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Sample records for monoamine neurotransmitter systems

  1. Involvement of the Cerebral Monoamine Neurotransmitters System in Antidepressant-Like Effects of a Chinese Herbal Decoction, Baihe Dihuang Tang, in Mice Model

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    Meng-Li Chen

    2012-01-01

    Full Text Available Baihe Dihuang Tang (BDT is a renowned Chinese herbal formula which is commonly used for treating patients with mental instability, absentmindedness, insomnia, deficient dysphoria, and other psychological diseases. These major symptoms closely associated with the depressive disorders. BDT was widely popular use for treating emotion-thought disorders for many years in China. In the present study, the antidepressant-like effect of BDT in mice was investigated by using the forced swim test (FST and the tail suspension test (TST. The underlying mechanism was explored by determining the effect of BDT on the level of cerebral monoamine neurotransmitters. BDT (9 and 18 g/kg, p.o. for 14 days administration significantly reduced the immobility time in both the FST and the TST without changing locomotion in the open field-test (OFT. Moreover, BDT treatment at the dose of 18 g/kg inhibited reserpine-induced ptosis. Meanwhile, BDT enhanced 5-HT and NA levels in mouse cerebrum as well as decreased the ratio of 5-HT compared to its metabolite, 5-HIAA, (turnover, 5-HIAA/5-HT after TST. The results demonstrated that the antidepressant-like effect of BDT is mediated, at least partially, via the central monoaminergic neurotransmitter system.

  2. Acupuncture Treatment Methods' Influence on the Monoamine Neurotransmitters and Correlative Diseases of Nervous System%针刺对单胺类神经递质及相关神经系统疾病的影响

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    陈乐乐; 岳增辉; 朱小姗

    2011-01-01

    The monoamine neurotransmitter regulates mammal's nervous system function, the visceral function, stress reaction and exciting or soothing to the central nerve system. The results from the present investigation suggest that many diseases of nervous system like Stroke, Parkinson Disease, Dementia, Depression and Morphine Dependence are both related to the abnormity of the monoamine neurotransmitters. Acupuncture has the good therapeutic action on many diseases of nervous system by adjusting the level of monoamine neurotransmitters.%单胺类(monoamines)神经递质对哺乳动物的神经系统功能、内脏功能、应激反应,以及对中枢神经系统的兴奋或抑制起着协调作用.目前的研究表明,许多神经系统疾病如脑卒中、帕金森病、老年性痴呆、抑郁症及吗啡戒断均与单胺类神经递质的异常有关.而针刺通过调节单胺类神经递质的水平,对许多神经系统疾病具有较好的治疗作用.

  3. Specific responses of monoamine neurotransmitters to various acute stressors

    Institute of Scientific and Technical Information of China (English)

    Rongrong He; Guanyu Lin; Yifang Li; Keiich Abe; Xinsheng Yao; Hiroshi Kurihara

    2011-01-01

    This study determined the composition of histamine, serotonin and dopamine using high performance liquid chromatography and electrochemical detection, and compared the changes in monoamine levels in plasma, the cortex and midbrain of mice exposed to acute stressors, such as blood-drawing stimulation or restraint. Results demonstrated that plasma histamine levels were markedly increased when mice were exposed to blood-drawing stimulation and restraint stress. However, serotonin levels decreased in plasma of mice treated with restraint stress, and dopamine levels in plasma had no significant response to the two acute stressors. The three monoamines (histamine, serotonin and dopamine) increased at different degrees in restraint mice, but not in brain regions of blood-drawing stressed mice. Results indicated that histaminergic, serotonergic or dopaminergic systems have their own specific response to different acute stressors.

  4. Focus On: Neurotransmitter Systems

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    Valenzuela, C. Fernando; Puglia, Michael P.; Zucca, Stefano

    2011-01-01

    Neurotransmitter systems have been long recognized as important targets of the developmental actions of alcohol (i.e., ethanol). Short- and long-term effects of ethanol on amino acid (e.g., γ-aminobutyric acid and glutamate) and biogenic amine (e.g., serotonin and dopamine) neurotransmitters have been demonstrated in animal models of fetal alcohol spectrum disorders (FASD). Researchers have detected ethanol effects after exposure during developmental periods equivalent to the first, second, a...

  5. Chronic Effect of Aspartame on Ionic Homeostasis and Monoamine Neurotransmitters in the Rat Brain.

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    Abhilash, M; Alex, Manju; Mathews, Varghese V; Nair, R Harikumaran

    2014-05-28

    Aspartame is one of the most widely used artificial sweeteners globally. Data concerning acute neurotoxicity of aspartame is controversial, and knowledge on its chronic effect is limited. In the current study, we investigated the chronic effects of aspartame on ionic homeostasis and regional monoamine neurotransmitter concentrations in the brain. Our results showed that aspartame at high dose caused a disturbance in ionic homeostasis and induced apoptosis in the brain. We also investigated the effects of aspartame on brain regional monoamine synthesis, and the results revealed that there was a significant decrease of dopamine in corpus striatum and cerebral cortex and of serotonin in corpus striatum. Moreover, aspartame treatment significantly alters the tyrosine hydroxylase activity and amino acids levels in the brain. Our data suggest that chronic use of aspartame may affect electrolyte homeostasis and monoamine neurotransmitter synthesis dose dependently, and this might have a possible effect on cognitive functions.

  6. Altered serous levels of monoamine neurotransmitter metabolites in patiens with refractory and non-refractory depression

    Institute of Scientific and Technical Information of China (English)

    Guiqing Zhang; Yanxia Zhang; Jianxia Yang; Min Hu; Yueqi Zhang; Xia Liang

    2012-01-01

    The study examined plasma metabolite changes of monoamine neurotransmitters in patients with treatment-resistant depression (TRD) and non-TRD before and after therapy. All 30 TRD and 30 non-TRD patients met the diagnostic criteria for a depressive episode in accordance with the International Classification of Diseases, Tenth Revision. Before treatment, and at 4, 6, and 8 weeks after treatment, the plasma metabolite products of monoamine neurotransmitters in TRD group, including 5-hydroxyindoleacetic acid, 3-methoxy-4-hydroxyphenyl ethylene glycol and homovanillic acid, were significantly lower than those in the non-TRD group. After two types of anti-depressive therapy with 5-serotonin and norepinephrine reuptake inhibitor, combined with psychotherapy, the Hamilton Depression Rating Scale scores were significantly reduced in both groups of patients, and the serous levels of 5-hydroxyindoleacetic acid and 3-methoxy-4-hydroxyphenyl ethylene glycol were significantly increased. In contrast, the homovanillic acid level exhibited no significant change. The levels of plasma metabolite products of peripheral monoamine neurotransmitters in depressive patients may predict the degree of depression and the therapeutic effects of treatment.

  7. The molecular mechanism for overcoming the rate-limiting step in monoamine neurotransmitter transport

    DEFF Research Database (Denmark)

    Sinning, Steffen; Said, Saida; Malinauskaite, Lina

    structures of the bacterial homolog, LeuT, captured in a new conformation without substrate or sodium bound shows a dramatic rotation of an absolutely conserved leucine into the substrate site. Molecular dynamics simulations combined with functional studies on SERT support that this leucine must act...... membrane. The rate-limiting step in monoamine reuptake is the return of the empty transporter from an inward-facing to an outward-facing conformation without neurotransmitter and sodium bound. The molecular mechanism underlying this important conformational transition has not been described. Crystal...

  8. Liquid chromatography-electrochemical detection for studying the effects of tetrahydrobiopterin on monoamine neurotransmitters in rat striatum

    Institute of Scientific and Technical Information of China (English)

    ZHANG; Wen; ZHU; Wei; XU; Haihong; WAN; Fangli; GU; Jing; HA

    2005-01-01

    Tetrahydrobiopterin (BH4) is an essential co-factor in the biosynthesis of monoamine neurotransmitters.A nano-Pt/Pd modified electrode as the electrochemical detector (ED) for high-performance liquid chromatography (HPLC) coupled with microdialysis sampling, is used to explore the effect of administration of BH4 on the monoamine neurotransmitters in the rat striatum.The researches demonstrate that the contents of dopamine (DA), 5-hydroxytryptamine (5-HT), 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA) increase significantly with the administration of BH4.The pharmaceutical kinetics is carried out to research into the time course of BH4 effect on the concentration of monoamine neurotransmitters in rat striatum, which provides reliable data for pathology and pharmacology research on neuroscience.

  9. Modulation of monoamine neurotransmitters in fighting fish Betta splendens exposed to waterborne phytoestrogens.

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    Clotfelter, Ethan D; McNitt, Meredith M; Carpenter, Russ E; Summers, Cliff H

    2010-12-01

    Endogenous estrogens are known to affect the activity of monoamine neurotransmitters in vertebrate animals, but the effects of exogenous estrogens on neurotransmitters are relatively poorly understood. We exposed sexually mature male fighting fish Betta splendens to environmentally relevant and pharmacological doses of three phytoestrogens that are potential endocrine disruptors in wild fish populations: genistein, equol, and β-sitosterol. We also exposed fish to two doses of the endogenous estrogen 17β-estradiol, which we selected as a positive control because phytoestrogens are putative estrogen mimics. Our results were variable, but the effects were generally modest. Genistein increased dopamine levels in the forebrains of B. splendens at both environmentally relevant and pharmacological doses. The environmentally relevant dose of equol increased dopamine levels in B. splendens forebrains, and the pharmacological dose decreased norepinephrine (forebrain), dopamine (hindbrain), and serotonin (forebrain) levels. The environmentally relevant dose of β-sitosterol decreased norepinephrine and dopamine in the forebrain and hindbrain, respectively. Our results suggest that sources of environmental phytoestrogens, such as runoff or effluent from agricultural fields, wood pulp mills, and sewage treatment plants, have the potential to modulate neurotransmitter activity in free-living fishes in a way that could interfere with normal behavioral processes.

  10. Radiotracers for PET and SPECT studies of neurotransmitter systems

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    Fowler, J.S.

    1991-01-01

    The study of neurotransmitter systems is one of the major thrusts in emission tomography today. The current generation of Positron Emission Tomography (PET) and Single Photon Emission Computed Tomography (SPECT) radiotracers examines neurotransmitter properties from a number of different perspectives including their pre and post synaptic sites and the activity of the enzymes which regulate their concentration. Although the dopamine system has been the most extensively investigated, other neurotransmitter systems including the acetylcholine muscarine, serotonin, benzodiazepine, opiate, NMDA and others are also under intensive development. Enzymes involved in the synthesis and regulation of neurotransmitter concentration, for example monoamine oxidase and amino acid decarboxylase has also been probed in vivo. Medical applications range from the study of normal function and the characterization of neurotransmitter activity in neurological and psychiatric diseases and in heart disease and cancer to the study of the binding of therapeutic drugs and substances of abuse. This chapter will provide an overview of the current generation of radiotracers for PET and SPECT studies of neurotransmitter systems including radiotracer design, synthesis localization mechanisms and applications in emission tomography. 60 refs., 1 tab.

  11. Simultaneous quantification of monoamine neurotransmitters and their biogenic metabolites intracellularly and extracellularly in primary neuronal cell cultures and in sub-regions of guinea pig brain

    DEFF Research Database (Denmark)

    Schou-Pedersen, Anne Marie Voigt; Hansen, Stine Normann; Tveden-Nyborg, Pernille

    2016-01-01

    In the present paper, we describe a validated chromatographic method for the simultaneous quantification of monoamine neurotransmitters and their biogenic metabolites intracellularly and extracellularly in primary neuronal cell culture and in sub-regions of the guinea pig brain. Electrochemical d...... and is broadly applicable to monoamine measurements in cell cultures as well as brain biopsies from animal models used in preclinical neurochemistry....

  12. Effects of Moxa Smoke on Monoamine Neurotransmitters in SAMP8 Mice

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    Huanfang Xu

    2013-01-01

    Full Text Available Objectives. To investigate the anti-aging effects of moxa smoke on SAMP8 mice. Methods. Using 2×3 factorial design, exposure length (15 or 30 minutes daily, and concentration (low, 5–15 mg/m3; middle, 25–35 mg/m3; high, 85–95 mg/m3, 70 SAMP8 mice were randomly assigned, n=10/group, to a model group or one of six moxa smoke groups: L1, L2, M1, M2, H1, or H2. Ten SAMR1 mice were used as normal control. Mice in moxa smoke groups were exposed to moxa smoke at respective concentrations and exposure lengths; the model and normal control mice were not exposed. Cerebral 5-HT, DA, and NE levels were determined using ELISA. Results. Compared to normal control, the model group showed a significant decrease in 5-HT, DA, and NE. Compared to model group, 5-HT and NE were significantly higher in groups L2, M1, and M2 and DA was significantly so in L2 and M1. 5-HT, DA, and NE levels were the highest in group M1 among moxa smoke groups. A marked exposure length × concentration interaction was observed for 5-HT, DA, and NE. Conclusion. Moxa smoke increases monoamine neurotransmitter levels, which varies according to concentration and exposure length. Our finding suggests that the middle concentration of moxa smoke for 15 minutes seems the most beneficial.

  13. Determination of monoamine neurotransmitters and their metabolites in a mouse brain microdialysate by coupling high-performance liquid chromatography with gold nanoparticle-initiated chemiluminescence

    Energy Technology Data Exchange (ETDEWEB)

    Li Na; Guo Jizhao; Liu Bo; Yu Yuqi [Department of Chemistry, University of Science and Technology of China (USTC), JinZhai Road No: 96, 230026 Hefei, Anhui (China); Cui Hua, E-mail: hcui@ustc.edu.cn [Department of Chemistry, University of Science and Technology of China (USTC), JinZhai Road No: 96, 230026 Hefei, Anhui (China); Mao Lanqun; Lin Yuqing [Beijing National Laboratory for Molecular Sciences, Institute of Chemistry, Chinese Academy of Sciences (CAS), 100080 Beijing (China)

    2009-07-10

    Our previous work showed that gold nanoparticles could trigger chemiluminescence (CL) between luminol and AgNO{sub 3}. In the present work, the effect of some biologically important reductive compounds, including monoamine neurotransmitters and their metabolites, reductive amino acids, ascorbic acid, uric acid, and glutathione, on the novel CL reaction were investigated for analytical purpose. It was found that all of them could inhibit the CL from the luminol-AgNO{sub 3}-Au colloid system. Among them, monoamine neurotransmitters and their metabolites exhibited strong inhibition effect. Taking dopamine as a model compound, the CL mechanism was studied by measuring absorption spectra during the CL reaction and the reaction kinetics via stopped-flow technique. The CL inhibition mechanism is proposed to be due to that these tested compounds competed with luminol for AgNO{sub 3} to inhibit the formation of luminol radicals and to accelerate deposition of Ag atoms on surface of gold nanoparticles, leading to a decrease in CL intensity. Based on the inhibited CL, a novel method for simultaneous determination of monoamine neurotransmitters and their metabolites was developed by coupling high-performance liquid chromatography with this CL reaction. The new method was successfully applied to determine the compounds in a mouse brain microdialysate. Compared with the reported HPLC-CL methods, the proposed method is simple, fast, and could determine more analytes. Moreover, the limits of linear ranges for NE, E, and DA using the proposed method were one order of magnitude lower than the luminol system without gold nanoparticles.

  14. Effect of aspartame on oxidative stress and monoamine neurotransmitter levels in lipopolysaccharide-treated mice.

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    Abdel-Salam, Omar M E; Salem, Neveen A; Hussein, Jihan Seid

    2012-04-01

    This study aimed at investigating the effect of the sweetener aspartame on oxidative stress and brain monoamines in normal circumstances and after intraperitoneal (i.p.) administration of lipopolysaccharide (LPS; 100 μg/kg) in mice. Aspartame (0.625-45 mg/kg) was given via subcutaneous route at the time of endotoxin administration. Mice were euthanized 4 h later. Reduced glutathione (GSH), lipid peroxidation (thiobarbituric acid-reactive substances; TBARS), and nitrite concentrations were measured in brain and liver. Tumor necrosis factor-alpha (TNF-α) and glucose were determined in brain. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) were measured in liver. The administration of only aspartame (22.5 and 45 mg/kg) increased brain TBARS by 17.7-32.8%, decreased GSH by 25.6-31.6%, and increased TNF-α by 16.7-44%. Aspartame caused dose-dependent inhibition of brain serotonin, noradrenaline, and dopamine. Aspartame did not alter liver TBARS, nitrite, GSH, AST, ALT, or ALP. The administration of LPS increased nitrite in brain and liver by 26.8 and 37.1%, respectively; decreased GSH in brain and liver by 21.6 and 31.1%, respectively; increased brain TNF-α by 340.4%, and glucose by 39.9%, and caused marked increase in brain monoamines. LPS increased AST, ALT, and ALP in liver tissue by 84.4, 173.7, and 258.9%, respectively. Aspartame given to LPS-treated mice at 11.25 and 22.5 mg/kg increased brain TBARS by 15.5-16.9%, nitrite by 12.6-20.1%, and mitigated the increase in monoamines. Aspartame did not alter liver TBARS, nitrite, GSH, ALT, AST, or ALP. Thus, the administration of aspartame alone or in the presence of mild systemic inflammatory response increases oxidative stress and inflammation in the brain, but not in the liver.

  15. Online micro-solid-phase extraction based on boronate affinity monolithic column coupled with high-performance liquid chromatography for the determination of monoamine neurotransmitters in human urine.

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    Yang, Xiaoting; Hu, Yufei; Li, Gongke

    2014-05-16

    Quantification of monoamine neurotransmitters is very important in diagnosing and monitoring of patients with neurological disorders. We developed an online analytical method to selectively determine urinary monoamine neurotransmitters, which coupled the boronate affinity monolithic column micro-solid-phase extraction with high-performance liquid chromatography (HPLC). The boronate affinity monolithic column was prepared by in situ polymerization of vinylphenylboronic acid (VPBA) and N,N'-methylenebisacrylamide (MBAA) in a stainless capillary column. The prepared monolithic column showed good permeability, high extraction selectivity and capacity. The column-to-column reproducibility was satisfactory and the enrichment factors were 17-243 for four monoamine neurotransmitters. Parameters that influence the online extraction efficiency, including pH of sample solution, flow rate of extraction and desorption, extraction volume and desorption volume were investigated. Under the optimized conditions, the developed method exhibited low limit of detection (0.06-0.80μg/L), good linearity (with R(2) between 0.9979 and 0.9993). The recoveries in urine samples were 81.0-105.5% for four monoamine neurotransmitters with intra- and inter-day RSDs of 2.1-8.2% and 3.7-10.6%, respectively. The online analytical method was sensitive, accurate, selective, reliable and applicable to analysis of trace monoamine neurotransmitters in human urine sample.

  16. In vivo study on the monoamine neurotransmitters and their metabolites change in the striatum of Parkinsonian rats by liquid chromatography with an acetylene black nanoparticles modified electrode.

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    Lin, Li; Yang, Jie; Lin, Ruipo; Yu, Li; Gao, Hongchang; Yang, Shulin; Li, Xiaokun

    2013-01-01

    The variation in the concentration of monoamine neurotransmitters and their metabolites in an experimental Parkinsonian animal model established by unilateral 6-hydroxydopamine administration was studied. For the purpose of detecting monoamine neurotransmitters and their metabolites more sensitively, an acetylene black nanoparticles modified electrode was fabricated and used as the working electrode for an electrochemical detector in HPLC. The results indicated that the modified electrode exhibited efficiently electrocatalytic oxidation for monoamine neurotransmitters and their metabolites with relatively high sensitivity, long life, and stability. The linear ranges spanned four orders of magnitude (r>0.998) and the detectability was on the level of 0.1 nmolL(-1). The percent relative standard deviation (%RSD) for each compound at all concentration levels was lower than 2.57% and 1.94% for intra-day and inter-day precision, respectively. The mean recovery values were between 98.75% and 105.25%, and the %RSD was found to be less than 1.02%. Coupled with in vivo microdialysis sampling, the validated method was successfully applied to measure monoamine neurotransmitters and their metabolites in both sides of the striatum of conscious and freely moving Parkinsonian rats, and the extracellular monoamine neurotransmitters and their metabolites in the lesioned-side striatum of unilateral 6-hydroxydopamine-lesioned rats were lower than that in the intact side striatum or in the striatum of control rats.

  17. A glial variant of the vesicular monoamine transporter is required to store histamine in the Drosophila visual system.

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    Rafael Romero-Calderón

    2008-11-01

    Full Text Available Unlike other monoamine neurotransmitters, the mechanism by which the brain's histamine content is regulated remains unclear. In mammals, vesicular monoamine transporters (VMATs are expressed exclusively in neurons and mediate the storage of histamine and other monoamines. We have studied the visual system of Drosophila melanogaster in which histamine is the primary neurotransmitter released from photoreceptor cells. We report here that a novel mRNA splice variant of Drosophila VMAT (DVMAT-B is expressed not in neurons but rather in a small subset of glia in the lamina of the fly's optic lobe. Histamine contents are reduced by mutation of dVMAT, but can be partially restored by specifically expressing DVMAT-B in glia. Our results suggest a novel role for a monoamine transporter in glia that may be relevant to histamine homeostasis in other systems.

  18. Vanillin-induced amelioration of depression-like behaviors in rats by modulating monoamine neurotransmitters in the brain.

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    Xu, Jinyong; Xu, Hui; Liu, Yang; He, Haihui; Li, Guangwu

    2015-02-28

    Olfaction plays an important role in emotions in our daily life. Pleasant odors are known to evoke positive emotions, inducing relaxation and calmness. The beneficial effects of vanillin on depressive model rats were investigated using a combination of behavioral assessments and neurotransmitter measurements. Before and after chronic stress condition (or olfactory bulbectomy), and at the end of vanillin or fluoxetine treatment, body weight, immobility time on the forced swimming test and sucrose consumption in the sucrose consumption test were measured. Changes in these assessments revealed the characteristic phenotypes of depression in rats. Neurotransmitters were measured using ultrahigh-performance liquid chromatography. Our results indicated that vanillin could alleviate depressive symptoms in the rat model of chronic depression via the olfactory pathway. Preliminary analysis of the monoamine neurotransmitters revealed that vanillin elevated both serotonin and dopamine levels in brain tissue. These results provide important mechanistic insights into the protective effect of vanillin against chronic depressive disorder via olfactory pathway. This suggests that vanillin may be a potential pharmacological agent for the treatment of major depressive disorder.

  19. The molecular mechanism for overcoming the rate-limiting step in monoamine neurotransmitter transport

    DEFF Research Database (Denmark)

    Sinning, Steffen; Said, Saida; Malinauskaite, Lina

    as an endogenous substrate mimic in the empty transporter in order for it to overcome the transition from the inward-facing to the outward-facing conformation. We also show that the local conformational changes associated with the rotation of this conserved leucine explains how cation sites are perturbed...... and are targets for drugs of abuse such as cocaine, amphetamine and ecstasy as well as anxiolytics and antidepressants. The transporters undergo a series of concerted conformational changes in order to harness the driving force of co-transported cations to translocate the neurotransmitter across the neuronal...

  20. Effects of Acupuncture on Monoamine Neurotransmitters in Raphe Nuclei in Obese Rats

    Institute of Scientific and Technical Information of China (English)

    魏群利; 刘志诚

    2003-01-01

    Effects of acupuncture on the levels of neurotransmitters in the raphe nuclei were investigated in obese rats. It was found that the levels of tryptophan (Trp) and 5-hydroxyindoleacetic acid (5-HIAA) were increased, and 5-hydroxytryptamine (5-HT) level and 5-HT/5-HIAA ratio decreased in the raphe nuclei of the obese group as compared with the normal group; and that acupuncture could produce weight reduction, increase the 5-HT level and 5-HT/5-HIAA ratio, and decrease the contents of Trp and 5-HIAA, but did not change the levels of dopamine (DA) and noradrenaline (NA). It is indicated that benign regulative action of acupuncture on 5-HT and its metabolism in the raphe nuclei is possibly one of the factors for reducing weight by acupuncture.

  1. Treatment with the MAO-A inhibitor clorgyline elevates monoamine neurotransmitter levels and improves affective phenotypes in a mouse model of Huntington disease.

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    Garcia-Miralles, Marta; Ooi, Jolene; Ferrari Bardile, Costanza; Tan, Liang Juin; George, Maya; Drum, Chester L; Lin, Rachel Yanping; Hayden, Michael R; Pouladi, Mahmoud A

    2016-04-01

    Abnormal monoamine oxidase A and B (MAO-A/B) activity and an imbalance in monoamine neurotransmitters have been suggested to underlie the pathobiology of depression, a major psychiatric symptom observed in patients with neurodegenerative diseases, such as Huntington disease (HD). Increased MAO-A/B activity has been observed in brain tissue from patients with HD and in human and rodent HD neural cells. Using the YAC128 mouse model of HD, we studied the effect of an irreversible MAO-A inhibitor, clorgyline, on the levels of select monoamine neurotransmitters associated with affective function. We observed a decrease in striatal levels of the MAO-A/B substrates, dopamine and norepinephrine, in YAC128 HD mice compared with wild-type mice, which was accompanied by increased anxiety- and depressive-like behaviour at five months of age. Treatment for 26 days with clorgyline restored dopamine, serotonin, and norepinephrine neurotransmitter levels in the striatum and reduced anxiety- and depressive-like behaviour in YAC128 HD mice. This study supports a potential therapeutic use for MAO-A inhibitors in the treatment of depression and anxiety in patients with HD.

  2. Antidepressant like effects of hydrolysable tannins of Terminalia catappa leaf extract via modulation of hippocampal plasticity and regulation of monoamine neurotransmitters subjected to chronic mild stress (CMS).

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    Chandrasekhar, Y; Ramya, E M; Navya, K; Phani Kumar, G; Anilakumar, K R

    2017-02-01

    Terminalia catappa L. belonging to Combretaceae family is a folk medicine, known for its multiple pharmacological properties, but the neuro-modulatory effect of TC against chronic mild stress was seldom explored. The present study was designed to elucidate potential antidepressant-like effect of Terminalia cattapa (leaf) hydro-alcoholic extract (TC) by using CMS model for a period of 7 weeks. Identification of hydrolysable tannins was done by using LC-MS. After the CMS exposure, mice groups were administered with imipramine (IMP, 10mg/kg, i.p.) and TC (25, 50 and 100mg/kg of TC, p.o.). Behavioural paradigms used for the study included forced swimming test (FST), tail suspension test (TST) and sucrose preference test (SPT). After behavioural tests, monoamine neurotransmitter, cortisol, AchE, oxidative stress levels and mRNA expression studies relevant to depression were assessed. TC supplementation significantly reversed CMS induced immobility time in FST and other behavioural paradigms. Moreover, TC administration significantly restored CMS induced changes in concentrations of hippocampal neurotransmitters (5-HT, DA and NE) as well as levels of acetyl cholinesterase, cortisol, monoamine oxidases (MAO-A, MAO-B), BDNF, CREB, and p-CREB. It suggests that TC supplementation could supress stress induced depression by regulating monoamine neurotransmitters, CREB, BDNF, cortisol, AchE level as well as by amelioration of oxidative stress. Hence TC can be used as a complementary medicine against depression-like disorder.

  3. Roles of monoamine neurotransmitters in the mechanism of drug addiction%单胺类神经递质在药物成瘾中的作用机制

    Institute of Scientific and Technical Information of China (English)

    杨黎华; 白洁

    2015-01-01

    药物成瘾是一种慢性复发性大脑疾病,各种成瘾性药物通过作用于奖赏系统,最终引起神经递质释放的改变,产生奖赏效应。其中,单胺类神经递质5-羟色胺(5-hydroxytryptamine,5-HT)、去甲肾上腺素( noradrenergic,NE)和多巴胺( dopamine,DA)在药物成瘾中起到重要作用,该文就单胺类神经递质在药物成瘾中的作用及机制进行综述。%Drug addiction is a chronic recrudescent brain dis-ease. Various addictive drugs acting on the reward system result in rewarding effects through changes in neurotransmitter patholog-ical release. Among these monoamine neurotransmitters, 5-hydroxytryptamine, norepinephrine and dopamine play key roles in drug addiction. This paper reviews, from a comprehensive perspective, the roles which monoamine neurotransmitters play in the drug addiction and the process of getting addictive.

  4. Associations between Purine Metabolites and Monoamine Neurotransmitters in First-Episode Psychosis

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    Jeffrey K Yao

    2013-06-01

    Full Text Available Schizophrenia (SZ is a biochemically complex disorder characterized by widespread defects in multiple metabolic pathways whose dynamic interactions, until recently, have been difficult to examine. Rather, evidence for these alterations has been collected piecemeal, limiting the potential to inform our understanding of the interactions amongst relevant biochemical pathways. We herein review perturbations in purine and neurotransmitter metabolism observed in early SZ using a metabolomic approach. Purine catabolism is an underappreciated, but important component of the homeostatic response of mitochondria to oxidant stress. We have observed a homeostatic imbalance of purine catabolism in first-episode neuroleptic-naive patients with SZ (FENNS. Precursor and product relationships within purine pathways are tightly correlated. Although some of these correlations persist across disease or medication status, others appear to be lost among FENNS suggesting that steady formation of the antioxidant uric acid via purine catabolism is altered early in the course of illness. As is the case for within-pathway correlations, there are also significant cross-pathway correlations between respective purine and tryptophan pathway metabolites. By contrast, purine metabolites show significant cross-pathway correlation only with tyrosine, and not with its metabolites. Furthermore, several purine metabolites (uric acid, guanosine, or xanthine are each significantly correlated with 5-hydroxyindoleacetic acid (5-HIAA in healthy controls, but not in FENNS at baseline or 4-week after antipsychotic treatment. Taken together, the above findings suggest that purine catabolism strongly associates with the tryptophan pathways leading to serotonin (5-HT and kynurenine metabolites. The Lack of a significant correlation between purine metabolites and 5-HIAA, suggests alterations in key 5-HT pathways that may both be modified by and contribute to oxidative stress via purine

  5. Mild closed head traumatic brain injury-induced changes in monoamine neurotransmitters in the trigeminal subnuclei of a rat model: mechanisms underlying orofacial allodynias and headache

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    Golam Mustafa

    2017-01-01

    Full Text Available Our recent findings have demonstrated that rodent models of closed head traumatic brain injury exhibit comprehensive evidence of progressive and enduring orofacial allodynias, a hypersensitive pain response induced by non-painful stimulation. These allodynias, tested using thermal hyperalgesia, correlated with changes in several known pain signaling receptors and molecules along the trigeminal pain pathway, especially in the trigeminal nucleus caudalis. This study focused to extend our previous work to investigate the changes in monoamine neurotransmitter immunoreactivity changes in spinal trigeminal nucleus oralis, pars interpolaris and nucleus tractus solitaries following mild to moderate closed head traumatic brain injury, which are related to tactile allodynia, touch-pressure sensitivity, and visceral pain. Our results exhibited significant alterations in the excitatory monoamine, serotonin, in spinal trigeminal nucleus oralis and pars interpolaris which usually modulate tactile and mechanical sensitivity in addition to the thermal sensitivity. Moreover, we also detected a robust alteration in the expression of serotonin, and inhibitory molecule norepinephrine in the nucleus tractus solitaries, which might indicate the possibility of an alteration in visceral pain, and existence of other morbidities related to solitary nucleus dysfunction in this rodent model of mild to moderate closed head traumatic brain injury. Collectively, widespread changes in monoamine neurotransmitter may be related to orofacial allodynhias and headache after traumatic brain injury.

  6. Simultaneous quantification of monoamine neurotransmitters and their biogenic metabolites intracellularly and extracellularly in primary neuronal cell cultures and in sub-regions of guinea pig brain.

    Science.gov (United States)

    Schou-Pedersen, Anne Marie V; Hansen, Stine N; Tveden-Nyborg, Pernille; Lykkesfeldt, Jens

    2016-08-15

    In the present paper, we describe a validated chromatographic method for the simultaneous quantification of monoamine neurotransmitters and their biogenic metabolites intracellularly and extracellularly in primary neuronal cell culture and in sub-regions of the guinea pig brain. Electrochemical detection provided limits of quantifications (LOQs) between 3.6 and 12nM. Within the linear range, obtained recoveries were from 90.9±9.9 to 120±14% and intra-day and inter-day precisions found to be less than 5.5% and 12%, respectively. The analytical method was applicable for quantification of intracellular and extracellular amounts of monoamine neurotransmitters and their metabolites in guinea pig frontal cortex and hippocampal primary neuronal cell cultures. Noradrenaline, dopamine and serotonin were found to be in a range from 0.31 to 1.7pmol per 2 million cells intracellularly, but only the biogenic metabolites could be detected extracellularly. Distinct differences in monoamine concentrations were observed when comparing concentrations in guinea pig frontal cortex and cerebellum tissue with higher amounts of dopamine and its metabolites, 3,4-dihydroxyphenylacetic acid and homovanillic acid in frontal cortex, as compared to cerebellum. The chemical turnover in frontal cortex tissue of guinea pig was for serotonin successfully predicted from the turnover observed in the frontal cortex cell culture. In conclusion, the present analytical method shows high precision, accuracy and sensitivity and is broadly applicable to monoamine measurements in cell cultures as well as brain biopsies from animal models used in preclinical neurochemistry.

  7. Effects of Electric Acupuncture on Monoamine Neurotransmitters in Brains of Newborn Rats with Cerebral Palsy%电针对新生脑性麻痹大鼠单胺类神经递质的影响

    Institute of Scientific and Technical Information of China (English)

    林世坚; 刘振寰; 潘佩光; 赵勇; 祁岩超

    2009-01-01

    objective to detect the content of monoamine neurotransmitters in hippocampus, cortex, basal nucleus and the brainstem of newborn rats with cerebral palsy, to observe the effects of acupuncture on monoamine neurotransmitters, and to explore the mechanism of acupuncture treatment to newborn rats with cerebral palsy. Methods using the method of hypoxic ischemic to make the model of newborn rats with cerebral palsy,decapitating brain after giving acupuncture treatment, separating the required brain regions, and detecting the content of monoamine neurotransmitters with speetrophotometer.Results Compared with the sham operation group, the content of dopamine (DA), 5-Hydroxytryptamine (5-HT) in basal nucleus area of newborn rats with cerebral palsy, and norepinephrine (NE) in Brainstem area decreased significantly(P<0.05), which elevated ignificantly(P<0.05)afler acupuncture treatment. Conclusion it indicated that to improve the ontent of monoamine neurotransmitters in related brain areas may be one of the mechanisms in the acupuncture treatment of newborn rats with cerebral paraly.

  8. Effect of Schisandra chinensis polysaccharide on intracerebral acetylcholinesterase and monoamine neurotransmitters in a D-galactose-induced aging brain mouse model

    Institute of Scientific and Technical Information of China (English)

    Mingsan Miao; Jianlian Gao; Guangwei Zhang; Xiao Ma; Ying Zhang

    2009-01-01

    BACKGROUND: The most prominent characteristic of brain aging is decreased learning and memory ability. The functions of learning and memory are closely related to intracerebral acetylcholinesterase (ACHE) and monoamine neurotransmitter activity. Previous studies have shown that Schisandra chinensis potysaccharide has an anti-aging effect. OBJECTIVE: To explore the effects of Schisandra chinensis polysaccharide on AChE activity and monoamine neurotransmitter content, as well as learning and memory ability in a D-galactose-induced aging mouse brain model compared with the positive control drug Kangnaoling. DESIGN, TIME AND SETTING: Completely randomized, controlled experiment based on neurobiochemistry was performed at the Pharmacological Laboratory, Henan University of Traditional Chinese Medicine from September to December 2003.MATERIALS: Schisandra chinensis was purchased from Henan Provincial Medicinal Company. Schisandra chinensis polysaccharide was obtained by water extraction and alcohol precipitation. Kangnaoling pellets were provided by Liaoning Tianlong Pharmaceutical (batch No. 20030804;state drug permit No. H21023095). A total of 50 six-week-old Kunming mice were randomly divided into five groups: blank control, model, Kangnaoling, high and low dosage Schisandra chinensis polysaccharide groups, with 10 mice per group. METHODS: Mice in the blank control group were subcutaneously injected with 0.5 mL/20 g normal saline into the nape of the neck each day, while the remaining mice were subcutaneously injected with 5% D-galactose saline solution (0.5 mL/20 g) in the nape for 40 days to induce a brain aging model. On day 11, mice in the high and low dosage Schisandra chinensis polysaccharide groups were intragastrically infused with 20 mg/mL and 10 mg/mL Schisandra chinensis polysaccharide solution (0.2 mL/10 g), respectively. Mice from the Kangnaoling group were intragastrically infused with 35 mg/mL Kangnaoling suspension (0.2 mL/10 g), and the mice in the

  9. Simultaneous extraction and determination of monoamine neurotransmitters in human urine for clinical routine testing based on a dual functional solid phase extraction assisted by phenylboronic acid coupled with liquid chromatography-tandem mass spectrometry.

    Science.gov (United States)

    Li, Xiaoguang Sunny; Li, Shu; Kellermann, Gottfried

    2017-02-10

    The major monoamine neurotransmitters, serotonin (5-HT) and catecholamines (i.e., norepinephrine (NE), epinephrine (E), and dopamine (DA)), are critical to the nervous system function, and imbalances of the neurotransmitters have been connected to a variety of diseases, making their measurement useful in a clinical setting. A simple, rapid, robust, sensitive, and specific LC-MS/MS method has been developed and validated for the simultaneous quantitation of urinary serotonin and catecholamines with low cost, which is ideal for routine clinical applications. A simple extraction from complex urine was accomplished using tailored solid phase extraction incorporating phenylboronic acid complexation on a 96-well HLB microplate for the sample extraction and resulted in significantly improved throughput, selectivity, and extraction recovery. Compared to 1-10 mL of urine typically used, this method required only 10 μL. A rapid chromatographic elution with a total cycle time of 6 min per sample compared to reported run times of 19-75 min was achieved on a PFP column. The sensitivity of l and 2 ng mL(-1) for the detection of low abundant E and NE combined with the high coverage of 1024 ng mL(-1) for DA enabled the multi-analyte detection of these biogenic amines in a single run. Good linearity (2.0-512, 1.0-512, 4.0-1024, and 4.0-1024 ng mL(-1) for NE, E, DA, and 5-HT, respectively), accuracy (87.6-104.0%), precision (≤8.0%), extraction recovery (69.6-103.7%), and matrix effect (87.1-113.1% for catecholamines and 63.6-71.4% for 5-HT) were obtained. No autosampler carryover was observed. The analytes were stable for 5 days at 20 °C, 14 days at 4 °C, and 30 days at -20 °C and five freeze-thaw cycles. The easy sample preparation, rapid LC, and multi-analyte MS detection allow two 96-well plates of samples to be extracted within 2 h and analyzed on an LC-MS/MS system within 24 h. The applicability and reliability of the assay were demonstrated by

  10. Effects of Yulangsan polysaccharide on monoamine neurotransmitters, adenylate cyclase activity and brain-derived neurotrophic factor expression in a mouse model of depression induced by unpredictable chronic mild stress

    Institute of Scientific and Technical Information of China (English)

    Shuang Liang; Renbin Huang; Xing Lin; Jianchun Huang; Zhongshi Huang; Huagang Liu

    2012-01-01

    The present study established a mouse model of depression induced by unpredictable chronic mild stress. The model mice were treated with Yulangsan polysaccharide (YLSPS; 150, 300 and 600 mg/kg) for 21 days, and compared with fluoxetine-treated and normal control groups. Enzyme-linked immunosorbent assay, radioimmunity and immunohistochemical staining showed that following treatment with YLSPS (300 and 600 mg/kg), monoamine neurotransmitter levels, prefrontal cortex adenylate cyclase activity and hippocampal brain-derived neurotrophic factor expression were significantly elevated, and depression-like behaviors were improved. Open-field and novelty-suppressed feeding tests showed that mouse activity levels were increased and feeding latency was shortened following treatment. Our results indicate that YLSPS inhibits depression by upregulating monoamine neurotransmitters, prefrontal cortex adenylate cyclase activity and hippocampal brain-derived neurotrophic factor expression.

  11. Cochlear Damage Affects Neurotransmitter Chemistry in the Central Auditory System

    Directory of Open Access Journals (Sweden)

    Donald Albert Godfrey

    2014-11-01

    Full Text Available Tinnitus, the perception of a monotonous sound not actually present in the environment, affects nearly 20% of the population of the United States. Although there has been great progress in tinnitus research over the past 25 years, the neurochemical basis of tinnitus is still poorly understood. We review current research about the effects of various types of cochlear damage on the neurotransmitter chemistry in the central auditory system and document evidence that different changes in this chemistry can underlie similar behaviorally measured tinnitus symptoms. Most available data have been obtained from rodents following cochlear damage produced by cochlear ablation, loud sound, or ototoxic drugs. Effects on neurotransmitter systems have been measured as changes in neurotransmitter level, synthesis, release, uptake, and receptors. In this review, magnitudes of changes are presented for neurotransmitter-related amino acids, acetylcholine, and serotonin. A variety of effects have been found in these studies that may be related to animal model, survival time, type of cochlear damage, or methodology. The overall impression from the evidence presented is that any imbalance of neurotransmitter-related chemistry could disrupt auditory processing in such a way as to produce tinnitus.

  12. 基于单胺类神经递质调节发育算法的机器人视觉定位%Robot Vision Location Based on Developmental Algorithm of Monoamine Neurotransmitters Modulation

    Institute of Scientific and Technical Information of China (English)

    钱夔; 宋爱国; 章华涛; 张立云

    2014-01-01

    A robot vision location based on developmental algorithm of monoamine neurotransmitters modulation is pro-posed to solve the problem that a large number of neurons need to be allocated in vision location task based on general developmental algorithms. Firstly, the monoamine neurotransmitter theory of dopamine and serotonin controlling a vari-ety of physiological functions in the brain is introduced to realize neural modulation. Then, the developmental algorithm of monoamine neurotransmitters modulation is established based on general developmental algorithms. The robot uses au-tonomous trial and error strategies to complete the process of reinforcement learning, store “memory”, and dynamically change the learning rate, and ultimately it realizes vision location task. Experimental results show that the number of neu-rons to be allocated in advance in the proposed method is as few as the number of required knowledge concepts, which can significantly reduce the required number of neurons and increase algorithm efficiency.%针对基于普通发育算法实现机器人视觉定位任务时需分配大量神经元的问题,提出一种基于单胺类神经递质调节发育算法的机器人视觉定位方法。首先引入在脑内控制多种生理功能的多巴胺(dopamine)与5-羟色胺(serotonin)的单胺类神经递质理论,实现神经调节作用;然后结合普通发育算法,建立基于神经递质调节的发育算法。机器人采用自主试错策略完成强化学习过程,存储“记忆”,并可动态改变学习速率,最终实现视觉定位任务。实验结果证明该方法仅需提前配置与所需相关知识概念个数相同数量的神经元,显著减少了所需神经元数量,提高算法效率。

  13. [Glutamatergic neurotransmitter system in regulation of the gastrointestinal tract motor activity].

    Science.gov (United States)

    Alekseeva, E V; Popova, T S; Sal'nikov, P S

    2015-01-01

    The review include actual facts, demonstrating high probability of glutamatergic neurotransmitter system role in the regulation of the gastrointestinal tract motor activity. These facts suggest significant role of the glutamatergic neurotransmitter system dysfunction in forming motor activity disorders of the digestive tract, including in patients in critical condition. The analysis is based on results of multiple experimental and clinical researches of glutamic acid and other components of the glutamatergic neurotransmitter system in central nervous system and autonomic nervous system (with the accent on the enteral nervous system) in normal conditions and with functioning changes of the glutamatergic neurotransmitter system in case of inflammation, hupoxia, stress and in critical condition.

  14. Kaempferia parviflora rhizome extract and Myristica fragrans volatile oil increase the levels of monoamine neurotransmitters and impact the proteomic profiles in the rat hippocampus: Mechanistic insights into their neuroprotective effects

    Directory of Open Access Journals (Sweden)

    Waluga Plaingam

    2017-10-01

    Full Text Available Potentially useful in the treatment of neurodegenerative disorders, Kaempferia parviflora and Myristica fragrans have been shown to possess a wide spectrum of neuropharmacological activities and neuroprotective effects in vivo and in vitro. In this study, we determined whether and how K. parviflora ethanolic extract and M. fragrans volatile oil could influence the levels of neurotransmitters and the whole proteomic profile in the hippocampus of Sprague Dawley (SD rats. The effects of K. parviflora and M. fragrans on protein changes were analyzed by two-dimensional gel electrophoresis (2D-gel, and proteins were identified by liquid chromatography tandem mass spectrometry (LC-MS/MS. The target proteins were then confirmed by Western blot. The levels of neurotransmitters were evaluated by reversed-phase high-performance liquid chromatography (RP-HPLC. The results showed that K. parviflora, M. fragrans and fluoxetine (the control drug for this study increased serotonin, norepinephrine and dopamine in the rat hippocampus compared to that of the vehicle-treated group. Our proteomic data showed that 37 proteins in the K. parviflora group were up-regulated, while 14 were down-regulated, and 27 proteins in the M. fragrans group were up-regulated, while 16 were down-regulated. In the fluoxetine treatment group, we found 29 proteins up-regulated, whereas 14 proteins were down-regulated. In line with the proteomic data, the levels of GFAP, PDIA3, DPYSL2 and p-DPYSL2 were modified in the SD rat groups treated with K. parviflora, M. fragrans and fluoxetine as confirmed by Western blot. K. parviflora and M. fragrans mediated not only the levels of monoamine neurotransmitters but also the proteomic profiles in the rat hippocampus, thus shedding light on the mechanisms targeting neurodegenerative diseases.

  15. A rapid and sensitive method for the analysis of brain monoamine neurotransmitters using ultra-fast liquid chromatography coupled to electrochemical detection.

    Science.gov (United States)

    Parrot, Sandrine; Neuzeret, Pierre-Charles; Denoroy, Luc

    2011-12-15

    Electrochemical detection is often used to detect catecholamines and indolamines in brain samples that have been separated by conventional reverse-phase high performance liquid chromatography (HPLC). This paper presents the transfer of an existing chromatographic method for the determination of monoamines in brain tissues using 5 μm granulometry HPLC columns to columns with a particle diameter less than 3 μm. Several parameters (repeatability, linearity, accuracy, limit of detection, and stability of samples) for this new ultrafast high performance liquid chromatography (UHPLC) method were examined after optimization of the analytical conditions. The separation of seven compounds, noradrenaline, dopamine and three of its metabolites, dihydroxyphenylacetic acid, homovanillic acid, and 3-methoxytyramine, and serotonin and its metabolite, 5-hydroxyindole-3-acetic acid was analyzed using this UHPLC-electrochemical detection method. The final method, which was applied to brain tissue extracts from mice, rats, and cats, decreased analysis time by a factor of 4 compared to HPLC, while guaranteeing good analytical performance.

  16. Rapid determination of monoamine neurotransmitters and their metabolites by high performance liquid chromatography%高效液相色谱法快速检测单胺类神经递质及其代谢产物

    Institute of Scientific and Technical Information of China (English)

    伦立民; 车琳杰; 李世伟

    2006-01-01

    BACKGROUND: The determination of monoamine neurotransmitters and their metabolites is important in the experimental.research of Parkinson disease (PD) and experimental diagnosis of phaochromocytoma.OBJECTIVE: To develop a high performance liquid chromatography (HPLC) method for simultaneous and rapid determination of monoamine neurotransmitters and their metabolites which include epinephrine(E), norepinephrine(NE), dopamine(DA), 5'-hydroxytryptamine(5'-HT), 5-hydroxy3-indoleacetic acid(5-HIAA), homovanillic acid(HVA) and 3,4-dihydroxyphenylacetic acid(DOPAC).DESIGN: Case control observation and a randomized controlled animal experiment.SETTING: Department of Clinical Laboratory, Affiliated Hospital of Medical College, Qingdao University; Haiyang Branch, Affiliated Hospital of Medical College, Qingdao University.PARTICIPANTS: This experiment was carried out at Staff Room of Physiology, edical College, Qingdao University and Department of Clinical Laboratory, Affiliated Hospital of Medical College of Qingdao University from October to December 2003. ①Two patients with phaeochromocytoma were all confirmed by CT, MRI or pathologic section as well as physical sign. Twelve health volunteers were all university students and were excluded to suffer hypertension, endocrine system diseases and other diseases. ② Total 12 healthy female Wister rats weighed between 150 g to 180 g were chosen and randomly divided into control group and PD group with 6 rats in each.METHODS: The standard chromatograms of the standard solution of mixtures of seven substances (E, NE, DA, 5'-HT, 5-HIAA, HVA and DOPAC)were prepared and the precisions and recovery rates of the same samples were determined respectively. Urine samples of 24 hours obtained from 12 healthy volunteers and 2 patients with phaeochromocytoma were analyzed respectively by HPLC. The unilateral forebrain bundles in PD group were destroyed with 6-hydroxydopamine (6-OHDA) for monitoring release characteristics of monoamine

  17. Effect of Wendan Tablets on Behaviors and Monoamine Neurotransmitters in Rat Model of Anxiety%温胆片对焦虑模型大鼠行为学和单胺类神经递质的影响

    Institute of Scientific and Technical Information of China (English)

    刘小河; 杨忠奇; 冼绍祥; 杨明晔; 沈淑静; 黄灿; 袁天慧; 王琼

    2012-01-01

    Objective To observe the anti-anxiety effect of Wendan Tablets and its influences on the contents of monoamine neurotransmitters of 5-hydroxytryptamine (5-HT) , norepinephrine (NE) and dopamine (DA) in the hippocampus of rats with anxiety. Methods SD male rats were randomized into blank group, model group, western medicine group and low-, middle-, and high-dose Wendan Tablets groups. Except for the blank group, the rats of the rest groups were stimulated irregularly by empty bottles to induce anxiety. One week later, the rats in the blank group were given oral use of distilled water, western medicine group were given oral use of 10mg/kg diazepam suspension, and low-, middle-, and high-dose Wendan Tablets groups were given oral use of 0. 6, 1.2 and 2. 4 g/kg suspension of Wendan Tablets respectively for 2 weeks. One week after treatment, the times of abnormal behaviors of the rats were observed, and neurotransmitter contents in rat hippocampus were detected by high performance liquid chromatography after treatment for 2 weeks. Results The times of attacking behavior and exploratory behavior of the rats in Wendan Tablets groups were significantly decreased, while the times of grooming behavior were significantly increased. 5-HT, NE and DA contents in the hippocampus of rats were also decreased in Wendan Tablets groups. Conclusion The anti-anxiety mechanism of Wendan Tablets may be associated with decreasing the release of cerebral monoamine neurotransmitters in rats.%[目的]观察温胆片的抗焦虑作用及对大鼠海马组织单胺类神经递质5-羟色胺(5-HT)、去甲肾上腺素(NE)及多巴胺(DA)含量的影响.[方法]选用SD雄性大鼠60只,随机分为6组,即空白对照组,模型组,西药组,温胆片低、中、高剂量组.除空白对照组外,其他组均采取不确定性空瓶应激的方法复制大鼠焦虑模型.空白对照组和模型组以双蒸水灌胃,西药组灌服10 mg/kg地西泮混悬液,温胆片低、

  18. A putative vesicular transporter expressed in Drosophila mushroom bodies that mediates sexual behavior may define a novel neurotransmitter system

    OpenAIRE

    Brooks, Elizabeth S.; Greer, Christina L.; Romero-Calderón, Rafael; Serway, Christine N.; Grygoruk, Anna; Haimovitz, Jasmine M.; Nguyen, Bac T.; Najibi, Rod; Tabone, Christopher J.; de Belle, J. Steven; Krantz, David E.

    2011-01-01

    Storage and release of classical and amino acid neurotransmitters requires vesicular transporters. Some neurons lack known vesicular transporters, suggesting additional neurotransmitter systems remain unidentified. Insect mushroom bodies (MBs) are critical for several behaviors, including learning, but the neurotransmitters released by the intrinsic Kenyon cells (KCs) remain unknown. Likewise, KCs do not express a known vesicular transporter. We report the identification of a novel Drosophila...

  19. A putative vesicular transporter expressed in Drosophila mushroom bodies that mediates sexual behavior may define a novel neurotransmitter system

    OpenAIRE

    Brooks, Elizabeth S.; Greer, Christina L.; Romero-Calderón, Rafael; Serway, Christine N.; Grygoruk, Anna; Haimovitz, Jasmine M.; Nguyen, Bac T.; Najibi, Rod; Tabone, Christopher J.; de Belle, J. Steven; Krantz, David E.

    2011-01-01

    Storage and release of classical and amino acid neurotransmitters requires vesicular transporters. Some neurons lack known vesicular transporters, suggesting additional neurotransmitter systems remain unidentified. Insect mushroom bodies (MBs) are critical for several behaviors, including learning, but the neurotransmitters released by the intrinsic Kenyon cells (KCs) remain unknown. Likewise, KCs do not express a known vesicular transporter. We report the identification of a novel Drosophila...

  20. Complexins facilitate neurotransmitter release at excitatory and inhibitory synapses in mammalian central nervous system.

    Science.gov (United States)

    Xue, Mingshan; Stradomska, Alicja; Chen, Hongmei; Brose, Nils; Zhang, Weiqi; Rosenmund, Christian; Reim, Kerstin

    2008-06-03

    Complexins (Cplxs) are key regulators of synaptic exocytosis, but whether they act as facilitators or inhibitors is currently being disputed controversially. We show that genetic deletion of all Cplxs expressed in the mouse brain causes a reduction in Ca(2+)-triggered and spontaneous neurotransmitter release at both excitatory and inhibitory synapses. Our results demonstrate that at mammalian central nervous system synapses, Cplxs facilitate neurotransmitter release and do not simply act as inhibitory clamps of the synaptic vesicle fusion machinery.

  1. Effect of laser acupoint irradiation on monoamine neurotransmitter in the hypothalamus of insomnia rats%激光穴位照射对失眠大鼠下丘脑单胺类递质的影响

    Institute of Scientific and Technical Information of China (English)

    周鹏; 赵仓焕; 马晓明; 房显辉; 陈丽华; 占大权; 周蔚华

    2012-01-01

    Objective To observe the effect of laser acupoint irradiation on the content of monoamine neuro-transmitter such as N-Acetyl-5-Hydroxytryptamine ( 5-HT) , 5-Hydroxyindole-3-acetic acid ( 5-HIAA) , Dopamine (DA) and L-Noradrenaline (NA) in the hypothalamus of insomnia rats caused by DL-P-Chlorophenylalanine (PC-PA) ,and investigate the mechanism of laser acupoint irradiation treatment of insomnia. Methods 24 female SD rats were divided randomly into 4 groups with 6 rats in each group,I. E. The control group,the model group,the diazepam group and the laser acupoint irradiation group. The model of insomnia rats were established by PCPA abdominal injection and the acupoints of Shenmen (HT7) and Sanyinjiao (SP6) were chosed to be irradiated by He-Ne laser. The change of 5-HT,5-HIAA,DA,NE in the hypothalamus of rats were observed by Fluorescence spectrophotometry. Results After laser acupoint irradiation treatment, the content of 5-HT and 5-HIAA increased obviously in contrast with the model group ( P < 0.01) and the diazepam group ( P < 0. 05 ) , while that of NE and DA decreased obviously in contrast with the model group (P < 0.05) and the diazepam group (P < 0.05). Conclusion The mechanisms of laser acupoint irradiation in treating insomnia may related to its regulation on monoamine neurotransmitter.%目的 观察激光穴位照射对对氯苯丙氨酸(PCPA)所致失眠大鼠下丘脑单胺类神经递质5-羟色胺(5-HT)、5-羟吲哚乙酸(5-HIAA)、多巴胺(DA)、去甲肾上腺素(NE)含量的影响,探讨激光穴位照射治疗失眠的机制.方法 将SD大鼠24只随机分为4组:对照组、模型组、安定组、激光组,每组6只.腹腔注射PCPA建立失眠大鼠模型,氦氖激光照射神门和三阴交穴各10 min,用荧光分光光度分析法检测下丘脑5-HT、5-HIAA、DA、NE的变化.结果 激光组大鼠下丘脑5-HT、5-HIAA含量明显升高,与模型组比较差异有统计学意义(P<0.01),与安定组比

  2. Effects of hexabromocyclododecane(HBCD) on monoamine neurotransmitters contents and monoamine oxidase activity of developmental rat brain%六溴环十二烷对发育期大鼠脑单胺类神经递质质量比及单胺氧化酶活性的影响

    Institute of Scientific and Technical Information of China (English)

    刘芳; 冀秀玲; 赵文娟; 殷明; 蒋惠男; 张江

    2012-01-01

    .01). As for the monoamine oxidase, an increase trend can be found with MAO activity in the range of 10 to 100 μg/kg doses and significantly changed at the dose of 100 μg/kg(p <0.05) . When the dose is kept at a level of 300 (μg/kg, the trend is likely to drop, though not enough significantly. DA, NE and 5 ~ HT were found to play a important role in the learning, memory and moods in the rats' brain. Changing the contents of DA, 5 - HT, disorders can be found with the central nervous system with the rats when the developmental HBCD was exposed to the NE and MAO activities. Compared with the dose of 300 μg/kg, severe effects were detected on the neurotransmitters and MAO at a level of 10-100 μg/kg. it indicates that HBCD has the feature of low-dosage and high toxicity to the developmental rat brain. Furthermore, the exposure dosages of 10 - 100 μg/kg can only produce a mirror effect in comparison with the content of HBCD in the real environment. However, HBCD of the environmental exposure levels proves to produce neurotoxicity and have effect on the learning and memory system of the developmental rats. Thus, it can be said that this paper has provided an important reference in the study of the HBCD exposure and its effect on the public health in the environment, especially on children ' s healthy growth.

  3. Monoamine neurotransmitter changes in hippocampus at reserpine induced chronic animal model of depression%慢性利血平抑郁模型大鼠海马单胺类神经递质的变化

    Institute of Scientific and Technical Information of China (English)

    王永志; 赵静洁; 韩玉; 杜仪; 李宝金; 李杨帆; 刘路遥; 张一帆; 张银凤

    2013-01-01

    目的 探索利血平致慢性抑郁大鼠模型的合适剂量,观察不同剂量利血平对大鼠自发活动和体质量的影响,分析模型大鼠海马单胺类神经递质的变化特点.方法 60只大鼠随机分为5组,空白组,利血平0.3 mg/kg、0.4 mg/kg、0.5 mg/kg、0.6 mg/kg组,每组n=12;动物造模给予腹腔注射利血平注射液1次/d(按分组中的给药剂量给予),空白组给予同体积蒸馏水,连续用药14 d.分别对大鼠open-field得分和体质量进行测量,酶联免疫法检测大鼠海马单胺类神经递质的水平.结果 慢性腹腔注射利血平(0.5、0.6 mg/kg)可引起大鼠体质量减轻(P<0.01,P<0.05),0.4、0.5、0.6 mg/kg组出现抑郁样行为;0.3 mg/kg组体质量、open-field得分变化不明显.与空白组体质量[(278.75±4.65)]和抑郁open-field评分[(60.3±19.9)分]比较,0.5 mg/kg组14 d大鼠体质量[(256.17±4.89)g]与open-field行为评分[(43.4±8.4)分]差异有显著性(P<0.01).0.5 mg/kg利血平对7d组抑郁大鼠海马5-羟色胺(5-HT)含量有影响[(2.83±1.09) ng/ml,P<0.05],对14 d组5-HT含量无明显影响.与空白组比较,0.5 mg/kg组14d腹腔注射利血平对单胺类神经递5-羟色胺(5-HT)、多巴胺(DA)、去甲肾上腺素(NA)影响差异无统计学意义(P>0.05),但可见5-HT与NA含量呈显著负相关(r=-0.449,P<0.01).结论 慢性腹腔注射0.5 mg/kg利血平能引起大鼠抑郁样行为,利血平对海马单胺类神经递质的影响与用药时间相关.%Objective To observe the suitable dosage of reserpine for the establishment of rat model of depression and analyze the changes of monoamine neurotransmitter in hippocampus.Methods 60 rats were randomly divided into five groups:the normal group,the 0.3 mg/kg group,0.4 mg/kg group,0.5 mg/kg group and 0.6 mg/kg group,and 12 rats in each group.The model groups were intraperitoneally administrated by different dosage of reserpine (according to the dosage of the grouping) for 14 days and rats in

  4. Mapping neurotransmitter networks with PET: an example on serotonin and opioid systems.

    Science.gov (United States)

    Tuominen, Lauri; Nummenmaa, Lauri; Keltikangas-Järvinen, Liisa; Raitakari, Olli; Hietala, Jarmo

    2014-05-01

    All functions of the human brain are consequences of altered activity of specific neural pathways and neurotransmitter systems. Although the knowledge of "system level" connectivity in the brain is increasing rapidly, we lack "molecular level" information on brain networks and connectivity patterns. We introduce novel voxel-based positron emission tomography (PET) methods for studying internal neurotransmitter network structure and intercorrelations of different neurotransmitter systems in the human brain. We chose serotonin transporter and μ-opioid receptor for this analysis because of their functional interaction at the cellular level and similar regional distribution in the brain. Twenty-one healthy subjects underwent two consecutive PET scans using [(11)C]MADAM, a serotonin transporter tracer, and [(11)C]carfentanil, a μ-opioid receptor tracer. First, voxel-by-voxel "intracorrelations" (hub and seed analyses) were used to study the internal structure of opioid and serotonin systems. Second, voxel-level opioid-serotonin intercorrelations (between neurotransmitters) were computed. Regional μ-opioid receptor binding potentials were uniformly correlated throughout the brain. However, our analyses revealed nonuniformity in the serotonin transporter intracorrelations and identified a highly connected local network (midbrain-striatum-thalamus-amygdala). Regionally specific intercorrelations between the opioid and serotonin tracers were found in anteromedial thalamus, amygdala, anterior cingulate cortex, dorsolateral prefrontal cortex, and left parietal cortex, i.e., in areas relevant for several neuropsychiatric disorders, especially affective disorders. This methodology enables in vivo mapping of connectivity patterns within and between neurotransmitter systems. Quantification of functional neurotransmitter balances may be a useful approach in etiological studies of neuropsychiatric disorders and also in drug development as a biomarker-based rationale for targeted

  5. Effects of 071031B, a novel serotonin and norepinephrine reuptake inhibitor, on monoamine system in mice and rats.

    Science.gov (United States)

    Xue, Rui; He, Xin-Hua; Yuan, Li; Chen, Hong-Xia; Zhang, Li-Ming; Yong, Zheng; Yu, Gang; Fan, Shi-Yong; Li, Yun-Feng; Zhong, Bo-Hua; Zhang, You-Zhi

    2016-01-01

    Our previous study indicated that 071031B, a novel potential serotonin and norepinephrine reuptake inhibitor, showed robust antidepressant activity in multiple depression models, and could simultaneously inhibit 5-HT and NE reuptake in vitro. The present study was to evaluate the effects of 071031B on monoamine system in vivo, by using pharmacological models, including 5-HTP induced head-twitch test, yohimbine toxicity potentiation test, and reserpine induced hypothermia test, and determining monoamine transmitter levels in reserpine induced monoamine depletion model or chronic unpredictable stress (CUS) model. Results in pharmacological models indicated that acute administration of 071031B at 5-20 mg/kg significantly enhanced 5-HTP induced head-twitch behavior, potentiated yohimbine induced lethal rate, and reversed reserpine induced hypothermia. Further monoamine assays demonstrated that acute or chronic administration of 071031B at 10 or 20 mg/kg increased 5-HT and/or NE levels in various brain regions in reserpine or CUS induced monoamine depletion models, respectively, without effect on DA and its metabolites. Our results revealed that 071031B produces potent inhibition of 5-HT and NE reuptake in vivo.

  6. Effects of 071031B, a novel serotonin and norepinephrine reuptake inhibitor, on monoamine system in mice and rats

    Directory of Open Access Journals (Sweden)

    Rui Xue

    2016-01-01

    Full Text Available Our previous study indicated that 071031B, a novel potential serotonin and norepinephrine reuptake inhibitor, showed robust antidepressant activity in multiple depression models, and could simultaneously inhibit 5-HT and NE reuptake in vitro. The present study was to evaluate the effects of 071031B on monoamine system in vivo, by using pharmacological models, including 5-HTP induced head-twitch test, yohimbine toxicity potentiation test, and reserpine induced hypothermia test, and determining monoamine transmitter levels in reserpine induced monoamine depletion model or chronic unpredictable stress (CUS model. Results in pharmacological models indicated that acute administration of 071031B at 5–20 mg/kg significantly enhanced 5-HTP induced head-twitch behavior, potentiated yohimbine induced lethal rate, and reversed reserpine induced hypothermia. Further monoamine assays demonstrated that acute or chronic administration of 071031B at 10 or 20 mg/kg increased 5-HT and/or NE levels in various brain regions in reserpine or CUS induced monoamine depletion models, respectively, without effect on DA and its metabolites. Our results revealed that 071031B produces potent inhibition of 5-HT and NE reuptake in vivo.

  7. 一次力竭运动小鼠中枢单胺类神经递质的代谢特点%Brain Monoamines Neurotransmitters Metabolism Induced by a Prolonged Exhaustive Exercise in Mice

    Institute of Scientific and Technical Information of China (English)

    赵丽; 吴建忠; 岳明; 吕媛媛; 王德刚

    2014-01-01

    Objective:To investigate the metabolic changes of central monoamine neurotransmitters in the prolonged exhaustive exercise,in order for the central mechanism of sports fatigue to provide a laboratory basis.Method:The C57/BL mice were 4 months of age,and randomly divided them into the sedentary control group(SC)and exhausted swimming group(SE).After exhaustive swimming the cortex,hypothalamus,striatum,hippocampus, brainstem and cerebellum were collected immediately.The brain monoamines levels(NE,DA,DOPAC,5-HT,5-HIAA)were measured with HPLC. Result:In exhaustive group,the concentrations of NE in the cerebral cortex,hippocampus and brainstem were significantly increased compared with the sedentary control group(P<0.05),but the concentrations of NE in the hypothalamus,striatum and cerebellum had a decreasing tendency.The levels of DA in the hippocampus and brainstem were significantly increased compared to those in the sedentary control group(P<0.01),in the cortex and striatum only had a increasing tendency,but the concentrations of DA in the hypothalamus was significantly increased compared to that in the sedentary control group.The levels of DOPAC only were increased in the brainstem.The levels of 5-HT in all six brain loci of SE group were significantly increased compared with those of SC group(P<0.05),and the metabolic product 5-HIAA were significantly increased in the cerebral cortex,hypothalamus and cerebellum (P<0.05).Conclusion:Exercise results in a different activation degree of brain monoamine neurons in brain loci.Exercise-induced increased 5-HT and NE levels can be indicators of central fatigue.%目的:探讨力竭运动中枢单胺类神经递质的代谢变化特点,以期为运动疲劳的中枢机制提供一定实验室依据。方法:4月龄C57/BL小鼠,随机分为安静对照组(SC组)和一次性游泳力竭组(SE组)。力竭游泳即刻取材(皮层、下丘脑、纹状体、海马、脑干和小脑)六个脑区,高功率

  8. The use of multiscale molecular simulations in understanding a relationship between the structure and function of biological systems of the brain: the application to monoamine oxidase enzymes

    Directory of Open Access Journals (Sweden)

    Robert Vianello

    2016-07-01

    Full Text Available Aging society and therewith associated neurodegenerative and neuropsychiatric diseases, including depression, Alzheimer’s disease, obsessive disorders, and Parkinson’s disease, urgently require novel drug candidates. Targets include monoamine oxidases A and B (MAOs, acetylcholinesterase (AChE and butyrylcholinesterase (BChE, and various receptors and transporters. For rational drug design it is particularly important to combine experimental synthetic, kinetic, toxicological and pharmacological information with structural and computational work. This paper describes the application of various modern computational biochemistry methods in order to improve the understanding of a relationship between the structure and function of large biological systems including ion channels, transporters, receptors and metabolic enzymes. The methods covered stem from classical molecular dynamics simulations to understand the physical basis and the time evolution of the structures, to combined QM and QM/MM approaches to probe the chemical mechanisms of enzymatic activities and their inhibition. As an illustrative example, the later will focus on the monoamine oxidase family of enzymes, which catalyze the degradation of amine neurotransmitters in various parts of the brain, the imbalance of which is associated with the development and progression of a range of neurodegenerative disorders. Inhibitors that act mainly on MAO A are used in the treatment of depression, due to their ability to raise serotonin concentrations, while MAO B inhibitors decrease dopamine degradation and improve motor control in patients with Parkinson disease. Our results give strong support that both MAO isoforms, A and B, operate through the hydride transfer mechanism. Relevance of MAO catalyzed reactions and MAO inhibition in the context of neurodegeneration will be discussed.

  9. The Use of Multiscale Molecular Simulations in Understanding a Relationship between the Structure and Function of Biological Systems of the Brain: The Application to Monoamine Oxidase Enzymes.

    Science.gov (United States)

    Vianello, Robert; Domene, Carmen; Mavri, Janez

    2016-01-01

    HIGHLIGHTS Computational techniques provide accurate descriptions of the structure and dynamics of biological systems, contributing to their understanding at an atomic level.Classical MD simulations are a precious computational tool for the processes where no chemical reactions take place.QM calculations provide valuable information about the enzyme activity, being able to distinguish among several mechanistic pathways, provided a carefully selected cluster model of the enzyme is considered.Multiscale QM/MM simulation is the method of choice for the computational treatment of enzyme reactions offering quantitative agreement with experimentally determined reaction parameters.Molecular simulation provide insight into the mechanism of both the catalytic activity and inhibition of monoamine oxidases, thus aiding in the rational design of their inhibitors that are all employed and antidepressants and antiparkinsonian drugs. Aging society and therewith associated neurodegenerative and neuropsychiatric diseases, including depression, Alzheimer's disease, obsessive disorders, and Parkinson's disease, urgently require novel drug candidates. Targets include monoamine oxidases A and B (MAOs), acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and various receptors and transporters. For rational drug design it is particularly important to combine experimental synthetic, kinetic, toxicological, and pharmacological information with structural and computational work. This paper describes the application of various modern computational biochemistry methods in order to improve the understanding of a relationship between the structure and function of large biological systems including ion channels, transporters, receptors, and metabolic enzymes. The methods covered stem from classical molecular dynamics simulations to understand the physical basis and the time evolution of the structures, to combined QM, and QM/MM approaches to probe the chemical mechanisms of enzymatic

  10. Exercise Benefits Brain Function: The Monoamine Connection

    OpenAIRE

    Tzu-Wei Lin; Yu-Min Kuo

    2013-01-01

    The beneficial effects of exercise on brain function have been demonstrated in animal models and in a growing number of clinical studies on humans. There are multiple mechanisms that account for the brain-enhancing effects of exercise, including neuroinflammation, vascularization, antioxidation, energy adaptation, and regulations on neurotrophic factors and neurotransmitters. Dopamine (DA), noradrenaline (NE), and serotonin (5-HT) are the three major monoamine neurotransmitters that are known...

  11. Changes of Mental Health Status and Monoamine Neurotransmitter under the Military Stress of Soldiers in Surface Ships%舰艇部队军事应激下心理及血单胺类递质的改变

    Institute of Scientific and Technical Information of China (English)

    朱成全; 韦林山; 洪加津; 孙学刚

    2013-01-01

    before and after stress. Conclusion Military stress has significant impact on the mental health status and monoamine neurotransmitter in the peripheral blood of the military men in surface ships.

  12. A putative vesicular transporter expressed in Drosophila mushroom bodies that mediates sexual behavior may define a novel neurotransmitter system

    Science.gov (United States)

    Brooks, Elizabeth S.; Greer, Christina L.; Romero-Calderón, Rafael; Serway, Christine N.; Grygoruk, Anna; Haimovitz, Jasmine M.; Nguyen, Bac T.; Najibi, Rod; Tabone, Christopher J.; de Belle, J. Steven; Krantz, David E.

    2011-01-01

    Summary Storage and release of classical and amino acid neurotransmitters requires vesicular transporters. Some neurons lack known vesicular transporters, suggesting additional neurotransmitter systems remain unidentified. Insect mushroom bodies (MBs) are critical for several behaviors, including learning, but the neurotransmitters released by the intrinsic Kenyon cells (KCs) remain unknown. Likewise, KCs do not express a known vesicular transporter. We report the identification of a novel Drosophila gene portabella (prt) that is structurally similar to known vesicular transporters. Both larval and adult brains express PRT in the KCs of the MBs. Additional PRT cells project to the central complex and optic ganglia. prt mutation causes an olfactory learning deficit and an unusual defect in the male’s position during copulation that is rescued by expression in KCs. Since prt is expressed in neurons that lack other known vesicular transporters or neurotransmitters, it may define a previously unknown neurotransmitter system responsible for sexual behavior and a component of olfactory learning. PMID:22017990

  13. 碳纳米管/聚吡咯修饰电极用于液相色谱测定帕金森大鼠脑中神经递质%Liquid Chromatography with Electrochemical Detection Using Multi-wall Carbon Nanotubes/Polypyrrole Composite Film Modified Electrode for in Vivo Analysis of Monoamine Neurotransmitters in Rat Striatal Microdialysate of Freely Moving Parkinsonian Rats

    Institute of Scientific and Technical Information of China (English)

    林丽; 余莉; 林瑞泼; 李雪燕; 杨树林; 李校堃

    2011-01-01

    A multi-wall carbon nanotubes/polypyrrole modified electrode that can be used as the working electrode in the high performance liquid chromatography with electrochemical detection to determine the monoamine neurotransmitters was developed. The voltammetric response of dopamine could be promoted by using the electrode. The peak currents of norepinephrine, epinephrine, dopa mine and 5-hydroxytryptamine were linear with their concentrations ranging from 5. 0 ×10-10 to 1. 0 ×10-6 mol/L, and the peak currents of 3 , 4-dihydroxyphenylacetic acid, 5-hydroxyindoleacetic acid and homovanillic acid were linear with their concentrations ranging from 1. 0 ×10-9 to 5. 0 × 10-4 mol/L.The correlation coefficients of the seven compounds were more than 0. 998. The detection limits were the level of 0. 1 nmol/L. Coupled with in vivo microdialysis sampling, the method had been success fully applied to measure monoamine neurotransmitters in rat striatum of freely moving Parkinsonian rats, and the monoamine neurotransmitters level of model group decreased compared with control group.%制备了碳纳米管/聚吡咯复合修饰电极,研究了多巴胺等单胺类神经递质在该修饰电极上的电化学行为.将此修饰电极作为电化学检测器,与高效液相色谱联用,测定了脑中7种神经递质及其代谢产物.结果表明:去甲肾上腺素、肾上腺素、多巴胺和5-羟色胺的线性范围为5.0×10(-10)~1.0×10(-5)mol/L;3,4-二羟基苯乙酸,5-羟吲哚乙酸和高香草酸的线性范围为1.0×10(9)~5.0×10(-4)mol/L;7种物质相关系数均大于0.998;检出限在0.1 nmol/L水平.结合微透析活体取样,测定了自由活动帕金森模型组大鼠脑纹状体中7种单胺类神经递质及其代谢产物的含量,较正常组有所降低.

  14. Detection and Quantification of Neurotransmitters in Dialysates

    OpenAIRE

    Zapata, Agustin; Chefer, Vladimir I.; Shippenberg, Toni S.; Denoroy, Luc

    2009-01-01

    Sensitive analytical methods are needed for the separation and quantification of neurotransmitters obtained in microdialysate studies. This unit describes methods that permit quantification of nanomolar concentrations of monoamines and their metabolites (high-pressure liquid chromatography electrochemical detection), acetylcholine (HPLC-coupled to an enzyme reactor), and amino acids (HPLC-fluorescence detection; capillary electrophoresis with laser-induced fluorescence detection).

  15. Monoamine transporters: Insights from molecular dynamics simulations

    Directory of Open Access Journals (Sweden)

    Julie eGrouleff

    2015-10-01

    Full Text Available The human monoamine transporters facilitate the reuptake of the neurotransmitters serotonin, dopamine, and norepinephrine from the synaptic cleft. Imbalance in monoaminergic neurotransmission is linked to various diseases including major depression, attention deficit hyperactivity disorder, schizophrenia and Parkinson’s disease. Inhibition of the monoamine transporters is thus an important strategy for treatment of such diseases. The monoamine transporters are sodium-coupled transport proteins belonging to the neurotransmitter/Na+ symporter (NSS family, and the publication of the first high-resolution structure of a NSS family member, the bacterial leucine transporter LeuT, in 2005, proved to be a major stepping stone for understanding this family of transporters. Structural data allows for the use of computational methods to study the monoamine transporters, which in turn has led to a number of important discoveries. The process of substrate translocation across the membrane is an intrinsically dynamic process. Molecular dynamics simulations, which can provide atomistic details of molecular motion on ns to ms timescales, are therefore well-suited for studying transport processes. In this review, we outline how molecular dynamics simulations have provided insight into the large scale motions associated with transport of the neurotransmitters, as well as the presence of external and internal gates, the coupling between ion and substrate transport, and differences in the conformational changes induced by substrates and inhibitors.

  16. Deletion of mouse FXR gene disturbs multiple neurotransmitter systems and alters neurobehavior.

    Science.gov (United States)

    Huang, Fei; Wang, Tingting; Lan, Yunyi; Yang, Li; Pan, Weihong; Zhu, Yonghui; Lv, Boyang; Wei, Yuting; Shi, Hailian; Wu, Hui; Zhang, Beibei; Wang, Jie; Duan, Xiaofeng; Hu, Zhibi; Wu, Xiaojun

    2015-01-01

    Farnesoid X receptor (FXR) is a nuclear hormone receptor involved in bile acid synthesis and homeostasis. Dysfunction of FXR is involved in cholestasis and atherosclerosis. FXR is prevalent in liver, gallbladder, and intestine, but it is not yet clear whether it modulates neurobehavior. In the current study, we tested the hypothesis that mouse FXR deficiency affects a specific subset of neurotransmitters and results in an unique behavioral phenotype. The FXR knockout mice showed less depressive-like and anxiety-related behavior, but increased motor activity. They had impaired memory and reduced motor coordination. There were changes of glutamatergic, GABAergic, serotoninergic, and norepinephrinergic neurotransmission in either hippocampus or cerebellum. FXR deletion decreased the amount of the GABA synthesis enzyme GAD65 in hippocampus but increased GABA transporter GAT1 in cerebral cortex. FXR deletion increased serum concentrations of many bile acids, including taurodehydrocholic acid, taurocholic acid, deoxycholic acid (DCA), glycocholic acid (GCA), tauro-α-muricholic acid, tauro-ω-muricholic acid, and hyodeoxycholic acid (HDCA). There were also changes in brain concentrations of taurocholic acid, taurodehydrocholic acid, tauro-ω-muricholic acid, tauro-β-muricholic acid, deoxycholic acid, and lithocholic acid (LCA). Taken together, the results from studies with FXR knockout mice suggest that FXR contributes to the homeostasis of multiple neurotransmitter systems in different brain regions and modulates neurobehavior. The effect appears to be at least partially mediated by bile acids that are known to cross the blood-brain barrier (BBB) inducing potential neurotoxicity.

  17. Neurotransmitter transporters

    DEFF Research Database (Denmark)

    Gether, Ulrik; Andersen, Peter H; Larsson, Orla M

    2006-01-01

    The concentration of neurotransmitters in the extracellular space is tightly controlled by distinct classes of membrane transport proteins. This review focuses on the molecular function of two major classes of neurotransmitter transporter that are present in the cell membrane of neurons and....../or glial cells: the solute carrier (SLC)1 transporter family, which includes the transporters that mediate the Na(+)-dependent uptake of glutamate, and the SLC6 transporter family, which includes the transporters that mediate the Na(+)-dependent uptake of dopamine, 5-HT, norepinephrine, glycine and GABA....... Recent research has provided substantial insight into the structure and function of these transporters. In particular, the recent crystallizations of bacterial homologs are of the utmost importance, enabling the first reliable structural models of the mammalian neurotransmitter transporters...

  18. A putative vesicular transporter expressed in Drosophila mushroom bodies that mediates sexual behavior may define a neurotransmitter system.

    Science.gov (United States)

    Brooks, Elizabeth S; Greer, Christina L; Romero-Calderón, Rafael; Serway, Christine N; Grygoruk, Anna; Haimovitz, Jasmine M; Nguyen, Bac T; Najibi, Rod; Tabone, Christopher J; de Belle, J Steven; Krantz, David E

    2011-10-20

    Vesicular transporters are required for the storage of all classical and amino acid neurotransmitters in synaptic vesicles. Some neurons lack known vesicular transporters, suggesting additional neurotransmitter systems remain unidentified. Insect mushroom bodies (MBs) are critical for several behaviors, including learning, but the neurotransmitters released by the intrinsic Kenyon cells (KCs) remain unknown. Likewise, KCs do not express a known vesicular transporter. We report the identification of a novel Drosophila gene portabella (prt) that is structurally similar to known vesicular transporters. Both larval and adult brains express PRT in the KCs of the MBs. Additional PRT cells project to the central complex and optic ganglia. prt mutation causes an olfactory learning deficit and an unusual defect in the male's position during copulation that is rescued by expression in KCs. Because prt is expressed in neurons that lack other known vesicular transporters or neurotransmitters, it may define a previously unknown neurotransmitter system responsible for sexual behavior and a component of olfactory learning. Copyright © 2011 Elsevier Inc. All rights reserved.

  19. Influence of component formula of Suanzaoren Tang on hippocampus monoamine neurotransmitters and their metabolites in rats in elevated plus maze test%酸枣仁汤组分配方对高架十字迷宫大鼠海马单胺类递质及其代谢物的影响

    Institute of Scientific and Technical Information of China (English)

    王守勇; 谢鸣

    2012-01-01

    目的 观察酸枣仁汤组分配方对高架十字迷宫大鼠海马单胺类递质及其代谢物的影响,探讨其抗焦虑效用的有效组分及作用机理.方法 采用国际上通用的高架十字迷宫焦虑动物模型,观察酸枣仁汤组分配方对大鼠行为学的影响,高效液相色谱法测定大鼠海马单胺类递质去甲肾上腺素(NE)、5-羟色胺(5 -HT)、多巴胺(DA)及其代谢物的含量.结果 与空白对照组比较,全组分配方组和有效组分配方组及地西泮组大鼠进入开放臂次数比、在开放臂停留时间比均显著升高(P<0.01或P<0.05);有效组分配方组和地西泮组大鼠海马5-HT的含量均见显著降低(P<0.05),全组分配方组海马5-HT含量呈降低作用趋势;有效组分配方组大鼠海马高香草酸(HVA)含量显著升高(P<0.01).结论 酸枣仁汤全组分配方及其有效组分配方与地西泮具有某些相同的抗焦虑作用机制,可能涉及到降低海马5-HT含量;全组分配方及其有效组分配方对大鼠海马单胺类递质代谢的影响有所不同.%Objective To observe the influence of component formula of Suanzaoren Tang on hippocampus monoamine neurotransmitters and their metabolites in rats in elevated plus maze test (EPM) , and discuss its effective components and mechanism of anti-anxiety. Methods The influence of component formula of Suanzaoren Tang on rat ethology was observed by using international common-used anxiety animal model in EPM. The levels of monoamine neurotransmitters including noradrenaline (NE) , 5-hydroxytryptamine (5-HT) and dopamine (DA) and their metabolites were detected by applying HPLC. Results Compared with blank group, the ratio of entering times and retention time ratio in open arm increased significantly in whole component formula group (whole CF group) , effective component formula group (effective CF group) and diazepam group (P <0. 01 or P <0. 05). The level of 5-HT decreased significantly in

  20. [Monoamines stimulations in experimental carcinogenesis].

    Science.gov (United States)

    Popov, I; Spuzić, I; Rakić, Lj

    1994-01-01

    Facts about the role of CNS monoamines in cancerogenesis have been accumulated for many years. The aim of the present study was to investigate the effect of interaction of psychoactive drug (Piracetam) and other treatments on survival time of tumour-bearing rats. 138 Wistar rats were used in the experiment. The animals were injected 1% 3--Methilcholantren suspension in 10% Tylose, s.c. under the dorsal skin of the neck in a dose of 3 mg/animal. Within 4-9 months after a single injection, the rats developed tumours at the site of injection. The surgical removal was performed when tumours reached the size of 1-3 cm. After surgical extirpation of tumours different groups of animals were treated by cyclophosphamide (s.c. one-time dose of 50 mg/kg for female and 100 mg/kg for male) or by psychoactive drug (Piracetam) administrated by GE tube 5 time/week, 100 mg/kg. Autopsy and histological examinations were carried out in all animals. Survival time (> 120 days) was the greatest in group B (Piracetam, after surgical removal of tumours) 81.2%, and group C (Cyclophosphamid, after surgical removal of tumours) 68.8% and in group A (only surgical removal of tumours) 50%. In group B the incidence of metastases was the smallest (87.1% of animals were without metastases), compared with group C (45.4% of animals were without metastases) and group A (27.3% of animals were without metastases). The diference is statistically significant. The mechanism of antineoplastic effect of Piracetam consisted of the interaction of influences both on metabolism of the Central nervous system and the tumour. Probably, it is the neurotransmitter modulation that had its effect on carcinogenesis not only by regulation/disregulation of brain homeostasis, but also via direct effect on intracellular processes during cell development and differentation.

  1. CXCL12 chemokine and GABA neurotransmitter systems crosstalk and their putative roles

    Directory of Open Access Journals (Sweden)

    Guyon eAlice

    2014-04-01

    Full Text Available Since CXCL12 and its receptors, CXCR4 and CXCR7, have been found in the brain, the role of this chemokine has been expanded from chemoattractant in the immune system to neuromodulatory in the brain. Several pieces of evidence suggest that this chemokine system could crosstalk with the GABAergic system, known to be the main inhibitory neurotransmitter system in the brain. Indeed, GABA and CXCL12 as well as their receptors are colocalized in many cell types including neurons and there are several examples in which these two systems interact. Several mechanisms can be proposed to explain how these systems interact, including receptor-receptor interactions, crosstalk at the level of second messenger cascades, or direct pharmacological interactions, as GABA and GABAB receptor agonists/antagonists have been shown to be allosteric modulators of CXCR4.The interplay between CXCL12/CXCR4-CXCR7 and GABA/GABAA-GABAB receptors systems could have many physiological implications in neurotransmission, cancer and inflammation. In addition, the GABAB agonist baclofen is currently used in medicine to treat spasticity in patients with spinal cord injury, cerebral palsy, traumatic brain injury, multiple sclerosis and other disorders. More recently it has also been used in the treatment of alcohol dependence and withdrawal. The allosteric effects of this agent on CXCR4 could contribute to these beneficial effects or at the opposite, to its side effects.

  2. The Effect of Functional Mandibular Shift on the Muscle Spindle Systems in Head-Neck Muscles and the Related Neurotransmitter Histamine.

    Science.gov (United States)

    Du, Bing-Li; Li, Jiang-Ning; Guo, Hong-Ming; Li, Song; Liu, Biao

    2017-09-01

    The aim of this study is to explore the effects of abnormal occlusion and functional recovery caused by functional mandible deviation on the head and neck muscles and muscle spindle sensory-motor system by electrophysiological response and endogenous monoamine neurotransmitters' distribution in the nucleus of the spinal tract. Seven-week-old male Wistar rats were randomly divided into 7 groups: normal control group, 2W experimental control group, 2W functional mandible deviation group, 2W functional mandible deviation recovery group, 4W experimental control group, 4W functional mandible deviation group, 4W functional mandible deviation recovery group. Chewing muscles, digastric muscle, splenius, and trapezius muscle spindles electrophysiological response activities at the opening and closing state were recorded. And then the chewing muscles, digastric, splenius, trapezius, and neck trigeminal nucleus were taken for histidine decarboxylase (HDC) detection by high performance liquid chromatography (HPLC), immunofluorescence, and reverse-transcription polymerase chain reaction (RT-PCR). Histamine receptor proteins in the neck nucleus of the spinal tract were also examined by immunofluorescence and RT-PCR. Electromyography activity of chewing muscles, digastric, and splenius muscle was significantly asymmetric; the abnormal muscle electromyography activity was mainly detected at the ipsilateral side. After functional mandibular deviation, muscle sensitivity on the ipsilateral sides of the chewing muscle and splenius decreased, muscle excitement weakened, modulation depth decreased, and the muscle spindle afferent impulses of excitation transmission speed slowed down. Changes for digastric muscle electrical activity were contrary. The functions recovered at different extents after removing the deflector. However, trapezius in all the experimental groups and recovery groups exhibited bilateral symmetry electrophysiological responses, and no significant difference

  3. 右美沙芬对小鼠大脑5-羟色胺含量的影响%Influences of Dextromethorphan on Monoamine Neurotransmitter 5-HT in Mouse Brain

    Institute of Scientific and Technical Information of China (English)

    李迎春; 张久亮; 周莉红

    2012-01-01

    Objective To study the antitussive mechanism of dextromethorphan. Methods By using reversed-phase high-performance liquid chromatography (RP-HPLC) with fluorescent light detector, we detected the effect of dextromethorphan on the contents of five kinds of monamine neurotransmitters in mouse brain with codeine phosphate serving as a positive drug. Results The results indicated that the antitussive mechanism of dextromethorphan was concerned with monanine neurotransmitter 5-HT. In the dextromethorphan group, 5-HT was 43. 50% higher than in the blank group (P<0.01) , and 5-HIAA was 35. 00% higher than in the blank group (P<0. 05). Dextromethorphan could increase the content of 5-HT in mouse brain to induce antitussive effects, while the antitussice effects of codeine phosphate had no relationship with serotonergic mechanisms. Conclusion The antitussive mechanism of dextromethorphan is related with the release of monanine neurotransmitter 5-HT in mouse brain.%目的 初步探讨右美沙芬通过增加小鼠脑部5-羟色胺(5-HT)的含量的镇咳机制.方法 采用反相高效液相-荧光检测(RP-HPLC-FLD)法,以磷酸可待因为对照药,测定右美沙芬对小鼠脑部5种单胺类神经递质含量的影响.结果 右美沙芬的镇咳机制与单胺类神经递质5-HT有关,右美沙芬组的5-HT含量比空白组增加了43.50%,差异有统计学意义(P <0.01),5-羟基吲哚乙酸(5-HIAA)含量比空白组增加35.00%,差异有统计学意义(P<0.05).结论 右美沙芬镇咳作用与小鼠脑部5-HT的释放有关.

  4. Early Antipsychotic Treatment in Juvenile Rats Elicits Long-Term Alterations to the Dopamine Neurotransmitter System.

    Science.gov (United States)

    De Santis, Michael; Lian, Jiamei; Huang, Xu-Feng; Deng, Chao

    2016-11-22

    Prescription of antipsychotic drugs (APDs) to children has substantially increased in recent years. Whilst current investigations into potential long-term effects have uncovered some alterations to adult behaviours, further investigations into potential changes to neurotransmitter systems are required. The current study investigated potential long-term changes to the adult dopamine (DA) system following aripiprazole, olanzapine and risperidone treatment in female and male juvenile rats. Levels of tyrosine hydroxylase (TH), phosphorylated-TH (p-TH), dopamine active transporter (DAT), and D₁ and D₂ receptors were measured via Western blot and/or receptor autoradiography. Aripiprazole decreased TH and D₁ receptor levels in the ventral tegmental area (VTA) and p-TH levels in the prefrontal cortex (PFC) of females, whilst TH levels decreased in the PFC of males. Olanzapine decreased PFC p-TH levels and increased D₂ receptor expression in the PFC and nucleus accumbens (NAc) in females only. Additionally, risperidone treatment increased D₁ receptor levels in the hippocampus of females, whilst, in males, p-TH levels increased in the PFC and hippocampus, D₁ receptor expression decreased in the NAc, and DAT levels decreased in the caudate putamen (CPu), and elevated in the VTA. These results suggest that early treatment with various APDs can cause different long-term alterations in the adult brain, across both treatment groups and genders.

  5. Short- and long-term memory: differential involvement of neurotransmitter systems and signal transduction cascades

    Directory of Open Access Journals (Sweden)

    MÔNICA R.M. VIANNA

    2000-09-01

    Full Text Available Since William James (1890 first distinguished primary from secondary memory, equivalent to short- and long-term memory, respectively, it has been assumed that short-term memory processes are in charge of cognition while long-term memory is being consolidated. From those days a major question has been whether short-term memory is merely a initial phase of long-term memory, or a separate phenomena. Recent experiments have shown that many treatments with specific molecular actions given into the hippocampus and related brain areas after one-trial avoidance learning can effectively cancel short-term memory without affecting long-term memory formation. This shows that short-term memory and long-term memory involve separate mechanisms and are independently processed. Other treatments, however, influence both memory types similarly, suggesting links between both at the receptor and at the post-receptor level, which should not be surprising as they both deal with nearly the same sensorimotor representations. This review examines recent advances in short- and long-term memory mechanisms based on the effect of intra-hippocampal infusion of drugs acting upon neurotransmitter and signal transduction systems on both memory types.

  6. Fluorescent Probes for Analysis and Imaging of Monoamine Oxidase Activity

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Dokyoung; Jun, Yong Woong; Ahn, Kyo Han [POSTECH, Pohang (Korea, Republic of)

    2014-05-15

    Monoamine oxidases catalyze the oxidative deamination of dietary amines and amine neurotransmitters, and assist in maintaining the homeostasis of the amine neurotransmitters in the brain. Dysfunctions of these enzymes can cause neurological and behavioral disorders including Parkinson's and Alzheimer's diseases. To understand their physiological roles, efficient assay methods for monoamine oxidases are essential. Reviewed in this Perspective are the recent progress in the development of fluorescent probes for monoamine oxidases and their applications to enzyme assays in cells and tissues. It is evident that still there is strong need for a fluorescent probe with desirable substrate selectivity and photophysical properties to challenge the much unsolved issues associated with the enzymes and the diseases.

  7. Analgesic effect of sinomenine on SSNI model rats and monoamine neurotransmitters in striatal extracellular fluid%青藤碱对SSNI模型大鼠镇痛效应和纹状体细胞外液单胺类递质的影响

    Institute of Scientific and Technical Information of China (English)

    张美玉; 李鹏; 王丹巧; 牛晓红; 王晔; 王志国; 张莹; 徐奭; 徐晓军

    2013-01-01

    Objective:To observe the analgesic effect of sinomenine on the neuropathic pain rat model induced by SSNI,and discuss its impact on monoamine neurotransmitters in striatal extracellular fluid.Method:Male SD rats were randomly divided into the sham operation group,the SSNI model group,the gabapentin group (100 mg·kg-1),the sinomenine high dose group (40mg·kg-1) and the sinomenine low dose group (20mg·kg-1).Mechanical hyperalgesia and cold pain sensitivity were evaluated by Von Frey hairs and cold spray.Striatum was sampled by microdialysis.High performance liquid chromatography-electrochemical detector (HPLC-ECD) were used to detect the content of such neurotransmitters as monoamine neurotransmitters noradrenaline (NE),dopamine (DA),5-hydroxy tryptamine (5-HT) and their metabolites dihydroxyphenylacetic phenylacetic acid (DOPAC) and 5-hydroxyindoleacetic acid (5-HIAA).Result:SSNI model rats showed significant improvement in mechanical withdrawal threshold and cold pain sensitivity,significant decrease in intracerebral NE and notable increase in DA,5-HT and their metabolites.Compared with the model group,the sinomenine high dose group showed significant increase in mechanical withdrawal threshold at 60,90,180 and 240 min after abdominal administration (P<0.01),significant decrease in cold pain sensitivity score during 30-240 min (P<0.05).Sinomenine can significantly up-regulated NE content in striatal extracellular fluid during 45-135 min (P<0.05),remarkably reduce DA content and DOPAC at 45,75 and 135 min (P<0.05),5-HT content during 45-135 min,DOPAC during 75-165 min (P<0.05),and 5-HIAA during 45-135 min (P<0.05).Conclusion:Sinomenine has the intervention effect on neuropathic pain in SSNI model rats.Its mechanism may be related to disorder of monoamine neurotransmitters in striatal extracellular fluid.%目的:观察青藤碱对部分坐骨神经损伤(SSNI)诱导的神经病理性疼痛大鼠模型镇痛效应,并探讨其对纹状体细胞外液

  8. The Effects of Monoamine Neurotransmitters and Their Receptors in the Brain on Exercise-Induced Central Fatigue under Heat Stress%热应激下脑内单胺类神经递质及其受体对运动性中枢疲劳影响的研究进展

    Institute of Scientific and Technical Information of China (English)

    张念云; 张蕴琨

    2012-01-01

    Neurotransmitters such as Acetylcholine(Ach),norepinephrine(NE) and 5-hydroxytryptamine(5-HT) regulate body temperature in the hypothalamic,the regulation of receptor lies on the difference of its subtypes.In the high temperature environment,The Concentration of dopamine(DA),5-HT,NE Increased with the rise of brain and core body temperature.The active of 5-HTR2 increased body temperature,while The Active of 5-HTR1A reduced body temperature.In addition,DAR1 and DAR2 synergy to reduce body temperature.The changes of concetration and balance breakage in monoamine neurotransmitters is one of the important factors which caused central fatigue.The temperature of brain and core body increased in Heat stress conditions.The temperature of brain increased can cause central fatigue.The active of DA and NE Improved will inhibit central fatigue,and improve the exercise capacity under Heat stress conditions.However,5-HT can not do as DA and NE.%乙酰胆碱(Ach)、去甲肾上腺素(NE)和5-羟色胺(5-HT)等神经递质参与下丘脑的体温调节,其受体亚型的不同也有不同的调节作用。在高温环境中,多巴胺(DA)、5-HT、NE伴随大脑和核心体温的升高而增加。提高5-HTR2活性会引起体温升高,而提高5-HTR1A活性的则会引起体温降低,DAR1、DAR2两者协同作用于体温的降低。单胺类神经递质含量改变及平衡的破坏是导致运动性中枢疲劳发生的因素之一。热应激条件下机体大脑和核心温度升高,脑内热储备过多,导致中枢疲劳的发生,提高DA、NE的活性可抑制高温介导的中枢疲劳,改善热应激下运动能力,但未能证明在高温环境下长时间运动5-HT介导疲劳的特殊作用。

  9. 束缚应激所致小鼠脑区的神经递质和行为改变及运动干预效果%Restrained stress induced changes of brain monoamine neurotransmitters and behaviors of mice as well as exercise intervention effects

    Institute of Scientific and Technical Information of China (English)

    马磊; 黄文英; 杨念恩; 肖晓玲; 孙飙; 康学军

    2015-01-01

    In order to probe into the effects of restrained stress on monoamine neurotransmitters and behaviors of mice as well as aerobic exercise intervention effects, the authors selected 80 1-month old C57BL/6 mice, randomly divided them into 4 groups: a control group (Control, n=20), a restrained stress group (Stress, n=20), an exercise group (Ex, n=20) and an exercise + restrained stress group (Stress + Ex, n=20), fed the control group in a calm con-dition, let the restrained stress group suffer restrained stress for 2 weeks, let the exercise group exercise on a tread-mill 2 hours a day, let the exercise + restrained stress group suffer restrained stress and exercise on a treadmill si-multaneously, and revealed the following findings: in the behavior experiment, the mice in the restrained stress group had significantly decreased social behaviors and significantly increased levels of anxiety and depression be-haviors (P<0.05), while exercise intervention could alleviate the effects of restrained stress on these behaviors. Bio-chemical indexes indicated as well that aerobic exercise effectively alleviated retrained stress induced changes of behaviors and monoamine neurotransmitters. Conclusion: restrained stress will cause changes of social communica-tion and emotion related behaviors, while exercise intervention will play an effective role of alleviation.%为了探讨束缚应激对小鼠神经递质、行为的影响及有氧运动的干预效果。选用1月龄C57BL/6小鼠80只,随机分为4组:控制组(Control,n=20只)、束缚应激组(Stress,n=20只)、运动组(Ex,n=20只)、运动束缚应激组(Stress+Ex,n=20只)。控制组安静饲养,束缚应激组进行2周的束缚应激,运动组每天进行2 h跑台锻炼,运动束缚应激组同时进行束缚应激和跑台锻炼。结果发现:行为试验中,束缚应激组小鼠社交行为显著下降、焦虑及抑郁行为水平发生显著上升(P<0.05),而运动

  10. Intranasal exposure to manganese disrupts neurotransmitter release from glutamatergic synapses in the central nervous system in vivo.

    Science.gov (United States)

    Moberly, Andrew H; Czarnecki, Lindsey A; Pottackal, Joseph; Rubinstein, Tom; Turkel, Daniel J; Kass, Marley D; McGann, John P

    2012-10-01

    Chronic exposure to aerosolized manganese induces a neurological disorder that includes extrapyramidal motor symptoms and cognitive impairment. Inhaled manganese can bypass the blood-brain barrier and reach the central nervous system by transport down the olfactory nerve to the brain's olfactory bulb. However, the mechanism by which Mn disrupts neural function remains unclear. Here we used optical imaging techniques to visualize exocytosis in olfactory nerve terminals in vivo in the mouse olfactory bulb. Acute Mn exposure via intranasal instillation of 2-200 μg MnCl(2) solution caused a dose-dependent reduction in odorant-evoked neurotransmitter release, with significant effects at as little as 2 μg MnCl(2) and a 90% reduction compared to vehicle controls with a 200 μg exposure. This reduction was also observed in response to direct electrical stimulation of the olfactory nerve layer in the olfactory bulb, demonstrating that Mn's action is occurring centrally, not peripherally. This is the first direct evidence that Mn intoxication can disrupt neurotransmitter release, and is consistent with previous work suggesting that chronic Mn exposure limits amphetamine-induced dopamine increases in the basal ganglia despite normal levels of dopamine synthesis (Guilarte et al., J Neurochem 2008). The commonality of Mn's action between glutamatergic neurons in the olfactory bulb and dopaminergic neurons in the basal ganglia suggests that a disruption of neurotransmitter release may be a general consequence wherever Mn accumulates in the brain and could underlie its pleiotropic effects.

  11. Spatial organization and dynamic properties of neurotransmitter release sites in the enteric nervous system.

    Science.gov (United States)

    Vanden Berghe, P; Klingauf, J

    2007-03-02

    Synaptic communication requires an efficient coupling of vesicle fusion to release neurotransmitter and vesicle retrieval to repopulate the synapse. In synapses of the CNS many proteins involved in exocytosis, endocytosis and refilling of vesicles have been identified. However, little is known about the organization and functioning of synaptic contacts in the enteric nervous system (ENS). We used fluorescent antibodies against presynaptic proteins (synaptobrevin, synaptophysin, synaptotagmin and bassoon) to identify synaptic contacts not only in guinea-pig enteric ganglia but also in the interconnecting fiber strands. Staining patterns were not altered by colchicine (100 microM), ruling out a contribution of protein transport at the time of fixation. Active release sites at fiber intersections and around neuronal cell bodies were labeled with FM1-43 (10 microM) by high K+ or electric field stimulation (EFS). During a second round of EFS, vesicles were reused, as reflected by dye loss. Destaining rates increased with stimulus frequency (2-30 Hz), reaching a maximum at about 15 Hz, likely caused by synaptic depression at higher frequencies. Tetrodotoxin (TTX, 1 microM) as well as nominally zero external Ca2+ (2 mM EGTA) prevented all destaining. The readily releasable pool (RRP, a subset of vesicles docked at the membrane and ready to fuse upon [Ca2+]i increase) can be specifically released by a hypertonic challenge (500 mM sucrose). We measured this pool to be approximately 27% of the total recycling pool, remarkably similar to synapses in the CNS. In whole-mount preparations, FM1-43 also reliably labeled active release sites in ganglia, fiber strands and in muscle bundles. The staining pattern indicated that the presynaptic antibodies mainly labeled active sites. The presence of numerous release sites suggests information processing capability within interconnecting fibers. With FM imaging, enteric synaptic function can be monitored independent of any postsynaptic

  12. 参芪解郁方对产后抑郁大鼠单胺递质及其代谢产物变化的干预研究%Research of influence of Shenqijieyu prescription on changes of monoamine neurotransmitter and metabolite in rats with postpartum depression

    Institute of Scientific and Technical Information of China (English)

    侯秀娟; 唐启盛; 杨歆科; 李小黎; 赵瑞珍; 王旭

    2013-01-01

    Objective To explore interventional mechanism of Shenqijieyu prescription on postpartum depression (PPD) from the perspectives of changes of monoamine neurotransmitter and its related metabolite. Methods Female 2-3 month SD rats were selected and randomly divided into a blank group, a sham-operated group, a model group, a Chinese medicinal group and a western medicine group. The time points at 1st, 2nd, 4th, 6th week were set for observation in each group. The contents of prefrontal cortex, monoamine neurotransmitter in the hippocampus and its metabolite were detected with high performance liquid chromatography. Results The 5-hydroxytryptamine (5—HT), norepinephrine (NE) and dopamine (DA) in the prefrontal cortex and the hippocampus at each time point in the model group were reduced compared with those in the blank group and the sham-operated group (P< 0.01, P< 0.05). The 5-HT,NE in the prefrontal cortex at 2nd, 4th, 6th week in the Chinese medicinal group and at each time point in the western medicine group, as well as the 5-HT, NE in the hippocampus at each time point in the Chinese medicinal group and the western medicine group were increased compared with those in the model group (P < 0.01, P< 0.05). The DA in the prefrontal cortex at 4th, 6th week in the Chinese medicinal group and at 2nd, 4th, 6th week in the western medicine group, as well as DA in the hippocampus at 1st, 6th week in the Chinese medicinal group and at 1st week in the western medicine group were increased compared with those in the model group (P < 0.01, P < 0.05). The 5—hydroxyindole acetic acid (5—HIAA)in the prefrontal cortex and hippocampus at 1st week in the model group were higher than those in the blank group and the sham-operated group (P < 0.01, P < 0.05); the contents of two parts of 5-HIAA at the other time points and two parts of 3, 4-dihydroxy-phenyl acetic acid (DOPAC) at each time point were decreased compared with those in the blank group and the sham-operated group (P

  13. [Effect of occupational stress on neurotransmitters in petroleum workers].

    Science.gov (United States)

    Jiang, Yu; Lian, Yulong; Tao, Ning; Ge, Hua; Liu, Jiwen

    2015-09-01

    To explore the effects of occupational stress on neurotransmitters in petroleum workers. 178 petroleum workers with the length of service ≥ 1 year were recruited to the subjects by the questionnaire of OSI-R. The levels of 5-hydroxy tryptamine (5-HT), norepinephrine (NE), neuropeptide Y (NPY) and substance P (SP) in serum were measured. The subjects were classified into 3 groups according to the scores of occupational stress. The levels of 5-HT NE and SP for over 15 working years were higher than those of less than 15 years (P petroleum workers (P petroleum workers is correlated with serum monoamine and neuropeptides neurotransmitters, and it may affect serum levels of monoamine and neuropeptides neurotransmitters.

  14. Histaminergic system in the cat hypothalamus with reference to type B monoamine oxidase.

    Science.gov (United States)

    Lin, J S; Kitahama, K; Fort, P; Panula, P; Denney, R M; Jouvet, M

    1993-04-15

    It is known that histamine (HA) and type B monoamine oxidase (MAO-B), an enzyme involved in its metabolism, are present in the posterior hypothalamus, but the sites where MAO-B intervenes in HA metabolism remain uncertain. The present study examined and compared the detailed distribution and morphology of neurons immunoreactive to HA (HA-ir) and MAO-B (MAO-B-ir) in the cat hypothalamus. HA-ir neurons were localized almost exclusively in the posterior hypothalamus with the largest group in the tuberomammillary nucleus and adjacent areas. MAO-B-ir staining was detected in the vast majority of HA-ir neurons, suggesting that the degradation of tele-methylhistamine (t-MHA), the direct metabolite of HA, may occur within these cells. Nevertheless, a few HA-ir cells showed no detectable or very weak MAO-B-ir labeling; a small group of neurons containing MAO-B alone was detected in the area dorsolateral to the caudal part of the arcuate nucleus. Numerous HA-ir axons and terminal-like structures were distributed unevenly in virtually all hypothalamic regions. One of their principal trajectories ascended through the ventrolateral part of the hypothalamus and rostrally formed an axon column, which ascended into the preoptic area and contributed fibers to the diagonal band of Broca and bed nucleus of the stria terminalis. Other HA-ir axons passed laterally, dorsal to the zona incerta or ventrally through a narrow zone dorsal to the optic tract. Numerous long HA-ir axons coursed dorsomedially from the ventrolateral posterior hypothalamus to the dorsal hypothalamic area. Many are oriented vertically to the thalamus in the midline. MAO-B-ir axons and fibers were detectable throughout the hypothalamus and overlapped the areas distributing HA-ir fibers. They were, however, weaker in staining intensity and apparently fewer than the HA-ir fibers. MAO-B-ir glial cells were numerous in all hypothalamic structures rich in HA-ir fibers. These results suggest that the metabolism of t

  15. Concentration-dependent effects of cocaine on monoamine-induced constriction of cannulated, pressurized cerebral arteries from fetal sheep.

    Science.gov (United States)

    Schreiber, M D; Madden, J A; Covert, R F; Hershenson, M B; Torgerson, L J

    1995-01-01

    Drugs, such as cocaine, which may alter monoamine neurotransmitter responsiveness, could adversely affect the regulation of cerebral vasculature. Cocaine exhibits at least two mechanisms that may alter vascular responsiveness: synaptic uptake inhibition, which may augment response to stimulation, and Na+ channel inhibition, which may attenuate response. To help elicit the concentration-dependent effects of cocaine, the effects of cocaine on monoamine neurotransmitter responsiveness were studied in vitro on fetal sheep cerebral arteries (120 days gestation). The changes in diameter of segments of cannulated, pressurized fetal sheep cerebral artery were measured with a videomicroscaler system. Cumulative concentration-response curves (10(-10) to 10(-4)M) were generated for two monoamines, norepinephrine and serotonin, alone and in the presence of cocaine (10(-5) or 10(-4)M). Cocaine caused concentration-dependent alteration of response. At 10(-4)M, cocaine attenuated mean maximal norepinephrine-induced vasoconstriction 46.2% (P < 0.05). At 10(-5)M, cocaine increased sensitivity to norepinephrine (log EC50 decreased -6.63 +/- 0.09 to -7.11 +/- 0.03) and to serotonin (log EC50 decreased -7.24 +/- 0.04 to -7.81 +/- 0.09) (P < 0.05). The higher concentration of cocaine (10(-4)M) did not significantly decrease log EC50 norepinephrine. Cocaine (10(-4)M) also attenuated the response to single doses of norepinephrine (10(-6)M) and serotonin (10(-6)M) by 26.5% and 40.0%, respectively (P < or = 0.05). It is concluded that cocaine has concentration-dependent effects on vasoconstriction of the fetal sheep cerebral artery in vitro. This cocaine-induced alteration of cerebral vascular responsiveness to monoamines may be important in the regulation of fetal cerebral blood flow.

  16. Alterations in Brain Monoamine Neurotransmitter Release at High Pressure

    Science.gov (United States)

    1989-01-01

    Services Division F 02-295-2188 ISD/ADMIN/hNXRI )D FORM 1473,84 MAR 83 APR edition may oe used until exnausted. SECURITY CLASIFICATION OF TWIS PAGE All...ml) of the synaptosomal preparation con- taining 3.0 3.5 mg ml protein were incubated for Is mm Of [3H]serotonin from synaptosome fractions iso- 370...Brauer R"’. Beaser RW. Sheehan ME (1978) Role of mono- S~napsin I ( protein I1). a nerse terminal-specific phospho- amnine neurotransmnitters in the

  17. Development of the Wireless Instantaneous Neurotransmitter Concentration System for intraoperative neurochemical monitoring using fast-scan cyclic voltammetry

    Science.gov (United States)

    Bledsoe, Jonathan M.; Kimble, Christopher J.; Covey, Daniel P.; Blaha, Charles D.; Agnesi, Filippo; Mohseni, Pedram; Whitlock, Sidney; Johnson, David M.; Horne, April; Bennet, Kevin E.; Lee, Kendall H.; Garris, Paul A.

    2009-01-01

    Object Emerging evidence supports the hypothesis that modulation of specific central neuronal systems contributes to the clinical efficacy of deep brain stimulation (DBS) and motor cortex stimulation (MCS). Real-time monitoring of the neurochemical output of targeted regions may therefore advance functional neurosurgery by, among other goals, providing a strategy for investigation of mechanisms, identification of new candidate neurotransmitters, and chemically guided placement of the stimulating electrode. The authors report the development of a device called the Wireless Instantaneous Neurotransmitter Concentration System (WINCS) for intraoperative neurochemical monitoring during functional neurosurgery. This device supports fast-scan cyclic voltammetry (FSCV) at a carbon-fiber microelectrode (CFM) for real-time, spatially and chemically resolved neurotransmitter measurements in the brain. Methods The FSCV study consisted of a triangle wave scanned between −0.4 and 1 V at a rate of 300 V/second and applied at 10 Hz. All voltages were compared with an Ag/AgCl reference electrode. The CFM was constructed by aspirating a single carbon fiber (r = 2.5 μm) into a glass capillary and pulling the capillary to a microscopic tip by using a pipette puller. The exposed carbon fiber (that is, the sensing region) extended beyond the glass insulation by ~ 100 μm. The neurotransmitter dopamine was selected as the analyte for most trials. Proof-of-principle tests included in vitro flow injection and noise analysis, and in vivo measurements in urethane-anesthetized rats by monitoring dopamine release in the striatum following high-frequency electrical stimulation of the medial forebrain bundle. Direct comparisons were made to a conventional hardwired system. Results The WINCS, designed in compliance with FDA-recognized consensus standards for medical electrical device safety, consisted of 4 modules: 1) front-end analog circuit for FSCV (that is, current-to-voltage transducer

  18. Effect of Stimulation of Neurotransmitter Systems on Heart Rate Variability and β-Adrenergic Responsiveness of Erythrocytes in Outbred Rats.

    Science.gov (United States)

    Kur'yanova, E V; Tryasuchev, A V; Stupin, V O; Teplyi, D L

    2017-05-01

    We studied heart rate variability and β-adrenergic responsiveness of erythrocytes and changes in these parameters in response to single administration of β-adrenoblocker propranolol (2 mg/kg) in outbred male rats against the background of activation of the noradrenergic, serotonergic, and dopaminergic neurotransmitter systems achieved by 4-fold injections maprotiline (10 mg/kg), 5-hydroxytryptophan (50 mg/kg) combined with fluoxetine (3 mg/kg), and L-DOPA (20 mg/kg) with amantadine (20 mg/kg), respectively. Stimulation of the noradrenergic system moderately enhanced the heart rhythm rigidity and β-adrenergic responsiveness of erythrocytes. In addition, it markedly augmented the moderating effect of subsequently administered propranolol on LF and VLF components in the heart rate variability and reversed the effect of propranolol on β-adrenergic responsiveness of erythrocytes. Stimulation of the serotonergic system dramatically decreased all components in the heart rate variability and pronouncedly enhanced β-adrenergic responsiveness of erythrocytes. Subsequent injection of propranolol slightly restored all components in the heart rate variability and decreased β-adrenergic responsiveness of erythrocytes to the control level. Stimulation of the dopaminergic system made the heart rate more rigid due to decrease of all components in the heart rate variability; in addition, it slightly but significantly enhanced β-adrenergic responsiveness of erythrocytes. Subsequent injection of propranolol produced no significant effects on all components in the heart rate variability and on β-adrenergic responsiveness of erythrocytes. Stimulation of noradrenergic, serotonergic, and dopaminergic neurotransmitter systems produced unidirectional and consorted effects on heart rate variability and β-adrenergic responsiveness of erythrocytes, although the magnitudes of these effects were different. Probably, the changes in the heart rate variability in rats with stimulated

  19. Effects of Albizia Julibrissin Flower Total Flavonoids on Learning and Memory Abilities and Plasma Monoamine Neurotransmitters of Depression Model Rats%合欢花总黄酮对抑郁模型大鼠学习记忆能力及血浆单胺类神经递质的影响

    Institute of Scientific and Technical Information of China (English)

    郭超峰; 银胜高; 夏猛; 施学丽

    2013-01-01

    This study was aimed to observe effects of Albizia Julibrissin Flower Total Flavonoids (AJFTF) on the learning and memory abilities and plasma monoamine neurotransmitters 5-HT and NE content of depression model rats . A total of 90 SD rats were randomly divided into the normal group , model group , western medicine group ( Venlafaxine Hydrochloride 0 . 0125 g•kg-1 ) and high , middle and low dosage groups of AJFTF ( equivalent to the crude drug of 10 , 5 , 2 . 5 g•kg-1 ) . Depression model rats were induced by solitary cultiva-tion and chronic unpredictable stress . The learning and memory abilities of model rats were evaluated with the Morris water maze . And the plasma contents of 5-HT and NE were determined by enzyme-linked immunosor-bent assay ( ELISA ) . The results showed that AJFTF ( administered with high , middle and low dosage for 21 days ) significantly shortened the incubation period of the Morris water maze positioning and navigation ( P <0 . 05 or P < 0 . 01 ) , and increased the times of crossing the platform in space exploration ( P < 0 . 05 or P <0 . 01 ) . There was a certain dose-effect relationship . The AJFTF ( high , middle and low dosage ) increased the plasma contents of 5-HT and NE ( P < 0 . 05 ) . It was concluded that AJFTF can improve learning and memory abilities of depression model rats which indicates that AJFTF have potential antidepressant effects . Its action mechanism may be related to increase plasma monoamine neurotransmitter content of 5-HT and NE .%目的:观察合欢花总黄酮对抑郁模型大鼠学习记忆能力及血浆单胺类神经递质5-羟色胺(5-HT)、去甲肾上腺素(NE)含量的影响。方法:将90只SD大鼠随机分为正常组、模型组、西药组(盐酸文拉法辛0.0125 g·kg-1)、合欢花总黄酮高、中、低剂量组(相当于生药量10、5、2.5 g·kg-1)。以孤养加慢性不可预见性应激建立抑郁症大鼠模型。采用Morris水迷宫评价各组大鼠的

  20. 刺五加对睡眠剥夺大鼠学习记忆及海马单胺类神经递质的影响%Effects of Acanthopanax on Learning and Memory andMonoamine Neurotransmitters in Hippocampus of Sleep Deprived Rats

    Institute of Scientific and Technical Information of China (English)

    朱蕾; 张茹; 李廷利

    2012-01-01

    Objective: To study the protective mechanism of acanthopanax on learning and memory and monoamine neurotransmitters acetylcholinesterase ( AchE ) , serotonin ( 5-HT ) , norepinephrine ( NE ) , 5-hydroxindole acetic acid (5-HIAA) of hippocampus in sleep deprivation rats. Method: Total of 75 male wistar rats were randomized into 5 groups, large platform group, sleep deprivation group, three treatment groups (high, middle and low dose). Treatment groups were given Acanthopanax solution (11.2, 5.6, 2. 8 g·kg-1) for 7 days. The others were given distilled water. A small platform was used to establish rapid eye movement sleep ( REMS) deprivation model in rats. After 4 days, the ability of learning memory and space exploration was tested by Hexagonal maze in rats. The level of AchE, 5-HT, NE, 5-HIAA in hippocampus homogenate were measured. Result: Compared with a large platform, the number of errors of sleep deprivation group increased, the rate of cognitive reduced ( P < 0. 01 ) , but finding time was shorten ( P < 0. 05 ) . After administration of Acanthopanax solution, the number of errors reduced significantly, the rate of cognitive increased(P <0. 01 ) , finding time was shorten(P <0. 01 ) , the level of 5-HT, NE. 5-HIAA was higher in Acanthopanax solution than sleep deprivation group (P <0. 05 or P <0. 01). The AchE level in treatment groups was lower thanthat in sleep deprivation groupbut higher than large platform group (P <0. 05 or P <0. 01) . Conclusion: Acanthopanax can improve learning and memory ablity in sleep deprived rats, and the mechanism may involve regulating the sleep deprivation caused by disorders of monoamine neurotransmitter, accelerating the metabolic conversion of 5-HT, regulating NE, and AchE activity in the hippocampus.%目的:探讨刺五加对睡眠剥夺大鼠学习记忆能力及对海马单胺类神经递质AchE(乙酰胆碱酯酶),5-HT(5-羟色胺)、NE(去甲肾上腺素)、5-HIAA(5-羟吲哚乙酸)的影响.方法:将75

  1. Diagnosis and treatment of neurotransmitter disorders.

    Science.gov (United States)

    Pearl, Phillip L; Hartka, Thomas R; Taylor, Jacob

    2006-11-01

    The neurotransmitter disorders represent an enigmatic and enlarging group of neurometabolic conditions caused by abnormal neurotransmitter metabolism or transport. A high index of clinical suspicion is important, given the availability of therapeutic strategies. This article covers disorders of monoamine (catecholamine and serotonin) synthesis, glycine catabolism, pyridoxine dependency, and gamma-aminobutyric acid (GABA) metabolism. The technological aspects of appropriate cerebrospinal fluid (CSF) collection, shipment, study, and interpretation merit special consideration. Diagnosis of disorders of monoamines requires analysis of CSF homovanillic acid, 5-hydroxyindoleacetic acid, ortho-methyldopa, BH4, and neopterin. The delineation of new disorders with important therapeutic implications, such as cerebral folate deficiency and PNPO deficiency, serves to highlight the value of measuring CSF neurotransmitter precursors and metabolites. The impressive responsiveness of Segawa fluctuating dystonia to levodopa is a hallmark feature of previously unrecognized neurologic morbidity becoming treatable at any age. Aromatic amino acid decarboxylase and tyrosine hydroxylase deficiency have more severe phenotypes and show variable responsiveness to levodopa. Glycine encephalopathy usually has a poor outcome; benzoate therapy may be helpful in less affected cases. Pyridoxine-dependent seizures are a refractory but treatable group of neonatal and infantile seizures; rare cases require pyridoxal-5-phosphate. Succinic semialdehyde dehydrogenase deficiency is relatively common in comparison to the remainder of this group of disorders. Treatment directed at the metabolic defect with vigabatrin has been disappointing, and multiple therapies are targeted toward specific but protean symptoms. Other disorders of GABA metabolism, as is true of the wide spectrum of neurotransmitter disorders, will require increasing use of CSF analysis for diagnosis, and ultimately, treatment.

  2. Evidence that the methylation state of the monoamine oxidase A (MAOA) gene predicts brain activity of MAO A enzyme in healthy men

    National Research Council Canada - National Science Library

    Shumay, Elena; Logan, Jean; Volkow, Nora D; Fowler, Joanna S

    2012-01-01

    ...). PET brain imaging of monoamine oxidase A (MAO A)-an enzyme metabolizing neurotransmitters-revealed that MAO A levels vary widely between healthy men and this variability was not explained by the common MAOA genotype (VNTR genotype...

  3. The plasma membrane monoamine transporter (PMAT): Structure, function, and role in organic cation disposition.

    Science.gov (United States)

    Wang, J

    2016-11-01

    Plasma membrane monoamine transporter (PMAT) is a new polyspecific organic cation transporter that transports a variety of biogenic amines and xenobiotic cations. Highly expressed in the brain, PMAT represents a major uptake2 transporter for monoamine neurotransmitters. At the blood-cerebrospinal fluid (CSF) barrier, PMAT is the principal organic cation transporter for removing neurotoxins and drugs from the CSF. Here I summarize our latest understanding of PMAT and its roles in monoamine uptake and xenobiotic disposition. © 2016 American Society for Clinical Pharmacology and Therapeutics.

  4. Modulation of the storage of social recognition memory by neurotransmitter systems in the insular cortex.

    Science.gov (United States)

    Cavalcante, Lorena E S; Zinn, Carolina G; Schmidt, Scheila D; Saenger, Bruna F; Ferreira, Flávia F; Furini, Cristiane R G; Myskiw, Jociane C; Izquierdo, Ivan

    2017-09-15

    The insular cortex (IC) receives projections from prefrontal, entorhinal and cingulate cortex, olfactory bulb and basal nuclei and has reciprocal connections with the amygdala and entorhinal cortex. These connections suggest a possible involvement in memory processes; this has been borne out by data on several behaviors. Social recognition memory (SRM) is essential to form social groups and to establish hierarchies and social and affective ties. Despite its importance, knowledge about the brain structures and the neurotransmitter mechanisms involved in its processing is still scarce. Here we study the participation of NMDA-glutamatergic, D1/D5-dopaminergic, H2-histaminergic, β-adrenergic and 5-HT1A-serotoninergic receptors of the IC in the consolidation of SRM. Male Wistar rats received intra-IC infusions of substances acting on these receptors immediately after the sample phase of a social discrimination task and 24h later were exposed to a 5-min retention test. The intra-IC infusion of antagonists of D1/D5, β-adrenergic or 5-HT1A receptors immediately after the sample phase impaired the consolidation of SRM. These effects were blocked by the concomitant intra-IC infusion of agonists of these receptors. Antagonists and agonists of NMDA and H2 receptors had no effect on SRM. The results suggest that the dopaminergic D1/D5, β-adrenergic and serotonergic 5-HT1A receptors in the IC, but not glutamatergic NMDA and the histaminergic H2 receptors, participate in the consolidation of SRM in the IC. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. A combined long-term recording system for single-unit activity and neurotransmitter efflux of a brain slice

    Science.gov (United States)

    Sheu, Y. H.; Young, M. S.

    1998-04-01

    A combined long-term measurement and recording system for neurotransmission research of brain slices is presented in this study. This system, based on the IBM PC or compatible computer, is capable of simultaneously measuring and recording both single-unit neural electropotential signals and the electrochemical signals of neurotransmitter efflux from the same neuron in a brain slice for long periods of time (time limited largely by hard disk capacity, 100 h or more not being unreasonable with contemporary hardware) using a single carbon microelectrode for both measurements. The combined long-term recording system uses a simple switching circuit to switch periodically the single microelectrode between two data acquisition subsystems, one for electrochemical data and one for electrophysiological data. The simple switching circuit separates the electrophysiological signals and electrochemical signals, overcoming the traditional interference problem caused by the two different measuring techniques. Software designed for the proposed system allows easy reconstruction of the full time course of the compressed measured data and easy, simultaneous display of both types of signals on the same time scale. On-line and recorded displays are available. Test results of a practical implementation of the proposed system verify that the combined long-term recording system meets actual requirements for electrophysiological and neurochemical research.

  6. Monoamine transporters: insights from molecular dynamics simulations

    Science.gov (United States)

    Grouleff, Julie; Ladefoged, Lucy Kate; Koldsø, Heidi; Schiøtt, Birgit

    2015-01-01

    The human monoamine transporters (MATs) facilitate the reuptake of the neurotransmitters serotonin, dopamine, and norepinephrine from the synaptic cleft. Imbalance in monoaminergic neurotransmission is linked to various diseases including major depression, attention deficit hyperactivity disorder, schizophrenia, and Parkinson’s disease. Inhibition of the MATs is thus an important strategy for treatment of such diseases. The MATs are sodium-coupled transport proteins belonging to the neurotransmitter/Na+ symporter (NSS) family, and the publication of the first high-resolution structure of a NSS family member, the bacterial leucine transporter LeuT, in 2005, proved to be a major stepping stone for understanding this family of transporters. Structural data allows for the use of computational methods to study the MATs, which in turn has led to a number of important discoveries. The process of substrate translocation across the membrane is an intrinsically dynamic process. Molecular dynamics simulations, which can provide atomistic details of molecular motion on ns to ms timescales, are therefore well-suited for studying transport processes. In this review, we outline how molecular dynamics simulations have provided insight into the large scale motions associated with transport of the neurotransmitters, as well as the presence of external and internal gates, the coupling between ion and substrate transport, and differences in the conformational changes induced by substrates and inhibitors. PMID:26528185

  7. 网络成瘾者血液中单胺类神经递质水平与治疗转归的相关性%Relationship of treatment outcome with monoamine neurotransmitter content in peripheral blood in patients with internet addiction disorder

    Institute of Scientific and Technical Information of China (English)

    宋来云; 黄淑燕; 郑小泳; 肖攀攀; 黄金焕; 梁雪玲; 李艳容; 徐伏莲

    2015-01-01

    目的 比较网络成瘾(IAD)者外周血中单胺类神经递质5-羟色胺(5-HT)、多巴胺(DA)、去甲肾上腺素(NE)浓度水平在治疗前后动态变化,分析其与治疗效果的相关性.方法 对治疗前后的35例网络成瘾者(研究组,IAD组)以及性别、年龄、受教育年限与之相匹配的35例健康志愿者(对照组)均采用高效液相色谱法(HPLC)检测外周血小板5-HT浓度,用酶联免疫吸附法(ELISA)检测血浆DA和NE浓度.用中文网络成瘾量表(CIAS)、家庭功能评定量表(FAD)、HAMD量表、HAMA量表评定两组网络成瘾严重程度和IAD组治疗效果.比较IAD组治疗前后5-HT、DA、NE浓度并与对照组比较,分析其与治疗效果(量表)的相关性.结果 (1)IAD组(治疗前)5-HT(427.82±136.28) ng/L,低于对照组的(522.63±123.25) ng/L(t=3.052,P<0.05),DA(65.29±32.52) ng/L,高于对照组的(35.76±22.34) ng/L(t=4.427,P<0.05),NE(493.24±137.65) ng/L,高于对照组的(415.28±118.34) ng/L(t=2.540,P<0.05).(2) IAD组(治疗后)5-HT(518.35±115.68) ng/L,高于IAD组的(治疗前)(427.82±136.28) ng/L(t=2.996,P<0.05),DA(36.45±29.47) ng/L,低于IAD组的(治疗前)(65.29±32.52) ng/L(t=3.887,P<0.05),NE (421.75±129.76) ng/L,低于IAD组的(治疗前)(493.24±137.65)(t=2.235,P<0.05).但IAD组(治疗后)与对照组比较,5-HT、DA和NE浓度差异均无统计学意义(均P>0.05).(3)5-HT浓度与量表评分(CIAS、FAD、HAMa+d)负相关(r=-0.653、-0.547、-0.409,均P<0.05),DA浓度与量表评分正相关(r=0.406、0.375、0.423,均P<0.05),NE浓度与量表评分正相关(r=0.505、0.338、0.545,均P<0.05).结论 网络成瘾者外周血中单胺类神经递质浓度可能与疗效相关;5-HT浓度与疗效正相关,DA、NE与疗效负相关.%Objective To investigate the changes of the concentrations of monoamine neurotransmitter serotonin (5-HT),dopamine (DA),norepinephrine (NE) in peripheral blood in patients with intemet addiction disorder (IAD) between before and

  8. Antidepressant-like effect of ethanol extract from Zuojin Pill, containing two herbal drugs of Rhizoma Coptidis and Fructus Evodiae, is explained by modulating the monoaminergic neurotransmitter system in mice.

    Science.gov (United States)

    Wang, Qiang-Song; Ding, Shi-Lan; Mao, Hao-Ping; Cui, Yuan-Lu; Qi, Xue-Jie

    2013-07-09

    Zuojin Pill (ZJP), a traditional Chinese medicinal decoction, contains two herbal drugs: Coptis chinensis Franch. and Evodia rutaecarpa (Juss.) Benth. in the ratio of 6:1 (w/w). Previous pharmacological studies have shown that two herbs in ZJP have the antagonistic effects on catecholamine secretion in bovine adrenal medullary cells. Furthermore, the alkaloids from the two herbs in ZJP may provide a protective effect for depression in individuals with a low expressing 5-HTT allele by increasing receptor concentration in serotonergic neurons. However, antidepressant effect has not been reported before and has not been fully clarified. The present study aimed to investigate the antidepressant potential of ethanol extract from ZJP and its monoaminergic mechanism in mice. Seven alkaloids were determined from the ethanol extract of ZJP using High Performance Liquid Chromatography (HPLC) with the gradient mobile phase. The ethanol extract from ZJP was used to evaluate the antidepressant potential in mice. Mouse models of depression including the tail suspension test (TST) and the forced swim test (FST) were used to evaluate the effects of the ethanol extract from ZJP. A possible mechanism was explored in the tests of antagonism of reserpine-induced ptosis and hypothermia, and 5-HTP induced head twitch response in mice. The contents of monoamine neurotransmitters including norepinephrine (NE), serotonin (5-hydroxytryptamine or 5-HT) in hippocampus of mice and NE, 5-HT, dopamine (DA) in striatum of mice were determined by HPLC system with Electrochemical Detector (ECD). The results showed that intragastric administration of the ethanol extract from ZJP (5, 10, 20mg/kg) or fluoxetine (7.5mg/kg) significantly reduced the duration of immobility in TST and FST. However, the effect was not dose-dependent. Ethanol extract from ZJP (5, 10, 20mg/kg) also increased the accumulative number of the 5-HTP-induced head twitch response in mice. The mice were treated with the ethanol

  9. 音乐电针和脉冲电针对慢性应激抑郁模型大鼠不同脑区单胺类神经递质表达的影响%Influence of Music Electro-acupuncture and Pulsed Electro-acupuncture on the Different Encephalic Regions of Monoamine Neurotransmitter Chronic Unpredictable Mild Stress Depression Model Rats

    Institute of Scientific and Technical Information of China (English)

    唐银杉; 纪倩; 曹瑾; 滕金艳; 邓晓丰; 李静; 李志刚

    2014-01-01

    electro-acupunc-ture group .All groups were treated with the chronic unpredictable mild stress stimulation combined with lonely rai-sing for 21 days except the normal control group .Behavior changes of rats were detected through open -field test , sugar consumption test and body weight examining .Detect the 5-HT,DA,NE of frontal lobe and hippocampal of each rat by radioimmunoassay .Results:After 21 days, Compared with normal control group ,the scores of behavior in model group decreased significantly (P<0.01).Compared with model group,the scores of horizontal activity and ver-tical activity,sugar consumption and weight in Fluoxetine group , music electro-acupuncture and pulsed electro -ac-upuncture increased significantly(P<0.05).Compared with normal control group ,the contents of frontal lobe and hippocampus’ 5-HT,DA,NE decreased significantly in model group (P<0.01).Compared with model group,the contents of frontal lobe and hippocampus ’ 5 -HT, DA, NE increased significantly in Fluoxetine group , music electro-acupuncture and pulsed electro-acupuncture group(P<0.05).Compared with pulsed electro-acupuncture group, the contents of 5-HT increased significantly in music electro -acupuncture group(P<0.05).Conclusion:Fluoxetine, pulsed electro-acupuncture and music electro-acupuncture could have a certain antidepressant effect on improving the behavior of depressive rats;music electro-acupuncture ’ s regulative effect on monoamine neuro-transmitter is much better than Fluoxetine and pulsed electro -acupuncture, which may be one of the mechanisms for treating depression .

  10. Experimental research on the effect of the Chaiyue decoction against MDD model of rat behavior and brain monoamine neurotransmitters%柴越汤对抑郁症模型大鼠行为学和脑内单胺类神经递质影响的实验研究

    Institute of Scientific and Technical Information of China (English)

    刘丽军; 张保伟

    2012-01-01

      目的:拟探讨柴越汤对慢性应激抑郁模型大鼠行为学和脑内单胺类神经递质影响,进而探讨其可能的作用及其机理.方法:采用孤养结合慢性轻度不可预见性应激复合造模法制备抑郁症模型,将60只雄性 Wistar 大鼠随机分成空白对照组、抑郁模型组、西药对照组、柴越汤组、小柴胡汤组和越鞠丸组.通过体重变化、糖水消耗和敞箱实验进行行为学评价,酶联免疫法测大鼠下丘脑神经递质5-HT和NE的变化,观察柴越汤对抑郁模型大鼠上述指标的影响.结果:21d造模和用药后发现模型组体重增长缓慢,治疗组体重较模型组体重明显增加(P<0.001);在敞箱实验中造模前各组大鼠行为学得分和糖水消耗百分比均无明显差异,造模和用药后发现模型组水平运动和垂直运动明显减少,治疗组能明显增加抑郁模型大鼠行为学得分和糖水消耗百分比与模型组比较均有统计学意义(P<0.001).酶联免疫法检测结果显示,与正常组比较模型组大鼠脑内5-HT、NE均明显下降有统计学意义(P<0.001),治疗组大鼠5-HT、NE均大于模型组,其中西药对照组、柴越汤组和越鞠丸组大鼠脑内5-HT、NE含量高于小柴胡汤组,有统计学意义(P<0.01).结论:柴越汤、小柴胡汤与越鞠丸对抑郁症具有良好的疗效,拆方后,小柴胡汤组、越鞠丸治疗抑郁症疗效较柴越汤略有下降.其作用机理可能与增加脑内5-HT、NE的含量,协调多种神经递质的失衡等有关.%  Objective:To investigate the effect of the Chaiyue decoction against MDD model of rat behavior and brain monoamine neurotransmitters, and provide the theory for clinical medication. Methods: All the groups except control group rats were induced and established the model of depression by isolated supporting and chronic unpredictable moderate intensity stimulation within the whole test. 60 healthy male

  11. Protection against 1,2-di-methylhydrazine-induced systemic oxidative stress and altered brain neurotransmitter status by probiotic Escherichia coli CFR 16 secreting pyrroloquinoline quinone.

    Science.gov (United States)

    Pandey, Sumeet; Singh, Ashish; Chaudhari, Nirja; Nampoothiri, Laxmipriya P; Kumar, G Naresh

    2015-05-01

    Exposure to environmental pollutant 1,2-dimethylhydrazine (DMH) is attributed to systemic oxidative stress and is known to cause neurotropic effect by altering brain neurotransmitter status. Probiotics are opted as natural therapeutic against oxidative stress and also have the ability to modulate gut-brain axis. Pyrroloquinoline quinone (PQQ) is water-soluble, heat-stable antioxidant molecule. Aim of the present study was to evaluate the antioxidant efficacy of PQQ-producing probiotic E. coli CFR 16 on DMH-induced systemic oxidative damage and altered neurotransmitter status in rat brain. Adult virgin Charles Forster rats (200-250 g) were given DMH dose (25 mg/kg body weight, s.c.) for 8 weeks. Blood lipid peroxidation levels exhibited a marked increase while antioxidant enzyme activities of superoxide dismutase, catalase, glucose-6-phosphate dehydrogenase and glutathione peroxidase were found to be reduced in DMH-treated rats. Likewise, brain serotonin and norepinephrine levels displayed a significant decrease, whereas epinephrine levels demonstrated a marked increase in brain of these rats. PQQ-producing E. coli CFR 16 supplementation reduced systemic oxidative stress and also restored brain neurotransmitter status. However, E. coli CFR 16 did not show any effect on these parameters. In contrast, E. coli CFR 16:: vgb-gfp and E. coli CFR 16:: vgb-gfp vector exhibited some degree of protection again oxidative stress but they were not able to modulate neurotransmitter levels. In conclusion, continuous and sustained release of PQQ by probiotic E. coli in rat intestine ameliorates systemic oxidative stress and restored brain neurotransmitter levels.

  12. Vesicular neurotransmitter transporter trafficking in vivo: moving from cells to flies.

    Science.gov (United States)

    Grygoruk, Anna; Fei, Hao; Daniels, Richard W; Miller, Bradley R; Chen, Audrey; DiAntonio, Aaron; Krantz, David E

    2010-01-01

    During exocytosis, classical and amino acid neurotransmitters are released from the lumen of synaptic vesicles to allow signaling at the synapse. The storage of neurotransmitters in synaptic vesicles and other types of secretory vesicles requires the activity of specific vesicular transporters. Glutamate and monoamines such as dopamine are packaged by VGLUTs and VMATs respectively. Changes in the localization of either protein have the potential to up- or down regulate neurotransmitter release, and some of the mechanisms for sorting these proteins to secretory vesicles have been investigated in cultured cells in vitro. We have used Drosophila molecular genetic techniques to study vesicular transporter trafficking in an intact organism and have identified a motif required for localizing Drosophila VMAT (DVMAT) to synaptic vesicles in vivo. In contrast to DVMAT, large deletions of Drosophila VGLUT (DVGLUT) show relatively modest deficits in localizing to synaptic vesicles, suggesting that DVMAT and DVGLUT may undergo different modes of trafficking at the synapse. Further in vivo studies of DVMAT trafficking mutants will allow us to determine how changes in the localization of vesicular transporters affect the nervous system as a whole and complex behaviors mediated by aminergic circuits.

  13. Neurotransmitter Switching? No Surprise.

    Science.gov (United States)

    Spitzer, Nicholas C

    2015-06-03

    Among the many forms of brain plasticity, changes in synaptic strength and changes in synapse number are particularly prominent. However, evidence for neurotransmitter respecification or switching has been accumulating steadily, both in the developing nervous system and in the adult brain, with observations of transmitter addition, loss, or replacement of one transmitter with another. Natural stimuli can drive these changes in transmitter identity, with matching changes in postsynaptic transmitter receptors. Strikingly, they often convert the synapse from excitatory to inhibitory or vice versa, providing a basis for changes in behavior in those cases in which it has been examined. Progress has been made in identifying the factors that induce transmitter switching and in understanding the molecular mechanisms by which it is achieved. There are many intriguing questions to be addressed.

  14. Thin film microelectrodes for electrochemical detection of neurotransmitters

    DEFF Research Database (Denmark)

    Larsen, Simon Tylsgaard

    An important signaling process in the nervous system is the release of chemical messengers called neurotransmitters from neurons. In this thesis alternative thin film electrode materials for applications targeting electrochemical detection of neurotransmitters in chip devices were evaluated...

  15. Neurotransmitter Systems in a Mild Blast Traumatic Brain Injury Model: Catecholamines and Serotonin.

    Science.gov (United States)

    Kawa, Lizan; Arborelius, Ulf P; Yoshitake, Takashi; Kehr, Jan; Hökfelt, Tomas; Risling, Mårten; Agoston, Denes

    2015-08-15

    Exposure to improvised explosive devices can result in a unique form of traumatic brain injury--blast-induced traumatic brain injury (bTBI). At the mild end of the spectrum (mild bTBI [mbTBI]), there are cognitive and mood disturbances. Similar symptoms have been observed in post-traumatic stress disorder caused by exposure to extreme psychological stress without physical injury. A role of the monoaminergic system in mood regulation and stress is well established but its involvement in mbTBI is not well understood. To address this gap, we used a rodent model of mbTBI and detected a decrease in immobility behavior in the forced swim test at 1 d post-exposure, coupled with an increase in climbing behavior, but not after 14 d or later, possibly indicating a transient increase in anxiety-like behavior. Using in situ hybridization, we found elevated messenger ribonucleic acid levels of both tyrosine hydroxylase and tryptophan hydroxylase 2 in the locus coeruleus and the dorsal raphe nucleus, respectively, as early as 2 h post-exposure. High-performance liquid chromatography analysis 1 d post-exposure primarily showed elevated noradrenaline levels in several forebrain regions. Taken together, we report that exposure to mild blast results in transient changes in both anxiety-like behavior and brain region-specific molecular changes, implicating the monoaminergic system in the pathobiology of mbTBI.

  16. Changes in the function of the inhibitory neurotransmitter system in the rat brain following subchronic inhalation exposure to 1-bromopropane.

    Science.gov (United States)

    Ueno, Susumu; Yoshida, Yasuhiro; Fueta, Yukiko; Ishidao, Toru; Liu, Jiqin; Kunugita, Naoki; Yanagihara, Nobuyuki; Hori, Hajime

    2007-03-01

    1-Bromopropane (1-BP) has been widely used as a cleaning agent and a solvent in industries, but the central neurotoxicity of 1-BP remains to be clarified. In the present study, we investigated the effects of subchronic inhalation exposure to 1-BP vapor on the function of the inhibitory neurotransmitter system mediated by gamma-aminobutyric acid (GABA) in the rat brain. Male Wistar rats were exposed to 1-BP vapor for 12 weeks (6h/day, 5 days/week) at a concentration of 400 ppm, and, in order to investigate the expression and function of brain GABA type A (GABAA) receptors, total/messenger RNA was prepared from the neocortex, hippocampus, and cerebellum of the control and 1-BP-exposed rats. Moreover, hippocampal slices were prepared, and the population spike (PS) amplitude and the slope of the field excitatory postsynaptic potential (fEPSP) were investigated in the paired-pulse configuration of the extracellular recording technique. Using the Xenopus oocyte expression system, we compared GABA concentration-response curves obtained from oocytes injected with brain subregional mRNAs of control and 1-BP exposed rats, and observed no significant differences in apparent GABA affinity. On the other hand, paired-pulse inhibition of PS amplitude was significantly decreased in the hippocampal dentate gyrus (DG) by exposure to 1-BP, without any effect on the paired-pulse ratio of the fEPSP slopes, suggesting neuronal disinhibition in the DG. Moreover, RT-PCR analysis indicated decreased levels of GABAA receptor beta3 and delta subunit mRNAs in the hippocampus of 1-BP-exposed rats. These results demonstrate that subchronic inhalation exposure to 1-BP vapor reduces the function of the hippocampal GABAergic system, which could be due to changes in the expression and function of GABAA receptors, especially the delta subunit-containing GABAA receptors.

  17. Subchronic exposure to arsenic disturbed the biogenic amine neurotransmitter level and the mRNA expression of synthetase in mice brains.

    Science.gov (United States)

    Zhang, J; Liu, X; Zhao, L; Hu, S; Li, S; Piao, F

    2013-06-25

    Little is known about the influence of arsenic (As) exposure on monoamine neurotransmitters and the underlying mechanisms, although arsenic toxicity on the central nervous system has been well documented. In the present study, the levels of norepinephrine (NE), dopamine (DA), and 5-HT were determined by high performance liquid chromatography in the cerebrum and cerebellum of mice exposed to 1, 2 and 4 ppm As2O3 through drinking water for 60 days. The ultra-structural change of vesicles in the synapses of mice brains was observed by transmission electron microscopy; the mRNA expressions of dopamine beta hydroxylase (DBH), tyrosine hydroxylase (TH) and tryptophan hydroxylase (TPH) as NE, DA and 5-HT synthetases were quantitatively assessed by real time reverse transcription-polymerase chain reaction. It was shown that the concentrations of NE, DA and 5-HT in the cerebrum or cerebellum of mice exposed to As were significantly lower than those in the control group. The number of synaptic vesicles significantly decreased in the brain of mice exposed to As. Moreover, the expressions of TH, TPH and DBH genes were significantly lower in the brains of mice exposed to As than those in the controls. These results suggested that subchronic exposure to As might decrease the concentrations of the three monoamine neurotransmitters in the mouse brain and downregulate TH, TPH and DBH gene expressions. It was also indicated that the decreased concentrations of the three monoamine neurotransmitters in the brain might be related to the down-regulated gene expressions of these synthetases by As.

  18. Electrochemical Analysis of Neurotransmitters.

    Science.gov (United States)

    Bucher, Elizabeth S; Wightman, R Mark

    2015-01-01

    Chemical signaling through the release of neurotransmitters into the extracellular space is the primary means of communication between neurons. More than four decades ago, Ralph Adams and his colleagues realized the utility of electrochemical methods for the study of easily oxidizable neurotransmitters, such as dopamine, norepinephrine, and serotonin and their metabolites. Today, electrochemical techniques are frequently coupled to microelectrodes to enable spatially resolved recordings of rapid neurotransmitter dynamics in a variety of biological preparations spanning from single cells to the intact brain of behaving animals. In this review, we provide a basic overview of the principles underlying constant-potential amperometry and fast-scan cyclic voltammetry, the most commonly employed electrochemical techniques, and the general application of these methods to the study of neurotransmission. We thereafter discuss several recent developments in sensor design and experimental methodology that are challenging the current limitations defining the application of electrochemical methods to neurotransmitter measurements.

  19. Electrochemical Analysis of Neurotransmitters

    Science.gov (United States)

    Bucher, Elizabeth S.; Wightman, R. Mark

    2015-07-01

    Chemical signaling through the release of neurotransmitters into the extracellular space is the primary means of communication between neurons. More than four decades ago, Ralph Adams and his colleagues realized the utility of electrochemical methods for the study of easily oxidizable neurotransmitters, such as dopamine, norepinephrine, and serotonin and their metabolites. Today, electrochemical techniques are frequently coupled to microelectrodes to enable spatially resolved recordings of rapid neurotransmitter dynamics in a variety of biological preparations spanning from single cells to the intact brain of behaving animals. In this review, we provide a basic overview of the principles underlying constant-potential amperometry and fast-scan cyclic voltammetry, the most commonly employed electrochemical techniques, and the general application of these methods to the study of neurotransmission. We thereafter discuss several recent developments in sensor design and experimental methodology that are challenging the current limitations defining the application of electrochemical methods to neurotransmitter measurements.

  20. Neurotransmitters and neuromodulators controlling the anterior byssus retractor muscle of Mytilus edulis.

    Science.gov (United States)

    Muneoka, Y; Fujisawa, Y; Matsuura, M; Ikeda, T

    1991-01-01

    1. The anterior byssus retractor muscle (ABRM) of Mytilus edulis is innervated by at least two kinds of nerves, excitatory and relaxing nerves. The principal neurotransmitters released from these nerves have been shown to be acetylcholine and serotonin, respectively. 2. Some other monoamines, such as dopamine and octopamine, and various peptides, such as FMRFamide-related peptides, Mytilus inhibitory peptides, SCP-related peptides and a catch-relaxing peptide, may also be involved in the regulation of the muscle as neurotransmitters or neuromodulators. 3. The ABRM seems to be typical of invertebrate muscles controlled by multiple neurotransmitters and neuromodulators.

  1. Fast methods for analysis of neurotransmitters from single cell and monitoring their releases in central nervous system by capillary electrophoresis, fluorescence microscopy and luminescence imaging

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Ziqiang [Iowa State Univ., Ames, IA (United States)

    1999-12-10

    Fast methods for separation and detection of important neurotransmitters and the releases in central nervous system (CNS) were developed. Enzyme based immunoassay combined with capillary electrophoresis was used to analyze the contents of amino acid neurotransmitters from single neuron cells. The release of amino acid neurotransmitters from neuron cultures was monitored by laser induced fluorescence imaging method. The release and signal transduction of adenosine triphosphate (ATP) in CNS was studied with sensitive luminescence imaging method. A new dual-enzyme on-column reaction method combined with capillary electrophoresis has been developed for determining the glutamate content in single cells. Detection was based on monitoring the laser-induced fluorescence of the reaction product NADH, and the measured fluorescence intensity was related to the concentration of glutamate in each cell. The detection limit of glutamate is down to 10-8 M level, which is 1 order of magnitude lower than the previously reported detection limit based on similar detection methods. The mass detection limit of a few attomoles is far superior to that of any other reports. Selectivity for glutamate is excellent over most of amino acids. The glutamate content in single human erythrocyte and baby rat brain neurons were determined with this method and results agreed well with literature values.

  2. Fast methods for analysis of neurotransmitters from single cell and monitoring their releases in central nervous system by capillary electrophoresis, fluorescence microscopy and luminescence imaging

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Ziqiang

    1999-12-10

    Fast methods for separation and detection of important neurotransmitters and the releases in central nervous system (CNS) were developed. Enzyme based immunoassay combined with capillary electrophoresis was used to analyze the contents of amino acid neurotransmitters from single neuron cells. The release of amino acid neurotransmitters from neuron cultures was monitored by laser induced fluorescence imaging method. The release and signal transduction of adenosine triphosphate (ATP) in CNS was studied with sensitive luminescence imaging method. A new dual-enzyme on-column reaction method combined with capillary electrophoresis has been developed for determining the glutamate content in single cells. Detection was based on monitoring the laser-induced fluorescence of the reaction product NADH, and the measured fluorescence intensity was related to the concentration of glutamate in each cell. The detection limit of glutamate is down to 10{sup {minus}8} M level, which is 1 order of magnitude lower than the previously reported detection limit based on similar detection methods. The mass detection limit of a few attomoles is far superior to that of any other reports. Selectivity for glutamate is excellent over most of amino acids. The glutamate content in single human erythrocyte and baby rat brain neurons were determined with this method and results agreed well with literature values.

  3. [Axolemmal transporters for neurotransmitter uptake].

    Science.gov (United States)

    García-López, M

    Neurotransmission is a fundamental process in interneuronal communication. It starts with the release of the neurotransmitter following a nerve impulse and ends either by uptake by specific specific transporters or by metabolization to an inactive compound. In this review we will consider the molecular, ion dependence and electrogenic properties of the axolemal transporters for neurotransmitters and also the pathological consequences of their impairment as well as the drugs that can interact with them. Most axolemmal transporters have been cloned and grouped into two large families according to their molecular characteristics and electrogenic properties: 1. Those dependent on Na+/Cl- include transporters of GABA, noradrenaline, dopamine, serotonin, choline, proline, betaine, glycine and taurine, and 2. Those dependent on Na+/K+, which include the transporters of glutamate, alanine, serine and cysteine. The clonation of transporters has permitted (and will continue to permit) the correlation of molecular alterations of transporters with different neuro-degenerative disorders (e.g. multiple sclerosis, Parkinson's disease, Alzheimer's disease), with brain lesions (e.g. cerebral ischemia, status epilepticus) and with psychiatric alterations (e.g. schizophrenia, depression). In this respect, chemical synthesis of new selective drugs which interact with the different systems for uptake of neurotransmitters will offer new approaches to the treatment of many disorders of the central nervous system which still have no satisfactory drug treatment.

  4. Neurotransmitters affecting time perception

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    BACKGROUND:It has been demonstrated that dopamine and acetylcholine are the main neurotransmitters that affect time perception,which is also affected by other neurotransmitters.OBJECTIVE:To summarize how the neurotransmitter affect the time perception,and put forward the perspectives for further study on time perception.RETRIEVE STRATEGY:An online search for related literatures published in English was conducted in Elsevier SDOL(ScienceDirect Online)database from May 1990 to March 2007 using key words of "timing neurotransmitter".Totally 69 literatures were collected,and they were primarily checked.Inclusive criteria:Reviews and experimental studies;correlative studies of timing neurotransmitter.Exclusive criteria:Repeated studies.LITERATURE EVALUATION:The literatures were mainly sourced from Cognitive Brain Research and Neuroscience,and they were analyzed according to the inclusive criteria.Nineteen of them were involved,and all were experimental studies and reviews.DATA SYNTHESIS:The studies on time perception are developed mainly concentrating on dopamine and acetylcholine.Dopamine D2 receptors mainly affect the speed of internal clock.Dopamine receptors play an important role in both timing excitation and inhibition,which suggests the bi-directional regulation of dopamine.Injection of dopamine agonist can affect the attention to timing information.Injection of BW813U(antagonist of acetylcholine) can induce memory disorder,which indicates the effect of acetylcholine on timing memory,and further study shows that it is the effect of acetylcholine in precentral medial area.In a word,the study on the neurotransmitters affecting time perception is still at the primary stage.CONCLUSION:Dopamine and acetylcholine are the neurotransmitters known to be related to time perception.Dopamine in the basal ganglia is related to internal-clock in the range of seconds and minutes;Acetylcholine in prefrontal cortex is related to the mechanisms of temporal memory and attention

  5. Monoamine fluctuations during the reproductive cycle of the Pacific lion's paw scallop Nodipecten subnodosus.

    Science.gov (United States)

    López-Sánchez, J Armando; Maeda-Martínez, Alfonso N; Croll, Roger P; Acosta-Salmón, Héctor

    2009-11-01

    The Pacific lion's paw scallop Nodipecten subnodosus has been one of the most important commercial species of mollusc in the Baja California peninsula in Mexico since 1990. This species is a functional hermaphrodite with tropical and sub-tropical distributions and experiences wide annual temperature oscillations influencing its physiological functions. We determined norepinephrine (NE), dopamine (DA), and serotonin (5-HT) concentrations in different organs (female and male gonads, digestive gland, adductor muscle, gill, mantle, and foot) of N. subnodosus, at 6 reproductive stages (resting, initial, maturing, mature, partially spent and fully spent). Monoamine concentrations were determined by HPLC fitted with an electrochemical detector. Results indicated that monoamine concentrations increased during maturing stage, peaked at mature stage and declined after spawning. NE concentrations were higher than the rest of monoamines followed by DA, and 5-HT. NE was present in all organs at all reproductive stages. DA concentrations were higher in the gill and digestive gland during all stages. 5-HT was only detectable in the male gonadic portion at all stages except at spent stage. NE was the most abundant neurotransmitter found in the female gonad of N. subnodosus, while 5-HT was the most abundant neurotransmitter found in the male gonad. Furthermore, these two neurotransmitters accumulated in the respective gonad tissues during the initial reproductive stages I to IV and then declined after spawning (stages V and VI). This suggests that this species utilized different neurotransmitters specific for each gender and that this utilization was related to the reproductive cycle.

  6. A Yang-invigorating compound mixture alters neurotransmitters in rat telencephalon after exercise-induced fatigue

    Institute of Scientific and Technical Information of China (English)

    Hongzhen Liu; Li Zeng; Xiliang Kong; Lei Zhu; Benhua Hou

    2011-01-01

    The aim of this study was to observe the changes in monoamine and amino acid neurotransmitters in the telencephalon of rats at four functional states after exhaustive exercise and treatment with a Yang-invigorating compound recipe.The main components of this Chinese traditional medicine preparation included Radix Ginseng,Rhizoma Chuanxiong,Fructus Schisandrae,Cortex Cinnamomi,Cornu Cervi Pantotrichum,Radix Morindae Officinalis,and Gecko.This experiment showed that dopamine (DA),5-hydroxyindole acetic acid (5-HIAA),and γ-aminobutyric acid levels noticeably decreased,while DA/5-hydroxytryptamine (5-HT) increased.Furthermore,glutamate (Glu) and Glu/γ-aminobutyric acid significantly increased after 1 hour of exercise in rats in the exercise + medication group.The 5-HT and 5-HT/5-HIAA levels noticeably decreased,and DA/5-HT and Glu levels showed a robust and significant increase immediately after exhaustive exercise.The 5-HT,5-HT/5-HIAA levels sharply decreased,while DA/5-HT,Glu and γ-aminobutyric acid levels increased at 12 hours after exhaustion recovery.The results prove that Chinese herbal formula for strengthening Yang can induce changes in neurotransmitters in the telencephalon of rats after exhaustive exercise during the recovery process,and further improve central nervous system function.

  7. Dysfunctional Neurotransmitter Systems in Fibromyalgia, Their Role in Central Stress Circuitry and Pharmacological Actions on These Systems

    Directory of Open Access Journals (Sweden)

    Susanne Becker

    2012-01-01

    Full Text Available Fibromyalgia is considered a stress-related disorder, and hypo- as well as hyperactive stress systems (sympathetic nervous system and hypothalamic-pituitary-adrenal axis have been found. Some observations raise doubts on the view that alterations in these stress systems are solely responsible for fibromyalgia symptoms. Cumulative evidence points at dysfunctional transmitter systems that may underlie the major symptoms of the condition. In addition, all transmitter systems found to be altered in fibromyalgia influence the body's stress systems. Since both transmitter and stress systems change during chronic stress, it is conceivable that both systems change in parallel, interact, and contribute to the phenotype of fibromyalgia. As we outline in this paper, subgroups of patients might exhibit varying degrees and types of transmitter dysfunction, explaining differences in symptomatoloy and contributing to the heterogeneity of fibromyalgia. The finding that not all fibromyalgia patients respond to the same medications, targeting dysfunctional transmitter systems, further supports this hypothesis.

  8. Ciproxifan, a histamine H3 receptor antagonist, reversibly inhibits monoamine oxidase A and B.

    Science.gov (United States)

    Hagenow, S; Stasiak, A; Ramsay, R R; Stark, H

    2017-01-13

    Ciproxifan is a well-investigated histamine H3 receptor (H3R) inverse agonist/antagonist, showing an exclusively high species-specific affinity at rodent compared to human H3R. It is well studied as reference compound for H3R in rodent models for neurological diseases connected with neurotransmitter dysregulation, e.g. attention deficit hyperactivity disorder or Alzheimer's disease. In a screening for potential monoamine oxidase A and B inhibition ciproxifan showed efficacy on both enzyme isoforms. Further characterization of ciproxifan revealed IC50 values in a micromolar concentration range for human and rat monoamine oxidases with slight preference for monoamine oxidase B in both species. The inhibition by ciproxifan was reversible for both human isoforms. Regarding inhibitory potency of ciproxifan on rat brain MAO, these findings should be considered, when using high doses in rat models for neurological diseases. As the H3R and monoamine oxidases are all capable of affecting neurotransmitter modulation in brain, we consider dual targeting ligands as interesting approach for treatment of neurological disorders. Since ciproxifan shows only moderate activity at human targets, further investigations in animals are not of primary interest. On the other hand, it may serve as starting point for the development of dual targeting ligands.

  9. Designing Modulators of Monoamine Transporters using Virtual Screening Techniques

    Directory of Open Access Journals (Sweden)

    Ole Valente Mortensen

    2015-09-01

    Full Text Available The plasma-membrane monoamine transporters (MATs, including the serotonin (SERT, norepinephrine (NET and dopamine (DAT transporters, serve a pivotal role in limiting monoamine-mediated neurotransmission through the reuptake of their respective monoamine neurotransmitters. The transporters are the main target of clinically used psychostimulants and antidepressants. Despite the availability of several potent and selective MAT substrates and inhibitors the continuing need for therapeutic drugs to treat brain disorders involving aberrant monoamine signaling provides a compelling reason to identify novel ways of targeting and modulating the MATs. Designing novel modulators of MAT function have been limited by the lack of three dimensional structure information of the individual MATs. However, crystal structures of LeuT, a bacterial homologue of MATs, in a substrate-bound occluded, substrate-free outward-open, and an apo inward-open state and also with competitive and noncompetitive inhibitors have been determined. In addition, several structures of the drosophila DAT have also been resolved. Together with computational modeling and experimental data gathered over the past decade, these structures have dramatically advanced our understanding of several aspects of SERT, NET, and DAT transporter function, including some of the molecular determinants of ligand interaction at orthosteric substrate and inhibitor binding pockets. In addition progress has been made in the understanding of how allosteric modulation of MAT function can be achieved. Here we will review all the efforts up to date that has been made through computational approaches employing structural models of MATs to design small molecule modulators to the orthosteric and allosteric sites using virtual screening techniques.

  10. Designing modulators of monoamine transporters using virtual screening techniques

    Science.gov (United States)

    Mortensen, Ole V.; Kortagere, Sandhya

    2015-01-01

    The plasma-membrane monoamine transporters (MATs), including the serotonin (SERT), norepinephrine (NET) and dopamine (DAT) transporters, serve a pivotal role in limiting monoamine-mediated neurotransmission through the reuptake of their respective monoamine neurotransmitters. The transporters are the main target of clinically used psychostimulants and antidepressants. Despite the availability of several potent and selective MAT substrates and inhibitors the continuing need for therapeutic drugs to treat brain disorders involving aberrant monoamine signaling provides a compelling reason to identify novel ways of targeting and modulating the MATs. Designing novel modulators of MAT function have been limited by the lack of three dimensional structure information of the individual MATs. However, crystal structures of LeuT, a bacterial homolog of MATs, in a substrate-bound occluded, substrate-free outward-open, and an apo inward-open state and also with competitive and non-competitive inhibitors have been determined. In addition, several structures of the Drosophila DAT have also been resolved. Together with computational modeling and experimental data gathered over the past decade, these structures have dramatically advanced our understanding of several aspects of SERT, NET, and DAT transporter function, including some of the molecular determinants of ligand interaction at orthosteric substrate and inhibitor binding pockets. In addition progress has been made in the understanding of how allosteric modulation of MAT function can be achieved. Here we will review all the efforts up to date that has been made through computational approaches employing structural models of MATs to design small molecule modulators to the orthosteric and allosteric sites using virtual screening techniques. PMID:26483692

  11. Transcriptional coordination of synaptogenesis and neurotransmitter signaling.

    Science.gov (United States)

    Kratsios, Paschalis; Pinan-Lucarré, Bérangère; Kerk, Sze Yen; Weinreb, Alexis; Bessereau, Jean-Louis; Hobert, Oliver

    2015-05-18

    During nervous system development, postmitotic neurons face the challenge of generating and structurally organizing specific synapses with appropriate synaptic partners. An important unexplored question is whether the process of synaptogenesis is coordinated with the adoption of specific signaling properties of a neuron. Such signaling properties are defined by the neurotransmitter system that a neuron uses to communicate with postsynaptic partners, the neurotransmitter receptor type used to receive input from presynaptic neurons, and, potentially, other sensory receptors that activate a neuron. Elucidating the mechanisms that coordinate synaptogenesis, neuronal activation, and neurotransmitter signaling in a postmitotic neuron represents one key approach to understanding how neurons develop as functional units. Using the SAB class of Caenorhabditis elegans motor neurons as a model system, we show here that the phylogenetically conserved COE-type transcription factor UNC-3 is required for synaptogenesis. UNC-3 directly controls the expression of the ADAMTS-like protein MADD-4/Punctin, a presynaptically secreted synapse-organizing molecule that clusters postsynaptic receptors. UNC-3 also controls the assembly of presynaptic specializations and ensures the coordinated expression of enzymes and transporters that define the cholinergic neurotransmitter identity of the SAB neurons. Furthermore, synaptic output properties of the SAB neurons are coordinated with neuronal activation and synaptic input, as evidenced by UNC-3 also regulating the expression of ionotropic neurotransmitter receptors and putative stretch receptors. Our study shows how synaptogenesis and distinct, function-defining signaling features of a postmitotic neuron are hardwired together through coordinated transcriptional control.

  12. Age and Heat Stress Related Changes in Monoamine Contents and Cholinesterase Activity in Some Central Nervous System Regions of Albino Rat Newborns

    Directory of Open Access Journals (Sweden)

    M. Bahgat

    2007-01-01

    Full Text Available The normal monoamine [norepinephrine (NE, epinephrine (E, dopamine (DA and serotonin (5-HT] contents and cholinestrase (chE activity were significantly and gradually increased with age progress between postnatal days 7 and 21 in cerebrum, cerebellum, medulla oblongata and spinal cord of rat newborns. The daily exposure of the newborns to 401C for 2 h induced deteriorated effects and the withdrawal period of 7 days failed to return these altered variables to normal levels. On the other hand, the high temperature exerted its most potent decreased effect on monoamine contents at 21 days old. This decrease may be attributed to the elevated activity of monoamine oxidase and/or the decreased activity of the key enzymes responsible for monoamine synthesis. The chE activity exhibited different effects in the tested CNS regions as a result of high temperature exposure; the enzyme activity was decreased markedly at days 7, 14 and 21 in cerebellum and medulla oblongata and lowered only at days 7 and 14 in cerebrum and at day 14 in spinal cord. The subsequent withdrawal for 7 days beyond day 21 produced marked weakening of effect of high temperature exposure on monoamine contents in all examined CNS regions except NE and 5-HT contents in cerebellum and DA level in medulla oblongata. In spite of this attenuation, the values recorded in the withdrawal group were still significantly lower than the normal levels. On the other hand, the chE activity became more deleteriously affected at day 28 in the treated CNS regions except in the medulla oblongata where it was profoundly ameliorated after the withdrawal period.

  13. Interaction of anesthetics with neurotransmitter release machinery proteins.

    Science.gov (United States)

    Xie, Zheng; McMillan, Kyle; Pike, Carolyn M; Cahill, Anne L; Herring, Bruce E; Wang, Qiang; Fox, Aaron P

    2013-02-01

    General anesthetics produce anesthesia by depressing central nervous system activity. Activation of inhibitory GABA(A) receptors plays a central role in the action of many clinically relevant general anesthetics. Even so, there is growing evidence that anesthetics can act at a presynaptic locus to inhibit neurotransmitter release. Our own data identified the neurotransmitter release machinery as a target for anesthetic action. In the present study, we sought to examine the site of anesthetic action more closely. Exocytosis was stimulated by directly elevating the intracellular Ca(2+) concentration at neurotransmitter release sites, thereby bypassing anesthetic effects on channels and receptors, allowing anesthetic effects on the neurotransmitter release machinery to be examined in isolation. Three different PC12 cell lines, which had the expression of different release machinery proteins stably suppressed by RNA interference, were used in these studies. Interestingly, there was still significant neurotransmitter release when these knockdown PC12 cells were stimulated. We have previously shown that etomidate, isoflurane, and propofol all inhibited the neurotransmitter release machinery in wild-type PC12 cells. In the present study, we show that knocking down synaptotagmin I completely prevented etomidate from inhibiting neurotransmitter release. Synaptotagmin I knockdown also diminished the inhibition produced by propofol and isoflurane, but the magnitude of the effect was not as large. Knockdown of SNAP-25 and SNAP-23 expression also changed the ability of these three anesthetics to inhibit neurotransmitter release. Our results suggest that general anesthetics inhibit the neurotransmitter release machinery by interacting with multiple SNARE and SNARE-associated proteins.

  14. Are vesicular neurotransmitter transporters potential treatment targets for temporal lobe epilepsy?

    Directory of Open Access Journals (Sweden)

    Joeri eVan Liefferinge

    2013-08-01

    Full Text Available The vesicular neurotransmitter transporters (VNTs are small proteins responsible for packing synaptic vesicles with neurotransmitters thereby determining the amount of neurotransmitter released per vesicle through fusion in both neurons and glial cells. Each transporter subtype was classically seen as a specific neuronal marker of the respective nerve cells containing that particular neurotransmitter or structurally related neurotransmitters. More recently, however, it has become apparent that common neurotransmitters can also act as co-transmitters, adding complexity to neurotransmitter release and suggesting intriguing roles for VNTs therein. We will first describe the current knowledge on vesicular glutamate transporters (VGLUT1/2/3, the vesicular excitatory amino acid transporter (VEAT, the vesicular nucleotide transporter (VNUT, vesicular monoamine transporters (VMAT1/2, the vesicular acetylcholine transporter (VAChT and the vesicular γ-aminobutyric acid (GABA transporter (VGAT in the brain. We will focus on evidence regarding transgenic mice with disruptions in VNTs in different models of seizures and epilepsy. We will also describe the known alterations and reorganizations in the expression levels of these VNTs in rodent models for temporal lobe epilepsy (TLE and in human tissue resected for epilepsy surgery. Finally, we will discuss perspectives on opportunities and challenges for VNTs as targets for possible future epilepsy therapies.

  15. The putative Na⁺/Cl⁻-dependent neurotransmitter/osmolyte transporter inebriated in the Drosophila hindgut is essential for the maintenance of systemic water homeostasis.

    Science.gov (United States)

    Luan, Zhuo; Quigley, Caitlin; Li, Hong-Sheng

    2015-01-23

    Most organisms are able to maintain systemic water homeostasis over a wide range of external or dietary osmolarities. The excretory system, composed of the kidneys in mammals and the Malpighian tubules and hindgut in insects, can increase water conservation and absorption to maintain systemic water homeostasis, which enables organisms to tolerate external hypertonicity or desiccation. However, the mechanisms underlying the maintenance of systemic water homeostasis by the excretory system have not been fully characterized. In the present study, we found that the putative Na(+)/Cl(-)-dependent neurotransmitter/osmolyte transporter inebriated (ine) is expressed in the basolateral membrane of anterior hindgut epithelial cells. This was confirmed by comparison with a known basolateral localized protein, the α subunit of Na(+)-K(+) ATPase (ATPα). Under external hypertonicity, loss of ine in the hindgut epithelium results in severe dehydration without damage to the hindgut epithelial cells, implicating a physiological failure of water conservation/absorption. We also found that hindgut expression of ine is required for water conservation under desiccating conditions. Importantly, specific expression of ine in the hindgut epithelium can completely restore disrupted systemic water homeostasis in ine mutants under both conditions. Therefore, ine in the Drosophila hindgut is essential for the maintenance of systemic water homeostasis.

  16. Secondary Abnormalities of Neurotransmitters in Infants with Neurological Disorders

    Science.gov (United States)

    Garcia-Cazorla, A.; Serrano, M.; Perez-Duenas, B.; Gonzalez, V.; Ormazabal, A.; Pineda, M.; Fernandez-Alvarez, E.; Campistol, J. M. D.; Artuch, R. M. D.

    2007-01-01

    Neurotransmitters are essential in young children for differentiation and neuronal growth of the developing nervous system. We aimed to identify possible factors related to secondary neurotransmitter abnormalities in pediatric patients with neurological disorders. We analyzed cerebrospinal fluid (CSF) and biogenic amine metabolites in 56 infants…

  17. Brain Monoamine Oxidase-A Activity Predicts Trait Aggression

    Science.gov (United States)

    Alia-Klein, Nelly; Goldstein, Rita Z.; Kriplani, Aarti; Logan, Jean; Tomasi, Dardo; Williams, Benjamin; Telang, Frank; Shumay, Elena; Biegon, Anat; Craig, Ian W.; Henn, Fritz; Wang, Gene-Jack; Volkow, Nora D.; Fowler, Joanna S.

    2008-01-01

    The genetic deletion of monoamine oxidase A (MAO A, an enzyme which breaks down the monoamine neurotransmitters norepinephrine, serotonin and dopamine) produces aggressive phenotypes across species. Therefore, a common polymorphism in the MAO A gene (MAOA, MIM 309850, referred to as high or low based on transcription in non-neuronal cells) has been investigated in a number of externalizing behavioral and clinical phenotypes. These studies provide evidence linking the low MAOA genotype and violent behavior but only through interaction with severe environmental stressors during childhood. Here, we hypothesized that in healthy adult males the gene product of MAO A in the brain, rather than the gene per se, would be associated with regulating the concentration of brain amines involved in trait aggression. Brain MAO A activity was measured in-vivo in healthy non-smoking men with positron emission tomography using a radioligand specific for MAO A (clorgyline labeled with carbon 11). Trait aggression was measured with the Multidimensional Personality Questionnaire (MPQ). Here we report for the first time that brain MAO A correlates inversely with the MPQ trait measure of aggression (but not with other personality traits) such that the lower the MAO A activity in cortical and subcortical brain regions the higher the self-reported aggression (in both MAOA genotype groups) contributing to more than a third of the variability. Since trait aggression is a measure used to predict antisocial behavior, these results underscore the relevance of MAO A as a neurochemical substrate of aberrant aggression. PMID:18463263

  18. Radiochemistry devoted to the production of monoamine oxidase (MAO-A and MAO-B) ligands for brain imaging with positron emission tomography.

    Science.gov (United States)

    Kersemans, Ken; Van Laeken, Nick; De Vos, Filip

    2013-01-01

    Monoamine oxidase (MAO) belongs to a family of flavin-containing integral enzymes that are present in the outer mitochondrial membrane in neurons and glial cells in the central nervous system. These enzymes catalyze the oxidative deamination of various neurotransmitters, biogenic amines, and xenobiotics, thereby influencing their availability and physiological activity in brain and body. Over the past decades, many potential positron emission tomography tracers have been put forward to visualize MAO in the brain with varying success, and recent publications on the topic illustrate the continuing interest in the field. The present review gives an overview of the compounds that have been put forward as possible MAO tracers in the brain and focuses on the radiochemical procedures that have been developed to produce them up till now. Relevant radioligands are grouped by the main radiochemical strategies that have been employed to synthesize them, and some interesting details and findings that are crucial to the radiosyntheses are provided.

  19. In vitro screening of major neurotransmitter systems possibly involved in the mechanism of action of antibodies to S100 protein in released-active form

    Directory of Open Access Journals (Sweden)

    Gorbunov EA

    2015-11-01

    Full Text Available Evgeniy A Gorbunov, Irina A Ertuzun, Evgeniya V Kachaeva, Sergey A Tarasov, Oleg I EpsteinOOO “NPF “MATERIA MEDICA HOLDING”, Moscow, Russian FederationAbstract: Experimentally and clinically, it was shown that released-active form of antibodies to S100 protein (RAF of Abs to S100 exerts a wide range of pharmacological activities: anxiolytic, antiasthenic, antiaggressive, stress-protective, antihypoxic, antiischemic, neuroprotective, and nootropic. The purpose of this study was to determine the influence of RAF of Abs to S100 on major neurotransmitter systems (serotoninergic, GABAergic, dopaminergic, and on sigma receptors as well which are possibly involved in its mechanism of pharmacological activity. Radioligand binding assays were used for assessment of the drug influence on ligand–receptor interaction. [35S]GTPγS binding assay, cyclic adenosine monophosphate HTRF™, cellular dielectric spectroscopy assays, and assays based on measurement of intracellular concentration of Ca2+ ions were used for assessment of agonist or antagonist properties of the drug toward receptors. RAF of Abs to S100 increased radioligand binding to 5-HT1F, 5-HT2B, 5-HT2Cedited, 5-HT3, and to D3 receptors by 142.0%, 131.9%, 149.3%, 120.7%, and 126.3%, respectively. Also, the drug significantly inhibited specific binding of radioligands to GABAB1A/B2 receptors by 25.8%, and to both native and recombinant human sigma1 receptors by 75.3% and 40.32%, respectively. In the functional assays, it was shown that the drug exerted antagonism at 5-HT1B, D3, and GABAB1A/B2 receptors inhibiting agonist-induced responses by 23.24%, 32.76%, and 30.2%, respectively. On the contrary, the drug exerted an agonist effect at 5-HT1A receptors enhancing receptor functional activity by 28.0%. The pharmacological profiling of RAF of Abs to S100 among 27 receptor provides evidence for drug-related modification of major neurotransmitter systems.Keywords: dopamine agent, released

  20. Effect of acute swim stress on plasma corticosterone and brain monoamine levels in bidirectionally selected DxH recombinant inbred mouse strains differing in fear recall and extinction.

    Science.gov (United States)

    Browne, Caroline A; Hanke, Joachim; Rose, Claudia; Walsh, Irene; Foley, Tara; Clarke, Gerard; Schwegler, Herbert; Cryan, John F; Yilmazer-Hanke, Deniz

    2014-12-01

    Stress-induced changes in plasma corticosterone and central monoamine levels were examined in mouse strains that differ in fear-related behaviors. Two DxH recombinant inbred mouse strains with a DBA/2J background, which were originally bred for a high (H-FSS) and low fear-sensitized acoustic startle reflex (L-FSS), were used. Levels of noradrenaline, dopamine, and serotonin and their metabolites 3,4-dihydroxyphenyacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA) were studied in the amygdala, hippocampus, medial prefrontal cortex, striatum, hypothalamus and brainstem. H-FSS mice exhibited increased fear levels and a deficit in fear extinction (within-session) in the auditory fear-conditioning test, and depressive-like behavior in the acute forced swim stress test. They had higher tissue noradrenaline and serotonin levels and lower dopamine and serotonin turnover under basal conditions, although they were largely insensitive to stress-induced changes in neurotransmitter metabolism. In contrast, acute swim stress increased monoamine levels but decreased turnover in the less fearful L-FSS mice. L-FSS mice also showed a trend toward higher basal and stress-induced corticosterone levels and an increase in noradrenaline and serotonin in the hypothalamus and brainstem 30 min after stress compared to H-FSS mice. Moreover, the dopaminergic system was activated differentially in the medial prefrontal cortex and striatum of the two strains by acute stress. Thus, H-FSS mice showed increased basal noradrenaline tissue levels compatible with a fear phenotype or chronic stressed condition. Low corticosterone levels and the poor monoamine response to stress in H-FSS mice may point to mechanisms similar to those found in principal fear disorders or post-traumatic stress disorder.

  1. The Role of Neurotrophins in Neurotransmitter Release

    OpenAIRE

    William J Tyler; Perrett, Stephen P.; Pozzo-Miller, Lucas D.

    2002-01-01

    The neurotrophins (NTs) have recently been shown to elicit pronounced effects on quantal neurotransmitter release at both central and peripheral nervous system synapses. Due to their activity-dependent release, as well as the subcellular localization of both protein and receptor, NTs are ideally suited to modify the strength of neuronal connections by “fine-tuning” synaptic activity through direct actions at presynaptic terminals. Here, using BDNF as a prototypical example, the authors provid...

  2. Neurotransmitters and putative neuromodulators in the gut of Anguilla anguilla (L.. Localizations in the enteric nervous and endocrine systems

    Directory of Open Access Journals (Sweden)

    A Veggetti

    2009-12-01

    Full Text Available The gut of silver eels (Anguilla anguilla L. was investigated in order to describe both the cholinergic and adrenergic intramural innervations, and the localization of possible accessory neuromediators. Histochemical reactions for the demonstration of nicotinamide adenine dinucleotide phosphate, reduced form-(NADPH-diaphorase and acetylcholinesterese (AChEase were performed, as well as the immunohistochemical testing of tyrosine hydroxylase, met-enkephalin, substance P, calcitonin gene-related peptide (CGRP, bombesin, vasoactive intestinal peptide (VIP, neuropeptide Y (NPY, somatostatin, cholecystokinin-octapeptide (CCK-8, serotonin, cholineacetyltransferase. The results evidenced a different pattern in comparison with other vertebrates, namely mammals, and with other fish. Both NADPH-diaphorase and AChEase activities were histochemically detected all along the gut in the myenteric plexus, the inner musculature and the propria-submucosa. Tyrosine hydroxylase immunoreactivity was observed in the intestinal tract only, both in the myenteric plexus and in the inner musculature. Several neuropeptides (metenkephalin, CGRP, bombesin, substance P, VIP, NPY, somatostatin were, in addition, detected in the intramural innervation; some of them also in epithelial cells of the diffuse endocrine system (met-enkephalin, substance P, NPY, somatostatin. Serotonin was only present in endocrine cells. Tyrosine hydroxylase immunoreactivity was present in localizations to those of similar NADPHdiaphorase- reactivity, and in the same nerve bundles in which substance P- and CGRP-likeimmunoreactivities were detectable in the intestinal tract. In addition, NADPH-diaphorase-reactive neurons showed an anatomical relationship with AChEase-reactive nerve terminals, and a similar relationship existed between the latter and substance P-like immunoreactivity.

  3. Sympathetic nervous system catecholamines and neuropeptide Y neurotransmitters are upregulated in human NAFLD and modulate the fibrogenic function of hepatic stellate cells.

    Directory of Open Access Journals (Sweden)

    Barbara Sigala

    Full Text Available BACKGROUND: Sympathetic nervous system (SNS signalling regulates murine hepatic fibrogenesis through effects on hepatic stellate cells (HSC, and obesity-related hypertension with SNS activation accelerates progression of non-alcoholic fatty liver disease (NAFLD, the commonest cause of chronic liver disease. NAFLD may lead to cirrhosis. The effects of the SNS neurotransmitters norepinephrine (NE, epinephrine (EPI and neuropeptide Y (NPY on human primary HSC (hHSC function and in NAFLD pathogenesis are poorly understood. AIMS: to determine the mechanistic effects of NE/EPI/NPY on phenotypic changes in cultured hHSC, and to study SNS signalling in human NAFLD livers. METHODS: Freshly isolated hHSC were assessed for expression of cathecholamine/neuropeptide Y receptors and for the synthesis of NE/EPI. The effects of NE/EPI/NPY and adrenoceptor antagonists prazosin (PRZ/propranolol (PRL on hHSC fibrogenic functions and the involved kinases and interleukin pathways were examined. Human livers with proven NAFLD were then assessed for upregulation of SNS signalling components. RESULTS: Activated hHSC express functional α/β-adrenoceptors and NPY receptors, which are upregulated in the livers of patients with cirrhotic NAFLD. hHSC in culture synthesize and release NE/EPI, required for their optimal basal growth and survival. Exogenous NE/EPI and NPY dose-dependently induced hHSC proliferation, mediated via p38 MAP, PI3K and MEK signalling. NE and EPI but not NPY increased expression of collagen-1α2 via TGF-β without involvement of the pro-fibrogenic cytokines leptin, IL-4 and IL-13 or the anti-fibrotic cytokine IL-10. CONCLUSIONS: hHSC synthesize and require cathecholamines for optimal survival and fibrogenic functionality. Activated hHSC express directly fibrogenic α/β-adrenoceptors and NPY receptors, upregulated in human cirrhotic NAFLD. Adrenoceptor and NPY antagonists may be novel anti-fibrotic agents in human NAFLD.

  4. Neurotensin. Immunohistochemical localization in central and peripheral nervous system and in endocrine cells and its functional role as neurotransmitter and endocrine hormone.

    Science.gov (United States)

    Reinecke, M

    1985-01-01

    The present study attempts to compile information on the possible physiologic role of the endogenous peptide neurotensin (NT) as a hormone and/or neurotransmitter. The methodological approach is immunohistochemical localization of NT in the entero-endocrine system as well as in the central and peripheral nervous systems. The results found in the three systems are first related to the pharmalogical and physiological findings in the literature. Subsequently their significance is discussed for each organ separately before attempting a final overall interpretation. Briefly, the present study reveals the following essential findings: The occurrence and distribution of NT-IR entero-endocrine cells (N-cells) in different mammals including man, as well as in representative members of all classes of vertebrates and higher invertebrates, are analyzed and evaluated morphometrically. The NT-IR cells in all investigated species are demonstrated to be of the open type. The innervation of paravertebral and prevertebral ganglia by NT-IR fibers is described; at least a portion of these fibers is thought to originate in NT-IR perikarya of the substantia intermedia of the spinal cord. The involvement of these NT-IR fibers in the regulation of systemic blood flow (hypertension) is suggested. The existence of NT-IR innervation of the gastro-intestinal tract is considered to be a general phenomenon. This notion is reaffirmed by phylogenetic investigation of the NT-IR enteric nerves. The pharmacological effects of NT in different portions of the gastro-intestinal tract, reported in the literature are related to the immunohistochemical localization of NT. In light of the present results, some of the effects of NT which were previously considered to be of an endocrine or paracrine nature - such as contraction of the guinea-pig ileum - are interpreted as effects of NT of neuronal origin. The specific NT-IR innervation of target cells in the exocrine pancreas (vascular smooth muscle, acinar

  5. Effect of canagliflozin and metformin on cortical neurotransmitters in a diabetic rat model.

    Science.gov (United States)

    Arafa, Nadia M S; Marie, Mohamed-Assem S; AlAzimi, Sara Abdullah Mubarak

    2016-10-25

    The rapid economic development in the Arabian Gulf has resulted in lifestyle changes that have increased the prevalence of obesity and type 2 diabetes, with the greatest increases observed in Kuwait. Dyslipidemia and diabetes are risk factors for disruptions in cortical neurotransmitter homeostasis. This study investigated the effect of the antidiabetic medications canagliflozin (CAN) and metformin (MET) on the levels of cortical neurotransmitters in a diabetic rat model. The rats were assigned to the control (C) group, the diabetic group that did not receive treatment (D) or the diabetic group treated with either CAN (10 mg/kg) or MET (100 mg/kg) for 2 or 4 weeks. Blood and urine glucose levels and cortical acetylcholinesterase (AChE) activity were assayed, and amino acid and monoamine levels were measured using HPLC. The diabetic group exhibited a significant increase in AChE activity and a decrease in monoamine and amino acid neurotransmitter levels. In the CAN group, AChE was significantly lower than that in the D and D + MET groups after 2 weeks of treatment. In addition, a significant increase in some cortical monoamines and amino acids was observed in the D + MET and D + CAN groups compared with the D group. Histopathological analysis revealed the presence of severe focal hemorrhage, neuronal degeneration, and cerebral blood vessel congestion, with gliosis in the cerebrum of rats in the D group. The CAN-treated group exhibited severe cerebral blood vessel congestion after 2 weeks of treatment and focal gliosis in the cerebrum after 4 weeks of treatment. Focal gliosis in the cerebrum of rats in the MET-treated group was observed after 2 and 4 weeks of treatment. We conclude that the effect of CAN and MET on neurotransmitters is potentially mediated by their antihyperglycemic and antihyperlipidemic effects. In addition, the effects of CAN on neurotransmitters might be associated with its receptor activity, and the effect of MET on neurotransmitters

  6. Dynamic neurotransmitter interactions measured with PET

    Energy Technology Data Exchange (ETDEWEB)

    Schiffer, W.K.; Dewey, S.L.

    2001-04-02

    Positron emission tomography (PET) has become a valuable interdisciplinary tool for understanding physiological, biochemical and pharmacological functions at a molecular level in living humans, whether in a healthy or diseased state. The utility of tracing chemical activity through the body transcends the fields of cardiology, oncology, neurology and psychiatry. In this, PET techniques span radiochemistry and radiopharmaceutical development to instrumentation, image analysis, anatomy and modeling. PET has made substantial contributions in each of these fields by providing a,venue for mapping dynamic functions of healthy and unhealthy human anatomy. As diverse as the disciplines it bridges, PET has provided insight into an equally significant variety of psychiatric disorders. Using the unique quantitative ability of PET, researchers are now better able to non-invasively characterize normally occurring neurotransmitter interactions in the brain. With the knowledge that these interactions provide the fundamental basis for brain response, many investigators have recently focused their efforts on an examination of the communication between these chemicals in both healthy volunteers and individuals suffering from diseases classically defined as neurotransmitter specific in nature. In addition, PET can measure the biochemical dynamics of acute and sustained drug abuse. Thus, PET studies of neurotransmitter interactions enable investigators to describe a multitude of specific functional interactions in the human brain. This information can then be applied to understanding side effects that occur in response to acute and chronic drug therapy, and to designing new drugs that target multiple systems as opposed to single receptor types. Knowledge derived from PET studies can be applied to drug discovery, research and development (for review, see (Fowler et al., 1999) and (Burns et al., 1999)). Here, we will cover the most substantial contributions of PET to understanding

  7. Neurotransmitter: Sodium Symporters: Caught in the Act!

    DEFF Research Database (Denmark)

    Malinauskaite, Lina

    The neurotransmitter: sodium symporters in the neurons. Communication between neurons is mediated by the release of molecules called neurotransmitters (blue dots) from first neuron and sensed by receptors on the surface of the second (purple sphere). The signal is ended by active reuptake...... of these neurotransmitters by a family of proteins called neurotransmitter: sodium symporters (NSS), which are driven using the large concentration difference of sodium (orange dots) between the outside and the inside of the cell...

  8. Cognitive abnormalities and hippocampal alterations in monoamine oxidase A and B knockout mice.

    Science.gov (United States)

    Singh, Chanpreet; Bortolato, Marco; Bali, Namrata; Godar, Sean C; Scott, Anna L; Chen, Kevin; Thompson, Richard F; Shih, Jean C

    2013-07-30

    The monoamine oxidase isoenzymes (MAOs) A and B play important roles in the homeostasis of monoaminergic neurotransmitters. The combined deficiency of MAO A and B results in significantly elevated levels of serotonin (5-hydroxytryptamine), norepinephrine, dopamine, and β-phenylethylamine; in humans and mice, these neurochemical changes are accompanied by neurodevelopmental perturbations as well as autistic-like responses. Ample evidence indicates that normal levels of monoamines in the hippocampus, amygdala, frontal cortex, and cerebellum are required for the integrity of learning and memory. Thus, in the present study, the cognitive status of MAO A/B knockout (KO) mice was examined with a wide array of behavioral tests. In comparison with male wild-type littermates, MAO A/B KO mice exhibited abnormally high and overgeneralized fear conditioning and enhanced eye-blink conditioning. These alterations were accompanied by significant increases in hippocampal long-term potentiation and alterations in the relative expression of NMDA glutamate receptor subunits. Our data suggest that chronic elevations of monoamines, because of the absence of MAO A and MAO B, cause functional alterations that are accompanied with changes in the cellular mechanisms underlying learning and memory. The characteristics exhibited by MAO A/B KO mice highlight the potential of these animals as a useful tool to provide further insight into the molecular bases of disorders associated with abnormal monoaminergic profiles.

  9. Calcium-sensing beyond neurotransmitters

    DEFF Research Database (Denmark)

    Gustavsson, Natalia; Han, Weiping

    2009-01-01

    synaptotagmins are located in brain and endocrine cells, and some of these synaptotagmins bind to phospholipids and calcium at levels that trigger regulated exocytosis of SVs and LDCVs. This led to the proposed synaptotagmin-calcium-sensor paradigm, that is, members of the synaptotagmin family function...... as calcium sensors for the regulated exocytosis of neurotransmitters, neuropeptides and hormones. Here, we provide an overview of the synaptotagmin family, and review the recent mouse genetic studies aimed at understanding the functions of synaptotagmins in neurotransmission and endocrine-hormone secretion......Neurotransmitters, neuropeptides and hormones are released through the regulated exocytosis of SVs (synaptic vesicles) and LDCVs (large dense-core vesicles), a process that is controlled by calcium. Synaptotagmins are a family of type 1 membrane proteins that share a common domain structure. Most...

  10. Synthetic and Natural Monoamine Oxidase Inhibitors as Potential Lead Compounds for Effective Therapeutics.

    Science.gov (United States)

    Pathak, Ashish; Srivastava, Amit K; Singour, Pradeep K; Gouda, Panchanan

    2016-01-01

    Monoamine oxidases A and B (MAO-A and B) play a critical role in the metabolism of intracellular neurotransmitters of the central nervous system. For decades, MAO inhibitors have proven their clinical efficacy as potential drug targets for several neurological and neurodegenerative diseases. Use of first generation non selective MAO inhibitors as neuropsychiatric drugs elicited several side effects like hypertensive crisis and cheese reaction. Therefore their use is now limited due to non-selectivity towards MAO isoforms and inhibition of metabolizing enzymes like cytochrome P450. Development of selective and specific MAO inhibitors like moclobemide, toloxatone improves their efficacy as disease-modifying effects in monotherapy as well as adjunctive therapy. Recently a lot of research has been done to elucidate the pharmacological potential of medicinal plants and their isolated bioactive constituents having MAO inhibitory activity. Herbs containing MAO inhibitors are extensively used for the development of potent synthetic drugs and as safe and effective alternatives to the available synthetic drugs in the treatment of neurodegenerative diseases such as depression, Parkinson and Alzheimer's. In several diseases like Parkinson natural MAO inhibitors prevented the neuron denaturalization by their dual action via enhancing neurotransmission of dopamine as well as lowering the generation of free radicals and toxins. Currently development of selective MAO inhibitors is still under study to achieve more effective therapies by using Computer Aided Drug Designing, Ligand-based models and structure-activity hypothesis. These approaches also facilitate understanding the interaction of newly designed molecule with MAO enzymes and the rationalization of probable mechanisms of action.

  11. Regional brain monoamine concentrations and their alterations in bovine hypomagnesaemic tetany experimentally induced by a magnesium-deficient diet.

    Science.gov (United States)

    McCoy, M A; Young, P B; Hudson, A J; Davison, G; Kennedy, D G

    2000-12-01

    Monoamines are important brain neurotransmitters. An investigation was carried out to determine if hypomagnesaemic tetany was associated with alterations in regional brain monoamine concentrations in bovines. The results, established in cows with normal magnesium status, demonstrated that regional differences existed in the distribution and concentration of brain monoamines in the adult bovine, which were similar to those in other species. In magnesium-deficient cows, severe hypomagnesaemia and lowered cerebrospinal fluid (CSF) magnesium concentrations were associated with significant alterations in monoamine concentrations in some brain regions. Alterations in 3,4-dihydroxyphenylalanine (DOPA) and dihydroxyphenylacetic acid (DOPAC) concentrations in the corpus striatum, and dopamine (DA) in the cerebral cortex and cerebellum were recorded. These regions play an important role in both voluntary and involuntary motor function, and therefore these alterations may play a role in the aetiology of hypomagnesaemic tetany. However, there was no significant change in DA concentrations in the corpus striatum (the main dopaminergic region in the brain) associated with hypomagnesaemia. In addition, a significantly lower norepinephrine (NE) concentration in the corpus striatum of hypomagnesaemic animals was also recorded. Norephinephrine is generally excitatory and therefore lowered NE concentrations would be expected to result in depression rather than stimulation of motor function. Copyright 2000 Harcourt Publishers Ltd.

  12. NEUROTRANSMITTERS AND IMMUNITY: 1. DOPAMINE

    Directory of Open Access Journals (Sweden)

    Lucian Hritcu

    2007-08-01

    Full Text Available Dopamine is one of the principal neurotransmitters in the central nervous system (CNC, and its neuronal pathways are involved in several key functions such as behavior (Hefco et al., 2003a,b, control of movement, endocrine regulation, immune response (Fiserova et al., 2002; Levite et al., 2001, Hritcu et al., 2006a,b,c, and cardiovascular function. Dopamine has at least five G-protein, coupled receptor subtypes, D1-D5, each arising from a different gene (Sibley et al., 1993. Traditionally, these receptors have been classified into D1-like (the D1 and D5 and D2-like (D2, D3 and D4 receptors subtypes, primarily according to their ability to stimulate or inhibit adenylate cyclase, respectively, and to their pharmacological characteristics (Seeman et al., 1993. Receptors for dopamine (particularly of D2 subclass are the primary therapeutic target in a number of neuropathological disorders including schizophrenia, Parkinson’s disease and Huntington’s chorea (Seeman et al., 1987. Neither dopamine by itself, nor dopaminergic agonists by themselves, has been shown to activate T cell function. Nevertheless, lymphocytes are most probably exposed to dopamine since the primary and secondary lymphoid organs of various mammals are markedly innervated, and contain nerve fibers which stain for tyrosine hydroxylase (Weihe et al., 1991, the enzyme responsible for dopamine synthesis. Moreover, cathecolamines and their metabolites are present in single lymphocytes and in extracts of T and B cell clones, and pharmacological inhibition of tyrosine hydroxylase reduces catecholamine levels, suggesting catecholamine synthesis by lymphocytes (Bergquist et al., 1994. The existence of putative dopamine receptors of D2, D3, D4 and D5 subtypes on immune cells has been proposed of several authors, primarily on the basis of dopaminergic ligand binding assays and specific mRNA expression as monitored by reverse transcription-PCR. Several experiments evoked the idea of a

  13. The Role of Neurotrophins in Neurotransmitter Release

    Science.gov (United States)

    Tyler, William J.; Perrett, Stephen P.; Pozzo-Miller, Lucas D.

    2009-01-01

    The neurotrophins (NTs) have recently been shown to elicit pronounced effects on quantal neurotransmitter release at both central and peripheral nervous system synapses. Due to their activity-dependent release, as well as the subcellular localization of both protein and receptor, NTs are ideally suited to modify the strength of neuronal connections by “fine-tuning” synaptic activity through direct actions at presynaptic terminals. Here, using BDNF as a prototypical example, the authors provide an update of recent evidence demonstrating that NTs enhance quantal neurotransmitter release at synapses through presynaptic mechanisms. The authors further propose that a potential target for NT actions at presynaptic terminals is the mechanism by which terminals retrieve synaptic vesicles after exocytosis. Depending on the temporal demands placed on synapses during high-frequency synaptic transmission, synapses may use two alternative modes of synaptic vesicle retrieval, the conventional slow endosomal recycling or a faster rapid retrieval at the active zone, referred to as “kiss-and-run.” By modulating Ca2+ microdomains associated with voltage-gated Ca2+ channels at active zones, NTs may elicit a switch from the slow to the fast mode of endocytosis of vesicles at presynaptic terminals during high-frequency synaptic transmission, allowing more reliable information transfer and neuronal signaling in the central nervous system. PMID:12467374

  14. Monoamine theories of depression: historical impact on biomedical research.

    Science.gov (United States)

    Mulinari, Shai

    2012-01-01

    Monoamine theories associate depression with reduced brain monoamine levels. These theories achieved broad popularity in the mid-1960s. The present article reviews the historical development of monoamine theories and their subsequent impact on biomedical research. Alleged divisions between West European and US researchers over competing versions of the theories are investigated using bibliometrics. Subsequently, the application of monoamine theories in the NIMH Collaborative Program on the Psychobiology of Depression is covered. The article argues that the impact of monoamine theories is best explained by the ability of researchers, governmental agencies, and pharmaceutical companies to invoke theories that advance various projects and agendas.

  15. The effects of non-medically used psychoactive drugs on monoamine neurotransmission in rat brain.

    Science.gov (United States)

    Nagai, Fumiko; Nonaka, Ryouichi; Satoh Hisashi Kamimura, Kanako

    2007-03-22

    We developed a reproducible, simple, and small-scale method for determining the re-uptake and release of monoamines (dopamine, serotonin (5-HT) and norepinephrine) using rat brain synaptosomes. These assays were then applied to study the effects of different kinds of non-medically used psychoactive drugs on monoamine re-uptake and release. The phenethylamine derivatives, 4-fluoroamphetamine, 2-methylamino-3,4-methylene-dioxy-propiophenone (methylone), 1-(1,3-benzodioxol-5-yl)-2-butanamine (BDB), and N-methyl-1-(1,3-benzodioxol-5-yl)-2-butanamine (MBDB), had strong inhibitory effects on the re-uptake of dopamine, 5-HT and norepinephrine. 4-Fluoroamphetamine, methylone and BDB also strongly increased the release of the three monoamines, but MBDB increased 5-HT and norepinephrine release, but had little effect on dopamine release. However, 2,5-dimethoxy-4-iodophenethylamine (2C-I), 2,5-dimethoxy-4-ethylphenethylamine (2C-E), 2,5-dimethoxy-4-chlorophenethylamine (2C-C), 2,4,5-trimethoxyamphetamine (TMA-2) and 2,4,6-trimethoxyamphetamine (TMA-6), which are methoxylated phenethylamine derivatives, slightly influenced the re-uptake and release of monoamines. Alpha-metyltryptamine (AMT), a tryptamine derivative, was one of the strongest re-uptake inhibitors and releasers of the three monoamines. The tryptamine derivative, 5-methoxy-alpha-methyltryptamine (5-MeO-AMT), also strongly inhibited re-uptake and increased the release of the three monoamines. N,N-dipropyltryptamine (DPT), 5-methoxy-N,N-diisopropyltryptamine (5-MeO-DIPT), 5-methoxy-N,N-methylisopropyltryptamine (5-MeO-MIPT), and 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) inhibited monoamine re-uptake, but had a few effects on monoamine release. 1-(3-Chlorophenyl)piperazine (3CPP) and 1-(methoxyphenyl)piperazine (4MPP), which are piperazine derivatives, inhibited monoamine re-uptake and accelerated their release. The results suggest that some designer drugs strongly act on the central nerve system to the same

  16. Neurotransmitters, Pharmacologic Synergy, and Clinical Strategies

    National Research Council Canada - National Science Library

    Stark, Martha

    2006-01-01

    ... of neurotransmitters and their receptor sites, more ingenious methods of drug administration, and more creative combinations of the various drugs, more than half our patients have psychiatric sympto...

  17. Neurodevelopmental Animal Models Reveal the Convergent Role of Neurotransmitter Systems, Inflammation, and Oxidative Stress as Biomarkers of Schizophrenia: Implications for Novel Drug Development.

    Science.gov (United States)

    Möller, M; Swanepoel, T; Harvey, B H

    2015-07-15

    Schizophrenia is a life altering disease with a complex etiology and pathophysiology, and although antipsychotics are valuable in treating the disorder, certain symptoms and/or sufferers remain resistant to treatment. Our poor understanding of the underlying neuropathological mechanisms of schizophrenia hinders the discovery and development of improved pharmacological treatment, so that filling these gaps is of utmost importance for an improved outcome. A vast amount of clinical data has strongly implicated the role of inflammation and oxidative insults in the pathophysiology of schizophrenia. Preclinical studies using animal models are fundamental in our understanding of disease development and pathology as well as the discovery and development of novel treatment options. In particular, social isolation rearing (SIR) and pre- or postnatal inflammation (PPNI) have shown great promise in mimicking the biobehavioral manifestations of schizophrenia. Furthermore, the "dual-hit" hypothesis of schizophrenia states that a first adverse event such as genetic predisposition or a prenatal insult renders an individual susceptible to develop the disease, while a second insult (e.g., postnatal inflammation, environmental adversity, or drug abuse) may be necessary to precipitate the full-blown syndrome. Animal models that emphasize the "dual-hit" hypothesis therefore provide valuable insight into understanding disease progression. In this Review, we will discuss SIR, PPNI, as well as possible "dual-hit" animal models within the context of the redox-immune-inflammatory hypothesis of schizophrenia, correlating such changes with the recognized monoamine and behavioral alterations of schizophrenia. Finally, based on these models, we will review new therapeutic options, especially those targeting immune-inflammatory and redox pathways.

  18. Chloride binding site of neurotransmitter sodium symporters

    DEFF Research Database (Denmark)

    Kantcheva, Adriana Krassimirova; Quick, Matthias; Shi, Lei

    2013-01-01

    Neurotransmitter:sodium symporters (NSSs) play a critical role in signaling by reuptake of neurotransmitters. Eukaryotic NSSs are chloride-dependent, whereas prokaryotic NSS homologs like LeuT are chloride-independent but contain an acidic residue (Glu290 in LeuT) at a site where eukaryotic NSSs...

  19. Monoamine oxidase A is highly expressed in classical Hodgkin lymphoma.

    Science.gov (United States)

    Li, Pei Chuan; Siddiqi, Imran N; Mottok, Anja; Loo, Eric Y; Wu, Chieh Hsi; Cozen, Wendy; Steidl, Christian; Shih, Jean Chen

    2017-10-01

    Monoamine oxidase A (MAOA) is a mitochondrial enzyme that catalyzes oxidative deamination of neurotransmitters and dietary amines and produces H2 O2 . It facilitates the progression of gliomas and prostate cancer, but its expression and functional relevance have not been studied in lymphoma. Here, we evaluated MAOA in 427 cases of Hodgkin and non-Hodgkin lymphoma and in a spectrum of reactive lymphoid tissues by immunohistochemistry on formalin-fixed, paraffin-embedded specimens. MAOA was expressed by Hodgkin Reed-Sternberg (HRS) cells in the majority of classical Hodgkin lymphomas (cHLs) (181/241; 75%), with 34.8% showing strong expression. Weak MAOA was also noted in a minority of primary mediastinal large B-cell lymphomas (8/47; 17%) and in a mediastinal gray-zone lymphoma. In contrast, no MAOA was found in non-neoplastic lymphoid tissues, nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL; 0/8) or any other non-Hodgkin lymphomas studied (0/123). MAOA was more common in Epstein-Barr virus (EBV)-negative compared to EBV-positive cHL (p Hodgkin-lymphoma-derived cell lines did not. The MAOA inhibitor clorgyline reduced the growth of L1236 cells and U-HO1 cells, and shRNA knockdown of MAOA reduced the growth of L1236 cells. Conversely, ectopic overexpression of MAOA increased the growth of MAOA-negative HDLM2 cells. Combined treatment with clorgyline and ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) was more effective in reducing cell growth than either regimen alone. In summary, MAOA is highly expressed in cHL and may reflect the distinct biology of this lymphoma. Further studies on the potential utility of MAOA as a diagnostic marker and therapeutic target are warranted. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  20. Process characterization of a monoamine oxidase

    DEFF Research Database (Denmark)

    Ramesh, Hemalata; Woodley, John

    2014-01-01

    .e, on biocatalyst development (e.g. improvement of expression levels), process development (e.g. improved oxygen supply, product removal strategies) or biocatalyst stabilization (e.g. through immobilization or directed evolution). This paper presents a systematic method to identify the bottleneck of a potential...... biocatalytic process using a monoamine oxidase to synthesise an intermediate in the manufacture of a drug for treating Hepatitis C (Telaprevir)....

  1. Imaging Monoamine Oxidase in the Human Brain

    Energy Technology Data Exchange (ETDEWEB)

    Fowler, J. S.; Volkow, N. D.; Wang, G-J.; Logan, Jean

    1999-11-10

    Positron emission tomography (PET) studies mapping monoamine oxidase in the human brain have been used to measure the turnover rate for MAO B; to determine the minimum effective dose of a new MAO inhibitor drug lazabemide and to document MAO inhibition by cigarette smoke. These studies illustrate the power of PET and radiotracer chemistry to measure normal biochemical processes and to provide information on the effect of drug exposure on specific molecular targets.

  2. The inhibition of monoamine oxidase by esomeprazole

    OpenAIRE

    2013-01-01

    Virtual screening of a library of drugs has suggested that esomeprazole, the S-enantiomer of omeprazole, may possess binding affinities for the active sites of the monoamine oxidase (MAO) A and B enzymes. Based on this finding, the current study examines the MAO inhibitory properties of esomeprazole. Using recombinant human MAO-A and MAO-B, IC50 values for the inhibition of these enzymes by esomeprazole were experimentally determined. To examine the reversibility of MAO inhibition by esomepra...

  3. Binding of Neurotransmitters to Lipid Membranes

    DEFF Research Database (Denmark)

    Peters, Günther H.J.; Werge, Mikkel; Elf-Lind, Maria Northved

    2014-01-01

    We have performed a series of thermodynamic measurements and molecular dynamics (MD) simulations to study the interactions between the neurotransmitters (NTs) 5-hydroxytryptamine (5-HT), g-aminobutyrate (GABA), glycine (GLY), acetylcholine (ACH) and glutamate (GLU) as well as the amidated...... as the most important interaction by which the NTs are anchored to the membrane. These distinctive interactions could be related to nonspecific effects of these neurotransmitters and could point to a bilayer-mediated modulation of nerve transmission. However, due to the strong variability in affinity observed...... for the different NTs, this attraction is not an inherent property of all neurotransmitters....

  4. Inherited disorders of brain neurotransmitters: pathogenesis and diagnostic approach.

    Science.gov (United States)

    Szymańska, Krystyna; Kuśmierska, Katarzyna; Demkow, Urszula

    2015-01-01

    Neurotransmitters (NTs) play a central role in the efficient communication between neurons necessary for normal functioning of the nervous system. NTs can be divided into two groups: small molecule NTs and larger neuropeptide NTs. Inherited disorders of NTs result from a primary disturbance of NTs metabolism or transport. This group of disorders requires sophisticated diagnostic procedures. In this review we discuss disturbances in the metabolism of tetrahydrobiopterin, biogenic amines, γ-aminobutyric acid, foliate, pyridoxine-dependent enzymes, and also the glycine-dependent encephalopathy. We point to pathologic alterations of proteins involved in synaptic neurotransmission that may cause neurological and psychiatric symptoms. We postulate that synaptic receptors and transporter proteins for neurotransmitters should be investigated in unresolved cases. Patients with inherited neurotransmitters disorders present various clinical presentations such as mental retardation, refractory seizures, pyramidal and extrapyramidal syndromes, impaired locomotor patterns, and progressive encephalopathy. Every patient with suspected inherited neurotransmitter disorder should undergo a structured interview and a careful examination including neurological, biochemical, and imaging.

  5. Analysis of microdialysate monoamines, including noradrenaline, dopamine and serotonin, using capillary ultra-high performance liquid chromatography and electrochemical detection.

    Science.gov (United States)

    Ferry, Barbara; Gifu, Elena-Patricia; Sandu, Ioana; Denoroy, Luc; Parrot, Sandrine

    2014-03-01

    Electrochemical methods are very often used to detect catecholamine and indolamine neurotransmitters separated by conventional reverse-phase high performance liquid chromatography (HPLC). The present paper presents the development of a chromatographic method to detect monoamines present in low-volume brain dialysis samples using a capillary column filled with sub-2μm particles. Several parameters (repeatability, linearity, accuracy, limit of detection) for this new ultrahigh performance liquid chromatography (UHPLC) method with electrochemical detection were examined after optimization of the analytical conditions. Noradrenaline, adrenaline, serotonin, dopamine and its metabolite 3-methoxytyramine were separated in 1μL of injected sample volume; they were detected above concentrations of 0.5-1nmol/L, with 2.1-9.5% accuracy and intra-assay repeatability equal to or less than 6%. The final method was applied to very low volume dialysates from rat brain containing monoamine traces. The study demonstrates that capillary UHPLC with electrochemical detection is suitable for monitoring dialysate monoamines collected at high sampling rate.

  6. Prion-derived copper-binding peptide fragments catalyze the generation of superoxide anion in the presence of aromatic monoamines

    Directory of Open Access Journals (Sweden)

    Tomonori Kawano

    2007-01-01

    Full Text Available Objectives: Studies have proposed two opposing roles for copper-bound forms of prion protein (PrP as an anti-oxidant supporting the neuronal functions and as a pro-oxidant leading to neurodegenerative process involving the generation of reactive oxygen species. The aim of this study is to test the hypothesis in which putative copper-binding peptides derived from PrP function as possible catalysts for monoamine-dependent conversion of hydrogen peroxide to superoxide in vitro. Materials and methods: Four peptides corresponding to the copper (II-binding motifs in PrP were synthesized and used for analysis of peptide-catalyzed generation of superoxide in the presence of Cu (II and other factors naturally present in the neuronal tissues. Results: Among the Cu-binding peptides tested, the amino acid sequence corresponding to the Cu-binding site in the helical region was shown to be the most active for superoxide generation in the presence of Cu(II, hydrogen peroxide and aromatic monoamines, known precursors or intermediates of neurotransmitters. Among monoamines tested, three compounds namely phenylethylamine, tyramine and benzylamine were shown to be good substrates for superoxide-generating reactions by the Cu-bound helical peptide. Conclusions: Possible roles for these reactions in development of prion disease were suggested.

  7. Neurotransmitters and neuronal apoptotic cell death of chronically aluminum intoxicated Nile catfish (Clarias gariepinus) in response to ascorbic acid supplementation.

    Science.gov (United States)

    Khalil, Samah R; Hussein, Mohamed M A

    2015-12-01

    Few studies have been carried out to assess the neurotoxic effect of aluminum (Al) on the aquatic creatures. This study aims to evaluate the neurotoxic effects of long term Al exposure on the Nile catfish (Clarias gariepinus) and the potential ameliorative influence of ascorbic acid (ASA) over a 180 days exposure period. Forty eight Nile catfish were divided into four groups: control group, placed in clean water, ASA exposed group (5mg/l), AlCl3 received group (28.96 μg/l; 1/20 LC50), and group received AlCl3 concomitantly with ASA. Brain tissue was examined by using flow cytometry to monitor the apoptotic cell population, HPLC analysis for the quantitative estimation of brain monoamine neurotransmitters [serotonin (5-HT), dopamine (DA), norepinephrine (NE)]. The amino acid neurotransmitters [serum taurine, glycine, aspartate and glutamine and brain gamma aminobutyric acid (GABA)] levels were assessed, plus changes in brain tissue structure using light microscopy. The concentration of Al in both brain tissue and serum was determined by using atomic absorption spectrophotometery. The Al content in serum and brain tissue were both elevated and Al exposure induced an increase in the number of apoptotic cells, a marked reduction of the monoamine and amino acids neurotransmitters levels and changes in tissue morphology. ASA supplementation partially abolished the effects of AL on the reduced neurotransmitter, the degree of apoptosis and restored the morphological changes to the brain. Overall, our results indicate that, ASA is a promising neuroprotective agent against for Al-induced neurotoxicity in the Nile catfish.

  8. Immunocytochemical localization of monoamine oxidase type B in rat’s peripheral nervous system%单胺氧化酶B在大鼠外周神经系统中的定位

    Institute of Scientific and Technical Information of China (English)

    陈强; 徐洋

    2015-01-01

    Objective To investigate the expression of monoamine oxidase type B (MAOB)in rat’s peripheral nerv-ous system to provide morphologic basis for further study about MAOB and the relationship between axon transporta-tion and nerve impulse transduction.Methods The present study used immunohistochemical method to observe the lo-calization of MAOB in rat’s peripheral nervous system.Results Light microscopy reveals that MAOB immunoreactivi-ty is presented in epithelium above the lamina propria and lamina propria of rat’s tongue.Electron microscopy reveals that MAOB immunoreactivity is found in the myelinated axons and unmyelinated axons.MAOB immunoreactivity is al-so observed in the Schwann cell.In these MAO-B-positive structures,MAOB immunohistochemical reaction products are found on and around the mitochondrial outer membrane.Conclusion The abundeant MAOB in rat’s peripheral nervous system indicates that MAO-B plays a critical role in axon transportation and nerve impulse transduction.%目的:研究单胺氧化酶 B(MAOB)在大鼠外周神经系统中的表达,为进一步研究 MAOB 与外周神经系统中轴突运输和神经传导的关系提供形态学依据。方法采用免疫组织化学的方法,通过光镜和电镜观察 MAOB 在大鼠外周神经系统中的分布。结果光镜下,MAOB 免疫反应阳性细胞分布在舌体的上皮及固有层中。电镜下, MAOB 免疫反应阳性细胞分布在大鼠舌体有髓鞘和无髓鞘轴突中。阳性物质分布于细胞质中,准确来说为线粒体外膜上。结论 MAOB 在大鼠外周神经系统轴突的表达,提示 MAOB 可能与轴突的运输和神经传导有着非常重要的作用。

  9. Neurotransmitter and imaging studies in anorexia nervosa: new targets for treatment.

    Science.gov (United States)

    Barbarich, Nicole C; Kaye, Walter H; Jimerson, David

    2003-02-01

    Anorexia and Bulimia Nervosa are disorders of unknown etiology that invariably begin during adolescence and near in time to puberty in young women. These disorders are associated with aberrant eating behaviors, body image distortions, impulse and mood disturbances, as well as characteristic temperament and personality traits. It is well known that malnutrition produces changes in neuroendocrine function. More recently, disturbances in neuronal systems have been found to play a role in the modulation of feeding, mood, and impulse control. These neuronal systems include neuropeptides (CRH, opioids, neuropeptide-Y (NPY) and peptide YY (PYY), vasopressin and oxytocin, CCK, and leptin) and monoamines (serotonin, dopamine, norepinephrine). Disturbances of most of these neuronal systems have been found when people are ill with an eating disorder, but it was not certain whether they were a cause or consequence of symptoms. In order to address these questions, a growing number of studies have investigated whether neuromodulatory disturbances persist after recovery. Studies from several centers tend to show altered serotonin activity persists after prolonged normalization of weight, nutrition, and menstrual function, as do anxiety, obsessionality, and perfectionism. While there are fewer data, there may be persistent alterations of dopamine or some neuropeptides in some subjects in a recovered state. The inaccessibility of the central nervous system has made it difficult to understand brain and behavior. In the past decade, new tools, such as brain imaging, have offered the possibility of better characterization of complex neuronal function and behavior. Such studies have tended to consistently find that alterations of brain regions, such as the temporal lobe, occur in people who are ill with anorexia nervosa and appear to persist after some degree of weight gain and recovery. New imaging technology, that marries Positron Emission Tomography (PET) imaging with selective

  10. No changes in lymphocyte muscarinic receptors and platelet monoamine oxidase-B examined as surrogate central nervous system biomarkers in a Faroese children cohort prenatally exposed to methylmercury and polychlorinated biphenyls

    DEFF Research Database (Denmark)

    Coccini, Teresa; Manzo, Luigi; Debes, Frodi

    2009-01-01

    Experimental evidence suggests that monoamine oxidase B (MAO-B) and muscarinic cholinergic receptors (mAChRs) are involved in the pathogenesis of neurotoxicity caused by methylmercury and polychlorinated biphenyls (PCBs). Blood samples from 7-year-old exposed children were analyzed for platelet M....../or PCB exposure, whereas these markers are significantly altered in sustained exposure scenarios, as shown by clinical studies in drug addicts or patients treated with psychopharmacological agents....

  11. Vesicular monoamine transporter 2 and the acute and long-term response to 3,4-(±)-methylenedioxymethamphetamine.

    Science.gov (United States)

    Lizarraga, Lucina E; Cholanians, Aram B; Phan, Andy V; Herndon, Joseph M; Lau, Serrine S; Monks, Terrence J

    2015-01-01

    3,4-(±)-Methylenedioxymethamphetamine (MDMA, Ecstasy) is a ring-substituted amphetamine derivative with potent psychostimulant properties. The neuropharmacological effects of MDMA are biphasic in nature, initially causing synaptic monoamine release, primarily of serotonin (5-HT). Conversely, the long-term effects of MDMA manifest as prolonged depletions in 5-HT, and reductions in 5-HT reuptake transporter (SERT), indicative of serotonergic neurotoxicity. MDMA-induced 5-HT efflux relies upon disruption of vesicular monoamine storage, which increases cytosolic 5-HT concentrations available for release via a carrier-mediated mechanism. The vesicular monoamine transporter 2 (VMAT2) is responsible for packaging monoamine neurotransmitters into cytosolic vesicles. Thus, VMAT2 is a molecular target for a number of psychostimulant drugs, including methamphetamine and MDMA. We investigated the effects of depressed VMAT2 activity on the adverse responses to MDMA, via reversible inhibition of the VMAT2 protein with Ro4-1284. A single dose of MDMA (20 mg/kg, subcutaneous) induced significant hyperthermia in rats. Ro4-1284 (10 mg/kg, intraperitoneal) pretreatment prevented the thermogenic effects of MDMA, instead causing a transient decrease in body temperature. MDMA-treated rats exhibited marked increases in horizontal velocity and rearing behavior. In the presence of Ro4-1284, MDMA-mediated horizontal hyperlocomotion was delayed and attenuated, whereas rearing activity was abolished. Finally, Ro4-1284 prevented deficits in 5-HT content in rat cortex and striatum, and reduced depletions in striatal SERT staining, 7 days after MDMA administration. In summary, acute inhibition of VMAT2 by Ro4-1284 protected against MDMA-mediated hyperthermia, hyperactivity, and serotonergic neurotoxicity. The data suggest the involvement of VMAT2 in the thermoregulatory, behavioral, and neurotoxic effects of MDMA.

  12. Research progress in monoamine transporters and monoamine transmitter reuptake inhibitors%单胺转运蛋白与单胺重摄取抑制剂研究进展

    Institute of Scientific and Technical Information of China (English)

    张亭亭; 薛瑞; 李云峰; 洪浩; 张有志

    2013-01-01

    Presynaptic membrane serotonin transporters ( SERT ) and norepinephrine transporter ( NET ), which are important neurotransmitter transporters, are responsible for reuptake of released serotonin ( 5-HT ) and norepinephrine ( NE ), respectively. The major function of these transporters is to terminate monoamine transmission by mediating uptake of neurotransmitters from extracellular space into neurons and glial cells. Drugs that inhibit the activity of monoamine transporters produce increased neurotransmitter levels in the synaptic cleft, leading to their therapeutic use in depression. As SERT and NET are pharmacological targets for most antidepressants, understanding about the molecular pharmacology of these transporters, including their localization and function, molecular structure and regulation, as well as drug binding sites and mechanism of action, is important to new antidepressant development.%5-羟色胺转运蛋白(serotonin transporter,SERT)和去甲肾上腺素转运蛋白(norepinephrine transporter,NET)是单胺类神经递质转运体,其功能是将释放到突触间隙的5-羟色胺(serotonin,5-HT)和去甲肾上腺素(norepinephrine,NE)分别转运入突触前神经细胞,以终止相应的突触信号传递.SERT、NET抑制剂可阻断5-HT和NE的重摄取,提高突触间隙单胺递质水平,从而发挥抗抑郁效应.SERT、NET作为主流抗抑郁药物的作用靶标,了解其分布与功能、分子结构和活性调节因素,以及单胺重摄取抑制剂的作用机制对抗抑郁药物研发及应用具有重要意义.

  13. Dynamics of change of lipid and monoamine metabolisms and the blood coagulation system during experimental atherosclerosis caused by restriction of movement

    Science.gov (United States)

    Gvishiani, G. S.; Kobakhidze, N. G.

    1980-01-01

    Shifts in lipid, catecholamine, and blood coagulation systems following various periods (1, 2, 3, and 4 months) of experimentally induced atherosclerosis were studied. The same indices were studied in the tissues of the myocardium, liver, and brain stem-reticular formation after decapitation of the animals at the end of the experiment. Periodic motion restriction caused an increase in blood beta-lipoproteins in the rabbits at the beginning of the experiment. An increase in general cholesterol content and a decrease in the lecithincholesterol index were established at the end of the experiment. Myocardial beta-lipoprotein and brain stem reticular formation general cholesterol contents were elevated; catecholamine content was increased at the end of the experiment. In the initial months, free adrenaline basically increased, while in later months blood adrenaline decreased and blood noradrenaline increased.

  14. Liquid chromatography-mass spectrometry platform for both small neurotransmitters and neuropeptides in blood, with automatic and robust solid phase extraction

    Science.gov (United States)

    Johnsen, Elin; Leknes, Siri; Wilson, Steven Ray; Lundanes, Elsa

    2015-03-01

    Neurons communicate via chemical signals called neurotransmitters (NTs). The numerous identified NTs can have very different physiochemical properties (solubility, charge, size etc.), so quantification of the various NT classes traditionally requires several analytical platforms/methodologies. We here report that a diverse range of NTs, e.g. peptides oxytocin and vasopressin, monoamines adrenaline and serotonin, and amino acid GABA, can be simultaneously identified/measured in small samples, using an analytical platform based on liquid chromatography and high-resolution mass spectrometry (LC-MS). The automated platform is cost-efficient as manual sample preparation steps and one-time-use equipment are kept to a minimum. Zwitter-ionic HILIC stationary phases were used for both on-line solid phase extraction (SPE) and liquid chromatography (capillary format, cLC). This approach enabled compounds from all NT classes to elute in small volumes producing sharp and symmetric signals, and allowing precise quantifications of small samples, demonstrated with whole blood (100 microliters per sample). An additional robustness-enhancing feature is automatic filtration/filter back-flushing (AFFL), allowing hundreds of samples to be analyzed without any parts needing replacement. The platform can be installed by simple modification of a conventional LC-MS system.

  15. Maternal factors and monoamine changes in stress-resilient and susceptible mice: cross-fostering effects.

    Science.gov (United States)

    Prakash, Priya; Merali, Zul; Kolajova, Miroslava; Tannenbaum, Beth M; Anisman, Hymie

    2006-09-21

    Genetic factors influence stressor-provoked monoamine changes associated with anxiety and depression, but such effects might be moderated by early life experiences. To assess the contribution of maternal influences in determining adult brain monoamine responses to a stressor, strains of mice that were either stressor-reactive or -resilient (BALB/cByJ and C57BL/6ByJ, respectively) were assessed as a function of whether they were raising their biological offspring or those of the other strain. As adults, offspring were assessed with respect to stressor-provoked plasma corticosterone elevations and monoamine variations within discrete stressor-sensitive brain regions. BALB/cByJ mice demonstrated poorer maternal behaviors than C57BL/6ByJ dams, irrespective of the pups being raised. In response to a noise stressor, BALB/cByJ mice exhibited higher plasma corticosterone levels and elevated monoamine turnover in several limbic and hypothalamic sites. The stressor-provoked corticosterone increase in BALB/cByJ mice was diminished among males (but not females) raised by a C57BL/6ByJ dam. Moreover, increased prefrontal cortical dopamine utilization was attenuated among BALB/cByJ mice raised by a C57BL/6ByJ dam. These effects were asymmetrical as a C57BL/6ByJ mice raised by a BALB/cByJ dam did not exhibit increased stressor reactivity. It appears that stressors influence multiple neurochemical systems that have been implicated in anxiety and affective disorders. Although monoamine variations were largely determined by genetic factors, maternal influences contributed to stressor-elicited neurochemical changes in some regions, particularly dopamine activation within the prefrontal cortex.

  16. Short- and long-term effects of MDMA ("ecstasy") on synaptosomal and vesicular uptake of neurotransmitters in vitro and ex vivo.

    Science.gov (United States)

    Bogen, Inger Lise; Haug, Kristin Huse; Myhre, Oddvar; Fonnum, Frode

    2003-01-01

    3,4-Methylenedioxymethamphetamine (MDMA, "ecstasy") is a commonly abused drug which has been shown to be neurotoxic to serotonergic neurons in many species. The exact mechanism responsible for the neurotoxicity of MDMA is, however, poorly understood. In this study, the effects of MDMA on the synaptosomal and vesicular uptake of neurotransmitters were investigated. Our results show that MDMA (0.5-20 microM) reduces both synaptosomal and vesicular uptake of serotonin and dopamine in a dose dependent manner in vitro, while the uptake of glutamate and gamma-aminobutyric acid (GABA) remains unaffected. Ex vivo experiments support the importance of the monoamines, with predominant dopaminergic inhibition at short-term exposure (3 x 15 mg/kg; 2-h intervals), and exclusively serotonergic inhibition at long-term exposure (2 x 10 mg/kg per day; 4 days). This study also compares MDMA and the structurally related antidepressant paroxetine, in an attempt to reveal possible cellular mechanisms for the serotonergic toxicity of MDMA. One important difference between paroxetine and MDMA is that only MDMA has the capability of inhibiting vesicular uptake of monoamines at doses used. We suggest that inhibition of the vesicular monoamine transporter-2, and a following increase in cytoplasmatic monoamine concentrations, might be crucial for the neurotoxic effect of MDMA.

  17. Zn2+ modulation of neurotransmitter transporters

    DEFF Research Database (Denmark)

    Nørgaard-Nielsen, K.; Gether, U.

    2006-01-01

    Neurotransmitter transporters located at the presynaptic or glial cell membrane are responsible for the stringent and rapid clearance of the transmitter from the synapse, and hence they terminate signaling and control the duration of synaptic inputs in the brain. Two distinct families of neurotra......Neurotransmitter transporters located at the presynaptic or glial cell membrane are responsible for the stringent and rapid clearance of the transmitter from the synapse, and hence they terminate signaling and control the duration of synaptic inputs in the brain. Two distinct families...... of neurotransmitter transporters have been identified based on sequence homology: (1) the neurotransmitter sodium symporter family (NSS), which includes the Na+/C1(-)-dependent transporters for dopamine, norepinephrine, and serotonin; and (2) the dicarboxylate/amino acid cation symporter family (DAACS), which...... indirectly suggested the possibility that several of the transporters are modulated by Zn2+ in vivo, and thus that Zn2+ can play a role as a neuromodulator by affecting the function of neurotransmitter transporters....

  18. Determining the neurotransmitter concentration profile at active synapses.

    Science.gov (United States)

    Scimemi, Annalisa; Beato, Marco

    2009-12-01

    Establishing the temporal and concentration profiles of neurotransmitters during synaptic release is an essential step towards understanding the basic properties of inter-neuronal communication in the central nervous system. A variety of ingenious attempts has been made to gain insights into this process, but the general inaccessibility of central synapses, intrinsic limitations of the techniques used, and natural variety of different synaptic environments have hindered a comprehensive description of this fundamental phenomenon. Here, we describe a number of experimental and theoretical findings that has been instrumental for advancing our knowledge of various features of neurotransmitter release, as well as newly developed tools that could overcome some limits of traditional pharmacological approaches and bring new impetus to the description of the complex mechanisms of synaptic transmission.

  19. Role of antioxidants in the protection of the nitrergic neurotransmitter.

    Science.gov (United States)

    Colpaert, Erwin E; Lefebvre, Romain A

    2002-06-01

    There is now compelling evidence that the L-arginine/nitric oxide (NO) pathway generates the non-adrenergic non-cholinergic (NANC) neurotransmitter which mediates smooth muscle relaxation in a variety of nitrergically-innervated tissues. However, one strange aspect of this nitrergic neurotransmission process is that certain drugs (i.e. superoxide generators and NO-scavengers) powerfully inhibit relaxations to exogenous NO, but have little or no effect on relaxations to electrical field stimulation. This thesis examined the possibility that in the nitrergically-innervated gastric fundus of the pig tissue antioxidants present in the neuroeffector junction might protect the endogenous nitrergic neurotransmitter (free radical NO) from attack by superoxide anions and scavenging activity, while exogenous NO would still be vulnerable before it reaches the nitrergic synapses within the tissue. We found that several antioxidants (in casu Cu/Zn superoxide dismutase, reduced glutathione, bilirubin) exerted a partial or complete protection of the relaxation induced by exogenous NO against the differentiating drugs under investigation. A close interrelationship between the endogenous nitrergic neurotransmitter and the antioxidants Cu/Zn superoxide dismutase and bilirubin (produced by the heme oxygenase/biliverdin reductase system) was corroborated by immunohistochemical data showing the presence of these latter defense systems in all nitrergic neurons. Pharmacological depletion further established a role for Cu/Zn superoxide dismutase in peripheral nitrergic neurotransmission. For glutathione, only a partial depletion could be obtained and this did not influence nitrergic neurotransmission.

  20. Piperidine-Based Nocaine/Modafinil Hybrid Ligands as Highly Potent Monoamine Transporter Inhibitors: Efficient Drug Discovery by Rational Lead Hybridization

    Science.gov (United States)

    Zhou, Jia; He, Rong; Johnson, Kenneth M.; Ye, Yanping; Kozikowski, Alan P.

    2005-01-01

    Some piperidine-based nocaine/modafinil hybrid ligands have been designed, synthesized, and found to display an improved potency at all three monoamine transporters and particularly for DAT and/or NET. Some highly active and selective monoamine transporter inhibitors with low nanomolar to subnanomolar potency were identified. Ligands of this type may find important applications as positron emission tomography imaging tools and in the treatment of central nervous system disorders such as depression and sleep apnea. PMID:15537337

  1. Determination of neurotransmitter levels in models of Parkinson's disease by HPLC-ECD.

    Science.gov (United States)

    Yang, Lichuan; Beal, M Flint

    2011-01-01

    Parkinson's disease (PD) is a neurological disorder caused by progressive degeneration of dopaminergic neurons in the nigrostriatal area of the brain. The decrease in dopamine (DA) neurotransmitter levels in the striatum and substantia nigra pars compacta is a neurochemistry hallmark of PD. Therefore, determination of dopamine and its metabolites levels in biological samples provides an important key to understanding the neurochemistry profile of PD. This chapter describes the use of reversed-phase HPLC with electrochemical detection (ECD) for simultaneously measuring monoamine neurotransmitters, including dopamine and its metabolites, norepinephrine as well as serotonin and its metabolite. ECD provides an ultrasensitive measurement, which detects at the picogram level. One run for each sample finishes within 18 min, shows clear chromatographic peaks and a complete separation, and produces excellent precision and reproducibility. Once set up, HPLC-ECD is economic and efficient for analyzing a large number of samples. This method has been broadly used for analyzing a variety of biological samples, such as cerebrospinal fluids, plasma, microdialysis elutes, tissues, and cultured cells. In recent days, it has been reported to be able to detect the dopamine level in a single drosophila head.

  2. DNA cloning of human liver monoamine oxidase A and B: Molecular basis of differences in enzymatic properties

    Energy Technology Data Exchange (ETDEWEB)

    Back, A.W.J.; Lan, N.C.; Johnson, D.L.; Abell, C.W.; Bembenek, M.E.; Kwan, S.W.; Seeburg, P.H.; Shih, J.C. (Univ. of Heidelberg (West Germany))

    1988-07-01

    The monoamine oxidases play a vital role in the metabolism of biogenic amines in the central nervous system and in peripheral tissues. Using oligonucleotide probes derived from three sequenced peptide fragments, the authors have isolated cDNA clones that encode the A and B forms of monoamine oxidase and have determined the nucleotide sequences of these cDNAs. Comparison of the deduced amino acid sequences shows that the A and B forms have subunit molecular weights of 59,700 and 58,800, respectively, and have 70% sequence identity. Both sequences contain the pentapeptide Ser-Gly-Gly-Cys-Tyr, in which the obligatory cofactor FAD is covalently bound to cysteine. Based on differences in primary amino acid sequences and RNA gel blot analysis of mRNAs, the A and B forms of monoamine oxidase appear to be derived from separate genes.

  3. Profiling neurotransmitter receptor expression in the Ambystoma mexicanum brain.

    Science.gov (United States)

    Reyes-Ruiz, Jorge Mauricio; Limon, Agenor; Korn, Matthew J; Nakamura, Paul A; Shirkey, Nicole J; Wong, Jamie K; Miledi, Ricardo

    2013-03-22

    Ability to regenerate limbs and central nervous system (CNS) is unique to few vertebrates, most notably the axolotl (Ambystoma sp.). However, despite the fact the neurotransmitter receptors are involved in axonal regeneration, little is known regarding its expression profile. In this project, RT-PCR and qPCR were performed to gain insight into the neurotransmitter receptors present in Ambystoma. Its functional ability was studied by expressing axolotl receptors in Xenopus laevis oocytes by either injection of mRNA or by direct microtransplantation of brain membranes. Oocytes injected with axolotl mRNA expressed ionotropic receptors activated by GABA, aspartate+glycine and kainate, as well as metabotropic receptors activated by acetylcholine and glutamate. Interestingly, we did not see responses following the application of serotonin. Membranes from the axolotl brain were efficiently microtransplanted into Xenopus oocytes and two types of native GABA receptors that differed in the temporal course of their responses and affinities to GABA were observed. Results of this study are necessary for further characterization of axolotl neurotransmitter receptors and may be useful for guiding experiments aimed at understanding activity-dependant limb and CNS regeneration.

  4. Neurotransmitter receptor-mediated signaling pathways as modulators of carcinogenesis.

    Science.gov (United States)

    Schuller, Hildegard M

    2007-01-01

    The autonomic nervous system with its two antagonistic branches, the sympathicus and the parasympathicus, regulates the activities of all body functions that are not under voluntary control. While the autonomic regulation of organ functions has been extensively studied, little attention has been given to the potential role of neurohumoral transmission at the cellular level in the development of cancer. Studies conducted by our laboratory first showed that binding of the parasympathetic neurotransmitter, acetylcholine, as well as nicotine or its nitrosated cancer-causing derivative, NNK, to nicotinic acetylcholine receptors comprised of alpha7 subunits activated a mitogenic signal transduction pathway in normal and neoplastic pulmonary neuroendocrine cells. On the other hand, beta-adrenergic receptors (Beta-ARs), which transmit signals initiated by binding of the catecholamine neurotransmitters of the sympathicus, were identified by our laboratory as important regulators of cell proliferation in cell lines derived from human adenocarcinomas of the lungs, pancreas, and breast. The tobacco-specific carcinogen NNK bound with high affinity to Beta1- and Beta2-ARs, thus activating cAMP, protein kinase A, and the transcription factor CREB. Collectively, neurotransmitter receptors of the nicotinic and Beta-adrenergic families appear to regulate cellular functions essential for the development and survival of the most common human cancers.

  5. 神经递质在睡眠中的作用%Effect of neurotransmitter in sleep

    Institute of Scientific and Technical Information of China (English)

    初建平; 孟昭义

    2003-01-01

    @@ INTRODUCTION Sleep- wake rhythm is isolated from day- night rhythm of natural world;Sleep depends on the regulation of special structure of central nerve system and correlated neurotransmitters.This paper mainly introduces the research progress of neurotransmitter correlated to sleep.It benefits the comprehension of physiology,pathology and pharmacology of sleep and recognition of sleep.

  6. Secondary neurotransmitter deficiencies in epilepsy caused by voltage-gated sodium channelopathies: A potential treatment target?

    Science.gov (United States)

    Horvath, Gabriella A; Demos, Michelle; Shyr, Casper; Matthews, Allison; Zhang, Linhua; Race, Simone; Stockler-Ipsiroglu, Sylvia; Van Allen, Margot I; Mancarci, Ogan; Toker, Lilah; Pavlidis, Paul; Ross, Colin J; Wasserman, Wyeth W; Trump, Natalie; Heales, Simon; Pope, Simon; Cross, J Helen; van Karnebeek, Clara D M

    2016-01-01

    We describe neurotransmitter abnormalities in two patients with drug-resistant epilepsy resulting from deleterious de novo mutations in sodium channel genes. Whole exome sequencing identified a de novo SCN2A splice-site mutation (c.2379+1G>A, p.Glu717Gly.fs*30) resulting in deletion of exon 14, in a 10-year old male with early onset global developmental delay, intermittent ataxia, autism, hypotonia, epileptic encephalopathy and cerebral/cerebellar atrophy. In the cerebrospinal fluid both homovanillic acid and 5-hydroxyindoleacetic acid were significantly decreased; extensive biochemical and genetic investigations ruled out primary neurotransmitter deficiencies and other known inborn errors of metabolism. In an 8-year old female with an early onset intractable epileptic encephalopathy, developmental regression, and progressive cerebellar atrophy, a previously unreported de novo missense mutation was identified in SCN8A (c.5615G>A; p.Arg1872Gln), affecting a highly conserved residue located in the C-terminal of the Nav1.6 protein. Aside from decreased homovanillic acid and 5-hydroxyindoleacetic acid, 5-methyltetrahydrofolate was also found to be low. We hypothesize that these channelopathies cause abnormal synaptic mono-amine metabolite secretion/uptake via impaired vesicular release and imbalance in electrochemical ion gradients, which in turn aggravate the seizures. Treatment with oral 5-hydroxytryptophan, l-Dopa/Carbidopa, and a dopa agonist resulted in mild improvement of seizure control in the male case, most likely via dopamine and serotonin receptor activated signal transduction and modulation of glutamatergic, GABA-ergic and glycinergic neurotransmission. Neurotransmitter analysis in other sodium channelopathy patients will help validate our findings, potentially yielding novel treatment opportunities. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Anxiety and affective disorder comorbidity related to serotonin and other neurotransmitter systems: obsessive–compulsive disorder as an example of overlapping clinical and genetic heterogeneity

    Science.gov (United States)

    Murphy, Dennis L.; Moya, Pablo R.; Fox, Meredith A.; Rubenstein, Liza M.; Wendland, Jens R.; Timpano, Kiara R.

    2013-01-01

    Individuals with obsessive–compulsive disorder (OCD) have also been shown to have comorbid lifetime diagnoses of major depressive disorder (MDD; rates greater than 70%), bipolar disorder (rates greater than 10%) and other anxiety disorders (e.g. panic disorder, post-traumatic stress disorder (PTSD)). In addition, overlap exists in some common genetic variants (e.g. the serotonin transporter gene (SLC6A4), the brain-derived neurotrophic factor (BDNF) gene), and rare variants in genes/chromosomal abnormalities (e.g. the 22q11 microdeletion syndrome) found across the affective/anxiety disorder spectrums. OCD has been proposed as a possible independent entity for DSM-5, but by others thought best retained as an anxiety disorder subtype (its current designation in DSM-IV), and yet by others considered best in the affective disorder spectrum. This review focuses on OCD, a well-studied but still puzzling heterogeneous disorder, regarding alterations in serotonergic, dopaminergic and glutamatergic neurotransmission in addition to other systems involved, and how related genes may be involved in the comorbidity of anxiety and affective disorders. OCD resembles disorders such as depression, in which gene × gene interactions, gene × environment interactions and stress elements coalesce to yield OC symptoms and, in some individuals, full-blown OCD with multiple comorbid disorders. PMID:23440468

  8. DRD4 dopamine receptor genotype and CSF monoamine metabolites in Finnish alcoholics and controls

    Energy Technology Data Exchange (ETDEWEB)

    Adamson, M.D.; Dean, M.; Goldman, D. [National Institute on Alcohol Abuse and Alcoholism, Rockville, MD (United States)] [and others

    1995-06-19

    The DRD4 dopamine receptor is thus far unique among neurotransmitter receptors in having a highly polymorphic gene structure that has been reported to produce altered receptor functioning. These allelic variations are caused by a 48-bp segment in exon III of the coding region which may be repeated from 2-10 times. Varying the numbers of repeated segments changes the length, structure, and, possibly, the functional efficiency of the receptor, which makes this gene an intriguing candidate for variations in dopamine-related behaviors, such as alcoholism and drug abuse. Thus far, these DRD4 alleles have been investigated for association with schizophrenia, bipolar disorder, Parkinson`s disease, and chronic alcoholism, and all have been largely negative for a direct association. We evaluated the DRD4 genotype in 226 Finish adult males, 113 of whom were alcoholics, many of the early onset type with features of impulsivity and antisocial traits. Genotype frequencies were compared to 113 Finnish controls who were free of alcohol abuse, substance abuse, and major mental illness. In 70 alcoholics and 20 controls, we measured CSF homovanillic acid (HVA), the major metabolite of dopamine, and 5-hydroxyindoleacetic acid (5-HIAA). No association was found between a particular DRD4 dopamine receptor allele and alcoholism. CSF concentrations of the monoamine metabolites showed no significant difference among the DRD4 genotypes. This study of the DRD4 dopamine receptor in alcoholics is the first to be conducted in a clinically and ethnically homogeneous population and to relate the DRD4 genotype to CSF monoamine concentrations. The results indicate that there is no association of the DRD4 receptor with alcoholism. 52 refs., 3 figs., 1 tab.

  9. Distinct effects of the serotonin-noradrenaline reuptake inhibitors milnacipran and venlafaxine on rat pineal monoamines.

    Science.gov (United States)

    Muneoka, Katsumasa; Kuwagata, Makiko; Ogawa, Tetsuo; Shioda, Seiji

    2015-06-17

    Monoamine systems are involved in the pathology and therapeutic mechanism of depression. The pineal gland contains large amounts of serotonin as a precursor for melatonin, and its activity is controlled by noradrenergic sympathetic nerves. Pineal diurnal activity and its release of melatonin are relevant to aberrant states observed in depression. We investigated the effects on pineal monoamines of serotonin-noradrenaline reuptake inhibitors, which are widely used antidepressants. Four days of milnacipran treatment led to an increase in noradrenaline and serotonin levels, whereas 4 days of venlafaxine treatment reduced 5-hydroxyindoleacetic acid levels; both agents induced an increase in dopamine levels. Our data suggest that milnacipran increases levels of the precursor for melatonin synthesis by facilitating the noradrenergic regulation of pineal activity and that venlafaxine inhibits serotonin reuptake into noradrenergic terminals on the pineal gland.

  10. Two-step production of monoamines in monoenzymatic cells in the spinal cord: a different control strategy of neurotransmitter supply?

    DEFF Research Database (Denmark)

    Zhang, Mengliang

    2016-01-01

    that especially when the spinal cord is injured, they can also be produced in the spinal cord. In this review, I will present evidence for a possible pathway for two-step synthesis of dopamine and serotonin in the spinal cord. Published data from different sources and unpublished data from my own ongoing projects...

  11. Effects of Shuyusan on monoamine neurotransmitters expression in a rat model of chronic stress-induced depression

    Institute of Scientific and Technical Information of China (English)

    Yuanyuan Zhang; Jianjun Jia; Liping Chen; Zhitao Han; Yulan Zhao; Honghong Zhang; Yazhuo Hu

    2011-01-01

    Shuyusan, a traditional Chinese medicine, was shown to improve depression symptoms and behavioral scores, as well as increase 5-hydroxytryptamine (5-HT), 5-hydroxyindoleacetic acid, and 5-hydroxytryptophan levels, in a rat model of chronic stress-induced depression. However, dopamine, noradrenalin, and 3-methoxy-4-hydroxyphenylglycol expressions remained unchanged following Shuyusan treatment. Compared with the model group, the number of 5-HT-positive neurons in layers 4-5 of the frontal cortex, as well as hippocampal CA1 and CA3 regions, significantly increased following Shuyusan treatment. These results suggested that Shuyusan improved symptoms in a rat model of chronic stress-induced depression with mechanisms that involved 5-HT, 5-HT metabolite, 5-HT precursor expressions.

  12. Altered neurotransmitter metabolism in adolescents with high-functioning autism

    NARCIS (Netherlands)

    Drenthen, G.S.; Barendse, E.M.; Aldenkamp, A.P.; Veenendaal, T. van; Puts, N.A.J.; Edden, R.A.E.; Zinger, S.; Thoonen, G.H.J.; Hendriks, M.P.H.; Kessels, R.P.C.; Jansen, J.F.A.

    2016-01-01

    Previous studies have suggested that alterations in excitatory/inhibitory neurotransmitters might play a crucial role in autism spectrum disorder (ASD). Proton magnetic resonance spectroscopy (1H-MRS) can provide valuable information about abnormal brain metabolism and neurotransmitter concentration

  13. Study of a possible role of the monoamine oxidase A (MAOA) gene in paranoid schizophrenia among a Chinese population.

    Science.gov (United States)

    Sun, Yuhui; Zhang, Jiexu; Yuan, Yanbo; Yu, Xin; Shen, Yan; Xu, Qi

    2012-01-01

    Monoamine oxidase A (MAOA) is the enzyme responsible for degradation of several monoamines, such as dopamine and serotonin that are considered as being two of the most important neurotransmitters involved in the pathophysiology of schizophrenia. To study a possible role of the MAOA gene in conferring susceptibility to schizophrenia, the present study genotyped the variable number of tandem repeat (VNTR) polymorphism and 41 SNPs across this gene among 555 unrelated patients with paranoid schizophrenia and 567 unrelated healthy controls. Quantitative real-time PCR analysis was employed to quantify expression of MAOA mRNA in 73 drug-free patients. While none of these genotyped DNA markers showed allelic association with paranoid schizophrenia, haplotypic association was found for the VNTR-rs6323, VNTR-rs1137070, and VNTR-rs6323-rs1137070 haplotypes in female subjects. Nevertheless, no significant change of the expression of MAOA mRNA was detected in either female or male patients with paranoid schizophrenia. Our study suggests that the interaction between genetic variants within the MAOA gene may contribute to an increased risk of paranoid schizophrenia, but the precise mechanism needs further investigation.

  14. Inhibition of Excessive Monoamine Oxidase A/B Activity Protects Against Stress-induced Neuronal Death in Huntington Disease.

    Science.gov (United States)

    Ooi, Jolene; Hayden, Michael R; Pouladi, Mahmoud A

    2015-12-01

    Monoamine oxidases (MAO) are important components of the homeostatic machinery that maintains the levels of monoamine neurotransmitters, including dopamine, in balance. Given the imbalance in dopamine levels observed in Huntington disease (HD), the aim of this study was to examine MAO activity in a mouse striatal cell model of HD and in human neural cells differentiated from control and HD patient-derived induced pluripotent stem cell (hiPSC) lines. We show that mouse striatal neural cells expressing mutant huntingtin (HTT) exhibit increased MAO expression and activity. We demonstrate using luciferase promoter assays that the increased MAO expression reflects enhanced epigenetic activation in striatal neural cells expressing mutant HTT. Using cellular stress paradigms, we further demonstrate that the increase in MAO activity in mutant striatal neural cells is accompanied by enhanced susceptibility to oxidative stress and impaired viability. Treatment of mutant striatal neural cells with MAO inhibitors ameliorated oxidative stress and improved cellular viability. Finally, we demonstrate that human HD neural cells exhibit increased MAO-A and MAO-B expression and activity. Altogether, this study demonstrates abnormal MAO expression and activity and suggests a potential use for MAO inhibitors in HD.

  15. Ligand Binding in the Extracellular Vestibule of the Neurotransmitter Transporter Homologue LeuT.

    Science.gov (United States)

    Grouleff, Julie; Koldsø, Heidi; Miao, Yinglong; Schiøtt, Birgit

    2017-03-15

    The human monoamine transporters (MATs) facilitate the reuptake of monoamine neurotransmitters from the synaptic cleft. MATs are linked to a number of neurological diseases and are the targets of both therapeutic and illicit drugs. Until recently, no high-resolution structures of the human MATs existed, and therefore, studies of this transporter family have relied on investigations of the homologues bacterial transporters such as the leucine transporter LeuT, which has been crystallized in several conformational states. A two-substrate transport mechanism has been suggested for this transporter family, which entails that high-affinity binding of a second substrate in an extracellular site is necessary for the substrate in the central binding site to be transported. Compelling evidence for this mechanism has been presented, however, a number of equally compelling accounts suggest that the transporters function through a mechanism involving only a single substrate and a single high-affinity site. To shed light on this apparent contradiction, we have performed extensive molecular dynamics simulations of LeuT in the outward-occluded conformation with either one or two substrates bound to the transporter. We have also calculated the substrate binding affinity in each of the two proposed binding sites through rigorous free energy simulations. Results show that substrate binding is unstable in the extracellular vestibule and the substrate binding affinity within the suggested extracellular site is very low (0.2 and 3.3 M for the two dominant binding modes) compared to the central substrate binding site (14 nM). This suggests that for LeuT in the outward-occluded conformation only a single high-affinity substrate binding site exists.

  16. Leflunomide, a Reversible Monoamine Oxidase Inhibitor.

    Science.gov (United States)

    Petzer, Jacobus P; Petzer, Anél

    2016-01-01

    A screening study aimed at identifying inhibitors of the enzyme, monoamine oxidase (MAO), among clinically used drugs have indicated that the antirheumatic drug, leflunomide, is an inhibitor of both MAO isoforms. Leflunomide inhibits human MAO-A and MAO-B and exhibits IC50 values of 19.1 μM and 13.7 μM, respectively. The corresponding Ki values are 17.7 μM (MAO-A) and 10.1 μM (MAO-B). Dialyses of mixtures of the MAO enzymes and leflunomide show that inhibition of the MAOs by leflunomide is reversible. The principal metabolite of leflunomide, teriflunomide (A77 1726), in contrast is not an MAO inhibitor. This study concludes that, although leflunomide is only moderately potent as an MAO inhibitor, isoxazole derivatives may represent a general class of MAO inhibitors and this heterocycle may find application in MAO inhibitor design. In this respect, MAO inhibitors are used in the clinic for the treatment of depressive illness and Parkinson's disease, and are under investigation as therapy for certain types of cancer, Alzheimer's disease and age-related impairment of cardiac function.

  17. MONOAMINE OXIDASE: RADIOTRACER DEVELOPMENT AND HUMAN STUDIES.

    Energy Technology Data Exchange (ETDEWEB)

    FOWLER,J.S.; LOGAN,J.; VOLKOW,N.D.; WANG,G.J.; MACGREGOR,R.R.; DING,Y.S.

    2000-09-28

    PET is uniquely capable of providing information on biochemical transformations in the living human body. Although most of the studies of monoamine oxidase (MAO) have focused on measurements in the brain, the role of peripheral MAO as a phase 1 enzyme for the metabolism of drugs and xenobiotics is gaining attention (Strolin Benedetti and Tipton, 1998; Castagnoli et al., 1997.). MAO is well suited for this role because its concentration in organs such as kidneys, liver and digestive organs is high sometimes exceeding that in the brain. Knowledge of the distribution of the MAO subtypes within different organs and different cells is important in determining which substrates (and which drugs and xenobiotics) have access to which MAO subtypes. The highly variable subtype distribution with different species makes human studies even more important. In addition, the deleterious side effects of combining MAO inhibitors with other drugs and with foodstuffs makes it important to know the MAO inhibitory potency of different drugs both in the brain and in peripheral organs (Ulus et al., 2000). Clearly PET can play a role in answering these questions, in drug research and development and in discovering some of the factors which contribute to the highly variable MAO levels in different individuals.

  18. Monoamine oxidase inhibitory activities of heterocyclic chalcones.

    Science.gov (United States)

    Minders, Corné; Petzer, Jacobus P; Petzer, Anél; Lourens, Anna C U

    2015-11-15

    Studies have shown that natural and synthetic chalcones (1,3-diphenyl-2-propen-1-ones) possess monoamine oxidase (MAO) inhibition activities. Of particular importance to the present study is a report that a series of furanochalcones acts as MAO-B selective inhibitors. Since the effect of heterocyclic substitution, other than furan (and more recently thiophene, piperidine and quinoline) on the MAO inhibitory properties of the chalcone scaffold remains unexplored, the aim of this study was to synthesise and evaluate further heterocyclic chalcone analogues as inhibitors of the human MAOs. For this purpose, heterocyclic chalcone analogues that incorporate pyrrole, 5-methylthiophene, 5-chlorothiophene and 6-methoxypyridine substitution were examined. Seven of the nine synthesised compounds exhibited IC50 values chalcones are reversible and competitive MAO inhibitors. 4h, however, may exhibit tight-binding to MAO-B, a property linked to its thiophene moiety. We conclude that high potency chalcones such as 4h represent suitable leads for the development of MAO-B inhibitors for the treatment of Parkinson's disease and possibly other neurodegenerative disorders.

  19. Receptor desensitization by neurotransmitters in membranes: are neurotransmitters the endogenous anesthetics?

    Science.gov (United States)

    Cantor, Robert S

    2003-10-21

    A mechanism of anesthesia is proposed that addresses one of the most troubling peculiarities of general anesthesia: the remarkably small variability of sensitivity within the human population and across a broad range of animal phyla. It is hypothesized that in addition to the rapid, saturable binding of a neurotransmitter to its receptor that results in activation, the neurotransmitter also acts indirectly on the receptor by diffusing into the postsynaptic membrane and changing its physical properties, causing a shift in receptor conformational equilibrium (desensitization). Unlike binding, this slower indirect mechanism is nonspecific: each neurotransmitter will, in principle, affect all receptors in the membrane. For proteins modeled as having only resting and active conformational states, time-dependent ion currents are predicted that exhibit many characteristics of desensitization for both inhibitory and excitatory channels. If receptors have been engineered to regulate the time course of ion currents by this mechanism, then (a) mutations that significantly alter receptor sensitivity to this effect would be lethal and (b) by design, excitatory receptors would be inhibited, but inhibitory receptors activated, so that their effects are not counterproductive. The wide range of exogenous molecules that affect the physical properties of membranes as do neurotransmitters, but that do not bind to receptors, would thus inhibit excitatory channels and activate inhibitory channels, i.e., they would act as anesthesics. The endogenous anesthetics would thus be the neurotransmitters, the survival advantage conferred by their proper membrane-mediated desensitization of receptors explaining the selection pressure for anesthesic sensitivity.

  20. Monoamines tissue content analysis reveals restricted and site-specific correlations in brain regions involved in cognition.

    Science.gov (United States)

    Fitoussi, A; Dellu-Hagedorn, F; De Deurwaerdère, P

    2013-01-01

    The dopamine (DA), noradrenalin (NA) and serotonin (5-HT) monoaminergic systems are deeply involved in cognitive processes via their influence on cortical and subcortical regions. The widespread distribution of these monoaminergic networks is one of the main difficulties in analyzing their functions and interactions. To address this complexity, we assessed whether inter-individual differences in monoamine tissue contents of various brain areas could provide information about their functional relationships. We used a sensitive biochemical approach to map endogenous monoamine tissue content in 20 rat brain areas involved in cognition, including 10 cortical areas and examined correlations within and between the monoaminergic systems. Whereas DA content and its respective metabolite largely varied across brain regions, the NA and 5-HT contents were relatively homogenous. As expected, the tissue content varied among individuals. Our analyses revealed a few specific relationships (10%) between the tissue content of each monoamine in paired brain regions and even between monoamines in paired brain regions. The tissue contents of NA, 5-HT and DA were inter-correlated with a high incidence when looking at a specific brain region. Most correlations found between cortical areas were positive while some cortico-subcortical relationships regarding the DA, NA and 5-HT tissue contents were negative, in particular for DA content. In conclusion, this work provides a useful database of the monoamine tissue content in numerous brain regions. It suggests that the regulation of these neuromodulatory systems is achieved mainly at the terminals, and that each of these systems contributes to the regulation of the other two.

  1. Monoamine content during the reproductive cycle of Perna perna depends on site of origin on the Atlantic Coast of Morocco.

    Science.gov (United States)

    Klouche, Mounia S; De Deurwaerdère, Philippe; Dellu-Hagedorn, Françoise; Lakhdar-Ghazal, Nouria; Benomar, Soumaya

    2015-09-09

    Bivalve molluscs such as Perna perna display temporal cycles of reproduction that result from the complex interplay between endogenous and exogenous signals. The monoamines serotonin, dopamine and noradrenaline represent possible endocrine and neuronal links between these signals allowing the molluscs to modulate reproductive functions in conjunction with environmental constraints. Here, we report a disruption of the reproductive cycle of mussels collected from two of three sites along the Moroccan atlantic coast soiled by industrial or domestic waste. Using high pressure liquid chromatography, we show that the temporal pattern of monoamine content in the gonads, pedal and cerebroid ganglia varied throughout the reproductive cycle (resting, developing, maturing, egg-laying) of mussels from the unpolluted site. Marked modification of monoamine tissue content was found between sites, notably in noradrenaline content of the gonads. Discriminant statistics revealed a specific impact of mussel location on the temporal variations of noradrenaline and serotonin levels in gonads and cerebroid ganglia. Correlation analyses showed profound and temporal changes in the monoamine content between organs and ganglia, at the two sites where the reproduction was disrupted. We suggest that environmental constraints lead to profound changes of monoaminergic systems, which thereby compromises the entry of mussels into their reproductive cycle.

  2. Characterizing Enzymatic Deposition for Microelectrode Neurotransmitter Detection

    Energy Technology Data Exchange (ETDEWEB)

    Hosein, W. K. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Yorita, A. M. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Tolosa, V. M. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2016-08-12

    The enzyme immobilization process, one step in creating an enzymatic biosensor, was characterized and analyzed as a function of its physical properties. The neural glutamic biosensor is a flexible device, effectively minimizing trauma to the area of implantation. The Multielectrode Array (MEA) is composed primarily of a proprietary polymer which has been successfully implanted into human subjects in recent years. This polymer allows the device the pliability that other devices normally lack, though this poses some challenges to implantation. The electrodes are made of Platinum (Pt), and can range in number from eight to thirty two electrodes per device. These electrodes are electroplated with a semipermeable polymer layer to improve selectivity of the electrode to the neurotransmitter of interest, in this case glutamate. A signal is created from the interaction of glutamate in the brain with the glutamate oxidase (GluOx) which is immobilized on the surface of the electrode by using crosslinking chemistry in conjunction with glutaraldehyde and Bovine Serum Albumin (BSA). The glutamate is oxidized by glutamate oxidase, producing α-ketoglutarate and hydrogen peroxide (H2O2) as a by-product. The production of H2O2 is crucial for detection of the presence of the glutamate within the enzymatic coating, as it diffuses through the enzyme layer and oxidizes at the surface of the electrode. This oxidation is detectable by measurable change in the current using amperometry. Hence, the MEA allows for in vivo monitoring of neurotransmitter activity in real time. The sensitivity of the sensor to these neurotransmitters is dependent on the thickness of the layer, which is investigated in these experiments in order to optimize the efficacy of the device to detecting the substrate, once implanted.

  3. Interaction of neurotransmitters with a phospholipid bilayer

    DEFF Research Database (Denmark)

    Peters, Günther H.J.; Werge, Mikkel; Elf-Lind, Maria Northved

    2014-01-01

    We have performed a series of molecular dynamics simulations to study the interactions between the neurotransmitters (NTs) γ-aminobutyrate (GABA), glycine (GLY), acetylcholine (ACH) and glutamate (GLU) as well as the amidated/acetylated γ-aminobutyrate (GABAneu) and the osmolyte molecule glycerol...... umbrella sampling simulations, which were conducted for the four naturally occurring NTs. Free energy profiles for ACH and GLU show a minimum of ∼2–3 kJ/mol close to the bilayer interface, while for GABA and GLY, a minimum of respectively ∼2 kJ/mol and ∼5 kJ/mol is observed when these NTs are located...

  4. Neurotransmitter transporters expressed in glial cells as regulators of synapse function.

    Science.gov (United States)

    Eulenburg, Volker; Gomeza, Jesús

    2010-05-01

    Synaptic neurotransmission at high temporal and spatial resolutions requires efficient removal and/or inactivation of presynaptically released transmitter to prevent spatial spreading of transmitter by diffusion and allow for fast termination of the postsynaptic response. This action must be carefully regulated to result in the fine tuning of inhibitory and excitatory neurotransmission, necessary for the proper processing of information in the central nervous system. At many synapses, high-affinity neurotransmitter transporters are responsible for transmitter deactivation by removing it from the synaptic cleft. The most prevailing neurotransmitters, glutamate, which mediates excitatory neurotransmission, as well as GABA and glycine, which act as inhibitory neurotransmitters, use these uptake systems. Neurotransmitter transporters have been found in both neuronal and glial cells, thus suggesting high cooperativity between these cell types in the control of extracellular transmitter concentrations. The generation and analysis of animals carrying targeted disruptions of transporter genes together with the use of selective inhibitors have allowed examining the contribution of individual transporter subtypes to synaptic transmission. This revealed the predominant role of glial expressed transporters in maintaining low extrasynaptic neurotransmitter levels. Additionally, transport activity has been shown to be actively regulated on both transcriptional and post-translational levels, which has important implications for synapse function under physiological and pathophysiological conditions. The analysis of these mechanisms will enhance not only our understanding of synapse function but will reveal new therapeutic strategies for the treatment of human neurological diseases.

  5. Wireless Power Transfer for Autonomous Wearable Neurotransmitter Sensors.

    Science.gov (United States)

    Nguyen, Cuong M; Kota, Pavan Kumar; Nguyen, Minh Q; Dubey, Souvik; Rao, Smitha; Mays, Jeffrey; Chiao, J-C

    2015-09-23

    In this paper, we report a power management system for autonomous and real-time monitoring of the neurotransmitter L-glutamate (L-Glu). A low-power, low-noise, and high-gain recording module was designed to acquire signal from an implantable flexible L-Glu sensor fabricated by micro-electro-mechanical system (MEMS)-based processes. The wearable recording module was wirelessly powered through inductive coupling transmitter antennas. Lateral and angular misalignments of the receiver antennas were resolved by using a multi-transmitter antenna configuration. The effective coverage, over which the recording module functioned properly, was improved with the use of in-phase transmitter antennas. Experimental results showed that the recording system was capable of operating continuously at distances of 4 cm, 7 cm and 10 cm. The wireless power management system reduced the weight of the recording module, eliminated human intervention and enabled animal experimentation for extended durations.

  6. Wireless Power Transfer for Autonomous Wearable Neurotransmitter Sensors

    Directory of Open Access Journals (Sweden)

    Cuong M. Nguyen

    2015-09-01

    Full Text Available In this paper, we report a power management system for autonomous and real-time monitoring of the neurotransmitter L-glutamate (L-Glu. A low-power, low-noise, and high-gain recording module was designed to acquire signal from an implantable flexible L-Glu sensor fabricated by micro-electro-mechanical system (MEMS-based processes. The wearable recording module was wirelessly powered through inductive coupling transmitter antennas. Lateral and angular misalignments of the receiver antennas were resolved by using a multi-transmitter antenna configuration. The effective coverage, over which the recording module functioned properly, was improved with the use of in-phase transmitter antennas. Experimental results showed that the recording system was capable of operating continuously at distances of 4 cm, 7 cm and 10 cm. The wireless power management system reduced the weight of the recording module, eliminated human intervention and enabled animal experimentation for extended durations.

  7. Chloride binding site of neurotransmitter sodium symporters.

    Science.gov (United States)

    Kantcheva, Adriana K; Quick, Matthias; Shi, Lei; Winther, Anne-Marie Lund; Stolzenberg, Sebastian; Weinstein, Harel; Javitch, Jonathan A; Nissen, Poul

    2013-05-21

    Neurotransmitter:sodium symporters (NSSs) play a critical role in signaling by reuptake of neurotransmitters. Eukaryotic NSSs are chloride-dependent, whereas prokaryotic NSS homologs like LeuT are chloride-independent but contain an acidic residue (Glu290 in LeuT) at a site where eukaryotic NSSs have a serine. The LeuT-E290S mutant displays chloride-dependent activity. We show that, in LeuT-E290S cocrystallized with bromide or chloride, the anion is coordinated by side chain hydroxyls from Tyr47, Ser290, and Thr254 and the side chain amide of Gln250. The bound anion and the nearby sodium ion in the Na1 site organize a connection between their coordinating residues and the extracellular gate of LeuT through a continuous H-bond network. The specific insights from the structures, combined with results from substrate binding studies and molecular dynamics simulations, reveal an anion-dependent occlusion mechanism for NSS and shed light on the functional role of chloride binding.

  8. Temperature dependence of electrical properties of mixture of exogenous neurotransmitters dopamine and epinephrine

    Science.gov (United States)

    Patki, Mugdha; Patil, Vidya

    2016-05-01

    Neurotransmitters are chemical messengers that support the communication between the neurons. In vitro study of exogenous neurotransmitters Dopamine and Epinephrine and their mixture, carried out to learn about their electrical properties being dielectric constant and conductivity amongst others. Dielectric constant and conductivity of the selected neurotransmitters are found to increase with temperature. As a result, the time constant of the system increases with temperature. This change leads to increase in the time taken by the synapse to transport the action potential. The correlation between physical properties of exogenous neurotransmitters and psychological and physiological behaviour of human being may be understood with the help of current study. The response time of Epinephrine is in microseconds whereas response time of Dopamine is in milliseconds. The response time for both the neurotransmitters and their mixture is found to be increasing with temperature indicating the symptoms such as depression, apathy, chronic fatigue and low physical energy with no desire to exercise the body, which are observed during the fever.

  9. Microfluidic platform for neurotransmitter sensing based on cyclic voltammetry and dielectrophoresis for in vitro experiments.

    Science.gov (United States)

    Mathault, Jessy; Zamprogno, Pauline; Greener, Jesse; Miled, Amine

    2015-08-01

    This paper presents a new microfluidic platform that can simultaneously measure and locally modulate neurotransmitter concentration in a neuron network. This work focuses on the development of a first prototype including a potentiostat and electrode functionalization to detect several neurotransmitter's simultaneously. We tested dopamine as proof of concept to validate functionality. The system is based on 320 bidirectional electrode array for dielectrophoretic manipulation and cyclic voltammetry. Each electrode is connected to a mechanical multiplexer in order to reduce noise interference and fully isolate the electrode. The multiplexing rate is 476 kHz and each electrode can drive a signal with an amplitude of 60 V pp for dielectrophoretic manipulation.

  10. Marine Toxins Potently Affecting Neurotransmitter Release

    Science.gov (United States)

    Meunier, Frédéric A.; Mattei, César; Molgó, Jordi

    Synapses are specialised structures where interneuronal communication takes place. Not only brain function is absolutely dependent on synaptic activity, but also most of our organs are intimately controlled by synaptic activity. Synapses re therefore an ideal target to act upon and poisonous species have evolved fascinating neurotoxins capable of shutting down neuronal communication by blocking or activating essential components of the synapse. By hijacking key proteins of the communication machinery, neurotoxins are therefore extremely valuable tools that have, in turn, greatly helped our understanding of synaptic biology. Moreover, analysis and understanding of the molecular strategy used by certain neurotoxins has allowed the design of entirely new classes of drugs acting on specific targets with high selectivity and efficacy. This chapter will discuss the different classes of marine neurotoxins, their effects on neurotransmitter release and how they act to incapacitate key steps in the process leading to synaptic vesicle fusion.

  11. Microtransplantation of membranes from cultured cells to Xenopus oocytes: A method to study neurotransmitter receptors embedded in native lipids

    OpenAIRE

    Palma, Eleonora; Trettel, Flavia; Fucile, Sergio; Renzi, Massimiliano; Miledi, Ricardo; Eusebi, Fabrizio

    2003-01-01

    The Xenopus oocyte is used as a convenient cell expression system to study the structure and function of heterogenic transmitter receptors and ion channels. Recently, we introduced a method to microtransplant already assembled neurotransmitter receptors from the human brain to the plasma membrane of Xenopus oocytes. The same approach was used here to transplant neurotransmitter receptors expressed from cultured cells to the oocytes. Membrane vesicles prepared from a human embryonic kidney cel...

  12. Human pharmacology of ayahuasca: subjective and cardiovascular effects, monoamine metabolite excretion, and pharmacokinetics.

    Science.gov (United States)

    Riba, Jordi; Valle, Marta; Urbano, Gloria; Yritia, Mercedes; Morte, Adelaida; Barbanoj, Manel J

    2003-07-01

    The effects of the South American psychotropic beverage ayahuasca on subjective and cardiovascular variables and urine monoamine metabolite excretion were evaluated, together with the drug's pharmacokinetic profile, in a double-blind placebo-controlled clinical trial. This pharmacologically complex tea, commonly obtained from Banisteriopsis caapi and Psychotria viridis, combines N,N-dimethyltryptamine (DMT), an orally labile psychedelic agent showing 5-hydroxytryptamine2A agonist activity, with monoamine oxidase (MAO)-inhibiting beta-carboline alkaloids (harmine, harmaline, and tetrahydroharmine). Eighteen volunteers with prior experience in the use of psychedelics received single oral doses of encapsulated freeze-dried ayahuasca (0.6 and 0.85 mg of DMT/kg of body weight) and placebo. Ayahuasca produced significant subjective effects, peaking between 1.5 and 2 h, involving perceptual modifications and increases in ratings of positive mood and activation. Diastolic blood pressure showed a significant increase at the high dose (9 mm Hg at 75 min), whereas systolic blood pressure and heart rate were moderately and nonsignificantly increased. Cmax values for DMT after the low and high ayahuasca doses were 12.14 ng/ml and 17.44 ng/ml, respectively. Tmax (median) was observed at 1.5 h after both doses. The Tmax for DMT coincided with the peak of subjective effects. Drug administration increased urinary normetanephrine excretion, but, contrary to the typical MAO-inhibitor effect profile, deaminated monoamine metabolite levels were not decreased. This and the negligible harmine plasma levels found suggest a predominantly peripheral (gastrointestinal and liver) site of action for harmine. MAO inhibition at this level would suffice to prevent first-pass metabolism of DMT and allow its access to systemic circulation and the central nervous system.

  13. Monoamine transporter availability in Parkinson's disease patients with or without depression

    Energy Technology Data Exchange (ETDEWEB)

    Hesse, Swen; Meyer, Philipp M.; Barthel, Henryk; Sabri, Osama [University of Leipzig, Department of Nuclear Medicine, Leipzig (Germany); Strecker, Karl; Wegner, Florian; Isaias, Ioannis Ugo; Schwarz, Johannes [University of Leipzig, Department of Neurology, Leipzig (Germany); Oehlwein, Christian [Specialized Parkinson' s Disease Outpatient Centre, Gera (Germany)

    2009-03-15

    Depression is a common symptom in patients suffering from Parkinson's disease (PD) and markedly reduces their quality of life. As post-mortem studies have shown, its presence may reflect extensive cell loss in the midbrain and brainstem with imbalances in monoaminergic neurotransmitters. However, in vivo evidence of specific monoaminergic deficits in depressed PD patients is still sparse. Therefore, we studied PD patients with depression (PD+D) and without depression (PD-D) using high-resolution single-photon emission computed tomography (SPECT) and the monoamine transporter marker [{sup 123}I]FP-CIT. A magnetic resonance imaging-based region-of-interest analysis was applied to quantify the specific-to-nondisplaceable [{sup 123}I]FP-CIT binding coefficient V{sub 3}'' in the striatum, thalamus and midbrain/brainstem regions. PD+D patients had significantly lower V{sub 3}'' compared with PD-D patients in the striatum (p<0.001), thalamus (p=0.002), and midbrain/brainstem (p=0.025). Only PD+D patients without selective serotonin reuptake inhibitor (SSRI) treatment showed lower thalamic and midbrain V{sub 3}'' than controls (p<0.001, p=0.029). In a small sub-group of SSRI-treated PD+D patients neither thalamic V{sub 3}'' nor midbrain/brainstem V{sub 3}'' differed from those in PD-D patients (p=0.168, p=0.201) or controls (p=0.384, p=0.318). Our data indicate that depression in PD is associated with a more pronounced loss of striatal dopamine transporter availability that is most likely secondary to increased dopaminergic degeneration. In addition, depressed PD patients have a lower availability of midbrain/brainstem monoamine transporters than nondepressed PD patients. These findings provide in vivo evidence in support of the known post-mortem data demonstrating more extensive nerve cell loss in PD with depression and indicate that SPECT imaging can help to identify pathophysiological changes underlying nonmotor

  14. Antidepressant-Like Effects of Fractions Prepared from Danzhi-Xiaoyao-San Decoction in Rats with Chronic Unpredictable Mild Stress: Effects on Hypothalamic-Pituitary-Adrenal Axis, Arginine Vasopressin, and Neurotransmitters

    Directory of Open Access Journals (Sweden)

    Li-Li Wu

    2016-01-01

    Full Text Available The aim of the present study was to investigate the antidepressant-like effects of two fractions, including petroleum ether soluble fraction (Fraction A, FA and water-EtOH soluble fraction (Fraction B, FB prepared from the Danzhi-xiaoyao-san (DZXYS by using chronic unpredictable mild stress-induced depressive rat model. The results indicated that DZXYS could ameliorate the depression-like behavior in chronic stress model of rats. The inhibition of hyperactivity of HPA axis and the modulation of monoamine and amino acid neurotransmitters in the hippocampus may be the important mechanisms underlying the action of DZXYS antidepressant-like effect in chronically stressed rats.

  15. Catecholaminergic System of Invertebrates: Comparative and Evolutionary Aspects in Comparison With the Octopaminergic System.

    Science.gov (United States)

    Gallo, Valentina P; Accordi, Fiorenza; Chimenti, Claudio; Civinini, Annalena; Crivellato, Enrico

    2016-01-01

    In this review we examined the catecholaminergic system of invertebrates, starting from protists and getting to chordates. Different techniques used by numerous researchers revealed, in most examined phyla, the presence of catecholamines dopamine, noradrenaline, and adrenaline or of the enzymes involved in their synthesis. The catecholamines are generally linked to the nervous system and they can act as neurotransmitters, neuromodulators, and hormones; moreover they play a very important role as regards the response to a large number of stress situations. Nevertheless, in some invertebrate phyla belonging to Protostoma, the monoamine octopamine is the main biogenic amine. The presence of catecholamines in some protists suggests a role as intracellular or interorganismal signaling molecules and an ancient origin of their synthetic pathways. The catecholamines appear also involved in the regulation of bioluminescence and in the control of larval development and metamorphosis in some marine invertebrate phyla. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Quantitative distribution of monoamine oxidase A in brainstem monoamine nuclei is normal in major depression.

    Science.gov (United States)

    Ordway, G A; Farley, J T; Dilley, G E; Overholser, J C; Meltzer, H Y; Balraj, E K; Stockmeier, C A; Klimek, V

    1999-11-13

    An abnormal expression of noradrenergic proteins (e.g., tyrosine hydroxylase, norepinephrine transporters) in the locus coeruleus has recently been demonstrated in subjects with major depression and/or victims of suicide. Monoamine oxidase A (MAO-A) is a key enzyme in the catabolism of biogenic amines and is expressed in brain noradrenergic neurons. In this study, the binding of [3H]Ro41-1049 to MAO-A was measured by quantitative autoradiography at multiple levels along the rostral-caudal axis of the noradrenergic locus coeruleus from subjects with major depression and age- and postmortem interval-matched control subjects who were psychiatrically normal. [3H]Ro41-1049 binding to MAO-A was unevenly distributed along the axis of the locus coeruleus, paralleling an uneven number of neuromelanin-containing (noradrenergic) neurons throughout the nucleus. Accordingly, there was a significant correlation between the number of neuromelanin-containing neurons per section and the specific binding of [3H]Ro41-1049 at any particular level of the locus coeruleus in control subjects (r(2)=0.25; pdepression (r(2)=0.14; pdepression to psychiatrically normal control subjects. These findings demonstrate that the pathophysiology of major depression is not likely to involve abnormalities in MAO-A.

  17. Cytoplasmic permeation pathway of neurotransmitter transporters.

    Science.gov (United States)

    Rudnick, Gary

    2011-09-06

    Ion-coupled solute transporters are responsible for transporting nutrients, ions, and signaling molecules across a variety of biological membranes. Recent high-resolution crystal structures of several transporters from protein families that were previously thought to be unrelated show common structural features indicating a large structural family representing transporters from all kingdoms of life. This review describes studies that led to an understanding of the conformational changes required for solute transport in this family. The first structure in this family showed the bacterial amino acid transporter LeuT, which is homologous to neurotransmitter transporters, in an extracellularly oriented conformation with a molecule of leucine occluded at the substrate site. Studies with the mammalian serotonin transporter identified positions, buried in the LeuT structure, that defined a potential pathway leading from the cytoplasm to the substrate binding site. Modeling studies utilized an inverted structural repeat within the LeuT crystal structure to predict the conformation of LeuT in which the cytoplasmic permeation pathway, consisting of positions identified in SERT, was open for diffusion of the substrate to the cytoplasm. From the difference between the model and the crystal structures, a simple "rocking bundle" mechanism was proposed, in which a four-helix bundle changed its orientation with respect to the rest of the protein to close the extracellular pathway and open the cytoplasmic one. Subsequent crystal structures from structurally related proteins provide evidence supporting this model for transport.

  18. Dirty electricity, chronic stress, neurotransmitters and disease.

    Science.gov (United States)

    Milham, Samuel; Stetzer, David

    2013-12-01

    Dirty electricity, also called electrical pollution, is high-frequency voltage transients riding along the 50 or 60 Hz electricity provided by the electric utilities. It is generated by arcing, by sparking and by any device that interrupts current flow, especially switching power supplies. It has been associated with cancer, diabetes and attention deficit hyperactivity disorder in humans. Epidemiological evidence also links dirty electricity to most of the diseases of civilization including cancer, cardiovascular disease, diabetes and suicide, beginning at the turn of the twentieth century. The dirty electricity level in a public library was reduced from over 10 000 Graham/Stetzer (G/S) units to below 50 G/S units by installing plug-in capacitive filters. Before cleanup, the urinary dopamine level of only one of seven volunteers was within normal levels, while four of seven phenylethylamine levels were normal. After an initial decline, over the next 18 weeks the dopamine levels gradually increased to an average of over 215 μg/g creatinine, which is well above 170 μg/g creatinine, the high normal level for the lab. Average phenylethylamine levels also rose gradually to slightly above 70 μg/g creatinine, the high normal level for the lab. Neurotransmitters may be biomarkers for dirty electricity and other electromagnetic field exposures. We believe that dirty electricity is a chronic stressor of electrified populations and is responsible for many of their disease patterns.

  19. Taltirelin improves motor ataxia independently of monoamine levels in rolling mouse nagoya, a model of spinocerebellar atrophy.

    Science.gov (United States)

    Nakamura, Tomoka; Honda, Motoko; Kimura, Satoko; Tanabe, Mitsuo; Oda, Sen-ichi; Ono, Hideki

    2005-12-01

    To examine the relationship between motor ataxia and monoamine levels in the central nervous system, the contents and concentrations of noradrenaline (NA), dopamine (DA) and serotonin (5-HT) in the cerebellum, brain stem and spinal cord were measured in rolling mouse Nagoya (RMN), a murine model of spinocerebellar atrophy. The tissue weight of the cerebellum and spinal cord, but not that of the brain stem was significantly lower in RMN than in the control group. In RMN, the NA content of the brain stem and spinal cord, but not the cerebellum were decreased relative to the control, and the concentration of NA in the spinal cord was also lower, but not significant. The DA and 5-HT contents in each tissue did not differ from those of the control, but the concentrations of monoamines, except for DA, were elevated in the brain stem and spinal cord in RMN. In particular, the concentrations of NA, DA and 5-HT in the cerebellum were significantly increased in RMN. Repeated administration of tartilerin hydrate, an analog of thyrotropin-releasing hormone, improved the ataxia of RMN, and elicited no obvious changes in either monoamine content or concentration of cerebellum, brain stem and spinal cord. These results indicate that the concentration of DA, as well as NA and 5-HT, increased in the RMN cerebellum, and that tartilerin improves the motor function of these mice via mechanisms other than changes in the levels of NA, DA and 5-HT in the central nervous system.

  20. Synthesis of symmetrical and non-symmetrical bivalent neurotransmitter ligands

    DEFF Research Database (Denmark)

    Stuhr-Hansen, Nicolai; Andersen, Jacob; Thygesen, Mikkel Boas

    2016-01-01

    A novel procedure for synthesis of bivalent neurotransmitter ligands was developed by reacting O-benzyl protected N-nosylated dopamine and serotonin with alkyl- or PEG-linked diols under Fukuyama-Mitsunobu conditions in the presence of DIAD/PPh3 generating three different bivalent neurotransmitter...... ligands in a one-pot reaction. The methodol. establishes a facile route towards bivalent neurotransmitter ligands, and libraries of in total 40 sym. and non-sym. bivalent and monovalent dopamine and serotonin compds. linked through alkyl or PEG spacers of varying length were prepd. Interestingly...

  1. Nitrogen heterocycles as potential monoamine oxidase inhibitors: Synthetic aspects

    Directory of Open Access Journals (Sweden)

    Pravin O. Patil

    2014-12-01

    Full Text Available The present review highlights the synthetic methods of monoamine oxidase inhibitors (MAO belonging to a group of nitrogen heterocycles such as pyrazoline, indole, xanthine, oxadiazole, benzimidazole, pyrrole, quinoxaline, thiazole and other related compounds (1990–2012. Moreover, it emphasizes salient findings related to chemical structures and the bioactivities of these heterocycles as MAO inhibitors. The aim of this review is to find out different methods for the synthesis of nitrogen containing heterocycles and their bioactivity related aspects as MAO inhibitors.

  2. A novel fluorogenic probe for monoamine oxidase assays

    Institute of Scientific and Technical Information of China (English)

    You You Lu; Yu Guang Wang; Bin Dai; Yi Qi Dai; Zhao Wang; Zheng Wei Fu; Qing Zhu

    2008-01-01

    Monoamine oxidase is flavoenzymes, widely distributed in mammals. It is well recognized that MAOs serve an important role in metabolism that they have close relationship with health .Along with the discoveries between MAOs and neurotic disease, more and more studies have been jumped in .In this paper, we design a new probe for assaying the activities of MAOs. The results showed that the probe [7-(3-aminopropoxy)coumarin] is simple, effective and sensitive for MAOB.

  3. Monoamines, BDNF, Dehydroepiandrosterone, DHEA-Sulfate, and Childhood Depression—An Animal Model Study

    Directory of Open Access Journals (Sweden)

    O. Malkesman

    2009-01-01

    Full Text Available Basal levels of monoamines and DHEA in four main limbic brain regions were measured in prepubertal Wistar Kyoto (WKY rats (a putative animal model of childhood depression. Basal levels of “Brain-Derived Neurotrophic Factor (BDNF” were also determined in two regions in the hippocampus, compared with Wistar strain controls. In the second phase, we examined the responsiveness of prepubertal WKY rats to different types of chronic antidepressant treatments: Fluoxetine, Desipramine, and dehydroepiandrosterone sulfate (DHEAS. WKY prepubertal rats exhibited different monoamine levels in the limbic system, reduced DHEA levels in the VTA and lower levels of BDNF in the hippocampus CA3 region compared to controls. In prepubertal WKY rats, only treatment with DHEAS produced a statistically significant decrease in immobility, compared to saline-administered controls in the forced swim test. Wistar controls were not affected by any antidepressant. The results imply that DHEA(S and BDNF may be involved in the pathophysiology and pharmacotherapy of childhood depression.

  4. Mechanism for alternating access in neurotransmitter transporters.

    Science.gov (United States)

    Forrest, Lucy R; Zhang, Yuan-Wei; Jacobs, Miriam T; Gesmonde, Joan; Xie, Li; Honig, Barry H; Rudnick, Gary

    2008-07-29

    Crystal structures of LeuT, a bacterial homologue of mammalian neurotransmitter transporters, show a molecule of bound substrate that is essentially exposed to the extracellular space but occluded from the cytoplasm. Thus, there must exist an alternate conformation for LeuT in which the substrate is accessible to the cytoplasm and a corresponding mechanism that switches accessibility from one side of the membrane to the other. Here, we identify the cytoplasmic accessibility pathway of the alternate conformation in a mammalian serotonin transporter (SERT) (a member of the same transporter family as LeuT). We also propose a model for the cytoplasmic-facing state that exploits the internal pseudosymmetry observed in the crystal structure. LeuT contains two structurally similar repeats (TMs1-5 and TMs 6-10) that are inverted with respect to the plane of the membrane. The conformational differences between them result in the formation of the extracellular pathway. Our model for the cytoplasm-facing state exchanges the conformations of the two repeats and thus exposes the substrate and ion-binding sites to the cytoplasm. The conformational change that connects the two states primarily involves the tilting of a 4-helix bundle composed of transmembrane helices 1, 2, 6, and 7. Switching the tilt angle of this bundle is essentially equivalent to switching the conformation of the two repeats. Extensive mutagenesis of SERT and accessibility measurements, using cysteine reagents, are accommodated by our model. These observations may be of relevance to other transporter families, many of which contain internal inverted repeats.

  5. 美沙酮维持治疗者中枢神经递质功能的变化%Functional change of neurotransmitters in central nervous system for outpatients with methadone maintenance treatment

    Institute of Scientific and Technical Information of China (English)

    龚斌; 朱千

    2014-01-01

    Objective To detect neurotransmitters function in the brain and the brain functional index of outpatients with methadone maintenance treatment,and understand the change features of brain function.Methods Collect brain electrical power signals were collected from 58 outpatients with methadone maintenance treatment (MMT) and 44 healthy adults,and the correlations between the power of the neurotransmitters and the brain functional status were analyzed.Results (1) In MMT group,all neurotransmitters were lower generally than those in the control group,and the differences of GABA ((17.73±3.54) μV2 vs.(121.48±44.64) iμV2,P<0.01),Glu ((42.18±12.84) μV2 vs.(105.31 ± 34.95) μV2,P<0.05) were significant.(2) The relative powers of GABA ((17.10±51.72) μV2 vs.(78.67± 10.93) μV2,P<0.001) and Glu((30.48±21.61) μV2 vs.(69.23±42.26) μV2,P<0.001) reduced significantly,while 5-HT((297.18±31.54) μ V2 vs.(280.18±31.54) μV2,P<0.01),ACh ((235.08±37.72) μV2 vs.(217.23±40.60)μV2,P<0.05),NE((164.11±33.05) μV2 vs (146.39±30.80) μV2,P <0.01),DA((98.87±22.48) μV2 vs.(91.49±21.04)μV2,P<0.05) rised significantly in MMT group.(3)The global power was lower((1012.01± 195.09)μV2 Vs.(1775.94±458.99) μV2,P<0.01),and the excitement-inhibition index(2.19± 1.46 vs.0.99±0.47,P<0.001) and the relative entropy((89.45±9.71) % vs.(75.48±9.97) %,P <0.01)were higher than those in the controls.(4) In MMT group,there were positive correlation between all neurotransmitters and global power,as well as that between Glu and excitement-inhibition index (r=0.264,P<0.05),NE and Vasomotor index(r=0.269,P<0.05),but negative correlation between relative entropy and 5-HT(r=-0.276,P<0.05) as well as DA(r=-0.375,P<0.01)significantly.Conclusion The brain function of outpatients with MMT are lower than the normal significantly,and there are clearly imbalance between the excitement and inhibition among the brain neurotransmitters.%目的

  6. Extracellular Neurotransmitter Receptor Clustering: Think Outside the Box

    Institute of Scientific and Technical Information of China (English)

    Matthias Kneussel

    2010-01-01

    @@ Postsynaptic submembrane scaffolds cluster neurotransmitter receptors through intracellular protein-protein interactions. Growing evidence supports the view that extracellular factors can be almost as important to trigger synaptic receptor aggregation.

  7. SLC6 Neurotransmitter Transporters: Structure, Function, and Regulation

    DEFF Research Database (Denmark)

    Kristensen, Anders S; Andersen, Jacob; Jørgensen, Trine N

    2011-01-01

    The neurotransmitter transporters (NTTs) belonging to the solute carrier 6 (SLC6) gene family (also referred to as the neurotransmitter-sodium-symporter family or Na(+)/Cl(-)-dependent transporters) comprise a group of nine sodium- and chloride-dependent plasma membrane transporters for the monoa......The neurotransmitter transporters (NTTs) belonging to the solute carrier 6 (SLC6) gene family (also referred to as the neurotransmitter-sodium-symporter family or Na(+)/Cl(-)-dependent transporters) comprise a group of nine sodium- and chloride-dependent plasma membrane transporters....... Furthermore, psychostimulants such as cocaine and amphetamines have the SLC6 NTTs as primary targets. Beginning with the determination of a high-resolution structure of a prokaryotic homolog of the mammalian SLC6 transporters in 2005, the understanding of the molecular structure, function, and pharmacology...

  8. Analysis of neurotransmitters, neurosteroids and their metabolites in biological samples

    OpenAIRE

    2015-01-01

    Neurotransmitters and neurosteroids are compounds that regulate the functions of the brain. The neurotransmitters dopamine (DA) and serotonin (5-HT) play a role in several psychological conditions, including schizophrenia, depression and anxiety. DA also has an important role in Parkinson s disease. Neurosteroids are involved in neurodegenerative diseases. In Alzheimer s disease and multiple sclerosis, the levels of neurosteroids are decreased in certain areas of the brain. Neurosteroids diff...

  9. Development of new radiopharmaceuticals for imaging monoamine oxidase B

    Energy Technology Data Exchange (ETDEWEB)

    Vasdev, Neil, E-mail: neil.vasdev@utoronto.ca; Sadovski, Oleg; Moran, Matthew D.; Parkes, Jun; Meyer, Jeffrey H.; Houle, Sylvain; Wilson, Alan A.

    2011-10-15

    Introduction: Imaging monoamine oxidase B (MAO-B) in the central nervous system with PET is an important goal for psychiatric studies. We here report an improved and automated radiosynthesis of N-(6-[{sup 18}F]-fluorohexyl)-N-methylpropargylamine ([{sup 18}F]FHMP; [{sup 18}F]-1), as well as the radiosynthesis of two new promising candidates for imaging cerebral MAO-B, namely, carbon-11-labeled 3-(4-[{sup 11}C]-methoxyphenyl)-6-methyl-2H-1-benzopyran-2-one ([{sup 11}C]-2) and N-((1H-pyrrol-2-yl)methyl)-N-[{sup 11}C]-methyl-1-phenylmethanamine ([{sup 11}C]-3). Methods: Fluorine-18-labeled 1 was prepared via a tosyloxy precursor in 29%{+-}5% uncorrected radiochemical yield, relative to [{sup 18}F]-fluoride. Both carbon-11-labeled compounds were prepared with [{sup 11}C]CH{sub 3}I using the 'LOOP' method in 11% and 18% uncorrected radiochemical yields, respectively, relative to starting [{sup 11}C]CO{sub 2}. All radiotracers had specific activities >37 GBq/{mu}mol and were >98% radiochemically pure at end of synthesis (<40 min). All radiotracers were evaluated by ex vivo biodistribution studies in conscious rodents. Results: A major radioactive metabolite in the rodent brain was observed following administration of [{sup 18}F]-1. While [{sup 11}C]-2 had moderate brain penetration and good clearance from normal brain tissue, distribution of radioactivity in brain was indicative of free and nonspecific binding. Good brain uptake was observed with [{sup 11}C]-3 (0.8%-1.4% injected dose per gram at 5 min postinjection), binding appeared to be reversible and distribution conformed with regional distribution of MAO-B in the rat brain. Preinjection of 3 or L-deprenyl showed a modest reduction (up to 25%) of brain activity. Conclusion: Carbon-11-labeled 3 was found to have the most favorable properties of the radiotracers evaluated; however, the signal-to-noise ratio was too low to warrant further in vivo imaging studies. Alternative radiotracers for imaging MAO

  10. Selected hormonal and neurotransmitter mechanisms regulating feed intake in sheep.

    Science.gov (United States)

    Sartin, J L; Daniel, J A; Whitlock, B K; Wilborn, R R

    2010-11-01

    Appetite control is a major issue in normal growth and in suboptimal growth performance settings. A number of hormones, in particular leptin, activate or inhibit orexigenic or anorexigenic neurotransmitters within the arcuate nucleus of the hypothalamus, where feed intake regulation is integrated. Examples of appetite regulatory neurotransmitters are the stimulatory neurotransmitters neuropeptide Y (NPY), agouti-related protein (AgRP), orexin and melanin-concentrating hormone and the inhibitory neurotransmitter, melanocyte-stimulating hormone (MSH). Examination of messenger RNA (using in situ hybridization and real-time PCR) and proteins (using immunohistochemistry) for these neurotransmitters in ruminants has indicated that physiological regulation occurs in response to fasting for several of these critical genes and proteins, especially AgRP and NPY. Moreover, intracerebroventricular injection of each of the four stimulatory neurotransmitters can increase feed intake in sheep and may also regulate either growth hormone, luteinizing hormone, cortisol or other hormones. In contrast, both leptin and MSH are inhibitory to feed intake in ruminants. Interestingly, the natural melanocortin-4 receptor (MC4R) antagonist, AgRP, as well as NPY can prevent the inhibition of feed intake after injection of endotoxin (to model disease suppression of appetite). Thus, knowledge of the mechanisms regulating feed intake in the hypothalamus may lead to mechanisms to increase feed intake in normal growing animals and prevent the wasting effects of severe disease in animals.

  11. [Detection of neurotransmitter interactions with PET and SPECT by pharmacological challenge paradigms].

    Science.gov (United States)

    Schlösser, R

    2000-01-01

    Functional brain imaging with positron emission tomography (PET) and single photon emission computerized tomography (SPECT) enables the in vivo study of specific neurochemical processes in the context of normal regulatory mechanisms and pathophysiological alterations of the brain. By combining these methods with pharmacological challenge-paradigms, the study of functional interactions of different neurotransmitter systems is possible. This review will present data from animal and healthy volunteer studies as well as first data from investigations in different patient populations with regard to this research direction. Especially, interactions of different neurotransmitter systems with the dopaminergic and the cholinergic system will be discussed. The database acquired so far confirms existing models of neuronal feedback-circuits, and the first clinical results are consistent with the hypothesis of an increased dopaminergic responsivity in schizophrenic patients. These results open up new perspectives for a further evaluation of treatment response predictors from drug-challenge studies and for the development of new drug treatments for neuropsychiatric disorders.

  12. Swim pacemaker response to bath applied neurotransmitters in the cubozoan Tripedalia cystophora.

    Science.gov (United States)

    Bielecki, Jan; Nachman, Gösta; Garm, Anders

    2013-09-01

    The four rhopalia of cubomedusae are integrated parts of the central nervous system carrying their many eyes and thought to be the centres of visual information processing. Rhopalial pacemakers control locomotion through a complex neural signal transmitted to the ring nerve and the signal frequency is modulated by the visual input. Since electrical synapses have never been found in the cubozoan nervous system all signals are thought to be transmitted across chemical synapses, and so far information about the neurotransmitters involved are based on immunocytochemical or behavioural data. Here we present the first direct physiological evidence for the types of neurotransmitters involved in sensory information processing in the rhopalial nervous system. FMRFamide, serotonin and dopamine are shown to have inhibitory effect on the pacemaker frequency. There are some indications that the fast acting acetylcholine and glycine have an initial effect and then rapidly desensitise. Other tested neuroactive compounds (GABA, glutamate, and taurine) could not be shown to have a significant effect.

  13. 经前期综合征相关神经递质及其受体研究进展%Research Progress of Neurotransmitters and the Receptors Involved in Premenstrual Syndrome

    Institute of Scientific and Technical Information of China (English)

    高兴笑

    2011-01-01

    经前期综合征(PMS)的发病机制十分复杂,目前尚未完全明确,与该病可能相关的神经递质主要包括单胺类、氨基酸类和肽类.国内外已有研究表明PMS与单胺类(以5-羟色胺为主)及氨基酸类(以谷氨酸、氨酪酸为主)神经递质有关,但有关肽类对PMS影响的研究较少较浅.现对可能涉及该病的神经递质及其受体进行归类综述,以期为进一步探讨PMS神经生化方面的微观机制提供参考.%Pathogenesis of premenstrual syndrome is so complicated that a clear understanding of it is still missing. Neurotransmitters,which may have close relation to PMS,including monoamines,aminoacids and neuropeptides. Domestic and abroad researches have found that PMS is closely related to monoamines( 5-HE、 DA and NE )and aminoacids( GABA and Glu are of greater importance ),but studies on neuropeptides are less and supeificial. Here is to introduce the development of neurotransmitters and their receptors related to PMS according to their categories, with expectation to provide references on neural and biochemical micro-mechanism for PMS.

  14. Alteration of behavior and monoamine levels attributable to Lactobacillus plantarum PS128 in germ-free mice.

    Science.gov (United States)

    Liu, Wei-Hsien; Chuang, Hsiao-Li; Huang, Yen-Te; Wu, Chien-Chen; Chou, Geng-Ting; Wang, Sabrina; Tsai, Ying-Chieh

    2016-02-01

    Probiotics, defined as live bacteria or bacterial products, confer a significant health benefit to the host, including amelioration of anxiety-like behavior and psychiatric illnesses. Here we administered Lactobacillus plantarum PS128 (PS128) to a germ-free (GF) mouse model to investigate the impact of the gut-brain axis on emotional behaviors. First, we demonstrated that chronic administration of live PS128 showed no adverse effects on physical health. Then, we found that administration of live PS128 significantly increased the total distance traveled in the open field test and decreased the time spent in the closed arm in the elevated plus maze test, whereas the administration of PS128 had no significant effects in the depression-like behaviors of GF mice. Also, chronic live PS128 ingestion significantly increased the levels of both serotonin and dopamine in the striatum, but not in the prefrontal cortex or hippocampus. These results suggest that the chronic administration of PS128 is safe and could induce changes in emotional behaviors. The behavioral changes are correlated with the increase in the monoamine neurotransmitters in the striatum. These findings suggest that daily intake of the L. plantarum strain PS128 could improve anxiety-like behaviors and may be helpful in ameliorating neuropsychiatric disorders.

  15. Microfluidic in-channel multi-electrode platform for neurotransmitter sensing

    Science.gov (United States)

    Kara, A.; Mathault, J.; Reitz, A.; Boisvert, M.; Tessier, F.; Greener, J.; Miled, A.

    2016-03-01

    In this project we present a microfluidic platform with in-channel micro-electrodes for in situ screening of bio/chemical samples through a lab-on-chip system. We used a novel method to incorporate electrochemical sensors array (16x20) connected to a PCB, which opens the way for imaging applications. A 200 μm height microfluidic channel was bonded to electrochemical sensors. The micro-channel contains 3 inlets used to introduce phosphate buffer saline (PBS), ferrocynide and neurotransmitters. The flow rate was controlled through automated micro-pumps. A multiplexer was used to scan electrodes and perform individual cyclic voltammograms by a custom potentiostat. The behavior of the system was linear in terms of variation of current versus concentration. It was used to detect the neurotransmitters serotonin, dopamine and glutamate.

  16. Spintronic characteristics of self-assembled neurotransmitter acetylcholine molecular complexes enable quantum information processing in neural networks and brain

    Science.gov (United States)

    Tamulis, Arvydas; Majauskaite, Kristina; Kairys, Visvaldas; Zborowski, Krzysztof; Adhikari, Kapil; Krisciukaitis, Sarunas

    2016-09-01

    Implementation of liquid state quantum information processing based on spatially localized electronic spin in the neurotransmitter stable acetylcholine (ACh) neutral molecular radical is discussed. Using DFT quantum calculations we proved that this molecule possesses stable localized electron spin, which may represent a qubit in quantum information processing. The necessary operating conditions for ACh molecule are formulated in self-assembled dimer and more complex systems. The main quantum mechanical research result of this paper is that the neurotransmitter ACh systems, which were proposed, include the use of quantum molecular spintronics arrays to control the neurotransmission in neural networks.

  17. Neuronal monoamine reuptake inhibitors enhance in vitro susceptibility to chloroquine in resistant Plasmodium falciparum.

    OpenAIRE

    Coutaux, A F; Mooney, J. J.; Wirth, D. F.

    1994-01-01

    Chloroquine resistance in Plasmodium falciparum was reversed in vitro by the neuronal monoamine reuptake inhibitors and antidepressants desipramine, sertraline, fluoxetine, and norfluoxetine but not by carbamazepine, an antiseizure and mood-stabilizing tricyclic drug resembling desipramine which only weakly inhibits neuronal monoamine reuptake. These findings have important clinical implications for drug combination therapy.

  18. Mechanical tension contributes to clustering of neurotransmitter vesicles at presynaptic terminals

    OpenAIRE

    2009-01-01

    Memory and learning in animals are mediated by neurotransmitters that are released from vesicles clustered at the synapse. As a synapse is used more frequently, its neurotransmission efficiency increases, partly because of increased vesicle clustering in the presynaptic neuron. Vesicle clustering has been believed to result primarily from biochemical signaling processes that require the connectivity of the presynaptic terminal with the cell body, the central nervous system, and the postsynapt...

  19. REM sleep at its core—Circuits, neurotransmitters and pathophysiology

    Directory of Open Access Journals (Sweden)

    John ePeever

    2015-05-01

    Full Text Available REM sleep is generated and maintained by the interaction of a variety of neurotransmitter systems in the brainstem, forebrain and hypothalamus. Within these circuits lies a core region that is active during REM sleep, known as the subcoeruleus nucleus (SubC or sublaterodorsal nucleus. It is hypothesized that glutamatergic SubC neurons regulate REM sleep and its defining features such as muscle paralysis and cortical activation. REM sleep paralysis is initiated when glutamatergic SubC activate neurons in the ventral medial medulla (VMM, which causes release of GABA and glycine onto skeletal motoneurons. REM sleep timing is controlled by activity of GABAergic neurons in the ventrolateral periaqueductal gray (vlPAG and dorsal paragigantocellular reticular nucleus (DPGi as well as melanin-concentrating hormone (MCH neurons in the hypothalamus and cholinergic cells in the laterodorsal (LDT and pedunculo-pontine tegmentum (PPT in the brainstem. Determining how these circuits interact with the SubC is important because breakdown in their communication is hypothesized to underlie cataplexy/narcolepsy and REM sleep behaviour disorder (RBD. This review synthesizes our current understanding of mechanisms generating healthy REM sleep and how dysfunction of these circuits contributes to common REM sleep disorders such as cataplexy/narcolepsy and RBD.

  20. REM Sleep at its Core – Circuits, Neurotransmitters, and Pathophysiology

    Science.gov (United States)

    Fraigne, Jimmy J.; Torontali, Zoltan A.; Snow, Matthew B.; Peever, John H.

    2015-01-01

    Rapid eye movement (REM) sleep is generated and maintained by the interaction of a variety of neurotransmitter systems in the brainstem, forebrain, and hypothalamus. Within these circuits lies a core region that is active during REM sleep, known as the subcoeruleus nucleus (SubC) or sublaterodorsal nucleus. It is hypothesized that glutamatergic SubC neurons regulate REM sleep and its defining features such as muscle paralysis and cortical activation. REM sleep paralysis is initiated when glutamatergic SubC cells activate neurons in the ventral medial medulla, which causes release of GABA and glycine onto skeletal motoneurons. REM sleep timing is controlled by activity of GABAergic neurons in the ventrolateral periaqueductal gray and dorsal paragigantocellular reticular nucleus as well as melanin-concentrating hormone neurons in the hypothalamus and cholinergic cells in the laterodorsal and pedunculo-pontine tegmentum in the brainstem. Determining how these circuits interact with the SubC is important because breakdown in their communication is hypothesized to underlie narcolepsy/cataplexy and REM sleep behavior disorder (RBD). This review synthesizes our current understanding of mechanisms generating healthy REM sleep and how dysfunction of these circuits contributes to common REM sleep disorders such as cataplexy/narcolepsy and RBD. PMID:26074874

  1. Potential Antidepressant Role of Neurotransmitter CART: Implications for Mental Disorders

    Directory of Open Access Journals (Sweden)

    Peizhong Mao

    2011-01-01

    Full Text Available Depression is one of the most prevalent and debilitating public health concerns. Although no single cause of depression has been identified, it appears that interaction among genetic, epigenetic, biochemical, environmental, and psychosocial factors may explain its etiology. Further, only a fraction of depressed patients show full remission while using current antidepressants. Therefore, identifying common pathways of the disorder and using that knowledge to develop more effective pharmacological treatments are two primary targets of research in this field. Brain-enriched neurotransmitter CART (cocaine- and amphetamine-regulated transcript has multiple functions related to emotions. It is a potential neurotrophic factor and is involved in the regulation of hypothalamic-pituitary-adrenal axis and stress response as well as in energy homeostasis. CART is also highly expressed in limbic system, which is considered to have an important role in regulating mood. Notably, adolescents carrying a missense mutation in the CART gene exhibit increased depression and anxiety. Hence, CART peptide may be a novel promising antidepressant agent. In this paper, we summarize recent progress in depression and CART. In particular, we emphasize a new antidepressant function for CART.

  2. Liquid Chromatography-Tandem Mass Spectrometry in Studies of Neurotransmitters and Their Metabolites in the Brain

    OpenAIRE

    Uutela, PÀivi

    2009-01-01

    Neurotransmitters transfer chemically the electrical impulse from one neuron to another in the brain. The concentration of neurotransmitters in many neurological disorders is altered. The measurement of neurotransmitters in the brain is needed to understand how these diseases develop and how they can be treated. Neurotransmitters can be extracted from the brains of freely moving, alert animals by microdialysis technique. The concentration of neurotransmitters and their metabolites in brain mi...

  3. Correlation between changes of central neurotransmitter expression and stress response in mice A restraint time-course analysis

    Institute of Scientific and Technical Information of China (English)

    Li Bao; Xinsheng Yao; Liang Zhao; Yanqing Lü; Hiroshi Kurihara

    2008-01-01

    BACKGROUND:Changes in central neurotransmitter expression play an important role in stress response and forms the basis for stress-induced psychological and behavior changes.OBJECTIVE:To observe the effects of different restraint stress intervals on brain monoamine neurotransmitter expression,and to investigate the correlation between stress response and neurotransmitter levels.DESIGN:Randomized controlled animal study.SETTING:Chinese Herb and Natural Medicine Institute,Pharmacological College of Jinan University.MATERIALS:Sixty 7-week-old male Kunming mice of clean grade,weighing 18-22 g,were provided by the Guangdong Medical Experimental Animal Center.The experiment was in accordance with animal ethics standards.METHODS:This study was performed at the Chinese Herb and Natural Medicine Institute,Pharmacological College of Jinan University from June 2006 to May 2007.A restraint device for mice was constructed according to published reports.Experimental mice were adaptively fed for 1 week and randomly divided into a control group(n=10)and an experimental group(n=50).The experimental group was sub-divided into five restraint intervals:4,8,12,18,and 24 hours(n=10 mice per time point).Animals in the experimental group were not allowed to eat or drink during the restraint period.Mice in the control group did not undergo restraint,but had identical food and water restrictions.Cerebral cortex and hypothalamus were separated based on observational times and protein was extracted using perchloric acid.Central monoamine neurotransmitter levels were measured using high performance liquid chromatography with electrochemical detection.MAIN OUTCOME MEASURES:Levels of norepinephrine(NE),dopamine hydrochloride(DA),3,4-dihydroxyphen-ylanetic acid (DOPAC),homovanillic acid(HVA),5-hydroxytryptamine(5-HT),and 5-hydroxyindoleac-etic acid(5-HIAA)in the cerebral cortex and hypothalamus of mice.RESULTS:Sixty mice were included in the final analysis.①NE levels in the cerebral

  4. The Met receptor tyrosine kinase prevents zebrafish primary motoneurons from expressing an incorrect neurotransmitter

    Directory of Open Access Journals (Sweden)

    Eisen Judith S

    2008-07-01

    Full Text Available Abstract Background Expression of correct neurotransmitters is crucial for normal nervous system function. How neurotransmitter expression is regulated is not well-understood; however, previous studies provide evidence that both environmental signals and intrinsic differentiation programs are involved. One environmental signal known to regulate neurotransmitter expression in vertebrate motoneurons is Hepatocyte growth factor, which acts through the Met receptor tyrosine kinase and also affects other aspects of motoneuron differentiation, including axonal extension. Here we test the role of Met in development of motoneurons in embryonic zebrafish. Results We found that met is expressed in all early developing, individually identified primary motoneurons and in at least some later developing secondary motoneurons. We used morpholino antisense oligonucleotides to knock down Met function and found that Met has distinct roles in primary and secondary motoneurons. Most secondary motoneurons were absent from met morpholino-injected embryos, suggesting that Met is required for their formation. We used chemical inhibitors to test several downstream pathways activated by Met and found that secondary motoneuron development may depend on the p38 and/or Akt pathways. In contrast, primary motoneurons were present in met morpholino-injected embryos. However, a significant fraction of them had truncated axons. Surprisingly, some CaPs in met morpholino antisense oligonucleotide (MO-injected embryos developed a hybrid morphology in which they had both a peripheral axon innervating muscle and an interneuron-like axon within the spinal cord. In addition, in met MO-injected embryos primary motoneurons co-expressed mRNA encoding Choline acetyltransferase, the synthetic enzyme for their normal neurotransmitter, acetylcholine, and mRNA encoding Glutamate decarboxylase 1, the synthetic enzyme for GABA, a neurotransmitter never normally found in these motoneurons, but

  5. Synapsin II desynchronizes neurotransmitter release at inhibitory synapses by interacting with presynaptic calcium channels.

    Science.gov (United States)

    Medrihan, Lucian; Cesca, Fabrizia; Raimondi, Andrea; Lignani, Gabriele; Baldelli, Pietro; Benfenati, Fabio

    2013-01-01

    In the central nervous system, most synapses show a fast mode of neurotransmitter release known as synchronous release followed by a phase of asynchronous release, which extends over tens of milliseconds to seconds. Synapsin II (SYN2) is a member of the multigene synapsin family (SYN1/2/3) of synaptic vesicle phosphoproteins that modulate synaptic transmission and plasticity, and are mutated in epileptic patients. Here we report that inhibitory synapses of the dentate gyrus of Syn II knockout mice display an upregulation of synchronous neurotransmitter release and a concomitant loss of delayed asynchronous release. Syn II promotes γ-aminobutyric acid asynchronous release in a Ca(2+)-dependent manner by a functional interaction with presynaptic Ca(2+) channels, revealing a new role in synaptic transmission for synapsins.

  6. CDK5 serves as a major control point in neurotransmitter release.

    Science.gov (United States)

    Kim, Sung Hyun; Ryan, Timothy A

    2010-09-09

    CDK5 is an important kinase in nervous system function, controlling neural development and postsynaptic signal integration. Here we show that CDK5 plays a major role in controlling neurotransmitter release. Inhibition of CDK5 activity, by either acute or genetic means, leads to profound potentiation of presynaptic function, including unmasking of previously "silent" synapses. Removal of CDK5 activity additionally unlocks access to the resting synaptic vesicle pool, which normally remains recalcitrant to exocytosis and recycling even following prolonged action potential stimuli. Presynaptic CDK5 levels are additionally severely depleted by chronic neuronal silencing, a treatment that is functionally similar to CDK5 knockdown with regard to presynaptic potentiation. Thus CDK5 appears to be an integral element in presynaptic homeostatic scaling, and the resting vesicle pool appears to provide a potent functional presynaptic homeostatic control parameter. These studies thus pinpoint CDK5 as a major control point for modulation of neurotransmitter release in mammalian neurons.

  7. Activity-dependent neurotransmitter-receptor matching at the neuromuscular junction.

    Science.gov (United States)

    Borodinsky, Laura N; Spitzer, Nicholas C

    2007-01-02

    Signaling in the nervous system requires matching of neurotransmitter receptors with cognate neurotransmitters at synapses. The vertebrate neuromuscular junction is the best studied cholinergic synapse, but the mechanisms by which acetylcholine is matched with acetylcholine receptors are not fully understood. Because alterations in neuronal calcium spike activity alter transmitter specification in embryonic spinal neurons, we hypothesized that receptor expression in postsynaptic cells follows changes in transmitter expression to achieve this specific match. We find that embryonic vertebrate striated muscle cells normally express receptors for glutamate, GABA, and glycine as well as for acetylcholine. As maturation progresses, acetylcholine receptor expression prevails. Receptor selection is altered when early neuronal calcium-dependent activity is perturbed, and remaining receptor populations parallel changes in transmitter phenotype. In these cases, glutamatergic, GABAergic, and glycinergic synaptic currents are recorded from muscle cells, demonstrating that activity regulates matching of transmitters and their receptors in the assembly of functional synapses.

  8. Analysis of neurotransmitter tissue content of Drosophila melanogaster in different life stages.

    Science.gov (United States)

    Denno, Madelaine E; Privman, Eve; Venton, B Jill

    2015-01-21

    Drosophila melanogaster is a widely used model organism for studying neurological diseases with similar neurotransmission to mammals. While both larva and adult Drosophila have central nervous systems, not much is known about how neurotransmitter tissue content changes through development. In this study, we quantified tyramine, serotonin, octopamine, and dopamine in larval, pupal, and adult fly brains using capillary electrophoresis coupled to fast-scan cyclic voltammetry. Tyramine and octopamine content varied between life stages, with almost no octopamine being present in the pupa, while tyramine levels in the pupa were very high. Adult females had significantly higher dopamine content than males, but no other neurotransmitters were dependent on sex in the adult. Understanding the tissue content of different life stages will be beneficial for future work comparing the effects of diseases on tissue content throughout development.

  9. Lack of platelet monoamine oxidase activity in Cebus monkeys (Cebus albifrons).

    Science.gov (United States)

    Heintz, R; Richardson, M A; Perumal, A S; Casey, D E

    1989-01-01

    1. Recent evidence suggests that monoamine oxidase (MAO) plays an important role modulating the extrapyramidal syndromes produced by neuroleptic drugs in both human and nonhuman primates. 2. To evaluate the possibility of using peripheral blood platelet MAO-B levels as indices of central nervous system MAO-B effects, we measured platelet MAO-B levels in Cebus monkeys that were previously tested with neuroleptics (N = 36) or drug naive (N = 6). 3. No platelet MAO-B was consistently detectable in these blood samples. 4. Thus platelet measures of MAO-B do not reliably reflect brain MAO-B function in nonhuman primates and do not offer a useful model for studying blood-brain MAO-B relationships.

  10. Morphological alterations and acetylcholinesterase and monoamine oxidase inhibition in liver of zebrafish exposed to Aphanizomenon flos-aquae DC-1 aphantoxins.

    Science.gov (United States)

    Zhang, De Lu; Zhang, Jing; Hu, Chun Xiang; Wang, Gao Hong; Li, Dun Hai; Liu, Yong Ding

    2014-12-01

    Aphanizomenon flos-aquae is a cyanobacterium that produces neurotoxins or paralytic shellfish poisons (PSPs) called aphantoxins, which present threats to environmental safety and human health via eutrophication of water bodies worldwide. Although the molecular mechanisms of this neurotoxin have been studied, many questions remain unsolved, including those relating to in vivo hepatic neurotransmitter inactivation, physiological detoxification and histological and ultrastructural alterations. Aphantoxins extracted from the natural strain of A. flos-aquae DC-1 were analyzed by high-performance liquid chromatography. The main components were gonyautoxins 1 and 5 (GTX1, GTX5) and neosaxitoxin (neoSTX), which comprised 34.04%, 21.28%, and 12.77% respectively. Zebrafish (Danio rerio) were exposed intraperitoneally to 5.3 or 7.61 μg STX equivalents (eq)/kg (low and high doses, respectively) of A. flos-aquae DC-1 aphantoxins. Morphological alterations and changes in neurotransmitter conduction functions of acetylcholinesterase (AChE) and monoamine oxidase (MAO) in zebrafish liver were detected at different time points 1-24h post-exposure. Aphantoxin significantly enhanced hepatic alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities and histological and ultrastructural damage in zebrafish liver at 3-12 h post-exposure. Toxin exposure increased the reactive oxygen species content and reduced total antioxidative capacity in zebrafish liver, suggesting oxidative stress. AChE and MAO activities were significantly inhibited, suggesting neurotransmitter inactivation/conduction function abnormalities in zebrafish liver. All alterations were dose- and time-dependent. Overall, the results indicate that aphantoxins/PSPs induce oxidative stress through inhibition of AChE and MAO activities, leading to neurotoxicity in zebrafish liver. The above parameters may be useful as bioindicators for investigating aphantoxins/PSPs and cyanobacterial blooms in nature

  11. Affinity of four polar neurotransmitters for lipid bilayer membranes

    DEFF Research Database (Denmark)

    Wang, Chunhua; Ye, Fengbin; Valardez, Gustavo F.

    2011-01-01

    Weak interactions of neurotransmitters and the lipid matrix in the synaptic membrane have been hypothesized to play a role in synaptic transmission of nerve signals, particularly with respect to receptor desensitization (Cantor, R. S. Biochemistry 2003, 42, 11891). The strength of such interactions......, however, was not measured, and this is an obvious impediment for further evaluation and understanding of a possible role for desensitization. We have used dialysis equilibrium to directly measure the net affinity of selected neurotransmitters for lipid membranes and analyzed this affinity data...... with respect to calorimetric measurements and molecular dynamics simulations. We studied an anionic (glutamate), a cationic (acetylcholine), and two zwitterionic (-aminobutyric acid and glycine) neurotransmitters, and membranes of pure dimyristoyl phosphatidylcholine (DMPC), DMPC doped with 10% anionic lipid...

  12. Leukemia Inhibitory Factor Induces Neurotransmitter Switching in Transgenic Mice

    Science.gov (United States)

    Bamber, Bruce A.; Masters, Brian A.; Hoyle, Gary W.; Brinster, Ralph L.; Palmiter, Richard D.

    1994-08-01

    Leukemia inhibitory factor (LIF) is a cytokine growth factor that induces rat sympathetic neurons to switch their neurotransmitter phenotype from noradrenergic to cholinergic in vitro. To test whether LIF can influence neuronal differentiation in vivo, we generated transgenic mice that expressed LIF in pancreatic islets under the control of the insulin promoter and evaluated the neurotransmitter phenotype of the pancreatic sympathetic innervation. We also used the insulin promoter to coexpress nerve growth factor in the islets, which greatly increased the density of sympathetic innervation and facilitated analysis of the effects of LIF. Our data demonstrate that tyrosine hydroxylase and catecholamines declined and choline acetyltransferase increased in response to LIF. We conclude that LIF can induce neurotransmitter switching of sympathetic neurons in vivo.

  13. Neuromodulating mice and men: Are there functional species differences in neurotransmitter concentration?

    Science.gov (United States)

    Fitzgerald, Paul J

    2009-07-01

    I examine evidence that the concentration of certain modulatory neurotransmitters varies across species, including differences between rodents and primates. Microdialysis studies indicate that the baseline concentration of serotonin, norepinephrine, dopamine, and acetylcholine, as measured in the prefrontal cortex of awake animals, may differ between rats and macaque monkeys. These differences may extend to mice and humans, as well. If there are differences in the tonic concentration of these neurotransmitters, this may affect the functioning of these transmitter systems in multiple ways, including potential effects on neuropsychiatric conditions such as the various mental illnesses and modeling of them in animals. Species differences in transmitter concentration may also have neuropharmacological implications, and may be relevant to the phenomenon of differences in speed of drug response between humans and rodents. This paper is divided into three sections that address related questions about the potential concentration differences: (1) Are there species differences in baseline neurotransmitter concentration? (2) Are the putative differences functional? (3) What might the functional differences be? Consideration of the existing evidence indicates that there may indeed be functional species differences in the modulatory transmitter systems.

  14. 2-acetylphenol analogs as potent reversible monoamine oxidase inhibitors

    Directory of Open Access Journals (Sweden)

    Legoabe LJ

    2015-07-01

    Full Text Available Lesetja J Legoabe,1 Anél Petzer,1 Jacobus P Petzer1,21Centre of Excellence for Pharmaceutical Sciences, 2Department of Pharmaceutical Chemistry, School of Pharmacy, North-West University, Potchefstroom, South AfricaAbstract: Based on a previous report that substituted 2-acetylphenols may be promising leads for the design of novel monoamine oxidase (MAO inhibitors, a series of C5-substituted 2-acetylphenol analogs (15 and related compounds (two were synthesized and evaluated as inhibitors of human MAO-A and MAO-B. Generally, the study compounds exhibited inhibitory activities against both MAO-A and MAO-B, with selectivity for the B isoform. Among the compounds evaluated, seven compounds exhibited IC50 values <0.01 µM for MAO-B inhibition, with the most selective compound being 17,000-fold selective for MAO-B over the MAO-A isoform. Analyses of the structure–activity relationships for MAO inhibition show that substitution on the C5 position of the 2-acetylphenol moiety is a requirement for MAO-B inhibition, and the benzyloxy substituent is particularly favorable in this regard. This study concludes that C5-substituted 2-acetylphenol analogs are potent and selective MAO-B inhibitors, appropriate for the design of therapies for neurodegenerative disorders such as Parkinson’s disease.Keywords: monoamine oxidase, MAO, inhibition, 2-acetylphenol, structure–activity relationship

  15. GABA not only a neurotransmitter: osmotic regulation by GABAAR signalling

    Directory of Open Access Journals (Sweden)

    Tiziana eCesetti

    2012-01-01

    Full Text Available In neurons the anionic channel γ-aminobutyric (GABA A receptor (GABAAR plays a central role in mediating both the neurotrophic and neurotransmitter role of GABA. Activation of this receptor by GABA also affects the function of non-neuronal cells in the central nervous system (CNS, as GABAARs are expressed in mature macroglia and in almost all progenitor types, including neural stem cells. The relevance of GABA signalling in non-neuronal cells has been comparatively less investigated than in neurons. However, it is becoming increasingly evident that these cells are direct targets of GABA regulation. In non-neuronal cells GABAAR activation leads to influx or efflux of chloride (Cl- depending on the electrochemical gradient. Ion transport is indissolubly associated to water fluxes across the plasma membrane and plays a key role in brain physiology. Therefore, GABAAR could affect osmotic tension in the brain by modulating ion gradients. In addition, since water movements also occur through specialized water channels and transporters, GABAAR signalling could affect the movement of water also by regulating the function of the channels and transporters involved, thereby affecting not only the direction of the water fluxes but also their dynamics. This regulation has consequences at the cellular level as it modulates cell volume and activates multiple intracellular signalling mechanisms important for cell proliferation, maturation and survival. It may also have consequences at the systemic level. For example, it may indirectly control neuronal excitability, by regulating the extracellular space and interstitial concentration of Cl-, and contribute to brain water homeostasis. Therefore, GABAergic osmotic regulation should be taken into account during the treatment of pathologies requiring the administration of GABAAR modulators and for the development of therapies for diseases causing water unbalance in the brain.

  16. Sympathetic Neurotransmitters Modulate Osteoclastogenesis and Osteoclast Activity in the Context of Collagen-Induced Arthritis.

    Directory of Open Access Journals (Sweden)

    Dominique Muschter

    Full Text Available Excessive synovial osteoclastogenesis is a hallmark of rheumatoid arthritis (RA. Concomitantly, local synovial changes comprise neuronal components of the peripheral sympathetic nervous system. Here, we wanted to analyze if collagen-induced arthritis (CIA alters bone marrow-derived macrophage (BMM osteoclastogenesis and osteoclast activity, and how sympathetic neurotransmitters participate in this process. Therefore, BMMs from Dark Agouti rats at different CIA stages were differentiated into osteoclasts in vitro and osteoclast number, cathepsin K activity, matrix resorption and apoptosis were analyzed in the presence of acetylcholine (ACh, noradrenaline (NA vasoactive intestinal peptide (VIP and assay-dependent, adenylyl cyclase activator NKH477. We observed modulation of neurotransmitter receptor mRNA expression in CIA osteoclasts without affecting protein level. CIA stage-dependently altered marker gene expression associated with osteoclast differentiation and activity without affecting osteoclast number or activity. Neurotransmitter stimulation modulated osteoclast differentiation, apoptosis and activity. VIP, NA and adenylyl cyclase activator NKH477 inhibited cathepsin K activity and osteoclastogenesis (NKH477, 10(-6 M NA whereas ACh mostly acted pro-osteoclastogenic. We conclude that CIA alone does not affect metabolism of in vitro generated osteoclasts whereas stimulation with NA, VIP plus specific activation of adenylyl cyclase induced anti-resorptive effects probably mediated via cAMP signaling. Contrary, we suggest pro-osteoclastogenic and pro-resorptive properties of ACh mediated via muscarinic receptors.

  17. Simultaneous analysis of multiple neurotransmitters by hydrophilic interaction liquid chromatography coupled to tandem mass spectrometry.

    Science.gov (United States)

    Tufi, Sara; Lamoree, Marja; de Boer, Jacob; Leonards, Pim

    2015-05-22

    Neurotransmitters are endogenous metabolites that allow the signal transmission across neuronal synapses. Their biological role is crucial for many physiological functions and their levels can be changed by several diseases. Because of their high polarity, hydrophilic interaction liquid chromatography (HILIC) is a promising tool for neurotransmitter analysis. Due to the large number of HILIC stationary phases available, an evaluation of the column performances and retention behaviors has been performed on five different commercial HILIC packing materials (silica, amino, amide and two zwitterionic stationary phases). Several parameters like the linear correlation between retention and the distribution coefficient (logD), the separation factor k and the column resolution Rs have been investigated and the column performances have been visualized with a heat map and hierarchical clustering analysis. An optimized and validated HILIC-MS/MS method based on the ZIC-cHILIC column is proposed for the simultaneous detection and quantification of twenty compounds consisting of neurotransmitters, precursors and metabolites: 3-methoxytyramine (3-MT), 5-hydroxyindoleacetic acid (5-HIAA), 5-hydroxy-L-tripthophan, acetylcholine, choline, L-3,4-dihydroxyphenylalanine (L-DOPA), dopamine, epinephrine, γ-aminobutyric acid (GABA), glutamate, glutamine, histamine, histidine, L-tryptophan, L-tyrosine, norepinephrine, normetanephrine, phenylalanine, serotonin and tyramine. The method was applied to neuronal metabolite profiling of the central nervous system of the freshwater snail Lymnaea stagnalis. This method is suitable to explore neuronal metabolism and its alteration in different biological matrices.

  18. Involvement of monoamines and proinflammatory cytokines in mediating the anti-stress effects of Panax quinquefolium.

    Science.gov (United States)

    Rasheed, Naila; Tyagi, Ethika; Ahmad, Ausaf; Siripurapu, Kiran Babu; Lahiri, Shawon; Shukla, Rakesh; Palit, Gautam

    2008-05-08

    Panax quinquefolium (PQ) is well acclaimed in literature for its effects on central and peripheral nervous system. The present study explores the effects of PQ on stress induced changes of corticosterone level in plasma, monoamines (NA, DA and 5-HT) and interleukin (IL-2 and IL-6) levels in cortex and hippocampus regions of brain and also indicate their possible roles in modulating stress. Mice subjected to chronic unpredictable stress (CUS, for 7 days) showed significant increase in plasma corticosterone level and depletion of noradrenaline (NA), dopamine (DA) and 5-hydroxytryptamine (5-HT) levels in cortex and hippocampal regions along with an increased level of IL-2 and IL-6 in the same areas. Aqueous suspension of PQ was administered daily at a dose of 100 and 200mg/kg p.o. prior to the stress regimen and its effects on selected stress markers in plasma and brain was evaluated. PQ at a dose of 200mg/kg p.o. was found to be effective in normalizing the CUS induced elevation of plasma corticosterone and IL-2, IL-6 levels in brain. Moreover, it was significantly effective in reinstating the CUS induced depletion of NA, DA and 5-HT in hippocampus, while NA and 5-HT in cortex of brain. However, PQ at a dose of 100mg/kg p.o. was found ineffective in regulating any of these CUS induced changes. Present study provides an insight into the possible role of PQ on hyperactive HPA axis in the regulation of immediate stress effectors like corticosterone, cytokines and brain monoamines. In this study, PQ has emerged as a potential therapeutic in the cure of stress related disorders and needs to be evaluated in clinical studies to ascertain its efficacy.

  19. Spontaneous recurrent seizures in rats: amino acid and monoamine determination in the hippocampus.

    Science.gov (United States)

    Cavalheiro, E A; Fernandes, M J; Turski, L; Naffah-Mazzacoratti, M G

    1994-01-01

    Rats subjected to structural brain damage induced by sustained convulsions triggered by systemic administration of pilocarpine (PILO) are a useful model for investigation of the mechanisms essential for seizure generation and spread in rodents. After PILO administration, three distinct phases are observed: (a) an acute period of 1-2 days' duration corresponding to a pattern of repetitive limbic seizures and status epilepticus; (b) a seizure-free (silent) period characterized by a progressive return to normal EEG and behavior of 4-44 days' duration; and (c) a period of spontaneous recurrent seizures (SRS) starting 5-45 days after PILO administration and lasting throughout the animal's life. PILO (320-350 mg/kg intraperitoneally, i.p.) was administered to rats, and the content of hippocampal monoamines and amino acids was measured in the acute, silent, and SRS periods by liquid chromatography. Norepinephrine (NE) level was decreased during all periods whereas dopamine (DA) content was increased. Serotonin (5-hydroxytryptamine, 5-HT) was increased only in the acute period. Utilization rate measurement of monoamines showed increased NE consumption and decreased DA consumption during all phases. 5-HT utilization rate was increased only in the acute period. Amino acid content showed a decrease in aspartate (ASP) and glutamate (GLU) concentrations associated with increased gamma-aminobutyric acid (GABA) level during the acute period. The silent phase was characterized by a decrease in glycine (GLY) and GABA levels and an increase in GLU concentration. The SRS period showed an increase in all amino acid concentrations. These findings show important neurochemical changes in the course of establishment of an epileptic focus after brain damage induced by status epilepticus triggered by pilocarpine.

  20. Monoamine oxidase inhibitors: nature of their interaction with rabbit pancreatic islets to alter insluin secretion.

    Science.gov (United States)

    Feldman, J M; Chapman, B

    1975-12-01

    Using an in vitro rabbit pancreas system, we studied the effect of monoamine oxidase (MAO) inhibitors on flucose-stimulated insulin secretion. We evaluated the effect of both brief (15 min) and prolonged (60 min) exposure of pancreas segments to non-hydrazine (harmine, alpha-methyltryptamine, tranylcypromine and pargyline) and hydrazine (phenelzine, nialamide, iproniazid) type MAO inhibitors. All of the hydrazine type MAO inhibitors potentiated glucose-stimulated insulin secretion. Of the non-hydrazine inhibitors, only harmine and alpha-methyltryptamine potentiated glucose-stimulated insulin secretion. Hydrazine, although not itself an MAO inhibitor, also potentiated insulin secretion. Sixty minutes of exposure to tranylcypromine or alpha-methyltryptamine caused a decrease in insulin secretion. These MAO inhibitors are primary amines and primary amines can inhibit insulin secretion. The dopamine (DA) or serotonin (5-HT) content of the B-cells was increased by incubating rabbit pancreas with L-3, 4-dihydroxyphenylalanine (L-Dopa) or 5-hydroxytryptophan (5-HTP) for forty-five minutes prior to stimulation with glucose. Non-hydrazine MAO inhibitors increased dopamine inhibition of insulin secretion and either did not alter, or decreased serotonin inhibition of insulin secretion. Rabbit pancreatic islets were isolated using the collagenase digestion technique. The MAO activity of islet homogenates was determined using 5-HT and DA as substrates. Rabbit islet MAO has only one-tenth the specific activity against 5-HT (35 +/- 8.7 mumumoles/mg/min, M +/- SEM) that it has against DA (357 +/- 62.3 mumumoles/mg/min). This suggests that one reason that MAT inhibitors do not increase serotonin inhibition of insulin secretion is because MAO is not the major pathway for 5-HT inactivation in rabbit pancreatic islets. These studies suggest that MAO inhibitors alter insulin secretion, by both decreasing B-cell monoamine degradation and by mechanisms that do not involve MAO inhibition.

  1. Exposure to (12)C particles alters the normal dynamics of brain monoamine metabolism and behaviour in rats.

    Science.gov (United States)

    Belov, Oleg V; Belokopytova, Ksenia V; Bazyan, Ara S; Kudrin, Vladimir S; Narkevich, Viktor B; Ivanov, Aleksandr A; Severiukhin, Yury S; Timoshenko, Gennady N; Krasavin, Eugene A

    2016-09-01

    Planning of the deep-space exploration missions raises a number of questions on the radiation protection of astronauts. One of the medical concerns is associated with exposure of a crew to highly energetic particles of galactic cosmic rays. Among many other health disorders, irradiation with these particles has a substantial impact on the central nervous system (CNS). Although radiation damage to CNS has been addressed extensively during the last years, the mechanisms underlying observed impairments remain mostly unknown. The present study reveals neurochemical and behavioural alterations induced in rats by 1Gy of 500MeV/u (12)C particles with a relatively moderate linear energy transfer (10.6keV/μm). It is found that exposure to carbon ions leads to significant modification of the normal monoamine metabolism dynamics as well as the locomotor, exploratory, and anxiety-like behaviours during a two-month period. The obtained results indicate an abnormal redistribution of monoamines and their metabolites in different brain regions after exposure. The most pronounced impairments are detected in the prefrontal cortex, nucleus accumbens, and hypothalamus that illustrate the sensitivity of these brain regions to densely ionizing radiations. It is also shown that exposure to (12)C particles enhances the anxiety in animals and accelerates the age-related reduction in their exploratory capability. The observed monoamine metabolism pattern may indicate the presence of certain compensatory mechanisms being induced in response to irradiation and capable of partial restoration of monoaminergic systems' functions. Overall, these findings support a possibility of CNS damage by space-born particles of a relatively moderate linear energy transfer.

  2. Ricardo Miledi and the calcium hypothesis of neurotransmitter release.

    Science.gov (United States)

    Jeng, Jade-Ming

    2002-01-01

    Ricardo Miledi has made significant contributions to our basic understanding of how synapses work. Here I discuss aspects of Miledi's research that helped to establish the requirement of presynaptic calcium for neurotransmitter release, from his earliest scientific studies to his classic experiments in the squid giant synapse.

  3. Bound to be different: neurotransmitter transporters meet their bacterial cousins.

    Science.gov (United States)

    Henry, L Keith; Meiler, Jens; Blakely, Randy D

    2007-12-01

    The neurotransmitter transporters belonging to the solute carrier 6 (SLC6) family, including the gamma-aminobutyric acid (GAT), norepinephrine (NET), serotonin (SERT) and dopamine (DAT) transporters are extremely important drug targets of great clinical relevance. These Na+, Cl(-)-dependent transporters primarily function following neurotransmission to reset neuronal signaling by transporting neurotransmitter out of the synapse and back into the pre-synaptic neuron. Recent studies have tracked down an elusive binding site for Cl(-) that facilitates neurotransmitter transport using structural differences evident with bacterial family members (e.g., the Aquifex aeolicus leucine transporter LeuT Aa) that lack Cl(-) dependence. Additionally, the crystal structures of antidepressant-bound LeuT Aa reveals a surprising mode of drug interaction that may have relevance for medication development. The study of sequence and structural divergence between LeuT Aa and human SLC6 family transporters can thus inform us as to how and why neurotransmitter transporters evolved a reliance on extracellular Cl(-) to propel the transport cycle; what residue changes and helical rearrangements give rise to recognition of different substrates; and how drugs such as antidepressants, cocaine, and amphetamines halt (or reverse) the transport process.

  4. The Top 5 Neurotransmitters from a Clinical Neurologist's Perspective

    DEFF Research Database (Denmark)

    Kondziella, Daniel

    2017-01-01

    Neurologists are proficient in neuroanatomy and -physiology but their understanding of neurochemistry tends to be mediocre. As a rule, we do not think in biochemical pathways and complex metabolic interactions but rather associate a few neurotransmitters with well-known brain diseases or drugs th...

  5. On-line radiochemical assay for monoamine oxidase utilizing high-performance liquid chromatography

    Energy Technology Data Exchange (ETDEWEB)

    Nissinen, E.; Linko-Loeppoenen SMae; Maennistoe P4

    1984-12-01

    A fast and sensitive assay for the determination of monoamine oxidase activity was developed. The method is based on the separation and quantitation of /sup 14/C-labeled assay products by high-performance liquid chromatography, which is interfaced directly into a flow-through radioactivity detector. This allows on-line quantitation of the radioactive compounds with picomole sensitivity. The method makes possible the complete separation and detection of the deaminated products of monoamine oxidase A and B substrates benzylamine and 5-hydroxytryptamine, respectively. This assay has been applied to the measurement of monoamine oxidase A and B activities in rat brain.

  6. Regulation of neurosteroid biosynthesis by neurotransmitters and neuropeptides

    Directory of Open Access Journals (Sweden)

    Jean-Luc eDo-Rego

    2012-01-01

    Full Text Available The enzymatic pathways leading to the synthesis of bioactive steroids in the brain are now almost completely elucidated in various groups of vertebrates and, during the last decade, the neuronal mechanisms involved in the regulation of neurosteroid production have received increasing attention. This report reviews the current knowledge concerning the effects of neurotransmitters, peptide hormones and neuropeptides on the biosynthesis of neurosteroids. Anatomical studies have been carried out to visualize the neurotransmitter- or neuropeptide-containing fibers contacting steroid-synthesizing neurons as well as the neurotransmitter, peptide hormones or neuropeptide receptors expressed in these neurons. Biochemical experiments have been conducted to investigate the effects of neurotransmitters, peptide hormones or neuropeptides on neurosteroid biosynthesis, and to characterize the type of receptors involved. Thus, it has been found that glutamate, acting through kainate and/or AMPA receptors, rapidly inactivates P450arom, and that melatonin produced by the pineal gland and eye inhibits the biosynthesis of 7-hydroxypregnenolone (7-OH-5P, while prolactin produced by the adenohypophysis enhances the formation of 7-OH-5P. It has also been demonstrated that the biosynthesis of neurosteroids is inhibited by GABA, acting through GABAA receptors, and neuropeptide Y, acting through Y1 receptors. In contrast, it has been shown that the octadecaneuropetide ODN, acting through central-type benzodiazepine receptors, the triakontatetraneuropeptide TTN, acting though peripheral-type benzodiazepine receptors, and vasotocine, acting through V1a-like receptors, stimulate the production of neurosteroids. Since neurosteroids are implicated in the control of various neurophysiological and behavioral processes, these data suggest that some of the neurophysiological effects exerted by neurotransmitters and neuropeptides may be mediated via the regulation

  7. Mechanism of chloride interaction with neurotransmitter:sodium symporters.

    Science.gov (United States)

    Zomot, Elia; Bendahan, Annie; Quick, Matthias; Zhao, Yongfang; Javitch, Jonathan A; Kanner, Baruch I

    2007-10-11

    Neurotransmitter:sodium symporters (NSS) have a critical role in regulating neurotransmission and are targets for psychostimulants, anti-depressants and other drugs. Whereas the non-homologous glutamate transporters mediate chloride conductance, in the eukaryotic NSS chloride is transported together with the neurotransmitter. In contrast, transport by the bacterial NSS family members LeuT, Tyt1 and TnaT is chloride independent. The crystal structure of LeuT reveals an occluded binding pocket containing leucine and two sodium ions, and is highly relevant for the neurotransmitter transporters. However, the precise role of chloride in neurotransmitter transport and the location of its binding site remain elusive. Here we show that introduction of a negatively charged amino acid at or near one of the two putative sodium-binding sites of the GABA (gamma-aminobutyric acid) transporter GAT-1 from rat brain (also called SLC6A1) renders both net flux and exchange of GABA largely chloride independent. In contrast to wild-type GAT-1, a marked stimulation of the rate of net flux, but not of exchange, was observed when the internal pH was lowered. Equivalent mutations introduced in the mouse GABA transporter GAT4 (SLC6A11) and the human dopamine transporter DAT (SLC6A3) also result in chloride-independent transport, whereas the reciprocal mutations in LeuT and Tyt1 render substrate binding and/or uptake by these bacterial NSS chloride dependent. Our data indicate that the negative charge, provided either by chloride or by the transporter itself, is required during binding and translocation of the neurotransmitter, probably to counterbalance the charge of the co-transported sodium ions.

  8. Amphetamines, new psychoactive drugs and the monoamine transporter cycle.

    Science.gov (United States)

    Sitte, Harald H; Freissmuth, Michael

    2015-01-01

    In monoaminergic neurons, the vesicular transporters and the plasma membrane transporters operate in a relay. Amphetamine and its congeners target this relay to elicit their actions: most amphetamines are substrates, which pervert the relay to elicit efflux of monoamines into the synaptic cleft. However, some amphetamines act as transporter inhibitors. Both compound classes elicit profound psychostimulant effects, which render them liable to recreational abuse. Currently, a surge of new psychoactive substances occurs on a global scale. Chemists bypass drug bans by ingenuous structural variations, resulting in a rich pharmacology. A credible transport model must account for their distinct mode of action and link this to subtle differences in activity and undesired, potentially deleterious effects.

  9. Amphetamines, new psychoactive drugs and the monoamine transporter cycle

    Science.gov (United States)

    Sitte, Harald H.; Freissmuth, Michael

    2015-01-01

    In monoaminergic neurons, the vesicular transporters and the plasma membrane transporters operate in a relay. Amphetamine and its congeners target this relay to elicit their actions: most amphetamines are substrates, which pervert the relay to elicit efflux of monoamines into the synaptic cleft. However, some amphetamines act as transporter inhibitors. Both compound classes elicit profound psychostimulant effects, which render them liable to recreational abuse. Currently, a surge of new psychoactive substances occurs on a global scale. Chemists bypass drug bans by ingenuous structural variations, resulting in a rich pharmacology. A credible transport model must account for their distinct mode of action and link this to subtle differences in activity and undesired, potentially deleterious effects. PMID:25542076

  10. Low platelet monoamine oxidase activity in pathological gambling

    Energy Technology Data Exchange (ETDEWEB)

    Carrasco, J.L. [Department of Psychiatry, Centro de Salud Mental, Parla Madrid (Spain); Saiz-Ruiz, J. [Department of Psychiatry and Haematology, Hospital Ramon y Cajal, Madrid (Spain); Hollander, E. [Department of Psychiatry, Mount Sinai School of Medicine, Queens Hospital Center, New York (United States); Cesar, J. [Department of Haematology, Hospital Ramon y Cajal, Madrid (Spain); Lopez-Ibor, J.J. Jr. [Department of Psychiatry, Hospital San Carlos, Complutense University, Madrid (Spain)

    1994-12-01

    Decreased platelet monoamine oxidase (MAO) activity has been reported in association with sensation-seeking personality type and in some mental disorders associated with a lack of impulse control. Pathological gambling itself has been related with both sensation-seeking and reduced impulse control. Platelet MAO activity was investigated in 15 DSM-III-R pathological gamblers from our outpatient clinic. Gamblers had a significantly lower platelet MAO activity than a group of 25 healthy controls. The range of MAO levels in gamblers was also significantly shorter than in controls. In controls, platelet MAO levels showed the previously described negative correlations with sensation-seeking scores but not in gamblers. The findings are consistent with previous studies showing an association of low platelet MAO activity with impulse control disorders and raise some interesting therapeutic alternatives for pathological gambling. (au) (40 refs.).

  11. Influence of parenting style on the offspring's behaviour and CSF monoamine metabolite levels in crossfostered and noncrossfostered female rhesus macaques.

    Science.gov (United States)

    Maestripieri, Dario; McCormack, Kai; Lindell, Stephen G; Higley, J Dee; Sanchez, Mar M

    2006-11-25

    We investigated the association between variation in parenting style and the offspring's behaviour and CSF monoamine metabolite (5-HIAA, HVA, and MHPG) levels in rhesus monkeys. Study subjects were 25 two-year-old females reared by their biological mothers and 15 same-aged females that were crossfostered at birth and reared by unrelated mothers. Subjects that were rejected more by their mothers in the first 6 months of life engaged in more solitary play and had lower CSF concentrations of 5-HIAA than subjects that were rejected less. The relation between these variables was generally similar in crossfostered and noncrossfostered females. CSF levels of 5-HIAA were negatively correlated with rates of scratching, a behavioural indicator of anxiety. These results suggest that that early exposure to high rates of maternal rejection can result in higher anxiety later in life, and that this effect may be mediated by serotonergic mechanisms. Variation in maternal protectiveness did not affect offspring behaviour and neither protectiveness nor rejection affected CSF levels of HVA and MHPG. CSF levels of MHPG, however, were negatively correlated with solitary play behaviour and avoidance of other individuals, suggesting that individuals with lower CSF MHPG were more fearful and socially phobic than those with higher CSF MHPG. Taken together, these findings suggest that individual differences in anxiety and fearfulness in young rhesus monkeys are accounted for, at least in part, by variation in CSF levels of monoamine metabolites, and that the development of brain monoamine systems, particularly serotonin, can be affected by early exposure to variable maternal behaviour.

  12. Syntheses of 8-(phenoxymethyl)caffeine analogues and their evaluation as inhibitors of monoamine oxidase and as antagonists of the adenosine A2A receptor / Rozanne Harmse.

    OpenAIRE

    Harmse, Rozanne

    2013-01-01

    Background and rationale: Parkinson’s disease (PD) is a progressive, degenerative disorder of the central nervous system and is characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta. The loss of functional dopamine in the striatum is thought to be responsible for the typical symptoms of PD. Cardinal features of PD include bradykinesia, muscular rigidity, resting tremor and impairment of postural balance. This study focuses on the inhibition of monoamine oxida...

  13. Effects of chronic delta-9-tetrahydrocannabinol (THC) administration on neurotransmitter concentrations and receptor binding in the rat brain.

    Science.gov (United States)

    Ali, S F; Newport, G D; Scallet, A C; Gee, K W; Paule, M G; Brown, R M; Slikker, W

    1989-01-01

    THC is the major psychoactive constituent of marijuana and is also known as an hallucinogenic compound. Numerous reports have shown that large doses of THC produce significant alterations in various neurotransmitter systems. The present study was designed to determine whether chronic exposure to THC produces significant alterations in selected neurotransmitter systems (dopamine, serotonin, acetylcholine, GABAergic, benzodiazepine, and opiate) in the rat brain. In Experiment 1, male Sprague-Dawley rats were gavaged with vehicle, 10 or 20 mg THC/kg body weight daily, 5 days/week for 90 days. Animals were killed either 24 hours or two months after the last dose. Brains were dissected into different regions for neurochemical analyses. Two months after the cessation of chronic administration, there was a significant decrease in GABA receptor binding in the hippocampus of animals in the high dose group. However, no other significant changes were found in neurotransmitter receptor binding characteristics in the hippocampus or in neurotransmitter concentrations in the caudate nucleus, hypothalamus or septum after chronic THC administration. In an attempt to replicate the GABA receptor binding changes and also to determine the [35S]TBPS binding in hippocampus, we designed Experiment 2. In this experiment, we dosed the animals by gavage with 0, 5, 10 or 20 mg THC/kg daily, 5 days/week or with 20 mg THC/kg Monday through Thursday and 60 mg/kg on Friday for 90 days. Results from this experiment failed to replicate the dose-dependent effect of THC on GABA receptor binding in hippocampus. Modulation of [35S]TBPS binding by GABA or 3 alpha-OH-DHP or inhibition by cold TBPS in frontal cortex did not show any significant dose-related effects. Results from these experiments suggest that chronic exposure to THC does not produce significant alterations in catecholamine or indoleamine neurotransmitter systems or in opiate or GABA receptor systems in the rat brain.

  14. Bepaling van enkele neurotransmitters, monoaminen, en metabolieten, met behulp van Continuous Flowapparatuur

    NARCIS (Netherlands)

    Eigeman L; Schonewille F; Borst M; van der Laan JW

    1986-01-01

    Bij het onderzoek in de psychofarmacologie kan kennis van de effecten van stoffen op de omzettingssnelheid van neurotransmitters een belangrijk aspect zijn. Met de huidige psychofarmaca lijken vooral de klassieke neurotransmitters zoals de monoaminen, noradrenaline, dopamine en serotonine van

  15. Acrylamide increases dopamine levels by affecting dopamine transport and metabolism related genes in the striatal dopaminergic system.

    Science.gov (United States)

    Pan, Xiaoqi; Guo, Xiongxiong; Xiong, Fei; Cheng, Guihong; Lu, Qing; Yan, Hong

    2015-07-01

    Dopaminergic system dysfunction is proved to be a possible mechanism in acrylamide (ACR) -induced neurotoxicity. The neurotransmitter dopamine (DA) has an increasingly important role in the dopaminergic system. Thus, the goal of this study is to evaluate effects of ACR on dopamine and its metabolite levels, dopamine transport and metabolic gene expression in dopaminergic neurons. Male Sprague-Dawley (SD) rats were dosed orally with ACR at 0 (saline), 20, 30, and 40 mg/kg/day for 20 days. Splayed hind limbs, reduced tail flick time and abnormal gait which preceded other neurologic parameters were observed in the above rats. ACR significantly increased dopamine levels, decreased 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanilic acid (HVA) contents in an area dependent manner in rat striatum. Immunohistochemical staining of the striatum revealed that the number of tyrosine hydroxylase (TH) positive cells significantly increased, while monoamine oxidase (MAO) positive cells were drastically reduced, which was consistent with changes in their mRNA and protein expressions. In addition, dopamine transporter (DAT) and vesicular monoamine transporter 2 (VMAT2) expression levels were both down-regulated in the striatum. These results suggest that dopamine levels increase significantly in response to ACR, presumably due to changes in the dopamine transport and metabolism related genes expression in the striatal dopaminergic neurons.

  16. An Interface for Sensitive Analysis of Monoamine Neurotransmitters by Ion-Pair Chromatography–ESI-MS with Continuous On-Line Elimination of Ion-Pair Reagents

    OpenAIRE

    Shi,Shuyun; Zhao, Binqing; Yagnik, Gargey; Zhou, Feimeng

    2013-01-01

    A challenge in coupling ion-pair chromatography (IPC) on-line with electrospray ionization-mass spectrometry (ESI-MS) is that the nonvolatile ion-pair reagent (e.g., alkyl sulfate for amines or tetrabutylammonium for carboxylic acids) in the mobile phase suppresses the ESI-MS signals in the gas phase and their accumulation can clog the MS sampling interface. Consequently, IPC–ESI-MS is conducted either with a volatile ion-pair reagent, which could compromise the analyte separation efficiency,...

  17. Effect of Dimethoate on serum monoamines neurotransmitter in rats%乐果对大鼠血清单胺类递质的影响

    Institute of Scientific and Technical Information of China (English)

    阮国洪; 吴强恩; 顾平; 郑力行; 顾锡安; 周志俊

    2006-01-01

    目的 观察乐果染毒对大鼠血清单胺类递质去甲肾上腺素(NE)、肾上腺素(E)、5-羟色胺(5-HT)、多巴胺(DA)及其代谢物3,4-二羟苯乙酸(DOPAC)浓度变化的影响,探讨乐果中毒的非胆碱能机制.方法 雄性SD大鼠104只随机分为对照组(生理盐水)、乐果低(38.9mg/kg)、中(83.7mg/kg)、高(180.0mg/kg)3个剂量组,一次性腹腔注射染毒,给药后0.5、2、8、24 h断头处死并分离血清,用高效液相色谱电化学检测法检测血清中NE、E、5-HT、DA及其代谢物DOPAC的浓度.结果 不同时程的染毒组(低、中、高剂量组)血清中DA及其代谢物DOPAC和5-HT的浓度比对照组分别增加8.42%~248.42%、17.22%~68.21%.不同时程的染毒组血清NE和E的浓度比对照组分别减少9.65%~38.26%和11.00%~32.62%.5-HT浓度开始随染毒剂量增加而减少,但随染毒时程的增加,则随染毒剂量增加而增加.DA、DOPAC、NE、E和5-HT的浓度在不同时程的低、中、高剂量组间差异均有统计学意义(P<0.05).结论 DA、DOPAC和5-HT浓度有随染毒剂量和时程的增加而增加的趋势,NE和E浓度有随染毒剂量和时程的增加而减少的趋势,存在剂量时程效应关系.

  18. The use of LeuT as a model in elucidating binding sites for substrates and inhibitors in neurotransmitter transporters

    DEFF Research Database (Denmark)

    Løland, Claus Juul

    2015-01-01

    Background: The mammalian neurotransmitter transporters are complex proteins playing a central role in synaptic transmission between neurons by rapid reuptake of neurotransmitters. The proteins which transport dopamine, noradrenaline and serotonin belong to the Neurotransmitter:Sodium Symporters...

  19. Effect of novel atypical antipsychotic, blonanserin, on extracellular neurotransmitter level in rat prefrontal cortex.

    Science.gov (United States)

    Ohoyama, Keiko; Yamamura, Satoshi; Hamaguchi, Tatsuya; Nakagawa, Masanori; Motomura, Eishi; Shiroyama, Takashi; Tanii, Hisashi; Okada, Motohiro

    2011-02-25

    To clarify the mechanisms of action of blonanserin, an atypical antipsychotic drug, we studied the effects of systemic administration of blonanserin and risperidone on extracellular levels of norepinephrine, dopamine, serotonin, GABA and glutamate in the medial prefrontal cortex using microdialysis, and neuronal firing in the ventral tegmental area, locus coeruleus, dorsal raphe nucleus and mediodorsal thalamic nucleus using radiotelemetry. The binding affinities of blonanserin to D(2) and 5-HT(2A) receptors in the rat brain were confirmed and found to be similar. Blonanserin transiently increased neuronal firing in locus coeruleus and ventral tegmental area but not in dorsal raphe nucleus or mediodorsal thalamic nucleus, whereas risperidone increased the firing in locus coeruleus, ventral tegmental area and dorsal raphe nucleus but not in mediodorsal thalamic nucleus. Blonanserin persistently increased frontal extracellular levels of norepinephrine and dopamine but not serotonin, GABA or glutamate, whereas risperidone persistently increased those of norepinephrine, dopamine and serotonin but not GABA or glutamate. These results suggest a pharmacological correlation between the stimulatory effects of these antipsychotics on frontal monoamine release and neuronal activity in monoaminergic nuclei. Inhibition of the α(2) adrenoceptor increased extracellular monoamine levels and enhanced blonanserin-induced increase in extracellular serotonin level. These results indicated that the combination of antagonism of D(2) and 5-HT(2A) receptors contribute to the rise in extracellular levels of norepinephrine and dopamine, and that α(2) adrenoceptors play important roles in frontal serotonin release. They also suggest that blonanserin-induced activation of monoaminergic transmission could be, at least partially, involved in atypical antipsychotic properties of blonanserin. Copyright © 2010 Elsevier B.V. All rights reserved.

  20. Antidepressant-like effect of hyperfoliatin, a polyisoprenylated phloroglucinol derivative from Hypericum perfoliatum (Clusiaceae) is associated with an inhibition of neuronal monoamines uptake.

    Science.gov (United States)

    do Rego, Jean-Claude; Benkiki, Naïma; Chosson, Elizabeth; Kabouche, Zahia; Seguin, Elisabeth; Costentin, Jean

    2007-08-27

    This study investigated, in mice, the antidepressant like effect of hyperfoliatin, a prenylated phloroglucinol derivative isolated from the aerial parts of Hypericum perfoliatum, as well as its action on monoaminergic systems. In the forced-swimming test, hyperfoliatin dose-dependently reduced immobility time. Immobility was interpreted as an expression of "behavioural despair", which could be a component of depression syndrome. The effect of hyperfoliatin did not result from the stimulation of animal motor activity. Hyperfoliatin inhibited, in a concentration-dependent manner, the [(3)H]-dopamine, [(3)H]-serotonin and [(3)H]-noradrenaline synaptosomal uptakes, but did not prevent the binding of specific ligands to the monoamine transporters. These data suggest that the antidepressant-like effect of hyperfoliatin on the forced-swimming test is probably associated to monoamine uptake inhibition, due to a mechanism of action different from that of known antidepressants.

  1. Morphological alterations and acetylcholinesterase and monoamine oxidase inhibition in liver of zebrafish exposed to Aphanizomenon flos-aquae DC-1 aphantoxins

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, De Lu, E-mail: deluzh@163.com [Department of Lifescience and Biotechnology, School of Chemistry, Chemical Engineering and Life Science, Wuhan University of Technology, Wuhan 430070 (China); Zhang, Jing [College of Chemistry and Molecular Sciences, Wuhan University, Wuhan 430072 (China); Hu, Chun Xiang, E-mail: cxhu@ihb.ac.cn [Key Laboratory of Algal Biology, Institute of Hydrobiology, The Chinese Academy of Sciences, Wuhan 430072 (China); Wang, Gao Hong; Li, Dun Hai; Liu, Yong Ding [Key Laboratory of Algal Biology, Institute of Hydrobiology, The Chinese Academy of Sciences, Wuhan 430072 (China)

    2014-12-15

    Highlights: • Aphantoxins induced zebrafish hepatic physiological and morphological changes. • AChE and MAO inhibition reflected abnormality of neurotransmitter inactivation. • ROS advance and T-AOC reduction suggested oxidative stress. • ALT, AST, histological and ultrastructural alterations indicated hepatic damage. - Abstract: Aphanizomenon flos-aquae is a cyanobacterium that produces neurotoxins or paralytic shellfish poisons (PSPs) called aphantoxins, which present threats to environmental safety and human health via eutrophication of water bodies worldwide. Although the molecular mechanisms of this neurotoxin have been studied, many questions remain unsolved, including those relating to in vivo hepatic neurotransmitter inactivation, physiological detoxification and histological and ultrastructural alterations. Aphantoxins extracted from the natural strain of A. flos-aquae DC-1 were analyzed by high-performance liquid chromatography. The main components were gonyautoxins 1 and 5 (GTX1, GTX5) and neosaxitoxin (neoSTX), which comprised 34.04%, 21.28%, and 12.77% respectively. Zebrafish (Danio rerio) were exposed intraperitoneally to 5.3 or 7.61 μg STX equivalents (eq)/kg (low and high doses, respectively) of A. flos-aquae DC-1 aphantoxins. Morphological alterations and changes in neurotransmitter conduction functions of acetylcholinesterase (AChE) and monoamine oxidase (MAO) in zebrafish liver were detected at different time points 1–24 h post-exposure. Aphantoxin significantly enhanced hepatic alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities and histological and ultrastructural damage in zebrafish liver at 3–12 h post-exposure. Toxin exposure increased the reactive oxygen species content and reduced total antioxidative capacity in zebrafish liver, suggesting oxidative stress. AChE and MAO activities were significantly inhibited, suggesting neurotransmitter inactivation/conduction function abnormalities in zebrafish

  2. Neurotransmitter segregation: functional and plastic implications.

    Science.gov (United States)

    Sámano, Cynthia; Cifuentes, Fredy; Morales, Miguel Angel

    2012-06-01

    Synaptic cotransmission is the ability of neurons to use more than one transmitter to convey synaptic signals. Cotransmission was originally described as the presence of a classic transmitter, which conveys main signal, along one or more cotransmitters that modulate transmission, later on, it was found cotransmission of classic transmitters. It has been generally accepted that neurons store and release the same set of transmitters in all their synaptic processes. However, some findings that show axon endings of individual neurons storing and releasing different sets of transmitters, are not in accordance with this assumption, and give support to the hypothesis that neurons can segregate transmitters to different synapses. Here, we review the studies showing segregation of transmitters in invertebrate and mammalian central nervous system neurons, and correlate them with our results obtained in sympathetic neurons. Our data show that these neurons segregate even classic transmitters to separated axons. Based on our data we suggest that segregation is a plastic phenomenon and responds to functional synaptic requirements, and to 'environmental' cues such as neurotrophins. We propose that neurons have the machinery to guide the different molecules required in synaptic transmission through axons and sort them to different axon endings. We believe that transmitter segregation improves neuron interactions during cotransmission and gives them selective and better control of synaptic plasticity.

  3. Peptides and neurotransmitters that affect renin secretion

    Science.gov (United States)

    Ganong, W. F.; Porter, J. P.; Bahnson, T. D.; Said, S. I.

    1984-01-01

    Substance P inhibits renin secretion. This polypeptide is a transmitter in primary afferent neurons and is released from the peripheral as well as the central portions of these neurons. It is present in afferent nerves from the kidneys. Neuropeptide Y, which is a cotransmitter with norepinephrine and epinephrine, is found in sympathetic neurons that are closely associated with and presumably innervate the juxtagolmerular cells. Its effect on renin secretion is unknown, but it produces renal vasoconstriction and natriuresis. Vasoactive intestinal polypeptide (VIP) is a cotransmitter with acetylocholine in cholinergic neurons, and this polypeptide stimulates renin secretion. We cannot find any evidence for its occurence in neurons in the kidneys, but various stimuli increase plasma VIP to levels comparable to those produced by doses of exogenous VIP which stimulated renin secretion. Neostigmine increases plasma VIP and plasma renin activity, and the VIP appears to be responsible for the increase in renin secretion, since the increase is not blocked by renal denervation or propranolol. Stimulation of various areas in the brain produces sympathetically mediated increases in plasma renin activity associated with increases in blood pressure. However, there is pharmacological evidence that the renin response can be separated from the blood pressure response. In anaesthetized dogs, drugs that increase central serotonergic discharge increase renin secretion without increasing blood pressure. In rats, activation of sertonergic neurons in the dorsal raphe nucleus increases renin secretion by a pathway that projects from this nucleus to the ventral hypothalamus, and from there to the kidneys via the sympathetic nervous system. The serotonin releasing drug parachloramphetamine also increases plasma VIP, but VIP does not appear to be the primary mediator of the renin response. There is preliminary evidence that the serotonergic neurons in the dorsal raphe nucleus are part of the

  4. Peptides and neurotransmitters that affect renin secretion

    Science.gov (United States)

    Ganong, W. F.; Porter, J. P.; Bahnson, T. D.; Said, S. I.

    1984-01-01

    Substance P inhibits renin secretion. This polypeptide is a transmitter in primary afferent neurons and is released from the peripheral as well as the central portions of these neurons. It is present in afferent nerves from the kidneys. Neuropeptide Y, which is a cotransmitter with norepinephrine and epinephrine, is found in sympathetic neurons that are closely associated with and presumably innervate the juxtagolmerular cells. Its effect on renin secretion is unknown, but it produces renal vasoconstriction and natriuresis. Vasoactive intestinal polypeptide (VIP) is a cotransmitter with acetylocholine in cholinergic neurons, and this polypeptide stimulates renin secretion. We cannot find any evidence for its occurence in neurons in the kidneys, but various stimuli increase plasma VIP to levels comparable to those produced by doses of exogenous VIP which stimulated renin secretion. Neostigmine increases plasma VIP and plasma renin activity, and the VIP appears to be responsible for the increase in renin secretion, since the increase is not blocked by renal denervation or propranolol. Stimulation of various areas in the brain produces sympathetically mediated increases in plasma renin activity associated with increases in blood pressure. However, there is pharmacological evidence that the renin response can be separated from the blood pressure response. In anaesthetized dogs, drugs that increase central serotonergic discharge increase renin secretion without increasing blood pressure. In rats, activation of sertonergic neurons in the dorsal raphe nucleus increases renin secretion by a pathway that projects from this nucleus to the ventral hypothalamus, and from there to the kidneys via the sympathetic nervous system. The serotonin releasing drug parachloramphetamine also increases plasma VIP, but VIP does not appear to be the primary mediator of the renin response. There is preliminary evidence that the serotonergic neurons in the dorsal raphe nucleus are part of the

  5. Appearance and distribution of peptidergic neurotransmitters in hippocampal primary culture

    OpenAIRE

    Thiele, Theodor

    2012-01-01

    The internal structure of the hippocampus, especially the development of neuronal circuits, is the subject of current research. The hippocampal primary culture represents a suitable model to study neuronal development and the impact of isolated stimuli and noxious. Focus of the following considerations are the neurons of the hippocampus, especially the peptidergic neurotransmitters somatostatin (SS), neuropeptide Y (NPY), vasoactive intestinal peptide (VIP) and cholecystokinin (CCK). By us...

  6. Application of PEDOT-CNT Microelectrodes for Neurotransmitter Sensing

    OpenAIRE

    Samba, Ramona; Fuchsberber, Kai; Matiychyn, Ilona; Epple, Sebastian; Kiesel, Lydia; Stett, Alfred; Schuhmann, Wolfgang; Stelzle, Martin

    2016-01-01

    In this work, composite microelectrodes from poly(3,4-ethylenedioxythiophene) (PEDOT) and carbon nanotubes (CNT) are characterized as electrochemical sensing material for neurotransmitters. Dopamine can be detected using square wave voltammetry at these microelectrodes. The CNTs improve the sensitivity by a factor of two. In addition, the selectivity towards dopamine in the presence of ascorbic acid and uric acid was examined. While both electrodes, PEDOT and PEDOT-CNT are able to detect all ...

  7. Terahertz identification and quantification of neurotransmitter and neurotrophy mixture

    OpenAIRE

    Peng, Yan; Yuan, Xiaorong; Zou, Xiang; Chen, Wanqing; Huang, Hui; Zhao, Hongwei; Song, Bo; Chen, Liang; Zhu, Yiming

    2016-01-01

    Terahertz spectroscopy has been widely used for investigating the fingerprint spectrum of different substances. For cancerous tissues, the greatest difficulty is the absorption peaks of various substances contained in tissues overlap with each other, which are hard to identify and quantitative analyze. As a result, it is very hard to measure the presence of cancer cell and then to diagnose accurately. In this paper, we select three typical neurotransmitters (γ-aminobutyric acid, L-glutamic ac...

  8. Electrochemical techniques for subsecond neurotransmitter detection in live rodents.

    Science.gov (United States)

    Hascup, Kevin N; Hascup, Erin R

    2014-08-01

    Alterations in neurotransmission have been implicated in numerous neurodegenerative and neuropsychiatric disorders, including Alzheimer disease, Parkinson disease, epilepsy, and schizophrenia. Unfortunately, few techniques support the measurement of real-time changes in neurotransmitter levels over multiple days, as is essential for ethologic and pharmacodynamic testing. Microdialysis is commonly used for these research paradigms, but its poor temporal and spatial resolution make this technique inadequate for measuring the rapid dynamics (milliseconds to seconds) of fast signaling neurotransmitters, such as glutamate and acetylcholine. Enzymatic microelectrode arrays (biosensors) coupled with electrochemical recording techniques have demonstrated fast temporal resolution (less than 1 s), excellent spatial resolution (micron-scale), low detection limits (≤200 nM), and minimal damage (50 to 100 μm) to surrounding brain tissue. Here we discuss the benefits, methods, and animal welfare considerations of using platinum microelectrodes on a ceramic substrate for enzyme-based electrochemical recording techniques for real-time in vivo neurotransmitter recordings in both anesthetized and awake, freely moving rodents.

  9. Exploration of inclusion complexes of neurotransmitters with β-cyclodextrin by physicochemical techniques

    Science.gov (United States)

    Roy, Mahendra Nath; Saha, Subhadeep; Kundu, Mitali; Saha, Binoy Chandra; Barman, Siti

    2016-07-01

    Molecular assemblies of β-cyclodextrin with few of the most important neurotransmitters, viz., dopamine hydrochloride, tyramine hydrochloride and (±)-epinephrine hydrochloride in aqueous medium have been explored by reliable spectroscopic and physicochemical techniques as potential drug delivery systems. Job plots confirm the 1:1 host-guest inclusion complexes, while surface tension and conductivity studies illustrate the inclusion process. The inclusion complexes were characterized by 1H NMR spectroscopy and association constants have been calculated by using Benesi-Hildebrand method. Thermodynamic parameters for the formation of inclusion complexes have been derived by van't Hoff equation, which demonstrate that the overall inclusion processes are thermodynamically favorable.

  10. Role of putative neurotransmitters in the central gastric antisecretory effect of prostaglandin E2 in rats.

    OpenAIRE

    Puurunen, J.

    1985-01-01

    The role of putative neurotransmitters of the central nervous system in the central gastric antisecretory effect of prostaglandin E2 (PGE2) was investigated in pylorus-ligated rats. Pretreatment of the rats with an intracerebroventricular (i.c.v.) injection of 6-hydroxydopamine (6-OHDA) prevented the antisecretory effect of the i.c.v. administration of PGE2, whereas pretreatment with 5,6-dihydroxytryptamine (5,6-DHT) plus p-chlorophenylalanine (PCPA) had no effect. I.c.v.-administered phentol...

  11. Chemical stimulation of rat retinal neurons: feasibility of an epiretinal neurotransmitter-based prosthesis

    Science.gov (United States)

    Inayat, Samsoon; Rountree, Corey M.; Troy, John B.; Saggere, Laxman

    2015-02-01

    Objective. No cure currently exists for photoreceptor degenerative diseases, which cause partial or total blindness in millions of people worldwide. Electrical retinal prostheses have been developed by several groups with the goal of restoring vision lost to these diseases, but electrical stimulation has limitations. It excites both somas and axons, activating retinal pathways nonphysiologically, and limits spatial resolution because of current spread. Chemical stimulation of retinal ganglion cells (RGCs) using the neurotransmitter glutamate has been suggested as an alternative to electrical stimulation with some significant advantages. However, sufficient scientific data to support developing a chemical-based retinal prosthesis is lacking. The goal of this study was to investigate the feasibility of a neurotransmitter-based retinal prosthesis and determine therapeutic stimulation parameters. Approach. We injected controlled amounts of glutamate into rat retinas from the epiretinal side ex vivo via micropipettes using a pressure injection system and recorded RGC responses with a multielectrode array. Responsive units were identified using a spike rate threshold of 3 Hz. Main results. We recorded both somal and axonal units and demonstrated successful glutamatergic stimulation across different RGC subtypes. Analyses show that exogenous glutamate acts on RGC synapses similar to endogenous glutamate and, unlike electrical prostheses, stimulates only RGC somata. The spatial spread of glutamate stimulation was ˜ 290 μm from the injection site, comparable to current electrical prostheses. Further, the glutamate injections produced spatially differential responses in OFF, ON, and ON-OFF RGC subtypes, suggesting that differential stimulation of the OFF and ON systems may be possible. A temporal resolution of 3.2 Hz was obtained, which is a rate suitable for spatial vision. Significance. We provide strong support for the feasibility of an epiretinal neurotransmitter

  12. Neurotransmitters act as paracrine signals to regulate insulin secretion from the human pancreatic islet.

    Science.gov (United States)

    Rodriguez-Diaz, Rayner; Menegaz, Danusa; Caicedo, Alejandro

    2014-08-15

    In this symposium review we discuss the role of neurotransmitters as paracrine signals that regulate pancreatic islet function. A large number of neurotransmitters and their receptors has been identified in the islet, but relatively little is known about their involvement in islet biology. Interestingly, neurotransmitters initially thought to be present in autonomic axons innervating the islet are also present in endocrine cells of the human islet. These neurotransmitters can thus be released as paracrine signals to help control hormone release. Here we propose that the role of neurotransmitters may extend beyond controlling endocrine cell function to work as signals modulating vascular flow and immune responses within the islet.

  13. How LeuT shapes our understanding of the mechanisms of sodium-coupled neurotransmitter transporters.

    Science.gov (United States)

    Penmatsa, Aravind; Gouaux, Eric

    2014-03-01

    Neurotransmitter transporters are ion-coupled symporters that drive the uptake of neurotransmitters from neural synapses. In the past decade, the structure of a bacterial amino acid transporter, leucine transporter (LeuT), has given valuable insights into the understanding of architecture and mechanism of mammalian neurotransmitter transporters. Different conformations of LeuT, including a substrate-free state, inward-open state, and competitive and non-competitive inhibitor-bound states, have revealed a mechanistic framework for the transport and transport inhibition of neurotransmitters. The current review integrates our understanding of the mechanistic and pharmacological properties of eukaryotic neurotransmitter transporters obtained through structural snapshots of LeuT.

  14. Marine omega-3 polyunsaturated fatty acids induce sex-specific changes in reinforcer-controlled behaviour and neurotransmitter metabolism in a spontaneously hypertensive rat model of ADHD

    Directory of Open Access Journals (Sweden)

    Dervola Kine S

    2012-12-01

    Full Text Available Abstract Background Previous reports suggest that omega-3 (n-3 polyunsaturated fatty acids (PUFA supplements may reduce ADHD-like behaviour. Our aim was to investigate potential effects of n-3 PUFA supplementation in an animal model of ADHD. Methods We used spontaneously hypertensive rats (SHR. SHR dams were given n-3 PUFA (EPA and DHA-enriched feed (n-6/n-3 of 1:2.7 during pregnancy, with their offspring continuing on this diet until sacrificed. The SHR controls and Wistar Kyoto (WKY control rats were given control-feed (n-6/n-3 of 7:1. During postnatal days (PND 25–50, offspring were tested for reinforcement-dependent attention, impulsivity and hyperactivity as well as spontaneous locomotion. The animals were then sacrificed at PND 55–60 and their neostriata were analysed for monoamine and amino acid neurotransmitters with high performance liquid chromatography. Results n-3 PUFA supplementation significantly enhanced reinforcement-controlled attention and reduced lever-directed hyperactivity and impulsiveness in SHR males whereas the opposite or no effects were observed in females. Analysis of neostriata from the same animals showed significantly enhanced dopamine and serotonin turnover ratios in the male SHRs, whereas female SHRs showed no change, except for an intermediate increase in serotonin catabolism. In contrast, both male and female SHRs showed n-3 PUFA-induced reduction in non-reinforced spontaneous locomotion, and sex-independent changes in glycine levels and glutamate turnover. Conclusions Feeding n-3 PUFAs to the ADHD model rats induced sex-specific changes in reinforcement-motivated behaviour and a sex-independent change in non-reinforcement-associated behaviour, which correlated with changes in presynaptic striatal monoamine and amino acid signalling, respectively. Thus, dietary n-3 PUFAs may partly ameliorate ADHD-like behaviour by reinforcement-induced mechanisms in males and partly via reinforcement-insensitive mechanisms

  15. [The APUD concept and its clinical significance. 2. Effect of gastrointestinal hormones, polypeptides and neurotransmitters on the physiological course and disease processes of the intestinal tract and the nervous system].

    Science.gov (United States)

    Neumayr, A

    1982-06-03

    The neurally programmed APUD-cells from ectodermal origin are of peculiar significance in two respects: 1. They represent the largest endocrine gland of the whole organism and the peptides, which are secreted by the different APUD-cells, exercise a great influence on most of the motoric and secretory processes within the whole gastrointestinal tract just as on many metabolic processes as demonstrated on the so-called "enteropancreatic axis". Neoplasias of these APUD-cells, the "Apudomes", give rise to peculiar clinical syndromes. Early diagnosis of an apudome can be reached today by radioimmunologic detection of high concentrations of the responsible peptide in the blood enabling us to initiate an effective therapy at least for some of the known apudomes. 2. Beyond that the APUD-cells and their corresponding peptides are representing the so-called "peptidergic" division of the nervous system which acts as third-line effector to modulate not only the actions of the autonomic division but also of each other. The given example of the modulating effect of substance P or of the endorphines on the perception of pain is only one single aspect of the broad functional spectrum of these neuropeptides. The discovery, that the very same peptide can be detected in endocrine cells as well as in neurones, has opened one of the most fascinating and provocative developments in biology of the present time and some surprising new details can be expected in the next future.

  16. Inf luence of Spirulina platensis exudates on the endocrine and nervous systems of a mammalian model

    Institute of Scientific and Technical Information of China (English)

    Samah; Mamdouh; Mohamed; Fathy; Ashraf; Mohamed; Mohamed; Essa

    2015-01-01

    Objective: To investigate the ef ect of intra-peritoneal injection of purii ed exudates of axenic Spirulina platensis on the mammalian endocrine and nervous systems. Methods: The intra-peritoneal injection of the cyanobacterial exudates in mice was applied. Sex hormonal levels of testosterone and progesterone were measured using radioimmunoassay while the follicular stimulating hormone and luteinizing hormone were evaluated by direct chemiluminescence. In addition, superoxide dismutase, catalase and glutathione peroxidase were monitored in the hippocampus region using spectrophotometric method. The levels of the hippocampal monoamines, dopamine, noradrenaline and serotonin were analyzed by high performance liquid chromatography while the acetyl choline neurotransmitter was measured by colorimetric method using choline/acetylcholine assay kit. Results: A sharp disruption in the sex hormones levels of testosterone, progesterone, follicular stimulating hormone and luteinizing hormone was demonstrated in the serum of the treated mice. At the same time, a signii cant reduction in the endogenous antioxidant defense enzymes, superoxide dismutase, catalase and glutathione peroxidase was observed in the hippocampus region of the injected mice. Moreover, levels of dopamine, noradrenaline, serotonin and acetyl choline neurotransmitter in the same region were signii cantly af ected as a result of the treatment with Spirulina i ltrate. The gas chromatography-mass spectrometer and liquid chromatography mass spectrometry/mass spectrometry analysis showed the presence of some sterol-like compounds in the cyanobacterial i ltrate. Conclusions: This study demonstrated the capability of Spirulina to release detrimental bioactive metabolites into their surrounding that can disrupt the mammalian endocrine and nervous systems.

  17. Selected chromone derivatives as inhibitors of monoamine oxidase.

    Science.gov (United States)

    Legoabe, Lesetja J; Petzer, Anél; Petzer, Jacobus P

    2012-09-01

    A previous study has shown that a series of C6-benzyloxy substituted chromones exhibit high binding affinities for human monoamine oxidase (MAO) B. In an attempt to discover additional chromones with potent and selective MAO-B inhibitory potencies and to further examine the structure-activity relationships of MAO-B inhibition by chromones, the series was expanded with homologues containing polar functional groups on C3 of the chromone ring. The results demonstrate that 6-[(3-bromobenzyl)oxy]chromones containing acidic and aldehydic functional groups on C3 act as potent reversible MAO-B inhibitors with IC(50) values of 2.8 and 3.7 nM, respectively. Interestingly, a 2-hydroxy-2,3-dihydro-1-benzopyran-4-one derivative as well as open-ring 2-acetylphenol analogues of the chromones also were potent MAO-B inhibitors with IC(50) values ranging from 4 to 11 nM. Chromone derivatives containing the benzyloxy substituent on C5 of the chromone ring, however, exhibit MAO-B inhibition potencies that are several orders of magnitude weaker. High potency inhibitors of MAO-B may find application in the therapy of neurodegenerative disorders such as Parkinson's disease. Copyright © 2012 Elsevier Ltd. All rights reserved.

  18. Selected C7-substituted chromone derivatives as monoamine oxidase inhibitors.

    Science.gov (United States)

    Legoabe, Lesetja J; Petzer, Anél; Petzer, Jacobus P

    2012-12-01

    A series of C7-substituted chromone (1-benzopyran-4-one) derivatives were synthesized and evaluated as inhibitors of recombinant human monoamine oxidase (MAO) A and B. The chromones are structurally related to a series of C7-functionalized coumarin (1-benzopyran-2-one) derivatives which has been reported to act as potent MAO inhibitors. The results of the current study document that the chromones are highly potent reversible inhibitors of MAO-B with IC(50) values ranging from 0.008 to 0.370 μM. While the chromone derivatives also exhibit affinities for MAO-A, with IC(50) values ranging from 0.495 to 8.03 μM, they are selective for the MAO-B isoform. Structure-activity relationships (SAR) show that 7-benzyloxy substitution of chromone is suitable for MAO-B inhibition with tolerance for a variety of substituents and substitution patterns on the benzyloxy ring. It may be concluded that 7-benzyloxychromones are appropriate lead compounds for the design of reversible and selective MAO-B inhibitors. With the aid of modeling studies, potential binding orientations and interactions of selected chromone derivatives in the MAO-A and -B active sites are examined. Copyright © 2012 Elsevier Inc. All rights reserved.

  19. The effects of two chronic intermittent stressors on brain monoamines.

    Science.gov (United States)

    Campmany, L; Pol, O; Armario, A

    1996-03-01

    The effects of chronic exposure (27 days) to two different stressors on brain monoaminergic activity was studied in adult male rats. The stressors used were restraint in tubes (RES) and immobilization in wooden boards (IMO). Both chronically stressed and stress naive (control) rats were subjected to 0, 15, and 60 min of the same stressor to which they were chronically exposed. Previous chronic exposure to either RES or IMO significantly reduced ACTH response to the same stressor. Monoaminergic response to these stressors was studied by measuring the levels of noradrenaline (NA), serotonin (5-HT) and their metabolites: 3-methoxy,4-hydroxyphenyletileneglycol sulfate (MHPG-SO4) and 5-hydroxyindoleacetic acid (5-HIAA), respectively. The regions studied were: pons plus medulla, midbrain, hypothalamus, hippocampus, and frontal cortex. Previous chronic exposure to the stressors induced only few changes in the resting levels of the monoamines and their metabolites. In addition, monoaminergic response to the same stressor to which they were chronically exposed was always similar in control and chronically stressed rats. These data indicate that brain NA and 5-HT metabolism is less sensitive than ACTH to the process of habituation to a repeated stressor, at least in the gross areas of the brain analyzed in the present study.

  20. Methylphenidate and its ethanol transesterification metabolite ethylphenidate: brain disposition, monoamine transporters and motor activity.

    Science.gov (United States)

    Williard, Robin L; Middaugh, Lawrence D; Zhu, Hao-Jie B; Patrick, Kennerly S

    2007-02-01

    Ethylphenidate is formed by metabolic transesterification of methylphenidate and ethanol. Study objectives were to (a) establish that ethylphenidate is formed in C57BL/6 (B6) mice; (b) compare the stimulatory effects of ethylphenidate and methylphenidate enantiomers; (c) determine methylphenidate and ethylphenidate plasma and brain distribution and (d) establish in-vitro effects of methylphenidate and ethylphenidate on monoamine transporter systems. Experimental results were that: (a) coadministration of ethanol with the separate methylphenidate isomers enantioselectively produced l-ethylphenidate; (b) d and dl-forms of methylphenidate and ethylphenidate produced dose-responsive increases in motor activity with stimulation being less for ethylphenidate; (c) plasma and whole-brain concentrations were greater for ethylphenidate than methylphenidate and (d) d and DL-methylphenidate and ethylphenidate exhibited comparably potent low inhibition of the dopamine transporter, whereas ethylphenidate was a less potent norepinephrine transporter inhibitor. These experiments establish the feasibility of the B6 mouse model for examining the interactive effects of ethanol and methylphenidate. As reported for humans, concurrent exposure of B6 mice to methylphenidate and ethanol more readily formed l-ethylphenidate than d-ethylphenidate, and the l-isomers of both methylphenidate and ethylphenidate were biologically inactive. The observed reduced stimulatory effect of d-ethylphenidate relative to d-methylphenidate appears not to be the result of brain dispositional factors, but rather may be related to its reduced inhibition of the norepinephrine transporter, perhaps altering the interaction of dopaminergic and noradrenergic neural systems.

  1. Regulation of Neurotransmitter Responses in the Central Nervous System

    Science.gov (United States)

    1990-02-05

    accordance with DoD 5200.1 -R, Information Security Program Regulation. Chapter V1 Section 2, V"-apaph 4-200. clasification markings are to be stamped...through pharmacologically distinct reports. Finally, the augmenting response does not appear to be mediated through protein kinase C. However, BAC...may facilitate second messenger production by altering the coupling of catecholamine receptor to C- proteins involved in the cAMP cascade. (( ( CONTRACT

  2. Influence of tramadol on neurotransmitter systems of the rat brain

    NARCIS (Netherlands)

    Frink, MC; Hennies, HH; Englberger, W; Haurand, M; Wilffert, B

    1996-01-01

    In in vitro receptor binding and synaptosomal uptake experiments the (+)-enantiomer of tramadol (GAS 148229-78-1) is specific for the mu-opioid receptor site and for the serotonin (5-HT) carrier, whereas the (-)-enantiomer (GAS 148229-79-2) has a higher affinity to the noradrenaline (NA)

  3. Influence of tramadol on neurotransmitter systems of the rat brain

    NARCIS (Netherlands)

    Frink, MC; Hennies, HH; Englberger, W; Haurand, M; Wilffert, B

    1996-01-01

    In in vitro receptor binding and synaptosomal uptake experiments the (+)-enantiomer of tramadol (GAS 148229-78-1) is specific for the mu-opioid receptor site and for the serotonin (5-HT) carrier, whereas the (-)-enantiomer (GAS 148229-79-2) has a higher affinity to the noradrenaline (NA) transporter

  4. Regulation of Neurotransmitter Responses in the Central Nervous System.

    Science.gov (United States)

    1987-05-01

    Phinucol. E-rp. flier. 230. ison of the effects of clonidine on ir-r. and postsvniaptic 31-323. adrenoceptors in the rapnit pulmonar \\ arter\\. .\\iinvn...E. (1982) J. Cell. Physiol. 112:42-50. 22. Jaken, S., Tashjian A.H. and Blumberg, P.M. (1981) Cancer Res. 41:2175-2181. 23. Niedel. J.E., Kuhn, LJ

  5. Evolution of neurotransmitter gamma-aminobutyric acid,glutamate and their receptors

    Institute of Scientific and Technical Information of China (English)

    Zhiheng GOU; Xiao WANG; Wen WANG

    2012-01-01

    Gamma-aminobutyric acid (GABA) and glutamate are two important amino acid neurotransmitters widely present in the nervous systems of ammals,insects,round worm,and platyhelminths,while their receptors are quite diversified across different animal phyla.However,the evolutionary mechanisms between the two conserved neurotransmitters and their diversified receptors remain elusive,and antagonistic interactions between GABA and glutamate signal transduction systems,in particular,have begun to attract significant attention.In this review,we summarize the extant results on the origin and evolution of GABA and glutamate,as well as their receptors,and analyze possible evolutionary processes and phylogenetic relationships of various GABAs and glutamate receptors.We further discuss the evolutionary history of Excitatory/Neutral Amino Acid Transporter (EAAT),a transport protein,which plays an important role in the GABA-glutamate "yin and yang" balanced regulation.Finally,based on current advances,we propose several potential directions of future research.

  6. High-throughput screening for monoamine oxidase-A and monoamine oxidase-B inhibitors using one-step fluorescence assay

    Institute of Scientific and Technical Information of China (English)

    Hong-mei GUANG; Guan-hua DU

    2006-01-01

    Aim: To develop high-throughput screening (HTS) assays for monoamine oxidase (MAO)-A and MAO-B inhibitors. Methods: A fluorescence probe based method measuring MAO-A and MAO-B activity was established and optimized, with its sensitivity, stability and specificity evaluated. Reaction conditions including enzyme sources, substrate concentrations, incubation volume and reaction time in 384-well format were optimized to achieve sensitive and low consumptive goal. Results: In optimized conditions, dynamic parameters of MAO-A and MAO-B were obtained. The Km value of serotonin to MAO-A was 1.66 μmol/L, while that of benzylamine to MAO-B was 0.80 umol/L. The IC50 value of clorgyline to MAO-A was 2.99 nmol/L, and that of deprenyl to MAO-B was 7.04 nmol/L, matching those obtained from traditional spectrometric assays. Among tested samples, one compound exerted an inhibitory effect on MAO-A activity with IC50 as 0.36 μmol/L, and three compounds had an inhibitory effect on MAO-B activity with IC50 as 0.13,0.19, and 0.13 μmol/L. The Z' factor was 0.71±0.03 and 0.75±0.03 in MAO-A-inhibitor and MAO-B-inhibitor HTS system, respectively. Conclusion: The established assays can be well applied to MAO-A and MAO-B inhibitor screening with high quality, precision and reproducibility.

  7. Neurotransmitters in the Gas Phase: La-Mb Studies

    Science.gov (United States)

    Cabezas, C.; Mata, S.; López, J. C.; Alonso, J. L.

    2011-06-01

    LA-MB-FTMW spectroscopy combines laser ablation with Fourier transform microwave spectroscopy in supersonic jets overcoming the problems of thermal decomposition associated with conventional heating methods. We present here the results on LA-MB-FTMW studies of some neurotransmitters. Six conformers of dopamine, four of adrenaline, five of noradrenaline and three conformers of serotonin have been characterized in the gas phase. The rotational and nuclear quadrupole coupling constants extracted from the analysis of the rotational spectrum are directly compared with those predicted by ab initio methods to achieve the conclusive identification of different conformers and the experimental characterization of the intramolecular forces at play which control conformational preferences.

  8. Glucagon-related peptide 1 (GLP-1): hormone and neurotransmitter

    DEFF Research Database (Denmark)

    Larsen, Philip J; Holst, Jens Juul

    2005-01-01

    The interest in glucagon-like petide-1 (GLP-1) and other pre-proglucagon derived peptides has risen almost exponentially since seminal papers in the early 1990s proposed to use GLP-1 agonists as therapeutic agents for treatment of type 2 diabetes. A wealth of interesting studies covering both...... normal and pathophysiological role of GLP-1 have been published over the last two decades and our understanding of GLP-1 action has widened considerably. In the present review, we have tried to cover our current understanding of GLP-1 actions both as a peripheral hormone and as a central neurotransmitter...

  9. Name that neurotransmitter: using music to teach psychopharmacology concepts.

    Science.gov (United States)

    Hermanns, Melinda; Lilly, Mary LuAnne; Wilson, Kathy; Russell, Nathan Andrew

    2012-09-01

    The purpose of this article is to discuss the use of music (i.e., two original songs, "Neurotransmitter Twitter" and "Parkinson's Shuffle") to teach aspects of psychopharmacology to students in the course Psychiatric/Mental Health Nursing. Songs were incorporated in both the clinical and classroom settings. This innovative teaching method allowed students the opportunity to revisit the information through multiple exposures of the content for reinforcement and enhancement of student learning in a fun, creative approach. Brain-based research will be discussed, along with the process of development.

  10. Calcium-sensitive regulation of monoamine oxidase-A contributes to the production of peroxyradicals in hippocampal cultures: implications for Alzheimer disease-related pathology

    Directory of Open Access Journals (Sweden)

    Li XinMin

    2007-09-01

    Full Text Available Abstract Background Calcium (Ca2+ has recently been shown to selectively increase the activity of monoamine oxidase-A (MAO-A, a mitochondria-bound enzyme that generates peroxyradicals as a natural by-product of the deamination of neurotransmitters such as serotonin. It has also been suggested that increased intracellular free Ca2+ levels as well as MAO-A may be contributing to the oxidative stress associated with Alzheimer disease (AD. Results Incubation with Ca2+ selectively increases MAO-A enzymatic activity in protein extracts from mouse hippocampal HT-22 cell cultures. Treatment of HT-22 cultures with the Ca2+ ionophore A23187 also increases MAO-A activity, whereas overexpression of calbindin-D28K (CB-28K, a Ca2+-binding protein in brain that is greatly reduced in AD, decreases MAO-A activity. The effects of A23187 and CB-28K are both independent of any change in MAO-A protein or gene expression. The toxicity (via production of peroxyradicals and/or chromatin condensation associated with either A23187 or the AD-related β-amyloid peptide, which also increases free intracellular Ca2+, is attenuated by MAO-A inhibition in HT-22 cells as well as in primary hippocampal cultures. Conclusion These data suggest that increases in intracellular Ca2+ availability could contribute to a MAO-A-mediated mechanism with a role in AD-related oxidative stress.

  11. Effects of ferulic acid on oxidative stress, heat shock protein 70, connexin 43, and monoamines in the hippocampus of pentylenetetrazole-kindled rats.

    Science.gov (United States)

    Hussein, Abdelaziz M; Abbas, Khaled M; Abulseoud, Osama A; El-Hussainy, El-Hussainy M A

    2017-06-01

    The present study investigated the effects of ferulic acid (FA) on pentylenetetrazole (PTZ)-induced seizures, oxidative stress markers (malondialdehyde (MDA), catalase, and reduced glutathione (GSH)), connexin (Cx) 43, heat shock protein 70 (Hsp 70), and monoamines (serotonin (5-HT) and norepinephrine (NE)) levels in a rat model of PTZ-induced kindling. Sixty Sprague Dawley rats were divided into 5 equal groups: (a) normal group; (b) FA group: normal rats received FA at a dose of 40 mg/kg daily; (c) PTZ group: normal rats received PTZ at a dose of 50 mg/kg i.p. on alternate days for 15 days; (d) FA-before group: treatment was the same as for the PTZ group, except rats received FA; and (e) FA-after group: rats received FA from sixth dose of PTZ. PTZ caused a significant increase in MDA, Cx43, and Hsp70 along with a significant decrease in GSH, 5-HT, and NE levels and CAT activity in the hippocampus (p < 0.05). Pre- and post-treatment with FA caused significant improvement in behavioral parameters, MDA, CAT, GSH, 5-HT, NE, Cx43 expression, and Hsp70 expression in the hippocampal region (p < 0.05). We conclude that FA has neuroprotective effects in PTZ-induced epilepsy, which might be due to attenuation of oxidative stress and Cx43 expression and upregulation of neuroprotective Hsp70 and neurotransmitters (5-HT and NE).

  12. Assessment of Mitochondrial Dysfunction and Monoamine Oxidase Contribution to Oxidative Stress in Human Diabetic Hearts

    Directory of Open Access Journals (Sweden)

    O. M. Duicu

    2016-01-01

    Full Text Available Mitochondria-related oxidative stress is a pathomechanism causally linked to coronary heart disease (CHD and diabetes mellitus (DM. Recently, mitochondrial monoamine oxidases (MAOs have emerged as novel sources of oxidative stress in the cardiovascular system and experimental diabetes. The present study was purported to assess the mitochondrial impairment and the contribution of MAOs-related oxidative stress to the cardiovascular dysfunction in coronary patients with/without DM. Right atrial appendages were obtained from 75 patients randomized into 3 groups: (1 Control (CTRL, valvular patients without CHD; (2 CHD, patients with confirmed CHD; and (3 CHD-DM, patients with CHD and DM. Mitochondrial respiration was measured by high-resolution respirometry and MAOs expression was evaluated by RT-PCR and immunohistochemistry. Hydrogen peroxide (H2O2 emission was assessed by confocal microscopy and spectrophotometrically. The impairment of mitochondrial respiration was substrate-independent in CHD-DM group. MAOs expression was comparable among the groups, with the predominance of MAO-B isoform but no significant differences regarding oxidative stress were detected by either method. Incubation of atrial samples with MAOs inhibitors significantly reduced the H2O2 in all groups. In conclusion, abnormal mitochondrial respiration occurs in CHD and is more severe in DM and MAOs contribute to oxidative stress in human diseased hearts with/without DM.

  13. Mesocorticolimbic monoamine correlates of methamphetamine sensitization and motivation

    Directory of Open Access Journals (Sweden)

    Kevin D Lominac

    2014-05-01

    Full Text Available Methamphetamine (MA is a highly addictive psychomotor stimulant, with life-time prevalence rates of abuse ranging from 5-10% world-wide. Yet, a paucity of research exists regarding MA addiction vulnerability/resiliency and neurobiological mediators of the transition to addiction that might occur upon repeated low-dose MA exposure, more characteristic of early drug use. As stimulant-elicited neuroplasticity within dopamine neurons innervating the nucleus accumbens (NAC and prefrontal cortex (PFC is theorized as central for addiction-related behavioral anomalies, we used a multi-disciplinary research approach in mice to examine the interactions between sub-toxic MA dosing, motivation for MA and mesocorticolimbic monoamines. Biochemical studies of C57BL/6J (B6 mice revealed short- (1 day, as well as longer-term (21 days, changes in extracellular dopamine, DAT and/or D2 receptors during withdrawal from 10, once daily, 2 mg/kg MA injections. Follow-up biochemical studies conducted in mice selectively bred for high versus low MA drinking (respectively, MAHDR vs. MALDR mice, provided novel support for anomalies in mesocorticolimbic dopamine as a correlate of genetic vulnerability to high MA intake. Finally, neuropharmacological targeting of NAC dopamine in MA-treated B6 mice demonstrated a bi-directional regulation of MA-induced place-conditioning. These results extend extant literature for MA neurotoxicity by demonstrating that even subchronic exposure to relatively low MA doses are sufficient to elicit relatively long-lasting changes in mesocorticolimbic dopamine and that drug-induced or idiopathic anomalies in mesocorticolimbic dopamine may underpin vulnerability/resiliency to MA addiction.

  14. 3-Coumaranone derivatives as inhibitors of monoamine oxidase

    Directory of Open Access Journals (Sweden)

    Van Dyk AS

    2015-10-01

    Full Text Available Adriaan S Van Dyk,1,2 Jacobus P Petzer,1,2 Anél Petzer,1 Lesetja J Legoabe1 1Centre of Excellence for Pharmaceutical Sciences, 2Pharmaceutical Chemistry, School of Pharmacy, North-West University, Potchefstroom, South Africa Abstract: The present study examines the monoamine oxidase (MAO inhibitory properties of a series of 20 3-coumaranone [benzofuran-3(2H-one] derivatives. The 3-coumaranone derivatives are structurally related to series of α-tetralone and 1-indanone derivatives, which have recently been shown to potently inhibit MAO, with selectivity for MAO-B (in preference to the MAO-A isoform. 3-Coumaranones are similarly found to selectively inhibit human MAO-B with half-maximal inhibitory concentration (IC50 values of 0.004–1.05 µM. Nine compounds exhibited IC50<0.05 µM for the inhibition of MAO-B. For the inhibition of human MAO-A, IC50 values ranged from 0.586 to >100 µM, with only one compound possessing an IC50<1 µM. For selected 3-coumaranone derivatives, it is established that MAO-A and MAO-B inhibition are reversible since dialysis of enzyme–inhibitor mixtures almost completely restores enzyme activity. On the basis of the selectivity profiles and potent action, it may be concluded that the 3-coumaranone derivatives are suitable leads for the development of selective MAO-B inhibitors as potential treatment for disorders such as Parkinson’s disease and Alzheimer’s disease. Keywords: benzofuran-3(2H-one, MAO, inhibition, reversible, competitive, Parkinson’s disease 

  15. The inhibition of monoamine oxidase by phenformin and pentamidine.

    Science.gov (United States)

    Barkhuizen, M; Petzer, A; Petzer, J P

    2014-09-01

    A computational study has suggested that phenformin, an oral hypoglycaemic drug, may bind to the active sites of the monoamine oxidase (MAO) A and B enzymes. The present study therefore investigates the MAO inhibitory properties of phenformin. Pentamidine, a structurally related diamidine compound, has previously been reported to be a MAO inhibitor and was included in this study as a reference compound. Using recombinant human MAO-A and MAO-B, this study finds that phenformin acts as a moderately potent MAO-A selective inhibitor with an IC50 value of 41 µM. Pentamidine, on the other hand, potently inhibits both MAO-A and MAO-B with IC50 values of 0.61 μM and 0.22 μM, respectively. An examination of the recoveries of the enzymatic activities after dilution and dialysis of the enzyme-inhibitor complexes shows that both compounds interact reversibly with the MAO enzymes. A kinetic analysis suggests that pentamidine acts as a competitive inhibitor with estimated Ki values of 0.41 μM and 0.22 μM for the inhibition of MAO-A and MAO-B, respectively. Phenformin also exhibited a competitive mode of MAO-A inhibition with an estimated Ki value of 65 µM. This study concludes that biguanide and amidine functional groups are most likely important structural features for the inhibition of the MAOs by phenformin and pentamidine, and compounds containing these and closely related functional groups should be considered as potential MAO inhibitors. Furthermore, the biguanide and amidine functional groups may act as useful moieties in the future design of MAO inhibitors.

  16. A survey of prescribing practices for monoamine oxidase inhibitors.

    Science.gov (United States)

    Balon, R; Mufti, R; Arfken, C L

    1999-07-01

    A survey examined prescribing practices for monoamine oxidase inhibitors (MAOIs) and explored reasons for the widely noted decline in their use. A one-page questionnaire was sent in 1997 to 1,129 members of the Michigan Psychiatric Association. A total of 717 responses were received, for a response rate of 64 percent. Only data from the 573 psychiatrists who were currently practicing were used. Twelve percent of the respondents never prescribed MAOIs, 27 percent had not prescribed them for at least three years, and 17 percent had prescribed them from one to three years ago. Thirty percent of the respondents had prescribed an MAOI within the past three months, and 14 percent between three and 12 months ago. The most frequent reasons for not prescribing the drugs were side effects and interactions with other medications (46 percent), preference for other medications (30 percent), and dietary restrictions necessary for patients taking MAOIs (19 percent). Ninety-two percent of respondents believed that MAOIs were useful for atypical depression, 64 percent for major depression, 54 percent for melancholic depression, 56 percent for panic disorder, 44 percent for social phobia, 27 percent for dysthymia, 12 percent for obsessive-compulsive disorder, and 19 percent for posttraumatic stress disorder. However, only 2 percent said they would use MAOIs as their first-line treatment in atypical depression, and only 3 percent would use them a first-line treatment in social phobia. The results document the commonly held view that practicing psychiatrists believe MAOIs are efficacious but use them infrequently, primarily due to concerns about side effects and drug interactions.

  17. Prenatal exposure to integerrimine N-oxide enriched butanolic residue from Senecio brasiliensis affects behavior and striatal neurotransmitter levels of rats in adulthood.

    Science.gov (United States)

    Sandini, Thaísa M; Udo, Mariana S B; Reis-Silva, Thiago M; Sanches, Daniel; Bernardi, Maria Martha; Flório, Jorge Camilo; Spinosa, Helenice de S

    2015-12-01

    Pyrrolizidine alkaloids (PAs) are toxins that are exclusively biosynthesized by plants and are commonly present in foods and herbs. PAs are usually associated with poisoning events in livestock and human beings. The aim of the present study was to evaluate the behavioral and neurochemical effects of prenatal exposure to PA integerrimine N-oxide of rats in adulthood. Pregnant Wistar rats received integerrimine N-oxide from the butanolic residue of Senecio brasiliensis by gavage on gestational days 6-20 at doses of 3, 6 and 9 mg/kg. During adulthood of the offspring, the following behavioral tests were performed: open-field, plus-maze, forced swimming, catalepsy and stereotypy. Histological analyses and monoamine levels were measured. Male offspring from dams that were exposed to 9 mg/kg showed an increase in locomotion in the open-field test, an increased frequency of entries and time spent in open arms in elevated plus-maze test, as well as decreased swimming time. In the female offspring from dams that were exposed to 9 mg/kg, there was an increased time of climbing in forced swimming and intensity of stereotyped behavior. The histological study indicates an increase in the number of multinucleated cells in the liver (6 and 9 mg/kg). In neurotransmitter analysis, specifically in the striatum, we observed change in dopamine and serotonin levels in the middle dose. Thus, our results indicate that prenatal exposure to integerrimine N-oxide changed behavior in adulthood and neurotransmitter levels in the striatum. Our results agree with previous studies, which showed that integerrimine N-oxide impaired physical and neurobehavioral development in childhood that can persist until adulthood. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Fine-tuning of defensive behaviors in the dorsal periaqueductal gray by atypical neurotransmitters

    Directory of Open Access Journals (Sweden)

    M.V. Fogaça

    2012-04-01

    Full Text Available This paper presents an up-to-date review of the evidence indicating that atypical neurotransmitters such as nitric oxide (NO and endocannabinoids (eCBs play an important role in the regulation of aversive responses in the periaqueductal gray (PAG. Among the results supporting this role, several studies have shown that inhibitors of neuronal NO synthase or cannabinoid receptor type 1 (CB1 receptor agonists cause clear anxiolytic responses when injected into this region. The nitrergic and eCB systems can regulate the activity of classical neurotransmitters such as glutamate and γ-aminobutyric acid (GABA that control PAG activity. We propose that they exert a ‘fine-tuning’ regulatory control of defensive responses in this area. This control, however, is probably complex, which may explain the usually bell-shaped dose-response curves observed with drugs that act on NO- or CB1-mediated neurotransmission. Even if the mechanisms responsible for this complex interaction are still poorly understood, they are beginning to be recognized. For example, activation of transient receptor potential vanilloid type-1 channel (TRPV1 receptors by anandamide seems to counteract the anxiolytic effects induced by CB1 receptor activation caused by this compound. Further studies, however, are needed to identify other mechanisms responsible for this fine-tuning effect.

  19. Probing interactions of neurotransmitters with twin tailed anionic surfactant: A detailed physicochemical study.

    Science.gov (United States)

    Kaur, Rajwinder; Sanan, Reshu; Mahajan, Rakesh Kumar

    2016-05-01

    Keeping in view the role of neurotransmitters (NTs) in central nervous system diseases and in controlling various physiological processes, present study is aimed to study the binding of neurotransmitters (NTs) such as norepinephrine hydrochloride (NE) and serotonin hydrochloride (5-HT) with twin tailed surfactant sodium bis(2-ethylhexyl)sulfosuccinate (AOT). Spectroscopic and electrochemical measurements combined with microcalorimetric measurements were used to characterize the interactions between AOT and NTs. Meteoric modifications to emission profile and absorption spectra of NTs upon addition of AOT are indicative of the binding of NTs with AOT. Distinct interactional states such as formation of ion-pairs, induced and regular micelles with adsorbed NTs molecules have been observed in different concentration regimes of AOT. The formation of ion-pairs from oppositely charged NTs and AOT is confirmed by the reduced absorbance, quenched fluorescence intensity and decrease in peak current (ipa) as well as shifts in peak potential (Epa) values. The stoichiometry and formation of the NTs-AOT complexes has been judged and the extent of interactions is quantitatively discussed in terms of binding constant (K) and free energy of binding (ΔG°). The enthalpy (ΔH°mic) and free energy of micellization (ΔG°mic) for AOT in presence and absence of NTs are determined from the enthalpy curves.

  20. [Mechanisms of neurotransmitter release facilitation in strontium solutions].

    Science.gov (United States)

    Mukhamed'iarov, M A; Kochunova, Iu O; Telina, E N; Zefirov, A L

    2008-02-01

    Mechanisms of neurotransmitter release facilitation were studied using electrophysiological recording of end-plate currents (EPC) and nerve ending (NE) responses after substitution of extracellular Ca ions with Sr ions at the frog neuromuscular junction. The solutions with 0.5 mM concentration of Ca ions (calcium solution) or 1 mM concentration of Sr ions (strontium solution) were used where baseline neurotransmitter release (at low-frequency stimulation) is equal. Decay of paired-pulse facilitation of EPC at calcium solutions with increase of interpulse interval from 5 to 500 ms was well described by three-exponential function consisting of early, first and second components. Facilitation at strontium solutions was significantly diminished due mainly to decrease of early and first components. At the same time, EPC facilitation with rhythmic stimulation (10 or 50 imp/s) at strontium solutions was significantly increased. Also more pronounced decrease of NE response 3rd phase, reflecting potassium currents was detected under rhythmic stimulation of 50 imp/s at strontium solutions comparing to calcium solutions. It was concluded that facilitation sites underlying first and early components had lower affinity to Sr ions than to Ca ions. The enhancement of frequency facilitation at strontium solutions is mediated by two mechanisms: more pronounced broadening of NE action potential and increase of bivalent cation influx due to feebly marked activation of Ca(2+)-dependent potassium current by Sr ions, and slower dynamics of Sr(2+) removal from NE axoplasm comparing to Ca(2+).

  1. "Stiff neonate" with mitochondrial DNA depletion and secondary neurotransmitter defects.

    LENUS (Irish Health Repository)

    Moran, Margaret M

    2011-12-01

    Mitochondrial disorders comprise a heterogenous group. A neonate who presented with episodes of severe truncal hypertonia and apnea progressed to a hypokinetic rigid syndrome characterized by hypokinesia, tremulousness, profound head lag, absent suck and gag reflexes, brisk deep tendon reflexes, ankle and jaw clonus, and evidence of autonomic dysfunction. Analysis of cerebrospinal fluid neurotransmitters from age 7 weeks demonstrated low levels of amine metabolites (homovanillic acid and 5-hydroxyindoleacetic acid), tetrahydrobiopterin, and pyridoxal phosphate. Mitochondrial DNA quantitative studies on muscle homogenate demonstrated a mitochondrial DNA depletion disorder. Respiratory chain enzymology demonstrated decreased complex IV activity. Screening for mitochondrial DNA rearrangement disorders and sequencing relevant mitochondrial genes produced negative results. No clinical or biochemical response to treatment with pyridoxal phosphate, tetrahydrobiopterin, or l-dopa occurred. The clinical course was progressive, and the patient died at age 19 months. Mitochondrial disorders causing secondary neurotransmitter diseases are usually severe, but are rarely reported. This diagnosis should be considered in neonates or infants who present with hypertonia, hypokinesia rigidity, and progressive neurodegeneration.

  2. Identification of catecholamine neurotransmitters using fluorescence sensor array

    Energy Technology Data Exchange (ETDEWEB)

    Ghasemi, Forough [Department of Chemistry, Sharif University of Technology, Tehran 11155-9516 (Iran, Islamic Republic of); Hormozi-Nezhad, M. Reza, E-mail: hormozi@sharif.edu [Department of Chemistry, Sharif University of Technology, Tehran 11155-9516 (Iran, Islamic Republic of); Institute for Nanoscience and Nanotechnology, Sharif University of Technology, Tehran (Iran, Islamic Republic of); Mahmoudi, Morteza, E-mail: mahmoudi@stanford.edu [Department of Nanotechnology and Nanotechnology Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran 13169-43551 (Iran, Islamic Republic of); Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA 94305-5101 (United States)

    2016-04-21

    A nano-based sensor array has been developed for identification and discrimination of catecholamine neurotransmitters based on optical properties of their oxidation products under alkaline conditions. To produce distinct fluorescence response patterns for individual catecholamine, quenching of thioglycolic acid functionalized cadmium telluride (CdTe) quantum dots, by oxidation products, were employed along with the variation of fluorescence spectra of oxidation products. The spectral changes were analyzed with hierarchical cluster analysis (HCA) and principal component analysis (PCA) to identify catecholamine patterns. The proposed sensor could efficiently discriminate the individual catecholamine (i.e., dopamine, norepinephrine, and L-DOPA) and their mixtures in the concentration range of 0.25–30 μmol L{sup −1}. Finally, we found that the sensor had capability to identify the various catecholamines in urine sample. - Highlights: • We have proposed a fluorescence sensor array to detect catecholamine neurotransmitters. • Visual differentiation of catecholamines is provided by fluorescence array fingerprints. • Discrimination of catecholamines from each other, and from their mixture is obtained on a PCA plot. • Proposed sensor array can be used for detection of catecholamines in urine samples.

  3. The amyloid pathology progresses in a neurotransmitter-specific manner.

    Science.gov (United States)

    Bell, Karen F S; Ducatenzeiler, Adriana; Ribeiro-da-Silva, Alfredo; Duff, Karen; Bennett, David A; Cuello, A Claudio

    2006-11-01

    Past studies using transgenic models of early-staged amyloid pathology, have suggested that the amyloid pathology progresses in a neurotransmitter-specific manner where cholinergic terminals appear most vulnerable, followed by glutamatergic terminals and finally by somewhat more resistant GABAergic terminals. To determine whether this neurotransmitter-specific progression persists at later pathological stages, presynaptic bouton densities, and the areas of occupation and localization of plaque adjacent dystrophic neurites were quantified in 18-month-old APP(K670N, M671L)+PS1(M146L) doubly transgenic mice. Quantification revealed that transgenic animals had significantly lower cholinergic, glutamatergic and GABAergic presynaptic bouton densities. Cholinergic and glutamatergic dystrophic neurites appear to be heavily influenced by fibrillar Abeta as both types displayed a decreasing area of occupation with respect to increasing plaque size. Furthermore, cholinergic dystrophic neurites reside in closer proximity to plaques than glutamatergic dystrophic neurites, while GABAergic dystrophic neurites were minimal regardless of plaque size. To investigate whether similarities exist in the human AD pathology, a monoclonal antibody (McKA1) against the human vesicular glutamate transporter 1 (VGluT1) was developed. Subsequent staining in AD brain tissue revealed the novel presence of glutamatergic dystrophic neurites, to our knowledge the first evidence of a structural glutamatergic deficit in the AD pathology.

  4. Brain monoamine metabolism is altered in rats following spontaneous, long-distance running.

    Science.gov (United States)

    Elam, M; Svensson, T H; Thorén, P

    1987-06-01

    Brain monoamine metabolism in rats was studied during spontaneous, long-term running in a microprocessor-controlled wheel cage. Immediately after heavy spontaneous exercise, DOPA accumulation was decreased in dopamine-rich brain regions such as the limbic forebrain and corpus striatum, indicating a decreased rate of synthesis of dopamine in brain. In contrast, DOPA accumulation was increased in the noradrenaline-predominated region of the brain stem, indicating an increased synthesis of noradrenaline in this region. Alterations in brain monoamine metabolism were normalized in exercising animals analysed 24 h after the last running period. Changes in brain monoamine metabolism may be involved in the mechanisms underlying the clinically observed psychological effects of physical exercise.

  5. A kinome wide screen identifies novel kinases involved in regulation of monoamine transporter function

    DEFF Research Database (Denmark)

    Vuorenpää, Anne Elina; Ammendrup-Johnsen, Ina; Jorgensen, Trine N.

    2016-01-01

    cells (CAD) and rat chromocytoma (PC12) cells. Whereas SIK3 likely transcriptionally regulated expression of the three transfected transporters, depletion of PKA C-α was shown to decrease SERT function. Depletion of PrKX caused decreased surface expression and function of DAT without changing protein...... levels, suggesting that PrKX stabilizes the transporter at the cell surface. Summarized, our data provide novel insight into kinome regulation of the monoamine transporters and identifies PrKX as a yet unappreciated possible regulator of monoamine transporter function....... in regulation of monoamine transporter function and surface expression. A primary screen in HEK 293 cells stably expressing DAT or SERT with siRNAs against 573 human kinases revealed 93 kinases putatively regulating transporter function. All 93 hits, which also included kinases previously implicated...

  6. Octyl-methoxycinnamate (OMC), an ultraviolet (UV) filter, alters LHRH and amino acid neurotransmitters release from hypothalamus of immature rats.

    Science.gov (United States)

    Szwarcfarb, B; Carbone, S; Reynoso, R; Bollero, G; Ponzo, O; Moguilevsky, J; Scacchi, P

    2008-02-01

    OMC (octyl-methoxycinnamate), is an endocrine disruptor with estrogenic activity, which is used in sunscreen creams as a UV filter. We studied its " IN VITRO" effects on the hypothalamic release of LHRH as well as on the amino acid neurotransmitter system in immature rats of 15 (prepubertal) and 30 (peripubertal) days of age. OMC decreased the LH-RH release significantly in male and female rats of both age. In male rats OMC increased the release of GABA while in the female ones It diminished the excitatory amino acid aspartate (ASP) and Glutamate (GLU) without modifications in the hypothalamic GABA release. These results suggest that during sexual maturation the inhibitory effect of OMC on LH-RH release appears to be related to its action on the inhibitory and excitatory amino acid neurotransmitters in male and female rats.

  7. [Electrical activity of the visual cortex under conditions of altered monoamine levels in the brain of animals].

    Science.gov (United States)

    Vorob'ev, V V; Gal'chenko, A A; Deriugina, O N

    1990-01-01

    In experiments on 8 rabbits and 12 rats changes in electrograms of the visual cortex of alert animals were studied under photic stimulation in conditions of pharmacological action on monoamine (MA) brain systems. After injection of MA precursors (5-oxitriptophane and d, 1-dioxiphenylalanine) following phenomena were observed: a) decrease of the amplitude of the averaged evoked potentials to rhythmic photic stimuli (1-20 imp. sec.-1); b) an enhancement of fast (15-25 Hz) oscillations in the cortical spontaneous electrical activity and weakening and modification of the effects of the blockader of synthesis of MA-alpha-methyl-dioxiphenylalanine. Under light stimulation potentiation of MA precursors effects was observed in the frequency spectra of electrocorticograms. In the same conditions the specificity of action of cathecholamines precursor was revealed in the form of an increase of power of rhythms of 5-7 Hz and it; decrease in 2-3 Hz. Possible mechanisms of the revealed phenomena are discussed.

  8. Neuropsychological measures of attention and memory function in schizophrenia: relationships with symptom dimensions and serum monoamine activity

    Directory of Open Access Journals (Sweden)

    Henning Uwe

    2005-08-01

    Full Text Available Abstract Background Some clinical symptoms or cognitive functions have been related to the overall state of monoamine activity in patients with schizophrenia, (e.g. inverse correlation of the dopamine metabolite HVA with delusions or visual-masking performance. However, profiles (as presented here of the relations of the activity of dopamine, noradrenaline and serotonin to neuropsychologic (dysfunctions in major patient sub-groups with their very different symptomatic and cognitive characteristics have not been reported. Methods Serum measures of dopamine, noradrenaline and serotonin turnover were examined by regression analyses for the prediction of performance on 10 neuropsychological measures reflecting left- and right-hemispheric and frontal-, parietal- and temporal-lobe function in 108 patients with schizophrenia and 63 matched controls. The neuropsychological battery included tests of verbal fluency, Stroop interference, trail-making, block-design, Mooney faces recognition, picture-completion, immediate and delayed visual and verbal recall. Paranoid and nonparanoid subgroups were based on ratings from the Positive and Negative Syndrome Scale (PANSS. Groups with high and low ratings of ideas-of-reference and thought-disorder were formed from a median split on the Scale for Assessment of Positive Symptoms (SAPS. Results Verbal-fluency and Stroop-interference (left frontal and fronto-cingulate function were negatively associated with noradrenergic turnover in nonparanoid and thought-disordered patients. High dopamine turnover related to speeded trail-making (frontal modulation of set switching in those with many ideas-of-reference. In contrast, low dopamine turnover predicted poor recall in nonparanoid patients and those with little thought disorder. Serotonin metabolism did not independently contribute to the prediction any measure of cognitive performance. But, with regard to the relative activity between monoaminergic systems, increased

  9. Effects of chronic delta-9-tetrahydrocannabinol (THC) administration on neurotransmitter concentrations and receptor binding in the rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Ali, S.F.; Newport, G.D.; Scallet, A.C.; Gee, K.W.; Paule, M.G.; Brown, R.M.; Slikker, W. Jr. (National Center for Toxicological Research, Jefferson, Arkansas (USA))

    THC is the major psychoactive constituent of marijuana and is also known as an hallucinogenic compound. Numerous reports have shown that large doses of THC produce significant alterations in various neurotransmitter systems. The present study was designed to determine whether chronic exposure to THC produces significant alterations in selected neurotransmitter systems (dopamine, serotonin, acetylcholine, GABAergic, benzodiazepine, and opiate) in the rat brain. In Experiment 1, male Sprague-Dawley rats were gavaged with vehicle, 10 or 20 mg THC/kg body weight daily, 5 days/week for 90 days. Animals were killed either 24 hours or two months after the last dose. Brains were dissected into different regions for neurochemical analyses. Two months after the cessation of chronic administration, there was a significant decrease in GABA receptor binding in the hippocampus of animals in the high dose group. However, no other significant changes were found in neurotransmitter receptor binding characteristics in the hippocampus or in neurotransmitter concentrations in the caudate nucleus, hypothalamus or septum after chronic THC administration. In an attempt to replicate the GABA receptor binding changes and also to determine the (35S)TBPS binding in hippocampus, we designed Experiment 2. In this experiment, we dosed the animals by gavage with 0, 5, 10 or 20 mg THC/kg daily, 5 days/week or with 20 mg THC/kg Monday through Thursday and 60 mg/kg on Friday for 90 days. Results from this experiment failed to replicate the dose-dependent effect of THC on GABA receptor binding in hippocampus. Modulation of (35S)TBPS binding by GABA or 3 alpha-OH-DHP or inhibition by cold TBPS in frontal cortex did not show any significant dose-related effects.

  10. Activities of autonomic neurotransmitters in meibomian gland tissues are associated with menopausal dry eye

    Institute of Scientific and Technical Information of China (English)

    Lianxiang Li; Dongling Jin; Jinsheng Gao; Liguang Wang; Xianjun Liu; Jingzhang Wang; Zhongxin Xu

    2012-01-01

    The secretory activities of meibomian glands are regulated by the autonomic nervous system. The change in density and activity of autonomic nerves in meibomian glands during menopause play an important role in the pathogenesis of dry eye. In view of this, we established a dry eye rat model by removing the bilateral ovaries. We used neuropeptide Y and vasoactive intestinal polypeptide as markers of autonomic neurotransmitters. Our results showed that the concentration of estradiol in serum significantly decreased, the density of neuropeptide Y immunoreactivity in nerve fibers significantly increased, the density of vasoactive intestinal polypeptide immunoreactivity in nerve fibers significantly decreased, and the ratio of vasoactive intestinal polypeptide/neuropeptide Y positive staining significantly decreased. These results suggest that a decrease in ovary activity may lead to autonomic nervous system dysfunction, thereby affecting the secretory activity of the meibomian gland, which participates in sexual hormone imbalance-induced dry eye.

  11. The influence of anesthetics, neurotransmitters and antibiotics on the relaxation processes in lipid membranes

    CERN Document Server

    Seeger, H M; Heimburg, T; Gudmundsson, Marie L.; Heimburg, Thomas; Seeger, Heiko M.

    2007-01-01

    In the proximity of melting transitions of artificial and biological membranes fluctuations in enthalpy, area, volume and concentration are enhanced. This results in domain formation, changes of the elastic constants, changes in permeability and slowing down of relaxation processes. In this study we used pressure perturbation calorimetry to investigate the relaxation time scale after a jump into the melting transition regime of artificial lipid membranes. This time corresponds to the characteristic rate of domain growth. The studies were performed on single-component large unilamellar and multilamellar vesicle systems with and without the addition of small molecules such as general anesthetics, neurotransmitters and antibiotics. These drugs interact with membranes and affect melting points and profiles. In all systems we found that heat capacity and relaxation times are related to each other in a simple manner. The maximum relaxation time depends on the cooperativity of the heat capacity profile and decreases...

  12. Biophysics of risk aversion based on neurotransmitter receptor theory

    CERN Document Server

    Takahashi, Taiki

    2011-01-01

    Decision under risk and uncertainty has been attracting attention in neuroeconomics and neuroendocrinology of decision-making. This paper demonstrated that the neurotransmitter receptor theory-based value (utility) function can account for human and animal risk-taking behavior. The theory predicts that (i) when dopaminergic neuronal response is efficiently coupled to the formation of ligand-receptor complex, subjects are risk-aversive (irrespective of their satisfaction level) and (ii) when the coupling is inefficient, subjects are risk-seeking at low satisfaction levels, consistent with risk-sensitive foraging theory in ecology. It is further suggested that some anomalies in decision under risk are due to inefficiency of the coupling between dopamine receptor activation and neuronal response. Future directions in the application of the model to studies in neuroeconomics of addiction and neuroendocrine modulation of risk-taking behavior are discussed.

  13. Antidepressant Binding Site in a Bacterial Homologue of Neurotransmitter Transporters

    Energy Technology Data Exchange (ETDEWEB)

    Singh,S.; Yamashita, A.; Gouaux, E.

    2007-01-01

    Sodium-coupled transporters are ubiquitous pumps that harness pre-existing sodium gradients to catalyse the thermodynamically unfavourable uptake of essential nutrients, neurotransmitters and inorganic ions across the lipid bilayer. Dysfunction of these integral membrane proteins has been implicated in glucose/galactose malabsorption, congenital hypothyroidism, Bartter's syndrome, epilepsy, depression, autism and obsessive-compulsive disorder. Sodium-coupled transporters are blocked by a number of therapeutically important compounds, including diuretics, anticonvulsants and antidepressants, many of which have also become indispensable tools in biochemical experiments designed to probe antagonist binding sites and to elucidate transport mechanisms. Steady-state kinetic data have revealed that both competitive and noncompetitive modes of inhibition exist. Antagonist dissociation experiments on the serotonin transporter (SERT) have also unveiled the existence of a low-affinity allosteric site that slows the dissociation of inhibitors from a separate high-affinity site. Despite these strides, atomic-level insights into inhibitor action have remained elusive. Here we screen a panel of molecules for their ability to inhibit LeuT, a prokaryotic homologue of mammalian neurotransmitter sodium symporters, and show that the tricyclic antidepressant (TCA) clomipramine noncompetitively inhibits substrate uptake. Cocrystal structures show that clomipramine, along with two other TCAs, binds in an extracellular-facing vestibule about 11 {angstrom} above the substrate and two sodium ions, apparently stabilizing the extracellular gate in a closed conformation. Off-rate assays establish that clomipramine reduces the rate at which leucine dissociates from LeuT and reinforce our contention that this TCA inhibits LeuT by slowing substrate release. Our results represent a molecular view into noncompetitive inhibition of a sodium-coupled transporter and define principles for the

  14. Neurotransmitter GABA activates muscle but not α7 nicotinic receptors.

    Science.gov (United States)

    Dionisio, Leonardo; Bergé, Ignacio; Bravo, Matías; Esandi, María Del Carmen; Bouzat, Cecilia

    2015-01-01

    Cys-loop receptors are neurotransmitter-activated ion channels involved in synaptic and extrasynaptic transmission in the brain and are also present in non-neuronal cells. As GABAA and nicotinic receptors (nAChR) belong to this family, we explored by macroscopic and single-channel recordings whether the inhibitory neurotransmitter GABA has the ability to activate excitatory nAChRs. GABA differentially activates nAChR subtypes. It activates muscle nAChRs, with maximal peak currents of about 10% of those elicited by acetylcholine (ACh) and 15-fold higher EC50 with respect to ACh. At the single-channel level, the weak agonism is revealed by the requirement of 20-fold higher concentration of GABA for detectable channel openings, a major population of brief openings, and absence of clusters of openings when compared with ACh. Mutations at key residues of the principal binding-site face of muscle nAChRs (αY190 and αG153) affect GABA activation similarly as ACh activation, whereas a mutation at the complementary face (εG57) shows a selective effect for GABA. Studies with subunit-lacking receptors show that GABA can activate muscle nAChRs through the α/δ interface. Interestingly, single-channel activity elicited by GABA is similar to that elicited by ACh in gain-of-function nAChR mutants associated to congenital myasthenic syndromes, which could be important in the progression of the disorders due to steady exposure to serum GABA. In contrast, GABA cannot elicit single-channel or macroscopic currents of α7 or the chimeric α7-serotonin-type 3 receptor, a feature important for preserving an adequate excitatory/inhibitory balance in the brain as well as for avoiding activation of non-neuronal receptors by serum GABA. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

  15. Acrylamide-functionalized graphene micro-solid-phase extraction coupled to high-performance liquid chromatography for the online analysis of trace monoamine acidic metabolites in biological samples.

    Science.gov (United States)

    Yang, Xiaoting; Hu, Yufei; Li, Gongke; Zhang, Zhuomin

    2015-05-01

    Monoamine acidic metabolites in biological samples are essential biomarkers for the diagnosis of neurological disorders. In this work, acrylamide-functionalized graphene adsorbent was successfully synthesized by a chemical functionalization method and was packed in a homemade polyether ether ketone micro column as a micro-solid-phase extraction unit. This micro-solid-phase extraction unit was directly coupled to high-performance liquid chromatography to form an online system for the separation and analysis of three monoamine acidic metabolites including homovanillic acid, 5-hydroxyindole-3-acetic acid, and 3,4-dihydroxyphenylacetic acid in human urine and plasma. The online system showed high stability, permeability, and adsorption capacity toward target metabolites. The saturated extraction amount of this online system was 213.1, 107.0, and 153.4 ng for homovanillic acid, 5-hydroxyindole-3-acetic acid, and 3,4-dihydroxyphenylacetic acid, respectively. Excellent detection limits were achieved in the range of 0.08-0.25 μg/L with good linearity and reproducibility. It was interesting that three targets in urine and plasma could be actually quantified to be 0.94-3.93 μg/L in plasma and 7.15-19.38 μg/L in urine. Good recoveries were achieved as 84.8-101.4% for urine and 77.8-95.1% for plasma with the intra- and interday relative standard deviations less than 9.3 and 10.3%, respectively. This method shows great potential for online analysis of trace monoamine acidic metabolites in biological samples.

  16. Effect of handling on neurotransmitter profile in pig brain according to fear related behaviour.

    Science.gov (United States)

    Arroyo, Laura; Carreras, Ricard; Valent, Daniel; Peña, Raquel; Mainau, Eva; Velarde, Antonio; Sabrià, Josefa; Bassols, Anna

    2016-12-01

    Chemical neurotransmitters (NT) are principal actors in all neuronal networks of animals. The central nervous system plays an important role in stress susceptibility and organizes the response to a stressful situation through the interaction of the dopaminergic and the serotonergic pathways, leading to the activation of the hypothalamus-pituitary-adrenal axis (HPA). This study was designed to investigate: a) the effects of stressful handling of pigs at the slaughterhouse on the neurotransmitter profile in four brain areas: amygdala, prefrontal cortex (PFC), hippocampus and hypothalamus, and b) whether the alterations in the brain NT profile after stressful handling were associated with fear, determined by the tonic immobility (TI) test. In the first place, the characterization of the NT profile allowed to distinguish the four brain areas in a principal component analysis. The most crucial pathway involved in the reaction of pigs to a stressful handling was the serotonergic system, and changes were observed in the amygdala with a decrease in serotonin (5-HT) and total indoleamines, and in the hippocampus, where this pathway was activated. Fearful and non-fearful pigs did not show significant differences in their NT profile in control conditions, but when subjected to a stressful handling in the slaughterhouse, fearful animals showed a significant variation in the serotonin pathway and, in a lesser extent, the dopamine (DA) pathway. In conclusion, the existence of an underlying biological trait - possibly fearfulness - may be involved in the pig's response toward stressful challenges, and the serotonergic system seems to play a central role in this response. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Prepulse inhibition (PPI) disrupting effects of Glycyrrhiza glabra extract in mice: a possible role of monoamines.

    Science.gov (United States)

    Michel, Haidy E; Tadros, Mariane G; Abdel-Naim, Ashraf B; Khalifa, Amani E

    2013-06-07

    Liquorice extract was reported to have nootropic and/or antiamnestic effects. Prepulse inhibition (PPI) of startle response is a multimodal, cross-species phenomenon used as a measure of sensorimotor gating. Previous studies indicated that liquorice/its constituents augmented mouse brain monoamine levels. Increased brain monoamines' transmission was suggested to underlie PPI disruption. However, the effect of antiamnestic dose(s) of the extract on PPI has not been investigated despite the coexistence of impaired memory and PPI deficit in some neurological disorders. The effect of administration of the antiamnestic dose of the extract (150 mg/kg for 7 days) was tested on PPI of acoustic startle response in mice. It resulted in PPI disruption and therefore its effect on monoamines' levels was investigated in a number of mouse brain areas involved in PPI response mediation. Results demonstrated that the extract antiamnestic dose augmented cortical, hippocampal and striatal monoamine levels. It was therefore concluded that liquorice extract (150 mg/kg)-induced PPI deficit was mediated through augmenting monoaminergic transmission in the cortex, hippocampus and striatum. These findings can be further investigated in experimental models for autism, psychosis and Huntington's disease to decide the safety of using liquorice extract in ameliorating memory disturbance in disorders manifesting PPI deficit.

  18. Reducing the Burden of Difficult-to-Treat Major Depressive Disorder: Revisiting Monoamine Oxidase Inhibitor Therapy

    OpenAIRE

    Culpepper, Larry

    2013-01-01

    Objective: Difficult-to-treat depression (eg, depression with atypical or anxious symptoms, treatment-resistant depression, or depression with frequent recurrence) is a challenging real-world health issue. This critical review of the literature focuses on monoamine oxidase inhibitor (MAOI) therapy and difficult-to-treat forms of depression.

  19. Effects of rhynchophylline on monoamine transmitters of striatum and hippocampus in cerebral ischemic rats

    Institute of Scientific and Technical Information of China (English)

    LUYuan-Fu; XIEXiao-Long; WUQin; WENGuo-Rong; YANGSu-Fen; SHIJing-Shan

    2004-01-01

    AIM To investigate the effects of rhynchophylline ( Rhy on monoamine transmitters and its metabolites in striatum and hippocampus of cerebral ischemic rats. METItODS The cerebral ischemic injury of rat was induced by middle cerebral artery occlusion (MCAO). The extracellular fluid of striatum and hippocampus in cerebral ischemic rats was collected by using

  20. Monoamine Oxidase a Promoter Gene Associated with Problem Behavior in Adults with Intellectual/Developmental Disabilities

    Science.gov (United States)

    May, Michael E.; Srour, Ali; Hedges, Lora K.; Lightfoot, David A.; Phillips, John A., III; Blakely, Randy D.; Kennedy, Craig H.

    2009-01-01

    A functional polymorphism in the promoter of the gene encoding monoamine oxidase A has been associated with problem behavior in various populations. We examined the association of MAOA alleles in adult males with intellectual/developmental disabilities with and without established histories of problem behavior. These data were compared with a…

  1. Double-staining techniques allows electrophysiological identification of monoamine-containing neurons.

    Science.gov (United States)

    Audesirk, T E; Audesirk, G J

    1985-08-01

    Electrophysiological recording provides important evidence for positive identification of many neurons in gastropods. We describe a technique which combines intracellular recording and injection of a persistent, non-fluorescent dye (Fast Green) with subsequent histofluorescence treatment using a modification of the wholemount glyoxylic acid procedure developed by Barber (1983) to establish the presence or absence of monoamine transmitters in positively identified single gastropod neurons.

  2. Sudden infant death syndrome (SIDS) and polymorphisms in Monoamine oxidase A gene (MAOA): a revisit.

    Science.gov (United States)

    Groß, Maximilian; Bajanowski, Thomas; Vennemann, Mechtild; Poetsch, Micaela

    2014-01-01

    Literature describes multiple possible links between genetic variations in the neuroadrenergic system and the occurrence of sudden infant death syndrome. The X-chromosomal Monoamine oxidase A (MAOA) is one of the genes with regulatory activity in the noradrenergic and serotonergic neuronal systems and a polymorphism of the promoter which affects the activity of this gene has been proclaimed to contribute significantly to the prevalence of sudden infant death syndrome (SIDS) in three studies from 2009, 2012 and 2013. However, these studies described different significant correlations regarding gender or age of children. Since several studies, suggesting associations between genetic variations and SIDS, were disproved by follow-up analysis, this study was conducted to take a closer look at the MAOA gene and its polymorphisms. The functional MAOA promoter length polymorphism was investigated in 261 SIDS cases and 93 control subjects. Moreover, the allele distribution of 12 coding and non-coding single nucleotide polymorphisms (SNPs) of the MAOA gene was examined in 285 SIDS cases and 93 controls by a minisequencing technique. In contrast to prior studies with fewer individuals, no significant correlations between the occurrence of SIDS and the frequency of allele variants of the promoter polymorphism could be demonstrated, even including the results from the abovementioned previous studies. Regarding the SNPs, three statistically significant associations were observed which had not been described before. This study clearly disproves interactions between MAOA promoter polymorphisms and SIDS, even if variations in single nucleotide polymorphisms of MAOA should be subjected to further analysis to clarify their impact on SIDS.

  3. The effect of venlafaxine on behaviour, body weight and striatal monoamine levels on sleep-deprived female rats.

    Science.gov (United States)

    de Oliveira, Ricardo A; Cunha, Geanne M A; Borges, Karla Daisy M; de Bruin, Gabriela S; dos Santos-Filho, Emídio A; Viana, Glauce S B; de Bruin, Veralice M S

    2004-11-01

    Partial sleep deprivation is clinically associated with fatigue, depressive symptoms and reduced memory. Previously, it has been demonstrated that venlafaxine, an atypical antidepressant, increases the levels of noradrenaline and serotonin in rat hippocampus. The aim of this study was to evaluate the effects of venlafaxine on depression, anxiety, locomotor activity and memory in a model of REM sleep (REMs) deprivation in rats. We have also studied the influence of venlafaxine on monoamine levels in the striatum. Six groups of animals (N=20 each) were treated with saline or venlafaxine (1 or 10 mg/kg) during 10 days, submitted or not to REMs deprivation and studied with the forced swimming test of Porsolt (STP), plus-maze, passive avoidance and open-field tests right after sleep deprivation. Animals were also studied for passive avoidance 24 h later (rebound period). Brain samples for monoamine measurements were collected either immediately after REMs deprivation or after 24 h. Both REMs deprivation and venlafaxine showed an antidepressant effect. An anxiolytic effect was also observed after REMs deprivation. Previous treatment with venlafaxine blocked the antidepressant and anxiolytic effects of REMs deprivation. REMs deprivation alone and treatment with venlafaxine 10 mg/kg increased locomotor activity, and this effect was inhibited by venlafaxine in REMs deprived rats. Both venlafaxine treatment and REMs deprivation induced weight loss. Venlafaxine treatment, but not REMs deprivation, induced an increase in striatal dopamine (DA) levels. The combination of REMs deprivation and venlafaxine treatment was associated with an increase in serotonin turnover 24 h after rebound sleep. In this study, venlafaxine treatment hindered most behavioral effects of REMs deprivation and was associated with an interference on dopamine and serotonin systems in the striatum.

  4. Neurotransmitter CART as a New Therapeutic Candidate for Parkinson’s Disease

    Directory of Open Access Journals (Sweden)

    Philippe Thuillier

    2013-01-01

    Full Text Available Parkinson’s disease (PD is one of the most common neurodegenerative diseases. To date, there is no effective treatment that halts its progression. Increasing evidence indicates that mitochondria play an important role in the development of PD. Hence mitochondria-targeted approaches or agents may have therapeutic promise for treatment of the disease. Neuropeptide CART (cocaine-amphetamine-regulated transcript, a hypothalamus and midbrain enriched neurotransmitter with an antioxidant property, can be found in mitochondria, which is the main source of reactive oxygen species. Systemic administration of CART has been found to ameliorate dopaminergic neuronal loss and improve motor functions in a mouse model of PD. In this article, we summarize recent progress in studies investigating the relationship between CART, dopamine, and the pathophysiology of PD, with a focus on mitochondria-related topics.

  5. VLSI Potentiostat Array With Oversampling Gain Modulation for Wide-Range Neurotransmitter Sensing.

    Science.gov (United States)

    Stanacevic, M; Murari, K; Rege, A; Cauwenberghs, G; Thakor, N V

    2007-03-01

    A 16-channel current-measuring very large-scale integration (VLSI) sensor array system for highly sensitive electrochemical detection of electroactive neurotransmiters like dopamine and nitric-oxide is presented. Each channel embeds a current integrating potentiostat within a switched-capacitor first-order single-bit delta-sigma modulator implementing an incremental analog-to-digital converter. The duty-cycle modulation of current feedback in the delta-sigma loop together with variable oversampling ratio provide a programmable digital range selection of the input current spanning over six orders of magnitude from picoamperes to microamperes. The array offers 100-fA input current sensitivity at 3.4-muW power consumption per channel. The operation of the 3 mm times3 mm chip fabricated in 0.5-mum CMOS technology is demonstrated with real-time multichannel acquisition of neurotransmitter concentration.

  6. Microtransplantation of neurotransmitter receptors from postmortem autistic brains to Xenopus oocytes

    Science.gov (United States)

    Limon, Agenor; Reyes-Ruiz, Jorge Mauricio; Miledi, Ricardo

    2008-01-01

    Autism is a complex disorder that arises from the pervasive action of genetic and epigenetic factors that alter synaptic connectivity of the brain. Although GABA and glutamate receptors seem to be two of those factors, very little is known about the functional properties of the autistic receptors. Autistic tissue samples stored in brain banks usually have relatively long postmortem times, and it is highly desirable to know whether neurotransmitter receptors in such tissues are still functional. Here we demonstrate that native receptors microtransplanted from autistic brains, as well as de novo mRNA-expressed receptors, are still functional and susceptible to detailed electrophysiological characterization even after long postmortem intervals. The opportunity to study the properties of human receptors present in diseased brains not only opens new avenues toward understanding autism and other neurological disorders, but it also makes the microtransplantation method a useful translational system to evaluate and develop novel medicinal drugs. PMID:18645182

  7. Agrin promotes synaptic differentiation by counteracting an inhibitory effect of neurotransmitter.

    Science.gov (United States)

    Misgeld, Thomas; Kummer, Terrance T; Lichtman, Jeff W; Sanes, Joshua R

    2005-08-02

    Synaptic organizing molecules and neurotransmission regulate synapse development. Here, we use the skeletal neuromuscular junction to assess the interdependence of effects evoked by an essential synaptic organizing protein, agrin, and the neuromuscular transmitter, acetylcholine (ACh). Mice lacking agrin fail to maintain neuromuscular junctions, whereas neuromuscular synapses differentiate extensively in the absence of ACh. We now demonstrate that agrin's action in vivo depends critically on cholinergic neurotransmission. Using double-mutant mice, we show that synapses do form in the absence of agrin provided that ACh is also absent. We provide evidence that ACh destabilizes nascent postsynaptic sites, and that one major physiological role of agrin is to counteract this "antisynaptogenic" influence. Similar interactions between neurotransmitters and synaptic organizing molecules may operate at synapses in the central nervous system.

  8. Afferent Inputs to Neurotransmitter-Defined Cell Types in the Ventral Tegmental Area

    Directory of Open Access Journals (Sweden)

    Lauren Faget

    2016-06-01

    Full Text Available The ventral tegmental area (VTA plays a central role in the neural circuit control of behavioral reinforcement. Though considered a dopaminergic nucleus, the VTA contains substantial heterogeneity in neurotransmitter type, containing also GABA and glutamate neurons. Here, we used a combinatorial viral approach to transsynaptically label afferents to defined VTA dopamine, GABA, or glutamate neurons. Surprisingly, we find that these populations received qualitatively similar inputs, with dominant and comparable projections from the lateral hypothalamus, raphe, and ventral pallidum. However, notable differences were observed, with striatal regions and globus pallidus providing a greater share of input to VTA dopamine neurons, cortical input preferentially on to glutamate neurons, and GABA neurons receiving proportionally more input from the lateral habenula and laterodorsal tegmental nucleus. By comparing inputs to each of the transmitter-defined VTA cell types, this study sheds important light on the systems-level organization of diverse inputs to VTA.

  9. Co-existence of functionally different vesicular neurotransmitter transporters

    Directory of Open Access Journals (Sweden)

    Agnieszka eMünster-Wandowski

    2016-02-01

    Full Text Available The vesicular transmitter transporters VGLUT, VGAT, VMAT2 and VAChT, define phenotype and physiological properties of neuronal subtypes. VGLUTs concentrate the excitatory amino acid glutamate, VGAT the inhibitory amino acid GABA, VMAT2 monoamines, and VAChT acetylcholine into synaptic vesicle (SV. Following membrane depolarization SV release their content into the synaptic cleft. A strict segregation of vesicular transporters is mandatory for the precise functioning of synaptic communication and of neuronal circuits. In the last years, evidence accumulates that subsets of neurons express more than one of these transporters leading to synaptic co-release of different and functionally opposing transmitters and modulation of synaptic plasticity. Synaptic co-existence of transporters may change during pathological scenarios in order to ameliorate misbalances in neuronal activity. In addition, evidence increases that transporters also co-exist on the same vesicle providing another layer of regulation. Generally, vesicular transmitter loading relies on an electrochemical gradient µH+ driven by the proton ATPase rendering the lumen of the vesicle with respect to the cytosol positive ( and acidic (pH. While the activity of VGLUT mainly depends on the component, VMAT, VGAT and VAChT work best at a high pH. Thus, a vesicular synergy of transporters depending on the combination may increase or decrease the filling of SV with the principal transmitter. We provide an overview on synaptic co-existence of vesicular transmitter transporters including changes in the excitatory/inhibitory balance under pathological conditions. Additionally, we discuss functional aspects of vesicular synergy of transmitter transporters.

  10. Co-existence of Functionally Different Vesicular Neurotransmitter Transporters.

    Science.gov (United States)

    Münster-Wandowski, Agnieszka; Zander, Johannes-Friedrich; Richter, Karin; Ahnert-Hilger, Gudrun

    2016-01-01

    The vesicular transmitter transporters VGLUT, VGAT, VMAT2 and VAChT, define phenotype and physiological properties of neuronal subtypes. VGLUTs concentrate the excitatory amino acid glutamate, VGAT the inhibitory amino acid GABA, VMAT2 monoamines, and VAChT acetylcholine (ACh) into synaptic vesicle (SV). Following membrane depolarization SV release their content into the synaptic cleft. A strict segregation of vesicular transporters is mandatory for the precise functioning of synaptic communication and of neuronal circuits. In the last years, evidence accumulates that subsets of neurons express more than one of these transporters leading to synaptic co-release of different and functionally opposing transmitters and modulation of synaptic plasticity. Synaptic co-existence of transporters may change during pathological scenarios in order to ameliorate misbalances in neuronal activity. In addition, evidence increases that transporters also co-exist on the same vesicle providing another layer of regulation. Generally, vesicular transmitter loading relies on an electrochemical gradient ΔμH(+) driven by the proton ATPase rendering the lumen of the vesicle with respect to the cytosol positive (Δψ) and acidic (ΔpH). While the activity of VGLUT mainly depends on the Δψ component, VMAT, VGAT and VAChT work best at a high ΔpH. Thus, a vesicular synergy of transporters depending on the combination may increase or decrease the filling of SV with the principal transmitter. We provide an overview on synaptic co-existence of vesicular transmitter transporters including changes in the excitatory/inhibitory balance under pathological conditions. Additionally, we discuss functional aspects of vesicular synergy of transmitter transporters.

  11. Insulin modulates cocaine-sensitive monoamine transporter function and impulsive behavior.

    Science.gov (United States)

    Schoffelmeer, Anton N M; Drukarch, Benjamin; De Vries, Taco J; Hogenboom, François; Schetters, Dustin; Pattij, Tommy

    2011-01-26

    Because insulin acutely enhances the function of dopamine transporters, the tyrosine kinase receptors activated by this hormone may modulate transporter-dependent neurochemical and behavioral effects of psychoactive drugs. In this respect, we examined the effects of insulin on exocytotic monoamine release and the efficacy of the monoamine transporter blocker cocaine in rat nucleus accumbens. Whereas insulin reduced electrically evoked exocytotic [(3)H]dopamine release in nucleus accumbens slices, the hormone potentiated the release-enhancing effect of cocaine thereon. The phosphatidylinositol 3-kinase inhibitor LY294002 abolished these effects, indicating the involvement of insulin receptors. Similar insulin effects were observed on the release of [(3)H]norepinephrine in nucleus accumbens slices, but not on that of [(3)H]serotonin, and were also apparent in medial prefrontal cortex slices. As might then be expected, insulin also potentiated the dopamine and norepinephrine release-enhancing effects of the selective monoamine uptake inhibitors GBR12909 and desmethylimipramine, respectively. In subsequent behavioral experiments, we investigated the role of insulin in motor impulsivity that depends on monoamine neurotransmission in the nucleus accumbens. Intracranial administration of insulin in the nucleus accumbens alone reduced premature responses in the five-choice serial reaction time task and enhanced the stimulatory effect of peripheral cocaine administration on impulsivity, resembling the observed neurochemical effects of the hormone. In contrast, cocaine-induced locomotor activity remained unchanged by intra-accumbal insulin application. These data reveal that insulin presynaptically regulates cocaine-sensitive monoamine transporter function in the nucleus accumbens and, as a consequence, impulsivity. Therefore, insulin signaling proteins may represent targets for the treatment of inhibitory control deficits such as addictive behaviors.

  12. Aquatic contaminants alter genes involved in neurotransmitter synthesis and gonadotropin release in largemouth bass

    Energy Technology Data Exchange (ETDEWEB)

    Martyniuk, Christopher J. [Department of Physiological Sciences and Center for Environmental and Human Toxicology, University of Florida, Gainesville, FL 32611 (United States); Sanchez, Brian C. [Department of Forestry and Natural Resources and School of Civil Engineering, 195 Marsteller St., Purdue University, West Lafayette, IN 47907 (United States); Szabo, Nancy J.; Denslow, Nancy D. [Department of Physiological Sciences and Center for Environmental and Human Toxicology, University of Florida, Gainesville, FL 32611 (United States); Sepulveda, Maria S., E-mail: mssepulv@purdue.edu [Department of Forestry and Natural Resources and School of Civil Engineering, 195 Marsteller St., Purdue University, West Lafayette, IN 47907 (United States)

    2009-10-19

    Many aquatic contaminants potentially affect the central nervous system, however the underlying mechanisms of how toxicants alter normal brain function are not well understood. The objectives of this study were to compare the effects of emerging and prevalent environmental contaminants on the expression of brain transcripts with a role in neurotransmitter synthesis and reproduction. Adult male largemouth bass (Micropterus salmoides) were injected once for a 96 h duration with control (water or oil) or with one of two doses of a single chemical to achieve the following body burdens ({mu}g/g): atrazine (0.3 and 3.0), toxaphene (10 and 100), cadmium (CdCl{sub 2}) (0.000067 and 0.00067), polychlorinated biphenyl (PCB) 126 (0.25 and 2.5), and phenanthrene (5 and 50). Partial largemouth bass gene segments were cloned for enzymes involved in neurotransmitter (glutamic acid decarboxylase 65, GAD65; tyrosine hydroxylase) and estrogen (brain aromatase; CYP19b) synthesis for real-time PCR assays. In addition, neuropeptides regulating feeding (neuropeptide Y) and reproduction (chicken GnRH-II, cGnRH-II; salmon GnRH, sGnRH) were also investigated. Of the chemicals tested, only cadmium, PCB 126, and phenanthrene showed any significant effects on the genes tested, while atrazine and toxaphene did not. Cadmium (0.000067 {mu}g/g) significantly increased cGnRH-II mRNA while PCB 126 (0.25 {mu}g/g) decreased GAD65 mRNA. Phenanthrene decreased GAD65 and tyrosine hydroxylase mRNA levels at the highest dose (50 {mu}g/g) but increased cGnRH-II mRNA at the lowest dose (5 {mu}g/g). CYP19b, NPY, and sGnRH mRNA levels were unaffected by any of the treatments. A hierarchical clustering dendrogram grouped PCB 126 and phenanthrene more closely than other chemicals with respect to the genes tested. This study demonstrates that brain transcripts important for neurotransmitter synthesis neuroendocrine function are potential targets for emerging and prevalent aquatic contaminants.

  13. Carrier-mediated release of monoamines induced by the nicotinic acetylcholine receptor agonist DMPP.

    Science.gov (United States)

    Szász, Bernadett K; Mayer, Aliz; Zsilla, Gabriella; Lendvai, Balázs; Vizi, E Sylvester; Kiss, János P

    2005-09-01

    We have previously shown that dimethylphenylpiperazinium (DMPP) increases the release of noradrenaline (NA) from rat hippocampal slices via two distinct mechanisms: a nicotinic acetylcholine receptor (nAChR)-mediated exocytosis and a carrier-mediated release induced by the reversal of NA transporters. Our aim was to investigate whether other monoaminergic systems are also affected by the multiple actions of DMPP. In our experiments DMPP dose-dependently increased the release of dopamine (DA) and serotonin (5-HT) from rat striatal and hippocampal slices, respectively. The dual effect was observed, however, only in case of DA at a lower DMPP concentration (30 microM), where the response was partly inhibited by mecamylamine, TTX and Ca2+-free medium (nAChR-mediated exocytosis) while the other part of the response was blocked only by the DA uptake inhibitor nomifensine (carrier-mediated release). In contrast, the DMPP-evoked 5-HT release and the DA release induced by high concentration DMPP was not inhibited by nicotinic antagonists, TTX and Ca2+-free medium but only by selective uptake inhibitors. In addition, DMPP dose-dependently inhibited the [3H]DA and [3H]5-HT uptake in striatal and hippocampal synaptosome preparation with an IC50 of 3.18 and 0.49 microM, respectively. Our data show that DMPP interacts with monoamine transporters and induces a substantial carrier-mediated release of DA and 5-HT, therefore caution is needed for the interpretation of data, when this drug is used as a nAChR agonist.

  14. The novel trisubstituted pyran derivative D-142 has triple monoamine reuptake inhibitory activity and exerts potent antidepressant-like activity in rodents

    Science.gov (United States)

    Dutta, Aloke K.; Gopishetty, Bhaskar; Gogoi, Sanjib; Ali, Solav; Zhen, Juan; Reith, Maarten

    2011-01-01

    Major depression disorder is a significant health problem with 10-20% of all adults suffering from this disease. The underlying causes of depression are still unclear and 15% of depressed patients are resistant to all known therapies. Monoamine therapies have so far been the most successful approach for treating depression. Triple monoamine reuptake inhibitors have recently been implicated in generation of potent antidepressant activity while possibly exhibiting a low side-effect profile in addition to treating anhedonia. The additional, previously under-appreciated involvement of dopaminergic systems in depression prompted our efforts to develop novel asymmetric trisubstituted and disubstituted pyran derivatives as triple reuptake inhibitors. One of the lead compounds, D-142, exhibited uptake inhibition (Ki) values of 29.3 nM, 14.7 nM and 37.4 nM for norepinephrine, serotonin and dopamine transporters, respectively. Its affinity for serotonin transporter was comparable to fluoxetine , a well known SSRI. In the rat forced swimming test, compound D-142 exhibited potent antidepressant activity in the dose range tested (2.5, 5 and 10 mg/kg) and was far more efficacious than the reference compound imipramine. In the mouse tail suspension test, compound D-142 reduced immobility in a dose (2.5, 5 and 10 mg/kg) dependent manner, indicating a potent antidepressant effect. In locomotor activity tests, compound D-142 did not exhibit any stimulation in the same dose ranges. In the extended CNS receptors screening assay this molecule exhibited little or no non-specific interaction in the CNS, indicating high specificity for monoamine transporters. These results advance D-142 as a potential potent antidepressant. PMID:21963455

  15. Kv3 voltage-gated potassium channels regulate neurotransmitter release from mouse motor nerve terminals.

    Science.gov (United States)

    Brooke, Ruth E; Moores, Thomas S; Morris, Neil P; Parson, Simon H; Deuchars, Jim

    2004-12-01

    Voltage-gated potassium (Kv) channels are critical to regulation of neurotransmitter release throughout the nervous system but the roles and identity of the subtypes involved remain unclear. Here we show that Kv3 channels regulate transmitter release at the mouse neuromuscular junction (NMJ). Light- and electron-microscopic immunohistochemistry revealed Kv3.3 and Kv3.4 subunits within all motor nerve terminals of muscles examined [transversus abdominus, lumbrical and flexor digitorum brevis (FDB)]. To determine the roles of these Kv3 subunits, intracellular recordings were made of end-plate potentials (EPPs) in FDB muscle fibres evoked by electrical stimulation of tibial nerve. Tetraethylammonium (TEA) applied at low concentrations (0.05-0.5 mM), which blocks only a few known potassium channels including Kv3 channels, did not affect muscle fibre resting potential but significantly increased the amplitude of all EPPs tested. Significantly, this effect of TEA was still observed in the presence of the large-conductance calcium-activated potassium channel blockers iberiotoxin (25-150 nM) and Penitrem A (100 nM), suggesting a selective action on Kv3 subunits. Consistent with this, 15-microM 4-aminopyridine, which blocks Kv3 but not large-conductance calcium-activated potassium channels, enhanced evoked EPP amplitude. Unexpectedly, blood-depressing substance-I, a toxin selective for Kv3.4 subunits, had no effect at 0.05-1 microM. The combined presynaptic localization of Kv3 subunits and pharmacological enhancement of EPP amplitude indicate that Kv3 channels regulate neurotransmitter release from presynaptic terminals at the NMJ.

  16. Biochemical evidence that L-glutamate is a neurotransmitter of primary vagal afferent nerve fibers

    Energy Technology Data Exchange (ETDEWEB)

    Perrone, M.H. (Cornell Univ., New York (USA). Medical Coll.)

    1981-12-28

    To determine in rat if vagal afferent fibers projecting into the intermediate one third of the nucleus tractus solitarius (NTS), the site of termination of baroafferents, utilize glutamate as a neurotransmitter, the high-affinity uptake of (/sup 3/H)L-glutamate and content of glutamate were analyzed in micropunches of rat brain stem. The intermediate NTS contains a high-affinity synaptosomal uptake system for (/sup 3/H)L-glutamate that is greater in capacity than that in areas adjacent to the NTS; it is almost two-fold higher than uptake in medial septum and nucleus accumbens and equal to that of hippocampal regions purportedly containing a rich glutamatergic innervation. Unilateral ablation of the nodose ganglion (i.e. cells of origin of vagal afferents) resulted, within 24 h in a prolonged significant reduction, to 56% of control, of (/sup 3/H)L-glutamate uptake, bilaterally in the NTS. The reduction of Na/sup +/-dependent synaptosomal uptake of (/sup 3/H)L-glutamate, resulted from a decrease in Vsub(max) without change in the Ksub(m) of the process, was anatomically restricted to the intermediate NTS, and was not associated with changes in (/sup 3/H)GABA uptake. The content of glutamate in the NTS was significantly (P < 0.01) decreased by 30% 7 days following unilateral extirpation of the nodose ganglion without changes in the concentrations of aspartate, glycine, glutamine, or GABA. A population of vagal afferent fibers projecting to NTS are glutamatergic. The results are consistent with the hypothesis obtained by physiological and pharmacological techniques that glutamate is a neurotransmitter of baroafferents.

  17. Four-dimensional multi-site photolysis of caged neurotransmitters

    Directory of Open Access Journals (Sweden)

    Mary Ann eGo

    2013-12-01

    Full Text Available Neurons receive thousands of synaptic inputs that are distributed in space and time. The systematic study of how neurons process these inputs requires a technique to stimulate multiple yet highly targeted points of interest along the neuron's dendritic tree. Three-dimensional multi-focal patterns produced via holographic projection combined with two-photon photolysis of caged compounds can provide for highly localized release of neurotransmitters within each diffraction-limited focus, and in this way emulate simultaneous synaptic inputs to the neuron. However, this technique so far cannot achieve time-dependent stimulation patterns due to fundamental limitations of the hologram-encoding device and other factors that affect the consistency of controlled synaptic stimulation. Here, we report an advanced technique that enables the design and application of arbitrary spatio-temporal photostimulation patterns that resemble physiological synaptic inputs. By combining holographic projection with a programmable high-speed light-switching array, we have overcome temporal limitations with holographic projection, allowing us to mimic distributed activation of synaptic inputs leading to action potential generation. Our experiments uniquely demonstrate multi-site two-photon glutamate uncaging in three dimensions with submillisecond temporal resolution. Implementing this approach opens up new prospects for studying neuronal synaptic integration in four dimensions.

  18. Contributions to the field of neurotransmitters by Japanese scientists, and reflections on my own research.

    Science.gov (United States)

    Otsuka, Masanori

    2007-03-01

    PART I DESCRIBES IMPORTANT CONTRIBUTIONS MADE BY SOME JAPANESE PIONEERS IN THE FIELD OF NEUROTRANSMITTERS: (their achievements in parentheses) J. Takamine (isolation and crystallization of adrenaline); K. Shimidzu (early hint for acetylcholine as a neurotransmitter); F. Kanematsu (donation of the Kanematsu Memorial Institute in Sydney); T. Hayashi (discovery of the excitatory action of glutamate and the inhibitory action of GABA); and I. Sano (discovery of a high concentration of dopamine in striatum, its reduction in a patient with Parkinson's disease and the treatment with DOPA). In Part II, I present some of my reflections on my research on neurotransmitters. The work of my colleagues and myself has made some significant contributions to the establishment of neurotransmitter roles played by GABA and substance P, the first amino acid and the first peptide neurotransmitters, respectively. By the early 1960s, 3 substances, i.e., acetylcholine, noradrenaline, and adrenaline, had been established as neurotransmitters. Now the number of neurotransmitters is believed to be as many as 50 or even more mainly due to the inclusion of several amino acids and a large number of peptide transmitters.

  19. Influence of circadian disruption on neurotransmitter levels, physiological indexes, and behaviour in rats.

    Science.gov (United States)

    Matsumura, Takeru; Nakagawa, Hikaru; Suzuki, Kota; Ninomiya, Chisa; Ishiwata, Takayuki

    2015-01-01

    Brain monoamines - such as noradrenaline (NA), dopamine (DA) and serotonin (5-HT) - regulate several important physiological functions, including the circadian rhythm. The purpose of this study was to examine changes in NA, DA and 5-HT levels in various brain regions and their effect on core body temperature (Tc), heart rate (HR) and locomotor activity (Act) in rats following exposure to an artificial light/dark (LD) cycle. For this, male Wistar rats were housed at an ambient temperature (Ta) of 23 °C and 50% relative humidity with free access to food and water. Rats were exposed to either natural (12 h:12 h) or artificial (6 h:6 h) LD cycles for 1 month, after which each brain region was immediately extracted and homogenized to quantify the amounts of NA, DA and 5-HT by high-performance liquid chromatography. Behavioural changes were also monitored by the ambulatory activity test (AAT). Notably, we found that artificial LD cycles disrupted the physiological circadian rhythms of Tc, HR and Act. Although the 5-HT levels of rats with a disrupted circadian rhythm decreased in cell bodies (dorsal and median raphe nuclei) and projection areas (frontal cortex, caudate putamen, preoptic area and suprachiasmatic nucleus) relative to the control group, NA levels increased both in the cell body (locus coeruleus) and projection area (paraventricular hypothalamus). No significant changes were found with respect to DA. Moreover, circadian rhythm-disrupted rats also showed anxious behaviours in AAT. Collectively, the results of this study suggest that the serotonergic and noradrenergic systems, but not the dopaminergic system, are affected by artificial LD cycles in brain regions that control several neural and physiological functions, including the regulation of physiological circadian rhythms, stress responses and behaviour.

  20. Antidepressant Drugs Transactivate TrkB Neurotrophin Receptors in the Adult Rodent Brain Independently of BDNF and Monoamine Transporter Blockade

    OpenAIRE

    Tomi Rantamäki; Liisa Vesa; Hanna Antila; Antonio Di Lieto; Päivi Tammela; Angelika Schmitt; Klaus-Peter Lesch; Maribel Rios; Eero Castrén

    2011-01-01

    BACKGROUND: Antidepressant drugs (ADs) have been shown to activate BDNF (brain-derived neurotrophic factor) receptor TrkB in the rodent brain but the mechanism underlying this phenomenon remains unclear. ADs act as monoamine reuptake inhibitors and after prolonged treatments regulate brain bdnf mRNA levels indicating that monoamine-BDNF signaling regulate AD-induced TrkB activation in vivo. However, recent findings demonstrate that Trk receptors can be transactivated independently of their ne...

  1. Distinct pharmacological properties and distribution in neurons and endocrine cells of two isoforms of the human vesicular monoamine transporter.

    OpenAIRE

    Erickson, J.D.; Schafer, M K; Bonner, T I; Eiden, L. E.; Weihe, E.

    1996-01-01

    A second isoform of the human vesicular monoamine transporter (hVMAT) has been cloned from a pheochromocytoma cDNA library. The contribution of the two transporter isoforms to monoamine storage in human neuroendocrine tissues was examined with isoform-specific polyclonal antibodies against hVMAT1 and hVMAT2. Central, peripheral, and enteric neurons express only VMAT2. VMAT1 is expressed exclusively in neuroendocrine, including chromaffin and enterochromaffin, cells. VMAT1 and VMAT2 are coexpr...

  2. Effect of single-use versus combined-use moschus and diazepam on expression of amino acid neurotransmitters in the rat corpus striatum

    Institute of Scientific and Technical Information of China (English)

    Na Zhang; Ping Liu; Xinrong He

    2012-01-01

    The present study analyzed expressional changes of excitatory neurotransmitters and inhibitory neurotransmitters in the rat corpus striatum after single-use and combined-use diazepam and Chinese herb moschus. The influence of moschus on the central nervous system was analyzed, in particular whether moschus increased penetration of other drugs into the brain. Reverse-phase high-performance liquid chromatography, which included pre-column derivation with orthophthaladehyde detection, showed varied increased levels of excitatory neurotransmitters, including aspartate and glutamate, and inhibitory neurotransmitters, including glycine and γ-aminobutyric acid, in the corpus striatum after treatment with moschus alone, diazepam alone, or a combination of both. Compared with the diazepam group, aspartate levels significantly decreased at 30 and 60-105 minutes after combined treatment with moschus, while glutamate significantly increased at 45 and 75-105 minutes, glycine levels significantly increased at 105 minutes, and γ-aminobutyric acid increased at 30 and 75-105 minutes. These findings suggested that moschus increased the inhibition effects of diazepam on the brain.

  3. Depolarization by K*O+ and glutamate activates different neurotransmitter release mechanisms in gabaergic neurons: vesicular versus non-vesicular release of gaba

    DEFF Research Database (Denmark)

    Belhage, Bo; Hansen, G.H.; Schousboe, Arne

    1993-01-01

    Neurotransmitter release, gaba release, membrane transporter, vesicles, intracellular CA*OH, neuron cultures......Neurotransmitter release, gaba release, membrane transporter, vesicles, intracellular CA*OH, neuron cultures...

  4. Efficacy, safety, and patient preference of monoamine oxidase B inhibitors in the treatment of Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Bradley J Robottom

    2011-01-01

    Full Text Available Bradley J RobottomDepartment of Neurology, University of Maryland School of Medicine, Baltimore, MD, USAAbstract: Parkinson's disease (PD is the second most common neurodegenerative disease and the most treatable. Treatment of PD is symptomatic and generally focuses on the replacement or augmentation of levodopa. A number of options are available for treatment, both in monotherapy of early PD and to treat complications of advanced PD. This review focuses on rasagiline and selegiline, two medications that belong to a class of antiparkinsonian drugs called monoamine oxidase B (MAO-B inhibitors. Topics covered in the review include mechanism of action, efficacy in early and advanced PD, effects on disability, the controversy regarding disease modification, safety, and patient preference for MAO-B inhibitors.Keywords: monoamine oxidase inhibitors, rasagiline, selegiline, Parkinson's disease, efficacy, safety

  5. Desmodeleganine, a new alkaloid from the leaves of Desmodium elegans as a potential monoamine oxidase inhibitor.

    Science.gov (United States)

    Zhi, Kang-Kang; Yang, Zhong-Duo; Shi, Dan-Feng; Yao, Xiao-Jun; Wang, Ming-Gang

    2014-10-01

    Desmodeleganine (1), a new potential monoamine oxidase inhibitor, along with three known alkaloids, bufotenin (2), hydroxy-N, N-dimethyltryptamine N(12)-oxide (3), 2-(5-methoxy-1H-indol-3-yl)-N, and N-dimethylethylamine (4) were isolated from the leaves of Desmodium elegans. Their structures were elucidated by IR, MS, 1D and 2D NMR spectra. 1 showed strong monoamine oxidase inhibitory activity with IC50 value of 13.92 ± 1.5 μM, when the IC50 value of iproniazid as a standard was 6.5 ± 0.5 μM. The molecular modeling was also performed to explore the binding mode of compounds 1, 2 at the active site of MAO-A and MAO-B.

  6. Frightening music triggers rapid changes in brain monoamine receptors: a pilot PET study.

    Science.gov (United States)

    Zhang, Ying; Chen, Qiaozhen; Du, Fenglei; Hu, Yanni; Chao, Fangfang; Tian, Mei; Zhang, Hong

    2012-10-01

    Frightening music can rapidly arouse emotions in listeners that mimic those from actual life-threatening experiences. However, studies of the underlying mechanism for perceiving danger created by music are limited. We investigated monoamine receptor changes induced by frightening music using (11)C-N-methyl-spiperone ((11)C-NMSP) PET. Ten healthy male volunteers were included, and their psychophysiologic changes were evaluated. Compared with the baseline condition, listening to frightening music caused a significant decrease in (11)C-NMSP in the right and left caudate nuclei, right limbic region, and right paralimbic region; a particularly significant decrease in the right anterior cingulate cortex; but an increase in the right frontal occipital and left temporal lobes of the cerebral cortex. Transient fright triggers rapid changes in monoamine receptors, which decrease in the limbic and paralimbic regions but increase in the cerebral cortex.

  7. Changes in free amino acid and monoamine concentrations in the chick brain associated with feeding behavior.

    Science.gov (United States)

    Tran, Phuong V; Chowdhury, Vishwajit S; Nagasawa, Mao; Furuse, Mitsuhiro

    2015-01-01

    Domesticated chicks are precocial and therefore have relatively well-developed feeding behavior. The role of hypothalamic neuropeptides in food-intake regulation in chicks has been reported for decades. However, we hypothesized that nutrients and their metabolites in the brain may be involved in food intake in chicks because these animals exhibit a very frequent feeding pattern. Therefore, the purpose of this study was to examine the feeding behavior of chicks as well as the associated changes in free amino acid and monoamine concentrations in the chick brain. The feeding behavior of chicks was recorded continuously for 6 h. The next day, brain and blood samples were collected when the chicks either attempted to have food (hungry group) or turned food down (satiated group), in order to analyze the concentrations of the free amino acids and monoamines. We confirmed that the feeding behavior of neonatal chicks was characterized by short resting periods between very brief times spent on food intake. Several free amino acids in the mesencephalon were significantly lower in the satiated group than in the hungry group, while l-histidine and l-glutamine were significantly higher. Notably, there was no change in the free amino acid concentrations in other brain regions or plasma. As for monoamines, serotonin and norepinephrine were significantly lower in the mesencephalon of the hungry group compared with the satiated group, but 5 hydroxyindolacetic acid (5-HIAA) was higher. In addition, serotonin and norepinephrine levels were significantly higher in the brain stem of the hungry chicks compared with the satiated group, but levels of 5-HIAA and homovanillic acid were lower. Levels of both dopamine and its metabolite, 3,4-dihydroxyphenylacetic acid, were significantly higher in the diencephalon and telencephalon of the chicks in the hungry group. In conclusion, the changes in the free amino acids and monoamines in the brain may have some role in the feeding behavior of

  8. Altered monoamine and acylcarnitine metabolites in HIV-positive and HIV-negative subjects with depression

    Science.gov (United States)

    Cassol, Edana; Misra, Vikas; Morgello, Susan; Kirk, Gregory D.; Mehta, Shruti H.; Gabuzda, Dana

    2015-01-01

    Background Depression is a frequent comorbidity in HIV infection that has been associated with worse treatment outcomes and increased mortality. Recent studies suggest that increased innate immune activation and tryptophan catabolism are associated with higher risk of depression in HIV infection and other chronic inflammatory diseases, but the mechanisms leading to depression remain poorly understood. Methods The severity of depressive symptoms was assessed by Beck Depression Inventory or Center for Epidemiological Studies Depression Scale. Untargeted metabolomic profiling of plasma from 104 subjects (68 HIV-positive and 36 HIV-negative) across three independent cohorts was performed using liquid or gas chromatography followed by mass spectrometry. Cytokine profiling was by Bioplex array. Bioinformatic analysis was performed in Metaboanalyst and R. Results Decreased monoamine metabolites (phenylacetate, 4-hydroxyphenylacetate) and acylcarnitines (propionylcarnitine, isobutyrylcarnitine, isovalerylcarnitine, 2-methylbutyrylcarnitine) in plasma distinguished depressed subjects from controls in HIV-positive and HIV-negative cohorts, and these alterations correlated with the severity of depressive symptoms. In HIV-positive subjects, acylcarnitines and other markers of mitochondrial function correlated inversely with tryptophan catabolism, a marker of IFN responses, suggesting inter-relationships between inflammatory pathways, tryptophan catabolism, and metabolic alterations associated with depression. Altered metabolites mapped to pathways involved in monoamine metabolism, mitochondrial function, and inflammation, suggesting a model in which complex relationships between monoamine metabolism and mitochondrial bioenergetics contribute to biological mechanisms involved in depression that may be augmented by inflammation during HIV infection. Conclusions Integrated approaches targeting inflammation, monoamine metabolism, and mitochondrial pathways may be important for

  9. Genetic studies of two inherited human phenotypes : Hearing loss and monoamine oxidase activity

    OpenAIRE

    Balciuniene, Jorune

    2001-01-01

    This thesis focuses on the identification of genetic factors underlying two inherited human phenotypes: hearing loss and monoamine oxidase activity. Non-syndromic hearing loss segregating in a Swedish family was tested for linkage to 13 previously reported candidate loci for hearing disabilities. Linkage was found to two loci: DFNA12 (llq22-q24) and DFNA2 (lp32). A detailed analysis of the phenotypes and haplotypes shared by the affected individuals supported the hypothesis of digenic inheri...

  10. Synthesis, inhibition and binding of simple non-nitrogen inhibitors of monoamine transporters.

    Science.gov (United States)

    Petersen, Mikkel Due; Boye, Søren Valdgård; Nielsen, Erik Holm; Willumsen, Jeanette; Sinning, Steffen; Wiborg, Ove; Bols, Mikael

    2007-06-15

    A series of simple truncated analogues of phenyl tropanes, 2-arylcycloalk-1-enyl carboxylic acid methylesters, were prepared and investigated for their activity towards the dopamine, serotonin and norepinephrine transporters. The compounds were prepared from cyclic ketoesters, which were converted to enolic triflates and reacted with arylboronates using the Suzuki coupling. For comparison the corresponding piperidines were also made and investigated. The new compounds inhibit monoamine-transporters with Ki values ranging from 0.1 to 1000 microM.

  11. Mimicking Neurotransmitter Release in Chemical Synapses via Hysteresis Engineering in MoS2 Transistors.

    Science.gov (United States)

    Arnold, Andrew J; Razavieh, Ali; Nasr, Joseph R; Schulman, Daniel S; Eichfeld, Chad M; Das, Saptarshi

    2017-03-10

    Neurotransmitter release in chemical synapses is fundamental to diverse brain functions such as motor action, learning, cognition, emotion, perception, and consciousness. Moreover, improper functioning or abnormal release of neurotransmitter is associated with numerous neurological disorders such as epilepsy, sclerosis, schizophrenia, Alzheimer's disease, and Parkinson's disease. We have utilized hysteresis engineering in a back-gated MoS2 field effect transistor (FET) in order to mimic such neurotransmitter release dynamics in chemical synapses. All three essential features, i.e., quantal, stochastic, and excitatory or inhibitory nature of neurotransmitter release, were accurately captured in our experimental demonstration. We also mimicked an important phenomenon called long-term potentiation (LTP), which forms the basis of human memory. Finally, we demonstrated how to engineer the LTP time by operating the MoS2 FET in different regimes. Our findings could provide a critical component toward the design of next-generation smart and intelligent human-like machines and human-machine interfaces.

  12. Effect of realgar on extracellular amino acid neurotransmitters in hippocampal CA1 region determined by online microdialysis–dansyl chloride derivatization–high-performance liquid chromatography and fluorescence detection.

    Science.gov (United States)

    Huo, Taoguang; Zhang, Yinghua; Li, Weikai; Yang, Huilei; Jiang, Hong; Sun, Guifan

    2014-09-01

    An online microdialysis (MD)–dansyl chloride (Dns) derivatization–high-performance liquid chromatography (HPLC) and fluorescence detection (FD) system was developed for simultaneous determination of eight extracellular amino acid neurotransmitters in hippocampus. The MD probe was implanted in hippocampal CA1 region. Dialysate and Dns were online mixed and derivatized. The derivatives were separated on an ODS column and detected by FD. The developed online system showed good linearity, precision, accuracy and recovery. This online MD-HPLC system was applied to monitor amino acid neurotransmitters levels in rats exposed to realgar (0.3, 0.9 and 2.7 g/kg body weight). The result shows that glutamate concentrations were significantly increased (pHPLC–FD system provides a new experimental method for studying the effect of toxic Chinese medicines on amino acid neurotransmitters.

  13. FMRP Regulates Neurotransmitter Release and Synaptic Information Transmission by Modulating Action Potential Duration via BK channels

    OpenAIRE

    Deng, Pan-Yue; Rotman, Ziv; Blundon, Jay A.; Cho, Yongcheol; Cui, Jianmin; Cavalli, Valeria; Zakharenko, Stanislav S; Klyachko, Vitaly A.

    2013-01-01

    Loss of FMRP causes Fragile X syndrome (FXS), but the physiological functions of FMRP remain highly debatable. Here we show that FMRP regulates neurotransmitter release in CA3 pyramidal neurons by modulating action potential (AP) duration. Loss of FMRP leads to excessive AP broadening during repetitive activity, enhanced presynaptic calcium influx and elevated neurotransmitter release. The AP broadening defects caused by FMRP loss have a cell-autonomous presynaptic origin and can be acutely r...

  14. Predator exposure/psychosocial stress animal model of post-traumatic stress disorder modulates neurotransmitters in the rat hippocampus and prefrontal cortex.

    Directory of Open Access Journals (Sweden)

    C Brad Wilson

    Full Text Available Post-Traumatic Stress Disorder (PTSD can develop in response to a traumatic event involving a threat to life. To date, no diagnostic biomarkers have been identified for PTSD. Recent research points toward physiological abnormalities in the hypothalamic-pituitary-adrenal (HPA axis, sympathoadrenal medullary and immune system that may be implicated in the disorder. The modulation of neurotransmitters is another possible mechanism, but their role in the progression of PTSD is poorly understood. Low serotonin (5-HT may be a factor, but it may not be the only neurotransmitter affected as modulation affects levels of other neurotransmitters. In this study, we hypothesized the predator exposure/psychosocial stress rodent model of PTSD may alter levels of 5-HT and other neurotransmitters in the rat hippocampus and prefrontal cortex (PFC. Male Sprague-Dawley rats were used in this experiment. We induced PTSD via a predator exposure/psychosocial stress model, whereby rats were placed in a cage with a cat for 1 hour on days 1 and 11 of the 31-day experiment. Rats also received psychosocial stress via daily cage cohort changes. On day 32, the rats were sacrificed and the brains dissected to remove the hippocampus and PFC. Norepinephrine (NE, 5-Hydroxyindoleacetic acid (5-HIAA, homovanillic acid (HVA, dopamine (DA, and 3,4-Dihydroxyphenylacetic acid (DOPAC, and 5-HT levels in the hippocampus and PFC were measured with high-performance liquid chromatography (HPLC. In the hippocampus, 5-HT and HVA were lower, while NE and DOPAC were higher, in the PTSD group vs. controls. In the PFC, only 5-HT was lower, while NE, DA, and DOPAC were higher, in the PTSD group vs. controls. The rate limiting enzymes tyrosine hydroxylase and tryptophan hydroxylase were also examined and confirmed our findings. These results demonstrate that the predator exposure/psychosocial stress model of PTSD produces neurotransmitter changes similar to those seen in human patients and may

  15. (/sup 11/C)clorgyline and (/sup 11/C)-L-deprenyl and their use in measuring functional monoamine oxidase activity in the brain using positron emission tomography

    Science.gov (United States)

    Fowler, J.S.; MacGregor, R.R.; Wolf, A.P.

    1986-04-17

    This invention involves a new strategy for imaging the activity of the enzyme monoamine oxidase in the living body by using /sup 11/C-labeled enzyme inhibitors which bind irreversibly to an enzyme as a result of catalysis. By using positron emission tomography to image the distribution of radioactivity produced by the body penetrating radiation emitted by carbon-11, a map of functionally active monoamine oxidase activity is obtained. Clorgyline and L-deprenyl are suicide enzyme inhibitors and irreversibly inhibit monoamine oxidase. When these inhibitors are labeled with carbon-11 they provide selective probes for monoamine oxidase localization and reactivity in vivo using positron emission tomography. 2 figs.

  16. The mitochondrial monoamine oxidase-aldehyde dehydrogenase pathway: a potential site of action of daidzin.

    Science.gov (United States)

    Rooke, N; Li, D J; Li, J; Keung, W M

    2000-11-02

    Recent studies showed that daidzin suppresses ethanol intake in ethanol-preferring laboratory animals. In vitro, it potently and selectively inhibits the mitochondrial aldehyde dehydrogenase (ALDH-2). Further, it inhibits the conversion of monoamines such as serotonin (5-HT) and dopamine (DA) into their respective acid metabolites, 5-hydroxyindole-3-acetic acid (5-HIAA) and 3,4-dihydroxyphenylacetic acid (DOPAC) in isolated hamster or rat liver mitochondria. Studies on the suppression of ethanol intake and inhibition of 5-HIAA (or DOPAC) formation by six structural analogues of daidzin suggested a potential link between these two activities. This, together with the finding that daidzin does not affect the rates of mitochondria-catalyzed oxidative deamination of these monoamines, raised the possibility that the ethanol intake-suppressive (antidipsotropic) action of daidzin is not mediated by the monoamines but rather by their reactive biogenic aldehyde intermediates such as 5-hydroxyindole-3-acetaldehyde (5-HIAL) and/or 3,4-dihydroxyphenylacetaldehyde (DOPAL) which accumulate in the presence of daidzin. To further evaluate this possibility, we synthesized more structural analogues of daidzin and tested and compared their antidipsotropic activities in Syrian golden hamsters with their effects on monoamine metabolism in isolated hamster liver mitochondria using 5-HT as the substrate. Effects of daidzin and its structural analogues on the activities of monoamine oxidase (MAO) and ALDH-2, the key enzymes involved in 5-HT metabolism in the mitochondria, were also examined. Results from these studies reveal a positive correlation between the antidipsotropic activities of these analogues and their abilities to increase 5-HIAL accumulation during 5-HT metabolism in isolated hamster liver mitochondria. Daidzin analogues that potently inhibit ALDH-2 but have no or little effect on MAO are most antidipsotropic, whereas those that also potently inhibit MAO exhibit little, if

  17. Hydrophilic interaction chromatography combined with dispersive liquid-liquid microextraction as a preconcentration tool for the simultaneous determination of the panel of underivatized neurotransmitters in human urine samples.

    Science.gov (United States)

    Konieczna, Lucyna; Roszkowska, Anna; Niedźwiecki, Maciej; Bączek, Tomasz

    2016-01-29

    A simple and sensitive method using dispersive liquid-liquid microextraction (DLLME) followed by liquid chromatography coupled to mass spectrometry (LC-MS) with a hydrophilic interaction chromatography (HILIC) column was developed for the simultaneous determination of 13 compounds of different polarities, comprising monoamine neurotransmitters (dopamine, norepinephrine, epinephrine and serotonin) along with their respective precursors and metabolites, in human urine samples. The microextraction procedure was based on the fast injection of a mixture of ethanol (disperser solvent) and dichloromethane (extraction solvent) into a human urine sample, forming a cloudy solution in the Eppendorf tube. After centrifugation, the sedimented phase was collected and subsequently analyzed by LC-HILIC-MS in about 12min without a derivatization step. The separation was performed on an XBridge Amide™ BEH column 3.0×100mm, 3.5mm and the mobile phase consisted of phase A: 10mM ammonium formate buffer in water pH 3.0 and phase B: 10 mM ammonium formate buffer in acetonitrile, under gradient program elution. Tyrosine, tryptophan, 5-hydroxytryptophan, dopamine, epinephrine, norepinephrine, serotonin, 3-methoxytyramine, 5-hydroxyindole-3-acetic acid, 3,4-dihydroxy-l-phenylalanine and norvaline (internal standard) were detected in the positive ionization mode. While vanillylmandelic acid, homovanillic acid, 3,4-dihydroxyphenylacetic acid and 3,4-dihydroxybenzylamine (internal standard) were detected in the negative ionization mode. Parameters influencing DLLME and LC-HILIC-MS were investigated. Under the optimum conditions, the proposed method exhibited a low detection limit (5-10ngmL(-1)), and good linearity with R between 0.9991 and 0.9998. The recoveries in human urine samples were 99.0%±3.6%. for the 13 studied biogenic amines with intra- and inter-day RSDs of 0.24-9.55% and 0.31-10.0%, respectively. The developed DLLME-LC-MS method could be successfully applied for the

  18. Mechanical tension contributes to clustering of neurotransmitter vesicles at presynaptic terminals.

    Science.gov (United States)

    Siechen, Scott; Yang, Shengyuan; Chiba, Akira; Saif, Taher

    2009-08-04

    Memory and learning in animals are mediated by neurotransmitters that are released from vesicles clustered at the synapse. As a synapse is used more frequently, its neurotransmission efficiency increases, partly because of increased vesicle clustering in the presynaptic neuron. Vesicle clustering has been believed to result primarily from biochemical signaling processes that require the connectivity of the presynaptic terminal with the cell body, the central nervous system, and the postsynaptic cell. Our in vivo experiments on the embryonic Drosophila nervous system show that vesicle clustering at the neuromuscular presynaptic terminal depends on mechanical tension within the axons. Vesicle clustering vanishes upon severing the axon from the cell body, but is restored when mechanical tension is applied to the severed end of the axon. Clustering increases when intact axons are stretched mechanically by pulling the postsynaptic muscle. Using micro mechanical force sensors, we find that embryonic axons that have formed neuromuscular junctions maintain a rest tension of approximately 1 nanonewton. If the rest tension is perturbed mechanically, axons restore the rest tension either by relaxing or by contracting over a period of approximately 15 min. Our results suggest that neuromuscular synapses employ mechanical tension as a signal to modulate vesicle accumulation and synaptic plasticity.

  19. Gaseous neurotransmitter nitric oxide: Its role in experimental models of epilepsy

    Directory of Open Access Journals (Sweden)

    Hrnčić D.

    2012-01-01

    Full Text Available Epilepsy is one of the leading neurological disorders and affects 1-2% of the world’s population. Generally, it is a result of an imbalance between excitatory and inhibitory phenomena in the central nervous system (CNS, but the mechanisms of its initiation and propagation still require further investigations. Experimental models represent one of the most powerful tools to better understand the mechanisms of epileptogenesis. Nitric oxide (NO is gaseous molecule with pleiotropic physiological and pathological effects in almost all organ systems and intriguing biological relevance, especially in the CNS where it acts as a gaseous neurotransmitter. The role of NO in the generation of epilepsy is highly contradictory, since there is evidence of its anticonvulsive, as well as proconvulsive properties. Therefore, we will discuss in this review the involvement of NO-mediated signaling pathways in the mechanisms of epileptogenesis, taking into account the findings revealed in experimental studies on animal models of epilepsy. [Acknowledgments. This study was supported by Ministry of Education and Science of Serbia, Grant No. 175032

  20. Behavioral and pharmacokinetic interactions between monoamine oxidase inhibitors and the hallucinogen 5-methoxy-N,N-dimethyltryptamine.

    Science.gov (United States)

    Halberstadt, Adam L

    2016-04-01

    Monoamine oxidase inhibitors (MAOIs) are often ingested together with tryptamine hallucinogens, but relatively little is known about the consequences of their combined use. We have shown previously that monoamine oxidase-A (MAO-A) inhibitors alter the locomotor profile of the hallucinogen 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) in rats, and enhance its interaction with 5-HT2A receptors. The goal of the present studies was to investigate the mechanism for the interaction between 5-MeO-DMT and MAOIs, and to determine whether other behavioral responses to 5-MeO-DMT are similarly affected. Hallucinogens disrupt prepulse inhibition (PPI) in rats, an effect typically mediated by 5-HT2A activation. 5-MeO-DMT also disrupts PPI but the effect is primarily attributable to 5-HT1A activation. The present studies examined whether an MAOI can alter the respective contributions of 5-HT1A and 5-HT2A receptors to the effects of 5-MeO-DMT on PPI. A series of interaction studies using the 5-HT1A antagonist WAY-100,635 and the 5-HT2A antagonist MDL 11,939 were performed to assess the respective contributions of these receptors to the behavioral effects of 5-MeO-DMT in rats pretreated with an MAOI. The effects of MAO-A inhibition on the pharmacokinetics of 5-MeO-DMT and its metabolism to bufotenine were assessed using liquid chromatography-electrospray ionization-selective reaction monitoring-tandem mass spectrometry (LC-ESI-SRM-MS/MS). 5-MeO-DMT (1mg/kg) had no effect on PPI when tested 45-min post-injection but disrupted PPI in animals pretreated with the MAO-A inhibitor clorgyline or the MAO-A/B inhibitor pargyline. The combined effect of 5-MeO-DMT and pargyline on PPI was antagonized by pretreatment with either WAY-100,635 or MDL 11,939. Inhibition of MAO-A increased the level of 5-MeO-DMT in plasma and whole brain, but had no effect on the conversion of 5-MeO-DMT to bufotenine, which was found to be negligible. The present results confirm that 5-MeO-DMT can disrupt PPI by

  1. Behavioral and Pharmacokinetic Interactions Between Monoamine Oxidase Inhibitors and the Hallucinogen 5-Methoxy-N,N-dimethyltryptamine

    Science.gov (United States)

    Halberstadt, Adam L.

    2016-01-01

    Monoamine oxidase inhibitors (MAOIs) are often ingested together with tryptamine hallucinogens, but relatively little is known about the consequences of their combined use. We have shown previously that monoamine oxidase-A (MAO-A) inhibitors alter the locomotor profile of the hallucinogen 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) in rats, and enhance its interaction with 5-HT2A receptors. The goal of the present studies was to investigate the mechanism for the interaction between 5-MeO-DMT and MAOIs, and to determine whether other behavioral responses to 5-MeO-DMT are similarly affected. Hallucinogens disrupt prepulse inhibition (PPI) in rats, an effect typically mediated by 5-HT2A activation. 5-MeO-DMT also disrupts PPI but the effect is primarily attributable to 5-HT1A activation. The present studies examined whether an MAOI can alter the respective contributions of 5-HT1A and 5-HT2A receptors to the effects of 5-MeO-DMT on PPI. A series of interaction studies using the 5-HT1A antagonist WAY-100635 and the 5-HT2A antagonist MDL 11,939 were performed to assess the respective contributions of these receptors to the behavioral effects of 5-MeO-DMT in rats pretreated with an MAOI. The effects of MAO-A inhibition on the pharmacokinetics of 5-MeO-DMT and its metabolism to bufotenine were assessed using liquid chromatography–electrospray ionization–selective reaction monitoring–tandem mass spectrometry (LC-ESI-SRM-MS/MS). 5-MeO-DMT (1 mg/kg) had no effect on PPI when tested 45-min post-injection but disrupted PPI in animals pretreated with the MAO-A inhibitor clorgyline or the MAO-A/B inhibitor pargyline. The combined effect of 5-MeO-DMT and pargyline on PPI was antagonized by pretreatment with either WAY-100635 or MDL 11,939. Inhibition of MAO-A increased the level of 5-MeO-DMT in plasma and whole brain, but had no effect on the conversion of 5-MeO-DMT to bufotenine, which was found to be negligible. The present results confirm that 5-MeO-DMT can disrupt PPI

  2. The role of the serotonergic system in suicidal behavior

    Directory of Open Access Journals (Sweden)

    Sadkowski M

    2013-11-01

    Full Text Available Marta Sadkowski,1,* Brittany Dennis,2–4,* Robert C Clayden,2 Wala ElSheikh,5 Sumathy Rangarajan,5 Jane DeJesus,5 Zainab Samaan3–6 1Arts and Sciences Program, 2Faculty of Health Sciences, 3Department of Clinical Epidemiology and Biostatistics, 4Population Genomics Program, McMaster University, Hamilton, ON, Canada; 5Population Health Research Institute, Hamilton, ON, Canada; 6Department of Psychiatry and Behavioral Neurosciences, McMaster University, Hamilton, ON, Canada *These authors contributed equally to this work Abstract: Serotonin is a widely investigated neurotransmitter in several psychopathologies, including suicidal behavior (SB; however, its role extends to several physiological functions involving the nervous system, as well as the gastrointestinal and cardiovascular systems. This review summarizes recent research into ten serotonergic genes related to SB. These genes – TPH1, TPH2, SLC6A4, SLC18A2, HTR1A, HTR1B, HTR2A, DDC, MAOA, and MAOB – encode proteins that are vital to serotonergic function: tryptophan hydroxylase; the serotonin transporter 5-HTT; the vesicular transporter VMAT2; the HTR1A, HTR1B, and HTR2A receptors; the L-amino acid decarboxylase; and the monoamine oxidases. This review employed a systematic search strategy and a narrative research methodology to disseminate the current literature investigating the link between SB and serotonin. Keywords: serotonin, suicide, genetic

  3. Aromatherapy and the central nerve system (CNS): therapeutic mechanism and its associated genes.

    Science.gov (United States)

    Lv, Xiao Nan; Liu, Zhu Jun; Zhang, Huan Jing; Tzeng, Chi Meng

    2013-07-01

    Molecular medical research on aromatherapy has been steadily increasing for use as an adjuvant therapy in managing psychiatric disorders and to examine its therapeutic mechanisms. Most studies, as well as clinically applied experience, have indicated that various essential oils, such as lavender, lemon and bergamot can help to relieve stress, anxiety, depression and other mood disorders. Most notably, inhalation of essential oils can communicate signals to the olfactory system and stimulate the brain to exert neurotransmitters (e.g. serotonin and dopamine) thereby further regulating mood. However, little research has been done on the molecular mechanisms underlying these effects, thus their mechanism of action remains ambiguous. Several hypotheses have been proposed regarding the therapeutic mechanism of depression. These have mainly centered on possible deficiencies in monoamines, neurotrophins, the neuroendocrine system, c-AMP, cation channels as well as neuroimmune interactions and epigenetics, however the precise mechanism or mechanisms related to depression have yet to be elucidated. In the current study, the effectiveness of aromatherapy for alleviating psychiatric disorders was examined using data collected from previously published studies and our unpublished data. A possible signaling pathway from olfactory system to the central nerve system and the associated key molecular elements of aromatherapy are also proposed.

  4. Discovery of highly selective and potent monoamine oxidase B inhibitors: Contribution of additional phenyl rings introduced into 2-aryl-1,3,4-oxadiazin-5(6H)-one.

    Science.gov (United States)

    Lee, Jungeun; Lee, Yeongcheol; Park, So Jung; Lee, Joohee; Kim, Yeong Shik; Suh, Young-Ger; Lee, Jeeyeon

    2017-03-01

    Monoamine oxidase B (MAO-B) is a flavin adenine dinucleotide (FAD)-containing enzyme that plays a major role in the oxidative deamination of biogenic amines and neurotransmitters. Inhibiting MAO-B activity is a promising approach in the treatment of neurological disorders. Here, we report a series of 2-aryl-1,3,4-oxadiazin-5(6H)-one derivatives as highly selective and potent MAO-B inhibitors. Analysis of the binding sites of hMAO-A and hMAO-B led to design of linear analogs of 2-aryl-1,3,4-oxadiazin-5(6H)-one with an additional phenyl ring. Biological evaluation of the 26 new derivatives resulted in the identification of highly potent and selective inhibitors with optimal physicochemical properties to potentially cross the blood-brain barrier (BBB). Compounds 18a, 18b, 18e and 25b potently inhibited MAO-B, with IC50 values of 4-25 nM and excellent SI over MAO-A (18a > 25000, 18b > 8333 and 18e > 4000 and 25b > 4545). Docking results suggest that an optimal linker between two aromatic rings on the 2-aryl-1,3,4-oxadiazin-5(6H)-one scaffold is a key element in the binding and inhibition of MAO-B.

  5. Melanoma tumors alter proinflammatory cytokine production and monoamine brain function, and induce depressive-like behavior in male mice.

    Science.gov (United States)

    Lebeña, Andrea; Vegas, Oscar; Gómez-Lázaro, Eneritz; Arregi, Amaia; Garmendia, Larraitz; Beitia, Garikoitz; Azpiroz, Arantza

    2014-10-01

    Depression is a commonly observed disorder among cancer patients; however, the mechanisms underlying the relationship between these disorders are not well known. We used an animal model to study the effects of tumor development on depressive-like behavior manifestation, proinflammatory cytokine expression, and central monoaminergic activity. Male OF1 mice were inoculated with B16F10 melanoma tumor cells and subjected to a 21-day behavioral evaluation comprising the novel palatable food (NPF) test and tail suspension test (TST). The mRNA expression levels of proinflammatory cytokines, interleukin (IL)-1β and IL-6, and tumor necrosis factor-alpha (TNF-α), were measured in the hypothalamus and hippocampus and the levels of IL-6 and TNF-α were measured in the blood plasma. We similarly determined the monoamine turnover in various brain areas. The tumors resulted in increasing the immobility in TST and the expression level of IL-6 in the hippocampus. These increases corresponded with a decrease in dopaminergic activity in the striatum and a decrease in serotonin turnover in the prefrontal cortex. Similarly, a high level of tumor development produced increases in the brain expression levels of IL-6 and TNF-α and plasma levels of IL-6. Our findings suggest that these alterations in inflammatory cytokines and monoaminergic system function might be responsible for the manifestation of depressive-like behaviors in tumor-bearing mice.

  6. Electrical activity of the visual cortex under conditions of change in the levels of monoamines in the brain of animals.

    Science.gov (United States)

    Borob'ev, V V; Gal'chenko, A A; Deryugina, O N

    1991-01-01

    The changes in the electrograms of the visual cortex of awake animals under the influence of light stimulation in conditions of a pharmacological effect on the monoamine (MA) systems of the brain were investigated in experiments on 8 rabbits and 12 rats. The following was found following the administration of MA precursors (5-hydroxytryptophan and d,l-dihydroxyphenylalanine): a) a decrease in the amplitude of the averaged evoked potentials in response to rhythmical light stimuli (1-20 pulses/sec); b) intensification of rapid (15-25 Hz) oscillations in the spontaneous electrical activity of the cortex, as well as attenuation and modification of the effects of the blocker of MA synthesis, a-methyl-dihydroxyphenylalanine. A potentiation of the MA precursors was observed with light stimulation in the frequency spectra of the electrocorticograms. The specific characteristics of the action of the catecholamine precursor were manifested in the same conditions in the form of an intensification of the power of the 5-7 Hz rhythms, and an attenuation of the power of the 2-3 Hz rhythms.

  7. Neurotransmitters as food supplements: the effects of GABA on brain and behavior.

    Science.gov (United States)

    Boonstra, Evert; de Kleijn, Roy; Colzato, Lorenza S; Alkemade, Anneke; Forstmann, Birte U; Nieuwenhuis, Sander

    2015-01-01

    Gamma-aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the human cortex. The food supplement version of GABA is widely available online. Although many consumers claim that they experience benefits from the use of these products, it is unclear whether these supplements confer benefits beyond a placebo effect. Currently, the mechanism of action behind these products is unknown. It has long been thought that GABA is unable to cross the blood-brain barrier (BBB), but the studies that have assessed this issue are often contradictory and range widely in their employed methods. Accordingly, future research needs to establish the effects of oral GABA administration on GABA levels in the human brain, for example using magnetic resonance spectroscopy. There is some evidence in favor of a calming effect of GABA food supplements, but most of this evidence was reported by researchers with a potential conflict of interest. We suggest that any veridical effects of GABA food supplements on brain and cognition might be exerted through BBB passage or, more indirectly, via an effect on the enteric nervous system. We conclude that the mechanism of action of GABA food supplements is far from clear, and that further work is needed to establish the behavioral effects of GABA.

  8. Soft X-ray photoemission spectroscopy of selected neurotransmitters in the gas phase

    Energy Technology Data Exchange (ETDEWEB)

    Maris, Assimo; Melandri, Sonia; Evangelisti, Luca; Caminati, Walther [Dipartimento di Chimica ' G. Ciamician' dell' Universita, Via Selmi 2, I-40126 Bologna (Italy); Giuliano, Barbara M. [Departamento de Quimica da Universidade de Coimbra, 3004-535 Coimbra (Portugal); Plekan, Oksana [Sincrotrone Trieste, in Area Science Park, I-34149 Basovizza, Trieste (Italy); Feyer, Vitaliy [Sincrotrone Trieste, in Area Science Park, I-34149 Basovizza, Trieste (Italy); Electronic Properties (PGI-6), Peter Gruenberg Institute, Forschungszentrum Juelich GmbH, Leo-Brandt-Strasse, 52428 Juelich (Germany); Richter, Robert [Sincrotrone Trieste, in Area Science Park, I-34149 Basovizza, Trieste (Italy); Coreno, Marcello [CNR-IMIP, Montelibretti, I-00016 Rome (Italy); Prince, Kevin C., E-mail: kevin.prince@elettra.trieste.it [Sincrotrone Trieste, in Area Science Park, I-34149 Basovizza, Trieste (Italy); CNR-IOM, Laboratorio TASC, I-34149 Basovizza, Trieste (Italy)

    2012-09-15

    Highlights: Black-Right-Pointing-Pointer Neurotransmitter molecules. Black-Right-Pointing-Pointer Photoelectron spectroscopy. Black-Right-Pointing-Pointer Electronic structure. Black-Right-Pointing-Pointer Weak hydrogen bonding. -- Abstract: The valence molecular orbitals and core levels of tyramine, tryptamine and tryptophol in the gas phase have been studied using X-ray photoelectron spectroscopy (XPS) and theoretical methods. The energies of the outer valence region spectrum are found to be in agreement with previously reported He I spectra, while new data on the inner valence molecular orbitals are reported. The structures in the carbon, nitrogen and oxygen core level spectra of these molecules have been identified and assigned. These compounds are characterised by conformers with hydrogen bonding in which the {pi} systems of the phenol and indole groups act as hydrogen acceptors, but a spectroscopic signature of this hydrogen bond was not observed. This is in contrast with our previous spectra of amino acids, where conformers with specific hydrogen bonding showed strong effects in core level spectra. We attribute the difference to the weaker strength of the {pi}-hydrogen bonding.

  9. Expression of Caenorhabditis elegans neurotransmitter receptors and ion channels in Xenopus oocytes

    Science.gov (United States)

    Martínez-Torres, Ataúlfo; Miledi, Ricardo

    2006-01-01

    Injection of Caenorhabditis elegans polyA RNA into Xenopus laevis oocytes led to the expression of neurotransmitter receptors that generated some unique responses, including ionotropic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors as well as receptors that coupled to G proteins, such as those to octopamine, norepinephrine, and angiotensin, which activated the oocyte’s own phosphatidylinositol system and calcium-gated chloride channels. The oocytes also expressed chloride-conducting glutamate receptors, muscarinic acetylcholine receptors, and voltage-operated calcium channels. Unexpectedly, serotonin (5-hydroxytryptamine), dopamine, GABA, and kainate did not generate ionic currents, suggesting that the corresponding receptors were not expressed or were not functional in the oocytes. The use of X. laevis oocytes for expressing worm RNA demonstrates that there are many molecular components whose role remains to be clarified in the nematode. Among them are the nature of the endogenous agonists for the octopamine and angiotensin receptors and the subunits that compose the ionotropic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors and the norepinephrine receptors that couple to the phosphoinositide cascade. PMID:16549772

  10. Sex hormones affect neurotransmitters and shape the adult female brain during hormonal transition periods

    Directory of Open Access Journals (Sweden)

    Claudia eBarth

    2015-02-01

    Full Text Available Sex hormones have been implicated in neurite outgrowth, synaptogenesis, dendritic branching, myelination and other important mechanisms of neural plasticity. Here we review the evidence from animal experiments and human studies reporting interactions between sex hormones and the dominant neurotransmitters, such as serotonin, dopamine, GABA and glutamate. We provide an overview of accumulating data during physiological and pathological conditions and discuss currently conceptualized theories on how sex hormones potentially trigger neuroplasticity changes through these four neurochemical systems. Many brain regions have been demonstrated to express high densities for estrogen- and progesterone receptors, such as the amygdala, the hypothalamus, and the hippocampus. As the hippocampus is of particular relevance in the context of mediating structural plasticity in the adult brain, we put particular emphasis on what evidence could be gathered thus far that links differences in behavior, neurochemical patterns and hippocampal structure to a changing hormonal environment. Finally, we discuss how physiologically occurring hormonal transition periods in humans can be used to model how changes in sex hormones influence functional connectivity, neurotransmission and brain structure in vivo.

  11. Determining Ca2+-sensor binding time and its variability in evoked neurotransmitter release.

    Science.gov (United States)

    Yoon, Ava Chomee; Kathpalia, Vinnie; D'Silva, Sahana; Cimenser, Aylin; Hua, Shao-Ying

    2008-02-15

    The speed and reliability of neuronal reactions are important factors for proper functioning of the nervous system. To understand how organisms use protein molecules to carry out very fast biological actions, we quantified single-molecule reaction time and its variability in synaptic transmission. From the synaptic delay of crayfish neuromuscular synapses the time for a few Ca(2+) ions to bind with their sensors in evoked neurotransmitter release was estimated. In standard crayfish saline at room temperature, the average Ca(2+) binding time was 0.12 ms for the first evoked quanta. At elevated extracellular Ca(2+) concentrations this binding time reached a limit due to saturation of Ca(2+) influx. Analysis of the synaptic delay variance at various Ca(2+) concentrations revealed that the variability of the Ca(2+)-sensor binding time is the major source of the temporal variability of synaptic transmission, and that the Ca(2+)-independent molecular reactions after Ca(2+) influx were less stochastic. The results provide insights into how organisms maximize reaction speed and reliability.

  12. Proton magnetic resonance spectroscopy detection of neurotransmitters in dorsomedial medulla correlate with spontaneous baroreceptor reflex function.

    Science.gov (United States)

    Garcia-Espinosa, Maria A; Shaltout, Hossam A; Olson, John; Westwood, Brian M; Robbins, Mike E; Link, Kerry; Diz, Debra I

    2010-02-01

    Control of heart rate variability via modulation of sympathovagal balance is a key function of nucleus tractus solitarii and the dorsal motor nucleus of the vagus localized in the dorsomedial medulla oblongata. Normal blood pressure regulation involves precise balance of glutamate (Glu)-glutamine-gamma-aminobutyric acid transmitter systems, and angiotensin II modulates these transmitters to produce tonic suppression of reflex function. It is not known, however, whether other brain transmitters/metabolites are indicators of baroreflex function. This study establishes the concept that comprehensive baseline transmitter/metabolite profiles obtained using in vivo (1)H magnetic resonance spectroscopy in rats with well-characterized differences in resting blood pressure and baroreflex function can be used as indices of autonomic balance or baroreflex sensitivity. Transgenic rats with over-expression of renin [m(Ren2)27] or under-expression of glial-angiotensinogen (ASrAogen) were compared with Sprague-Dawley rats. Glu concentration in the dorsal medulla is significantly higher in ASrAogen rats compared with either Sprague-Dawley or (mRen2)27 rats. Glu levels and the ratio of Glu:glutamine correlated positively with indices of higher vagal tone consistent with the importance of these neurotransmitters in baroreflex function. Interestingly, the levels of choline-containing metabolites showed a significant positive correlation with spontaneous baroreflex sensitivity and a negative correlation with sympathetic tone. Thus, we demonstrate the concept that noninvasive assessment of neurochemical biomarkers may be used as an index of baroreflex sensitivity.

  13. Microtransplantation of membranes from cultured cells to Xenopus oocytes: A method to study neurotransmitter receptors embedded in native lipids

    Science.gov (United States)

    Palma, Eleonora; Trettel, Flavia; Fucile, Sergio; Renzi, Massimiliano; Miledi, Ricardo; Eusebi, Fabrizio

    2003-01-01

    The Xenopus oocyte is used as a convenient cell expression system to study the structure and function of heterogenic transmitter receptors and ion channels. Recently, we introduced a method to microtransplant already assembled neurotransmitter receptors from the human brain to the plasma membrane of Xenopus oocytes. The same approach was used here to transplant neurotransmitter receptors expressed from cultured cells to the oocytes. Membrane vesicles prepared from a human embryonic kidney cell line (HEK293) stably expressing the rat glutamate receptor 1 were injected into oocytes, and, within a few hours, the oocyte plasma membrane acquired α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-type glutamate receptors, which had the same properties as those expressed in the original HEK cells. Analogously, oocytes injected with membranes prepared from rat pituitary GH(4)C1 cells, stably expressing homomeric human neuronal α7 nicotinic acetylcholine receptors (α7-AcChoRs), incorporated in their plasma membrane AcChoRs that behaved as those expressed in GH(4)C1 cells. Similar results were obtained with HEK cells stably expressing heteromeric human neuronal α4β2-AcChoRs. All this makes the Xenopus oocyte a powerful tool for detailed investigations of receptors and other proteins expressed in the membrane of cultured cells. PMID:12595576

  14. Binding Mode Selection Determines the Action of Ecstasy Homologs at Monoamine Transporters.

    Science.gov (United States)

    Sandtner, Walter; Stockner, Thomas; Hasenhuetl, Peter S; Partilla, John S; Seddik, Amir; Zhang, Yuan-Wei; Cao, Jianjing; Holy, Marion; Steinkellner, Thomas; Rudnick, Gary; Baumann, Michael H; Ecker, Gerhard F; Newman, Amy Hauck; Sitte, Harald H

    2016-01-01

    Determining the structural elements that define substrates and inhibitors at the monoamine transporters is critical to elucidating the mechanisms underlying these disparate functions. In this study, we addressed this question directly by generating a series of N-substituted 3,4-methylenedioxyamphetamine analogs that differ only in the number of methyl substituents on the terminal amine group. Starting with 3,4-methylenedioxy-N-methylamphetamine, 3,4-methylenedioxy-N,N-dimethylamphetamine (MDDMA) and 3,4-methylenedioxy-N,N,N-trimethylamphetamine (MDTMA) were prepared. We evaluated the functional activities of the compounds at all three monoamine transporters in native brain tissue and cells expressing the transporters. In addition, we used ligand docking to generate models of the respective protein-ligand complexes, which allowed us to relate the experimental findings to available structural information. Our results suggest that the 3,4-methylenedioxyamphetamine analogs bind at the monoamine transporter orthosteric binding site by adopting one of two mutually exclusive binding modes. 3,4-methylenedioxyamphetamine and 3,4-methylenedioxy-N-methylamphetamine adopt a high-affinity binding mode consistent with a transportable substrate, whereas MDDMA and MDTMA adopt a low-affinity binding mode consistent with an inhibitor, in which the ligand orientation is inverted. Importantly, MDDMA can alternate between both binding modes, whereas MDTMA exclusively binds to the low-affinity mode. Our experimental results are consistent with the idea that the initial orientation of bound ligands is critical for subsequent interactions that lead to transporter conformational changes and substrate translocation.

  15. The evolution of dopamine systems in chordates

    Directory of Open Access Journals (Sweden)

    Kei eYamamoto

    2011-03-01

    Full Text Available Dopamine (DA neurotransmission in the central nervous system (CNS is found throughout chordates, and its emergence predates the divergence of chordates. Many of the molecular components of DA systems, such as biosynthetic enzymes, transporters and receptors, are shared with those of other monoamine systems, suggesting the common origin of these systems. In the mammalian CNS, the DA neurotransmitter systems are diversified and serve for visual and olfactory perception, sensory-motor programming, motivation, memory, emotion, and endocrine regulations. Some of the functions are conserved among different vertebrate groups, while others are not, and this is reflected in the anatomical aspects of DA systems in the forebrain and midbrain. Recent findings concerning a second tyrosine hydroxylase gene (TH2 revealed new populations of DA synthesizing cells, as evidenced in the periventricular hypothalamic zones of teleost fish. It is likely that the ancestor of vertebrates possessed TH2 DA-synthesizing cells, and the TH2 gene has been lost secondarily in placental mammals. All the vertebrates possess DA cells in the olfactory bulb, retina and in the diencephalon. Midbrain DA cells are abundant in amniotes while absent in some groups, e.g. teleosts. Studies of protochordate DA cells suggest that the diencephalic DA cells were present before the divergence of the chordate lineage. In contrast, the midbrain cell populations have probably emerged in the vertebrate lineage following the development of the midbrain-hindbrain boundary. The functional flexibility of the DA systems, and the evolvability provided by duplication of the corresponding genes permitted a large diversification of these systems. These features were instrumental in the adaptation of brain functions to the very variable way of life of vertebrates.

  16. The evolution of dopamine systems in chordates.

    Science.gov (United States)

    Yamamoto, Kei; Vernier, Philippe

    2011-01-01

    Dopamine (DA) neurotransmission in the central nervous system (CNS) is found throughout chordates, and its emergence predates the divergence of chordates. Many of the molecular components of DA systems, such as biosynthetic enzymes, transporters, and receptors, are shared with those of other monoamine systems, suggesting the common origin of these systems. In the mammalian CNS, the DA neurotransmitter systems are diversified and serve for visual and olfactory perception, sensory-motor programming, motivation, memory, emotion, and endocrine regulations. Some of the functions are conserved among different vertebrate groups, while others are not, and this is reflected in the anatomical aspects of DA systems in the forebrain and midbrain. Recent findings concerning a second tyrosine hydroxylase gene (TH2) revealed new populations of DA-synthesizing cells, as evidenced in the periventricular hypothalamic zones of teleost fish. It is likely that the ancestor of vertebrates possessed TH2 DA-synthesizing cells, and the TH2 gene has been lost secondarily in placental mammals. All the vertebrates possess DA cells in the olfactory bulb, retina, and in the diencephalon. Midbrain DA cells are abundant in amniotes while absent in some groups, e.g., teleosts. Studies of protochordate DA cells suggest that the diencephalic DA cells were present before the divergence of the chordate lineage. In contrast, the midbrain cell populations have probably emerged in the vertebrate lineage following the development of the midbrain-hindbrain boundary. The functional flexibility of the DA systems, and the evolvability provided by duplication of the corresponding genes permitted a large diversification of these systems. These features were instrumental in the adaptation of brain functions to the very variable way of life of vertebrates.

  17. Monoamines and sexual function in rats bred for increased catatonic reactivity.

    Science.gov (United States)

    Klochkov, D V; Alekhina, T A; Kuznetsova, E G; Barykina, N N

    2009-07-01

    Body weight, ovary and uterus weight, the nature of estral cycles, and hypothalamus dopamine and noradrenaline levels and plasma testosterone levels were studied in female GC rats, bred for increased catatonic reactivity, at different stages of the estral cycle (estrus, proestrus). The outbred Wistar strain served as controls. On the background of decreased body weight, GC females showed impairments to the morphological cyclical changes in the ovaries and uterus, with a reduction in ovary weight in diestrus (p rats showed higher levels of these monoamines in estrus and lower levels in diestrus. Plasma testosterone levels in female GC rats were higher in diestrus than in estrus and in Wistar rats.

  18. Relationship between pancreatic vesicular monoamine transporter 2 (VMAT2) and insulin expression in human pancreas

    OpenAIRE

    Saisho, Yoshifumi; Harris, Paul E.; Butler, Alexandra E.; Galasso, Ryan; GURLO, TATYANA; Rizza, Robert A.; Butler, Peter C.

    2008-01-01

    Vesicular monoamine transporter 2 (VMAT2) is expressed in pancreatic beta cells and has recently been proposed as a target for measurement of beta cell mass in vivo. We questioned, (1) What proportion of beta cells express VMAT2? (2) Is VMAT2 expressed by other pancreatic endocrine or non-endocrine cells? (3) Is the relationship between VMAT2 and insulin expression disturbed in type 1 (T1DM) or type 2 diabetes (T2DM)? Human pancreas (7 non-diabetics, 5 T2DM, 10 T1DM) was immunostained for ins...

  19. Chromone-2- and -3-carboxylic acids inhibit differently monoamine oxidases A and B.

    Science.gov (United States)

    Alcaro, Stefano; Gaspar, Alexandra; Ortuso, Francesco; Milhazes, Nuno; Orallo, Francisco; Uriarte, Eugenio; Yáñez, Matilde; Borges, Fernanda

    2010-05-01

    Chromone carboxylic acids were evaluated as human monoamine oxidase A and B (hMAO-A and hMAO-B) inhibitors. The biological data indicated that only chromone-3-carboxylic acid is a potent hMAO-B inhibitor, with a high degree of selectivity for hMAO-B compared to hMAO-A. Conversely the chromone-2-carboxylic acid resulted almost inactive against both MAO isoforms. Docking experiments were performed to elucidate the reasons of the different MAO IC(50) data and to explain the absence of activity versus selectivity, respectively. 2010 Elsevier Ltd. All rights reserved.

  20. Monoamine oxidase B inhibitors from the fruits of Opuntia ficus-indica var. saboten.

    Science.gov (United States)

    Han, Y N; Choo, Y; Lee, Y C; Moon, Y I; Kim, S D; Choi, J W

    2001-02-01

    Three varieties of methyl citrate and 1-methyl malate were isolated from the fruits of Opuntia ficus-indica var. saboten Makino through in vitro bioassay-guided isolation for the inhibition on monoamine oxidase(MAO). The IC50 values for MAO-B of 1-monomethyl citrate, 1,3-dimethyl citrate, trimethyl citrate and 1-methyl malate were 0.19, 0.23, 0.61 and 0.25 mM, respectively. However, on MAO-A, their inhibitions showed only marginal activity.

  1. In vitro effect of octyl - methoxycinnamate (OMC) on the release of Gn-RH and amino acid neurotransmitters by hypothalamus of adult rats.

    Science.gov (United States)

    Carbone, S; Szwarcfarb, B; Reynoso, R; Ponzo, O J; Cardoso, N; Ale, E; Moguilevsky, J A; Scacchi, P

    2010-05-01

    OMC (octyl-methoxycinnamate), an endocrine disruptor having estrogenic activity, is used in sunscreen creams as UV filter. We studied its "in vitro" effects on the hypothalamic release of Gn-RH as well as on the amino acid neurotransmitter system. OMC significantly decreased Gn-RH release in normal male and female rats as well as in castrated rats with substitutive therapy. No effects were observed in castrated rats without substitutive therapy. In males OMC increases the release of GABA, decreasing the production of glutamate (GLU) while in the female decreases the excitatory amino acid aspartate (ASP) and GLU without modifications in the hypothalamic GABA release. These results suggest that OMC acting as endocrine disruptor could alter the sex hormone-neurotransmitter-Gn-RH axis relationships in adult rats.

  2. In utero exposure to a low concentration of diesel exhaust affects spontaneous locomotor activity and monoaminergic system in male mice

    Directory of Open Access Journals (Sweden)

    Odagiri Takashi

    2010-03-01

    Full Text Available Abstract Background Epidemiological studies have suggested that suspended particulate matter (SPM causes detrimental health effects such as respiratory and cardiovascular diseases, and that diesel exhaust particles from automobiles is a major contributor to SPM. It has been reported that neonatal and adult exposure to diesel exhaust damages the central nervous system (CNS and induces behavioral alteration. Recently, we have focused on the effects of prenatal exposure to diesel exhaust on the CNS. In this study, we examined the effects of prenatal exposure to low concentration of diesel exhaust on behaviour and the monoaminergic neuron system. Spontaneous locomotor activity (SLA and monoamine levels in the CNS were assessed. Methods Mice were exposed prenatally to a low concentration of diesel exhaust (171 μg DEP/m3 for 8 hours/day on gestational days 2-16. SLA was assessed for 3 days in 4-week-old mice by analysis of the release of temperature-associated infrared rays. At 5 weeks of age, the mice were sacrificed and the brains were used for analysis by high-performance liquid chromatography (HPLC. Results and Discussion Mice exposed to a low concentration of diesel exhaust showed decreased SLA in the first 60 minutes of exposure. Over the entire test period, the mice exposed prenatally to diesel exhaust showed decreased daily SLA compared to that in control mice, and the SLA in each 3 hour period was decreased when the lights were turned on. Neurotransmitter levels, including dopamine and noradrenaline, were increased in the prefrontal cortex (PFC in the exposure group compared to the control group. The metabolites of dopamine and noradrenaline also increased in the PFC. Neurotransmitter turnover, an index of neuronal activity, of dopamine and noradrenaline was decreased in various regions of the CNS, including the striatum, in the exposure group. The serum corticosterone level was not different between groups. The data suggest that decreased

  3. Convergent Pathways for Steroid Hormone-and Neurotransmitter-Induced Rat Sexual Behavior

    Science.gov (United States)

    Mani, S. K.; Allen, J. M. C.; Clark, J. H.; Blaustein, J. D.; O'Malley, B. W.

    1994-08-01

    Estrogen and progesterone modulate gene expression in rodents by activation of intracellular receptors in the hypothalamus, which regulate neuronal networks that control female sexual behavior. However, the neurotransmitter dopamine has been shown to activate certain steroid receptors in a ligand-independent manner. A dopamine receptor stimulant and a D_1 receptor agonist, but not a D_2 receptor agonist, mimicked the effects of progesterone in facilitating sexual behavior in female rats. The facilitatory effect of the neurotransmitter was blocked by progesterone receptor antagonists, a D_1 receptor antagonist, or antisense oligonucleotides to the progesterone receptor. The results suggest that in rodents neurotransmitters may regulate in vivo gene expression and behavior by means of cross-talk with steroid receptors in the brain.

  4. Growth cone neurotransmitter receptor activation modulates electric field-guided nerve growth.

    Science.gov (United States)

    Erskine, L; McCaig, C D

    1995-10-01

    We have studied the interactions between two nerve guidance cues, which alone induce substantial growth cone turning: endogenous neurotransmitters and small dc electric fields. d-tubocurarine, a nicotinic AChR (acetylcholine receptor) antagonist, inhibited field-induced cathodal orientation of cultured neurites, whereas atropine, a muscarinic AChR blocker, and suramin, a P2-purinoceptor antagonist, markedly enhanced the guidance properties of the applied field. These experiments implicate the activation of growth cone nicotinic AChRs by self-released acetylcholine in the mechanism underpinning electric field-induced neurite orientation and raise the possibility that growth cones release neurotransmitter prior to target interaction in order to assist their own pathfinding. Additionally, they provide the first evidence that coactivation of several neurotransmitter receptors may interact to regulate directed nerve growth. Such interaction in vivo, where guidance signals coexist, would add further levels of control to neurite guidance.

  5. Differential stimulation of the retina with subretinally injected exogenous neurotransmitter: A biomimetic alternative to electrical stimulation

    Science.gov (United States)

    Rountree, Corey M.; Inayat, Samsoon; Troy, John B.; Saggere, Laxman

    2016-12-01

    Subretinal stimulation of the retina with neurotransmitters, the normal means of conveying visual information, is a potentially better alternative to electrical stimulation widely used in current retinal prostheses for treating blindness from photoreceptor degenerative diseases. Yet, no subretinal electrical or chemical stimulation study has stimulated the OFF and ON pathways differentially through inner retinal activation. Here, we demonstrate the feasibility of differentially stimulating retinal ganglion cells (RGCs) through the inner nuclear layer of the retina with glutamate, a primary neurotransmitter chemical, in a biomimetic way. We show that controlled pulsatile delivery of glutamate into the subsurface of explanted wild-type rat retinas elicits highly localized simultaneous inhibitory and excitatory spike rate responses in OFF and ON RGCs. We also present the spatiotemporal characteristics of RGC responses to subretinally injected glutamate and the therapeutic stimulation parameters. Our findings could pave the way for future development of a neurotransmitter-based subretinal prosthesis offering more naturalistic vision and better visual acuity than electrical prostheses.

  6. Neurotransmitter Specific, Cellular-Resolution Functional Brain Mapping Using Receptor Coated Nanoparticles: Assessment of the Possibility.

    Directory of Open Access Journals (Sweden)

    Ebrahim Forati

    Full Text Available Receptor coated resonant nanoparticles and quantum dots are proposed to provide a cellular-level resolution image of neural activities inside the brain. The functionalized nanoparticles and quantum dots in this approach will selectively bind to different neurotransmitters in the extra-synaptic regions of neurons. This allows us to detect neural activities in real time by monitoring the nanoparticles and quantum dots optically. Gold nanoparticles (GNPs with two different geometries (sphere and rod and quantum dots (QDs with different sizes were studied along with three different neurotransmitters: dopamine, gamma-Aminobutyric acid (GABA, and glycine. The absorption/emission spectra of GNPs and QDs before and after binding of neurotransmitters and their corresponding receptors are reported. The results using QDs and nanorods with diameter 25nm and aspect rations larger than three were promising for the development of the proposed functional brain mapping approach.

  7. Neurotransmitter Specific, Cellular-Resolution Functional Brain Mapping Using Receptor Coated Nanoparticles: Assessment of the Possibility

    Science.gov (United States)

    Forati, Ebrahim; Sabouni, Abas; Ray, Supriyo; Head, Brian; Schoen, Christian; Sievenpiper, Dan

    2015-01-01

    Receptor coated resonant nanoparticles and quantum dots are proposed to provide a cellular-level resolution image of neural activities inside the brain. The functionalized nanoparticles and quantum dots in this approach will selectively bind to different neurotransmitters in the extra-synaptic regions of neurons. This allows us to detect neural activities in real time by monitoring the nanoparticles and quantum dots optically. Gold nanoparticles (GNPs) with two different geometries (sphere and rod) and quantum dots (QDs) with different sizes were studied along with three different neurotransmitters: dopamine, gamma-Aminobutyric acid (GABA), and glycine. The absorption/emission spectra of GNPs and QDs before and after binding of neurotransmitters and their corresponding receptors are reported. The results using QDs and nanorods with diameter 25nm and aspect rations larger than three were promising for the development of the proposed functional brain mapping approach. PMID:26717196

  8. The dose-dependent toxicological effects and potential perturbation on the neurotransmitter secretion in brain following intranasal instillation of copper nanoparticles.

    Science.gov (United States)

    Zhang, Lili; Bai, Ru; Liu, Ying; Meng, Li; Li, Bai; Wang, Liming; Xu, Ligeng; Le Guyader, Laurent; Chen, Chunying

    2012-08-01

    Increasing production and application of metallic nanomaterials are likely to result in the release of these particles into the environment. These released nanoparticles may enter into the lungs and the central nervous system (CNS) directly through inhalation, which therefore poses a potential risk to human health. Herein, we focus on the systemic toxicity and potential influence on the neurotransmitter secretion of intranasally instilled copper nanoparticles (23.5 nm) at three different doses. Copper nanoparticle-exposed mice exhibit pathological lesions at different degrees in certain tissues and especially in lung tissue as revealed by histopathology and transmission electron microscopy (TEM) observations. Inductively-coupled plasma mass spectrometry (ICP-MS) results show that the liver, lung and olfactory bulb are the main tissues in which the copper concentrations increased significantly after exposure to a higher level of Cu nanoparticles (40 mg/kg of body weight). The secretion levels of various neurotransmitters changed as well in some brain regions, especially in the olfactory bulb. Our results indicate that the intranasally instilled copper nanoparticles not only cause the lesions where the copper accumulates, but also affect the neurotransmitter levels in the brain.

  9. Elevated levels of the vesicular monoamine transporter and a novel repetitive behavior in the Drosophila model of fragile X syndrome.

    Directory of Open Access Journals (Sweden)

    John M Tauber

    Full Text Available Fragile X Syndrome (FXS is characterized by mental impairment and autism in humans, and it often features hyperactivity and repetitive behaviors. The mechanisms for the disease, however, remain poorly understood. Here we report that the dfmr1 mutant in the Drosophila model of FXS grooms excessively, which may be regulated differentially by two signaling pathways. Blocking metabotropic glutamate receptor signaling enhances grooming in dfmr1 mutant flies, whereas blocking the vesicular monoamine transporter (VMAT suppresses excessive grooming. dfmr1 mutant flies also exhibit elevated levels of VMAT mRNA and protein. These results suggest that enhanced monoamine signaling correlates with repetitive behaviors and hyperactivity associated with FXS.

  10. Wide-range, picoampere-sensitivity multichannel VLSI potentiostat for neurotransmitter sensing.

    Science.gov (United States)

    Murari, Kartikeya; Thakor, Nitish; Stanacevic, Milutin; Cauwenberghs, Gert

    2004-01-01

    Neurotransmitter sensing is critical in studying nervous pathways and neurological disorders. A 16-channel current-measuring VLSI potentiostat with multiple ranges from picoamperes to microamperes is presented for electrochemical detection of electroactive neurotransmitters like dopamine, nitric oxide etc. The analog-to-digital converter design employs a current-mode, first-order single-bit delta-sigma modulator architecture with a two-stage, digitally reconfigurable oversampling ratio for ranging the conversion scale. An integrated prototype is fabricated in CMOS technology, and experimentally characterized. Real-time multi-channel acquisition of dopamine concentration in vitro is performed with a microfabricated sensor array.

  11. Astrocytic control of biosynthesis and turnover of the neurotransmitters glutamate and GABA

    DEFF Research Database (Denmark)

    Schousboe, Arne; Bak, Lasse Kristoffer; Waagepetersen, Helle S

    2013-01-01

    Glutamate and GABA are the quantitatively major neurotransmitters in the brain mediating excitatory and inhibitory signaling, respectively. These amino acids are metabolically interrelated and at the same time they are tightly coupled to the intermediary metabolism including energy homeostasis....... Astrocytes play a pivotal role in the maintenance of the neurotransmitter pools of glutamate and GABA since only these cells express pyruvate carboxylase, the enzyme required for de novo synthesis of the two amino acids. Such de novo synthesis is obligatory to compensate for catabolism of glutamate and GABA...

  12. Transition metal ion FRET uncovers K(+) regulation of a neurotransmitter/sodium symporter

    DEFF Research Database (Denmark)

    Billesbølle, Christian B; Mortensen, Jonas S; Sohail, Azmat

    2016-01-01

    Neurotransmitter/sodium symporters (NSSs) are responsible for Na(+)-dependent reuptake of neurotransmitters and represent key targets for antidepressants and psychostimulants. LeuT, a prokaryotic NSS protein, constitutes a primary structural model for these transporters. Here we show that K(+) in......(+)-effect. The K(+)-effect depended on an intact Na1 site and mutating the Na2 site potentiated K(+) binding by facilitating transition to the inward-facing state. The data reveal an unrecognized ability of K(+) to regulate the LeuT transport cycle....

  13. Long-lasting effects of feline amygdala kindling on monoamines, seizures and sleep.

    Science.gov (United States)

    Shouse, M N; Staba, R J; Saquib, S F; Farber, P R

    2001-02-16

    This report describes the relationship between monoamines, sleep and seizures before and 1-month after amygdala kindling in young cats (kindling (n=2); 5-min recording epochs were temporally adjusted to correspond to dialysate samples and differentiated according to dominant sleep or waking state (lasting > or =80% of 5-min epoch) and degree of spontaneous seizure activity (number and duration of focal versus generalized spikes and spike trains and behavioral seizure correlates). Post-kindling records in each cat were divided into two groups (n=1 record each) based on higher or lower spontaneous EEG and behavioral seizure activity and compared to pre-kindling records. We found: (1) before and after kindling, NE and 5-HT but not DA concentrations were significantly lower in sleep than waking at both sites; (2) after kindling, each cat showed cyclic patterns, as follows: (a) higher NE, 5-HT and DA concentrations accompanied increased seizure activity with delayed sleep onset latency and increased sleep fragmentation (reduced sleep state percentages, number of epochs and/or epoch duration) in one recording versus (b) lower monoaminergic concentrations accompanied reduced seizure activity, rapid sleep onset and reduced sleep disruption in the other recording. The alternating, post-kindling pattern suggested "rebound" effects which could explain some controversies in the literature about chronic effects of kindling on monoamines and sleep-waking state patterns.

  14. Monoamine oxidase B layer-by-layer film fabrication and characterization toward dopamine detection

    Energy Technology Data Exchange (ETDEWEB)

    Miyazaki, Celina Massumi; Pereira, Tamyris Paschoal [Universidade Federal de São Carlos, UFSCar, CCTS, Sorocaba, São Paulo (Brazil); Mascagni, Daniela Branco Tavares [Universidade Estadual de São Paulo — UNESP, Sorocaba, São Paulo (Brazil); Leite de Moraes, Marli [Universidade Federal de São Paulo, Unifesp, São José dos Campos, São Paulo (Brazil); Ferreira, Marystela, E-mail: marystela@ufscar.br [Universidade Federal de São Carlos, UFSCar, CCTS, Sorocaba, São Paulo (Brazil)

    2016-01-01

    In this work nanostructured film composites of the monoamine oxidase B (MAO-B) enzyme, free or encapsulated in liposomes, were fabricated by the layer-by-layer (LbL) self-assembly technique, employing polyethylene imine (PEI) as polycation. Initially, the MAO-B enzyme was incorporated into liposomes in order to preserve its enzymatic structure ensuring their activity and catalytic stability. The LbL film growth was monitored by surface plasmon resonance (SPR) by gold resonance angle shift analysis after each bilayer deposition. Subsequently, the films were applied as amperometric biosensors for dopamine detection using Prussian Blue (PB) as the electron mediator. The biosensor fabricated by MAO-B incorporated into liposomes composed of DPPG:POPG in the ratio (1:4) (w/w) showed the best performance with a sensitivity of 0.86 (μA cm{sup −2})/(mmol L{sup −1}) and a detection limit of 0.33 mmol L{sup −1}. - Highlights: • Monoamine oxidase B incorporation in liposomes was proposed to preserve the enzyme. • Layer-by-layer films composed of MAO-B (free and in liposomes) were fabricated. • Amperometric response using ITO/Prussian Blue covered with the MAO-B films was studied. • Sensitivity, limit of detection and apparent Michaelis–Menten constant were compared.

  15. Parasite manipulation of brain monoamines in California killifish (Fundulus parvipinnis) by the trematode Euhaplorchis californiensis

    Science.gov (United States)

    Shaw, J.C.; Korzan, W.J.; Carpenter, R.E.; Kuris, A.M.; Lafferty, K.D.; Summers, C.H.; Overli, O.

    2009-01-01

    California killifish (Fundulus parvipinnis) infected with the brain-encysting trematode Euhaplorchis californiensis display conspicuous swimming behaviours rendering them more susceptible to predation by avian final hosts. Heavily infected killifish grow and reproduce normally, despite having thousands of cysts inside their braincases. This suggests that E. californiensis affects only specific locomotory behaviours. We hypothesised that changes in the serotonin and dopamine metabolism, essential for controlling locomotion and arousal may underlie this behaviour modification. We employed micropunch dissection and HPLC to analyse monoamine and monoamine metabolite concentrations in the brain regions of uninfected and experimentally infected fish. The parasites exerted density-dependent changes in monoaminergic activity distinct from those exhibited by fish subjected to stress. Specifically, E. californiensis inhibited a normally occurring, stress-induced elevation of serotonergic metabolism in the raphae nuclei. This effect was particularly evident in the experimentally infected fish, whose low-density infections were concentrated on the brainstem. Furthermore, high E. californiensis density was associated with increased dopaminergic activity in the hypothalamus and decreased serotonergic activity in the hippocampus. In conclusion, the altered monoaminergic metabolism may explain behavioural differences leading to increased predation of the infected killifish by their final host predators. ?? 2008 The Royal Society.

  16. Potential of Natural Products of Herbal Origin as Monoamine Oxidase Inhibitors.

    Science.gov (United States)

    Orhan, Ilkay Erdogan

    2016-01-01

    Monoamine oxidase (MAO, E.C. 1.4.3.4) is a flavin-adenine type of enzyme with two isoforms referred to MAO-A and MAO-B that function for oxidation of monoamines. While MAO-A inhibitors are effective as antidepressant and anxiolytic drugs (e.g. chlorgyline, moclobemide, and lazabemide), inhibitors of MAO-B (e.g. Ldeprenyl, pargyline, and rasagiline) are used against neurodegenerative diseases such as Parkinson's and Alzheimer's diseases. Considering the need for novel MAO inhibitors due to side effects of the current ones, natural products have become attractive targets for researchers. Up till now, many studies revealed strong MAO inhibitory activity of flavonoid, xanthone, alkaloid, and coumarin derivatives from herbal sources, which also become good models for the synthetic MAO inhibitors. For this purpose, the present review focuses on examples of in vitro and in vivo MAO-inhibiting natural compounds of plant origin from a wide variety of chemical classes isolated mainly between 2000 - 2015.

  17. Functional localization of neurotransmitter receptors and synaptic inputs to mature neurons of the medial superior olive.

    Science.gov (United States)

    Couchman, Kiri; Grothe, Benedikt; Felmy, Felix

    2012-02-01

    Neurons of the medial superior olive (MSO) code for the azimuthal location of low-frequency sound sources via a binaural coincidence detection system operating on microsecond time scales. These neurons are morphologically simple and stereotyped, and anatomical studies have indicated a functional segregation of excitatory and inhibitory inputs between cellular compartments. It is thought that this morphological arrangement holds important implications for the computational task of these cells. To date, however, there has been no functional investigation into synaptic input sites or functional receptor distributions on mature neurons of the MSO. Here, functional neurotransmitter receptor maps for amino-3-hydroxyl-5-methyl-4-isoxazole propionate (AMPA), N-methyl-D-aspartate (NMDA), glycine (Gly), and ionotropic γ-aminobutyric acid (GABA(A)) receptors (Rs) were compared and complemented by their corresponding synaptic input map. We find in MSO neurons from postnatal day 20-35 gerbils that AMPARs and their excitatory inputs target the soma and dendrites. Functional GlyRs and their inhibitory inputs are predominantly refined to the somata, although a pool of functional GlyRs is present extrasynaptically on MSO dendrites. GABA(A)R responses are present throughout the cell but lack direct synaptic contact indicating an involvement in volume transmission. NMDARs are present both synaptically and extrasynaptically with an overall distribution similar to GlyRs. Interestingly, even at physiological temperatures these functional NMDARs can be potentiated by synaptically released Gly. The functional receptor and synaptic input maps produced here led to the identification of a cross talk between transmitter systems and raises the possibility that extrasynaptic receptors could be modulating leak conductances as a homeostatic mechanism.

  18. PCLO rs2522833 modulates HPA system response to antidepressant treatment in major depressive disorder.

    Science.gov (United States)

    Schuhmacher, Anna; Mössner, Rainald; Höfels, Susanne; Pfeiffer, Ute; Guttenthaler, Vera; Wagner, Michael; Schwab, Sibylle G; Maier, Wolfgang; Zobel, Astrid

    2011-03-01

    Variant rs2522833 of the Piccolo-encoding gene PCLO has recently been found to be associated with major depressive disorder (MDD). PCLO encodes a presynaptic cytomatrix protein which influences monoamine neurotransmitter release. Piccolo could therefore play an important role in treatment response to antidepressant therapy and the improvement of alterations in HPA system reactivity. We investigated the influence of the coding variant rs2522833 in the PCLO gene on treatment response in 205 in-patients with unipolar depression. Treatment response was measured (1) at the level of psychopathology using the Hamilton Depression Rating Scale (HAMD) and (2) with the combined dexamethasone/corticotropin-releasing hormone (Dex/CRH) test, which is a refined tool for showing dysregulation of the hypothalamic-pituitary-adrenocortical (HPA) system, a neurobiological finding in depression. While we did not find an association between variation in PCLO and HAMD scores, HPA dysregulation was less pronounced in carriers of the AA genotype than in carriers of one or two C alleles. HPA activity of individuals with the AA genotype only marginally changed during 4-wk antidepressant treatment, whereas C allele carriers showed a higher hormonal secretion at admission than carriers of the AA genotype but lower responsivity to the Dex/CRH challenge after 4 wk. Our results point to a moderating role of PCLO SNP rs2522833 on HPA regulation during antidepressant treatment, which may represent a neurobiological feature of stability of clinical response.

  19. Effects of lamotrigine on PCP-evoked elevations in monoamine levels in the medial prefrontal cortex of freely moving rats.

    Science.gov (United States)

    Quarta, Davide; Large, Charles H

    2011-12-01

    Lamotrigine is suggested to have potential as an add-on treatment for patients with schizophrenia. Supporting evidence comes from the efficacy of the drug in models of psychotic-like behaviour induced by N-methyl-D-aspartate (NMDA) receptor antagonists, such as phencyclidine (PCP). These drugs enhance levels of the monoamines in the cortex, which may contribute to their psychotomimetic effects. The ability of lamotrigine to prevent these neurochemical changes has not been examined. We studied PCP-evoked overflow of noradrenaline, dopamine and serotonin in the medial prefrontal cortex of awake rats using microdialysis. Rats were administered lamotrigine or vehicle, followed by PCP. Locomotor activity was also recorded before and after drug treatment. Lamotrigine did not have an influence on basal levels of the monoamines, but significantly reduced PCP-evoked overflow of dopamine and serotonin; PCP-evoked overflow of noradrenaline was also reduced by lamotrigine, but not to a significant degree. In contrast, PCP-induced hyperactivity was unaffected by lamotrigine. It is concluded that lamotrigine can modify PCP-evoked monoamine overflow in the cortex, consistent with an ability to prevent the psychotomimetic effects of NMDA receptor antagonists in rodents and humans. The dissociation between monoamine overflow and locomotor activity suggests the involvement of different brain circuits; relevance to the treatment of schizophrenia is also discussed.

  20. Wireless Power Transfer for Autonomous Wearable Neurotransmitter Sensors

    National Research Council Canada - National Science Library

    Nguyen, Cuong M; Kota, Pavan Kumar; Nguyen, Minh Q; Dubey, Souvik; Rao, Smitha; Mays, Jeffrey; Chiao, J-C

    2015-01-01

    ...). A low-power, low-noise, and high-gain recording module was designed to acquire signal from an implantable flexible L-Glu sensor fabricated by micro-electro-mechanical system (MEMS)-based processes...

  1. Neurotransmitters as food supplements: the effects of GABA on brain and behavior

    NARCIS (Netherlands)

    Boonstra, E.; Kleijn, R.; Colzato, L.S.; Alkemade, A.; Forstmann, B.U.; Nieuwenhuis, S.

    2015-01-01

    Gamma-aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the human cortex. The food supplement version of GABA is widely available online. Although many consumers claim that they experience benefits from the use of these products, it is unclear whether these supplements confer benef

  2. Effect of methylmercury on some neurotransmitters and oxidative damage of rats

    Institute of Scientific and Technical Information of China (English)

    CHENG Jin-ping; YANG Yi-chen; HU Wei-xuan; YANG Liu; WANG Wen-hua; JIA Jin-ping; LIN Xue-yu

    2005-01-01

    In order to study the molecular mechanism of injury in rat organs induced by methylmercury, and the relationship between neurotransmitter and oxidative damage in the toxicity process of rat injury by methylmercury was studied. The control group was AChE, ACh, NOS, NO, MDA, SOD, GSH-Px and GSH in different organs of rats were determined with conventional methods. The results showed that after exposure to methylmercury for 7 d, the mercury content in brain of exposure groups increased clearly and had significant difference compared with the control group( P< 0.01). In rat's brain, serum, liver and kidney, the content of ACh and AChE were all decreased; the content of NOS and NO were all increased; the content of MDA was increased compared with the control group,the exposure groups had significant difference ( P < 0.01 ); the content of SOD, GSH and GSH-Px was decreased compared with the control group, the exposure groups had significant difference( P < 0.01). It could be concluded that methylmercury did effect the change of neurotransmitter and free radical. They participated in the toxicity process of injury by methylmercury. The damage of neurotransmitter maybe cause the chaos of free radical and the chaos of free radical may also do more damage to neurotransmitter vice versa.

  3. Decreased cerebral spinal fluid neurotransmitter levels in Smith-Lemli-Opitz syndrome.

    Science.gov (United States)

    Sparks, S E; Wassif, C A; Goodwin, H; Conley, S K; Lanham, D C; Kratz, L E; Hyland, K; Gropman, A; Tierney, E; Porter, F D

    2014-05-01

    Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive, multiple congenital anomaly syndrome with cognitive impairment and a distinct behavioral phenotype that includes autistic features. SLOS is caused by a defect in 3β-hydroxysterol Δ(7)-reductase which leads to decreased cholesterol levels and elevated cholesterol precursors, specifically 7- and 8-dehydrocholesterol. However, the pathological processes contributing to the neurological abnormalities in SLOS have not been defined. In view of prior data suggesting defects in SLOS in vesicular release and given the association of altered serotonin metabolism with autism, we were interested in measuring neurotransmitter metabolite levels in SLOS to assess their potential to be used as biomarkers in therapeutic trials. We measured cerebral spinal fluid levels of serotonin and dopamine metabolites, 5-hydroxyindoleacetic acid (5HIAA) and homovanillic acid (HVA) respectively, in 21 SLOS subjects. Results were correlated with the SLOS anatomical severity score, Aberrant Behavior Checklist scores and concurrent sterol biochemistry. Cerebral spinal fluid (CSF) levels of both 5HIAA and HVA were significantly reduced in SLOS subjects. In individual patients, the levels of both 5HIAA and HVA were reduced to a similar degree. CSF neurotransmitter metabolite levels did not correlate with either CSF sterols or behavioral measures. This is the first study demonstrating decreased levels of CSF neurotransmitter metabolites in SLOS. We propose that decreased levels of neurotransmitters in SLOS are caused by a sterol-related defect in synaptic vesicle formation and that CSF 5HIAA and HVA will be useful biomarkers in development of future therapeutic trials.

  4. Treatment with Tyrosine a Neurotransmitter Precursor Reduces Environmental Stress in Humans

    Science.gov (United States)

    1989-01-01

    brain norepinephrine and dopamine. catecholaminergic neurotransmitters. In animals, administration of tyrosine, a food constituent and precursor of the...Profile of Mood States. Stanford Sleepiness Scale) ENVIRONMENTAL STRESSORS that have been employed to evaluate a variety of psychoactive drugs foods ... tyramine . However. Plasma tyrosine levels were significantly elevated during behav- this amine is not detectable in the plasma of animals after they

  5. Sensing small neurotransmitter-enzyme interaction with nanoporous gated ion-sensitive field effect transistors.

    Science.gov (United States)

    Kisner, Alexandre; Stockmann, Regina; Jansen, Michael; Yegin, Ugur; Offenhäusser, Andreas; Kubota, Lauro Tatsuo; Mourzina, Yulia

    2012-01-15

    Ion-sensitive field effect transistors with gates having a high density of nanopores were fabricated and employed to sense the neurotransmitter dopamine with high selectivity and detectability at micromolar range. The nanoporous structure of the gates was produced by applying a relatively simple anodizing process, which yielded a porous alumina layer with pores exhibiting a mean diameter ranging from 20 to 35 nm. Gate-source voltages of the transistors demonstrated a pH-dependence that was linear over a wide range and could be understood as changes in surface charges during protonation and deprotonation. The large surface area provided by the pores allowed the physical immobilization of tyrosinase, which is an enzyme that oxidizes dopamine, on the gates of the transistors, and thus, changes the acid-base behavior on their surfaces. Concentration-dependent dopamine interacting with immobilized tyrosinase showed a linear dependence into a physiological range of interest for dopamine concentration in the changes of gate-source voltages. In comparison with previous approaches, a response time relatively fast for detecting dopamine was obtained. Additionally, selectivity assays for other neurotransmitters that are abundantly found in the brain were examined. These results demonstrate that the nanoporous structure of ion-sensitive field effect transistors can easily be used to immobilize specific enzyme that can readily and selectively detect small neurotransmitter molecule based on its acid-base interaction with the receptor. Therefore, it could serve as a technology platform for molecular studies of neurotransmitter-enzyme binding and drugs screening.

  6. Tetanus Toxin Action : Inhibition of Neurotransmitter Release Linked to Synaptobrevin Proteolysis

    NARCIS (Netherlands)

    Link, Egenhard; Edelmann, Lambert; Chou, Judy H.; Binz, Thomas; Yamasaki, Shinji; Eisel, Uli; Baumert, Marion; Südhof, Thomas C.; Niemann, Heiner; Jahn, Reinhard

    1992-01-01

    Tetanus toxin is a potent neurotoxin that inhibits the release of neurotransmitters from presynaptic nerve endings. The mature toxin is composed of a heavy and a light chain that are linked via a disulfide bridge. After entry of tetanus toxin into the cytoplasm, the released light chain causes block

  7. Glucose is necessary to maintain neurotransmitter homeostasis during synaptic activity in cultured glutamatergic neurons

    DEFF Research Database (Denmark)

    Bak, Lasse K; Schousboe, Arne; Sonnewald, Ursula

    2006-01-01

    Glucose is the primary energy substrate for the adult mammalian brain. However, lactate produced within the brain might be able to serve this purpose in neurons. In the present study, the relative significance of glucose and lactate as substrates to maintain neurotransmitter homeostasis was inves...

  8. Tetanus Toxin Action : Inhibition of Neurotransmitter Release Linked to Synaptobrevin Proteolysis

    NARCIS (Netherlands)

    Link, Egenhard; Edelmann, Lambert; Chou, Judy H.; Binz, Thomas; Yamasaki, Shinji; Eisel, Uli; Baumert, Marion; Südhof, Thomas C.; Niemann, Heiner; Jahn, Reinhard

    1992-01-01

    Tetanus toxin is a potent neurotoxin that inhibits the release of neurotransmitters from presynaptic nerve endings. The mature toxin is composed of a heavy and a light chain that are linked via a disulfide bridge. After entry of tetanus toxin into the cytoplasm, the released light chain causes block

  9. Direct assessment of substrate binding to the Neurotransmitter:Sodium Symporter LeuT by solid state NMR

    DEFF Research Database (Denmark)

    Erlendsson, Simon; Gotfryd, Kamil; Larsen, Flemming Hofmann

    2017-01-01

    The Neurotransmitter:Sodium Symporters (NSSs) represent an important class of proteins mediating sodium-dependent uptake of neurotransmitters from the extracellular space. The substrate binding stoichiometry of the bacterial NSS protein, LeuT, and thus the principal transport mechanism, has been ...

  10. Aminorex, a metabolite of the cocaine adulterant levamisole, exerts amphetamine like actions at monoamine transporters.

    Science.gov (United States)

    Hofmaier, Tina; Luf, Anton; Seddik, Amir; Stockner, Thomas; Holy, Marion; Freissmuth, Michael; Ecker, Gerhard F; Schmid, Rainer; Sitte, Harald H; Kudlacek, Oliver

    2014-07-01

    Psychostimulants such as amphetamine and cocaine are illicitly used drugs that act on neurotransmitter transporters for dopamine, serotonin or norepinephrine. These drugs can by themselves already cause severe neurotoxicity. However, an additional health threat arises from adulterant substances which are added to the illicit compound without declaration. One of the most frequently added adulterants in street drugs sold as cocaine is the anthelmintic drug levamisole. We tested the effects of levamisole on neurotransmitter transporters heterologously expressed in HEK293 cells. Levamisole was 100 and 300-fold less potent than cocaine in blocking norepinephrine and dopamine uptake, and had only very low affinity for the serotonin transporter. In addition, levamisole did not trigger any appreciable substrate efflux. Because levamisole and cocaine are frequently co-administered, we searched for possible allosteric effects; at 30μM, a concentration at which levamisole displayed already mild effects on norepinephrine transport it did not enhance the inhibitory action of cocaine. Levamisole is metabolized to aminorex, a formerly marketed anorectic drug, which is classified as an amphetamine-like substance. We examined the uptake-inhibitory and efflux-eliciting properties of aminorex and found it to exert strong effects on all three neurotransmitter transporters in a manner similar to amphetamine. We therefore conclude that while the adulterant levamisole itself has only moderate effects on neurotransmitter transporters, its metabolite aminorex may exert distinct psychostimulant effects by itself. Given that the half-time of levamisole and aminorex exceeds that of cocaine, it may be safe to conclude that after the cocaine effect "fades out" the levamisole/aminorex effect "kicks in".

  11. Aminorex, a metabolite of the cocaine adulterant levamisole, exerts amphetamine like actions at monoamine transporters☆

    Science.gov (United States)

    Hofmaier, Tina; Luf, Anton; Seddik, Amir; Stockner, Thomas; Holy, Marion; Freissmuth, Michael; Ecker, Gerhard F.; Schmid, Rainer; Sitte, Harald H.; Kudlacek, Oliver

    2014-01-01

    Psychostimulants such as amphetamine and cocaine are illicitly used drugs that act on neurotransmitter transporters for dopamine, serotonin or norepinephrine. These drugs can by themselves already cause severe neurotoxicity. However, an additional health threat arises from adulterant substances which are added to the illicit compound without declaration. One of the most frequently added adulterants in street drugs sold as cocaine is the anthelmintic drug levamisole. We tested the effects of levamisole on neurotransmitter transporters heterologously expressed in HEK293 cells. Levamisole was 100 and 300-fold less potent than cocaine in blocking norepinephrine and dopamine uptake, and had only very low affinity for the serotonin transporter. In addition, levamisole did not trigger any appreciable substrate efflux. Because levamisole and cocaine are frequently co-administered, we searched for possible allosteric effects; at 30 μM, a concentration at which levamisole displayed already mild effects on norepinephrine transport it did not enhance the inhibitory action of cocaine. Levamisole is metabolized to aminorex, a formerly marketed anorectic drug, which is classified as an amphetamine-like substance. We examined the uptake-inhibitory and efflux-eliciting properties of aminorex and found it to exert strong effects on all three neurotransmitter transporters in a manner similar to amphetamine. We therefore conclude that while the adulterant levamisole itself has only moderate effects on neurotransmitter transporters, its metabolite aminorex may exert distinct psychostimulant effects by itself. Given that the half-time of levamisole and aminorex exceeds that of cocaine, it may be safe to conclude that after the cocaine effect “fades out” the levamisole/aminorex effect “kicks in”. PMID:24296074

  12. Changes in neurotransmitter receptor expression levels in rat brain after 4-week exposure to 1-bromopropane.

    Science.gov (United States)

    Mohideen, Sahabudeen Sheik; Ichihara, Sahoko; Banu, Shameema; Liu, Fang; Kitoh, Junzoh; Ichihara, Gaku

    2009-11-01

    1-Bromopropane (1-BP), an alternative to ozone-depleting solvents, exhibits neurotoxicity and reproductive toxicity in animals and humans. The present study investigated the effects of exposure to 1-BP on expression of neurotransmitter receptor genes in the rat brain to explore possible biomarkers for central neurotoxicity and find brain regions sensitive for microarray analysis. Thirty-six F344 rats were divided at random into four equal groups of nine and exposed to 1-BP at 0, 400, 800 and 1000 ppm for 8 h/day; 7 days/week for 4 weeks. Total RNA from different brain regions was extracted and real-time PCR was conducted to quantify the mRNA levels of serotonin, dopamine and GABA receptors. Western blot analysis for specific regions of interest was also carried out to determine the protein levels. The mRNAs of 5HTr2a, D2R and GABAa1 were down regulated in a 1-BP dose-dependent manner in the hippocampus. The mRNA levels of 5HTr1a, 5HTr2a, D1R and GABAa1 were significantly decreased in the cortex of rats exposed to 800 ppm, but not to 1000 ppm. The mRNAs of 5HTr1a and 5HTr3a in the pons-medulla were decreased in rats exposed to 400 ppm or higher concentrations. The mRNA expression of D2R in the hippocampus and 5HTr1a and 5HTr3a in the pons-medulla oblongata were the most sensitive indicators of 1-BP neurotoxicity. The results suggest that mRNA expression analysis is useful in identifying brain regions susceptible to 1-BP, as well as providing potential biomarkers for central nervous system toxicity.

  13. Transcriptomic responses in mouse brain exposed to chronic excess of the neurotransmitter glutamate

    Directory of Open Access Journals (Sweden)

    Pal Ranu

    2010-06-01

    Full Text Available Abstract Background Increases during aging in extracellular levels of glutamate (Glu, the major excitatory neurotransmitter in the brain, may be linked to chronic neurodegenerative diseases. Little is known about the molecular responses of neurons to chronic, moderate increases in Glu levels. Genome-wide gene expression in brain hippocampus was examined in a unique transgenic (Tg mouse model that exhibits moderate Glu hyperactivity throughout the lifespan, the neuronal Glutamate dehydrogenase (Glud1 mouse, and littermate 9 month-old wild type mice. Results Integrated bioinformatic analyses on transcriptomic data were used to identify bio-functions, pathways and gene networks underlying neuronal responses to increased Glu synaptic release. Bio-functions and pathways up-regulated in Tg mice were those associated with oxidative stress, cell injury, inflammation, nervous system development, neuronal growth, and synaptic transmission. Increased gene expression in these functions and pathways indicated apparent compensatory responses offering protection against stress, promoting growth of neuronal processes (neurites and re-establishment of synapses. The transcription of a key gene in the neurite growth network, the kinase Ptk2b, was significantly up-regulated in Tg mice as was the activated (phosphorylated form of the protein. In addition to genes related to neurite growth and synaptic development, those associated with neuronal vesicle trafficking in the Huntington's disease signalling pathway, were also up-regulated. Conclusions This is the first study attempting to define neuronal gene expression patterns in response to chronic, endogenous Glu hyperactivity at brain synapses. The patterns observed were characterized by a combination of responses to stress and stimulation of nerve growth, intracellular transport and recovery.

  14. The action of orexin B on passive avoidance learning. Involvement of neurotransmitters.

    Science.gov (United States)

    Palotai, Miklós; Telegdy, Gyula; Ekwerike, Alphonsus; Jászberényi, Miklós

    2014-10-01

    The extensive projection of orexigenic neurons and the diffuse expression of orexin receptors suggest that endogenous orexins are involved in several physiological functions of the central nervous system, including learning and memory. Our previous study demonstrated that orexin A improves learning, consolidation and retrieval processes, which involves α- and β-adrenergic, cholinergic, dopaminergic, GABA-A-ergic, opiate and nitrergic neurotransmissions. However, we have little evidence about the action of orexin B on memory processes and the underlying neuromodulation. Therefore, the aim of the present study was to investigate the action of orexin B on passive avoidance learning and the involvement of neurotransmitters in this action in rats. Accordingly, rats were pretreated with the selective orexin 2 receptor (OX2R) antagonist, EMPA; the γ-aminobutyric acid subunit A (GABA-A) receptor antagonist, the bicuculline; a D2, D3, D4 dopamine receptor antagonist, haloperidol; the nonselective opioid receptor antagonist, naloxone; the non-specific nitric oxide synthase (NOS) inhibitor, nitro-l-arginine; the nonselective α-adrenergic receptor antagonist, phenoxybenzamine and the β-adrenergic receptor antagonist, propranolol. Our results demonstrate that orexin B can improve learning, consolidation of memory and retrieval. EMPA reversed completely the action of orexin B on memory consolidation. Bicuculline blocked fully; naloxone, nitro-l-arginine, phenoxybenzamine and propranolol attenuated the orexin B-induced memory consolidation, whereas haloperidol was ineffective. These data suggest that orexin B improves memory functions through OX2R and GABA-ergic, opiate, nitrergic, α- and β-adrenergic neurotransmissions are also involved in this action.

  15. Therapeutic applications of selective and non-selective inhibitors of monoamine oxidase A and B that do not cause significant tyramine potentiation.

    Science.gov (United States)

    Youdim, Moussa B H; Weinstock, Marta

    2004-01-01

    The major side effect with the use of first generation of non selective monoamine oxidase (MAO) inhibitors as neuropsychiatric drugs was what became known as the "cheese reaction". Namely, potentiation of sympathomimetic activity of ingested tyramine present in cheese and other food stuff, resulting from its ability to release noradrenaline, when prevented from metabolism by MAO. The identification of two forms of MAO, termed types A and B and their selective irreversible inhibitors resolved some of this problems. However irreversible MAO-A inhibitors continue to induce a cheese reaction, whereas MAO-B inhibitors at their selective dosage did not and led to introduction of L-deprenyl (selegiline) as an anti-Parkinson drug, since dopamine is equally well metabolized by both enzyme forms. The cheese reaction is a consequence of inhibition of MAO-A, the enzyme responsible for metabolism of noradrenaline and serotonin, located in peripheral adrenergic neurons. The consequence of these findings were the development of reversible MAO-A inhibitors (RIMA), moclobemide and brofaromin, as antidepressants and possible anti-Parkinson activity, with limited tyramine potentiation, since the amine can displace the inhibitor from its binding site on the enzyme. It has always been deemed a greater pharmacological advantage to inhibit both forms of the enzymes to get the full functional activities of the amine neurotransmitters, and without inducing a "cheese reaction". This was not possible until recently, with the development of the novel cholinesterase-brain selective MAO-AB inhibitor, TV3326 (N-propargyl-(3R)-aminoidnan-5-yl-ethyl methylcarbamate hemitartiate), a carbamate derivative of the irreversible MAO-B inhibitor anti-Parkinson drug, rasagiline. This drug is a brain selective MAO-A and B inhibitor, with little inhibition of liver and small intestine enzymes. Pharmacologically it has limited tyramine potentiation, very similar to moclobemide and being a MAO-AB inhibitor it

  16. Dopamine in the Auditory Brainstem and Midbrain: Co-localization with Amino Acid Neurotransmitters and Gene Expression following Cochlear Trauma

    Directory of Open Access Journals (Sweden)

    Avril Genene eHolt

    2015-07-01

    Full Text Available Dopamine (DA modulates the effects of amino acid neurotransmitters, including GABA and glutamate, in motor, visual, olfactory and reward systems (Hnasko et al., 2010; Stuber et al., 2010; Hnasko and Edwards, 2012. The results suggest that DA may play a similar modulatory role in the auditory pathways. Previous studies have shown that deafness results in decreased GABA release, changes in excitatory neurotransmitter levels, and increased spontaneous neuronal activity within brainstem regions related to auditory function. Modulation of the expression and localization of tyrosine hydroxylase (TH; the rate limiting enzyme in the production of DA in the IC following cochlear trauma has been previously reported (Tong et al., 2005. In the current study the possibility of co-localization of TH with amino acid neurotransmitters (AANs was examined. Changes in the gene expression of TH were compared with changes in the gene expression of markers for AANs in the cochlear nucleus (CN and IC to determine whether those deafness related changes occur concurrently. The results indicate that bilateral cochlear ablation significantly reduced TH gene expression in the CN after two months while in the IC the reduction in TH was observed at both three days and two months following ablation. Furthermore, in the CN, glycine transporter 2 (GlyT2 and the GABA transporter (GABAtp were also significantly reduced only after two months. However, in the IC, DA receptor 1 (DRDA1, vesicular glutamate transporters 2 and 3 (vGluT2, vGluT3, GABAtp and GAD67 were reduced in expression both at the three day and two month time points. A close relationship between the distribution of TH and several of the AANs was determined in both the CN and the IC. In addition, GlyT2 and vGluT3 each co-localized with TH within IC somata and dendrites. Therefore, the results of the current study suggest that DA is spatially well positioned to influence the effects of AANs on auditory neurons.

  17. Expression Profiles of Neuropeptides, Neurotransmitters, and Their Receptors in Human Keratocytes In Vitro and In Situ.

    Science.gov (United States)

    Słoniecka, Marta; Le Roux, Sandrine; Boman, Peter; Byström, Berit; Zhou, Qingjun; Danielson, Patrik

    2015-01-01

    Keratocytes, the quiescent cells of the corneal stroma, play a crucial role in corneal wound healing. Neuropeptides and neurotransmitters are usually associated with neuronal signaling, but have recently been shown to be produced also by non-neuronal cells and to be involved in many cellular processes. The aim of this study was to assess the endogenous intracellular and secreted levels of the neuropeptides substance P (SP) and neurokinin A (NKA), and of the neurotransmitters acetylcholine (ACh), catecholamines (adrenaline, noradrenaline and dopamine), and glutamate, as well as the expression profiles of their receptors, in human primary keratocytes in vitro and in keratocytes of human corneal tissue sections in situ. Cultured keratocytes expressed genes encoding for SP and NKA, and for catecholamine and glutamate synthesizing enzymes, as well as genes for neuropeptide, adrenergic and ACh (muscarinic) receptors. Keratocytes in culture produced SP, NKA, catecholamines, ACh, and glutamate, and expressed neurokinin-1 and -2 receptors (NK-1R and NK-2R), dopamine receptor D2, muscarinic ACh receptors, and NDMAR1 glutamate receptor. Human corneal sections expressed SP, NKA, NK-1R, NK-2R, receptor D2, choline acetyl transferase (ChAT), M3, M4 and M5 muscarinic ACh receptors, glutamate, and NMDAR1, but not catecholamine synthesizing enzyme or the α1 and β2 adrenoreceptors, nor M1 receptor. In addition, expression profiles assumed significant differences between keratocytes from the peripheral cornea as compared to those from the central cornea, as well as differences between keratocytes cultured under various serum concentrations. In conclusion, human keratocytes express an array of neuropeptides and neurotransmitters. The cells furthermore express receptors for neuropeptides/neurotransmitters, which suggests that they are susceptible to stimulation by these substances in the cornea, whether of neuronal or non-neuronal origin. As it has been shown that neuropeptides/neurotransmitters

  18. The dependence of neuronal encoding efficiency on Hebbian plasticity and homeostatic regulation of neurotransmitter release

    Science.gov (United States)

    Faghihi, Faramarz; Moustafa, Ahmed A.

    2015-01-01

    Synapses act as information filters by different molecular mechanisms including retrograde messenger that affect neuronal spiking activity. One of the well-known effects of retrograde messenger in presynaptic neurons is a change of the probability of neurotransmitter release. Hebbian learning describe a strengthening of a synapse between a presynaptic input onto a postsynaptic neuron when both pre- and postsynaptic neurons are coactive. In this work, a theory of homeostatic regulation of neurotransmitter release by retrograde messenger and Hebbian plasticity in neuronal encoding is presented. Encoding efficiency was measured for different synaptic conditions. In order to gain high encoding efficiency, the spiking pattern of a neuron should be dependent on the intensity of the input and show low levels of noise. In this work, we represent spiking trains as zeros and ones (corresponding to non-spike or spike in a time bin, respectively) as words with length equal to three. Then the frequency of each word (here eight words) is measured using spiking trains. These frequencies are used to measure neuronal efficiency in different conditions and for different parameter values. Results show that neurons that have synapses acting as band-pass filters show the highest efficiency to encode their input when both Hebbian mechanism and homeostatic regulation of neurotransmitter release exist in synapses. Specifically, the integration of homeostatic regulation of feedback inhibition with Hebbian mechanism and homeostatic regulation of neurotransmitter release in the synapses leads to even higher efficiency when high stimulus intensity is presented to the neurons. However, neurons with synapses acting as high-pass filters show no remarkable increase in encoding efficiency for all simulated synaptic plasticity mechanisms. This study demonstrates the importance of cooperation of Hebbian mechanism with regulation of neurotransmitter release induced by rapid diffused retrograde

  19. Monoamine concentrations changes in the PTU-induced hypothyroid rat brain and the ameliorating role of folic acid.

    Science.gov (United States)

    Tousson, E; Ibrahim, W; Arafa, N; Akela, M A

    2012-03-01

    Thyroid hormones are recognized as the key metabolic hormones that play a critical role in the development of central nervous system (CNS) throughout life. The present study was designed to determine the changes in brain monoamine concentrations in 6-n-propyl thiouracil (PTU)-induced hypothyroid rats, in addition to the ameliorating role of folic acid treatment. Fifty male albino rats were equally divided into five groups; first and second groups were the control and folic acid groups, respectively, while the third group was the hypothyroid group in which the rats received PTU in drinking water for 6 weeks. The fourth and fifth groups were co- and post-treated folic acid groups with hypothyroid rats, respectively. Our results revealed that serotonin and norepinephrine concentrations were significantly decreased in the hypothalamus and cortex, while it significantly increased in the hippocampus of hypothyroid rats when compared with control group. Serotonin and norepinephrine concentrations were decreased in hypothalamus and cortex in co- and post-treated folic acid groups with hypothyroid rats, while the concentration of dopamine were significantly increased in the hypothalamus and hippocampus of the hypothyroid rats and co-treated folic acid group with hypothyroid rats. In cortex, the dopamine concentration was significantly increased in hypothyroid rats and post-treated folic acid group with hypothyroid rats, while it significantly decreased in co-treated folic acid group with hypothyroid rats when compared with the control group. Also, our results revealed that, folic acid treatment was better if it is administered as an adjuvant after returning to the euthyroid state by withdrawing PTU from the drinking water.

  20. Miniaturized ultra-high performance liquid chromatography coupled to electrochemical detection: Investigation of system performance for neurochemical analysis.

    Science.gov (United States)

    Van Schoors, Jolien; Maes, Katrien; Van Wanseele, Yannick; Broeckhoven, Ken; Van Eeckhaut, Ann

    2016-01-04

    The interest in implementation of miniaturized ultra-high performance liquid chromatography (UHPLC) in neurochemical research is growing because of the need for faster, more selective and more sensitive neurotransmitter analyses. The instrument performance of a tailor designed microbore UHPLC system coupled to electrochemical detection (ECD) is investigated, focusing on the quantitative monoamine determination in in vivo microdialysis samples. The use of a microbore column (1.0mm I.D.) requires miniaturization of the entire instrument, though a balance between extra-column band broadening and injection volume must be considered. This is accomplished through the user defined Performance Optimizing Injection Sequence, whereby 5 μL sample is injected on the column with a measured extra-column variance of 4.5-9.0 μL(2) and only 7 μL sample uptake. Different sub-2 μm and superficially porous particle stationary phases are compared by means of the kinetic plot approach. Peak efficiencies of about 16000-35000 theoretical plates are obtained for the Acquity UPLC BEH C18 column within 13 min analysis time. Furthermore, the coupling to ECD is shown suitable for microbore UHPLC analysis thanks to the miniaturized flow cell design, sufficiently fast data acquisition and mathematical data filtering. Ultimately, injection of in vivo samples demonstrates the applicability of the system for microdialysis analysis.

  1. Monoamine oxidase B layer-by-layer film fabrication and characterization toward dopamine detection.

    Science.gov (United States)

    Miyazaki, Celina Massumi; Pereira, Tamyris Paschoal; Mascagni, Daniela Branco Tavares; de Moraes, Marli Leite; Ferreira, Marystela

    2016-01-01

    In this work nanostructured film composites of the monoamine oxidase B (MAO-B) enzyme, free or encapsulated in liposomes, were fabricated by the layer-by-layer (LbL) self-assembly technique, employing polyethylene imine (PEI) as polycation. Initially, the MAO-B enzyme was incorporated into liposomes in order to preserve its enzymatic structure ensuring their activity and catalytic stability. The LbL film growth was monitored by surface plasmon resonance (SPR) by gold resonance angle shift analysis after each bilayer deposition. Subsequently, the films were applied as amperometric biosensors for dopamine detection using Prussian Blue (PB) as the electron mediator. The biosensor fabricated by MAO-B incorporated into liposomes composed of DPPG:POPG in the ratio (1:4) (w/w) showed the best performance with a sensitivity of 0.86 (μA cm(-2))/(mmol L(-1)) and a detection limit of 0.33 mmol L(-1).

  2. Monoamine oxidase and transaminase screening: biotransformation of 2-methyl-6-alkylpiperidines by Neopestalotiopsis sp. CBMAI 2030.

    Science.gov (United States)

    Costa, Jonas Henrique; da Costa, Bruna Zucoloto; de Angelis, Derlene Attili; Marsaioli, Anita Jocelyne

    2017-08-01

    High-throughput screening detected transaminases (TAs) and monoamine oxidases (MAOs) in fungi by applying a fluorogenic probe. Strains F026, F037, F041, F053, and F057 showed the highest enzymatic conversions (31, 60, 30, 40, and 32%, respectively) and where evaluated for their ability to transform piperidines. Strain F053 (Neopestalotiopsis sp. CBMAI 2030) revealed unusual enzymatic activity to deracemize 2-methyl-6-alkylpiperidines. Neopestalotiopsis sp. CBMAI 2030 was capable to convert 2-methyl-6-propylpiperidine, 2-methyl-6-butylpiperidine, and 2-methyl-6-pentylpiperidine in piperideine with 11, 14, and 24% conversion, respectively. The activity was enhanced by cultivating the fungus with 2-methyl-6-pentylpiperidine (38% conversion and 73% ee).

  3. [Substrate-inhibitory analysis of monoamine oxidase from hepatopancreas of the octopus Bathypolypus arcticus].

    Science.gov (United States)

    Basova, I N; Iagodina, O V

    2012-01-01

    Study of the substrate-inhibitory specificity of mitochondrial monoamine oxidase (MAO) of hepatopancreas of the octopus Bathypolypus arcticus revealed distinctive peculiarities of catalytic properties of this enzyme. The studied enzyme, on one hand, like the classic MAO of homoiothermal animals, is able to deaminate tyramine, serotonin, benzylamine, tryptamine, beta-phenylethylamine, while, on the other hand, deaminates histamine and does not deaminate putrescine--classic substrates of diamine oxidase (DAO). Results of the substrate-inhibitory analysis with use of chlorgiline and deprenyl are indirect proofs of the existence in the octopus hepatopancreas of one molecular MAO form. Semicarbazide and pyronine G turned out to be weak irreversible inhibitors, four derivatives of acridine--irreversible inhibitors of the intermediate effectiveness with respect to the octopus hepatopancreas MAO; specificity of action of inhibitors at deamination of different substrates was equal.

  4. ”Ping-pong gaze” secondary to monoamine oxidase inhibitor overdose

    Directory of Open Access Journals (Sweden)

    Amy Attaway

    2016-01-01

    Full Text Available An infrequent manifestation of monoamine oxidase inhibitor (MAOI toxicity is “ping-pong gaze” (PPG. We describe the case of a 26-year-old female who was found unresponsive after taking 40 tablets of phenelzine. On presentation to the hospital, her eyes were moving in characteristic “ping pong” fashion. After 6 hours her gaze terminated. The following day her neurologic exam was benign and she had no long-term sequelae. While the etiology of PPG is unknown, it is most often seen with irreversible structural brain damage. However, a detailed literature review revealed that previous cases of MAOI toxicity where the patient survived have all had complete neurologic recovery.

  5. Improved method for HPLC analysis of polyamines, agmatine and aromatic monoamines in plant tissue

    Science.gov (United States)

    Slocum, R. D.; Flores, H. E.; Galston, A. W.; Weinstein, L. H.

    1989-01-01

    The high performance liquid chromatographic (HPLC) method of Flores and Galston (1982 Plant Physiol 69: 701) for the separation and quantitation of benzoylated polyamines in plant tissues has been widely adopted by other workers. However, due to previously unrecognized problems associated with the derivatization of agmatine, this important intermediate in plant polyamine metabolism cannot be quantitated using this method. Also, two polyamines, putrescine and diaminopropane, also are not well resolved using this method. A simple modification of the original HPLC procedure greatly improves the separation and quantitation of these amines, and further allows the simulation analysis of phenethylamine and tyramine, which are major monoamine constituents of tobacco and other plant tissues. We have used this modified HPLC method to characterize amine titers in suspension cultured carrot (Daucas carota L.) cells and tobacco (Nicotiana tabacum L.) leaf tissues.

  6. Improved method for HPLC analysis of polyamines, agmatine and aromatic monoamines in plant tissue

    Science.gov (United States)

    Slocum, R. D.; Flores, H. E.; Galston, A. W.; Weinstein, L. H.

    1989-01-01

    The high performance liquid chromatographic (HPLC) method of Flores and Galston (1982 Plant Physiol 69: 701) for the separation and quantitation of benzoylated polyamines in plant tissues has been widely adopted by other workers. However, due to previously unrecognized problems associated with the derivatization of agmatine, this important intermediate in plant polyamine metabolism cannot be quantitated using this method. Also, two polyamines, putrescine and diaminopropane, also are not well resolved using this method. A simple modification of the original HPLC procedure greatly improves the separation and quantitation of these amines, and further allows the simulation analysis of phenethylamine and tyramine, which are major monoamine constituents of tobacco and other plant tissues. We have used this modified HPLC method to characterize amine titers in suspension cultured carrot (Daucas carota L.) cells and tobacco (Nicotiana tabacum L.) leaf tissues.

  7. A Study on Antitoxic Role of Vesicular Monoamine Transporter 2 in Transgenic Chinese Hamster Overy Cells

    Institute of Scientific and Technical Information of China (English)

    叶民; 丁新生; 董海蓉; 仇镇宁; 管晓虹

    2003-01-01

    Objective:To study the antitoxic role of vesicular monoamine transporter 2 (VMAT2) in transpgenic Chinese Hamster ovary(CHO) cell.Methods:With the technology of transgene from PC12 to CHO,MTT reduction assay was used to detect MPP+ toxic effect on wild type CHO(wtCHO) and transgenic CHO.Meanwhile,the role of reserpine was also observed in MPP+ toxic effects.Results:The sensitivity of transgenic CHO to MPP+ was much less than that of wtCHO with 0.5 mmol/L MPP+.Transgenic CHO had the same sensitivity as wtCHO if rotenone was given.WtCHO,by given reserpine alone,didn''''''''t change its sensitivity to MPP+.Conclusions:VMAT2 has protective effect on transgenic CHO by transporting MPP+ to vesicles.

  8. Protective effect of taurine on the decreased biogenic amine neurotransmitter levels in the brain of mice exposed to arsenic.

    Science.gov (United States)

    Liu, Xiaohui; Piao, Fengyuan; Li, Yachen

    2013-01-01

    Arsenic (As) exposure has a toxic effect on the central nervous system, especially on learning and memory. Norepinephrine (NE), dopamine (DA), and serotonin (5-HT) play an important role in learning and memory function of the brain. In the present study, the protective effect of taurine on the disturbed biogenic amine neurotransmitter levels in the mouse brain induced by arsenic was examined. Sixty SPF mice were divided into three groups. The As exposure group was administered with 4 ppm As(2)O(3) through drinking water for 60 days. The protective group was treated with both 4 ppm As(2)O(3) and 150 mg/kg taurine. The control group was given drinking water alone. The levels of NE, DA, and 5-HT were determined by HPLC in the cerebrum and cerebellum of mice. Ultrastructure of synapses in brain tissue of mice was observed in these groups by transmission electron microscopy. The mRNA expressions of dopamine beta hydroxylase (DBH), tyrosine hydroxylase (TH), and tryptophan hydroxylase (TPH) as NE, DA, and 5-HT synzymes were also analyzed by real-time RT-PCR. The results showed that the concentrations of NE, DA, and 5-HT; the number of synaptic vesicles; and the expressions of TH, TPH, and DBH genes in the brains of mice exposed to As alone were significantly decreased. However, administration of taurine significantly alleviated the toxic effect on biochemicals detected in the experiment, compared with that in the brain of mice exposed to As alone. These results indicated that taurine was effective in counteracting the decreased biogenic amine neurotransmitter level and the mRNA expressions of their synzymes induced by arsenic.

  9. The resurgence of neurotransmitter modulation in Parkinson’s disease with safinamide

    Directory of Open Access Journals (Sweden)

    Müller T

    2015-03-01

    Full Text Available Thomas Müller Department of Neurology, St Joseph Hospital Berlin-Weißensee, Berlin, Germany Abstract: The main feature of Parkinson’s disease is slowly ongoing neuronal death. Changes of neurotransmission of biogenic amines, such as dopamine, cause the heterogeneity of motor and non-motor symptoms. Therefore, compounds with a broad spectrum of mechanisms of action are ideal candidates for the treatment of the disease. Safinamide reduces dopamine turnover by reversible monoamine oxidase B inhibition, blockage of voltage-dependent sodium channels, and modulation of calcium channels and of glutamate release. Safinamide requires one-time daily intake within a dose range of 50 and 100 mg. Clinical trials demonstrated that safinamide is well tolerated and safe and ameliorates motor behavior when combined with dopamine agonist only or dopamine agonist and levodopa. Safinamide is a putative, important drug for the therapy of Parkinson’s disease with an efficacy superior to available irreversible monoamine oxidase B inhibitors or N-methyl-D-aspartate receptor antagonists. Keywords: MAO-B inhibition, glutamate release inhibition, dopamine substitution, glutamate

  10. Interference of the noradrenergic neurotoxin DSP4 with neuronal and nonneuronal monoamine transporters.

    Science.gov (United States)

    Wenge, Birger; Bönisch, Heinz

    2009-12-01

    The haloalkylamine DSP4 (N[-2-chloroethyl]-N-ethyl-2-bromobenzylamine) is a noradrenergic neurotoxin, which is used for the chemical denervation of noradrenergic neurons, and it has been proposed to be a selective substrate for the neuronal, Na(+)- and Cl(-)-dependent noradrenaline transporter (NAT). In the present study, we investigated whether DSP4 not only interacts with the human NAT (hNAT) but also with other neuronal monoamine transporters such as the transporters for dopamine (hDAT) and serotonin (hSERT) or with nonneuronal (Na(+)-independent) monoamine transporters also known as organic cation transporters (OCTs), such as hOCT(1), hOCT(2), and hOCT(3). Using human embryonic kidney HEK293 cells heterologously expressing the corresponding transporter, we show that DSP4 irreversibly inhibits the hNAT, hDAT, hSERT, and hOCT(3). However, this inhibition includes a reversible component at the hDAT, hSERT, and hOCT(3) but not at the hNAT. The inhibitory potency of DSP4 at the neuronal transporters was highest at the hNAT (IC(50) about 5 microM), and it was about five and 40 times lower at the hSERT and hDAT, respectively. DSP4 inhibited all three hOCTs with high potency (IC(50) about 1 microM) but in a completely reversible manner at hOCT(1) and hOCT(2). Cytotoxicity by 24-h exposure of hNAT- or hOCT-expressing cells to low DSP4 concentrations (DSP4's high-affinity uptake through the NAT together with its completely irreversible mode of interaction with the NAT may contribute to its selectivity as noradrenergic neurotoxin.

  11. The designer methcathinone analogs, mephedrone and methylone, are substrates for monoamine transporters in brain tissue.

    Science.gov (United States)

    Baumann, Michael H; Ayestas, Mario A; Partilla, John S; Sink, Jacqueline R; Shulgin, Alexander T; Daley, Paul F; Brandt, Simon D; Rothman, Richard B; Ruoho, Arnold E; Cozzi, Nicholas V

    2012-04-01

    The nonmedical use of 'designer' cathinone analogs, such as 4-methylmethcathinone (mephedrone) and 3,4-methylenedioxymethcathinone (methylone), is increasing worldwide, yet little information is available regarding the mechanism of action for these drugs. Here, we employed in vitro and in vivo methods to compare neurobiological effects of mephedrone and methylone with those produced by the structurally related compounds, 3,4-methylenedioxymethamphetamine (MDMA) and methamphetamine. In vitro release assays using rat brain synaptosomes revealed that mephedrone and methylone are nonselective substrates for plasma membrane monoamine transporters, similar to MDMA in potency and selectivity. In vivo microdialysis in rat nucleus accumbens showed that i.v. administration of 0.3 and 1.0 mg/kg of mephedrone or methylone produces dose-related increases in extracellular dopamine and serotonin (5-HT), with the magnitude of effect on 5-HT being greater. Both methcathinone analogs were weak motor stimulants when compared with methamphetamine. Repeated administrations of mephedrone or methylone (3.0 and 10.0 mg/kg, s.c., 3 doses) caused hyperthermia but no long-term change in cortical or striatal amines, whereas similar treatment with MDMA (2.5 and 7.5 mg/kg, s.c., 3 doses) evoked robust hyperthermia and persistent depletion of cortical and striatal 5-HT. Our data demonstrate that designer methcathinone analogs are substrates for monoamine transporters, with a profile of transmitter-releasing activity comparable to MDMA. Dopaminergic effects of mephedrone and methylone may contribute to their addictive potential, but this hypothesis awaits confirmation. Given the widespread use of mephedrone and methylone, determining the consequences of repeated drug exposure warrants further study.

  12. Iododerivative of pargyline: A potential tracer for the exploration of monoamine oxidase sites by SPECT

    Energy Technology Data Exchange (ETDEWEB)

    Lena, Isabelle; Ombetta, Jean-Edouard; Chalon, Sylvie; Dognon, Anne-Marie; Baulieu, Jean-Louis; Frangin, Yves; Garreau, Lucette; Besnard, Jean-Claude; Guilloteau, Denis

    1995-08-01

    Monoamine oxidases are important in the regulation of monoaminergic neurotransmission. An increase in monoamine oxidase B (MAO B) has been observed in some neurodegenerative diseases, and therefore quantification of cerebral MAO B activity by SPECT would be useful for the diagnosis and therapeutic follow-up of these disorders. We have developed an iodinated derivative of pargyline, a selective inhibitor of MAO B, in order to explore this enzyme by SPECT. Stable bromo and iodo derivatives of pargyline were synthesized and chemically characterized. The radioiodinated ligand [{sup 125}I]-2-iodopargyline was obtained with high specific activity from the bromo precursor by nucleophilic exchange. Affinity and selectivity of 2-iodopargyline were tested in vitro. Biodistribution study of [{sup 125}I]-2-iodopargyline was performed in rats. Radioiodinated ligand were obtained in a no-carrier-added form. 2-iodopargyline has a higher in vitro affinity for MAO B than pargyline. However, the in vitro selectivity for MAO B was better for pargyline than for 2-iodopargyline. Ex vivo autoradiographic studies and in vivo saturation studies with selective inhibitors of MAO showed that the cerebral biodistribution of [{sup 125}I]-2-iodopargyline in the rat is consistent with high level binding to MAO B sites in the pineal gland and in the thalamus. In conclusion, 2-iodopargyline preferentially binds in vivo to MAO B sites with high affinity. However, its selectivity for MAO B in rats is not very high, whereas this ligand binds to a lesser extent to MAO A. It will be then of great value to evaluate the specificity of 2-iodopargyline in humans. This new ligand labeled with {sup 123}I should therefore be a suitable tool for SPECT exploration of MAO B in the human brain.

  13. The Designer Methcathinone Analogs, Mephedrone and Methylone, are Substrates for Monoamine Transporters in Brain Tissue

    Science.gov (United States)

    Baumann, Michael H; Ayestas, Mario A; Partilla, John S; Sink, Jacqueline R; Shulgin, Alexander T; Daley, Paul F; Brandt, Simon D; Rothman, Richard B; Ruoho, Arnold E; Cozzi, Nicholas V

    2012-01-01

    The nonmedical use of ‘designer' cathinone analogs, such as 4-methylmethcathinone (mephedrone) and 3,4-methylenedioxymethcathinone (methylone), is increasing worldwide, yet little information is available regarding the mechanism of action for these drugs. Here, we employed in vitro and in vivo methods to compare neurobiological effects of mephedrone and methylone with those produced by the structurally related compounds, 3,4-methylenedioxymethamphetamine (MDMA) and methamphetamine. In vitro release assays using rat brain synaptosomes revealed that mephedrone and methylone are nonselective substrates for plasma membrane monoamine transporters, similar to MDMA in potency and selectivity. In vivo microdialysis in rat nucleus accumbens showed that i.v. administration of 0.3 and 1.0 mg/kg of mephedrone or methylone produces dose-related increases in extracellular dopamine and serotonin (5-HT), with the magnitude of effect on 5-HT being greater. Both methcathinone analogs were weak motor stimulants when compared with methamphetamine. Repeated administrations of mephedrone or methylone (3.0 and 10.0 mg/kg, s.c., 3 doses) caused hyperthermia but no long-term change in cortical or striatal amines, whereas similar treatment with MDMA (2.5 and 7.5 mg/kg, s.c., 3 doses) evoked robust hyperthermia and persistent depletion of cortical and striatal 5-HT. Our data demonstrate that designer methcathinone analogs are substrates for monoamine transporters, with a profile of transmitter-releasing activity comparable to MDMA. Dopaminergic effects of mephedrone and methylone may contribute to their addictive potential, but this hypothesis awaits confirmation. Given the widespread use of mephedrone and methylone, determining the consequences of repeated drug exposure warrants further study. PMID:22169943

  14. Relationship of monoamine oxidase A binding to adaptive and maladaptive personality traits.

    Science.gov (United States)

    Soliman, A; Bagby, R M; Wilson, A A; Miler, L; Clark, M; Rusjan, P; Sacher, J; Houle, S; Meyer, J H

    2011-05-01

    Monoamine oxidase A (MAOA) is an important enzyme that metabolizes monoamines such as serotonin, norepinephrine and dopamine in the brain. In prefrontal cortex, low MAOA binding is associated with aggression and high binding is associated with major depressive disorder (MDD) and also risk for recurrence of depressive episodes. In rodent models, low MAOA levels are associated with increased aggression and fear conditioning, and decreased social and exploratory investigative behaviors. Our objective was to measure MAOA binding in prefrontal cortex and concurrently evaluate a broad range of validated personality traits. We hypothesized that prefrontal MAOA binding would correlate negatively with angry-hostility, a trait related to aggression/anger, and positively with traits intuitively related to adaptive investigative behavior. Participants were aged 19-49 years, healthy and non-smoking. MAOA binding was measured with [11C]harmine positron emission tomography (PET) in prefrontal brain regions and personality traits were measured with the NEO Personality Inventory Revised (NEO PI-R). Prefrontal MAOA binding correlated negatively with angry-hostility (r=-0.515, p=0.001) and positively with deliberation (r=0.514, p=0.001). In a two-factor regression model, these facets explained 38% of variance in prefrontal MAOA binding. A similar relationship was found in prefrontal cortex subregions. We propose a new continuum describing the relationship between personality and MAOA: deliberate/thoughtful contrasting aggressive/impulsive. Additionally, the association between high MAOA binding and greater deliberation may explain why some people have moderately high levels of MAOA, although very high levels occur during MDD. In health, higher MAOA binding is associated with an adaptive personality facet.

  15. Selective Detection of Neurotransmitters by Fluorescence and Chemiluminescence Imaging

    Energy Technology Data Exchange (ETDEWEB)

    Ziqiang Wang; Edward S. Yeung

    2001-08-06

    In recent years, luminescence imaging has been widely employed in neurochemical analysis. It has a number of advantages for the study of neuronal and other biological cells: (1) a particular molecular species or cellular constituent can be selectively visualized in the presence of a large excess of other species in a heterogeneous environment; (2) low concentration detection limits can be achieved because of the inherent sensitivity associated with fluorescence and chemiluminescence; (3) low excitation intensities can be used so that long-term observation can be realized while the viability of the specimen is preserved; and (4) excellent spatial resolution can be obtained with the light microscope so subcellular compartments can be identified. With good sensitivity, temporal and spatial resolution, the flux of ions and molecules and the distribution and dynamics of intracellular species can be measured in real time with specific luminescence probes, substrates, or with native fluorescence. A noninvasive detection scheme based on glutamate dehydrogenase (GDH) enzymatic assay combined with microscopy was developed to measure the glutamate release in cultured cells from the central nervous system (CNS). The enzyme reaction is very specific and sensitive. The detection limit with CCD imaging is down to {micro}M levels of glutamate with reasonable response time. They also found that chemiluminescence associated with the ATP-dependent reaction between luciferase and luciferin can be used to image ATP at levels down to 10 nM in the millisecond time scale. Similar imaging experiments should be feasible in a broad spectrum of biological systems.

  16. Laurate Biosensors Image Brain Neurotransmitters In Vivo: Can an Antihypertensive Medication Alter Psychostimulant Behavior?

    Directory of Open Access Journals (Sweden)

    Vivek Murthy

    2008-07-01

    Full Text Available Neuromolecular Imaging (NMI with novel biosensors enables the selective detection of neurotransmitters in vivo within seconds, on line and in real time. Biosensors remain in place for continuing studies over a period of months. This biotechnological advance is based on conventional electrochemistry; the biosensors detect neurotransmitters by electron transfer. Simply stated, biosensors adsorb electrons from each neurotransmitter at specific oxidation potentials; the current derived from electron transfer is proportional to neurotransmitter concentration. Selective electron transfer properties of these biosensors permit the imaging of neurotransmitters, metabolites and precursors. The novel BRODERICK PROBE® biosensors we have developed, differ in formulation and detection capabilities from biosensors/electrodes used in conventional electrochemistry/ voltammetry. In these studies, NMI, specifically, the BRODERICK PROBE® laurate biosensor images neurotransmitter signals within mesolimbic neuronal terminals, nucleus accumbens (NAc; dopamine (DA, serotonin (5-HT, homovanillic acid (HVA and Ltryptophan (L-TP are selectively imaged. Simultaneously, we use infrared photobeams to monitor open-field movement behaviors on line with NMI in the same animal subjects. The goals are to investigate integrated neurochemical and behavioral effects of cocaine and caffeine alone and co-administered and further, to use ketanserin to decipher receptor profiles for these psychostimulants, alone and co-administered. The rationale for selecting this medication is: ketanserin (a is an antihypertensive and cocaine and caffeine produce hypertension and (b acts at 5-HT2A/2C receptors, prevalent in NAc and implicated in hypertension and cocaine addiction. Key findings are: (a the moderate dose of caffeine simultaneously potentiates cocaine's neurochemical and behavioral responses. (b ketanserin simultaneously inhibits cocaine-increased DA and 5-HT release in

  17. Study on Psychoprophylaxis and Monoamines Neurotransmitter of Patients with Burning Month Syndrome%灼口综合征患者的心理健康状况及其单胺类神经递质研究

    Institute of Scientific and Technical Information of China (English)

    林梅; 李秉琦; 顾芳; 岳玉敏; 黄玉云; 陈谦明; 曾光明; 夏娟

    2001-01-01

    目的从与痛觉联系紧密的心理因素和单胺类神经递质方面对灼口综合征患者进行测定和分析.方法灼口综合征(BMS)组选择初诊患者30例,其中男性4例,女性26例.对照组为30例年龄、性别相似的健康人.采用艾森克个性问卷量表(EPQ)对受试者进行个性测定,并将L值(谎言值)>50分者排除.采用修订的临床症状自评量表(SCL-90)检测受试者的情绪状况.在晨9时平和状态下抽空腹静脉血2ml,用高效液相色谱-电化学检测法测定血浆中肾上腺素和去甲肾上腺素浓度.结果BMS组P值(精神质)、N值(神经质)分高于对照组(P<0.05),E值(内外相)低于对照组(P<0.05),两组间个性类型分布具有显著性差异(P<0.05).BMS组以内向不稳定型为主,对照组以外向稳定型为主.BMS组有强迫、忧郁、人际关系敏感度、焦虑等9个因子分值高于对照组(P<0.05),存在明显的情绪障碍.BMS女性患者血浆去甲肾上腺素水平高于对照组(P<0.01).结论BMS患者的个性特征提高了机体对各种不良刺激的反应性,明显的情绪障碍可导致中枢神经系统和交感神经功能的失调,这可能与BMS的发生有内在的联系.

  18. 抽动-秽语综合征患儿尿香草扁桃酸的变化及意义%Changes and significances of monoamine neurotransmitter vanillyl mandelic acids in urine of Tourette's syndrome patients

    Institute of Scientific and Technical Information of China (English)

    常会波; 王珺; 李尔珍; 王立文; 吴建新

    2013-01-01

    目的 了解抽动-秽语综合征(tourette's syndrome,TS)患儿尿单氨类神经递质代谢产物香草扁桃酸(vanillylmandelic acid,VMA)水平,探讨其与疾病发生的意义.方法 以40例TS患儿为病例组,33例健康儿童作为正常对照组.采集研究对象的尿液,经高效液相色谱法分离后利用库仑阵列电化学检测香草扁桃酸(VMA)水平,紫外检测器检测作为校正因素的肌酐含量.利用VMA/Cr代表尿样中VMA的水平.结果 病例组尿液VMA/Cr值为:(1.597±0.095)μg/mg,对照组VMA/Cr值为(2.198±0.112)μg/mg,病例组尿液VMA/Cr均值显著低于对照组(P<0.001),病例组和对照组VMA/Cr均值男女之间差异均无统计学意义.结论 TS患儿中存在VMA水平异常.

  19. Modulation of neurotransmitter release via histamine H3 heteroreceptors.

    Science.gov (United States)

    Schlicker, E; Malinowska, B; Kathmann, M; Göthert, M

    1994-01-01

    Presynaptic H3 receptors occur on histaminergic neurones of the CNS (autoreceptors) and on non-histaminergic neurones of the central and autonomic nervous system (heteroreceptors). H3 heteroreceptors, most probably located on the postganglionic sympathetic nerve fibres innervating the resistance vessels and the heart, have been identified in the model of the pithed rat. Furthermore, we could show in superfusion experiments that H3 heteroreceptors also occur on the sympathetic neurones supplying the human saphenous vein and the vasculature of the pig retina and on the serotoninergic, dopaminergic and noradrenergic neurones in the brain of various mammalian species, including man. The effects of three recently described H3 receptor ligands were studied in superfused mouse brain cortex slices. The potency of the novel H3 receptor agonist imetit exceeded that of R-(-)-alpha-methylhistamine (the reference H3 receptor agonist) by one log unit and that of histamine by almost two log units. Clobenpropit was shown to be a competitive H3 receptor antagonist, exhibiting a pA2 as high as 9.6 (exceeding the pA2 of the reference H3 receptor antagonist thioperamide by one log unit). The irreversible antagonism of N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) was also studied. Interactions of the H3 heteroreceptor with the dopamine autoreceptor in mouse striatal slices and the alpha 2-autoreceptor in mouse brain cortex slices could be demonstrated. Activation of alpha 2-autoreceptors decreases the H3 receptor-mediated effect. Blockade of alpha 2-autoreceptors increases the H3 receptor-mediated effect only if the alpha 2-autoreceptors are simultaneously activated by endogenous noradrenaline. The H3 receptor-mediated inhibition of noradrenaline release in mouse brain cortex slices was attenuated by the K+ channel blocker tetraethylammonium but this attenuation was abolished by reduction of the Ca2+ concentration in the medium (to compensate for the facilitatory effect of

  20. A trans-synaptic nanocolumn aligns neurotransmitter release to receptors.

    Science.gov (United States)

    Tang, Ai-Hui; Chen, Haiwen; Li, Tuo P; Metzbower, Sarah R; MacGillavry, Harold D; Blanpied, Thomas A

    2016-08-11

    Synaptic transmission is maintained by a delicate, sub-synaptic molecular architecture, and even mild alterations in synapse structure drive functional changes during experience-dependent plasticity and pathological disorders. Key to this architecture is how the distribution of presynaptic vesicle fusion sites corresponds to the position of receptors in the postsynaptic density. However, while it has long been recognized that this spatial relationship modulates synaptic strength, it has not been precisely described, owing in part to the limited resolution of light microscopy. Using localization microscopy, here we show that key proteins mediating vesicle priming and fusion are mutually co-enriched within nanometre-scale subregions of the presynaptic active zone. Through development of a new method to map vesicle fusion positions within single synapses in cultured rat hippocampal neurons, we find that action-potential-evoked fusion is guided by this protein gradient and occurs preferentially in confined areas with higher local density of Rab3-interacting molecule (RIM) within the active zones. These presynaptic RIM nanoclusters closely align with concentrated postsynaptic receptors and scaffolding proteins, suggesting the existence of a trans-synaptic molecular 'nanocolumn'. Thus, we propose that the nanoarchitecture of the active zone directs action-potential-evoked vesicle fusion to occur preferentially at sites directly opposing postsynaptic receptor-scaffold ensembles. Remarkably, NMDA receptor activation triggered distinct phases of plasticity in which postsynaptic reorganization was followed by trans-synaptic nanoscale realignment. This architecture suggests a simple organizational principle of central nervous system synapses to maintain and modulate synaptic efficiency.

  1. Antidepressant drugs transactivate TrkB neurotrophin receptors in the adult rodent brain independently of BDNF and monoamine transporter blockade.

    Directory of Open Access Journals (Sweden)

    Tomi Rantamäki

    Full Text Available BACKGROUND: Antidepressant drugs (ADs have been shown to activate BDNF (brain-derived neurotrophic factor receptor TrkB in the rodent brain but the mechanism underlying this phenomenon remains unclear. ADs act as monoamine reuptake inhibitors and after prolonged treatments regulate brain bdnf mRNA levels indicating that monoamine-BDNF signaling regulate AD-induced TrkB activation in vivo. However, recent findings demonstrate that Trk receptors can be transactivated independently of their neurotrophin ligands. METHODOLOGY: In this study we examined the role of BDNF, TrkB kinase activity and monoamine reuptake in the AD-induced TrkB activation in vivo and in vitro by employing several transgenic mouse models, cultured neurons and TrkB-expressing cell lines. PRINCIPAL FINDINGS: Using a chemical-genetic TrkB(F616A mutant and TrkB overexpressing mice, we demonstrate that ADs specifically activate both the maturely and immaturely glycosylated forms of TrkB receptors in the brain in a TrkB kinase dependent manner. However, the tricyclic AD imipramine readily induced the phosphorylation of TrkB receptors in conditional bdnf⁻/⁻ knock-out mice (132.4±8.5% of control; P = 0.01, indicating that BDNF is not required for the TrkB activation. Moreover, using serotonin transporter (SERT deficient mice and chemical lesions of monoaminergic neurons we show that neither a functional SERT nor monoamines are required for the TrkB phosphorylation response induced by the serotonin selective reuptake inhibitors fluoxetine or citalopram, or norepinephrine selective reuptake inhibitor reboxetine. However, neither ADs nor monoamine transmitters activated TrkB in cultured neurons or cell lines expressing TrkB receptors, arguing that ADs do not directly bind to TrkB. CONCLUSIONS: The present findings suggest that ADs transactivate brain TrkB receptors independently of BDNF and monoamine reuptake blockade and emphasize the need of an intact tissue context for the

  2. FMRP regulates neurotransmitter release and synaptic information transmission by modulating action potential duration via BK channels.

    Science.gov (United States)

    Deng, Pan-Yue; Rotman, Ziv; Blundon, Jay A; Cho, Yongcheol; Cui, Jianmin; Cavalli, Valeria; Zakharenko, Stanislav S; Klyachko, Vitaly A

    2013-02-20

    Loss of FMRP causes fragile X syndrome (FXS), but the physiological functions of FMRP remain highly debatable. Here we show that FMRP regulates neurotransmitter release in CA3 pyramidal neurons by modulating action potential (AP) duration. Loss of FMRP leads to excessive AP broadening during repetitive activity, enhanced presynaptic calcium influx, and elevated neurotransmitter release. The AP broadening defects caused by FMRP loss have a cell-autonomous presynaptic origin and can be acutely rescued in postnatal neurons. These presynaptic actions of FMRP are translation independent and are mediated selectively by BK channels via interaction of FMRP with BK channel's regulatory β4 subunits. Information-theoretical analysis demonstrates that loss of these FMRP functions causes marked dysregulation of synaptic information transmission. FMRP-dependent AP broadening is not limited to the hippocampus, but also occurs in cortical pyramidal neurons. Our results thus suggest major translation-independent presynaptic functions of FMRP that may have important implications for understanding FXS neuropathology.

  3. Miniaturized and Wireless Optical Neurotransmitter Sensor for Real-Time Monitoring of Dopamine in the Brain

    Directory of Open Access Journals (Sweden)

    Min H. Kim

    2016-11-01

    Full Text Available Real-time monitoring of extracellular neurotransmitter concentration offers great benefits for diagnosis and treatment of neurological disorders and diseases. This paper presents the study design and results of a miniaturized and wireless optical neurotransmitter sensor (MWONS for real-time monitoring of brain dopamine concentration. MWONS is based on fluorescent sensing principles and comprises a microspectrometer unit, a microcontroller for data acquisition, and a Bluetooth wireless network for real-time monitoring. MWONS has a custom-designed application software that controls the operation parameters for excitation light sources, data acquisition, and signal processing. MWONS successfully demonstrated a measurement capability with a limit of detection down to a 100 nanomole dopamine concentration, and high selectivity to ascorbic acid (90:1 and uric acid (36:1.

  4. LeuT-Desipramine Structure Reveals How Antidepressants Block Neurotransmitter Reuptake

    Energy Technology Data Exchange (ETDEWEB)

    Zhou,Z.; Zhen, J.; Karpowich, N.; Goetz, R.; Law, C.; Reith, M.; Wang, D.

    2007-01-01

    Tricyclic antidepressants exert their pharmacological effect -- inhibiting the reuptake of serotonin, norepinephrine, and dopamine -- by directly blocking neurotransmitter transporters (SERT, NET, and DAT, respectively) in the presynaptic membrane. The drug-binding site and the mechanism of this inhibition are poorly understood. We determined the crystal structure at 2.9 angstroms of the bacterial leucine transporter (LeuT), a homolog of SERT, NET, and DAT, in complex with leucine and the antidepressant desipramine. Desipramine binds at the inner end of the extracellular cavity of the transporter and is held in place by a hairpin loop and by a salt bridge. This binding site is separated from the leucine-binding site by the extracellular gate of the transporter. By directly locking the gate, desipramine prevents conformational changes and blocks substrate transport. Mutagenesis experiments on human SERT and DAT indicate that both the desipramine-binding site and its inhibition mechanism are probably conserved in the human neurotransmitter transporters.

  5. Neurotransmitter evaluation in the hippocampus of rats after intracerebral injection of TsTX scorpion toxin

    Directory of Open Access Journals (Sweden)

    ALA Nencioni

    2009-01-01

    Full Text Available TsTX is an α-type sodium channel toxin that stimulates the discharge of neurotransmitters from neurons. In the present study we investigated which neurotransmitters are released in the hippocampus after TsTX injection and if they are responsible for electrographic or histopathological effects. Microdialysis revealed that the toxin increased glutamate extracellular levels in the hippocampus; however, levels of gamma-aminobutyric acid (GABA, glycine, 5-hydroxyindoleacetic acid (5-HIAA, homovanillic acid (HVA and 3,4-dihydroxyphenylacetic acid (DOPAC were not significantly altered. Neurodegeneration in pyramidal cells of hippocampus and electroencephalographic alterations caused by the toxin were blocked by pretreatment with riluzole, a glutamate release inhibitor. The present results suggest a specific activity of TsTX in the hippocampus which affects only glutamate release.

  6. Parallel expression of synaptophysin and evoked neurotransmitter release during development of cultured neurons

    DEFF Research Database (Denmark)

    Ehrhart-Bornstein, M; Treiman, M; Hansen, Gert Helge;

    1991-01-01

    and neurotransmitter release were measured in each of the culture types as a function of development for up to 8 days in vitro, using the same batch of cells for both sets of measurements to obtain optimal comparisons. The content and the distribution of synaptophysin in the developing cells were assessed...... by quantitative immunoblotting and light microscope immunocytochemistry, respectively. In both cell types, a close parallelism was found between the temporal pattern of development in synaptophysin expression and neurotransmitter release. This temporal pattern differed between the two types of neurons....... The cerebral cortex neurons showed a biphasic time course of increase in synaptophysin content, paralleled by a biphasic pattern of development in their ability to release [3H]GABA in response to depolarization by glutamate or elevated K+ concentrations. In contrast, a monophasic, approximately linear increase...

  7. LeuT-desipramine structure reveals how antidepressants block neurotransmitter reuptake.

    Science.gov (United States)

    Zhou, Zheng; Zhen, Juan; Karpowich, Nathan K; Goetz, Regina M; Law, Christopher J; Reith, Maarten E A; Wang, Da-Neng

    2007-09-07

    Tricyclic antidepressants exert their pharmacological effect-inhibiting the reuptake of serotonin, norepinephrine, and dopamine-by directly blocking neurotransmitter transporters (SERT, NET, and DAT, respectively) in the presynaptic membrane. The drug-binding site and the mechanism of this inhibition are poorly understood. We determined the crystal structure at 2.9 angstroms of the bacterial leucine transporter (LeuT), a homolog of SERT, NET, and DAT, in complex with leucine and the antidepressant desipramine. Desipramine binds at the inner end of the extracellular cavity of the transporter and is held in place by a hairpin loop and by a salt bridge. This binding site is separated from the leucine-binding site by the extracellular gate of the transporter. By directly locking the gate, desipramine prevents conformational changes and blocks substrate transport. Mutagenesis experiments on human SERT and DAT indicate that both the desipramine-binding site and its inhibition mechanism are probably conserved in the human neurotransmitter transporters.

  8. Control of neurotransmitter release by an internal gel matrix in synaptic vesicles.

    Science.gov (United States)

    Reigada, David; Díez-Pérez, Ismael; Gorostiza, Pau; Verdaguer, Albert; Gómez de Aranda, Inmaculada; Pineda, Oriol; Vilarrasa, Jaume; Marsal, Jordi; Blasi, Joan; Aleu, Jordi; Solsona, Carles

    2003-03-18

    Neurotransmitters are stored in synaptic vesicles, where they have been assumed to be in free solution. Here we report that in Torpedo synaptic vesicles, only 5% of the total acetylcholine (ACh) or ATP content is free, and that the rest is adsorbed to an intravesicular proteoglycan matrix. This matrix, which controls ACh and ATP release by an ion-exchange mechanism, behaves like a smart gel. That is, it releases neurotransmitter and changes its volume when challenged with small ionic concentration change. Immunodetection analysis revealed that the synaptic vesicle proteoglycan SV2 is the core of the intravesicular matrix and is responsible for immobilization and release of ACh and ATP. We suggest that in the early steps of vesicle fusion, this internal matrix regulates the availability of free diffusible ACh and ATP, and thus serves to modulate the quantity of transmitter released.

  9. The magnitude and significance of Ca2+ domains for release of neurotransmitter.

    Science.gov (United States)

    Aharon, S; Parnas, H; Parnas, I

    1994-11-01

    It is now widely accepted that localized high concentrations of Ca2+ (Ca2+ domains) play a major role in controlling the time course of neurotransmitter release. In the present work we calculate the magnitude and the time course of Ca2+ domains that evolve in the vicinity of a Ca2+ channel and an adjacent release site. In the calculations we consider a accurately dimensioned Ca2+ channel. Moreover, the Ca2+ current is continuously adjusted with regard to the accumulated intracellular Ca2+ and, in addition, endogenous buffers are considered. The calculations, carried out by the software FIDAP, based on finite element method, show that the Ca2+ concentrations achieved near the release sites are significantly lower than claimed by other investigators. Furthermore, we present arguments indicating that the Ca2+ domains, regardless of their magnitude, do not play a role in controlling the time course of release of neurotransmitter.

  10. Effects of the Bee Venom Herbal Acupuncture on the Neurotransmitters of the Rat Brain Cortex

    Directory of Open Access Journals (Sweden)

    Hyoung-Seok Yun

    2001-02-01

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

  11. Influence of ketamine on amino acid neurotransmitters secretion by nerve cells in vitro

    Directory of Open Access Journals (Sweden)

    Mingxian Shi

    2016-04-01

    Full Text Available In order to study the influence of amino acid neurotransmitters secreted by the nerve cells after ketamine treatment, the nerve cells were cultured in vitro to exclude the interference of other factors in vivo and treated with three different doses of ketamine (1, 3 and 5 µg/mL. Then, the concentration of neuronal amino acid neurotransmitters was examined at 0, 15, 30, 45, 60, 90, 120 min after treatment. The trends of each amino acid concentration after ketamine treatment were nearly the same among the different treatment doses. After 15 min of adapting time, ketamine decreased the excitatory amino acid glutamic acid and aspartic acid concentration, and increased the concentration of the inhibitory amino acid glycine. Their concentrations showed a tendency to return approximately to the original level after 120 min.

  12. Corticosterone modulation of neurotransmitter receptors in rat hippocampus: a quantitative autoradiographic study

    Energy Technology Data Exchange (ETDEWEB)

    Biegon, A. (Hoffmann-La Roche, Inc., Nutley, NJ (USA). Dept. of Pharmacology); Rainbow, T.C. (Pennsylvania Univ., Philadelphia (USA). School of Medicine); McEwen, B.S. (Rockefeller Univ., New York (USA))

    1985-04-22

    The effect of adrenalectomy (ADX) and corticosterone (CORT) replacement on neurotransmitter receptors was studied in dorsal hippocampus of rat using quantitative autoradiography. ADX for one week causes an increase in (/sup 3/H)5-HT binding to 5-HT/sub 1/ receptors which is significant in the CA1 cell field. CORT treatment of ADX rats for 3-5 days results in localized reductions of (/sup 3/H)5-HT binding including a partial reversal of the increase observed after ADX in CA1. CORT treatment of ADX animals also decreases binding of (/sup 3/H)QNB to muscarinic receptors in the dorsal hippocampus, with a significant effect in an area designated as subiculum. No influence of CORT was detected on (/sup 3/H)prazosin binding to alpha/sub 1/ adrenergic receptors in dorsal hippocampus. Possible mechanisms for hormone effects on neurotransmitter receptor levels are discussed.

  13. Duck cerebellum participates in regulation of food intake via the neurotransmitters serotonin and neuropeptide Y.

    Science.gov (United States)

    Liu, Hua Z; Li, Xin Y; Tong, Jing J; Qiu, Zheng Y; Zhan, Han C; Sha, Jun N; Peng, Ke M

    2008-10-01

    Two important neurotransmitters, serotonin (5-hydroxytryptamine, 5-HT) and neuropeptide Y (NPY), have been confirmed to be involved in food intake regulation. To clarify whether the cerebellum participates in modulation of food intake through these two neurotransmitters, we investigated the distribution and expression levels of 5-HT and NPY in cerebellum of the duck. Our results showed that 5-HT and NPY were distributed only at the Purkinje cell layer of the duck cerebellum. Moreover, the expression level of 5-HT in fasted (4 h) and tryptophan (100-200 mg/kg)-treated ducks was significantly higher than that in control animals (Pfood intake respectively increased and decreased cerebellar 5-HT and NPY in the duck.

  14. New Trends and Perspectives in the Evolution of Neurotransmitters in Microbial, Plant, and Animal Cells.

    Science.gov (United States)

    Roshchina, Victoria V

    2016-01-01

    The evolutionary perspective on the universal roles of compounds known as neurotransmitters may help in the analysis of relations between all organisms in biocenosis-from microorganisms to plant and animals. This phenomenon, significant for chemosignaling and cellular endocrinology, has been important in human health and the ability to cause disease or immunity, because the "living environment" influences every organism in a biocenosis relationship (microorganism-microorganism, microorganism-plant, microorganism-animal, plant-animal, plant-plant and animal-animal). Non-nervous functions of neurotransmitters (rather "biomediators" on a cellular level) are considered in this review and ample consideration is given to similarities and differences that unite, as well as distinguish, taxonomical kingdoms.

  15. Voltammetric characterization of the effect of monoamine uptake inhibitors and releasers on dopamine and serotonin uptake in mouse caudate-putamen and substantia nigra slices

    OpenAIRE

    John, Carrie E.; Jones, Sara R

    2007-01-01

    Fast scan cyclic voltammetry is an electrochemical technique used to measure dynamics of transporter-mediated monoamine uptake in real time and provides a tool to evaluate the detailed effects of monoamine uptake inhibitors and releasers on dopamine and serotonin transporter function. We measured the effects of cocaine, methylphenidate, 2β-propanoyl–3β-(4tolyl) tropane (PTT), fluoxetine, amphetamine, methamphetamine, 3,4-methylenedioxymethamphetamine (MDMA), phentermine and fenfluramine on do...

  16. Aspects of astrocyte energy metabolism, amino acid neurotransmitter homoeostasis and metabolic compartmentation

    DEFF Research Database (Denmark)

    Kreft, Marko; Bak, Lasse Kristoffer; Waagepetersen, Helle S

    2012-01-01

    Astrocytes are key players in brain function; they are intimately involved in neuronal signalling processes and their metabolism is tightly coupled to that of neurons. In the present review, we will be concerned with a discussion of aspects of astrocyte metabolism, including energy-generating pat......-generating pathways and amino acid homoeostasis. A discussion of the impact that uptake of neurotransmitter glutamate may have on these pathways is included along with a section on metabolic compartmentation....

  17. The dependence of neuronal encoding efficiency on Hebbian plasticity and homeostatic regulation of neurotransmitter release

    Directory of Open Access Journals (Sweden)

    Faramarz eFaghihi

    2015-04-01

    Full Text Available Synapses act as information filters by different molecular mechanisms including retrograde messenger that affect neuronal spiking activity. One of the well-known effects of retrograde messenger in presynaptic neurons is a change of the probability of neurotransmitter release. Hebbian learning describe a strengthening of a synapse between a presynaptic input onto a postsynaptic neuron when both pre- and postsynaptic neurons are coactive. In this work, a theory of homeostatic regulation of neurotransmitter release by retrograde messenger and Hebbian plasticity in neuronal encoding is presented. Encoding efficiency was measured for different synaptic conditions. In order to gain high encoding efficiency, the spiking pattern of a neuron should be dependent on the intensity of the input and show low levels of noise. In this work, we represent spiking trains as zeros and ones (corresponding to non-spike or spike in a time bin, respectively as words with length equal to three. Then the frequency of each word (here eight words is measured using spiking trains. These frequencies are used to measure neuronal efficiency in different conditions and for different parameter values. Results show that neurons that have synapses acting as band-pass filters show the highest efficiency to encode their input when both Hebbian mechanism and homeostatic regulation of neurotransmitter release exist in synapses. Specifically, the integration of homeostatic regulation of feedback inhibition with Hebbian mechanism and homeostatic regulation of neurotransmitter release in the synapses leads to even higher efficiency when high stimulus intensity is presented to the neurons. However, neurons with synapses acting as high-pass filters show no remarkable increase in encoding efficiency for all simulated synaptic plasticity mechanisms.

  18. Oxytocin-Induced Changes in Monoamine Level in Symmetric Brain Structures of Isolated Aggressive C57Bl/6 Mice.

    Science.gov (United States)

    Karpova, I V; Mikheev, V V; Marysheva, V V; Bychkov, E R; Proshin, S N

    2016-03-01

    Changes in activity of monoaminergic systems of the left and right brain hemispheres after administration of saline and oxytocin were studied in male C57Bl/6 mice subjected to social isolation. The concentrations of dopamine, norepinephrine, serotonin, and their metabolites dihydroxyphenylacetic, homovanillic, and 5-hydroxyindoleacetic acids were measured in the cerebral cortex, hippocampus, olfactory tubercle, and striatum of the left and right brain hemispheres by HPLC. In isolated aggressive males treated intranasally with saline, the content of serotonin and 5-hydroxyindoleacetic acid was significantly higher in the right hippocampus. Oxytocin reduces aggression caused by long-term social isolation, but has no absolute ability to suppress this type of behavior. Oxytocin reduced dopamine content in the left cortex and serotonin content in the right hippocampus and left striatum. Furthermore, oxytocin evened the revealed asymmetry in serotonin and 5-hydroxyindoleacetic acid concentrations in the hippocampus. At the same time, asymmetry in dopamine concentration appeared in the cortex with predominance of this transmitter in the right hemisphere. The data are discussed in the context of lateralization of neurotransmitter systems responsible for intraspecific aggression caused by long-term social isolation.

  19. Effect of paroxetine combined with climen on hormone levels and neurotransmitters in patients with perimenopausal depression

    Institute of Scientific and Technical Information of China (English)

    Wei-Ling Huang

    2016-01-01

    Objective:To analyze the effect of paroxetine combined with climen on hormone levels and neurotransmitters in patients with perimenopausal depression. Methods:A total of 96 cases of perimenopausal women who met the diagnosis of depression and were treated in our hospital from July 2012 to March 2015 were selected as research subjects and randomly divided into observation group and control group, each group with 48 cases. Control group received paroxetine therapy alone, observation group received paroxetine combined with climen therapy, serum hormone and neurotransmitter levels of two groups were compared, and severity of menopause and depression was detected after treatment. Results:E2 level of observation group after treatment was higher than that of control group, and levels of FSH and LH were lower than those of control group;serum NE, 5-HT, DA, Glu and Asp values of observation group after treatment were higher than those of control group, and values of GABA and Gly were lower than those of control group;KI, MRS and HAMD scores of observation group after treatment were lower than those of control group. Conclusion:Paroxetine combined with climen therapy for patients with perimenopausal depression can effectively optimize the levels of hormones and neurotransmitters in patients and reduce the symptom severity of menopause and depression.

  20. [Single and combining effects of Calculus Bovis and zolpidem on inhibitive neurotransmitter of rat striatum corpora].

    Science.gov (United States)

    Liu, Ping; He, Xinrong; Guo, Mei

    2010-04-01

    To investigate the correlation effects between single or combined administration of Calculus Bovis or zolpidem and changes of inhibitive neurotransmitter in rat striatum corpora. Sampling from rat striatum corpora was carried out through microdialysis. The content of two inhibitive neurotransmitters in rat corpus striatum- glycine (Gly) and gama aminobutyric acid (GABA), was determined by HPLC, which involved pre-column derivation with orthophthaladehyde, reversed-phase gradient elution and fluorescence detection. GABA content of rat striatum corpora in Calculus Bovis group was significantly increased compared with saline group (P Calculus Boris plus zolpidem group were increased largely compared with saline group as well (P Calculus Bovis group was higher than combination group (P Calculus Bovis or zolpidem group was markedly increased compared with saline group or combination group (P Calculus Bovis group, zolpidem group and combination group. The magnitude of increase was lower in combination group than in Calculus Bovis group and Zolpidem group, suggesting that Calculus Bovis promoted encephalon inhibition is more powerful than zolpidem. The increase in two inhibitive neurotransmitters did not show reinforcing effect in combination group, suggesting that Calculus Bovis and zolpidem may compete the same receptors. Therefore, combination of Calculus Bovis containing drugs and zolpidem has no clinical significance. Calculus Bovis shouldn't as an aperture-opening drugs be used for resuscitation therapy.

  1. Excitatory and inhibitory neurotransmitters in the generation and degeneration of hippocampal neuroarchitecture.

    Science.gov (United States)

    Mattson, M P; Kater, S B

    1989-01-30

    The possibility that excitatory and inhibitory inputs to neurons can affect the generation and degeneration of neuroarchitecture was examined in hippocampal pyramidal neurons in isolated cell culture. Dendritic outgrowth and cell survival were directly monitored in neurons exposed to: the excitatory neurotransmitter glutamate, the inhibitory transmitter GABA, anticonvulsants or combinations of these agents. Glutamate caused a graded series of changes in pyramidal neuron cytoarchitecture: a selective inhibition in dendritic outgrowth and dendritic pruning was observed with subtoxic levels of glutamate while cell death was induced by higher levels. Low levels of GABA alone or in combination with diazepam, carbamazepine, phenobarbital or phenytoin were without effect on dendrite outgrowth while higher levels caused moderate reductions in outgrowth. Neither GABA nor the anticonvulsants affected cell survival. GABA plus diazepam, phenobarbital, carbamazepine and phenytoin each significantly reduced the dendritic regression and cell death normally caused by glutamate. Elevation of extracellular K+ to 50 mM caused dendritic regression and 100 mM K+ caused cell death; these effects were greatly reduced by GABA and anticonvulsants. The calcium channel blocker Co2+ prevented the dendritic regression and cell death caused by both glutamate and K+ indicating that calcium influx was required for the neuroarchitectural responses. Taken together, these results demonstrate that neurotransmitters and neuromodulatory drugs can have direct and interactive effects on both neurite outgrowth and cell survival. Such neurotransmitter actions may play roles in both the formation and degeneration of the neuronal circuits in which they participate in information coding.

  2. The Molecular Basis of Memory. Part 3: Tagging with emotive neurotransmitters.

    Directory of Open Access Journals (Sweden)

    Gerard eMarx

    2014-04-01

    Full Text Available Many neurons of all animals that exhibit memory (snails, worms, flies, vertebrae present arborized shapes with many varicosities and boutons. These neurons, release neurotransmitters and contain ionotropic receptors that produce and sense electrical signals (ephaptic transmission. The extended shapes maximize neural contact with the surrounding neutrix (neural extracellular matrix (nECM+ diffusible (neurometals and neurotransmitters as well as with other neurons. We propose a tripartite mechanism of animal memory based on the dynamic interactions of splayed neurons with the neutrix. Their interactions form cognitive units of information (cuinfo, metal-centered complexes within the nECM around the neuron. Emotive content is provided by NTs, which embody molecular links between physiologic (body responses and psychic feelings. We propose that neurotransmitters form mixed complexes with cuinfo used for tagging emotive memory.Thus, NTs provide encoding option not available to a Turing, binary-based, device.The neurons employ combinatorially diverse options, with > 10 NMs and > 90 NTs for encoding (flavoring cuinfo with emotive tags. The neural network efficiently encodes, decodes and consolidates related (entangled sets of cuinfo into a coherent pattern, the basis for emotionally imbued memory, critical for determining a behavioral choice aimed at survival. The tripartite mechanism with tagging of NTs permits of a causal connection between physiology and psychology.

  3. Detection of amino acid neurotransmitters by surface enhanced Raman scattering and hollow core photonic crystal fiber

    Science.gov (United States)

    Tiwari, Vidhu S.; Khetani, Altaf; Monfared, Ali Momenpour T.; Smith, Brett; Anis, Hanan; Trudeau, Vance L.

    2012-03-01

    The present work explores the feasibility of using surface enhanced Raman scattering (SERS) for detecting the neurotransmitters such as glutamate (GLU) and gamma-amino butyric acid (GABA). These amino acid neurotransmitters that respectively mediate fast excitatory and inhibitory neurotransmission in the brain, are important for neuroendocrine control, and upsets in their synthesis are also linked to epilepsy. Our SERS-based detection scheme enabled the detection of low amounts of GLU (10-7 M) and GABA (10-4 M). It may complement existing techniques for characterizing such kinds of neurotransmitters that include high-performance liquid chromatography (HPLC) or mass spectrography (MS). This is mainly because SERS has other advantages such as ease of sample preparation, molecular specificity and sensitivity, thus making it potentially applicable to characterization of experimental brain extracts or clinical diagnostic samples of cerebrospinal fluid and saliva. Using hollow core photonic crystal fiber (HC-PCF) further enhanced the Raman signal relative to that in a standard cuvette providing sensitive detection of GLU and GABA in micro-litre volume of aqueous solutions.

  4. A cellular and regulatory map of the cholinergic nervous system of C. elegans.

    Science.gov (United States)

    Pereira, Laura; Kratsios, Paschalis; Serrano-Saiz, Esther; Sheftel, Hila; Mayo, Avi E; Hall, David H; White, John G; LeBoeuf, Brigitte; Garcia, L Rene; Alon, Uri; Hobert, Oliver

    2015-12-25

    Nervous system maps are of critical importance for understanding how nervous systems develop and function. We systematically map here all cholinergic neuron types in the male and hermaphrodite C. elegans nervous system. We find that acetylcholine (ACh) is the most broadly used neurotransmitter and we analyze its usage relative to other neurotransmitters within the context of the entire connectome and within specific network motifs embedded in the connectome. We reveal several dynamic aspects of cholinergic neurotransmitter identity, including a sexually dimorphic glutamatergic to cholinergic neurotransmitter switch in a sex-shared interneuron. An expression pattern analysis of ACh-gated anion channels furthermore suggests that ACh may also operate very broadly as an inhibitory neurotransmitter. As a first application of this comprehensive neurotransmitter map, we identify transcriptional regulatory mechanisms that control cholinergic neurotransmitter identity and cholinergic circuit assembly.

  5. Effects of long-term exposure of 3,4-methylenedioxymethamphetamine (MDMA; "ecstasy") on neuronal transmitter transport, brain immuno-regulatory systems and progression of experimental periodontitis in rats.

    Science.gov (United States)

    Breivik, Torbjørn; Bogen, Inger Lise; Haug, Kristin Huse; Fonnum, Frode; Opstad, Per-Kristian; Eide, Dag Marcus; Myhre, Oddvar

    2014-06-01

    The present study was designed to investigate the effects of long-term exposure (4 weeks) to the widely used narcotic drug and putative neurotoxicant 3,4-methylenedioxymetamphetamine (MDMA; "ecstasy") on neuronal transmitter transport and progression of experimental periodontitis in male Wistar rats. The rats were exposed to MDMA (10mg/kg/day i.p.) or saline five days a week for four consecutive weeks. Exposure to MDMA induced a significant reduction in the synaptosomal reuptake of serotonin, while the uptake of dopamine was significantly increased 24h after the last injection of MDMA. In contrast, the synaptosomal uptake of noradrenaline and the vesicular uptake through the vesicular monoamine transporter 2 were not affected. In the experiments of periodontitis development, ligature-induced periodontitis was induced three days prior to MDMA administration. Compared to controls, MDMA-treated rats developed significantly more periodontitis. In conclusion, our results show that long-term exposure to MDMA affects the serotonergic and dopaminergic transport systems in the rat brain and increased the susceptibility to the psychosomatic ailment periodontitis following disturbances of brain immune-regulatory systems. These results are interesting with respect to recent research showing that changes in neurotransmitter signalling may alter the reactivity of brain-controlled immunoregulatory systems controlling pathogenic microorganisms colonizing mucosal surfaces.

  6. [Changes in the monoamine content in different parts of hypothalamus depending on the stages of the estrous cycle].

    Science.gov (United States)

    Babichev, V N; Adamskaia, E I

    1976-01-01

    Fluorimetric determination of monoamines in various regions of the hypothalamus and at different stages of the estral cycle in rats showed that the serotonin, noradrenaline, and particularly dophamine content changed both in the course of the cycle and at different time (10, 15 and 18 hours) of the same stage of the cycle. Dophamine concentration in the arcuate area--the centre of the tonic activity--reached its maximum at 18 hours of the diestrus-2 (D2) and fell to the minimum at 10 hours of the proestrus (P). Noradrenaline level in the preoptic area increased at 18 hours of the D2 and fell at 10 hours of the P. It is supposed that in the hypothalamic regulation of the estral cycle at least two monoamines (dopamine and noradrenaline) took part; the trigger role belongs to noradrenaline of the preoptic area (the cyclic centre).

  7. The role of the monoamine oxidase A gene in moderating the response to adversity and associated antisocial behavior: a review

    Directory of Open Access Journals (Sweden)

    Buades-Rotger M

    2014-07-01

    Full Text Available Macià Buades-Rotger,1,2 David Gallardo-Pujol1,3 1Department of Personality, Faculty of Psychology, University of Barcelona, Barcelona, Spain; 2Department of Neurology, University of Lübeck, Lübeck, Germany; 3Institute for Brain, Cognition and Behavior (IR3C, University of Barcelona, Barcelona, Spain Abstract: Hereditary factors are increasingly attracting the interest of behavioral scientists and practitioners. Our aim in the present article is to introduce some state-of-the-art topics in behavioral genetics, as well as selected findings in the field, in order to illustrate how genetic makeup can modulate the impact of environmental factors. We focus on the most-studied polymorphism to date for antisocial responses to adversity: the monoamine oxidase A gene. Advances, caveats, and promises of current research are reviewed. We also discuss implications for the use of genetic information in applied settings. Keywords: behavioral genetics, antisocial behaviors, monoamine oxidase A

  8. Vascular dysfunction in Chronic Mild Stress (CMS) induced depression model in rats: monoamine homeostasis and endothelial dysfunction

    DEFF Research Database (Denmark)

    Bouzinova, Elena; Wiborg, Ove; Aalkjær, Christian

    -dependent relaxation and endothelial NO synthase (eNOS) were increased in arteries from anhedonic rats. Inhibition of cyclooxygenase (COX) activity revealed increased COX-2-dependent relaxation in anhedonic group. In contrast, eNOS- and COXindependent relaxation to acetylcholine (EDH-like response) was significantly...... decreased cardiac output and unchanged blood pressure, suggesting increased total peripheral resistance. Small mesenteric and femoral arteries from CMS and non-stressed rats responded similarly to noradrenaline (NA) under control conditions but inhibition of neuronal reuptake with cocaine increased NA...... sensitivity stronger in anhedonic than in resilient and non-stressed groups. In contrast, corticosterone-sensitive extra-neuronal monoamine uptake was diminished in rats exposed to CMS. These changes in monoamine homeostasis were associated with upregulation neuronal NA transporter and reduced expression...

  9. Vascular dysfunction in Chronic Mild Stress (CMS) induced depression model in rats: monoamine homeostasis and endothelial dysfunction

    DEFF Research Database (Denmark)

    Bouzinova, Elena; Wiborg, Ove; Aalkjær, Christian;

    Major depression and cardiovascular diseases have strong co-morbidity but the reason for this is unknown. In CMS model of depression only some rats develop depression-like symptoms (i.e. anhedonia, measured by sucrose intake) while others are resilient to 8 weeks of CMS. Anhedonic rats have...... decreased cardiac output and unchanged blood pressure, suggesting increased total peripheral resistance. Small mesenteric and femoral arteries from CMS and non-stressed rats responded similarly to noradrenaline (NA) under control conditions but inhibition of neuronal reuptake with cocaine increased NA...... sensitivity stronger in anhedonic than in resilient and non-stressed groups. In contrast, corticosterone-sensitive extra-neuronal monoamine uptake was diminished in rats exposed to CMS. These changes in monoamine homeostasis were associated with upregulation neuronal NA transporter and reduced expression...

  10. Chemical stimulants of leaf-trenching by cabbage loopers: natural products, neurotransmitters, insecticides, and drugs.

    Science.gov (United States)

    Dussourd, David E

    2003-09-01

    Larvae of the cabbage looper, Trichoplusia ni (Lepidoptera: Noctuidae), often transect leaves with a narrow trench before eating the distal section. The trench reduces larval exposure to exudates, such as latex, during feeding. Plant species that do not emit exudate, such as Plantago lanceolata, are not trenched. However, if exudate is applied to a looper's mouth during feeding on P. lanceolata, the larva will often stop and cut a trench. Dissolved chemicals can be similarly applied and tested for effectiveness at triggering trenching. With this assay, I have documented that lactucin from lettuce latex (Lactuca sativa), myristicin from parsley oil (Petroselinum crispum), and lobeline from cardinal flower (Lobelia cardinalis) elicit trenching. These compounds are the first trenching stimulants reported. Several other constituents of lettuce and parsley, including some phenylpropanoids, monoterpenes, and furanocoumarins had little or no activity. Cucurbitacin E glycoside found in cucurbits, another plant family trenched by cabbage loopers, also was inactive. Lactucin, myristicin, and lobeline all affect the nervous system of mammals, with lobeline acting specifically as an antagonist of nicotinic acetylcholine receptors. To determine if cabbage loopers respond selectively to compounds active at acetylcholine synapses, I tested several neurotransmitters, insecticides, and drugs with known neurological activity, many of which triggered trenching. Active compounds included dopamine, serotonin, the insecticide imidacloprid, and various drugs such as ipratropium, apomorphine, buspirone, and metoclopramide. These results document that noxious plant chemicals trigger trenching, that loopers respond to different trenching stimulants in different plants, that diverse neuroactive chemicals elicit the behavior, and that feeding deterrents are not all trenching stimulants. The trenching assay offers a novel approach for identifying defensive plant compounds with potential uses

  11. Lower Monoamine Oxidase-A Total Distribution Volume in Impulsive and Violent Male Offenders with Antisocial Personality Disorder and High Psychopathic Traits: An [(11)C] Harmine Positron Emission Tomography Study.

    Science.gov (United States)

    Kolla, Nathan J; Matthews, Brittany; Wilson, Alan A; Houle, Sylvain; Bagby, R Michael; Links, Paul; Simpson, Alexander I; Hussain, Amina; Meyer, Jeffrey H

    2015-10-01

    Antisocial personality disorder (ASPD) often presents with highly impulsive, violent behavior, and pathological changes in the orbitofrontal cortex (OFC) and ventral striatum (VS) are implicated. Several compelling reasons support a relationship between low monoamine oxidase-A (MAO-A), an enzyme that regulates neurotransmitters, and ASPD. These include MAO-A knockout models in rodents evidencing impulsive aggression and positron emission tomography (PET) studies of healthy subjects reporting associations between low brain MAO-A levels and greater impulsivity or aggression. However, a fundamental gap in the literature is that it is unknown whether brain MAO-A levels are low in more severe, clinical disorders of impulsivity, such as ASPD. To address this issue, we applied [(11)C] harmine PET to measure MAO-A total distribution volume (MAO-A VT), an index of MAO-A density, in 18 male ASPD participants and 18 age- and sex-matched controls. OFC and VS MAO-A VT were lower in ASPD compared with controls (multivariate analysis of variance (MANOVA): F2,33=6.8, P=0.003; OFC and VS MAO-A VT each lower by 19%). Similar effects were observed in other brain regions: prefrontal cortex, anterior cingulate cortex, dorsal putamen, thalamus, hippocampus, and midbrain (MANOVA: F7,28=2.7, P=0.029). In ASPD, VS MAO-A VT was consistently negatively correlated with self-report and behavioral measures of impulsivity (r=-0.50 to -0.52, all P-values<0.05). This study is the first to demonstrate lower brain MAO-A levels in ASPD. Our results support an important extension of preclinical models of impulsive aggression into a human disorder marked by pathological aggression and impulsivity.

  12. Lower Monoamine Oxidase-A Total Distribution Volume in Impulsive and Violent Male Offenders with Antisocial Personality Disorder and High Psychopathic Traits: An [11C] Harmine Positron Emission Tomography Study

    Science.gov (United States)

    Kolla, Nathan J; Matthews, Brittany; Wilson, Alan A; Houle, Sylvain; Michael Bagby, R; Links, Paul; Simpson, Alexander I; Hussain, Amina; Meyer, Jeffrey H

    2015-01-01

    Antisocial personality disorder (ASPD) often presents with highly impulsive, violent behavior, and pathological changes in the orbitofrontal cortex (OFC) and ventral striatum (VS) are implicated. Several compelling reasons support a relationship between low monoamine oxidase-A (MAO-A), an enzyme that regulates neurotransmitters, and ASPD. These include MAO-A knockout models in rodents evidencing impulsive aggression and positron emission tomography (PET) studies of healthy subjects reporting associations between low brain MAO-A levels and greater impulsivity or aggression. However, a fundamental gap in the literature is that it is unknown whether brain MAO-A levels are low in more severe, clinical disorders of impulsivity, such as ASPD. To address this issue, we applied [11C] harmine PET to measure MAO-A total distribution volume (MAO-A VT), an index of MAO-A density, in 18 male ASPD participants and 18 age- and sex-matched controls. OFC and VS MAO-A VT were lower in ASPD compared with controls (multivariate analysis of variance (MANOVA): F2,33=6.8, P=0.003; OFC and VS MAO-A VT each lower by 19%). Similar effects were observed in other brain regions: prefrontal cortex, anterior cingulate cortex, dorsal putamen, thalamus, hippocampus, and midbrain (MANOVA: F7,28=2.7, P=0.029). In ASPD, VS MAO-A VT was consistently negatively correlated with self-report and behavioral measures of impulsivity (r=−0.50 to −0.52, all P-values<0.05). This study is the first to demonstrate lower brain MAO-A levels in ASPD. Our results support an important extension of preclinical models of impulsive aggression into a human disorder marked by pathological aggression and impulsivity. PMID:26081301

  13. High temporal resolution for in vivo monitoring of neurotransmitters in awake epileptic rats using brain microdialysis and capillary electrophoresis with laser-induced fluorescence detection.

    Science.gov (United States)

    Parrot, Sandrine; Sauvinet, Valérie; Riban, Véronique; Depaulis, Antoine; Renaud, Bernard; Denoroy, Luc

    2004-12-30

    A method for high temporal resolution monitoring of five neurotransmitters, dopamine (DA), noradrenaline (NA), gamma-aminobutyric acid (GABA), glutamate (Glu), l-aspartate (L-Asp), in freely-moving rats using microdialysis and capillary electrophoresis with laser-induced fluorescence detection (CE-LIFD) was developed. An on-line device, including microdialysis and derivatization with naphthalene-2,3-dicarboxaldehyde, mixes the dialysate with derivatization reagents directly in the collection tube, i.e. with no reactor. Thereafter, collected derivatized samples are analyzed off-line with an automated CE system coupled to a LIFD using a 442 nm excitation. The sampling time was limited by the minimal volume required for the analysis by the automated CE system used: neurotransmitters could be determined in 667 nl dialysates (940 nl after derivatization), i.e. in samples collected every 20 s with a flow rate of 2 microl/min. The detection limits at the dialysis probe were 3 x 10(-9), 1 x 10(-9), 1.9 x 10(-8), 4.2 x 10(-7), 2.1 x 10(-7) mol/l for DA, NA, GABA, Glu and L-Asp, respectively. The protocol was validated using in vitro/in vivo tests and the performances--repeatability, linearity, characteristics of the probes--were determined. Finally, the high temporal resolution allowed the simultaneous monitoring of these neurotransmitters in rats with genetic absence epilepsy and revealed, for the first time, increases in GABA concentrations concomitantly with the seizures, detected when our new microdialysis method was combined to electroencephalographic recordings.

  14. Environment- and activity-dependent dopamine neurotransmitter plasticity in the adult substantia nigra.

    Science.gov (United States)

    Aumann, Tim D

    2016-04-01

    The ability of neurons to change the amount or type of neurotransmitter they use, or 'neurotransmitter plasticity', is an emerging new form of adult brain plasticity. For example, it has recently been shown that neurons in the adult rat hypothalamus up- or down-regulate dopamine (DA) neurotransmission in response to the amount of light the animal receives (photoperiod), and that this in turn affects anxiety- and depressive-like behaviors (Dulcis et al., 2013). In this Chapter I consolidate recent evidence from my laboratory suggesting neurons in the adult mouse substantia nigra pars compacta (SNc) also undergo DA neurotransmitter plasticity in response to persistent changes in their electrical activity, including that driven by the mouse's environment or behavior. Specifically, we have shown that the amounts of tyrosine hydroxylase (TH, the rate-limiting enzyme in DA synthesis) gene promoter activity, TH mRNA and TH protein in SNc neurons increases or decreases after ∼20h of altered electrical activity. Also, infusion of ion-channel agonists or antagonists into the midbrain for 2 weeks results in ∼10% (∼500 neurons) more or fewer TH immunoreactive (TH+) SNc neurons, with no change in the total number of SNc neurons (TH+ and TH-). Targeting ion-channels mediating cell-autonomous pacemaker activity in, or synaptic input and afferent pathways to, SNc neurons are equally effective in this regard. In addition, exposing mice to different environments (sex pairing or environment enrichment) for 1-2 weeks induces ∼10% more or fewer TH+ SNc (and ventral tegmental area or VTA) neurons and this is abolished by concurrent blockade of synaptic transmission in midbrain. Although further research is required to establish SNc (and VTA) DA neurotransmitter plasticity, and to determine whether it alters brain function and behavior, it is an exciting prospect because: (1) It may play important roles in movement, motor learning, reward, motivation, memory and cognition; and (2

  15. Azure B, a metabolite of methylene blue, is a high-potency, reversible inhibitor of monoamine oxidase

    OpenAIRE

    Petzer, Anél; Harvey, Brian H; Wegener, Gregers; Petzer, Jacobus P.

    2012-01-01

    Methylene blue (MB) has been shown to act at multiple cellular and molecular targets and as a result possesses diverse medical applications. Among these is a high potency reversible inhibition of monoamine oxidase A (MAO-A) that may, at least in part, underlie its adverse effects but also its psycho- and neuromodulatory actions. MB is metabolized to yield N-demethylated products of which azure B, the monodemethyl species, is the major metabolite. Similar to MB, azure B also displa...

  16. Comparison of time-dependent effects of (+-methamphetamine or forced swim on monoamines, corticosterone, glucose, creatine, and creatinine in rats

    Directory of Open Access Journals (Sweden)

    Gudelsky Gary A

    2008-05-01

    Full Text Available Abstract Background Methamphetamine (MA use is a worldwide problem. Abusers can have cognitive deficits, monoamine reductions, and altered magnetic resonance spectroscopy findings. Animal models have been used to investigate some of these effects, however many of these experiments have not examined the impact of MA on the stress response. For example, numerous studies have demonstrated (+-MA-induced neurotoxicity and monoamine reductions, however the effects of MA on other markers that may play a role in neurotoxicity or cell energetics such as glucose, corticosterone, and/or creatine have received less attention. In this experiment, the effects of a neurotoxic regimen of (+-MA (4 doses at 2 h intervals on brain monoamines, neostriatal GFAP, plasma corticosterone, creatinine, and glucose, and brain and muscle creatine were evaluated 1, 7, 24, and 72 h after the first dose. In order to compare MA's effects with stress, animals were subjected to a forced swim test in a temporal pattern similar to MA administration [i.e., (30 min/session 4 times at 2 h intervals]. Results MA increased corticosterone from 1–72 h with a peak 1 h after the first treatment, whereas glucose was only increased 1 h post-treatment. Neostriatal and hippocampal monoamines were decreased at 7, 24, and 72 h, with a concurrent increase in GFAP at 72 h. There was no effect of MA on regional brain creatine, however plasma creatinine was increased during the first 24 h and decreased by 72 h. As with MA treatment, forced swim increased corticosterone more than MA initially. Unlike MA, forced swim reduced creatine in the cerebellum with no change in other brain regions while plasma creatinine was decreased at 1 and 7 h. Glucose in plasma was decreased at 7 h. Conclusion Both MA and forced swim increase demand on energy substrates but in different ways, and MA has persistent effects on corticosterone that are not attributable to stress alone.

  17. Neurotransmitter matters

    DEFF Research Database (Denmark)

    Gerlach, Christian

    2004-01-01

    It weighs like half a bag of flour and has more holes than a sponge, but if we look closely, we find that the brain is also a complex and vibrant part of our body, one that undergoes physical changes as we learn. Join neuroscience for a brief sojourn into the realm of memory ? a world of neurons...

  18. CSF monoamine metabolites, cholinesterases and lactate in the adult hydrocephalus syndrome (normal pressure hydrocephalus) related to CSF hydrodynamic parameters.

    Science.gov (United States)

    Malm, J; Kristensen, B; Ekstedt, J; Adolfsson, R; Wester, P

    1991-03-01

    Monoamine metabolites, cholinesterases and lactic acid in lumbar cerebrospinal fluid (CSF) were investigated on patients with the adult hydrocephalus syndrome (idiopathic normal pressure syndrome; AHS, n = 15), Alzheimer's disease (AD, n = 14), multi-infarct dementia (MID, n = 13) and controls (n = 21). Patients had clinical and CSF hydrodynamic investigations. Monoamine concentrations were determined by reversed-phase liquid chromatography, cholinesterases and lactate were determined photometrically. In the AHS patients, CSF monoamine concentrations were not significantly different compared with controls, AD or MID patients. AHS and AD patients showed a similar reduction of CSF acetylcholinesterase activity compared with controls. Positive correlations were found in concentrations of CSF homovanillic acid, CSF 5-hydroxyindoleacetic acid and CSF lactic acid versus CSF outflow conductance (that is, resistance against CSF outflow) in the AHS patients. A similar pattern was observed in a