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Neuropeptides are the largest group of chemical signals in the brain. More than 100 different neuropeptides modulate various brain functions and their dysregulation has been associated with neurological disorders. Neuropeptides are packed into dense core vesicles (DCVs), which fuse with the plasma membrane in a calcium-dependent manner. Here, we describe a novel high-throughput assay for DCV exocytosis using a chimera of Nanoluc luciferase and the DCV-cargo neuropeptide Y (NPY). The NPY-Nanoluc reporter colocalized with endogenous DCV markers in all neurons with little mislocalization to other cellular compartments. NPY-Nanoluc reported DCV exocytosis in both rodent and induced pluripotent stem cell-derived human neurons, with similar depolarization, Ca2+, RAB3, and STXBP1/MUNC18 dependence as low-throughput assays. Moreover, NPY-Nanoluc accurately reported modulation of DCV exocytosis by known modulators diacylglycerol analog and Ca2+ channel blocker and showed a higher assay sensitivity than a widely used single-cell low-throughput assay. Lastly, we showed that Nanoluc coupled to other secretory markers reports on constitutive secretion. In conclusion, the NPY-Nanoluc is a sensitive reporter of DCV exocytosis in mammalian neurons, suitable for pharmacological and genomic screening for DCV exocytosis genes and for mechanism-based treatments for central nervous system disorders. [ABSTRACT FROM AUTHOR]

Aims: Cardiac dysfunction is commonly observed in patients with subarachnoid haemorrhage (SAH). However, the specific timeline of cardiac remodelling and the underlying mechanisms responsible for this effect following SAH remain unknown. This study aims to explore the impact of SAH on cardiac dysfunction and its potential mechanisms over time. Methods and results: In Protocol 1, we investigated cardiac function and potential mechanisms in a Sprague‐Dawley rat model of SAH at six time points (baseline and Days 1, 3, 7, 14, and 28) while exploring the underlying mechanisms. Our assessments included the haemodynamic profile, echocardiography, and the concentrations of plasma biomarkers at various time points post‐SAH. We determined neuropeptide Y (NPY) 1–5 receptor protein expression levels through western blotting. In Protocol 2, we administered an NPY1 receptor antagonist to evaluate the effects of cardiac dysfunction induced by SAH on Day 3. In Protocol 1, SAH gradually provoked cardiac systolic dysfunction during the acute phase, reaching its peak on Day 3 without concurrent alterations in wall thickness. However, no significant changes were observed from Days 14 to 28 compared with Day 0. The changes in cardiac dysfunction were consistent with myocardial injury, inflammatory biomarkers, and NPY levels. SAH resulted in a heightened heart rate and systolic blood pressure, correlating with elevated epinephrine and norepinephrine levels. In Protocol 2, the administration of the NPY1 receptor antagonist effectively ameliorated cardiac dysfunction. Conclusions: SAH induces transient cardiac dysfunction in the acute phase, and the underlying mechanisms for this response involve the NPY–NPY1 receptor pathway, otherwise known as catecholamines. [ABSTRACT FROM AUTHOR]

Abstract Osteoarthritis is a highly prevalent progressive joint disease that still requires an optimal therapeutic approach. Intermittent fasting is an attractive dieting strategy for improving health. Here this study shows that intermittent fasting potently relieves medial meniscus (DMM)‐ or natural aging‐induced osteoarthritic phenotypes. Osteocytes, the most abundant bone cells, secrete excess neuropeptide Y (NPY) during osteoarthritis, and this alteration can be altered by intermittent fasting. Both NPY and the NPY‐abundant culture medium of osteocytes (OCY‐CM) from osteoarthritic mice possess pro‐inflammatory, pro‐osteoclastic, and pro‐neurite outgrowth effects, while OCY‐CM from the intermittent fasting‐treated osteoarthritic mice fails to induce significant stimulatory effects on inflammation, osteoclast formation, and neurite outgrowth. Depletion of osteocyte NPY significantly attenuates DMM‐induced osteoarthritis and abolishes the benefits of intermittent fasting on osteoarthritis. This study suggests that osteocyte NPY is a key contributing factor in the pathogenesis of osteoarthritis and intermittent fasting represents a promising nonpharmacological antiosteoarthritis method by targeting osteocyte NPY.

The cell bodies of postganglionic sympathetic neurons innervating the heart primarily reside in the stellate ganglion (SG), alongside neurons innervating other organs and tissues. Whether cardiac-innervating stellate ganglionic neurons (SGNs) exhibit diversity and distinction from those innervating other tissues is not known. To identify and resolve the transcriptomic profiles of SGNs innervating the heart, we leveraged retrograde tracing techniques using adeno-associated virus (AAV) expressing fluorescent proteins (GFP or Td-tomato) with single cell RNA sequencing. We investigated electrophysiologic, morphologic, and physiologic roles for subsets of cardiac-specific neurons and found that three of five adrenergic SGN subtypes innervate the heart. These three subtypes stratify into two subpopulations; high (NA1a) and low (NA1b and NA1c) neuropeptide-Y (NPY) -expressing cells, exhibit distinct morphological, neurochemical, and electrophysiologic characteristics. In physiologic studies in transgenic mouse models modulating NPY signaling, we identified differential control of cardiac responses by these two subpopulations to high and low stress states. These findings provide novel insights into the unique properties of neurons responsible for cardiac sympathetic regulation, with implications for novel strategies to target specific neuronal subtypes for sympathetic blockade in cardiac disease.

We compared the effects of two different high-caloric diets administered to 4-week-old rats for 12 weeks: a diet rich in sugar (30% sucrose) and a cafeteria diet rich in sugar and high-fat foods. We focused on the hippocampus, particularly on the gamma-aminobutyric acid (GABA)ergic system, including the Ca2+-binding proteins parvalbumin (PV), calretinin (CR), calbindin (CB), and the neuropeptides somatostatin (SST) and neuropeptide Y (NPY). We also analyzed the density of cholinergic varicosities, brain-derived neurotrophic factor (BDNF), reelin (RELN), and cyclin-dependent kinase-5 (CDK-5) mRNA levels, and glial fibrillary acidic protein (GFAP) expression. The cafeteria diet reduced PV-positive neurons in the granular layer, hilus, and CA1, as well as NPY-positive neurons in the hilus, without altering other GABAergic populations or overall GABA levels. The high-sugar diet induced a decrease in the number of PV-positive cells in CA3 and an increase in CB-positive cells in the hilus and CA1. No alterations were observed in the cholinergic varicosities. The cafeteria diet also reduced the relative mRNA expression of RELN without significant changes in BDNF and CDK5 levels. The cafeteria diet increased the number but reduced the length of the astrocyte processes. These data highlight the significance of determining the mechanisms mediating the observed effects of these diets and imply that the cognitive impairments previously found might be related to both the neuroinflammation process and the reduction in PV, NPY, and RELN expression in the hippocampal formation. [ABSTRACT FROM AUTHOR]

Objective • Investigating the anatomical connections between cervical sympathetic ganglia and spinal ganglia in rabbits and assessing the role of Neuropeptide Y in the pathogenesis of cervical vertigo. Method • Part 1: 32 adult healthy male New Zealand white rabbits (whose skin is very sensitive, so rabbits are generally used for stimulation experiments) were randomly divided into the upper cervical sympathetic ganglia (SCSG) stimulation group and the lower cervical sympathetic ganglia (ICSG) stimulation group, with 16 rabbits in each group. The two groups were divided into an experimental group and a control group, with 8 rabbits in each group. The cervical ganglia of each group of white rabbits were injected with 4% FluoroGold solution and observed under a section microscope. Part 2: Sixty New Zealand white rabbits were randomly divided into a blank control (n = 12), SCSG stimulation group (n = 12), SCSG sham surgery control (n = 12), ICSG stimulation group (n = 12), and ICSG sham surgery control group (n = 12). The SCSG group and ICSG group were subjected to electrical stimulation (i.e. 30.0Hz, 10.0V, 5-minute pulse width of 0.5 ms square wave pulse), and specimens were made. The expression of NPY was detected using immunohistochemical methods. Result • Neuropeptide Y was weakly expressed in all cervical ganglia (C1-C8). Compared with the sham surgery group, the superior cervical sympathetic ganglion stimulation group showed an increase in Neuropeptide Y positive cells in C2, C3, C4, and C5, with C2 and C3 showing the most significant increase. The number of C6, C7, and C8 Neuropeptide Y positive cells in the 3 C, 3D and 4B, lower cervical sympathetic ganglion stimulated groups was higher than in the sham sham-operated group, and C6 and C7 significantly increased. Neuropeptide Y is like immunoreactive neurons in the cervical spinal ganglia, and the immunoreactive products are small brown particles distributed in the cytoplasm after electrical stimulation of the cervical sympathetic ganglia. The Neuropeptide Y content in the corresponding segment of the cervical spinal ganglia is significantly increased compared to the control group (P < .05). Conclusion • In New Zealand white rabbits, nerve fibers are interconnected between the cervical sympathetic ganglion and the cervical spinal ganglion, and this neural fiber connection has a certain segmental nature, providing experimental basis for the existence of the cervical spinal cord external nerve reflex arc and elucidating the pathogenesis of cervical vertigo in terms of neural anatomy. By using neuroelectrophysiological methods, it has been confirmed that electrical stimulation in the cervical spinal ganglia can reach the corresponding cervical sympathetic ganglia on the same side through a certain conduction pathway, providing experimental basis in neuroelectrophysiology for the existence of the cervical extraspinal nerve reflex arc and elucidating the pathogenesis of cervical vertigo. NPY may be involved in the pathogenesis of cervical vertigo, providing a theoretical basis for the clinical diagnosis of cervical vertigo. [ABSTRACT FROM AUTHOR]

Purpose: The retina contains a number of vasoactive neuropeptides and corresponding receptors, but the role of these neuropeptides for tone regulation of retinal arterioles has not been studied in detail. Methods: Porcine arterioles with preserved perivascular retinal tissue were mounted in a wire myograph, and the tone was measured after the addition of increasing concentrations of bradykinin, vasoactive intestinal peptide (VIP), neuropeptide Y (NPY), substance P (SP), calcitonin gene‐related peptide (CGRP) and brain natriuretic peptide (BNP). The experiments were performed during inhibition of the synthesis of nitric oxide (NO), prostaglandins and dopamine and were repeated after removal of the perivascular retinal tissue. Results: Bradykinin, VIP and CGRP induced significant concentration‐dependent dilatation and NPY significant concentration‐dependent contraction of the arterioles in the presence of perivascular retinal tissue (p < 0.03 for all comparisons) but not on isolated arterioles. BNP and SP had no effect on vascular tone. The NOS inhibitor L‐NAME reduced bradykinin‐ and VIP‐induced relaxation (p < 0.001 for both comparisons), whereas none of the other inhibitors influenced the vasoactive effects of the studied neuropeptides. Conclusion: The effects of neuropeptides on the tone of retinal arterioles depend on the perivascular retinal tissue and may involve effects other than those mediated by nitric oxide, prostaglandins and adrenergic compounds. Investigation of the mechanisms underlying the vasoactive effect of neuropeptides may be important for understanding and treating retinal diseases where disturbances in retinal flow regulation are involved in the disease pathogenesis. [ABSTRACT FROM AUTHOR]

Agouti-related protein (Agrp) is an orexigenic peptide hormone found in fish and other vertebrates. Understanding appetite regulation is important for improving production performance in aquaculture systems. However, information on appetite-related hormones in yellowtail is still fragmentary. In this study, two distinct agrpgenes (i.e., agrp1 and agrp2) were cloned from the yellowtail brain. Brain distribution and response of the agrp genes to fasting, along with other candidate orexigenic peptide hormone-related genes including neuropeptide Y (npy) and melanin-concentrating hormones (mch1 and mch2), were studied. The highest expression level of those genes was observed in the hypothalamus, except for npy. After fasting, agrp1 and npy increased significantly in the hypothalamus, whereas agrp2 in the olfactory bulb and cerebellum decreased significantly. After feeding with a fishmeal (FM)-based diet and addition of a fishmeal soluble fraction (FMS), hypothalamic agrp1, agrp2, mch1, and mch2 increased, whereas hypothalamic npy decreased significantly. From the fasting experiment, agrp1 and npy may function as orexigenic hormones in yellowtail; however, the function of other hormones warrants further research. Expression of all the analyzed appetite-related hormonal genes might respond to the smell/taste of fishmeal through sensory organs. Furthermore, npy and agrp1 may enhance appetite through different mechanisms in yellowtail. [ABSTRACT FROM AUTHOR]

BACKGROUND: Non‐nutritive sweeteners (NNS) are commonly used in sweetened foods and beverages; however their role in metabolic regulation is still not clear. In this experiment, we used guinea pigs as an animal model to study the effect of NNS on body growth and intestinal health by modifying gut microbiota and hypothalamus‐related proteins. RESULTS: For a 28‐day feeding experiment a total of 40 guinea pigs were randomly divided into four groups, one control (CN) group and three treatments, in which three NNS were added to the diet: rebaudioside A (RA, 330 mg kg−1), sodium saccharin (SS, 800 mg kg−1), and sucralose (TGS, 167 mg kg−1), respectively. The TGS group exhibited significantly reduced food consumption in comparison with the CN group (P < 0.05) whereas the RA group showed increased food consumption in comparison with the CN group (P < 0.05). Notably, Taste receptor type 1 subunit 2 (T1R2) expression in the hypothalamus was significantly higher in the RA group than in the CN group (P < 0.05). The mRNA expressions of appetite‐stimulated genes arouti‐related neuropeptide (AGRP), neuropeptide Y (NPY), and thyroid stimulating hormone (TSHB) were significantly higher than those in the CN group (P < 0.05) but mRNA expressions of appetite‐suppressed genes tryptophan hydroxylase 2(THP2) were significantly lower in the TGS group (P < 0.05). Furthermore, NNS in the guinea pig diets (RA, SS, TGS) significantly increased the relative abundance of Muribaculaceae but decreased the relative abundance of Clostridia_vadin BB60 in comparison with the CN group (P < 0.05). We also found that dietary supplementation with RA also significantly altered the relative abundance of Lactobacillus. CONCLUSION: Our finding confirmed that dietary supplementation with RA and TGS affected body growth and intestinal health by modulating hypothalamic RNA profiles and ileum microbiota, suggesting that NNS should be included in guinea‐pig feeding. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

NGLY1 deficiency is a genetic disease caused by biallelic mutations of the Ngly1 gene. Although epileptic seizure is one of the most severe symptoms in patients with NGLY1 deficiency, preclinical studies have not been conducted due to the lack of animal models for epileptic seizures in NGLY1 deficiency. Here, we observed the behaviors of male and female Ngly1−/− mice by video monitoring and found that these mice exhibit spontaneous seizure-like behaviors. Gene expression analyses and enzyme immunoassay revealed significant decreases in oxytocin, a well-known neuropeptide, in the hypothalamus of Ngly1−/− mice. Seizure-like behaviors in Ngly1−/− mice were transiently suppressed by a single intranasal administration of oxytocin. These findings suggest the therapeutic potential of oxytocin for epileptic seizure in patients with NGLY1 deficiency and contribute to the clarification of the disease mechanism. Epileptic seizure is one of the symptoms in patients with NGLY1 deficiency, a congenital disorder of deglycosylation. Here the authors show suppressive effects of oxytocin on seizure-like behaviors in a mouse model of NGLY1 deficiency. [ABSTRACT FROM AUTHOR]

Oxytocin is a neuropeptide associated with both psychological and somatic processes like parturition and social bonding. Although oxytocin homologs have been identified in many species, the evolutionary timeline of the entire oxytocin signaling gene pathway has yet to be described. Using protein sequence similarity searches, microsynteny, and phylostratigraphy, we assigned the genes supporting the oxytocin pathway to different phylostrata based on when we found they likely arose in evolution. We show that the majority (64%) of genes in the pathway are 'modern'. Most of the modern genes evolved around the emergence of vertebrates or jawed vertebrates (540 - 530 million years ago, 'mya'), including OXTR, OXT and CD38. Of those, 45% were under positive selection at some point during vertebrate evolution. We also found that 18% of the genes in the oxytocin pathway are 'ancient', meaning their emergence dates back to cellular organisms and opisthokonta (3500–1100 mya). The remaining genes (18%) that evolved after ancient and before modern genes were classified as 'medium-aged'. Functional analyses revealed that, in humans, medium-aged oxytocin pathway genes are highly expressed in contractile organs, while modern genes in the oxytocin pathway are primarily expressed in the brain and muscle tissue. A study on the evolution of the oxytocin system illustrates the varied role of this neuropeptide in physiology and behavior [ABSTRACT FROM AUTHOR]

This study investigates the combined effects of the neuropeptide Y Y1 receptor (NPY1R) agonist [Leu31-Pro34]NPY at a dose of 132 µg and Ketamine at 10 mg/Kg on cognitive functions and neuronal proliferation, against a backdrop where neurodegenerative diseases present an escalating challenge to global health systems. Utilizing male Sprague-Dawley rats in a physiological model, this research employed a single-dose administration of these compounds and assessed their impact 24 h after treatment on object-in-place memory tasks, alongside cellular proliferation within the dorsal hippocampus dentate gyrus. Methods such as the in situ proximity ligation assay and immunohistochemistry for proliferating a cell nuclear antigen (PCNA) and doublecortin (DCX) were utilized. The results demonstrated that co-administration significantly enhanced memory consolidation and increased neuronal proliferation, specifically neuroblasts, without affecting quiescent neural progenitors and astrocytes. These effects were mediated by the potential formation of NPY1R-TrkB heteroreceptor complexes, as suggested by receptor co-localization studies, although further investigation is required to conclusively prove this interaction. The findings also highlighted the pivotal role of brain-derived neurotrophic factor (BDNF) in mediating these effects. In conclusion, this study presents a promising avenue for enhancing cognitive functions and neuronal proliferation through the synergistic action of the NPY1R agonist and Ketamine, potentially via NPY1R-TrkB heteroreceptor complex formation, offering new insights into therapeutic strategies for neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Obesity, a worldwide epidemic, leads to various metabolic disorders threatening human health. In response to stress or fasting, glucocorticoid (GC) levels are elevated to promote food intake. This involves GC-induced expression of the orexigenic neuropeptides in agouti-related protein (AgRP) neurons of the hypothalamic arcuate nucleus (ARC) via the GC receptor (GR). Here, we report a selective GR modulator (SGRM) that suppresses GR-induced transcription of genes with non-classical glucocorticoid response elements (GREs) such as Agrp-GRE, but not with classical GREs, and via this way may serve as a novel anti-obesity agent. We have identified a novel SGRM, 2-O-trans-p-coumaroylalphitolic acid (Zj7), a triterpenoid extracted from the Ziziphus jujube plant, that selectively suppresses GR transcriptional activity in Agrp-GRE without affecting classical GREs. Zj7 reduces the expression of orexigenic genes in the ARC and exerts a significant anorexigenic effect with weight loss in both high fat diet-induced obese and genetically obese db/db mouse models. Transcriptome analysis showed that Zj7 represses the expression of a group of orexigenic genes including Agrp and Npy induced by the synthetic GR ligand dexamethasone (Dex) in the hypothalamus. Taken together, Zj7, as a selective GR modulator, showed beneficial metabolic activities, in part by suppressing GR activity in non-classical GREs in orexigenic genes. This study demonstrates that a potential anorexigenic molecule may allow GRE-specific inhibition of GR transcriptional activity, which is a promising approach for the treatment of metabolic disorders. [ABSTRACT FROM AUTHOR]

The present study was conducted to investigate the presence and distribution of the endocrine cells in the pancreas of the common pheasant using immunofluorescent staining. Totally, five adult male birds were used in the present work. The tissue samples were prepared, and different antibodies were applied to detect insulin, glucagon, somatostatin, pancreatic polypeptide (PP), and neuropeptide Y (NY). The percentage of staining was estimated using image J software. The glucagon-secreting cells (Alpha cells) with 32.4% ± 12.56 intensity were the most numerous cell type which were populated throughout the large islets especially at the periphery of islets. The insulin-secreting cells (Beta cells) with 27.73% ± 8.34 intensity were accumulated in the center of the small islets. Cells containing somatostatin (Delta cells) showed 13.38% ± 5.09 intensity. Despite their lower intensity, the distribution of D cells was like to A cells throughout the islets. PP cells and NY cells were distinguished with 19.55% ± 3.88 and 18.14% ± 7.15 intensities, respectively. Their distribution was evenly in the large islets. There were two types of islets: large alpha islets which were mainly composed of alpha and delta cells, and small beta islets constituted of beta cells and a few numbers of alpha cells. In conclusion, all investigated cell types were expressed in the endocrine pancreas and distributed in two types of islets as large alpha and small beta islets. Certainly, more detailed investigations are needed to reveal the exact population of each endocrine cells in the pancreas of the common pheasant. [ABSTRACT FROM AUTHOR]

Neuropeptide Y (NPY) is one of the most abundant peptides in the central nervous system of mammals and is involved in several physiological processes through NPY Y1, Y2, Y4 and Y5 receptors. Of those, the Y2 receptor has particular relevance for its autoreceptor role in inhibiting the release of NPY and other neurotransmitters and for its involvement in relevant mechanisms such as feeding behaviour, cognitive processes, emotion regulation, circadian rhythms and disorders such as epilepsy and cancer. PET imaging of the Y2 receptor can provide a valuable platform to understand this receptor's functional role and evaluate its potential as a therapeutic target. In this work, we set out to refine the chemical and radiochemical synthesis of the Y2 receptor antagonist N-[11C]Me-JNJ31020028 for in vivo PET imaging studies. The non-radioactive reference compound, N-Me-JNJ-31020028, was synthesised through batch synthesis and continuous flow methodology, with 43% and 92% yields, respectively. N-[11C]Me-JNJ-31020028 was obtained with a radiochemical purity > 99%, RCY of 31% and molar activity of 156 GBq/μmol. PET imaging clearly showed the tracer's biodistribution in several areas of the mouse brain and gut where Y2 receptors are known to be expressed. [ABSTRACT FROM AUTHOR]

Neurogenic inflammation is involved in the development and progression of respiratory inflammatory diseases. However, its role in community-acquired pneumonia (CAP) remains unclear. We therefore aimed to investigate plasma levels of neurogenic inflammation-related neuropeptides, calcitonin gene-related peptide (CGRP), substance P (SP), vasoactive intestinal peptide (VIP) and neuropeptide Y (NPY), and procalcitonin (PCT) in pediatric patients with CAP and to assess their diagnostic value in viral and bacterial/mixed pneumonia. A total of 124 pediatric patients with CAP (1 month-18 years old) and 56 healthy children of similar ages were prospectively enrolled. The patients were classified as viral (n = 99) and bacterial/mixed (n = 25) pneumonia. Plasma levels of the peptides were quantified by ELISA. ROC analysis was performed to evaluate possible diagnostic value of the peptides. While plasma levels of CGRP, VIP and PCT were significantly higher in patients with CAP than in the control group, respectively, NPY levels were significantly lower. Moreover, plasma levels of all neuropeptides and PCT were significantly higher in bacterial pneumonia patients compared to viral pneumonia patients. ROC analysis revealed that CGRP, SP and NPY had a diagnostic value in distinguishing viral and bacterial/mixed pneumonia. Conclusions: Our findings suggest that these neuropeptides may be implicated in pediatric CAP. CGRP, SP and NPY together may be a promising candidate in distinguishing viral and bacterial/mixed pneumonia, however, for this, further studies are needed. What is Known: • Neurogenic inflammation contributes to the development and progression of respiratory inflammatory diseases such as chronic obstructive pulmonary disease and bronchial asthma. What is New: • Plasma levels of neurogenic inflammation related neuropeptides calcitonin gene-related peptide, substance P, vasoactive intestinal peptide and neuropeptide Y are changed in pediatric community-acquired pneumonia. Calcitonin gene-related peptide, substance P and neuropeptide Y are promising candidates in distinguishing viral and bacterial/mixed pneumonia. [ABSTRACT FROM AUTHOR]

BACKGROUND: The maternal diet during gestation and lactation affects the health of the offspring. Konjac glucomannan (KGM) is a significantly functional polysaccharide in food research, possessing both antioxidant and prebiotic properties. However, the mechanisms of how KGM regulates maternal nutrition remain insufficient and limited. This study aimed to investigate maternal supplementation with KGM during late gestation and lactation to benefit both maternal and offspring generations. RESULTS: Our findings indicate that KGM improves serum low density lipoprotein cholesterol (LDL‐C) and antioxidant capacity. Furthermore, the KGM group displayed a significant increase in the feed intake‐related hormones neuropeptide tyrosine (NPY), Ghrelin, and adenosine monophosphate‐activated kinase (AMPK) levels. KGM modified the relative abundance of Clostridium, Candidatus Saccharimonas, unclassified Firmicutes, and unclassified Christensenellaceae in sow feces. Acetate, valerate, and isobutyrate were also improved in the feces of sows in the KGM group. These are potential target bacterial genera that may modulate the host's health. Furthermore, Spearman's correlation analysis unveiled significant correlations between the altered bacteria genus and feed intake‐related hormones. More importantly, KGM reduced interleukin‐6 (IL‐6) levels in milk, further improved IL‐10 levels, and reduced zonulin levels in the serum of offspring. CONCLUSION: In conclusion, maternal dietary supplementation with KGM during late gestation and lactation improves maternal nutritional status by modifying maternal microbial and increasing lactation feed intake, which benefits the anti‐inflammatory capacity of the offspring serum. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Itch is a somatosensory sensation to remove potential harmful stimulation with a scratching desire, which could be divided into mechanical and chemical itch according to diverse stimuli, such as wool fiber and insect biting. It has been reported that neuropeptide Y (NPY) neurons, a population of spinal inhibitory interneurons, could gate the transmission of mechanical itch, with no effect on chemical itch. In our study, we verified that chemogenetic activation of NPY neurons could inhibit the mechanical itch as well as the chemical itch, which also attenuated the alloknesis phenomenon in the chronic dry skin model. Afterwards, intrathecal administration of NPY1R agonist, [Leu31, Pro34]-NPY (LP-NPY), showed the similar inhibition effect on mechanical itch, chemical itch and alloknesis as chemo-activation of NPY neurons. Whereas, intrathecal administration of NPY1R antagonist BIBO 3304 enhanced mechanical itch and reversed the alloknesis phenomenon inhibited by LP-NPY treatment. Moreover, selectively knocking down NPY1R by intrathecal injection of Npy1r siRNA enhanced mechanical and chemical itch behavior as well. These results indicate that NPY neurons in spinal cord regulate mechanical and chemical itch, and alloknesis in dry skin model through NPY1 receptors. [ABSTRACT FROM AUTHOR]

On the verge of a theranostic approach to personalised medicine, copper-64 is one of the emerging radioisotopes in nuclear medicine due to its exploitable nuclear and biochemical characteristics. The increased demand for copper-64 for preclinical and clinical studies has prompted the development of production routes. This research aims to compare the (p,n) reaction on nickel-64 solid versus liquid targets and evaluate the effectiveness of [64Cu]CuCl2 solutions prepared by the two routes. As new treatments for neurotensin receptor-overexpressing tumours have developed, copper-64 was used to radiolabel Neurotensin (8-13) and Neuromedin N. High-quality [64Cu]CuCl2 solutions were prepared using ACSI TR-19 and IBA Cyclone Kiube cyclotrons. The radiochemical purity after post-irradiation processing reached 99% (LT) and 99.99% (ST), respectively. The irradiation of a solid target with 11.8 MeV protons and 150 μAh led to 704 ± 84 MBq/μA (17.6 ± 2.1 GBq/batch at EOB). At the end of the purification process (1 h, 90.90% activity yield), the solution for peptide radiolabelling had a radioactive concentration of 1340.4 ± 70.1 MBq/mL (n.d.c.). The irradiation of a liquid target with 16.9 MeV protons and 230 μAh resulted in 3.7 ± 0.2 GBq/batch at EOB, which corresponds to an experimental production yield of 6.89 GBq.cm3/(g.µA)sat. Benefiting from a shorter purification process (40 min), the activity yielded 90.87%, while the radioactive concentration of the radiolabelling solution was lower (492 MBq/mL, n.d.c.). The [64Cu]CuCl2 solutions were successfully used for the radiolabelling of DOTA-NT(8-13) and DOTA-NN neuropeptides, resulting in a high RCP (>99%) and high molar activity (27.2 and 26.4 GBq/μmol for LT route compared to 45 and 52 GBq/μmol for ST route, respectively). The strong interaction between the [64Cu]Cu-DOTA-NT(8-13) and the colon cancerous cell lines HT29 and HCT116 proved that the specificity for NTR had not been altered, as shown by the uptake and retention data. [ABSTRACT FROM AUTHOR]

Our objective was to investigate the effects of topically applied neuropeptide Y (NPY) on ischemic wounds. Initially, the animal model for ischemic wound healing was validated using 16 male Sprague Dawley albino rats. In the intervention study, an additional 28 rats were divided into three groups: NPY (0.025%), the positive control insulin-like growth factor-I (IGF-I, 0.0025%), and the hydrogel carrier alone (control). The hydrogel was selected due to its capacity to prolong NPY release (p < 0.001), as demonstrated in a Franz diffusion cell. In the animals, an 8 mm full-thickness wound was made in a pedunculated dorsal ischemic skin flap. Wounds were then treated and assessed for 14 days and collected at the end of the experiment for in situ hybridization analysis (RNAscope®) targeting NPY receptor Y2R and for meticulous histologic examination. Wound healing rates, specifically the percentage changes in wound area, did not show an increase with NPY (p = 0.907), but there was an increase with rhIGF-I (p = 0.039) compared to the control. Y2R mRNA was not detected in the wounds or adjacent skin but was identified in the rat brain (used as a positive control). Light microscopic examination revealed trends of increased angiogenesis and enhanced inflammatory cell infiltration with NPY compared to control. An interesting secondary discovery was the presence of melanophages in the wounds. Our findings suggest the potential of NPY to enhance neovascularization under ischemic wound healing conditions, but further optimization of the carrier and dosage is necessary. The mechanism remains elusive but likely involves NPY receptor subtypes other than Y2R. [ABSTRACT FROM AUTHOR]

The co-occurrence of asthma and obesity is becoming an increasingly common health problem. It became clear that both diseases are closely related, since overweight/obesity are associated with an increased risk of asthma development, and more than half of the subjects with severe or difficult-to-treat asthma are obese. Currently, there are no specific guidelines for the treatment of this group of patients. The mechanisms involved in the asthma–obesity phenotype include low-grade chronic inflammation and changes in pulmonary physiology. However, genetic predispositions, gender differences, comorbid conditions, and gut microbiota also seem to be important. Regulatory peptides affect many processes related to the functioning of the respiratory tract and adipose tissue. Adipokines such as leptin, adiponectin, resistin, and the less studied omentin, chemerin, and visfatin, as well as the gastrointestinal hormones ghrelin, cholecystokinin, glucagon-like peptide-1, and neuropeptides, including substance P or neuropeptide Y, can play a significant role in asthma with obesity. The aim of this article is to provide a concise review of the contribution of particular peptides in inflammatory reactions, obesity, asthma, and a combination of both diseases, as well as emphasize their potential role in the effective treatment of the asthma–obesity phenotype in the future. [ABSTRACT FROM AUTHOR]

(1) Background: Modulators of the Neuropeptide Y (NPY) system are involved in energy metabolism, but the effect of NPY receptor antagonists on metabolic-dysfunction-associated steatotic liver disease (MASLD), a common obesity-related comorbidity, are largely unknown. In this study, we report on the effects of antagonists of the NPY-2 receptor (Y2R) in comparison with empagliflozin and semaglutide, substances that are known to be beneficial in MASLD. (2) Methods: Diet-induced obese (DIO) male Wistar rats were randomized into the following treatment groups: empagliflozin, semaglutide ± PYY3-36, the Y2R antagonists JNJ 31020028 and a food-restricted group, as well as a control group. After a treatment period of 8 weeks, livers were weighed and histologically evaluated. QrtPCR was performed to investigate liver inflammation and de novo lipogenesis (in liver and adipose tissue). Serum samples were analysed for metabolic parameters. (3) Results: Semaglutide + PYY3-36 led to significant weight loss, reduced liver steatosis (p = 0.05), and decreased inflammation, insulin resistance, and leptin levels. JNJ-31020028 prevented steatosis (p = 0.03) without significant weight loss. Hepatic downregulation of de novo lipogenesis-regulating genes (SREBP1 and MLXIPL) was observed in JNJ-31020028-treated rats (p ≤ 0.0001). Food restriction also resulted in significantly reduced weight, steatosis, and hepatic de novo lipogenesis. (4) Conclusions: Body weight reduction (e.g., by food restriction or drugs like semaglutide ± PYY3-36) is effective in improving liver steatosis in DIO rats. Remarkably, the body-weight-neutral Y2R antagonists may be effective in preventing liver steatosis through a reduction in de novo lipogenesis, making this drug class a candidate for the treatment of (early) MASLD. [ABSTRACT FROM AUTHOR]

Background: Posttraumatic stress disorder (PTSD) and major depressive disorder (MDD) comorbidity occurs through exposure to trauma with genetic susceptibility. Neuropeptide-Y (NPY) and dopamine are neurotransmitters associated with anxiety and stress-related psychiatry through receptors. We attempted to explore the genetic association between two neurotransmitter receptor systems and the PTSD–MDD comorbidity. Methods: Four groups were identified using latent profile analysis (LPA) to examine the patterns of PTSD and MDD comorbidity among survivors exposed to earthquake-related trauma: low symptoms, predominantly depression, predominantly PTSD, and PTSD–MDD comorbidity. NPY2R (rs4425326), NPY5R (rs11724320), DRD2 (rs1079597), and DRD3 (rs6280) were genotyped from 1,140 Chinese participants exposed to earthquake-related trauma. Main, gene–environment interaction (G × E), and gene–gene interaction (G × G) effects for low symptoms, predominantly depression, and predominantly PTSD were tested using a multinomial logistic model with PTSD–MDD comorbidity as a reference. Results: The results demonstrated that compared to PTSD–MDD comorbidity, epistasis (G × G) NPY2R-DRD2 (rs4425326 × rs1079597) affects low symptoms (β = −0.66, OR = 0.52 [95% CI: 0.32–0.84], p = 0.008, pperm = 0.008) and predominantly PTSD (β = −0.56, OR = 0.57 [95% CI: 0.34–0.97], p = 0.037, pperm = 0.039), while NPY2R-DRD3 (rs4425326 × rs6280) impacts low symptoms (β = 0.82, OR = 2.27 [95% CI: 1.26–4.10], p = 0.006, pperm = 0.005) and predominantly depression (β = 1.08, R = 2.95 [95% CI: 1.55–5.62], p = 0.001, pperm = 0.001). The two G × G effects are independent. Conclusion: NPY and dopamine receptor genes are related to the genetic etiology of PTSD–MDD comorbidity, whose specific mechanisms can be studied at multiple levels. [ABSTRACT FROM AUTHOR]

Simple Summary: The basolateral amygdala (BLA) contains neurons that produce neuropeptide Y (NPY) and vasoactive intestinal polypeptide (VIP). These neuropeptides are involved in the regulation of several brain functions and behaviors, and there is evidence that, in some brain regions, the acetylcholine might modulate its expression. Thus, we study if aging alters the BLA densities of NPY- and VIP-positive neurons and cholinergic varicosities. We also investigate if any potential change in these parameters might be related to insufficient trophic support provided by the neurotrophin nerve growth factor (NGF). We found that the density of NPY-positive neurons was reduced in aged rats, whereas the density of VIP-immunoreactive neurons was unchanged. The decreased expression of NPY was fully reversed by intracerebroventricular administration of NGF. The density of cholinergic varicosities was similar in adult and old rats, and the infusion of NGF to aged rats increased their density to greater than the values of adult and old rats. These results indicate that the NPY expression in the BLA is affected by aging, and also show that this age-related change can be associated with alterations in the NGF trophic support. Furthermore, the results also show that the BLA cholinergic innervation is particularly resistant to age effects. The basolateral amygdala (BLA) contains interneurons that express neuropeptide Y (NPY) and vasoactive intestinal polypeptide (VIP), both of which are involved in the regulation of functions and behaviors that undergo deterioration with aging. There is considerable evidence that, in some brain areas, the expression of NPY and VIP might be modulated by acetylcholine. Importantly, the BLA is one of the brain regions that has one of the densest cholinergic innervations, which arise mainly from the basal forebrain cholinergic neurons. These cholinergic neurons depend on nerve growth factor (NGF) for their survival, connectivity, and function. Thus, in this study, we sought to determine if aging alters the densities of NPY- and VIP-positive neurons and cholinergic varicosities in the BLA and, in the affirmative, if those changes might rely on insufficient trophic support provided by NGF. The number of NPY-positive neurons was significantly reduced in aged rats, whereas the number of VIP-immunoreactive neurons was unaltered. The decreased NPY expression was fully reversed by the infusion of NGF in the lateral ventricle. The density of cholinergic varicosities was similar in adult and old rats. On the other hand, the density of cholinergic varicosities is significantly higher in old rats treated with NGF than in adult and old rats. Our results indicate a dissimilar resistance of different populations of BLA interneurons to aging. Furthermore, the present data also show that the BLA cholinergic innervation is particularly resistant to aging effects. Finally, our results also show that the reduced NPY expression in the BLA of aged rats can be related to changes in the NGF neurotrophic support. [ABSTRACT FROM AUTHOR]

BACKGROUND: Omnivores, including humans, have an inborn tendency to avoid risky or non‐nutritious foods. However, relatively little is known about how animals perceive and discriminate nutritious foods from risky substances. In this study, we explored the mechanism of feeding selection in Ostrinia furnacalis larvae, one of the most destructive pests to the maize crop. RESULTS: We identified a gustatory receptor, Gr43a, for feeding regulation in larvae of Ostrinia furnacalis, which highly expresses in the mouthparts of the first‐ (the period of just hatching out from eggs) and fifth‐instar larvae (the period of gluttony). The Gr43a regulates foraging plasticity by discriminating sorbitol, a nonsweet nutritious substance, and sucralose, a sweet non‐nutritious substance through the labra of mouthparts, while it differentiates fructose/sucrose and sucralose via the sensilla styloconica of mouthparts. Specially, Gr43a responds to fructose and sucrose via the medial and lateral sensilla styloconica in O. furnacalis, respectively. Furthermore, Gr43a is negatively regulated by the neuropeptide F system, a homologous mammalian neuropeptide Y system. CONCLUSION: This study reveals a smart feeding strategy for animals to meet both nutritional needs and sweet gratification, and offers an insight into complex feeding selections dependent on food resources in the surrounding environment. © 2023 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Abstract Neuropeptide Y (NPY), a 36‐amino‐acid peptide, functions as a neurotransmitter in both the central and peripheral nervous systems by activating the NPY receptor subfamily. Notably, NPY analogs display varying selectivity and exert diverse physiological effects through their interactions with this receptor family. [Pro34]–NPY and [Leu31, Pro34]–NPY, mainly acting on Y1R, reportedly increases blood pressure and postsynaptically potentiates the effect of other vasoactive substances above all, while N‐terminal cleaved NPY variants in human body primary mediates angiogenesis and neurotransmitter release inhibition through Y2R. However, the recognition mechanisms of Y1R and Y2R with specific agonists remain elusive, thereby hindering subtype receptor‐selective drug development. In this study, we report three cryo‐electron microscopy (cryo‐EM) structures of Gi2‐coupled Y1R and Y2R in complexes with NPY, as well as Y1R bound to a selective agonist [Leu31, Pro34]–NPY. Combined with cell‐based assays, our study not only reveals the conserved peptide‐binding mode of NPY receptors but also identifies an additional sub‐pocket that confers ligand selectivity. Moreover, our analysis of Y1R evolutionary dynamics suggests that this sub‐pocket has undergone functional adaptive evolution across different species. Collectively, our findings shed light on the molecular underpinnings of neuropeptide recognition and receptor activation, and they present a promising avenue for the design of selective drugs targeting the NPY receptor family.

Objective To explore the effects of clearing the stomach and strengthening the spleen in the treatment of simple obesity on serum neuropeptide Y (NPY) and leptin from the perspective of spleen and stomach. Methods A retrospective study was conducted on 86 patients with simple obesity who admitted to Heilongjiang University of Chinese Medicine from January 2020 to January 2022. According to different treatment methods, they were divided into control group and observation group, 43 cases in each group. The control group was given exercise combined with dietary guidance intervention, and the observation group was given clearing stomach and strengthening spleen prescription on the basis of the control group. The clinical efficacy, Chinese medicine symptom score, body fat content, body mass index (BMI), waist circumference, serum NPY, leptin and blood lipid levels were compared between the two groups. Results The total effective rate of observation group was higher than that of control group (95.35% vs 69.77%, χ2=9.771, P=0.002). After treatment, the scores of epigastric distensions, nausea and vomiting, bitter, sticky mouth odor and poor stool in the observation group were lower than those in the control group (P＜0.05). The body fat content, BMI and waist circumference of observation group were lower than those of control group after treatment （P＜0.05）. After treatment, serum levels of NPY, leptin, triglyceride (TG), total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) in observation group were lower than those in control group (P＜0.05), while high density lipoprotein cholesterol (HDL-C) in observation group was higher than that in control group (P＜0.05). Conclusion Clearing stomach and strengthening spleen has certain curative effect in the treatment of simple obesity, which can effectively reduce body weight, reduce abdominal circumference, relieve symptoms such as poor stool and abdominal distension, reduce serum NPY and leptin levels, and regulate blood lipid.

Evidence about bone health in people affected by psychiatric disorders is limited. This narrative review aims to highlight what is known, up to the present time, about clinical connections between bone health and psychiatric disorders, particularly depressive disorders (DD) and bipolar disorders (BD), in terms of common biological pathways. Besides inflammation, we focused on two molecules of growing interest: neuropeptide Y (NPY) and the neuro-hormone melatonin. Also, the role of psychoactive drugs on bone tissue was explored. For the preparation of this narrative review, the scientific literature of the most recent 7 years from PubMed, Springer Nature, Science Direct (Elsevier), Wiley Online, ResearchGate, and Google Scholar databases was analyzed. Reviewed evidence reveals that people diagnosed with BD or DD have an increased risk of both fractures and osteoporosis; NPY reduces bone loss induced by longer periods of depression and “buffers” psychological stress effects on bone health. MLT shows beneficial effects in osteoporosis and bone healing. Lithium, a mood stabilizer, shows potential bone-protective activity, while antipsychotic and antidepressant treatments may increase the risk of bone tissue damage, though further investigation is needed.

Abstract Background Carotid plaque (CP) formation is an important consequence of atherosclerosis and leads to significant complications. Levels of neuropeptide Y (NPY), which is a sympathetic neurotransmitter, are elevated in cardiovascular diseases. It also has important roles in inflammatory conditions. This study aimed to explore the relationship between serum NPY and CP and to study further the influence of NPY and inflammatory factors on CP. Methods This cross-sectional study was conducted among 300 adults who underwent a health examination at the Second Affiliated Hospital of Fujian Medical University in Fujian Province, of whom 177 were finally enrolled. The participants were divided into the CP (n = 120) and non-CP (NCP) or control (n = 57) groups according to the results of carotid artery color Doppler ultrasound. The CP group was further classified into stable plaque (SP, n = 80) and vulnerable plaque (VP, n = 40) groups based on plaque characteristics. Serum NPY and pro-inflammatory cytokine tumor necrosis factor-α (TNF-α) levels were examined. Univariate and correlation analyses were used to evaluate the correlation between serum NPY levels, pro-inflammatory cytokines, and the CP phenotype. Results The serum NPY and TNF-α levels of patients in the CP group were significantly higher than those in individuals from the NCP group [ (177.30 ± 43.29) pg.mL− 1 vs. (121.53 ± 40.16)pg.mL− 1, P

ABSTRACTThis study aimed to investigate the acute effect of 100 grams of germinated brown rice (GBR) intake on plasma glucose and insulin, serum levels of peptide YY (PYY) and neuropeptide Y (NPY), as well as appetite perception in healthy subjects compared to white rice (WR). Compared to WR (p

Background/Objectives: Heterodimer peptides targeting more than one receptor can be advantageous, as tumors can simultaneously express more than one receptor type. For human breast cancer, a promising biological target is tumor angiogenesis through αvβ3 integrin expression. Another promising target is Neuropeptide Y receptors, considering Y1R is overexpressed in 90% of human breast tumors. This article details the development and preclinical evaluation, both in vitro and in vivo, of a novel heterodimer peptide dual-receptor-targeting probe, [99mTc]HYNIC-cRGDfk-NPY, designed for imaging breast tumors. Methods: Female BALB/c healthy mice were used to perform biodistrubution studies and female SCID mice were subcutaneously injected with MCF-7 and MDA-MB-231 tumor cells. [99mTc]HYNIC-cRGDfk-NPY was intravenously administered to the mice, followed by ex vivo biodistribution studies and small-animal SPECT/CT imaging. Nonspecific tracer uptake in both models was determined by coinjecting an excess of unlabeled HYNIC-cRGDfk-NPY (100 µg) along with the radiolabeled tracer. Results: Imaging and biodistribution data demonstrate good uptake to estrogen receptor-positive (MCF-7) and triple-negative (MDA-MB-231) tumor models. The in vivo tumor uptakes of radiolabeled conjugate were 9.30 ± 3.25% and 4.93 ± 1.01% for MCF-7 and MDA-MB231, respectively. The tumor/muscle ratios were 5.65 ± 0.94 for the MCF-7 model and 7.78 ± 3.20 for MDA-MB231. Conclusions: [99mTc]HYNIC-cRGDfk-NPY demonstrated rapid blood clearance, renal excretion, and in vivo tumor uptake, highlighting its potential as a tumor imaging agent.

The claustrum, a structure having extensive connectivity with the rest of the brain and being involved in many high-cognitive processes, is still one of the least understood parts of the mammalian nervous system. Accelerated advancement of genetic tools for rodents in the last decade have resulted in many breakthroughs about its interaction with cortical and subcortical regions, while human/primate studies have been invaluable in revealing its effects on conscious behaviour. However, these findings did not elucidate conclusively the principles of its internal dynamics, which would clarify its function within the brain network. The first step in this direction is to know the characteristics of major types of neurons in the claustrum. In this review, we are looking at the data allowing a comparison between the main neuronal types of the claustrum in primates and rodents, with the aim of showing the extent of known commonalities and differences, and highlighting the research gap between the two orders. The results indicate that in both there is a ratio excitatory/inhibitory neurons higher than in the cortex, but with a lower baseline activity of the excitatory neurons due to the higher inhibition. The local excitation in the claustrum is provided by collaterals of neurons projecting to the cortex. Secondary neuronal markers such as Calcium binding proteins and somatostatin tend to be expressed differently in the claustrum of primates than in that of rodents, specifically in more classes of neurons and across a larger area. The spatial distribution of neuropeptide Y might be a conserved motif across the two orders. The work in rodents has an undisputable advance in the study of electrical properties for each class of claustrum neurons. However, for a deep understanding of the claustrum function in the human brain, primate studies remain indispensable. [ABSTRACT FROM AUTHOR]

Introduction: This study may unveil novel insights into the interactions between neuropeptide Y receptor 1 (NPY1R) and galanin receptor 2 (GALR2), in the dentate gyrus of the dorsal hippocampus, shedding light on their role in neurogenesis and cognitive functions. Existing literature highlights the potential of these interactions in enhancing learning and memory, yet detailed mechanisms remain underexplored. Methods: Utilizing intracerebroventricular injections of GALR2 and NPY1R agonists in Sprague-Dawley male rats, we examined neurogenesis via markers PCNA and DCX, and memory consolidation through the object-in-place task over a three-week period. Results: Significant increases in NPY1R-GALR2 co-localization and neuroblast proliferation were observed, alongside enhanced memory consolidation. These findings suggest a synergistic effect of NPY1R and GALR2 activation on cognitive functions. Discussion: Our findings may foster the development of novel heterobivalent or multitargeting drugs, affecting NPY1R-GALR2 interaction, and suggest a future pharmacogical strategy for improving learning and memory found in many brain diseases. Further research is encouraged to explore these mechanisms in pathological models. [ABSTRACT FROM AUTHOR]

Background: The vaso- and psychoactive endogenous Neuropeptide Y (NPY) has repeatedly been shown to be excessively released after subarachnoid hemorrhage and in numerous psychiatric disorders. NPY is stored in sympathetic perivascular nerve fibers around the major cerebral arteries. This prospective study was designed to analyze the impact of microsurgical and endovascular manipulation of the cerebral vasculature versus cranio- and durotomy alone on the serum levels of NPY. Methods: 58 patients (drop-out n = 3; m:f = 26:29; mean age 52.0 ± 14.1 years) were prospectively enrolled. The vascular group underwent repair for unruptured intracranial aneurysms (UIA) of the anterior circulation [endovascular aneurysm occlusion (EV) n = 13; microsurgical clipping (MS) n = 17]; in the non-vascular group, 14 patients received microsurgical resection of a small-sized convexity meningioma (CM), and 11 patients with surgically treated degenerative lumbar spine disease (LD) served as control. Plasma was drawn (1) before treatment (t0), (2) periprocedurally (t1), (3) 6 h postprocedurally (t2), (4) 72 h postprocedurally (t3), and (5) at the 6-week follow-up (FU; t4) to determine the NPY levels via competitive enzyme immunoassay in duplicate serum samples. We statistically evaluated differences between groups by calculating one-way ANOVA and for changes along the time points using repeated measure ANOVA. Results: Except for time point t0, the serum concentrations of NPY ranged significantly higher in the vascular than in the non-vascular group (p < 0.001), with a slight decrease in both vascular subgroups 6 h postprocedurally, followed by a gradual increase above baseline levels until FU. At t3, the EV subgroup showed significantly higher NPY levels (mean ± standard deviation) than the MS subgroup (0.569 ± 0.198 ng/mL vs. 0.415 ± 0.192 ng/mL, p = 0.0217). The highest NPY concentrations were measured in the EV subgroup at t1, t3, and t4, reaching a climax at FU (0.551 ± 0.304 ng/mL). Conclusion: Our study reveals a first insight into the short-term dynamics of the serum levels of endogenous NPY in neurosurgical and endovascular procedures, respectively: Direct manipulation within but also next to the major cerebral arteries induces an excessive release of NPY into the serum. Our findings raise the interesting question of the potential capacity of NPY in modulating the psycho-behavioral outcome of neurovascular patients. [ABSTRACT FROM AUTHOR]

Key points Cardiac disease is marked by sympathoexcitation and elevated levels of noradrenaline (NA) and cotransmitter neuropeptide Y (NPY). Increased NPY levels are associated with a greater risk of ventricular arrhythmias and mortality. Nonetheless, the factors that cause NPY release remain poorly understood. We hypothesized that circulating catecholamines might lead to NPY release from myocardial sympathetic nerve terminals via a β‐receptor‐mediated mechanism that enhances sympathoexcitation. Ventricular interstitial NA and NPY levels were measured in six Yorkshire pigs after i.v. administration of NA (1 mg) and before and after propranolol infusion (1 mg/kg). Real‐time interstitial NPY levels were measured using ventricular capacitive immunoprobes (CIs) affixed with NPY antibodies and quantified as the change in CI input current (INPY) upon binding of NPY. Interstitial NA was measured with adjacent fast‐scan cyclic voltammetry probes (INA). A left ventricular pressure catheter and continuous ECGs were used for haemodynamic recordings, and an epicardial 56‐electrode sock was used for measurements of activation recovery interval, a surrogate of action potential duration. Upon administration of NA, heart rate and left ventricular pressure increased, and activation recovery interval shortened. Notably, NA significantly increased interstitial myocardial NPY levels. After propranolol, changes in heart rate and activation recovery interval were largely mitigated. The INA increased to a similar extent post‐propranolol vs. pre‐propranolol, but changes in INPY were significantly reduced post‐propranolol. Coronary sinus plasma analyses confirmed fast‐scan cyclic voltammetry and CI findings. Hence, this study demonstrates that circulating NA induces NPY release from ventricular sympathetic nerve terminals, the mechanism for which is mediated via β‐adrenergic receptors and can be blocked by the non‐selective β‐blocker, propranolol. Cardiovascular disease is characterized by sympathovagal imbalance, with increased plasma noradrenaline (NA) and neuropeptide Y (NPY) concentrations. Increased NPY levels are associated with increased ventricular arrhythmias and mortality in heart failure. Limited data are available on the specific factors that cause NPY release. In this study, fast‐scan cyclic voltammetry and capacitive immunoprobes were used to allow for real‐time in vivo measurements of interstitial myocardial neurotransmitters and neuropeptides, respectively. Using an in vivo porcine model with cardiac fast‐scan cyclic voltammetry and capacitive immunoprobes, it was shown that systemic NA can increase ventricular interstitial NPY levels, suggesting that NA induces NPY release from postganglionic sympathetic nerves. The release of NPY was blocked by administration of the non‐selective β‐blocker propranolol, suggesting that release of NPY is dependent on activation of β‐adrenergic receptors by NA. [ABSTRACT FROM AUTHOR]

Although more than 30 different types of neuropeptides have been identified in various cell types and circuits of the cerebellum, their unique functions in the cerebellum remain poorly understood. Given the nature of their diffuse distribution, peptidergic systems are generally assumed to exert a modulatory effect on the cerebellum via adaptively tuning neuronal excitability, synaptic transmission, and synaptic plasticity within cerebellar circuits. Moreover, cerebellar neuropeptides have also been revealed to be involved in the neurogenetic and developmental regulation of the developing cerebellum, including survival, migration, differentiation, and maturation of the Purkinje cells and granule cells in the cerebellar cortex. On the other hand, cerebellar neuropeptides hold a critical position in the pathophysiology and pathogenesis of many cerebellar-related motor and psychiatric disorders, such as cerebellar ataxias and autism. Over the past two decades, a growing body of evidence has indicated neuropeptides as potential therapeutic targets to ameliorate these diseases effectively. Therefore, this review focuses on eight cerebellar neuropeptides that have attracted more attention in recent years and have significant potential for clinical application associated with neurodegenerative and/or neuropsychiatric disorders, including brain-derived neurotrophic factor, corticotropin-releasing factor, angiotensin II, neuropeptide Y, orexin, thyrotropin-releasing hormone, oxytocin, and secretin, which may provide novel insights and a framework for our understanding of cerebellar-related disorders and have implications for novel treatments targeting neuropeptide systems. [ABSTRACT FROM AUTHOR]

Overfeeding triggers homeostatic compensatory mechanisms that counteract weight gain. Here, we show that both lean and diet-induced obese (DIO) male mice exhibit a potent and prolonged inhibition of voluntary food intake following overfeeding-induced weight gain. We reveal that FGF21 is dispensable for this defense against weight gain. Targeted proteomics unveiled novel circulating factors linked to overfeeding, including the protease legumain (LGMN). Administration of recombinant LGMN lowers body weight and food intake in DIO mice. The protection against weight gain is also associated with reduced vascularization in the hypothalamus and sustained reductions in the expression of the orexigenic neuropeptide genes, Npy and Agrp, suggesting a role for hypothalamic signaling in this homeostatic recovery from overfeeding. Overfeeding of melanocortin 4 receptor (MC4R) KO mice shows that these mice can suppress voluntary food intake and counteract the enforced weight gain, although their rate of weight recovery is impaired. Collectively, these findings demonstrate that the defense against overfeeding-induced weight gain remains intact in obesity and involves mechanisms independent of both FGF21 and MC4R. Overfeeding triggers a mechanistically ill-defined compensatory response that counteracts weight gain. Here, the authors show that the defence against overfeeding is preserved in obesity, and that it is independent from FGF21 and MC4R. [ABSTRACT FROM AUTHOR]

Migraine is a highly prevalent neurological disorder. Among the risk factors identified, psychiatric comorbidities, such as depression, seem to play an important role in its onset and clinical course. Patients with migraine are 2.5 times more likely to develop a depressive disorder; this risk becomes even higher in patients suffering from chronic migraine or migraine with aura. This relationship is bidirectional, since depression also predicts an earlier/worse onset of migraine, increasing the risk of migraine chronicity and, consequently, requiring a higher healthcare expenditure compared to migraine alone. All these data suggest that migraine and depression may share overlapping biological mechanisms. Herein, this review explores this topic in further detail: firstly, by introducing the common epidemiological and risk factors for this comorbidity; secondly, by focusing on providing the cumulative evidence of common biological aspects, with a particular emphasis on the serotoninergic system, neuropeptides such as calcitonin-gene-related peptide (CGRP), pituitary adenylate cyclase-activating polypeptide (PACAP), substance P, neuropeptide Y and orexins, sexual hormones, and the immune system; lastly, by remarking on the future challenges required to elucidate the etiopathological mechanisms of migraine and depression and providing updated information regarding new key targets for the pharmacological treatment of these clinical entities. [ABSTRACT FROM AUTHOR]

Orexigenic neurons expressing agouti‐related protein (AgRP) and neuropeptide Y in the arcuate nucleus (ARC) of the hypothalamus are activated in response to dynamic variations in the metabolic state, including exercise. We previously observed that carnitine palmitoyltransferase 1a (CPT1A), a rate‐limiting enzyme of mitochondrial fatty acid oxidation, is a key factor in AgRP neurons, modulating whole‐body energy balance and fluid homeostasis. However, the effect of CPT1A in AgRP neurons in aged mice and during exercise has not been explored yet. We have evaluated the physical and cognitive capacity of adult and aged mutant male mice lacking Cpt1a in AgRP neurons (Cpt1a KO). Adult Cpt1a KO male mice exhibited enhanced endurance performance, motor coordination, locomotion, and exploration compared with control mice. No changes were observed in anxiety‐related behavior, cognition, and muscle strength. Adult Cpt1a KO mice showed a reduction in gastrocnemius and tibialis anterior muscle mass. The cross‐sectional area (CSA) of these muscles were smaller than those of control mice displaying a myofiber remodeling from type II to type I fibers. In aged mice, changes in myofiber remodeling were maintained in Cpt1a KO mice, avoiding loss of physical capacity during aging progression. Additionally, aged Cpt1a KO mice revealed better cognitive skills, reduced inflammation, and oxidative stress in the hypothalamus and hippocampus. In conclusion, CPT1A in AgRP neurons appears to modulate health and protects against aging. Future studies are required to clarify whether CPT1A is a potential antiaging candidate for treating diseases affecting memory and physical activity. [ABSTRACT FROM AUTHOR]

Objective: Neuropeptide Y (NPY) is a powerful regulator of anxious states, including social anxiety, but evidence from human genetic studies is limited. Associations of common gene variants with behaviour have been described as subject to birth cohort effects, especially if the behaviour is socially motivated. This study aimed to examine the association of NPY rs16147 and rs5574 with personality traits in highly representative samples of two birth cohorts of young adults, the samples having been formed during a period of rapid societal transition. Methods: Both birth cohorts (original n = 1238) of the Estonian Children Personality Behaviour and Health Study (ECPBHS) self-reported personality traits of the five-factor model at 25 years of age. Results: A significant interaction effect of the NPY rs16147 and rs5574 and birth cohort on Agreeableness was found. The T/T genotype of NPY rs16147 resulted in low Agreeableness in the older cohort (born 1983) and in high Agreeableness in the younger cohort (born 1989). The C/C genotype of NPY rs5574 was associated with higher Agreeableness in the younger but not in the older cohort. In the NPY rs16147 T/T homozygotes, the deviations from average in Agreeableness within the birth cohort were dependent on the serotonin transporter promoter polymorphism. Conclusions: The association between the NPY gene variants and a personality domain reflecting social desirability is subject to change qualitatively in times of rapid societal changes, serving as an example of the relationship between the plasticity genes and environment. The underlying mechanism may involve the development of the serotonergic system. [ABSTRACT FROM AUTHOR]

The egg-laying performance of Shan Ma ducks (Anas Platyrhynchos) is a crucial economic trait. Nevertheless, limited research has been conducted on the egg-laying performance of this species. We examined routine blood indicators and observed higher levels of metabolic and immune-related factors in the high-egg-production group compared with the low-egg-production group. Furthermore, we explored the ovarian transcriptome of both high- and low-egg-production groups of Shan Ma ducks using Illumina NovaSeq 6000 sequencing. A total of 1357 differentially expressed genes (DEGs) were identified, with 686 down-regulated and 671 up-regulated in the high-egg-production (HEP) ducks and low-egg-production (LEP) ducks. Several genes involved in the regulation of ovarian development, including neuropeptide Y (NPY), cell cycle protein-dependent kinase 1 (CDK1), and transcription factor 1 (E2F1), exhibited significant differential expressions at varying stages of egg production. Pathway functional analysis revealed that the DEGs were primarily associated with the steroid biosynthesis pathway, and the neuroactive ligand–receptor interaction pathway exhibited higher activity in the HEP group compared to the LEP group. This study offers valuable information about and novel insights into high egg production. [ABSTRACT FROM AUTHOR]

Hypoglycaemia-associated autonomic failure (HAAF) is characterised by an impairment in adrenal medullary and neurogenic symptom responses following episodes of recurrent hypoglycaemia. Here, we review the status quo of research related to the regulatory mechanisms of the adrenal medulla in its response to single and recurrent hypoglycaemia in both diabetic and non-diabetic subjects with particular focus given to catecholamine synthesis, enzymatic activity, and the impact of adrenal medullary peptides. Short-term post-transcriptional modifications, particularly phosphorylation at specific residues of tyrosine hydroxylase (TH), play a key role in the regulation of catecholamine synthesis. While the effects of recurrent hypoglycaemia on catecholamine synthetic enzymes remain inconsistent, long-term changes in TH protein expression suggest species-specific responses. Adrenomedullary peptides such as neuropeptide Y (NPY), galanin, and proenkephalin exhibit altered gene and protein expression in response to hypoglycaemia, suggesting a potential role in the modulation of catecholamine secretion. Of note is NPY, since its antagonism has been shown to prevent reductions in TH protein expression. This review highlights the need for further investigation into the molecular mechanisms involved in the adrenal medullary response to hypoglycaemia. Despite advancements in our understanding of HAAF in non-diabetic rodents, a reliable diabetic rodent model of HAAF remains a challenge. [ABSTRACT FROM AUTHOR]

The aim of this study was to carry out a systematic review of clinical trials followed by meta-analysis, to evaluate the effect of sourdough bread on glycemic control and appetite and satiety regulators such as leptin, ghrelin, GLP-1 (glucagon-like peptide-1), GLP-2 (glucagon-like peptide-2), NPY (neuropeptide Y), AgRP (agouti-related protein), PYY (peptide YY), and GIP (glucose-dependent insulinotropic polypeptide). Clinical trials compared the intake of sourdough bread to that of an industrially fermented one or control glucose solution in adults over 18 years of age. This systematic review included all randomized, parallel, or crossover trials published up to June 2021 in the EMBASE, MEDLINE, Scopus, and Web of Science databases. After the selection process, 18 studies were included. The analysis of the final average difference of the change in serum glucose after 60 minutes for the intervention indicated that the consumption of sourdough bread has a lower impact on blood glucose compared to that of industrial bread or glucose (MD = −0.29, IC 95% = [−0.46; −0.12]; I2 = 0%). The evaluation of blood glucose 120 minutes after the consumption of the intervention also indicated a lower increment in blood glucose when compared to the consumption of other types of bread or the same amount of glucose (MD = −0.21, IC 95% = [−0.32; −0.09]; I2 = 0%). The certainty of evidence varied from low to very low. The results showed that sourdough is effective in reducing the increment of postprandial glycemia, especially when prepared with whole wheat flour, although it does not reduce fasting serum insulin, nor does it change plasma PYY. [ABSTRACT FROM AUTHOR]

Background: Umbilical cord blood-derived therapeutics, such as serum (UCS) and platelet-rich plasma (UCPRP), are popular treatment options in clinical trials and can potentially be utilized to address a clinically unmet need caused by preservatives, specifically benzalkonium chloride (BAK), present in ophthalmic formulations. As current clinical interventions for secondary injuries caused by BAK are suboptimal, this study will explore the feasibility of utilizing UCS and UCPRP for cornea treatment and investigate the underlying mechanisms associated with this approach. Methods: Mice's corneas were administered BAK to induce damage. UCS and UCPRP were then utilized to attempt to treat the injuries. Ocular tests were performed on the animals to evaluate recovery, while immunostaining, RNA-seq, and subsequent bioinformatics analysis were conducted to investigate the treatment mechanism. Results: BAK administration led to widespread inflammatory responses in the cornea. Subsequent treatment with UCS and UCPRP led to the downregulation of immune-related 'interactions between cytokine receptors' and 'IL-17 signaling' pathways. Although axonal enhancers such as Ngf, Rac2, Robo2, Srgap1, and Rock2 were found to be present in the injured group, robust axonal regeneration was observed only in the UCS and UCPRP treatment groups. Further analysis revealed that, as compared to normal corneas, inflammation was not restored to pre-injury levels post-treatment. Importantly, Neuropeptide Y (Npy) was also involved in regulating immune responses, indicating neuroimmune axis interactions. Conclusions: Cord blood-derived therapeutics are feasible options for overcoming the sustained injuries induced by BAK in the cornea. They also have potential applications in areas where axonal regeneration is required. [ABSTRACT FROM AUTHOR]

Background and Objective: Radiation therapy is a routine clinical practice that has been used for a long time in the treatment of cancer patients. The most important dose-limiting organ in patients receiving radiotherapy for various conditions is the brain. The mechanisms underlying brain and pituitary gland damage caused by radiation are largely unknown. It is of great importance to use radioprotective agents to protect against damage. This study aims to evaluate the neuroprotective effects of quercetin in experimental radiation-induced brain and pituitary gland damage. Materials and Methods: A total of 60 adult male Wistar-albino rats were randomly divided into six groups (control, sham, radiation, quercetin, radiation + quercetin, and quercetin + radiation groups, with ten rats in each group). Quercetin was given to rats by oral gavage at 50 mg/kg/day. A whole-body single dose of 10 Gy radiation was applied to the rats. Tissue samples belonging to the groups were compared after excision. Histopathological changes in the brain tissue and pituitary gland were examined with hematoxylin-tissue samples in the groups and compared histologically and immunohistochemically. Results: The histopathological examination of the brain and anterior pituitary gland sections showed marked damage in the radiation-treated rats, while the quercetin-administered groups showed normal tissue architecture. While neuropeptid Y immunoreactivity was increased, synaptophysin immunoreactivity was decreased in the brains of radiation-treated rats. However, when neuropeptide Y and synaptophysin expression were assessed in the anterior pituitary gland, there was no significant difference between the groups. Conclusion: Consequently, quercetin may be a potential pharmacological agent in modulating radiation-induced damage in rats. However, extra experimental and preclinical studies are needed to confirm our findings before they can be used clinically. [ABSTRACT FROM AUTHOR]