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The simultaneous assessment of the electrophysiological and neuroendocrine activity during sleep by the sleep electroencephalogram (EEG) and by the collection of hormone profiles respectively showed a bidirectional interaction between the non-rapid eye movement (non-REM)–REM cycle and nocturnal hormone secretion. Certain hormones (neuropeptides and neuroactive steroids) participate in sleep regulation. A reciprocal interaction of the sleep-promoting peptide growth hormone-releasing hormone (GHRH) and the sleep-impairing corticotropin-releasing hormone (CRH) plays a key role in sleep regulation. Besides GHRH, galanin, ghrelin, and neuropeptide Y also promote sleep, at least in male subjects. In contrast, somatostatin is another sleep-impairing endogenous substance. The influence of peptides on sleep depends on age, sex, and time of administration. For example, GHRH impairs sleep in women, opposite to its effects in men. Vasoactive intestinal polypeptide affects the duration of non-REM and REM periods. In addition to peptides, steroids are involved in sleep regulation. GABA A receptors are targets of various neuroactive steroids exerting specific effects on sleep EEG. Cortisol appears to promote REM sleep. Sleep EEG changes in postmenopausal women and the beneficial effect of estrogen and progesterone replacement therapy suggests a sleep-promoting effect of these hormones.

Objectives The aims of this study were to investigate neuropeptide receptor expression regulation on STRO-1 +ve periodontal ligament stem cells (PDLSCs) in response to inflammatory cytokines and to investigate a potential osteogenic effect of neuropeptides. Background Nerve fibres innervating the periodontal tissues in humans contain several neuropeptides including neuropeptide Y and substance P. The role of neuropeptide receptors on PDLSCs, including their response to the local inflammatory environment of periodontitis, is currently unknown. Methods A homogenous population of STRO-1 +ve PDLSCs was prepared by immunomagnetic separation of cells obtained by the tissue out-growth method from healthy premolar teeth from a single donor. Regulation of gene expression of the neuropeptide Y Y1 receptor and substance P receptor tachykinin receptor 1 was investigated. A potential osteogenic effect of neuropeptide Y and substance P was also investigated by measuring alkaline phosphatase (ALP) activity, Alizarin red staining and quantifying osteogenic gene expression. Results Treatment of STRO-1 +ve PDLSCs with tumour necrosis factor-alpha or interleukin 1-beta up-regulated the expression of the neuropeptide Y's Y1 receptor, but down-regulated substance P's receptor. Significantly increased ALP activity was observed in STRO-1 +ve PDLSCs treated with neuropeptide Y but not substance P. Further studies showed that neuropeptide Y had a modest osteogenic effect on cells at both a functional level and a gene level. Conclusions Expression of the neuropeptide Y Y1 receptor gene on STRO-1 +ve PDLSCs was sensitive to local inflammatory cytokines. Treatment of cells with neuropeptide Y was found to produce a modest enhanced osteogenic effect.

Electroacupuncture (EA) is considered to have potential antidiabetic effects; however, the role of the pancreatic intrinsic nervous system (PINS) in EA-induced amelioration of type 2 diabetes (T2DM) remains unclear. Therefore, we investigated whether EA at ST25 exerts any beneficial effects on insulin resistance (IR), inflammation severity, and pancreatic β cell function via the PINS in a rat model of a high-fat diet-streptozotocin (HFD/STZ)-induced diabetes. To this end, Sprague Dawley rats were fed with HFD to induce IR, followed by STZ (35 mg/kg, i.p.) injection to establish the T2DM model. After hyperglycemia was confirmed as fasting glucose level > 16.7 mmol/L, the rats were treated with EA (2 mA, 2/15 Hz) for the next 28 days. Model rats showed increased serum glucose, insulin, IR, and TNF-α levels with a concomitant decrease in β cell function. Microscopy examination of the pancreas revealed pathological changes in islets, which reverted to near-normal levels after EA at ST25. EA improved islet cell morphology by increasing islet area and reducing vacuolation. EA at ST25 decreased transient receptor potential vanilloid 1 (TRPV1) and increased substance P (SP) and calcitonin gene-related peptide (CGRP) expression. Subsequently, insulin secretion decreased and impaired pancreatic endocrine function was restored through the TRPV1 channel (SP/CGRP)-insulin circuit. EA increased choline acetyltransferase and neuropeptide Y expression and controlled inflammation. It also enhanced the cocaine and amphetamine-regulated transcript prepropeptide expression and promoted glucagon-like peptide-1 secretion. Additionally, the electrophysiological activity of PINS during acupuncture (2.71 ± 1.72 Hz) was significantly increased compared to the pre-acupuncture frequency (0.32 ± 0.37 Hz, P < 0.05). Thus, our study demonstrated the beneficial effect of EA on β cell dysfunction via the PINS in rat models of HFD-STZ-induced T2DM.

The family of neuropeptide Y (NPY) receptors comprises four subtypes (Y1R, Y2R, Y4R, Y5R), which are addressed by at least three endogenous peptides, i.e., NPY, peptide YY, and pancreatic polypeptide (PP), the latter showing a preference for Y4R. A series of cyclic oligopeptidic Y4R ligands were prepared by applying a novel approach, i.e., N-terminus to arginine side-chain cyclization. Most peptides acted as Y4R partial agonists, showing up to 60-fold higher Y4R affinity compared to the linear precursor peptides. Two cyclic hexapeptides (18, 24) showed higher Y4R potency (Ca2+ aequorin assay) and, with pKi values >10, also higher Y4R affinity compared to human pancreatic polypeptide (hPP). Compounds such as 18 and 24, exhibiting considerably lower molecular weight and considerably more pronounced Y4R selectivity than PP and previously described dimeric peptidic ligands with high Y4R affinity, represent promising leads for the preparation of labeled tool compounds and might support the development of drug-like Y4R ligands.

Since the NAD+-dependent histone deacetylases sirtuin-1 (SIRT1) and sirtuin-2 (SIRT2) are critically involved in epigenetics, endocrinology and immunology and affect the longevity in model organisms, we investigated their expression in brains of 3-month-old and 14–15 months old rat model of depression Flinders Sensitive Line (FSL) and control Flinders Resistant Line (FRL) rats. In view of the dysregulated NPY system in depression, we also studied NPY in young and old FSL to explore the temporal trajectory of depressive-like–ageing interaction. Sirt1, Sirt2 and Npy mRNA were determined using qRT-PCR in prefrontal cortex (PFC) from young and old FSL and FRL, and in hippocampi from young FSL and FRL. PFC: Sirt1 expression was decreased in FSL (p = 0.001). An interaction between age and genotype was found (p = 0.032); young FSL had lower Sirt1 with respect to both age (p = 0.026) and genotype (p = 0.001). Sirt2 was lower in FSL (p = 0.003). Npy mRNA was downregulated in FSL (p = 0.001) but did not differ between the young and old rat groups. Hippocampus: Sirt1 was reduced in young FSL compared to young FRL (p = 0.005). There was no difference in Sirt2 between FSL and FRL. Npy levels were decreased in hippocampus of young FSL compared to young FRL (p = 0.003). Effects of ageing could not be investigated due to loss of samples. To conclude, i this is the first demonstration that SIRT1 and SIRT2 are changed in brain of FSL, a rat model of depression; ii the changes are age-dependent; iii sirtuins are potential targets for treatment of age-related neurodegenerative diseases.

Background. The safety of radiotherapy techniques in the treatment of vestibular schwannoma (VS) shows a high rate of tumor control with few side effects. Neuropeptide Y (NPY) may have a potential relevance to the recurrence of VS. Further research is still needed on the key genes that determine the sensitivity of VS to radiation therapy. Materials and Methods. Transcriptional microarray data and clinical information data from VS patients were downloaded from GSE141801, and vascular-related genes associated with recurrence after radiation therapy for VS were obtained by combining information from MSigDB. Logistics regression was applied to construct a column line graph prediction model for recurrence status after radiation therapy. Pan-cancer analysis was also performed to investigate the cooccurrence of these genes in tumorigenesis. Results. We identified eight VS recurrence-related genes from the GSE141801 dataset. All of these genes were highly expressed in the VS recurrence samples. Four collagen family genes (COL5A1, COL3A1, COL4A1, and COL15A1) were further screened, and a model was constructed to predict the risk of recurrence of VS. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses revealed that these four collagen family genes play important roles in a variety of biological functions and cellular pathways. Pan-cancer analysis further revealed that the expression of these genes was significantly heterogeneous across immune phenotypes and significantly associated with immune infiltration. Finally, Neuropeptide Y (NPY) was found to be significantly and negatively correlated with the expression of COL5A1, COL3A1, and COL4A1. Conclusions. Four collagen family genes have been identified as possible predictors of recurrence after radiation therapy for VS. Pan-cancer analysis reveals potential associations between the pathogenesis of VS and other tumorigenic factors. The relevance of NPY to VS was also revealed for the first time.

Glucagon-like peptide 1 (GLP-1) and its agonists exert anorexigenic effect at least partly via acting on GLP-1 receptors (GLP-1R) in the arcuate nucleus (ARC). While the anorexigenic, proopiomelanocortin (POMC) neurons of the ARC were shown previously to express GLP-1R, the putative GLP-1R-content of the orexigenic, neuropeptide Y (NPY) neurons remained so far undetected. As GLP-1R is abundant in the ventromedial ARC, where NPY neurons are located; here, we address the possibility that GLP-1 can act directly on the orexigenic NPY system via GLP-1R. Double-labeling immunocytochemistry and in situ hybridization were performed on tissues of adult male mice to detect GLP-1R in NPY neurons. In double-immunolabeled preparations, GLP-1R-immunoreactivity was observed in NPY neurons and in axons ensheathing the majority of NPY neurons. Ultrastructural studies confirmed that GLP-1R-immunoreactivity is associated with the outer membrane of NPY perikarya as well as with axons forming symmetric type, inhibitory synapses on NPY-containing neurons. Double-labeling in situ hybridization experiments demonstrated the expression of GLP-1R mRNA in approximately 20% of NPY mRNA-containing neurons of the ARC. In summary, our data demonstrate the presence of GLP-1R protein and mRNA in NPY neurons of ARC and also reveal the innervation of NPY neurons by GLP-1R-containing inhibitory neurons. These observations suggest that GLP-1 signaling can influence NPY neurons both directly and indirectly. Furthermore, GLP-1 signaling on energy homeostasis appears to involve both direct and indirect effects of GLP-1 on the orexigenic NPY neurons, in addition to the previously known effects via the anorexigenic POMC neuronal system.

Background Defining the optimal rehabilitation programs for rotator cuff healing remains a challenge. Early treadmill running may have negative effects on tendon-bone interface (TBI) healing with increased expression of Neuropeptide Y (NPY). However, the underlying mechanism is still unknown. Methods The mice were randomly assigned to four groups: control group, treadmill group, treadmill ​+ ​BIBO3304 group and BIBO3304 group alone. Specifically, the control group was allowed free cage activity without any treatment after surgery. The treadmill group received early treadmill running initiated from postoperative day 2. The treadmill ​+ ​BIBO3304 group received treadmill running combined with intra-articular injection of BIBO3304 postoperatively. The BIBO3304 group only received type 1 NPY receptor (Y1 receptor, Y1R) antagonist BIBO3304 postoperatively. Healing outcomes of the rotator cuff were evaluated by histological analysis, synchrotron radiation micro-computed tomography (SR-μCT) scanning, and biomechanical testing at 4 and 8 weeks after surgery. The expression of NPY and its Y1 receptor during the treadmill running were tested by immunofluorescence. In addition, the related signaling pathway of Neuropeptide Y among all groups was detected by immunohistochemistry and western-blot. Results Immunofluorescence results show that early treadmill training could lead to a significant increase in the expression of NPY at the healing site, and Y1R was widely expressed in both normal or injured rotator cuff without statistical difference. At the same time, early treadmill running delayed the healing of rotator cuff, as indicated with unsatisfactory outcomes, including a significantly lower histological score, decreased bone formation and inferior biomechanical properties at postoperative week 4 and 8. Moreover, the use of BIBO3304 could partly alleviate the negative effects of early treadmill running on the healing of rotator cuff and promote the natural healing process of rotator cuff, as evidenced by significant differences observed between the treadmill and treadmill ​+ ​BIBO3304 groups, as well as observed between the control and BIBO3304 groups. On the other hand, the expressions of Wnt3a and β-catenin in the treadmill group were significantly lower compared with the other groups, while the expression in the BIBO3304 group was the highest, as evaluated by immunohistochemistry and western-blot. Conclusions Early treadmill running increased the expression of NPY at the RC healing site, which might burden the expression of Wnt3a/β-catenin and delay the healing process, inhibition of Y1 receptor with BIBO3304 could promote bone-tendon healing through the Wnt/β-catenin signaling. The translational potential of this article: This is the first study to evaluate the specific role of the NPY-Y1R axis and its underlying mechanism by which early treadmill running delays bone-tendon healing. Further, our study may provide references of precise and individualized exercise-based rehabilitation strategies for TBI healing in clinic. The translational potential of this article This is the first study to evaluate the specific role of the NPY-Y1R axis and its underlying mechanism by which early treadmill running delays bone-tendon healing. Further, our study may provide references of precise and individualized exercise-based rehabilitation strategies for TBI healing in clinic.

Nociceptive markers in mice have been identified in two distinct peptidergic and nonpeptidergic neurons in the dorsal root ganglion (DRG) and distributed in different laminae of the dorsal horn of the spinal cord. Recently, however, a study in humans showed a significant overlapping in these two populations. In this study, we investigated the distribution of various nociceptive markers in the lumbar DRG and spinal cord of the dromedary camel. Immunohistochemical data showed a remarkable percentage of total neurons in the DRG expressed IB4 binding (54.5%), calcitonin gene-related peptide (CGRP; 49.5%), transient receptor potential vanilloid 1 (TRPV1; 48.2%), and nitric oxide synthase (NOS; 30.6%). The co-localization data showed that 89.6% and 74.0% of CGRP- and TRPV1-labeled neurons, respectively, were IB4 positive. In addition, 61.6% and 84.2% of TRPV1- and NOS-immunoreactive neurons, respectively, were also co-localized with CGRP. The distribution of IB4, CGRP, TRPV1, substance P, and NOS immunoreactivities in the spinal cord were observed in lamina I and outer lamina II (IIo). Quantitative data showed that 82.4% of IB4-positive nerve terminals in laminae I and IIo were co-localized with CGRP, and 86.0% of CGRP-labeled terminals were co-localized with IB4. Similarly, 85.1% of NOS-labeled nerve terminals were co-localized with CGRP. No neuropeptide Y (NPY) or cholecystokinin (CCK) immunoreactivities were detected in the DRG, and no co-localization between IB4, NPY, and CCK were observed in the spinal cord. Our results demonstrate marked convergence of nociceptive markers in the primary afferent neurons in camels, which is similar to humans rather than the mouse. The data also emphasizes the importance of interspecies differences when selecting ideal animal models for studying nociception and treating chronic pain.

A contributing factor to the development of obesity is the consumption of a diet high in saturated fatty acids, such as palmitate. These fats induce hypothalamic neuroinflammation, which dysregulates neuronal function and induces orexigenic neuropeptide Y (Npy) to promote food intake. An inflammatory cytokine array identified multiple candidates that could mediate palmitate-induced up-regulation of Npy mRNA levels. Of these, visfatin or nicotinamide phosphoribosyltransferase (NAMPT), macrophage migratory inhibitory factor (MIF), and IL-17F were chosen for further study. Direct treatment of the neuropeptide Y/agouti-related peptide (NPY/AgRP)-expressing mHypoE-46 neuronal cell line with the aforementioned cytokines demonstrated that visfatin could directly induce Npy mRNA expression. Preventing the intracellular metabolism of palmitate through long-chain acyl-CoA synthetase (ACSL) inhibition was sufficient to block the palmitate-mediated increase in Npy gene expression. Furthermore, thin-layer chromatography revealed that in neurons, palmitate is readily incorporated into ceramides and defined species of phospholipids. Exogenous C16 ceramide, dipalmitoyl-phosphatidylcholine, and dipalmitoyl-phosphatidylethanolamine were sufficient to significantly induce Npy expression. This study suggests that the intracellular metabolism of palmitate and elevation of metabolites, including ceramide and phospholipids, are responsible for the palmitate-mediated induction of the potent orexigen Npy. Furthermore, this suggests that the regulation of Npy expression is less reliant on inflammatory cytokines per se than palmitate metabolites in a model of NPY/AgRP neurons. These lipid species likely induce detrimental downstream cellular signaling events ultimately causing an increase in feeding, resulting in an overweight phenotype and/or obesity.

Neuropeptide Y receptor Y8 (NPY8R) is a fish-specific receptor, whose role in feeding regulation remains poorly understood. In the present study, two subtypes of NPY8R (NPY8Ra and NPY8Rb) were identified in Chinese perch, and their amino acid sequences were highly conserved in fish. The predicted tertiary protein structures of human NPY1R, Chinese perch NPY8Ra, and NPY8Rb tended to be conserved as a whole. However, the predicted tertiary protein structures of sc-NPY8Ra and sc-NPY8Rb were different at several sites. Chinese perch NPY8Ra and NPY8Rb were mainly expressed in brain. Intracerebroventricular administration of siRNA-NPY8Rb significantly decreased the mRNA expression levels of NPY8Rb and POMC (appetite-suppressive gene) and significantly increased the food intake of Chinese perch at 2 h and 8 h after injection. Similar result has not been observed in the siRNA-NPY8Ra administration group. The above results suggested that NPY8Ra might not play a role in appetite regulation and NPY8Rb might be an effector in the negative feedback regulation of feeding in Chinese perch.

The human internal carotid nerve (ICN) occasionally has a swelling beneath the external opening of the carotid canal. In this study, the presence and distribution of neuronal cells were investigated in the bilateral ICNs of nine human cadavers. Among 44.4% of the cadavers, swellings were detected in the ICN. Their diameters ranged from 1.7 to 3.6 mm (average ± SD = 2.6 ± 0.7 mm). Thirty-eight percent of these swellings were large (diameter > 3 mm) and showed an oval shape. The large swelling contained many neuronal cells. However, the ICNs with or without a swelling

Energy homeostasis, which refers to the physiological processes that the energy intake is exquisitely coordinated with energy expenditure, is critical for survival. Therefore, multiple and complex mechanisms have been involved in the regulation of energy homeostasis. The central melanocortin system plays an important role in modulating energy homeostasis. This system includes the orexigenic neurons, expressing neuropeptide Y/Agouti-related protein (NPY/AgRP), and the anorexigenic neurons expressing proopiomelanocortin (POMC). The downstream receptors of NPY, AgRP and post-translational products of POMC are G protein-coupled receptors (GPCRs). This review summarizes the compelling evidence demonstrating that NPY and melanocortin receptors are involved in energy homeostasis. Subsequently, the comparative studies on physiology and pharmacology of NPY and melanocortin receptors in humans, rodents and teleosts are summarized. Also, we provide a strategy demonstrating the potential application of the new ligands and/or specific variants of melanocortin system in aquaculture.

Neuropeptide Y (NPY) performs varied functions in the nervous system, including the regulation of vascular tone and gastrointestinal secretion. Specifically, it exerts a direct inhibitory effect on intestinal motility and secretion. Colocalization of NPY with choline acetyltransferase (ChAT), the enzyme catalyzing acetylcholine synthesis, as well as neuronal NO synthase (nNOS), vasoactive intestinal peptide (VIP) and calcium-binding protein calbindin (CB), was studied in enteric neurons of the submucosal plexus of the rat small intestine at different ages (from the moment of birth until old age) using double immunolabeling and fluorescence microscopy. From the moment of birth, all NPY-ergic neurons colocalize ChAT, while most of them also contain VIP and CB. In aged rats, the percentage of NPY-ergic neurons colocalizing CB, VIP and ChAT decreases. Both in juvenile (since birth until 20 days of age) and aged rats, NPY-ergic neurons were found to express nNOS. Thus, at early stages of ontogeny and in senescence, the rat enteric metasympathetic NPY-ergic submucosal neurons contain a wider range of neurotransmitters compared to adult animals.

Objective The gut microbiota is a complex ecosystem that shapes host metabolism, especially in early life. Maternal vaginal and gut microbiota is vertically transmitted to offspring during natural birth. Offspring born by cesarean section (CS) do not receive these bacteria and exhibit higher obesity risk later in life. The objective of this study was to examine differences in obesity risk between offspring born naturally (NB) or by CS to lean/obese dams. Methods Lean and obese rat dams gave birth to offspring naturally or by CS. Offspring obesity risk was analyzed via body weight/composition, food intake, sucrose preference, gut microbiota, and gene expression in gut and brain tissues. Results Obese (O)+CS offspring showed greater weight gain and caloric intake but a reduction in hypothalamic agouti related neuropeptide, neuropeptide Y, and interleukin 1β expression compared with O+NB offspring. Lean (L)+CS offspring had higher serum corticosterone concentration and reduced liver peroxisome proliferator-activated receptor γ expression compared with L+NB. O+CS offspring had long-term alterations to gut microbiota, including increased relative abundance of Faecalibaculum and reduced Muribaculaceae. Conclusions Overall, CS alters obesity risk differentially based on maternal obesity status. Further studies looking at the risks of obesity associated with CS are needed, with special attention paid to maternal obesity status and gut microbiota.

Introduction: Chronic Kidney Disease (CKD) is a pathological condition that occurs gradually and is irreversible, characterized by structural and functional abnormalities in the kidneys that lasts for more than three months. The C allele in the Neuropeptide Y (NPY) RS16147 gene is closely related to an increase in the incidence of hypertension, a decrease in glomerular filtration rate, and an increase in total cholesterol levels in CKD patients. Objective: To determine the effect of the NPY RS16147 gene polymorphism on the blood pressure of chronic kidney disease patients and control healthy in Medan Indonesia. Methods: This study is an analytical study with a case-control design at the Haji Adam Malik General Hospital Medan from July to August 2020. All subjects had Deoxyribonucleic Acid (DNA) analysis using Polymerase Chain Reaction Restriction Fragment Length Polymorphism (PCR-RFLP) method. Results: We obtained 100 study subjects, 43 was CKD patients with dialysis, 31 CKD patients without dialysis, and 26 control healthy groups. In this study, there were differences in the trend genotypes of NPY RS16147 polymorphism with the incidence of CKD and control healthy. We obtained a significant difference the mean systolic blood pressure patients with genotypes TT (139,05±21,42) and TC/CC (151,32±22,26) as evidenced by the value of P = 0.00 (≤0.05). The presence of the "C" allele in the NPY RS16147 gene sample increased blood pressure in all study subjects significantly (P=0.028; ≤0.05). Conclusion: the "C" allele in the NPY RS16147 gene affects systolic blood pressure. Keywords: NPY RS16147 polymorphism, Chronic kidney disease, Blood pressure.

We report the design, fabrication, and characterization of a silicon-nitride (SiN) microring-resonator-based label-free biosensor for the purpose of neuropeptide Y (NPY) protein detection. NPY is commonly associated with stress in human body. The device uses evanescent field sensing, its geometry is optimized for 1550-nm signal, and it is fabricated by following standard CMOS processes. Top surface of the device is designed to function in aqueous environment and appropriately functionalized to ensure the biomaterial-specific attachment. The time-dependent spectral response to the biomaterial attachment is observed by scanning a tunable laser source around 1550 nm and measuring the resonance shift in the transmission spectrum. We experimentally achieve the detection into nanomolar concentration level in a regular assay system with 0.1 nm/( $\mu \text{g}$ /mL) of sensitivity and $\sim ~30$ mins of analysis time. This sensitivity is further amplified by a factor of three with a sandwiched assay technique, with which $\sim ~58$ nM ( $0.25~\mu \text{g}$ /mL) concentration of NPY is successfully detected.

We compared the levels of functional activity of cells in each adrenal zone with blood levels of corticosterone, testosterone, and neuropeptide Y in control and hippocampectomized F1(C57BL/6×DBA/2) mice during modeling of metabolic, motivational, and cognitive tension. The morphofunctional state of the adrenal glands was studied using a new morphometric approach. It was found that hippocampectomy changed the testosterone response to neurobiological stimuli; similar changes were observed in the zona reticularis of the adrenal cortex producing dehydroepiandrosterone that is involved in the regulation of testosterone secretion. At the same time, hippocampectomy enhanced the response of the peptide hormone; the index of functional activity of chromaffin cells producing this hormone also increased. These findings allow us to put forward a hypothesis that the hippocampus is involved in the regulation of mutual influences of the studied hormones and that it modulates the sensitivity of testosterone and NPY to metabolic and cognitive factors.

Appetite is controlled by a complex system of central and peripheral signals interacting to modulate the ingestion response. Several brain mediators with complex networks adjust food intake in birds. Based on the available literature, these mediators have interactions with a number of other neurotransmitters (NTS) involved in feed intake. It means that, NTS regulate feeding behavior through mediating other peptide and NTs activity. In birds, insulin known as a hypophagic hormone that is interplaying with neuropeptide Y (NPY), pro-opiomelanocortin (POMC), and corticotropin-releasing factor (CRF) in brain. Another hormone ghrelin, inhibits food intake in birds and other mediators, such as glutamate, endocannabinoid system (ECS), serotonin (5-hydroxytryptamine, 5-HT), and norepinephrine (NE), which play a key role in ghrelin-induced hypophagia. Another involved peptide on feeding behavior in chickens called nociceptin/orphanin FQ (N/OFQ) is modulated by histamine, glutamate, dopamine (DA), gamma-aminobutyric acid (GABA), agouti-related protein (AgRP), and cocaine and amphetamine-regulated transcript (CART). Some of the NTS such as opioid have both orexigenic and anorexigenic effects in birds while has interaction with NE, glutamate, histamine, DA, and cannabinoids (CBs). Thus, interaction among mediators is a prominent process needs to be considered in order to understanding the mechanisms underlying feed intake regulation in birds. This review aims to investigate the role of major regulators and their mediatory interactions with one another in poultry feeding behavior. According to mentioned interactions, it seems that dopamine, serotonin, and glutamate have the most interactions with other NT systems. Therefore, they play an axial role in the central regulation of food intake in CNS.

Introduction: Orexin-A is a neuropeptide synthesized in the lateral hypothalamus. Orexin-A immunoreactive fibres overlap distribution with GnRH neurons. In adult rats, orexin A is known to affect LH secretion via GnRH release modulation. Because data concerning the impact of orexin-A on the hypothalamo-pituitary axis activity are limited, we focused on the involvement of orexin-A and receptors of NPY in the modulation of LH release and LH subunit b (Lhb) mRNA expression in prepubertal female rats. Material and methods: Forty immature female Wistar rats were divided into 4 groups and received 2 intracerebroventricular (icv) microinjections of: 1 — artificial cerebrospinal fluid (CSF) (controls); 2 — CSF followed by orexin A; 3 — selective NPY receptor antagonist (BIBP) followed by CSF; 4 — BIBP followed by orexin A. One hour after the last microinjection, all rats were decapitated. Trunk blood was collected, and serum was stored at –20°C for the LH RIA examination. The adenohypophysis was immediately excised, flash-frozen, and kept at –80°C for RNA extraction. Real-time PCR amplification was carried out, and relative Lhb gene expression was calculated. Results: In comparison to the CSF-treated controls with a mean LH serum concentration of 0.40 ± 0.02 ng/mL, the mean LH serum level was diminished both after orexin-A (0.27 ± 0.01 ng/mL) and after BIBP (0.30 ± 0.02 ng/mL) icv microinjections. In the presence of BIBP, orexin-A more effectively inhibited LH release (0.20 ± 0.01 ng/mL) when compared to the BIBP-treated group. Orexin-A and BIBP exerted a consistent inhibitory effect on Lhb mRNA expression levels in the anterior pituitary gland. In comparison to the CSF-treated controls, orexin-A, and BIBP-treated females responded with, respectively, 35% and 40% reduction of Lhb mRNA expression. Orexin-A and BIBP co-administration evoked a further reduction of Lhb gene transcriptional activity. Conclusions: Orexin-A exerts a down-regulatory effect on LH synthesis and release in immature female rats. Considering that Y1R-oriented down-regulation of endogenous NPY activity did not reverse the suppressive effect of exogenous orexin-A, it might be suggested that NPY and orexin A systems can operate independently to affect gonadotropin activity in the anterior pituitary of the immature female rats.

Vitiligo is an autoimmune disease characterized by depigmented patches of skin due to loss of the pigment-producing melanocytes. No cure exists for vitiligo. The available treatments are inefficient for many patients, suggesting that universal treatment approaches may be inappropriate. Deeper understanding of the mechanistic basis for variability in vitiligo aetiologies is necessary. Genetic mutations in neuropeptide Y (NPY), a widely distributed protein, are associated with increased NPY expression and increased susceptibility for vitiligo. NPY is also upregulated in the circulation and lesional skin of some vitiligo patients. However, the contributions of NPY to melanocyte pathology are not understood, and presently there are no models with which to investigate this possibility. In this study, we employed NPY-overexpressing mice to explore the role of NPY in melanocyte dysfunction. Our results show that NPY overexpression induces progressive hair greying (depigmentation) due to premature depletion of follicular melanocyte stem cells. Additionally, NPY transcripts and protein are elevated in the skin and melanocytes of these mice, respectively, suggesting that these effects may be mediated locally. Together, these results suggest that supraphysiological levels of NPY in the skin can induce melanocyte dysfunction, thus identifying this mouse line as a novel model to study NPY-mediated melanocyte pathology.

Seasonal energy intake of Tibetan sheep on the harsh Qinghai-Tibetan Plateau (QTP) fluctuates greatly and is often well below maintenance requirements. The aim of this study was to gain insight into how the hypothalamus regulates energy homoeostasis in Tibetan sheep. We compared Tibetan and Small-tailed Han sheep (n 24 of each breed), which were each allocated randomly into four groups and offered one of four diets that differed in digestible energy densities: 8·21, 9·33, 10·45 and 11·57 MJ/kg DM. Sheep were weighed every 2 weeks, and it was assumed that the change in body weight (BW) reflected the change in energy balance. The arcuate nucleus of the hypothalamus in Tibetan sheep had greater protein expressions of neuropeptide Y (NPY) and agouti-related peptide (AgRP) when in negative energy balance, but lesser protein expressions of proopiomelanocortin (POMC) and cocaine and amphetamine-regulated transcript (CART) when in positive energy balance than Small-tailed Han sheep. As a result, Tibetan sheep had a lesser BW loss when in negative energy balance and stored more energy and gained more BW when in positive energy balance than Small-tailed Han sheep with the same dietary intake. Moreover, in the hypothalamic adenosine monophosphate-activated protein kinase (AMPK) regulation pathway, Tibetan sheep had greater adenosine monophosphate-activated protein kinase-α 2 protein expression than Small-tailed Han sheep, which supported the premise of a better ability to regulate energy homoeostasis and better growth performance. These differences in the hypothalamic NPY/AgRP, POMC/CART and AMPK pathways between breeds conferred an advantage to the Tibetan over Small-tailed Han sheep to cope with low energy intake on the harsh QTP.

This study was aimed to determine the efficacy of multispecies probiotics in reducing the severity of post-weaning diarrhea caused by enterotoxigenic Escherichia coli (ETEC) F18+ on newly weaned pigs. Thirty-two pigs (16 barrows and 16 gilts, BW = 6.99 ± 0.33 kg) at 21 d of age were individually allotted in a randomized complete block design with 2 × 2 factorial arrangement of treatments. Pigs were selected from sows not infected previously and not vaccinated against ETEC. Pigs were fed experimental diets for 25 d based on 10 d phase 1 and 15 d phase 2. The factors were ETEC challenge (oral inoculation of saline solution or E. coli F18+ at 2 × 109 CFU) and probiotics (none or multispecies probiotics 0.15% and 0.10% for phase 1 and 2, respectively). Body weight and feed intake were measured on d 5, 9, 13, 19, and 25. Fecal scores were measured daily. Blood samples were taken on d 19 and 24. On d 25, all pigs were euthanized to obtain samples of digesta, intestinal tissues, and spleen. The tumor necrosis factor alpha (TNFα), malondialdehyde (MDA), peptide YY (PYY), and neuropeptide Y (NPY) were measured in serum and intestinal tissue. Data were analyzed using the MIXED procedure of SAS. The fecal score of pigs was increased (P

The internalization of G protein-coupled receptors (GPCRs) is an important mechanism regulating the signal strength and limiting the opportunity of receptor activation. Based on the importance of GPCRs, the detailed knowledge about the regulation of signal transduction is crucial. Here, current knowledge about the agonist-induced, arrestin-dependent internalization process of rhodopsin-like GPCRs is reviewed. Arrestins are conserved molecules that act as key players within the internalization process of many GPCRs. Based on highly conserved structural characteristics within the rhodopsin-like GPCRs, the identification of arrestin interaction sites in model systems can be compared and used for the investigation of internalization processes of other receptors. The increasing understanding of this essential regulation mechanism of receptors can be used for drug development targeting rhodopsin-like GPCRs. Here, we focus on the neuropeptide Y receptor family, as these receptors transmit various physiological processes such as food intake, energy homeostasis, and regulation of emotional behavior, and are further involved in pathophysiological processes like cancer, obesity and mood disorders. Hence, this receptor family represents an interesting target for the development of novel therapeutics requiring the understanding of the regulatory mechanisms influencing receptor mediated signaling.

Bile acids (BAs) are signalling molecules that mediate various cellular responses in both physiological and pathological processes. Several studies report that BAs can be detected in the brain1, yet their physiological role in the central nervous system is still largely unknown. Here we show that postprandial BAs can reach the brain and activate a negative-feedback loop controlling satiety in response to physiological feeding via TGR5, a G-protein-coupled receptor activated by multiple conjugated and unconjugated BAs2 and an established regulator of peripheral metabolism3–8. Notably, peripheral or central administration of a BA mix or a TGR5-specific BA mimetic (INT-777) exerted an anorexigenic effect in wild-type mice, while whole-body, neuron-specific or agouti-related peptide neuronal TGR5 deletion caused a significant increase in food intake. Accordingly, orexigenic peptide expression and secretion were reduced after short-term TGR5 activation. In vitro studies demonstrated that activation of the Rho–ROCK–actin-remodelling pathway decreases orexigenic agouti-related peptide/neuropeptide Y (AgRP/NPY) release in a TGR5-dependent manner. Taken together, these data identify a signalling cascade by which BAs exert acute effects at the transition between fasting and feeding and prime the switch towards satiety, unveiling a previously unrecognized role of physiological feedback mediated by BAs in the central nervous system. Bile acids are shown to enter the brain and regulate short-term reductions in food intake after a meal by inhibiting neuropeptide release from agouti-related peptide/neuropeptide Y neurons.

Cardiopulmonary arrest (CA) can greatly impact a patient’s life, causing long-term disability and death. Although multi-faceted treatment strategies against CA have improved survival rates, the prognosis of CA remains poor. We previously reported asphyxial cardiac arrest (ACA) can cause excessive activation of the sympathetic nervous system (SNS) in the brain, which contributes to cerebral blood flow (CBF) derangements such as hypoperfusion and, consequently, neurological deficits. Here, we report excessive activation of the SNS can cause enhanced neuropeptide Y levels. In fact, mRNA and protein levels of neuropeptide Y (NPY, a 36-amino acid neuropeptide) in the hippocampus were elevated after ACA-induced SNS activation, resulting in a reduced blood supply to the brain. Post-treatment with peptide YY(3–36) (PYY(3–36)), a pre-synaptic NPY2 receptor agonist, after ACA inhibited NPY release and restored brain circulation. Moreover, PYY(3–36) decreased neuroinflammatory cytokines, alleviated mitochondrial dysfunction, and improved neuronal survival and neurological outcomes. Overall, NPY is detrimental during/after ACA, but attenuation of NPY release via PYY(3–36) affords neuroprotection. The consequences of PYY(3–36) inhibit ACA-induced 1) hypoperfusion, 2) neuroinflammation, 3) mitochondrial dysfunction, 4) neuronal cell death, and 5) neurological deficits. The present study provides novel insights to further our understanding of NPY’s role in ischemic brain injury.

The aim of this study was to determine early weight loss-associated changes in subcutaneous abdominal white adipose tissue (WAT) gene expression in obese men with lowered serum testosterone by RNA next-generation sequencing. Fourteen men, mean age (IQR) 51.6 years (43.4–54.5), BMI 38.3 kg/m2 (34.6–40.8) and total testosterone 8.4 nmol/L (7.5–9.5) provided subcutaneous WAT samples at baseline and after 2 weeks of a very low energy diet. Body weight loss was similar in participants receiving testosterone (n = 6), −5.27 kg [95% CI −6.17; −4.26], and placebo (n = 8), −4.57 kg [95% CI −6.10; −3.55], p = 0.86. In placebo-treated men, of the 14,410 genes expressed in subcutaneous WAT, four genes, Angiopoietin-like 4, Semaphorin 3 G, Neuropilin 2 and Angiopoietin 4, were upregulated (adjusted false discovery rate P

WOS:000629439100001 PMID: 33722110 Gastric outlet obstruction (GOO) is caused mainly by pyloric or duodenal blockage; gastric surgery and vagotomy are effective treatments. We investigated the short term effects of experimental GOO and truncal vagotomy (TV) on gut hormone levels. We used 8-week-old male Wistar rats divided randomly into four groups: control, GOO, TV, and GOO + TV. At the end of the experiment, blood and tissue samples of the pylorus and fundus were obtained for biochemical and immunohistochemical analysis. Gastric motility decreased in the TV group, but there was no difference in food intake compared to the control group; water consumption and urine output were increased. Feces excretion and food intake decreased due to loss of food movement from the stomach of GOO and GOO + TV rats. Levels of insulin and ghrelin were lower than for the control group, but levels of cholecystokinin were higher. Leptin and glucagon-like peptide 1 levels were increased in the GOO group, while somatostatin was decreased. Leptin immunostaining levels were decreased in the GOO + TV group. Gastrin and neuropeptide Y levels were lower in the GOO and GOO + TV groups compared to the other groups. We found that both gut hormone levels related to gastric motility and metabolism, and immunohistochemical staining of the stomach tissue were altered by TV and GOO. Measuring changes in gut hormones following gastric surgery could be useful for monitoring the effectiveness of treatment

Human neuropeptide Y receptors (Y1R, Y2R, Y4R, and Y5R) belong to the superfamily of G protein-coupled receptors and play an important role in the regulation of food intake and energy metabolism. We identified and characterized the first selective Y4R allosteric antagonist (S)-VU0637120, an important step toward validating Y receptors as therapeutic targets for metabolic diseases. To obtain insight into the antagonistic mechanism of (S)-VU0637120, we conducted a variety of in vitro, ex vivo, and in silico studies. These studies revealed that (S)-VU0637120 selectively inhibits native Y4R function and binds in an allosteric site located below the binding pocket of the endogenous ligand pancreatic polypeptide in the core of the Y4R transmembrane domains. Taken together, our studies provide a first-of-its-kind tool for probing Y4R function and improve the general understanding of allosteric modulation, ultimately contributing to the rational development of allosteric modulators for peptide-activated G protein-coupled receptors (GPCRs).

The superficial gland of the third eyelid (SGTE) and deep gland of the third eyelid (DGTE) are classified as accessory lacrimal glands. The aim of the present study was to immunohistochemically investigate the expression of vasoactive intestinal peptide (VIP), dopamine beta-hydroxylase (DβH), substance P (SP), galanin, neuropeptide Y (NPY), pituitary adenylate cyclase-activating peptide (PACAP), somatostatin and calcitonin gene-related peptide (CGRP) in the porcine SGTE and DGTE. We demonstrated the distribution patterns of VIP, DβH, SP, NPY and galanin in the nerve fibres in the SGTE and DGTE. None of somatostatin-, PACAP- and CGRP-immunoreactive (IR) nerve fibres were found in the SGTE and DGTE. The majority of VIP- and DβH-IR nerves fibres were found near to glandular acini, tubules, secretory ducts and blood vessels in the SGTE and DGTE. VIP-IR nerve fibres were found in external connective tissue in SGTE and DGTE and only in interlobular connective tissue in the SGTE. DβH-IR nerve fibres were found in interlobular and external connective tissue in the DGTE but not in the SGTE. Single galanin-, SP- and NPY-IR nerve fibres were observed in close proximity to acini and tubules in the SGTE and DGTE. Single galanin-, SP-, NPY-IR nerve fibres were found in close proximity to the secretory ducts in the DGTE, however only SP-IR nerve fibres were found near to the secretory ducts in SGTE. In conclusion, our research aims to highlight some aspects of SGTE and DGTE innervation in pigs and may also be a source of basic knowledge for further studies.

The human neuropeptide Y (NPY) Y2 receptor (Y2R) plays essential roles in food intake, bone formation and mood regulation, and has been considered an important drug target for obesity and anxiety. However, development of drugs targeting Y2R remains challenging with no success in clinical application yet. Here, we report the crystal structure of Y2R bound to a selective antagonist JNJ-31020028 at 2.8 A resolution. The structure reveals molecular details of the ligand-binding mode of Y2R. Combined with mutagenesis studies, the Y2R structure provides insights into key factors that define antagonistic activity of diverse antagonists. Comparison with the previously determined antagonist-bound Y1R structures identified receptor-ligand interactions that play different roles in modulating receptor activation and mediating ligand selectivity. These findings deepen our understanding about molecular mechanisms of ligand recognition and subtype specificity of NPY receptors, and would enable structure-based drug design. The human neuropeptide Y receptor Y2 (Y2R) is a drug target for the treatment of obesity and anxiety. Crystal structure of Y2R bound to a selective antagonist and accompanying mutagenesis provide insights into ligand recognition and subtype specificity of NPY receptors.

Anxiety sensitivity (AS) refers to a fear of the negative implications of anxiety, and arises due to gene-environment interactions. We investigated whether genetic variation in two neuropeptides implicated in the stress response, neuropeptide Y (NPY) and pituitary adenylate cyclase-activating polypeptide receptor 1, interacted with childhood trauma (CT) to influence AS.This cross-sectional study examined the CT x genetic variant effects on AS in 951 adolescents who self-identified as Xhosa or South African Colored (SAC) ethnicity.In Xhosa females, theThe

BackgroundSeveral large clinical trials have confirmed the cardioprotective role of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in patients with type 2 diabetes. However, whether empagliflozin, as an SGLT2i, could alleviate atherosclerosis progression in non-diabetic states remain unknown.MethodsApoE-/- mice were fed a Western diet for 12 weeks to induce atherosclerosis. On the 7th week, a group of mice were treated with drinking water containing empagliflozin (10 mg/kg/day), while another group was given normal water. At the 12th week, the whole aortas of each group were harvested. Oil Red O, HE and Movat staining were performed for atherosclerotic lesion area and size. Mouse serum lipid profiles (total cholesterol [TC], triglyceride [TG], low-density lipoprotein-c [LDL], and high-density lipoprotein-c [HDL]), systemic inflammation levels (IL-1β, IL-6 and IL-10), renin-angiotensin-aldosterone system (RAAS) components and sympathetic activity (norepinephrine and neuropeptide Y) indicators were measured by ELISA.ResultsEmpagliflozin reduced the atherosclerotic lesion burden (-8.6 %,P = 0.004) at aortic root in ApoE-/- mice. In addition, empagliflozin decreased body weight (-3.27 g,P = 0.002), lipid profiles (TC: [-15.3 mmol/L,P = 0.011]; TG: [-2.4 mmol/L,P P = 0.010]), RAAS (renin [-9.3 ng/L,P = 0.047]; aldosterone [-16.7 ng/L,P P = 0.019]; neuropeptide Y [-8.8 ng/L,P = 0.002]). However, the anti-inflammatory effect of empagliflozin was not significantly evident.ConclusionsThe early atherosclerotic lesion size was less visible in empagliflozin-treated mice. Empagliflozin could decrease lipid profiles and sympathetic activity in atherosclerosis.

Caloric restriction (CR), an energy-restricted intervention with undernutrition instead of malnutrition, is widely known to prolong lifespan and protect against the age-related deteriorations. Recently it is found that CR significantly affects female reproduction via hypothalamic (corticotropin releasing hormone, neuropeptide Y, agouti-related peptide) and peripheral (leptin, ghrelin, insulin, insulin-like growth factor) mediators, which can regulate the energy homeostasis. Although CR reduces the fertility in female mammals, it exerts positive effects like preserving reproductive capacity. In this review, we aim to discuss the comprehensive effects of CR on the central hypothalamus-pituitary-gonad axis and peripheral ovary and uterus. In addition, we emphasize the influence of CR during pregnancy and highlight the relationship between CR and reproductive-associated diseases. Fully understanding and analyzing the effects of CR on the female reproduction could provide better strategies for the management and prevention of female reproductive dysfunctions.

Cardiac hypertrophy (CH) is a major risk factor for heart failure accompanied by maladaptive cardiac remodeling. The role and potential mechanism of neuropeptide Y (NPY) in CH are still unclear. We will explore the role and the mechanism of NPY inactivation (NPY-I) in CH caused by pressure overload. Abdominal aortic constriction (AAC) was used to induce CH model in rats. NPY or angiotensin II (Ang II) was used to trigger CH model in vitro in neonatal rat ventricular myocytes (NRVMs). We found that NPY was increased in the heart and plasma of hypertrophic rats. However, Ang II did not increase NPY expression in cardiomyocytes. NPY-I attenuated CH as decreasing CH-related markers (ANP, BNP and β-MHC mRNA) level, reducing cell surface area, and restoring cardiac function. NPY inactivation increased miR-216b and decreased FoxO4 expression in CH heart. Moreover, NPY decreased miR-216b and increased FoxO4 expression in NRVMs which were reversed by NPY type 1 receptor (NPY1R) antagonist BIBO3304. MiR-216b mimic and FoxO4 siRNA (small interfering RNA) inhibited NPY/Ang II-induced myocardial hypertrophy in vitro. Meanwhile, BIBO3304 reversed the pro-hypertrophy effect of NPY in vitro. Collectively, NPY deficiency attenuated CH by NPY1R-miR-216b-FoxO4 axis. These findings suggested that NPY would be a potential therapeutic target for the prevention and treatment of cardiac hypertrophy.

Introduction Low back pain (LBP) is common in warfighters. Noninvasive interventions are necessary to expedite return-to-function. Soft tissue manipulation, for example, massage, is a method used to treat LBP. Instrument-assisted soft tissue manipulation (IASTM) uses a rigid device to mobilize the tissue. This study explored the effects of IASTM on pain, function, and biomarkers. Methods Sprague-Dawley rats (n = 44) were randomized to groups (n = 6/grp): (A) cage control; (B) 3 days (3d) postinjury (inj), untreated; (C) 3d inj, Results The back pressure pain threshold (PPT) lowered bilaterally at 3 days postinjury (P Conclusions LBP increased pain sensitivity and diminished function. IASTM treatment increased pain sensitization acutely in the back but significantly reduced pain sensitivity in the contralateral rear paw. Findings suggest IASTM may positively influence pain modulation and inflammation while improving gait patterns. Soft tissue manipulation may be beneficial as a conservative treatment option for LBP.

The article presents a study of the effect of a modified fragment of neuropeptide Y (H-L-Ile-L-Asn-L-Leu-L-Nle-L-Ser- L-Arg-L-Asn-L-Arg-L-Tyr-NH2) named nonapeptide NP9 on the memory phases and extrapolation escape of animals. The study was performed in the passive avoidance test with intact animals, scopolamine-treated animals, and the extrapolation escape task. NP9 was investigated in the dose range of 0.04-0.4 mg/kg with a single intranasal administration. The comparison drug used peptide nootropic medicine Semax® (Met-Glu-His-Phe-Pro-Gly-Pro) at a dose of 0.1 mg/kg. Efficiency was assessed by the retention latency, the percentage of animals that have reached the learning criterion, the number of incomplete attempts to enter, the antiamnestic activity index calculated by Butlers formula, and the number of animals that successfully performed the extrapolation escape task. Peptide NP9 was superior to Semax® in most indicators. It demonstrated the ability to improve memorization due to its effect on I phase of memory and facilitated extinction of negative experiences when administered after a stress stimulus. NP9 also increased the cognitive ability of animals in the conditions an aversive environment in the extrapolation escape test. Thus, peptide NP9 is promising for a further study as a potential drug for the treatment of cognitive impairment and therapy of post-traumatic stress disorder.

The concept of metal chelation is based on simple coordination chemistry. The development of an ideal metal chelator that completely and selectively removes toxic metals from a specific metal binding site in proteins is required to prevent and or inhibit a variety of diseases, among them neurodegenerative diseases. This work examines neuropeptide Y (NPY) as a Zn2+ and Cu2+ chelator agent. NPY is a natural peptide that is produced in the human body; therefore, it is not a toxic agent and the complex that it forms is not toxic as well. Our simulations reveal that NPY has an efficient Zn2+ chelation activity but is less effective in chelating Cu2+. Moreover, while NPY demonstrates several conformations, the metal chelation occurs more efficiently in its native structure. Beyond the exploration of the activity of NPY as a Zn2+ and Cu2+ chelator agent, this work provides an insight into the molecular mechanisms of the chelation of these metals at the molecular level. The outcomes from this work may guide future experimental studies to examine NPY in metal chelation therapy for neurodegenerative diseases.

Introduction: Repeated traumatic events result in long-lasting neuropsychiatric ailments, including neuroendocrine imbalances. Neuropeptide Y (NPY) in the arcuate nucleus (Arc) is an important orexigenic peptide. However, the molecular underpinnings of its dysregulation owing to traumatic brain injury remain unknown. Methods: Rats were subjected to repeated mild traumatic brain injury (rMTBI) using the closed head weight-drop model. Feeding behavior and the regulatory epigenetic parameters of NPY expression were measured at 48 h and 30 days post-rMTBI. Further, sodium butyrate (SB), a pan-histone deacetylase (HDAC) inhibitor, was administered to examine whether histone deacetylation is involved in NPY expression post-rMTBI. Results: The rMTBI attenuated food intake, which was coincident with a decrease in NPY mRNA and protein levels in the Arc post-rMTBI. Further, rMTBI also reduced the mRNA levels of the cAMP response element-binding protein (CREB) and CREB-binding protein (CBP) and altered the mRNA levels of the various isoforms of the HDACs. Concurrently, the acetylated histone 3-lysine 9 (H3-K9) levels and the binding of CBP at the NPY promoter in the Arc of the rMTBI-exposed rats were reduced. However, the treatment with SB corrected the rMTBI-induced deficits in the H3-K9 acetylation levels and CBP occupancy at the NPY promoter, restoring both NPY expression and food intake. Conclusions: These findings suggest that histone deacetylation at the NPY promoter persistently controls NPY function in the Arc after rMTBI. This study also demonstrates the efficacy of HDAC inhibitors in mitigating trauma-induced neuroendocrine maladaptations in the hypothalamus.

Objectives The concrete mechanism underlying the pathogenesis of cervical vertigo has not been well illustrated. This study aims to determine the diagnostic and potential therapeutic values of the neurotransmitter neuropeptide Y (NPY) in cervical vertigo. Methods Sixty male rabbits were randomly divided into five groups: the blank control, superior cervical sympathetic ganglia (SCSG) stimulation, SCSG sham-operated control (ganglion exposure and electrode placement in SCSG), inferior cervical sympathetic ganglia (ICSG) stimulation, and ICSG sham-operated control (ganglion exposure and electrode placement in ICSG) groups. Electrical stimulation at 30.0 Hz and 10.0 V for 5 min was delivered to expose SCSG or ICSG. Immunochemistry was conducted to determine the expression levels of NPY in all cervical spinal ganglia (C1–C8) dissected immediately after electrical stimulation. Results According to the immunohistochemical results, the blank control group only had few NPY-positive cells and was not significantly different with the sham-operated group. However, after SCSG stimulation, more NPY-positive cells in C2, C3, C4, and C5 were observed (C2 and C3 were the most evident). After ICSG stimulation, more NPY-positive cells were found in C6, C7, and C8, particularly in C6 and C7. Conclusions The low expression of NPY in all cervical ganglia (C1–C8) can be enhanced by electrical stimulation, whereas the expression of NPY in the cervical sympathetic ganglia was not affected by mechanical stimulation. This study provided new insights into the possible relationship between the neurotransmitter NPY and the pathogenesis of cervical vertigo.

Long chain fatty acids (LCFAs) have been suggested to influence the activity of hypothalamic neurons, however, limited studies have attempted to identify the neurochemical phenotype of these neurons. We aimed to determine if physiological levels of LCFAs alter the electrical excitability of pro-opiomelanocortin (POMC) and neuropeptide Y (NPY) neurons in the arcuate nucleus of the hypothalamus. We utilised whole-cell patch-clamp electrophysiology on brain slice preparations from genetic mouse models where green fluorescent protein was expressed in either POMC or NPY expressing cells. All animals had undergone an overnight fast to replicate conditions in which fatty acids would usually increase. Bath application of LCFAs were found to predominantly inhibit POMC neurons and predominantly excite NPY neurons. Differences between oleic and palmitic acid were not observed. These results suggest that LCFAs in the cerebrospinal fluid exert an underlying orexigenic tone to key hypothalamic neurons known to regulate energy homeostasis.

Neuropeptide Y (NPY) plays a pivotal role in food intake and body weight regulation in both birds and mammals. Unlike imported broilers and layers, native Thai chicken, a tropical non-seasonal breeding species, has lower body weight and exhibits strongly maternal behaviors which, in turn, affect feeding behavior during the reproductive cycle. The aim of this study was to investigate the role(s) of NPY that might be associated with the reproductive cycle of female native Thai chickens using immunohistochemistry technique. The distributions of NPY-immunoreactive (-ir) neurons and fibers in the brain of laying and fasted chickens was also elucidated. Changes in body weight and number of NPY-ir neurons in the nucleus paraventricularis magnocellularis (PVN) were compared across reproductive stages. The results revealed that NPY-ir neurons and fibers were distributed throughout the brain with the greatest density located in the PVN. Differences in the number of NPY-ir neurons in the PVN were found across reproductive stages. The numbers were lowest in non-egg laying and egg laying stages and significantly higher during egg-incubating and chick-rearing stages. Changes in body weight were inversely related to the number of NPY-ir neurons across reproductive stages. In addition, food restriction caused an increase in NPY immunoreactivity, confirming the role of NPY in response to food restriction. Taken together, the present findings suggest that the NPYergic system in the PVN plays an important role in the regulation of food intake during the reproductive cycle in this non-seasonal breeding tropical species.