Levetiracetam plus Oxcarbazepine Combination Treatment Downregulates Serum Multidrug Resistance Protein 1 Levels and Upregulates Neuropeptide Y Levels in Children with Epilepsy

Abstract The aim of the present study was to investigate the usefulness of multidrug resistance protein 1 (MDR1) and neuropeptide Y (NPY) levels in predicting the efficacy of levetiracetam (LEV) plus oxcarbazepine (OXC) treatment administered to children with epilepsy and to determine their prognosis. Overall, 193 children with epilepsy admitted to the hospital were enrolled and randomly divided into two groups according to different treatment methods: group A (n = 106, treated with LEV plus OXC combination) and group B (n = 87, treated with OXC only). After treatment, compared with group B, group A exhibited a remarkably higher total effective rate and a significantly lower total adverse reaction rate. Areas under the curve for MDR1 and NPY for predicting ineffective treatment were 0.867 and 0.834, whereas those for predicting epilepsy recurrence were 0.916 and 0.829, respectively. Electroencephalography abnormalities, intracranial hemorrhage, neonatal convulsion, premature delivery, and MDR1 and NPY levels were independent risk factors for poor prognosis in children with epilepsy. Serum MDR1 and NPY levels exhibited a high predictive value for early epilepsy diagnosis, treatment efficacy assessment, and prognostication in children with epilepsy treated with LEV plus OXC combination.

Influence of Neuropeptide Y and Neuropeptide Y 2 Receptor Variants in Acute Coronary Syndrome

Abstract Background The neuropeptide Y (NPY) is one of the most abundant neurotransmitters in the nervous system. NPY acts as a potent stimulator of angiogenesis, inflammation, and adipogenesis, through the NPY 2 receptor (NPY2R). Changes in the NPY signaling pathway have been linked to Acute Coronary Syndrome (ACS). Objectives The purpose of this study is to determine the association between variants in the NPY and NPY2R genes, as well as the severity of acute coronary syndrome (ACS). Methods Approximately 221 ACS patients and 278 healthy controls were selected for this study. Four variants in NPY and two variants in NPY2R genes were genotyped using Taqman allelic discrimination and sequencing. The Chi-square and Fisher's exact tests were used to verify the genotype frequencies. The logistic regression analyses were used for the evaluation of the studied variables. Haplotype analysis was used to evaluate the linkage disequilibrium (LD) between the variants (p<0.05). Results An association of NPY c.20T>C variant was found with the ACS group when compared to the healthy group. In the analysis between variants and risk factors in the ACS group, NPY c.84G>A was associated with hypertension. The analysis between TIMI risk showed a significance for NPY c.20T>C between the low and intermediate/high TIMI risk groups. In the haplotype analysis, strong linkage disequilibrium (LD) was found between the variants NPY c.150G>A and NPY c.-485T>C. Conclusion The NPY c.20T>C variant appears to contribute to the development of ACS. The NPY2R c.-1116A>G variant may contribute to the early development of ACS and the NPY c.84G>A variant appears to contribute to the development of hypertension. In addition, the NPY c.20T>C is associated with a protective effect in ACS severity.

Expression of neuropeptide Y, calcitonin gene related peptide and inducible nitric oxide synthase in myocardium of rats with heart failure / 解剖学报

Objective To explore the relationship between the content of neuropeptide Y (NPY), calcitonin gene-related peptide (CGRP), inducible nitric oxide synthase (iNOS) and the changes of the corresponding receptors in myocardial tissue and the development of heart failure. Methods Doxorubicin was used to prepare rat heart failure models(10 rats), control group (10 rats), Cardiac ultrasound testing evaluated its cardiac function, the distribution of nerve fibers was detected by nerve staining kit method, the tissue expression levels of NPY, CGRP, iNOS and neuropeptide Y receptor Y1 (NPY1R), receptor activity modifying protein 1 (RAMP1), guanylate cyclase beta 1(GCYB1) were observed by immunofluorescence and immunohistochemical staining method. Western blotting was used to detect the protein expression levels of NPY, CGRP, iNOS and NPY1R, RAMP1, GCYB1 receptors in myocardial tissue. Results Compared with the control group, the protein expression level and tissue expression distribution of CGRP in the myocardial tissue of the heart failure group were significantly decreased (P<0.05), while the density of nerve fibers, the protein expression level and tissue expression distribution of NPY and iNOS were significantly increased (P<0.05). The protein expression levels of GCYB1 and RAMP1 in myocardial tissue of the heart failure group were significantly increased, while the protein expression levels of NPY1R were significantly decreased (P<0.05). Conclusion Heart failure can lead to remodeling of the content and distribution of nerve fibers, CGRP, NPY, iNOS and their receptors in myocardial tissue, which may be one of the causes of cardiac innervation disorders.

Advances in the study of neuropeptide Y and neural mechanisms of post-traumatic stress disorder / 中国临床药理学与治疗学

Post-traumatic stress disorder is a persistent psychological disorder that occurs for a period of time after an individual has been directly or indirectly exposed to a traumatic event, and this disorder can seriously affect the individual's daily living status and work situation. According to studies, about 1/3 of people with PTSD have the disorder for life, and the suicide rate is 6 times higher than that of the general population. The pathogenesis of the disease is still inconclusive, and the effect of conventional clinical drug therapy is limited and has significant side effects. At the same time, increasing attention has been paid to the importance of neuropeptide Y (NPY) for individuals to cope with stress and recover from traumatic events. In this paper, we explore the relationship between neuropeptide Y and the hypothalamic-pituitary-adrenal axis, Glutamate and γ-aminobutyric acid neurons, locus coeruleus-norepinephrine system, and corticotropin releasing factor, which are closely related to posttraumatic stress disorder, to identify the neural circuit of neuropeptide Y. It may provide a new perspective for the prevention and treatment of PTSD and for the understanding of its developmental mechanisms.

Research progress of melanin concentrating hormone on depression / 中国药理学通报

Melanin-concentrating hormone (MCH) is an essential neuromodulator involved with multiple neurophysiological functions,such as feeding, mood and sleep-wake cycle. In recent years, the effects of melanin concentrating hormone on depression have attracted much attention, gradually becoming a highlight of developing advanced antidepressants. This article focuses on the research progress of MCHergic system and depression, looking forward to its future research direction.

Modulation of neuropeptide Y levels is impaired in crack withdrawal patients

Abstract Introduction The dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis has a key role in drug addiction susceptibility. In addition to the well-known relationship between cortisol and the HPA axis, other molecules are involved with stress response and could modify the HPA activation, such as the neuropeptide Y (NPY), which has anxiolytic proprieties. There are few studies evaluating the effect of NPY levels on addiction, especially in crack cocaine dependence. Objective To evaluate NPY in crack users during early withdrawal to determine its relationship with drug use and cortisol levels. Methods We analyzed 25 male inpatient crack users. Serum NPY levels were measured at admission and discharge (mean of 24 days). Morning salivary cortisol was measured at admission. Results Serum NPY levels at admission and discharge were very similar. Lower NPY levels at discharge were associated with higher lifetime crack use. Also, a negative correlation was found between morning cortisol and delta NPY (NPY discharge - NPY admission). Conclusion These preliminary findings indicate that crack use influences the modulation of NPY levels and modifies stress response. The NPY pathway may play an important role in the pathophysiology of crack addiction, and the anxiolytic effect of NPY may be impaired in crack users. Future studies should consider NPY as a measurable indicator of the biological state in addiction.

Research progress of effect of anxiolytic traditional Chinese medicines and formulas on neurotransmitters / 中国中药杂志

Anxiety disorders are a common mental illness that seriously endangered physical and mental health of human beings. The etiology of anxiety disorders is closely related to the abnormality of monoamines neurotransmitters, amino acids neurotransmitters and neuropeptides. The long-term use of anti-anxiety chemical drugs has some adverse effects, such as constipation, muscle relaxation, lethargy, tolerance and withdrawal symptoms. However, traditional Chinese medicines have advantages of multi-component, multi-target coordination, with less adverse reactions. Therefore, it is a promising prospect to develop novel anti-anxiety drugs from traditional Chinese medicines and formulas. This article reviewed some traditional Chinese medicines and formulas that can relieve anxiety symptoms. These include traditional Chinese medicines(Panax ginseng, Lycium ruthenium, Morus alba, Bupleurum plus dragon bone oyster soup, Chailong Jieyu Pills, and Naogongtai Formulas) with the effect on monoamine neurotransmitters, such as serotonin, dopamine, and norepinephrine; traditional Chinese medicines(Rehmannia glutinosa, Ziziphus jujuba Mill. var. spinosa, Jielv Anshen Decoction, Baixiangdan Capsules, Antianxietic Compound Prescription Capsules) with the effect on amino acid neurotransmitters, such as glutamic acid, γ-aminobutyrc acid; and traditional Chinese medicines(P. ginseng, Xiaoyao San, Shuyu Ningxin Decoction)with the effect on neuropeptide Y pathway, with the aim to provide theoretical basis for the further development of some novel and more effective anti-anxiety therapeutics from traditional Chinese medicine and formulas.

Characteristics of Pruritus according to Morphological Phenotype of Psoriasis and Association with Neuropeptides and Interleukin-31

Effect of Modified Simiaosan on Inflammatory Factors and Neuropeptide Substances of Patients with Synovitis of Knee Joint and Damp-heat Obstruction Collateral Syndrome / 中国实验方剂学杂志

Objective::To observe the clinical efficacy of modified Simiaosan on synovitis of knee joint with damp-heat obstruction collateral syndrome and the effect on inflammatory factors and neuropeptide substances in synovial fluid. Method::One hundred and thirty-five patients were randomly divided into control group(67 cases) and observation group(68 cases) by random number table. Patients' intra-articular effusion was drawn out. Triamcinolone acetonide was injected into arthrosis for 2 times, 1 time/week, and aceclofenac sustained-release tablets were given for 4 weeks, 0.2 g/time, 1 time/day. In addition to the therapy of control group, patients in observation group were also given modified Simiaosan for 4 weeks, 1 dose/day. Before and after treatment, pain, swelling of knee joint and were scored, Western Ontario and McMaster University (WOMAC) were adopted for scoring knee score, and damp-heat obstruction syndrome and local signs of knee joint were also assessed. And levels of interleukin-1 beta (IL-1 beta), IL-6, tumor necrosis factor-alpha (TNF-alpha), hypersensitive C-reactive protein (hs-CRP), substance P (SP), calcitonin gene-related peptide (CGRP), neuropeptide Y (NPY) and vasoactive intestinal peptide (VIP) were detected. Result::After treatment, scores of pain and swelling of knee joint in observation group were lower than those in control group (P<0.01). Scores of WOMAC, the total score, integral of damp-heat obstruction collateral syndrome, knee flexion-extension range score and floating patella test were all lower than those in control group (P<0.01). And levels of IL-1β, IL-6, TNF-α, hs-CRP, SP, CGRP, NPY and VIP were all lower than those in control group (P<0.01). Analyzed by rank sum test, the clinical efficacy in observation group was better than those in control group (Z=2.089, P<0.05). Conclusion::Modified Simiaosan can significantly alleviate pain and swelling symptoms, promote the recovery of knee joint function, and inhibit the expressions of proinflammatory factors and neuropeptides in synovial fluid, with a better clinical efficacy.

Role of nociceptin/orphanin FQ and nociceptin opioid peptide receptor in depression and antidepressant effects of nociceptin opioid peptide receptor antagonists

Nociceptin/orphanin FQ (N/OFQ) and its receptor, nociceptin opioid peptide (NOP) receptor, are localized in brain areas implicated in depression including the amygdala, bed nucleus of the stria terminalis, habenula, and monoaminergic nuclei in the brain stem. N/OFQ inhibits neuronal excitability of monoaminergic neurons and monoamine release from their terminals by activation of G protein-coupled inwardly rectifying K⁺ channels and inhibition of voltage sensitive calcium channels, respectively. Therefore, NOP receptor antagonists have been proposed as a potential antidepressant. Indeed, mounting evidence shows that NOP receptor antagonists have antidepressant-like effects in various preclinical animal models of depression, and recent clinical studies again confirmed the idea that blockade of NOP receptor signaling could provide a novel strategy for the treatment of depression. In this review, we describe the pharmacological effects of N/OFQ in relation to depression and explore the possible mechanism of NOP receptor antagonists as potential antidepressants.

Moxa-stick moxibustion activates mast cells of small intestine tissue in rats / 针刺研究

OBJECTIVE: To explore the effect of moxa-stick moxibustion and joss-stick moxibustion at "Guanyuan" (CV4) on the activity of mast cells in the small intestine tissue in rats. METHODS: Twelve male SD rats were randomly divided into control, joss-stick moxibustion and moxa-stick moxibustion groups (n=4 rats in each group). Joss-stick or moxa-stick moxibustion was applied to CV4 for 10 min. After moxibustion, the skin temperature of the CV4 region was measured immediately with a thermometer. The mast cells and nerve fibers in the small intestine tissue were displayed by immunofluorescence histochemistry. RESULTS: Compared with the control group, the skin temperature of the CV4 region in both the joss-stick and the moxa-stick groups were significantly increased (P<0.05), while the skin temperature of the moxa-stick group was significantly higher than that in the joss-stick group (P<0.05). There were a large number of tryptase-positive mast cells in the small intestine of rats, some of which were co-expressed with lysosomal-associated membrane protein 1, displaying an activated state. The average numbers of mast cells in the control, joss-stick and moxa-stick groups were 9.2±3.6, 10.8±5.3 and 17.1±6.3, respectively, being significantly higher in the moxa-stick group than in the control and joss-stick groups (P<0.05). In addition, calcitonin gene-related peptide(CGRP) and neuropeptide Y(NPY) positive nerve fibers were found around the mast cells in the small intestinal tissues. CONCLUSION: Moxa-stick moxibustion gives rise a higher temperature at CV4 to activate mast cells surrounded by CGRP and NPY positive nerve fibers in the small intestine tissue in rats, suggesting an involvement of the sensory and sympathetic nervous system in the activation of intestinal mast cells possibly by way of somatic sympathetic reflex.

Identification of mouse organ endogenous peptides by high throughput mass spectrometry / 生物工程学报

Endogenous peptides, in the form of cytokines, growth hormones and hormone peptides, play an important role in human hormones, nerves, cell growth and reproduction. Neuropeptide is a kind of endogenous peptide, which is related to the physiological activities of pain, sleep, emotion, learning and memory. Neuropeptides exist not only in the nerve cells of the brain, but also in other body fluids and organs. At present, there is still a lack of research on endogenous peptides, especially on neuropeptides. In this study, high-throughput liquid chromatography tandem mass spectrometry was used to identify the distribution of endogenous peptides in the pancreas, heart, liver and kidney as well as the types of neuropeptides. The results showed that the number of endogenous peptides and neuropeptides in the liver was the highest while that of the pancreas was the lowest. The identified endogenous peptides were organ-specific and presented different dynamic distribution in four kinds of organs. The number of LPV (Longest peptide variant) of neuropeptide in the four organs varies greatly, and the distribution of gene family is also different. For example, neuropeptide in pancreas belongs to Glucagon family, while neuropeptide in heart belongs to ACBD7, Granins, PEBP and other families. The identification results will provide reference value for the mechanism study of diseases and the research and development of therapeutic drugs.

Progress in research on the role of cannabinoid receptor signaling pathway in Huntington's disease / 中华神经科杂志

Huntington's disease (HD),a single-gene autosomal dominant neurodegenerative disease,is pathologically characterized by the great loss of striatal neurons in the brain.Clinical manifestations of HD show involuntary dance-like movements,cognitive function and neuropsychiatric symptoms.The pathogenesis of HD is concerned with the protein expression of mutant huntingtin which leads to the selective degeneration of medium spiny neurons in the striatum and the onset of the disease.Cannabinoid receptor (CBR) plays a key role in the release of neurotransmitters,synaptic plasticity,gene expression and modulation of.neuronal activity through the CBR1 and CBR2 signaling pathways.Recent studies have found that CBR-mediated phosphoinositide3-kinases/protein kinase B/mammalian target of rapamycin complex1/brain derived neurotrophic factor,neuropeptide Y/neuronal nitric oxide synthase signaling pathway play a vital role in the regulation.of striatal neuroprotection in HD.This review reveals the research progress of CBR1 related signaling pathways in HD,which provides new theoretical basis and drug targets for the prevention and treatment of HD.

Clinical Observation of Acupuncture plus Chinese Medication for Functional Dyspepsia / 上海针灸杂志

Objective To observe the effect of acupuncture plus Chinese medication on the therapeutic efficacy and digestive function in treating patients with functional dyspepsia (FD). Method A retrospective analysis was carried out by targeting 68 FD patients admitted during August 2015 and August 2017. According to the treatment protocol the patients received, they were divided into an observation group and a control group. The control group (33 cases) received Chinese medication, and the observation group (35 cases) was intervened by acupuncture plus Chinese medication. The two groups were compared in terms of clinical efficacy, and post-treatment changes in dyspepsia symptom score, gastric emptying, and the levels of motilin and neuropeptide in serum. Result The total effective rate in the observation group (85.7％) was higher than that in the control group (63.6％), and the difference was statistically significant (P<0.05); before treatment, there were no significant differences between the two groups in the scores of bloating discomfort, early satiation, upper abdominal pain, and upper abdominal burning sensation (P>0.05), while the scores of the dyspepsia symptoms mentioned above were significantly lower in the observation group than in the control group after treatment (P<0.05); there was no significant difference in gastric emptying between the two groups before treatment (P>0.05), while the gastric emptying evaluation was better in the observation group than in the control group after treatment (P<0.05); the between-group differences in the serum levels of motilin and neuropeptide were statistically insignificant before treatment (P>0.05), while the levels of motilin and neuropeptide in serum of the observation group were significantly higher than those in the control group after treatment (P<0.05). Conclusion Acupuncture plus Chinese medication can effectively increase the levels of motilin and neuropeptide in serum, boost gastric emptying, and improve dyspepsia symptoms and gastrointestinal motility in treating FD.

Relations of neuropeptide Y and heme oxygenase-1 expressions with fetal brain injury in rats with intrahepatic cholestasis of pregnancy

Abstract Purpose: To investigate the relations of neuropeptide Y (NPY) and heme oxygenase-1 (HO-1) expressions with fetal brain injury in rats with intrahepatic cholestasis of pregnancy (ICP). Methods: Sixty rats pregnant for 15 days were randomly divided into experimental and control groups. The ICP model was established in experimental group. On the 21st day, the blood biochemical test, histopathological examination of pregnant rat liver and fetal brain tissues and immunohistochemical analysis of fetal rat brain tissues were performed. Results: On the 21st day, the alanineaminotransferase, aspartate aminotransferase and total bile acid levels in experimental group were significantly higher than control group (P<0.01). Compared with control group, there was obvious vacuolar degeneration in pregnant rat liver tissue and fetal brain tissue in experimental group. NPY expression in fetal brain tissue was negative in control group and positive in experimental group. HO-1 expression in fetal brain tissue was strongly positive in control group and positive in experimental group. There was significant difference of immunohistochemical staining optical density between two groups (P<0.01). Conclusion: In fetal brain of ICP rats, the NPY expression is increased, and the HO-1 expression is decreased, which may be related to the fetal brain injury.

Relationship between panic disorder and plasma neuropeptide-S level

Abstract Background: Panic disorder has long been associated with the changes in various neurotransmitters, such as Neuropeptide-S (NPS). Objective: In this study we aimed to determine whether there is a relationship between blood NPS levels and panic disorder. Methods: Twenty nine patients with panic disorder and thirty two healthy control subjects who were age and gender matched were enrolled to the study. Blood samples were taken from participants and plasma NPS levels were quantified by using an ELISA kit. Results: In the study group, median NPS blood level was 16.7 pg/mL and in the control group it was 32.5 pg/mL. There was a statistically significant difference (p = 0.021). Using receiver operating characteristics (ROC) curve, sensitivity and specificity of NPS blood level, for diagnosing panic disorder was calculated, and it was found 79.3% and 56.25% respectively (AUC:0.672, 95% CI: 0.540-0.787). Discussion: Malfunction at the NPS modulatory system in the cortical areas (which is causing excitations in brain areas, such as amygdala and hypothalamus) does not only increase anxiety symptoms and risk of panic disorder but also causes panic disorder patients to have lower plasma NPS levels than the control group. Therefore it can be argued that such malfunction can be treated with a systemic treatment. Baykan H et al. / Arch Clin Psychiatry. 2018;45(4):79-81

Effects of dexmedetomidine on the expressions of hypothalamus neuropeptide and skeletal muscle atrophy gene in endotoxemic rats / 医学研究生学报

Objective Sepsis is often accompanied by serious disorder of energy metabolism, which is characterized by high catabolism, leading to irreversible acute skeletal muscle decomposition. As a new sedative, dexmedetomidine can alleviate the hypercatabolism of sepsis to a certain extent, so it has the potential to improve acute skeletal muscle decomposition. The present work aims to investigate the effects of dexmedetomidine on the expressions of hypothalamus neuropeptides and skeletal muscle atrophy gene in endotoxemic rats.Methods Thirty-six male Sprague Dawley rats were randomly divided into three groups (n=12): control group(group CON),-model group(group LPS-CON) and intervention group(group LPS-DEX). The endotoxemic rat model was established by injecting lipopolysaccharide (LPS) intraperitoneally. After 24 hours intervention, the expressions of hypothalamic neuropeptide (POMC, CART, AgRP and NPY) mRNA as well as MuRF-1 and MAFbx mRNA in skeletal muscle in rats were detected by RT-PCR.Results Compared with control group, the expressions of POMC, CART, MuRF-1 and MAFbx mRNA were significantly up-regulated (P＜0.05), while the expression of AgRP mRNA was significantly down-regulated in-model group (P＜0.05). Compared with-model group, the expressions of POMC, CART, MuRF-1 and MAFbx mRNA were significantly down-regulated (P＜0.05), while the expression of AgRP mRNA was significantly up-regulated in intervention group (P＜0.05).Conclusion Dexmedetomidine could regulate the expressions of hypothalamus neuropeptides and skeletal muscle atrophy gene in endotoxemic rats.

Advance in Role of Neuropeptide Y Receptors System in Pain Modulation (review) / 中国康复理论与实践

@#The neuropeptide Y receptors system is a receptor-ligand system composed of neuropeptide Y and its receptors, which is represented by two subtypes, including Y1 receptor (Y1R) and Y2 receptor (Y2R). The system is widely involved in pain modulation in mammals. These receptors are G protein-coupled receptors, participating in neuronal membrane signaling. Neuropeptide Y receptors distribute in the pain-related regions of the central nervous system, play a variety of roles in maintains neuronal activity of pain transmission, relate to the specificity of distribution. At the spinal level, Y1R plays an analgesic role, whereas Y2R is usually related to pain-promoting. The system can also take part in cerebral pain modulation at different nuclei.

Laminar Distribution of Neurochemically-Identified Interneurons and Cellular Co-expression of Molecular Markers in Epileptic Human Cortex / 神经科学通报·英文版

Inhibitory GABAergic interneurons are fundamental elements of cortical circuits and play critical roles in shaping network activity. Dysfunction of interneurons can lead to various brain disorders, including epilepsy, schizophrenia, and anxiety. Based on the electrophysiological properties, cell morphology, and molecular identity, interneurons could be classified into various subgroups. In this study, we investigated the density and laminar distribution of different interneuron types and the co-expression of molecular markers in epileptic human cortex. We found that parvalbumin (PV) and somatostatin (SST) neurons were distributed in all cortical layers except layer I, while tyrosine hydroxylase (TH) and neuropeptide Y (NPY) were abundant in the deep layers and white matter. Cholecystokinin (CCK) neurons showed a high density in layers IV and VI. Neurons with these markers constituted ~7.2% (PV), 2.6% (SST), 0.5% (TH), 0.5% (NPY), and 4.4% (CCK) of the gray-matter neuron population. Double- and triple-labeling revealed that NPY neurons were also SST-immunoreactive (97.7%), and TH neurons were more likely to express SST (34.2%) than PV (14.6%). A subpopulation of CCK neurons (28.0%) also expressed PV, but none contained SST. Together, these results revealed the density and distribution patterns of different interneuron populations and the overlap between molecular markers in epileptic human cortex.