly-beta-hydroxybutyrate depolymerase, CR 1392, BCR-ABL fusion gene, high density lipoprotein sphingomyelin, pregnancy-associated murine protein 1, recQ4 helicase, immunoglobulin heavy chain variable domain, aglycotransferrin, host cell factor C1, ATP6V0D1, imipramine demethylase, TRIM40, H3C2 gene, COL1A1+COL1A2 gene, QARS gene, VPS54, TPM2, MPST, EXOSC2, ribosomal protein S10, TAP-144, gonadotropins, human gonadotropin releasing hormone 1, beta-lipotropin, octreotide, salmon calcitonin, des-n-octanoyl ghrelin, liraglutide, gastrins. Concepts were mapped to six physiological themes: altered endocrine function, 23.1%; inflammation or cytokine storm, 21.3%; lipid metabolism and atherosclerosis, 17.6%; sympathetic input to blood pressure regulation, 16.7%; altered entry of COVID-19 virus, 14.8%; and unknown, 6.5%. Full article

Prolactin-releasing peptide (PrRP) is an anorexigenic neuropeptide that has potential for the treatment of obesity and its complications. Recently, we designed a palmitoylated PrRP31 analog (palm¹¹-PrRP31) that is more stable than the natural peptide and able to act centrally after peripheral administration. This analog acted as an anti-obesity and glucose-lowering agent, attenuating lipogenesis in rats and mice with high-fat (HF) diet-induced obesity. In Wistar Kyoto (WKY) rats fed a HF diet for 52 weeks, we explored glucose intolerance, but also prediabetes, liver steatosis and insulin resistance-related changes, as well as neuroinflammation in the brain. A potential beneficial effect of 6 weeks of treatment with palm¹¹-PrRP31 and liraglutide as comparator was investigated. Liver lipid profiles, as well as urinary and plasma metabolomic profiles, were measured by lipidomics and metabolomics, respectively. Old obese WKY rats showed robust glucose intolerance that was attenuated by palm¹¹-PrRP31, but not by liraglutide treatment. On the contrary, liraglutide had a beneficial effect on insulin resistance parameters. Despite obesity and prediabetes, WKY rats did not develop steatosis owing to HF diet feeding, even though liver lipogenesis was enhanced. Plasma triglycerides and cholesterol were not increased by HFD feeding, which points to unincreased lipid transport from the liver. The liver lipid profile was significantly altered by a HF diet that remained unaffected by palm¹¹-PrRP31 or liraglutide treatment. The HF-diet-fed WKY rats revealed astrogliosis in the brain cortex and hippocampus, which was attenuated by treatment. In conclusion, this study suggested multiple beneficial anti-obesity-related effects of palm¹¹-PrRP31 and liraglutide in both the periphery and brain. Full article

Insect short neuropeptide F (sNPF), an ortholog of prolactin-releasing peptide of invertebrates, regulates diverse biological processes, including feeding, olfaction, locomotion, and sleep homeostasis in insects. However, its function is still unclear in an important model insect and agricultural pest, the pea aphid (Acyrthosiphon pisum). Here, we investigated short neuropeptide F (ApsNPF) and its receptor (ApsNPFR) in A. pisum. The sNPF gene contains three exons and two long introns. In addition, the genome contains a single sNPF receptor with seven transmembrane domains. Stage- and tissue-specific transcript profiling by qRT-PCR revealed that ApsNPF and ApsNPFR were mainly expressed in the central nervous system. The receptor was also detected in antennae, midgut, and integument. The highest expression levels were found in first instar nymphs compared to other developmental stages. Besides, the starvation-induced pattern indicated that the sNPF network depends on the nutritional state of the insect. An electrical penetration graph showed that probing time and phloem duration of A. pisum on broad bean plants decreased in response to dssNPF and dssNPFR in RNAi assays. sNPF silencing reduced the number of nymphs per female but not aphid survival. We believe that our results advance in-depth knowledge of the sNPF/sNPFR signaling cascade and its place in regulating feeding behavior in insects. In turn, it may contribute to the potential design of new strategies to control aphids, with a focus on the sNPF system. Full article

The anorexigenic neuropeptide prolactin-releasing peptide (PrRP) is involved in the regulation of food intake and energy expenditure. Lipidization of PrRP stabilizes the peptide, facilitates central effect after peripheral administration and increases its affinity for its receptor, GPR10, and for the neuropeptide FF (NPFF) receptor NPFF-R2. The two most potent palmitoylated analogs with anorectic effects in mice, palm¹¹-PrRP31 and palm-PrRP31, were studied in vitro to determine their agonist/antagonist properties and mechanism of action on GPR10, NPFF-R2 and other potential off-target receptors related to energy homeostasis. Palmitoylation of both PrRP31 analogs increased the binding properties of PrRP31 to anorexigenic receptors GPR10 and NPFF-R2 and resulted in a high affinity for another NPFF receptor, NPFF-R1. Moreover, in CHO-K1 cells expressing GPR10, NPFF-R2 or NPFF-R1, palm¹¹-PrRP and palm-PrRP significantly increased the phosphorylation of extracellular signal-regulated kinase (ERK), protein kinase B (Akt) and cAMP-responsive element-binding protein (CREB). Palm¹¹-PrRP31, unlike palm-PrRP31, did not activate either c-Jun N-terminal kinase (JNK), p38, c-Jun, c-Fos or CREB pathways in cells expressing NPFF-1R. Palm-PrRP31 also has higher binding affinities for off-target receptors, namely, the ghrelin, opioid (KOR, MOR, DOR and OPR-L1) and neuropeptide Y (Y₁, Y₂ and Y₅) receptors. Palm¹¹-PrRP31 exhibited fewer off-target activities; therefore, it has a higher potential to be used as an anti-obesity drug with anorectic effects. Full article

Reproductive function depends upon an operational hypothalamo–pituitary–gonadal (HPG) axis. Due to its role in determining survival versus reproductive strategies, the HPG axis is vulnerable to a diverse plethora of signals that ultimately manifest with Central Hypogonadism (CH) in all its many guises. Acquired CH can result from any pituitary or hypothalamic lesion, including its treatment (such as surgical resection and/or radiotherapy). The HPG axis is particularly sensitive to the suppressive effects of hyperprolactinaemia that can occur for many reasons, including prolactinomas, and as a side effect of certain drug therapies. Physiologically, prolactin (combined with the suppressive effects of autonomic neural signals from suckling) plays a key role in suppressing the gonadal axis and establishing temporary CH during lactation. Leptin is a further key endocrine regulator of the HPG axis. During starvation, hypoleptinaemia (from diminished fat stores) results in activation of hypothalamic agouti-related peptide neurons that have a dual purpose to enhance appetite (important for survival) and concomitantly suppresses GnRH neurons via effects on neural kisspeptin release. Obesity is associated with hyperleptinaemia and leptin resistance that may also suppress the HPG axis. The suppressibility of the HPG axis also leaves it vulnerable to the effects of external signals that include morphine, anabolic-androgenic steroids, physical trauma and stress, all of which are relatively common causes of CH. Finally, the HPG axis is susceptible to congenital malformations, with reports of mutations within >50 genes that manifest with congenital CH, including Kallmann Syndrome associated with hyposmia or anosmia (reduction or loss of the sense of smell due to the closely associated migration of GnRH with olfactory neurons during embryogenesis). Analogous to the HPG axis itself, patients with CH are often vulnerable, and their clinical management requires both sensitivity and empathy. Full article

The serotonin (5-hydroxytryptamine, 5-HT) signaling system is involved in a variety of physiological functions, including the control of cognition, reward, learning, memory, and vasoconstriction in vertebrates. Contrary to the extensive studies in the mammalian system, little is known about the molecular characteristics of the avian serotonin signaling network. In this study, we cloned and characterized the full-length cDNA of three serotonin receptor genes (HTR1B, HTR1E and HTR1F) in chicken pituitaries. Synteny analyses indicated that HTR1B, HTR1E and HTR1F were highly conserved across vertebrates. Cell-based luciferase reporter assays showed that the three chicken HTRs were functional, capable of binding their natural ligands (5-HT) or selective agonists (CP94253, BRL54443, and LY344864) and inhibiting intracellular cAMP production in a dose-dependent manner. Moreover, activation of these receptors could stimulate the MAPK/ERK signaling cascade. Quantitative real-time PCR analyses revealed that HTR1B, HTR1E and HTR1F were primarily expressed in various brain regions and the pituitary. In cultured chicken pituitary cells, we found that LY344864 could significantly inhibit the secretion of PRL stimulated by vasoactive intestinal peptide (VIP) or forskolin, revealing that HTR1F might be involved in the release of prolactin in chicken. Our findings provide insights into the molecular mechanism and facilitate a better understanding of the serotonergic modulation via HTR1B, HTR1E and HTR1F in avian species. Full article

Prolactin-releasing Peptide (PrRP) is a neuropeptide whose receptor is GPR10. Recently, the regulatory role of PrRP in the neuroendocrine field has attracted increasing attention. However, the influence of PrRP on macrophages, the critical housekeeper in the neuroendocrine field, has not yet been fully elucidated. Here, we investigated the effect of PrRP on the transcriptome of mouse bone marrow-derived macrophages (BMDMs) with RNA sequencing, bioinformatics, and molecular simulation. BMDMs were exposed to PrRP (18 h) and were subjected to RNA sequencing. Differentially expressed genes (DEGs) were acquired, followed by GO, KEGG, and PPI analysis. Eight qPCR-validated DEGs were chosen as hub genes. Next, the three-dimensional structures of the proteins encoded by these hub genes were modeled by Rosetta and Modeller, followed by molecular dynamics simulation by the Gromacs program. Finally, the binding modes between PrRP and hub proteins were investigated with the Rosetta program. PrRP showed no noticeable effect on the morphology of macrophages. A total of 410 DEGs were acquired, and PrRP regulated multiple BMDM-mediated functional pathways. Besides, the possible docking modes between PrRP and hub proteins were investigated. Moreover, GPR10 was expressed on the cell membrane of BMDMs, which increased after PrRP exposure. Collectively, PrRP significantly changed the transcriptome profile of BMDMs, implying that PrRP may be involved in various physiological activities mastered by macrophages. Full article