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Neuropeptide Y (NPY) is a 36-amino acid peptide that is widely expressed throughout the limbic system. Recent evidence has highlighted NPY as a marker of resilience to posttraumatic psychopathology, which may be due to its association with neural regions involved with emotion regulation. This study examined whether plasma NPY levels moderated the relationship between emotion regulation and psychopathology in a sample of adult survivors of childhood interpersonal trauma, a population known to be at high risk for psychopathology. Adults exposed to an interpersonal criterion A trauma during childhood (N = 54) were recruited from an urban population at a midwestern medical center and completed a baseline study visit as part of a larger clinical trial. Participants gave a blood sample in order to assess circulating levels of NPY and answered questions related to emotion regulation and mood-related pathology. Results of a moderated multiple regression showed that the overall model was significant R 2 = 0.26, F (5, 48) = 3.46, p <.01. Difficulties in emotion regulation was significantly predictive of psychopathology (unstandardized B = 0.032, p <.01), and this relationship was significantly moderated by levels of NPY (unstandardized B = −0.001, p <.05) such that the relationship between emotion regulation and psychopathology was weaker for those with higher levels of NPY. Results suggest that higher levels of NPY may lessen the association between emotion regulation and posttraumatic psychopathology in survivors of childhood interpersonal trauma. Further investigation of the contribution of NPY to psychopathology in this population is warranted. 02279290. • We assessed adult survivors of childhood interpersonal trauma. • Blood samples and self-report questionnaires were collected. • Higher neuropeptide-Y (NPY) was associated with better emotion regulation. • Better emotion regulation was associated with reduced mood-related symptoms. • NPY moderated the relationship between emotion regulation and mood-related symptoms. [ABSTRACT FROM AUTHOR]

Objective: Prostate cancer is a solid tumor that can be fatal in men. Early detection and proper management are essential for improving outcomes and reducing mortality rates associated with this disease. This study aimed to evaluate the potential of neuropeptide Y (NPY) as a biomarker to enhance the effectiveness of prostate specific antigen (PSA) testing in diagnosing and predicting prostate cancer prognosis. NPY, a well-known sympathetic neurotransmitter, possesses growth-promoting and angiogenic properties in various cell types, including those relevant to prostate cancer. Additionally, NPY has been linked to neuroendocrine differentiation of prostate cancer cells. By comparing the efficacy of PSA testing alone with the addition of NPY, this study aimed to determine whether NPY could offer additional predictive value for prostate cancer progression and prognosis. Materials and Methods: This study involved 90 patients each diagnosed with localized prostate cancer (LPC), metastatic prostate cancer (mPC) at diagnosis, and metastatic castration-resistant prostate cancer (mCRPC) who visited our urology clinic between 2022 and 2023. Blood samples were collected from all participants between 08:00 and 09:00 after a 12 hour fast. In the LPC and mPC groups, samples were collected upon diagnosis, whereas in the mCRPC group, samples were collected upon development of treatment resistance. NPY levels in blood samples were analyzed using enzyme-linked immunosorbent assay method. Serum NPY levels were compared between the LPC, mPC, and mCRPC groups. Results: PSA values were calculated as 12.6 (7.08-32.47) ng/L in the LPC group, 159 (73.1-405.2) ng/L in the mPC group, and 38.33 (18.4-132) ng/L in the mCRPC group, with a statistically significant difference between the groups (p<0.001). The average NPY values were 351.3±162.7 ng/L in the LPC group, 276.5±85 ng/L in the mPC group, and 272.13±94.7 ng/L in the mCRPC group. NPY values were found to be statistically significantly higher in the LPC group (p=0.018). Conclusion: The serum NPY levels were notably elevated in the LPC group compared with the mPC and mCRPC groups. This finding implies a potential association between low NPY levels and mPC as well as mCRPC. [ABSTRACT FROM AUTHOR]

Obesity, which develops especially in childhood and adolescence, is an important health problem at all ages. Hormones that stimulate the hypothalamus about the body's energy stores prevent eating and keep body weight within certain physiological limits. Investigating obesity and the hormones associated with obesity is very important in this context. We believe that the functions of obesity-associated hormones that have been identified to date can guide further studies. In this review, obesity-related hormones and their mechanisms of action are discussed.

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Introduction: The effectiveness of various extrinsic and intrinsic regulatory signals on food intake and body weight can be influenced by hypothalamic neuropeptide-Y (NPY) and proopiomelanocortin (POMC) neurons. While several studies emphasize the vital role of regular physical activity in effective weight management, how these molecular and cellular processes interact with physical activity remains an area in need of further exploration. Hence, this study aims to investigate the impact of various long-term physical activities intensities on the regulation of body weight and appetite. Methods: Twenty-one Wistar rats (n=7) were randomized into three groups: 1) Control group, 2) a group engaged in regular exercise at moderate intensity for 24 weeks (24-ME, 5 days each week), and 3) a group frequently and intensively exercising over 24 weeks (24-IE, 5 days each week). Subsequently, Reverse transcription polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) methods were performed to measure gene expression of hypothalamic arcuate nucleus NPY and POMC, as well as serum levels of acyl-ghrelin and leptin. Results: The POMC mRNA level decreased in the 24-ME group compared to the control rats. However, intensive regular exercise increased NPY expression compared to the control rats. Inversely, body weight and food intake levels were considerably higher in the 24-ME and 24-IE groups than in the control group. Different intensities of prolonged exercise seem to heighten appetite, eventually increasing body weight through distinct molecular pathways. Conclusion: Hence, it can be concluded that prolonged intensive exercise may not be a practical approach for weight loss. [ABSTRACT FROM AUTHOR]

Loss of neuropeptide Y (NPY)-expressing interneurons in the hippocampus and decaying cholinergic neuromodulation are thought to contribute to impaired cognitive function during aging. However, the interaction of these two neuromodulatory systems in maintaining hippocampal synaptic plasticity during healthy aging has not been explored so far. Here we report profound sex differences in the Neuropeptide-Y (NPY) levels in the dorsal dentate gyrus (DG) with higher NPY concentrations in the male mice compared to their female counterparts and a reduction of NPY levels during aging specifically in males. This change in aged males is accompanied by a deficit in theta burst-induced long-term potentiation (LTP) in the medial perforant path-to-dorsal DG (MPP-DG) synapse, which can be rescued by enhancing cholinergic activation with the acetylcholine esterase blocker, physostigmine. Importantly, NPYergic transmission is required for this rescue of LTP. Moreover, exogenous NPY application alone is sufficient to recover LTP induction in aged male mice, even in the absence of the cholinergic stimulator. Together, our results suggest that in male mice NPYergic neurotransmission is a critical factor for maintaining dorsal DG LTP during aging. [ABSTRACT FROM AUTHOR]

Loss of neuropeptide Y (NPY)-expressing interneurons in the hippocampus and decaying cholinergic neuromodulation are thought to contribute to impaired cognitive function during aging. However, the interaction of these two neuromodulatory systems in maintaining hippocampal synaptic plasticity during healthy aging has not been explored so far. Here we report profound sex differences in the Neuropeptide-Y (NPY) levels in the dorsal dentate gyrus (DG) with higher NPY concentrations in the male mice compared to their female counterparts and a reduction of NPY levels during aging specifically in males. This change in aged males is accompanied by a deficit in theta burst-induced long-term potentiation (LTP) in the medial perforant path-to-dorsal DG (MPP-DG) synapse, which can be rescued by enhancing cholinergic activation with the acetylcholine esterase blocker, physostigmine. Importantly, NPYergic transmission is required for this rescue of LTP. Moreover, exogenous NPY application alone is sufficient to recover LTP induction in aged male mice, even in the absence of the cholinergic stimulator. Together, our results suggest that in male mice NPYergic neurotransmission is a critical factor for maintaining dorsal DG LTP during aging.

Objective: To analyze the effects of sodium hyaluronate administration on the serum levels of antioxidase, substance P (SP), and neuropeptide Y (NPY) in patients undergoing locking plate fixation (LPF) for tibial plateau fractures (TPF). Methods: We retrospectively analyzed the records of 66 patients with TPF who received treatment in the Beijing Chao-yang Hospital from February 2017 to August 2020. According to the treatment records, 33 patients underwent LPF surgery (control-group), and 33 patients underwent LPF plus sodium hyaluronate treatment (observation-group). The levels of antioxidant enzymes (superoxide dismutase (SOD), catalase (CAT) and total antioxidant capacity (TAC)), SP and NPY. Results: Seven days after LPF operations, both groups showed lower levels of SOD, CAT, and TAC compared to presurgery levels, while levels of SP and NPY were higher. However, the observation group showed higher levels of SOD, CAT, and TAC compared to the control group, and lower levels of SP and NPY in the control group (P<0.05). Conclusion: The treatment of TPF with LPF plus sodium hyaluronate administration has been shown to effectively reduce oxidative stress reactions, improve SP and NPY levels. [ABSTRACT FROM AUTHOR]

Abstract Background Targeting G protein-coupled receptors on the surface of cancer cells with peptide ligands is a promising concept for the selective tumor delivery of therapeutically active cargos, including radiometals for targeted radionuclide therapy (TRT). Recently, the radiolanthanide terbium-161 (161Tb) gained significant interest for TRT application, since it decays with medium-energy β-radiation but also emits a significant amount of conversion and Auger electrons with short tissue penetration range. The therapeutic efficiency of radiometals emitting Auger electrons, like 161Tb, can therefore be highly boosted by an additional subcellular delivery into the nucleus, in order to facilitate maximum dose deposition to the DNA. In this study, we describe the design of a multifunctional, radiolabeled neuropeptide-Y (NPY) conjugate, to address radiolanthanides to the nucleus of cells naturally overexpressing the human Y1 receptor (hY1R). By using solid-phase peptide synthesis, the hY1R-preferring [F7,P34]-NPY was modified with a fatty acid, a cathepsin B-cleavable linker, followed by a nuclear localization sequence (NLS), and a DOTA chelator (compound pb12). In this proof-of-concept study, labeling was performed with either native terbium-159 (natTb), as surrogate for 161Tb, or with indium-111 (111In). Results [natTb]Tb-pb12 showed a preserved high binding affinity to endogenous hY1R on MCF-7 cells and was able to induce receptor activation and internalization similar to the hY1R-preferring [F7,P34]-NPY. Specific internalization of the 111In-labeled conjugate into MCF-7 cells was observed, and importantly, time-dependent nuclear uptake of 111In was demonstrated. Study of metabolic stability showed that the peptide is insufficiently stable in human plasma. This was confirmed by injection of [111In]In-pb12 in nude mice bearing MCF-7 xenograft which showed specific uptake only at very early time point. Conclusion The multifunctional NPY conjugate with a releasable DOTA-NLS unit represents a promising concept for enhanced TRT with Auger electron-emitting radiolanthanides. Our research is now focusing on improving the reported concept with respect to the poor plasmatic stability of this promising radiopeptide.

Background: Targeting G protein-coupled receptors on the surface of cancer cells with peptide ligands is a promising concept for the selective tumor delivery of therapeutically active cargos, including radiometals for targeted radionuclide therapy (TRT). Recently, the radiolanthanide terbium-161 (161Tb) gained significant interest for TRT application, since it decays with medium-energy β-radiation but also emits a significant amount of conversion and Auger electrons with short tissue penetration range. The therapeutic efficiency of radiometals emitting Auger electrons, like 161Tb, can therefore be highly boosted by an additional subcellular delivery into the nucleus, in order to facilitate maximum dose deposition to the DNA. In this study, we describe the design of a multifunctional, radiolabeled neuropeptide-Y (NPY) conjugate, to address radiolanthanides to the nucleus of cells naturally overexpressing the human Y1 receptor (hY1R). By using solid-phase peptide synthesis, the hY1R-preferring [F7,P34]-NPY was modified with a fatty acid, a cathepsin B-cleavable linker, followed by a nuclear localization sequence (NLS), and a DOTA chelator (compound pb12). In this proof-of-concept study, labeling was performed with either native terbium-159 (natTb), as surrogate for 161Tb, or with indium-111 (111In). Results: [natTb]Tb-pb12 showed a preserved high binding affinity to endogenous hY1R on MCF-7 cells and was able to induce receptor activation and internalization similar to the hY1R-preferring [F7,P34]-NPY. Specific internalization of the 111In-labeled conjugate into MCF-7 cells was observed, and importantly, time-dependent nuclear uptake of 111In was demonstrated. Study of metabolic stability showed that the peptide is insufficiently stable in human plasma. This was confirmed by injection of [111In]In-pb12 in nude mice bearing MCF-7 xenograft which showed specific uptake only at very early time point. Conclusion: The multifunctional NPY conjugate with a releasable DOTA-NLS unit represents a promising concept for enhanced TRT with Auger electron-emitting radiolanthanides. Our research is now focusing on improving the reported concept with respect to the poor plasmatic stability of this promising radiopeptide. [ABSTRACT FROM AUTHOR]

Huntington's Disease is a neurodegenerative condition caused by a polyglutamine expansion in the huntingtin (Htt) protein, which aggregates and also causes neuronal dysfunction. Pathogenic N-terminal htt fragments perturb axonal transport in vitro. To determine whether this occurs in vivo and to elucidate how transport is affected, we expressed htt exon 1 with either pathogenic (HttEx1Q93) or non-pathogenic (HttEx1Q20) polyglutamine tracts in Drosophila. We found that HttEx1Q93 expression causes axonal accumulation of GFP-tagged fast axonal transport vesicles in vivo and leads to aggregates within larval motor neuron axons. Time-lapse video microscopy, shows that vesicle velocity is unchanged in HttEx1Q93-axons compared to HttEx1Q20-axons, but vesicle stalling occurs to a greater extent. Whilst HttEx1Q93 expression did not affect locomotor behaviour, external heat stress unveiled a locomotion deficit in HttEx1Q93 larvae. Therefore vesicle transport abnormalities amidst axonal htt aggregation places a cumulative burden upon normal neuronal function under stressful conditions.

Loss of appetite affects one‐third of patients with CKD and is the leading cause of malnutrition in this population. Orexigenic Agouti‐related peptide (AgRP) with neuropeptide‐Y (NPY) and anorexigenic melanocyte‐stimulating hormone‐α (MSH‐α) with cocaine‐ and amphetamine‐regulated transcript (CART) are known to regulate appetite. In this study, we aimed to evaluate the levels of these peptides in CKD patients compared to healthy subjects and demonstrate the effects of dialysis treatment and erythropoiesis‐stimulating agent (ESA) therapy. The cross‐sectional study is composed of consecutive inclusion of 20 healthy individuals, 20 predialysis CKD patients, 20 HD, and 20 peritoneal dialysis (PD) patients. Exclusion criteria were an active infection, history of malignancy, hypo‐ or hyperthyroidism, and diabetes. Patients on dialysis had targeted Kt/Vs. Demographic features and BMIs of the four groups were similar. Levels of AgRP, NPY, AMSH, and CART were significantly different between groups. Nondialysis CKD patients had significantly lower hypothalamic hormones compared to healthy individuals, HD and PD patients (P = 0.02, P = 0.03, and P = 0.07 for AgRP; P = 0.02, P = 0.01, and P = 0.09 for NPY; P = 0.02, P = 0.02, and P = 0.03 for AMSH; P = 0.02, P = 0.005, and P = 0.030 for CART). Dialysis patients with or without ESA treatment had similar hormone levels (P = 0.13 for AgRP; P = 0.11 for NPY; P = 0.23 for AMSH, and P = 019 for CART). Predialysis CKD patients have lower orexigenic and presumably indirectly lower anorexigenic peptides compared to healthy subjects and dialysis patients. ESA treatment does not affect these hypothalamic peptides in dialysis patients. [ABSTRACT FROM AUTHOR]

Aims The co-transmitter neuropeptide-Y (NPY) is released during high sympathetic drive, including ST-elevation myocardial infarction (STEMI), and can be a potent vasoconstrictor. We hypothesized that myocardial NPY levels correlate with reperfusion and subsequent recovery following primary percutaneous coronary intervention (PPCI), and sought to determine if and how NPY constricts the coronary microvasculature. Methods and results Peripheral venous NPY levels were significantly higher in patients with STEMI (n  = 45) compared to acute coronary syndromes/stable angina (n  = 48) or with normal coronary arteries (NC, n  = 16). Overall coronary sinus (CS) and peripheral venous NPY levels were significantly positively correlated (r  = 0.79). STEMI patients with the highest CS NPY levels had significantly lower coronary flow reserve, and higher index of microvascular resistance measured with a coronary flow wire. After 2 days they also had significantly higher levels of myocardial oedema and microvascular obstruction on cardiac magnetic resonance imaging, and significantly lower ejection fractions and ventricular dilatation 6 months later. NPY (100–250 nM) caused significant vasoconstriction of rat microvascular coronary arteries via increasing vascular smooth muscle calcium waves, and also significantly increased coronary vascular resistance and infarct size in Langendorff hearts. These effects were blocked by the Y1 receptor antagonist BIBO3304 (1 μM). Immunohistochemistry of the human coronary microvasculature demonstrated the presence of vascular smooth muscle Y1 receptors. Conclusion High CS NPY levels immediately after reperfusion correlate with microvascular dysfunction, greater myocardial injury, and reduced ejection fraction 6 months after STEMI. NPY constricts the coronary microcirculation via the Y1 receptor, and antagonists may be a useful PPCI adjunct therapy. View large Download slide View large Download slide [ABSTRACT FROM AUTHOR]

Neuropeptide-Y (NPY) is widely distributed centrally and peripherally and plays an important role in regulating glucose metabolism, energy metabolism and vascular function. Several studies had found that NPY is involved in the pathophysiology of type-2 diabetes Mellitus (T2DM). The aim of this study was to evaluate the association of NPY -399 (T/C) gene polymorphism and its serum level with susceptibility to T2DM. Seventy diabetic patients and seventy age and gender matched healthy controls were enrolled in this study. Serum NPY was measured by ELISA and NPY rs16147(-399 T/C) polymorphism was analyzed using the TaqMan allelic discrimination assay technique. Results showed significant statistical differences between the two studied groups regarding serum NPY level and NPY rs16147 (-399T/C) genotype distribution with increased serum NPY level and increased frequency of the CC and TC genotype in patients with diabetes mellitus. Conclusion: CC genotypes of NPY (-399 T/C) gene polymorphism and its associated high serum NPY level might be a genetic risk factor for T2DM. [ABSTRACT FROM AUTHOR]

Objective: This study aims to evaluate the plasma levels of neuropeptide-Y (NPY), leptin and ghrelin and in children with attention deficit hyperactivity disorder (ADHD) and investigate the neurobiological mechanisms beneath side effects of methylphenidate such as lack of appetite, weight loss and/or decrease in weight gain. Methods: Thirty children diagnosed as ADHD with DSM-5 and 21 healthy children similar to study group with age and gender were included in the study. All subjects are evaluated with Kiddie Schedule for Affective Disorders and Schizophrenia-Present and Lifetime Version (K-SADS-PL). All parents filled sociodemographic data form, also parents of the chil-dren with ADHD filled Conners' Parent Rating Scale (CPRS). ADHD group evaluated with Barkley Stimulant Side Effect Evaluation Form after two months of extended release methylphenidate (OROS-MPH) therapy. Plasma NPY, leptin and ghrelin levels were evaluated in control group for once and in ADHD group for twice, before and 2 months after treatment with enzyme-like immune-sorbent assay (ELISA) kits. Results: In our study, when plasma leptin, ghrelin and NPY levels of healthy controls and ADHD group were compared; NPY level was lower in the ADHD group. Compared with healthy controls, post-treatment ADHD group leptin level was observed to be lower. In the ADHD group, only NPY level was found to be higher after treatment than before treatment. Conclusion: It was observed that NPY levels were found to be lower in the ADHD group than in the healthy group, and plasma levels increased after treatment. In addition, leptin and ghrelin levels not changed after treatment. Thus, further studies with larger study groups are needed whether these changes will be more meaningful when the treatment duration is prolonged. New studies may reveal neurobiological mechanisms beneath loss of appetite and/or weight loss associated with methylphenidate treatment. [ABSTRACT FROM AUTHOR]

Melanocortin and neuropeptide-Y (NPY) are both involved in feeding and energy regulation, and they have opposite effects in the paraventricular nucleus of the hypothalamus (PVN). The present study examined an interaction between melanocortin in the nucleus of the solitary tract (NTS) and NPY in the PVN. Male Sprague-Dawley rats were implanted with cannulae in the injection sites of interest. In Experiment 1, subjects received either the melanocortin 3/4-receptor (MC3/4) antagonist SHU9119 (0, 10, 50 and 100 pmol/0.5 μl) or the MC3/4 agonist MTII (0, 10, 50, 100 and 200 pmol/0.5 μl) into the NTS. Food intake was measured at 1, 2, 4, 6 and 24-h post-injection. Administration of SHU9119 into the NTS significantly and dose-dependently increased food intake at 1, 2, 4, 6 and 6-24-h, and administration of MTII into the NTS significantly and dose-dependently decreased 24-h free feeding. In Experiment 2, subjects received the MC3/4 agonist MTII (0, 10, 50, 100 and 200 pmol/0.5 μl) into the NTS just prior to NPY (0 and 1μg/0.5 μl) in the PVN. PVN injection of NPY stimulated feeding, and administration of MTII (50, 100 and 200 pmol) into the NTS significantly and dose-dependently decreased NPY-induced feeding at 2, 4, 6 and 6-24-h. These data suggest that there could be a neuronal association between melanocortin in the NTS and NPY in the PVN, and that the melanocortin system in the NTS has an antagonistic effect on NPY-induced feeding in the PVN. [ABSTRACT FROM AUTHOR]

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.

Neuropeptide-Y (NPY) has diverse physiological functions which are extensively studied in vertebrates. However, regulatory role of NPY in relation to brain ontogeny and recrudescence with reference to reproduction is less understood in fish. Present report for the first time evaluated the significance of NPY by transient esiRNA silencing and also analyzed its expression during brain development and gonadal recrudescence in the catfish, Clarias gariepinus . As a first step, full-length cDNA of NPY was cloned from adult catfish brain, which shared high homology with its counterparts from other teleosts upon phylogenetic analysis. Tissue distribution revealed dominant expression of NPY in brain and testis. NPY expression increased during brain development wherein the levels were higher in 100 and 150 days post hatch females than the respective age-matched males. Seasonal cycle analysis showed high expression of NPY in brain during pre-spawning phase in comparison with other reproductive phases. Localization studies exhibited the presence of NPY, abundantly, in the regions of preoptic area, hypothalamus and pituitary. Transient silencing of NPY -esiRNA directly into the brain significantly decreased NPY expression in both the male and female brain of catfish which further resulted in significant decrease of transcripts of tryptophan hydroxylase 2 , catfish gonadotropin-releasing hormone (cfGnRH) , tyrosine hydroxylase and 3β-hydroxysteroid dehydrogenase in brain and luteinizing hormone-β/gonadotropin-II ( lh-β / GTH-II ) in pituitary exhibiting its influence on gonadal axis. In addition, significant decrease of several ovary-related transcripts was observed in NPY-esiRNA silenced female catfish, indicating the plausible role of NPY in ovary through cfGnRH-GTH axis. [ABSTRACT FROM AUTHOR]

Persistent stress triggers a variety of mechanisms, which may ultimately lead to the occurrence of anxiety- and depression-related disorders. Epigenetic modifications represent a mechanism by which chronic stress mediates long-term effects. Here, we analyzed brain tissue from mice exposed to chronic unpredictable stress (CUS), which induced impaired emotional and nociceptive behaviors. As endocannabinoid (eCB) and neuropeptide-Y (Npy) systems modulate emotional processes, we hypothesized that CUS may affect these systems through epigenetic mechanisms. We found reduced Npy expression and Npy type 1 receptor (Npy1r) signaling, and decreased expression of the cannabinoid type 1 receptor (CB1) in the cingulate cortex of CUS mice specifically in low CB1-expressing neurons. Epigenetic investigations revealed reduced levels of histone H3K9 acetylation (H3K9ac) associated to Npy and CB1 genes, which may represent a factor determining the dysregulation occurring at expression and signaling level. CUS mice also showed increased nuclear protein levels and activity of the histone deacetylase type 2 (HDAC2) in the cingulate cortex as compared to controls. Chronic administration of URB597, an inhibitor of anandamide degradation, which is known to induce anxiolysis in CUS mice, reversed the epigenetic changes found in the Npy gene, but was ineffective in alleviating the dysregulation of Npy at transcriptional and signaling level. Our findings suggest that epigenetic alterations in the Npy and CB1 genes represent one of the potential mechanisms contributing to the emotional imbalance induced by CUS in mice, and that the Npy and eCB systems may represent therapeutic targets for the treatment of psychopathologies associated with or triggered by chronic stress states. [ABSTRACT FROM AUTHOR]

The objective of this study is to examine the effects of the endogenous ligands leptin, ghrelin, and neuropeptide Y (NPY) on seizure generation, the oxidant/antioxidant balance, and cytokine levels, which are a result of immune response in a convulsive seizure model. With this goal, Wistar rats were divided into 5 groups—Group 1: Saline, Group 2: Saline + PTZ (65 mg/kg), Group 3: leptin (4 mg/kg) + PTZ, Group 4: ghrelin (80 μg/kg) + PTZ, and Group 5: NPY (60 μg/kg) + PTZ. All injections were delivered intraperitoneally, and simultaneous electroencephalography (EEG) records were obtained. Seizure activity was scored by observing seizure behavior, and the onset time, latency, and seizure duration were determined according to the EEG records. At the end of the experiments, blood samples were obtained in all groups to assess the serum TNF-α, IL-1β, IL-6, FGF-2, galanin, nitric oxide (NOֹ), malondialdehyde (MDA), and glutathione (GSH) levels. The electrophysiological and biochemical findings ( p < 0.05) of this study show that all three peptides have anticonvulsant effects in the pentylenetetrazol (PTZ)-induced generalized tonic-clonic convulsive seizure model. The reduction of the levels of the pro-inflammatory cytokines TNF-α, IL-1β, and IL-6 caused by leptin, ghrelin, and NPY shows that these peptides may have anti-inflammatory effects in epileptic seizures. Also, leptin significantly increases the serum levels of the endogenous anticonvulsive agent galanin. The fact that each one of these endogenous peptides reduces the levels of MDA and increases the serum levels of GSH leads to the belief that they may have protective effects against oxidative damage that is thought to play a role in the pathogenesis of epilepsy. Our study contributes to the clarification of the role of these peptides in the brain in seizure-induced oxidative stress and immune system physiology and also presents new approaches to the etiology and treatment of tendency to epileptic seizures. [ABSTRACT FROM AUTHOR]

Objective: To analyze the effects of sodium hyaluronate administration on the serum levels of antioxidase, substance P (SP), and neuropeptide Y (NPY) in patients undergoing locking plate fixation (LPF) for tibial plateau fractures (TPF)., Methods: We retrospectively analyzed the records of 66 patients with TPF who received treatment in the Beijing Chao-yang Hospital[PJMS1][2] from February 2017 to August 2020. According to the treatment records, 33 patients underwent LPF surgery (control-group), and 33 patients underwent LPF plus sodium hyaluronate treatment (observation-group). The levels of antioxidant enzymes (superoxide dismutase (SOD), catalase (CAT) and total antioxidant capacity (TAC)), SP and NPY., Results: Seven days after LPF operations, both groups showed lower levels of SOD, CAT, and TAC compared to pre-surgery levels, while levels of SP and NPY were higher. However, the observation group showed higher levels of SOD, CAT, and TAC compared to the control group, and lower levels of SP and NPY in the control group ( P <0.05)., Conclusion: The treatment of TPF with LPF plus sodium hyaluronate administration has been shown to effectively reduce oxidative stress reactions, improve SP and NPY levels.[PJMS3][4]., (Copyright: © Pakistan Journal of Medical Sciences.)

Huntington's Disease is a neurodegenerative condition caused by a polyglutamine expansion in the huntingtin (Htt) protein, which aggregates and also causes neuronal dysfunction. Pathogenic N-terminal htt fragments perturb axonal transport in vitro. To determine whether this occurs in vivo and to elucidate how transport is affected, we expressed htt exon 1 with either pathogenic (HttEx1Q93) or non-pathogenic (HttEx1Q20) polyglutamine tracts in Drosophila. We found that HttEx1Q93 expression causes axonal accumulation of GFP-tagged fast axonal transport vesicles in vivo and leads to aggregates within larval motor neuron axons. Time-lapse video microscopy, shows that vesicle velocity is unchanged in HttEx1Q93-axons compared to HttEx1Q20-axons, but vesicle stalling occurs to a greater extent. Whilst HttEx1Q93 expression did not affect locomotor behaviour, external heat stress unveiled a locomotion deficit in HttEx1Q93 larvae. Therefore vesicle transport abnormalities amidst axonal htt aggregation places a cumulative burden upon normal neuronal function under stressful conditions.

In order to study the effects of bee venom Herbal Acupuncture on neurotransmitters in the rat brain cortex, herbal acupuncture with bee venom group and normal saline group was performed at LI4 bilaterally of the rat. the average optical density of neurotransmitters from the cerebral cortex was analysed 30 minutes after the herbal aqupuncture, by the immunohistochemistry. The results were as follows: 1. The density of NADPH-diaphorase in bee venom group was increased significantly at the motor cortex, visual cortex, auditory cortex, cingulate cortex, retrosplenial cortex and perirhinal cortex compared to the normal saline group. 2. The average optical density of vasoactive intestinal peptide in bee venom group had significant changes at the insular cortex, retrosplenial cortex and perirhinal cortex, compared to the normal saline group. 3. The average optical density of neuropeptide-Y in bee venom group increased significantly at the visual cortex and cingulate cortex, compared to the normal saline group.

Objective Breath-holding spells are common paroxysmal events in children. Although the spells have a benign prognosis in the long term, they may be complicated by loss of consciousness, tonic–clonic movements, and occasionally seizures. Hence, this study aimed to measure the levels of serum S-100B proteins and neuropeptide-Y in the blood of children who experience breath-holding spells. Methods The study groups consisted of 45 patients (13 females, 32 males) with breath-holding spells and a control group of 32 healthy individuals (12 females, 20 males). The serum S-100B levels were measured using commercially available ELISA kits. The neuropeptide-Y levels in the serum were measured with RayBio® Human/Mouse/Rat Neuropeptide Y ELISA kits. Results The mean serum S-100B protein level of the breath-holding spells group was 56.38 ± 13.26 pg/mL, and of the control group, 48.53 ± 16.77 pg/mL. The mean neuropeptide-Y level was 62.29 ± 13.89 pg/mL in the breath-holding spells group and 58.24 ± 12.30 pg/mL in the control group. There were significant differences between the groups with respect to serum S-100B protein levels (p = 0.025), while there was no statistically significant difference in neuropeptide-Y levels between the breath-holding spells group and the control group (p = 0.192). Conclusions The findings of this study suggest that frequent and lengthy breath-holding may lead to the development of neuronal metabolic dysfunction or neuronal damage which is most likely related to hypoxia. In light of these findings, future studies should be conducted using biochemical and radiological imaging techniques to support these results. [ABSTRACT FROM AUTHOR]

Neuropeptide Y (NPY) is a powerful orexigenic peptide secreted by hypothalamic neurons. The present study investigates how NPY injection into the lateral ventricle modulates masticatory movements and eating behavior. Behavioral experiments showed that cumulative food intake over a 4-h period and latency to eating were increased and decreased, respectively, in NPY-injected rats compared to saline-injected control rats. The feeding time for 2 g pellets was shorter in NPY-injected rats and resulted in an increased feeding rate, with more potent effects observed at 1 μg compared to 10 μg NPY. After injection of 10 μg NPY, a greater number of bouts with shorter average bout duration for eating 2 g, compared to 1 μg NPY, were observed. Furthermore, 10 μg NPY injection resulted in prolonged periods of moving and shortened sleep and grooming. Electromyography recordings from the digastric and masseter muscles showed two distinct patterns of bursts corresponding to the gnawing and chewing phases. After the injection of 1 μg NPY, the burst magnitude of masseter muscle during the gnawing phase increased, reflecting strong jaw-closing muscle activity. The relative integrated EMG of masseter muscle in both phases was smaller following injection of 10 μg NPY in comparison with that of 1 μg NPY. The present study indicates that 1 μg NPY administration promotes feeding behavior together with increased feeding rate and powerful jaw-closing muscle activity; whereas 10 μg NPY administration lowers jaw-closing muscle activity during biting and produces mastication with shorter and more frequent feeding bouts than 1 μg NPY. [ABSTRACT FROM AUTHOR]

Data from clinical trials, retrospective and cross-sectional studies have quantified the metabolic changes associated with long-term use of antiepileptic drugs (AEDs). AEDs can be associated with weight gain or weight loss, although most are weight neutral. Weight gain is not only a cosmetic problem but also a risk for obesity-related vascular disorders. Weight loss may compromise growth in children/adolescents. This review discusses the possible contribution of peripheral and central hormones/neuropeptides (as leptin, insulin, adiponectin, neuropeptide-Y, ghrelin and galanin) and pathways that influence energy balance in the pathogenesis of weight changes with AEDs. As AEDs may influence weight, physicians have to properly select and characterize the suitable AED as an initial step or modify the existing AED if it compromises patient's health. [ABSTRACT FROM AUTHOR]

Methods Twenty prepubertal children with epilepsy who were treated with topiramate were enrolled in the study. Topiramate was used at a daily dose of 5 mg/kg. Body mass index and fasting insulin-to-glucose ratio were calculated. Serum glucose, insulin, leptin, neuropeptide-Y, ghrelin, and cortisol levels were measured for all patients before the treatment and at the third and sixth months of the treatment. Results There were significant decreases in mean body mass index, fasting insulin-to-glucose ratio, and serum cortisol and leptin levels at the third and sixth months of the treatment compared with pretreatment levels. No significant changes were observed in serum glucose, ghrelin, neuropeptide-Y, or insulin levels. Conclusions The exact mechanism of topiramate on energy balance regulation is not clearly understood. Topiramate affects body mass index, fasting insulin-to-glucose ratio, and serum leptin and cortisol levels in prepubertal children. These changes may be key factors in weight loss due to topiramate. [ABSTRACT FROM AUTHOR]

Psychological hardiness characterizes people who remain healthy under psychosocial stress. The present exploratory study investigates possible links between hardiness and several immune and neuroendocrine markers: IL-6, IL-12, IL-4, IL-10, & neuropeptide-Y. A total of 21 Norwegian navy cadets were studied in the context of a highly stressful military field exercise. Blood samples were collected midway, and again late in the exercise when stress levels were highest. Psychological hardiness (including commitment, control, and challenge) was measured two days before the exercise. While all subjects scored high in hardiness, some were high only in commitment and control, but relatively low in challenge. These “unbalanced” hardiness subjects were also more stress reactive, showing suppressed proinflammatory cytokines (IL-12), increased anti-inflammatory cytokines (IL-4, IL-10), and lower neuropeptide-Y levels as compared to the hardiness-balanced group. This study thus shows that being high in hardiness with a balanced profile is linked to more moderate and healthy immune and neuroendocrine responses to stress. [ABSTRACT FROM PUBLISHER]

Highlights: [•] Repeated immobilization stress impairs spatial memory in rats to varying degrees. [•] Individual differences in anxiety and learning can serve as predictors of resiliency. [•] Stress resiliency is domain specific and dissociable across systems in an individual. [•] Cognitively resilient individuals suffered severe metabolic and immune dysfunctions. [•] Elevated NPY and ENK biomarkers are associated with domain-specific cognitive stress resiliency. [ABSTRACT FROM AUTHOR]

Objective: The neuropeptide-Y (NP-Y) gene is a strong candidate gene in the pathophysiology of obesity-linked behavior, and several single-nucleotide polymorphisms of NP-Y have already been linked to body weight and appetite. However, the results from current studies remain inconclusive. The aim of the present study was to test whether a certain functional genetic variant (SNP rs16147) in the NP-Y promoter gene is associated with serum leptin levels and body fat distribution. Method: We genotyped and measured the serum leptin levels of the NP-Y rs16147 polymorphism in 1,097 Caucasian subjects in the context of a population-based, case-control multicenter study. We measured weight, height and waist circumference, from which we then calculated BMI and waist-to-hip ratio (WHR). Results: We found the CT-genotype of the SNP rs16147 to be significantly associated with lower WHRs and higher serum leptin levels in women, compared to homozygote gene carriers. No association between rs16147, WHR and serum leptin levels was found in men. Conclusion: Our results provide evidence that the functionally relevant SNP in the NP-Y promoter gene affects body fat distribution and serum leptin levels in women, pointing towards possible behavioral effects of NPY in obesity. Copyright © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Nesfatin-1 was originally identified as a neuropeptide of the hypothalamus, which is a key integration area of the brain, where numerous neuropeptides and transmitters are released to participate in the control of essential body functions. In the literature, there are no studies showing the relationship between the nesfatin-1 level and paroxysmal supraventricular tachycardia. We hypothesize that the circulating levels of nesfatin-1 may increase during supraventricular tachycardia, to engage the vagal stimulation to terminate by the inhibition of neuropeptide-Y, and may activate oxytocin and the corticotropin-releasing hormone.This study includes 120 cases (80 patients and 40 controls). Patients with paroxysmal supraventricular tachycardia were compared with the control group with regard to sex, nesfatin-1 level, comorbid diseases, serum renal function values, and patients’ vital findings.The nesfatin-1 levels were significantly higher in the paroxysmal supraventricular tachycardia group than in the control group and positively correlated highly with heart rate (r = 0.634; P < 0.001). The area under the receiver operating characteristic curve was 0.644 for the nesfatin-1 levels (P = 0.0051). The sensitivity and specificity values of the nesfatin-1 levels were 41.2% and 95%, respectively (cutoff value >1743.7 pg/mL).At the end of this study, a statistically significant correlation was found between the serum nesfatin-1 level and supraventricular tachycardia. Although multifactorial causes may explain the relationship, we based our hypothesis on the relationship of the antagonistic effects of nesfatin-1 on the neuropeptide-Y and activated oxytocin. [ABSTRACT FROM AUTHOR]

Aims: This study was aimed to verify changes in the levels of hypothalamic neuropeptides in migraineurs under preventive treatment with amitryptiline and flunarizine. Thirty-nine migraine patients with a body mass index <25 kg/m2 and without endocrinological or metabolic diseases were assigned to two treatment groups, one receiving amitryptiline, the other flunarizine, for 3 months. Orexin-A, orexin-B and neuropeptide-Y plasma levels were measured at the basal time, at the 1st, 2nd and 3rd months of preventive treatment.Results: A statistically significant reduction in plasma orexin-A and orexin-B levels emerged in both groups. Conversely, plasma neuropeptide-Y levels were markedly increased, with the highest levels at the 2nd and 3rd months, in both patient groups. Orexin-A levels were also negatively correlated to weight gain in both groups during the treatment period. Conclusions: These results suggest that changes in the levels of hypothalamic orexinergic peptides may contribute to body weight increase occurring in migraineurs during amitryptiline or flunarizine prophylactic treatment. [ABSTRACT FROM PUBLISHER]