Neurotransmitters

Distribution by Scientific Domains
Distribution within Medical Sciences

Kinds of Neurotransmitters

  • acid neurotransmitter
  • amino acid neurotransmitter
  • excitatory neurotransmitter
  • important neurotransmitter
  • inhibitory neurotransmitter
  • key neurotransmitter
  • major excitatory neurotransmitter
  • major inhibitory neurotransmitter
  • other neurotransmitter
  • various neurotransmitter

  • Terms modified by Neurotransmitters

  • neurotransmitter acetylcholine
  • neurotransmitter concentration
  • neurotransmitter dopamine
  • neurotransmitter gaba
  • neurotransmitter glutamate
  • neurotransmitter pathway
  • neurotransmitter phenotype
  • neurotransmitter receptor
  • neurotransmitter release
  • neurotransmitter serotonin
  • neurotransmitter system
  • neurotransmitter transporter

  • Selected Abstracts


    Neurotransmitter and neuromodulatory mechanisms at peripheral arterial chemoreceptors

    EXPERIMENTAL PHYSIOLOGY, Issue 6 2010
    Colin A. Nurse
    The control of breathing depends critically on sensory inputs to the central pattern generator of the brainstem, arising from peripheral arterial chemoreceptors located principally in the carotid bodies (CBs). The CB receptors, i.e. glomus or type I cells, are excited by chemical stimuli in arterial blood, particularly hypoxia, hypercapnia, acidosis and low glucose, which initiate corrective reflex cardiorespiratory and cardiovascular adjustments. Type I cells occur in clusters and are innervated by petrosal afferent fibres. Synaptic specializations (both chemical and electrical) occur between type I cells and petrosal terminals, and between neighbouring type I cells. This, together with the presence of a wide array of neurotransmitters and neuromodulators linked to both ionotropic and metabotropic receptors, allows for a complex modulation of CB sensory output. Studies in several laboratories over the last ,20 years have provided much insight into the transduction mechanisms. More recent studies, aided by the development of a co-culture model of the rat CB, have shed light on the role of neurotransmitters and neuromodulators in shaping the afferent response. This review highlights some of these developments, which have contributed to our current understanding of information processing at CB chemoreceptors. [source]


    Physiological requirement for the glutamate transporter dEAAT1 at the adult Drosophila neuromuscular junction

    DEVELOPMENTAL NEUROBIOLOGY, Issue 10 2006
    Thomas Rival
    Abstract L -Glutamate is the major excitatory neurotransmitter in the mammalian brain. Specific proteins, the Na+/K+ -dependent high affinity excitatory amino acid transporters (EAATs), are involved in the extracellular clearance and recycling of this amino acid. Type I synapses of the Drosophila neuromuscular junction (NMJ) similarly use L -glutamate as an excitatory transmitter. However, the localization and function of the only high-affinity glutamate reuptake transporter in Drosophila, dEAAT1, at the NMJ was unknown. Using a specific antibody and transgenic strains, we observed that dEAAT1 is present at the adult, but surprisingly not at embryonic and larval NMJ, suggesting a physiological maturation of the junction during metamorphosis. We found that dEAAT1 is not localized in motor neurons but in glial extensions that closely follow motor axons to the adult NMJ. Inactivation of the dEAAT1 gene by RNA interference generated viable adult flies that were able to walk but were flight-defective. Electrophysiological recordings of the thoracic dorso-lateral NMJ were performed in adult dEAAT1-deficient flies. The lack of dEAAT1 prolonged the duration of the individual responses to motor nerve stimulation and this effect was progressively increased during physiological trains of stimulations. Therefore, glutamate reuptake by glial cells is required to ensure normal activity of the Drosophila NMJ, but only in adult flies. 2006 Wiley Periodicals, Inc. J Neurobiol, 2006 [source]


    Somatostatin receptors and autoimmune-mediated diabetes

    DIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 1 2005
    Xaio-Ping Wang
    Abstract Somatostatin (SST) peptide is produced by various SST-secreting cells throughout the body and acts as a neurotransmitter or paracrine/autocrine regulator in response to ions, nutrients, peptides hormones and neurotransmitters. SST is also widely distributed in the periphery to regulate the inflammatory and immune cells in response to hormones, growth factors, cytokines and other secretive molecules. SST peptides are considered the most important physiologic regulator of the islet cell, gastrointestinal cell and immune cell functions, and the importance of SST production levels has been implicated in several diseases including diabetes. The expression of SST receptors has also been found in T lymphocytes and primary immunologic organs. Interaction of SST and its receptors is also involved in T-cell proliferation and thymocyte selection. SSTR gene-ablated mice developed diabetes with morphologic, physiologic and immunologic alterations in the endocrine pancreas. Increased levels of mononuclear cell infiltration of the islets are associated with the increased levels of antigen-presenting cells located in the islets and peripancreatic lymph nodes. Increased levels of SST were also found in antigen-presenting cells and are associated with a significant increase of CD8 expression levels on CD4+/CD8+ immature thymocytes. These findings highlight the crucial role of this neuroendocrine peptide and its receptors in regulating autoimmune functions. Copyright 2004 John Wiley & Sons, Ltd. [source]


    Peripheral sensitization in migraine,role for P2X purinergic receptors in the dura,vascular sensory pathway

    DRUG DEVELOPMENT RESEARCH, Issue 6 2007
    Ernest A. Jennings
    Abstract Peripheral sensitization is still considered a prime contributor underlying the mechanisms of migraine. Trigeminal primary afferent neurons are the first neurons in the dural nociceptive pathway, and activation results in conscious perception of pain. Peripheral sensitization can lower the activation threshold of primary afferent neurons, rendering them more excitable, allowing for increases in release of neurotransmitter from both central and peripheral terminals. Increase in neurotransmitter release from central terminals contributes to excitation of second-order neurons, while the release of peptides from peripheral terminals has been implicated in neurogenic inflammation. Adenosine 5,-triphosphate (ATP) causes pain in human studies, and depolarize sensory neurons. There is evidence of the action of ATP at many levels in the dura,vascular sensory pathway. Animal studies have shown that some P2X receptors are located in neurons innervating the dura, including the P2X3 receptor, which is most often shown to be involved in nociceptive pathways. In this article, we briefly review peripheral sensitization in relation to migraine and provide emphasis for P2X receptor involvement where it is available. Drug Dev Res 68:321,328, 2007. 2007 Wiley-Liss, Inc. [source]


    Chitosan Incorporating Cetyltrimethylammonium Bromide Modified Glassy Carbon Electrode for Simultaneous Determination of Ascorbic Acid and Dopamine

    ELECTROANALYSIS, Issue 17 2007
    Xuelian Zou
    Abstract Simultaneous determination of a neurotransmitter, dopamine (DA), and ascorbic acid (AA) is achieved at neutral pH on a chitosan incorporating cetyltrimethylammonium bromide (CTAB) modified glassy carbon (GC) electrode. Differential pulse voltammetry (DPV) technique was used to investigate the electrochemical response of DA and AA at a glassy carbon electrode modified with chitosan incorporating CTAB. An optimum 6.0,mmol L,1 of CTAB together with 0.5 wt% of chitosan was used to improve the resolution and the determination sensitivity. In 0.1,mol L,1 aqueous phosphate buffer solution of pH,6.8, the chitosan-CTAB modified electrode showed a good electrocatalytic response towards DA and AA. The anodic peak potential of DA shifted positively, while that of AA shifted negatively. Thus, the difference of the anodic peaks of DA and AA reached 0.23,V, which was enough to separate the two anodic peaks very well. The presented method herein could be applied to the direct simultaneous determination of DA and AA without prior treatment. The anodic peak currents (Ipa) of DPV are proportional to DA in the concentration range of 8,,M to 1000,,M, to that of AA 10,,M to 2000,,M, with correlation coefficients of 0.9930 and 0.9945, respectively. The linear range is much wider than previously reported. [source]


    Ketosis and brain handling of glutamate, glutamine, and GABA

    EPILEPSIA, Issue 2008
    Marc Yudkoff
    Summary We hypothesize that one mechanism of the anti-epileptic effect of the ketogenic diet is to alter brain handling of glutamate. According to this formulation, in ketotic brain astrocyte metabolism is more active, resulting in enhanced conversion of glutamate to glutamine. This allows for: (a) more efficient removal of glutamate, the most important excitatory neurotransmitter; and (b) more efficient conversion of glutamine to GABA, the major inhibitory neurotransmitter. [source]


    Dark-rearing-induced reduction of GABA and GAD and prevention of the effect by BDNF in the mouse retina

    EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 8 2006
    Eun-Jin Lee
    Abstract Gamma-aminobutyric acid (GABA) is an important retinal neurotransmitter. We studied the expression of GABA, glutamate decarboxylase 65 (GAD65) and GAD67 by immunocytochemistry and Western blot, in the retinas of control and dark-reared C57BL/6J black mice. This study asked three questions. First, is visual input necessary for the normal expression of GABA, GAD65 and GAD67? Second, can the retina recover from the effects of dark-rearing if returned to a normal light,dark cycle? Third, does BDNF prevent the influence of dark-rearing on the expression of GABA and GAD? At postnatal day 10 (P10), before eye opening, GABA immunoreactivity was present in the ganglion cell layer (GCL), in the innermost rows of the inner nuclear layer (INL) and throughout the inner plexiform layer (IPL) of control and dark-reared retinas. In P30 control retinas, GABA immunoreactivity showed similar patterns to those at P10. However, in P30 dark-reared retinas, the density of GABA-immunoreactive cells was lower in both the INL and GCL than in control retinas. In addition, visual deprivation retarded GABA immunoreactivity in the IPL. Western blot analysis showed corresponding differences in the levels of GAD65 but not of GAD67 expression between control and dark-rearing conditions. In our study, dark-rearing effects were reversed when the mice were put in normal cyclic light,dark conditions for 2 weeks. Moreover, dark-reared retinas treated with BDNF showed normal expression of both GABA and GAD65. Our data indicate that normal expression of GABA and GAD65 is dependent on visual input. Furthermore, the data suggest that BDNF controls this dependence. [source]


    Role of the GLT-1 subtype of glutamate transporter in glutamate homeostasis: the GLT-1-preferring inhibitor WAY-855 produces marginal neurotoxicity in the rat hippocampus

    EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 12 2005
    Julie V. Selkirk
    Abstract Glutamate is the major excitatory neurotransmitter in the central nervous system and is tightly regulated by cell surface transporters to avoid increases in concentration and associated neurotoxicity. Selective blockers of glutamate transporter subtypes are sparse and so knock-out animals and antisense techniques have been used to study their specific roles. Here we used WAY-855, a GLT-1-preferring blocker, to assess the role of GLT-1 in rat hippocampus. GLT-1 was the most abundant transporter in the hippocampus at the mRNA level. According to [3H]- l -glutamate uptake data, GLT-1 was responsible for approximately 80% of the GLAST-, GLT-1-, and EAAC1-mediated uptake that occurs within dissociated hippocampal tissue, yet when this transporter was preferentially blocked for 120 h with WAY-855 (100 m), no significant neurotoxicity was observed in hippocampal slices. This is in stark contrast to results obtained with TBOA, a broad-spectrum transport blocker, which, at concentrations that caused a similar inhibition of glutamate uptake (10 and 30 m), caused substantial neuronal death when exposed to the slices for 24 h or longer. Likewise, WAY-855, did not significantly exacerbate neurotoxicity associated with simulated ischemia, whereas TBOA did. Finally, intrahippocampal microinjection of WAY-855 (200 and 300 nmol) in vivo resulted in marginal damage compared with TBOA (20 and 200 nmol), which killed the majority of both CA1,4 pyramidal cells and dentate gyrus granule cells. These results indicate that selective inhibition of GLT-1 is insufficient to provoke glutamate build-up, leading to NMDA receptor-mediated neurotoxic effects, and suggest a prominent role of GLAST and/or EAAC1 in extracellular glutamate maintenance. [source]


    Stabilizing effects of extracellular ATP on synaptic efficacy and plasticity in hippocampal pyramidal neurons

    EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 4 2005
    Eduardo D. Martn
    Abstract The role of adenosine triphosphate (ATP) as a neurotransmitter and extracellular diffusible messenger has recently received considerable attention because of its possible participation in the regulation of synaptic plasticity. However, the possible contribution of extracellular ATP in maintaining and regulating synaptic efficacy during intracellular ATP depletion is understudied. We tested the effects of extracellular ATP on excitatory postsynaptic currents (EPSCs) evoked in CA1 pyramidal neurons by Schaffer collateral stimulation. In the absence of intracellular ATP, EPSC rundown was neutralized when a low concentration of ATP (1 m) was added to the extracellular solution. Adenosine and ATP analogues did not prevent the EPSC rundown. The P2 antagonists piridoxal-5,-phosphate-azophenyl 2,,4,-disulphonate (PPADS) and reactive blue-2, and the P1 adenosine receptor antagonist 8-cyclopentyltheophylline (CPT) had no detectable effects in cells depleted of ATP. However, the protective action of extracellular ATP on synaptic efficacy was blocked by extracellular application of the protein kinase inhibitors K252b and staurosporine. In contrast, K252b and staurosporine per se did not interfere with synaptic transmission in ATP loaded cells. Without intracellular ATP, bath-applied caffeine induced a transient (< 35 min) EPSC potentiation that was transformed into a persistent long-term potentiation (> 80 min) when 1 m ATP was added extracellularly. An increased probability of transmitter release paralleled the long-term potentiation induced by caffeine, suggesting that it originated presynaptically. Therefore, we conclude that extracellular ATP may operate to maintain and regulate synaptic efficacy and plasticity in conditions of abnormal intracellular ATP depletion by phosphorylation of a surface protein substrate via activation of ecto-protein kinases. [source]


    Immune-related mechanisms participating in resistance and susceptibility to glutamate toxicity

    EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 4 2002
    Hadas Schori
    Abstract Glutamate is an essential neurotransmitter in the CNS. However, at abnormally high concentrations it becomes cytotoxic. Recent studies in our laboratory showed that glutamate evokes T cell-mediated protective mechanisms. The aim of the present study was to examine the nature of the glutamate receptors and signalling pathways that participate in immune protection against glutamate toxicity. We show, using the mouse visual system, that glutamate-induced toxicity is strain dependent, not only with respect to the amount of neuronal loss it causes, but also in the pathways it activates. In strains that are genetically endowed with the ability to manifest a T cell-dependent neuroprotective response to glutamate insult, neuronal losses due to glutamate toxicity were relatively small, and treatment with NMDA-receptor antagonist worsened the outcome of exposure to glutamate. In contrast, in mice devoid of T cell-dependent endogenous protection, NMDA receptor antagonist reduced the glutamate-induced neuronal loss. In all strains, blockage of the AMPA/KA receptor was beneficial. Pharmacological (with ,2 -adrenoceptor agonist) or molecular intervention (using either mice overexpressing Bcl-2, or DAP-kinase knockout mice) protected retinal ganglion cells from glutamate toxicity but not from the toxicity of NMDA. The results suggest that glutamate-induced neuronal toxicity involves multiple glutamate receptors, the types and relative contributions of which, vary among strains. We suggest that a multifactorial protection, based on an immune mechanism independent of the specific pathway through which glutamate exerts its toxicity, is likely to be a safer, more comprehensive, and hence more effective strategy for neuroprotection. It might suggest that, because of individual differences, the pharmacological use of NMDA-antagonist for neuroprotective purposes might have an adverse effect, even if the affinity is low. [source]


    Postnatal maturation of Na+, K+, 2Cl, cotransporter expression and inhibitory synaptogenesis in the rat hippocampus: an immunocytochemical analysis

    EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 2 2002
    Serge Marty
    Abstract GABA, a major inhibitory neurotransmitter, depolarizes hippocampal pyramidal neurons during the first postnatal week. These depolarizations result from an efflux of Cl, through GABAA -gated anion channels. The outward Cl, gradient that provides the driving force for Cl, efflux might be generated and maintained by the Na+, K+, 2Cl, cotransporter (NKCC) that keeps intracellular Cl, concentration above electrochemical equilibrium. The developmental pattern of expression of the cotransporter in the hippocampus is not known. We studied the postnatal distribution pattern of NKCC in the hippocampus using a monoclonal antibody (T4) against a conserved epitope in the C-terminus of the cotransporter molecule. We also examined the temporal relationships between the developmental pattern of NKCC expression and the formation of perisomatic GABAergic synapses. This study was aimed at determining, with antivesicular inhibitory amino acid transporter (VIAAT) antibodies, whether perisomatic GABAergic synapses are formed preferentially at the time when GABA is depolarizing. During the first postnatal week, NKCC immunolabelling was restricted to cell bodies in the pyramidal cell layer and in the strata oriens and radiatum. In contrast, at postnatal day 21 (P21) and in adult animals little or no labelling occurred in cell bodies; instead, a prominent dendritic labelling appeared in both pyramidal and nonpyramidal neurons. The ultrastructural immunogold study in P21 rat hippocampi corroborated the light-microscopy results. In addition, this study revealed that a portion of the silver-intensified colloidal gold particles were located on neuronal plasmalemma, as expected for a functional cotransporter. The formation of inhibitory synapses on perikarya of the pyramidal cell layer was a late process. The density of VIAAT-immunoreactive puncta in the stratum pyramidale at P21 reached four times the P7 value in CA3, and six times the P7 value in CA1. Electron microscopy revealed that the number of synapses per neuronal perikaryal profile in the stratum pyramidale of the CA3 area at P21 was three times higher than at P7, even if a concomitant 20% increase in the area of these neuronal perikaryal profiles occurred. It is concluded that, in hippocampal pyramidal cells, there is a developmental shift in the NKCC localization from a predominantly somatic to a predominantly dendritic location. The presence of NKCC during the first postnatal week is consistent with the hypothesis that this transporter might be involved in the depolarizing effects of GABA. The depolarizing effects of GABA may not be required for the establishment of the majority of GABAergic synapses in the stratum pyramidale, because their number increases after the first postnatal week, when GABA action becomes hyperpolarizing. [source]


    Expression of c-Met in developing rat hippocampus: evidence for HGF as a neurotrophic factor for calbindin D-expressing neurons

    EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 10 2000
    Laura Korhonen
    Abstract Hepatocyte growth factor-scatter factor (HGF) is expressed in different parts of the nervous system, and has been shown to exhibit neurotrophic activity. Here we show that c-Met, the receptor for HGF, is expressed in developing rat hippocampus, with the highest levels during the first postnatal weeks. To study the function of HGF, hippocampal neurons were prepared from embryonic rats and treated with different HGF concentrations. In these cultures, HGF increased the number of neurons expressing the 28-kDa calcium-binding protein (calbindin D) in a dose-dependent manner. The effect of HGF was larger than that observed with either brain-derived neurotrophic factor (BDNF) or neurotrophin-3 (NT-3), and cotreatment of the cultures with HGF and the neurotrophins was additive with respect to calbindin D neurons. Besides affecting the number of neurons, HGF significantly increased the degree of sprouting of calbindin D-positive neurons, suggesting an influence on neuronal maturation. BDNF and NT-3 stimulated neurite outgrowth of calbindin D neurons to a much smaller degree. In contrast to calbindin D neurons, HGF did not significantly increase the number of neurons immunoreactive with the neurotransmitter ,-aminobutyric acid (GABA) in the hippocampal cultures. Immunohistochemical studies showed that c-Met-, calbindin D- and HGF-immunoreactive cells are all present in the dentate gyrus and partly colocalize within neurons. These results show that HGF acts on calbindin D-containing hippocampal neurons and increases their neurite outgrowth, suggesting that HGF plays an important role for the maturation and function of these neurons in the hippocampus. [source]


    Possible Contribution of Central Gamma-Aminobutyric Acid Receptors to Resting Vascular Tone in Freely Moving Rats

    EXPERIMENTAL PHYSIOLOGY, Issue 5 2000
    Yumi Takemoto
    Previous studies have shown that central administration of GABA (gamma-aminobutyric acid), an inhibitory neurotransmitter, preferentially reduces hindquarters and carotid vascular resistances but not renal and coeliac vascular resistances in conscious rats. This study tested the hypothesis that these preferential actions of central GABA receptors are related to differences between vessels in resting autonomic vascular tone in freely moving rats. Rats were chronically implanted with intracisternal cannulas and/or electromagnetic probes to measure regional blood flows. In response to GABA administration, the changes in vascular resistance (arterial blood pressure/regional blood flow) of the hindquarters (n = 23) and carotid (n = 12) vascular beds were significantly and negatively correlated with basal vascular resistance. No such relationship was found for the renal (n = 21), coeliac (n = 13) and superior mesenteric (n = 23) vascular beds. This finding indicates that the responsiveness to GABA of brainstem pathways controlling the hindquarters and carotid vascular beds co-varies with resting resistance in hindquarters and carotid vessels. A similar analysis was performed, correlating the ongoing vascular resistance of each vessel with its response to ganglionic blockade by chlorisondamine. In this case, a significant negative correlation was also found for the hindquarters (n = 26) and carotid (n = 15) vascular beds, but not for the coeliac (n = 17) or superior mesenteric (n = 19) vessels. Together, these findings suggest that central GABA receptors accessible from the cisterna magna preferentially affect two vascular beds which, in the freely moving rat, show resting autonomic vascular tone. [source]


    A gene duplication led to specialized ,-aminobutyrate and ,-alanine aminotransferase in yeast

    FEBS JOURNAL, Issue 7 2007
    Gorm Andersen
    In humans, ,-alanine (BAL) and the neurotransmitter ,-aminobutyrate (GABA) are transaminated by a single aminotransferase enzyme. Apparently, yeast originally also had a single enzyme, but the corresponding gene was duplicated in the Saccharomyces kluyveri lineage. SkUGA1 encodes a homologue of Saccharomyces cerevisiae GABA aminotransferase, and SkPYD4 encodes an enzyme involved in both BAL and GABA transamination. SkPYD4 and SkUGA1 as well as S. cerevisiaeUGA1 and Schizosaccharomyces pombeUGA1 were subcloned, over-expressed and purified. One discontinuous and two continuous coupled assays were used to characterize the substrate specificity and kinetic parameters of the four enzymes. It was found that the cofactor pyridoxal 5,-phosphate is needed for enzymatic activity and ,-ketoglutarate, and not pyruvate, as the amino group acceptor. SkPyd4p preferentially uses BAL as the amino group donor (Vmax/Km = 0.78 Umg,1mm,1), but can also use GABA (Vmax/Km = 0.42 Umg,1mm,1), while SkUga1p only uses GABA (Vmax/Km = 4.01 Umg,1mm,1). SpUga1p and ScUga1p transaminate only GABA and not BAL. While mammals degrade BAL and GABA with only one enzyme, but in different tissues, S. kluyveri and related yeasts have two different genes/enzymes to apparently ,distinguish' between the two reactions in a single cell. It is likely that upon duplication ,200 million years ago, a specialized Uga1p evolved into a ,novel' transaminase enzyme with broader substrate specificity. [source]


    Association of tryptophan hydroxylase gene polymorphism with depression, anxiety and comorbid depression and anxiety in a population-based sample of postpartum Taiwanese women

    GENES, BRAIN AND BEHAVIOR, Issue 6 2004
    H. S. Sun
    Depression and anxiety disorders often coexist clinically and both are known to have a genetic basis, but the mode of inheritance is too complicated to be determined so far. Serotonin is the biogenic amine neurotransmitter most commonly associated with depression and anxiety. Since tryptophan hydroxylase (TPH1) is the rate-limiting enzyme in serotonin biosynthesis, its role in the pathophysiology of these psychiatric diseases has been intensively studied. In this study, we examined whether polymorphism of the TPH1 gene is related to the etiology of major depression, anxiety and comorbid depression and anxiety. Five single nucleoside polymorphisms of the TPH1 gene were studied in a population-based sample of postpartum Taiwanese women consisting of 120 subjects with depression or/and anxiety and 86 matched normal controls. A significant difference (P = 0.0107) in genotype frequency for the T27224C polymorphism was found between the comorbid and normal groups, and risk analysis showed that the C allele conferred a strong protective effect (odds ratio = 0.27; 95% confident interval = 0.11,0.7). Three-allele haplotypes involving T27224C polymorphism were constructed and haplotype associations between particular haplotype combinations and various diseases identified. However, the associations were weak and the overall haplotype frequency profiles in all groups were similar. The results suggest that depression, anxiety, and comorbid depression and anxiety disorders may have related etiologies. In addition, this study suggests that the TPH1 gene might play a role in the pathogenesis of these closely related disorders. [source]


    Axon-glia communication evokes calcium signaling in olfactory ensheathing cells of the developing olfactory bulb

    GLIA, Issue 4 2007
    Anne Rieger
    Abstract Olfactory ensheathing cells (OECs) accompany receptor axons in the olfactory nerve and promote axonal growth into the central nervous system. The mechanisms underlying the communication between axons and OECs, however, have not been studied in detail yet. We investigated the effect of activity-dependent neuronal transmitter release on Ca2+ signaling of OECs in acute mouse olfactory bulb slices using confocal Ca2+ imaging. TTX-sensitive axonal activity upon electrical nerve stimulation triggers a rise in cytosolic Ca2+ in OECs, which can be mimicked by application of DHPG, an agonist of metabotropic glutamate receptors (mGluRs). Both stimulation- and DHPG-induced Ca2+ transients in OECs were abolished by depletion of intracellular Ca2+ stores with cyclopiazonic acid (CPA). The mGluR1 -specific antagonist CPCCOEt completely inhibited DHPG-evoked Ca2+ transients, but reduced stimulation-induced Ca2+ transients only partly, suggesting the involvement of another neurotransmitter. Application of ATP evoked CPA-sensitive Ca2+ transients in OECs, which were inhibited by the P2Y1 -specific antagonist MRS2179. Co-application of CPCCOEt and MRS2179 almost completely blocked the stimulation-induced Ca2+ transients, indicating that they were mediated by mGluR1 and P2Y1 receptors. Our results show that OECs are able to respond to olfactory nerve activity with an increase in cytosolic Ca2+ due to glutamate and ATP release. 2006 Wiley-Liss, Inc. [source]


    Plasticity of perisynaptic astroglia during synaptogenesis in the mature rat hippocampus

    GLIA, Issue 1 2007
    Mark R. Witcher
    Abstract Astroglia are integral components of synapse formation and maturation during development. Less is known about how astroglia might influence synaptogenesis in the mature brain. Preparation of mature hippocampal slices results in synapse loss followed by recuperative synaptogenesis during subsequent maintenance in vitro. Hence, this model system was used to discern whether perisynaptic astroglial processes are similarly plastic, associating more or less with recently formed synapses in mature brain slices. Perisynaptic astroglia was quantified through serial section electron microscopy in perfusion-fixed or sliced hippocampus from adult male Long-Evans rats that were 65,75 days old. Fewer synapses had perisynaptic astroglia in the recovered hippocampal slices (42.4% 3.4%) than in the intact hippocampus (62.2% 2.6%), yet synapses were larger when perisynaptic astroglia was present (0.055 0.003 ,m2) than when it was absent (0.036 0.004 ,m2) in both conditions. Importantly, the length of the synaptic perimeter surrounded by perisynaptic astroglia and the distance between neighboring synapses was not proportional to synapse size. Instead, larger synapses had longer astroglia-free perimeters where substances could escape from or enter into the synaptic clefts. Thus, smaller presumably newer synapses as well as established larger synapses have equal access to extracellular glutamate and secreted astroglial factors, which may facilitate recuperative synaptogenesis. These findings suggest that as synapses enlarge and release more neurotransmitter, they attract astroglial processes to a discrete portion of their perimeters, further enhancing synaptic efficacy without limiting the potential for cross talk with neighboring synapses in the mature rat hippocampus. 2006 Wiley-Liss, Inc. [source]


    5-hydroxytryptamine-mediated increase in glutamate uptake by the leech giant glial cell

    GLIA, Issue 8 2006
    Ingolf C. Hirth
    Abstract The clearance of synaptically released glutamate is one of the pivotal functions of glial cells. We have studied the role of 5-hydroxytryptamine (5-HT, 30 ,M), a neurotransmitter and neurohormone in the leech central nervous system with a versatile action spectrum, on the efficacy of glial glutamate uptake. The activity of the glutamate uptake carrier in the giant glial cell in isolated ganglia of Hirudo medicinalis was monitored by measuring the membrane current and the change in the intracellular Na+ concentration (Na+i) as induced by the glutamate carrier substrate D -aspartate (D -asp, 1 mM). 5-HT increased the D -asp-induced current (EC50 at 5 ,M) and rise in Na+i, an effect which was mimicked by the membrane-permeable cyclic nucleotide analogue dibutyryl-cyclic AMP (db-cAMP). The adenylyl cyclase inhibitor SQ 22,536 and the protein kinase A antagonist Rp-cAMP inhibited the effect of 5-HT. Blocking the G protein in the giant glial cell by injecting GDP-,-S suppressed the effect of 5-HT, but not the effect of db-cAMP, on the D -asp-induced current. Our results suggest that 5-HT enhances the glial uptake of glutamate via cAMP- and PKA-mediated pathway. 2006 Wiley-Liss, Inc. [source]


    Role of glial amino acid transporters in synaptic transmission and brain energetics

    GLIA, Issue 3 2004
    Pakan Marcaggi
    Abstract This article reviews how the uptake of neurotransmitter by glial amino acid transporters limits the spatial spread of transmitter to preserve the independent operation of nearby synapses, temporally shapes postsynaptic currents, and regulates the effects of tonic transmitter release. We demonstrate the importance of amino acid uptake and recycling mechanisms for preventing the loss of energetically costly neurotransmitter from the brain, and also examine the suggestion that glutamate uptake into glia plays a key role in regulating the energy production of the brain. Finally, we assess the role of glial amino acid transporters in transmitter recycling pathways. 2004 Wiley-Liss, Inc. [source]


    Evidence for Antinociceptive Activity of Botulinum Toxin Type A in Pain Management

    HEADACHE, Issue 2003
    K. Roger Aoki PhD
    The neurotoxin, botulinum toxin type A, has been used successfully, in some patients, as an analgesic for myofascial pain syndromes, migraine, and other headache types. The toxin inhibits the release of the neurotransmitter, acetylcholine, at the neuromuscular junction thereby inhibiting striated muscle contractions. In the majority of pain syndromes where botulinum toxin type A is effective, inhibiting muscle spasms is an important component of its activity. Even so, the reduction of pain often occurs before the decrease in muscle contractions suggesting that botulinum toxin type A has a more complex mechanism of action than initially hypothesized. Current data points to an antinociceptive effect of botulinum toxin type A that is separate from its neuromuscular activity. The common biochemical mechanism, however, remains the same between botulinum toxin type A's effect on the motor nerve or the sensory nerve: enzymatic blockade of neurotransmitter release. The antinociceptive effect of the toxin was reported to block substance P release using in vitro culture systems.1 The current investigation evaluated the in vivo mechanism of action for the antinociceptive action of botulinum toxin type A. In these studies, botulinum toxin type A was found to block the release of glutamate. Furthermore, Fos, a product of the immediate early gene, c- fos, expressed with neuronal stimuli was prevented upon peripheral exposure to the toxin. These findings suggest that botulinum toxin type A blocks peripheral sensitization and, indirectly, reduces central sensitization. The recent hypothesis that migraine involves both peripheral and central sensitization may help explain how botulinum toxin type A inhibits migraine pain by acting on these two pathways. Further research is needed to determine whether the antinociceptive mechanism mediated by botulinum toxin type A affects the neuronal signaling pathways that are activated during migraine. [source]


    Spatial learning results in elevated agmatine levels in the rat brain

    HIPPOCAMPUS, Issue 11 2008
    Ping Liu
    Abstract Accumulating evidence suggests that agmatine, a metabolite of L -arginine by arginine decarboxylase, is a novel neurotransmitter, and exogenous agmatine can modulate behavior functions including learning and memory. However, direct evidence of its involvement in learning and memory processes is currently lacking. This study measured agmatine levels in the hippocampus, parahippocampal region, cerebellum, and vestibular nucleus in rats that were trained to find a hidden escape platform in the water-maze task, or forced to swim in the pool with no platform presented, or kept in the holding-box, using liquid chromatography/mass spectrometry. Compared with the swimming only group and holding-box group, agmatine levels were significantly increased in the CA1 and dentate gyrus subregions of the hippocampus, the entorhinal cortex and the vestibular nucleus in the water-maze training group. These results, for the first time, demonstrate spatial learning-induced region-specific elevation in agmatine, and raise a novel issue of the involvement of agmatine in the processes of learning and memory. 2008 Wiley-Liss, Inc. [source]


    Glutamate and its role in psychiatric illness

    HUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 2 2001
    Brendan Belsham
    Abstract Glutamate, a dicarboxylic amino acid, is the most abundantly active neurotransmitter in the mammalian brain; it is also the principal excitatory neurotransmitter in the cerebral cortex. As our knowledge of this neurotransmitter deepens, it is increasingly being implicated in the pathophysiology of mental illness. This review begins by examining the physiology of glutamate and its receptors. Its role in memory, movement, perception and neuronal development is discussed. The development of the glutamate hypothesis of schizophrenia is traced, and the emerging lines of evidence for attenuated function of the N -methyl- D -aspartate receptor in schizophrenia are examined. For ease of discussion, these are divided into pharmacological, post-mortem, imaging, platelet and genetic studies. Interactions between glutamate and other neurotransmitters are discussed, as are possible mechanisms by which such altered receptor activity might result in the clinical expression of schizophrenia. The possible role of glutamate in major depression and bipolar disorder is explored. The review concludes by highlighting the importance of avoiding a reductionist approach to the pathophysiology of any mental illness. Copyright 2001 John Wiley & Sons, Ltd. [source]


    Association of serotonin transporter gene-linked polymorphic region and variable number of tandem repeat polymorphism of the serotonin transporter gene in lichen simplex chronicus patients with psychiatric status

    INTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 10 2008
    Necmettin Kirtak MD
    Background, The serotonin (5-hydroxytryptamine; 5-HT) is a key neurotransmitter in the central nervous system and a responsible mediator for the itch. Dysregulation of serotonergic pathways has been implicated in the pathogenesis of many complex neuropsychiatric diseases. Objectives, The purpose of this study was to evaluate the relationship between lichen simplex chronicus and dysfunction and serotonin transporter (5-HTT) gene polymorphism. Methods, Thirty-nine patients with lichen simplex chronicus and 61 healthy control subjects were examined. Results, The results for the patients and control subjects were not significantly different (P > 0.05) in long/long (L/L) and long/short (L/S) genotypes of 5-HTT gene-linked polymorphic region (HTTLPR) polymorphism, but short/short S/S genotype was lower in lichen simplex chronicus patients (17.9%) than in controls (42.6%). This difference was statistically significant (P = 0.028). The results for the patients and control subjects were not significantly different in 12/12, 10/12 and 10/10 genotypes of variable number of tandem repeat (VNTR) polymorphism (P > 0.05). Beck depression inventory (BDI) scores and symptom checklist-90-revised (SCL-90) psychotic subscale were overrepresented significantly in the 12/12 genotypes than 10/12 genotypes. State and Trait Anxiety Inventory tests (STAI-I and -II) point averages were not statistically significant (P > 0.05) Conclusion, S/S genotypes of HTTLPR polymorphism in the 5-HTT gene may be related to lichen simplex chronicus and that patients who have 12/12 genotypes of VNTR polymorphism may be affected psychiatrically. [source]


    Brain dopamine is associated with eating behaviors in humans

    INTERNATIONAL JOURNAL OF EATING DISORDERS, Issue 2 2003
    Nora D. Volkow
    Abstract Objective Eating behavior in humans is influenced by variables other than just hunger-satiety including cognitive restraint, emotional distress, and sensitivity to food stimuli. We investigate the role of dopamine (DA), a neurotransmitter involved with food motivation, in these variables. Methods We used the Dutch Eating Behavior Questionnaire (DEBQ) to measure Restraint, Emotionality, and Externality in 10 subjects. We correlated DEBQ scores with brain DA levels. Positron emission tomography and {11C}raclopride uptake were used to measure baseline D2 receptors (neutral stimulation) and to assess changes in extracellular DA to food stimulation (display of food). Results Restraint was correlated with DA changes with food stimulation (higher restraint, greater responsivity), emotionality was negatively correlated with baseline D2 receptors (higher emotionality, lower D2 receptors), whereas externality was not. These correlations were significant in the dorsal but not in the ventral striatum. Discussion These results provide evidence that DA in the dorsal striatum is involved with the restraint and emotionality components regulating eating behavior and that these two dimensions reflect different neurobiologic processes. 2003 by Wiley Periodicals, Inc.Int J Eat Disord 33: 136,142, 2003. [source]


    Glutamate and the glutamate receptor system: a target for drug action

    INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY, Issue S1 2003
    Stefan Bleich
    Abstract Glutamate is the most important excitatory neurotransmitter in the central nervous system. In the process, glutamate fulfills numerous physiological functions, but also plays an important role in the pathophysiology of different neurological and psychiatric diseases, especially when an imbalance in glutamatergic neurotransmission occurs. Under certain conditions, glutamate has a toxic action resulting from an activation of specific glutamate receptors, which leads to acute or chronic death of nerve cells. Such mechanisms are currently under discussion in acute neuronal death within the context of hypoxia, ischaemia and traumas, as well as in chronic neurodegenerative or neurometabolic diseases, idiopathic parkinsonian syndrome, Alzheimer's dementia and Huntington's disease. It is hoped that glutamate antagonists will lead to novel therapies for these diseases, whereby the further development of glutamate antagonists for blocking disease-specific subtypes of glutamate receptors may be of major importance in the future. Copyright 2003 John Wiley & Sons, Ltd. [source]


    Molecular regulation of postsynaptic differentiation at the neuromuscular junction

    IUBMB LIFE, Issue 11 2005
    Raghavan Madhavan
    Abstract The neuromuscular junction (NMJ) is a synapse that develops between a motor neuron and a muscle fiber. A defining feature of NMJ development in vertebrates is the re-distribution of muscle acetylcholine (ACh) receptors (AChRs) following innervation, which generates high-density AChR clusters at the postsynaptic membrane and disperses aneural AChR clusters formed in muscle before innervation. This process in vivo requires MuSK, a muscle-specific receptor tyrosine kinase that triggers AChR re-distribution when activated; rapsyn, a muscle protein that binds and clusters AChRs; agrin, a nerve-secreted heparan-sulfate proteoglycan that activates MuSK; and ACh, a neurotransmitter that stimulates muscle and also disperses aneural AChR clusters. Moreover, in cultured muscle cells, several additional muscle- and nerve-derived molecules induce, mediate or participate in AChR clustering and dispersal. In this review we discuss how regulation of AChR re-distribution by multiple factors ensures aggregation of AChRs exclusively at NMJs. IUBMB Life, 57: 719-730, 2005 [source]


    Effects of the paratemnus elongatus pseudoscorpion venom in the uptake and binding of the L -glutamate and GABA from rat cerebral cortex

    JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, Issue 1 2006
    Wagner Ferreira dos Santos
    Abstract L -Glu is the most important and widespread excitatory neurotransmitter of the vertebrates. Four types of receptors for L -glu have been described. This neurotransmitter modulates several neuronal processes, and its dysfunction causes chronic and acute diseases. L -Glu action is terminated by five distinct transporters. Antagonists for these receptors and modulators of these transporters have anticonvulsant and neuroprotective potentials, as observed with the acylpoliamines and peptides isolated from spiders, solitary and social wasp venoms. On the other hand, the major inhibitory neurotransmitter in mammalian nervous tissue is the GABA. Drugs that enhance GABA neurotransmission comprise effective approaches to protecting the brain against neuronal injury. Is this study, we demonstrate for the first time the inhibition of the [3H]L -glu binding to its specific sites in synaptosomal membranes from rat cerebral cortex, produced by 0.027 U of Paratemnus elongatus venom (EC50). The venom of P. elongatus changes Km and Vmax into the high affinity uptake of the L -glu and decreases Km and Vmax into the parameters of the GABA uptake from rat synaptosomes. This leads us to speculate on the possible presence of selective and specific compounds in this venom that act in L -glu and GABA dynamics, and therefore, that can serve as tools and new drug models for understanding these neurotransmissions. 2006 Wiley Periodicals, Inc. J Biochem Mol Toxicol 20:27,34, 2006; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20113 [source]


    The biological activity of ubiquitinated BoNT/B light chain in vitro and in human SHSY-5Y neuronal cells,

    JOURNAL OF CELLULAR BIOCHEMISTRY, Issue 3 2009
    Xuerong Shi
    Abstract BoNT/B light chain is a zinc-dependent endopeptidase. After entering its target, the neuronal cell, BoNT/B is responsible for synaptobrevin-2 (VAMP-2) cleavage. This results in reduced neurotransmitter (acetylcholine) release from synaptic vesicles, yielding muscular paralysis. Since the toxin persists in neuronal cells for an extended period, regeneration of VAMP-2 is prevented. We evaluated therapeutic targets to overcome botulinum persistence because early removal would rescue the neuronal cell. The ubiquitination/proteasome cellular pathway is responsible for removing "old" or undesirable proteins. Therefore, we assessed ubiquitination of BoNT/B light chain in vitro, and characterized the effects of ubiquitination modulating drugs, PMA (phorbol 12-myristate 13-acetate) and expoxomicin, on ubiquitination of BoNT/B light chain in neuronal cells. Both drugs altered BoNT/B light chain ubiquitination. Ubiquitination in vitro and in cells decreased the biological activity of BoNT/B light chain. These results further elucidate BoNT protein degradation pathways in intoxicated neuronal cells and mechanisms to enhance toxin removal. J. Cell. Biochem. 108: 660,667, 2009. Published 2009 Wiley-Liss, Inc. [source]


    Medullary motor neurones associated with drinking behaviour of Japanese eels

    JOURNAL OF FISH BIOLOGY, Issue 1 2003
    T. Mukuda
    A fluorescent dye, Evans blue (EB), was injected into the following seven drinking-associated muscles of the Japanese eel Anguilla japonica: the sternohyoid, third branchial, fourth branchial, opercular, pharyngeal, upper oesophageal sphincter and oesophageal body muscles. The sternohyoid muscle promotes ,ingestion', and the remaining muscles contribute to ,swallowing'. All neurones stained by EB were located ipsilaterally in the caudal medulla oblongata (MO) of the Japanese eel. Neurones projecting into the sternohyoid muscle were identified as those in the spino-occipital motor nucleus (NSO), and neurones projecting into the remaining muscles as those in the glossopharyngeal,vagal motor complex (GVC). Within the GVC, the neuronal arrangement was topological, and hence, ,swallowing' will be completed if the GVC neurones ,fire' progressively from rostral to caudal. These neurones in the NSO and GVC may use acetylcholine (ACh) as a neurotransmitter, as the EB-positive neurones in both nuclei were immunoreactive against anticholine acetyltransferase (anti-ChAT) antibody. Besides the MO, some somata in a ganglion of the vagal nerve were also stained by EB injected into the pharyngeal, the upper oesophageal sphincter and the oesophageal body muscles. The localization and the shape of the somata suggest that they are sensory neurones. These sensory neurones were not ChAT-immunoreactive. Combining these results, based on a model for ,swallowing' in mammals, a plausible model for central organization of ,drinking' in the Japanese eel is proposed, which suggests that ,drinking' in the fishes is regulated by the neuronal circuit for ,swallowing' in mammals. [source]


    Repetitive and ritualistic behaviour in children with Prader,Willi syndrome and children with autism

    JOURNAL OF INTELLECTUAL DISABILITY RESEARCH, Issue 2 2006
    N. Greaves
    Abstract Background Recent research has shown that the range of repetitive behaviour seen in individuals with Prader,Willi syndrome (PWS) extends beyond food-related behaviour. Methods The presence and intensity of repetitive, rigid and routinized behaviour in children with PWS was compared with that seen in children with another neurodevelopmental condition in which repetitive behaviour is common: children with autism. Parents completed the Childhood Routines Inventory (CRI). Results Contrary to our predictions, controlling for developmental level, children with PWS and children with autism showed similar levels of repetitive and ritualistic behaviour overall and on the two CRI factors measuring ,just right' and ,repetitive' behaviour. Indeed, the majority of the sample of parents of children with PWS endorsed most items on the CRI. However there was some specificity at the level of individual items with parents of children with PWS more frequently endorsing an item on ,collecting and storing objects' and parents of children with autism more frequently endorsing ,lining up objects', ,has a strong preference for certain foods' and ,seems aware of detail at home'. Conclusions These findings confirm the range of repetitive behaviours that form part of the behavioural phenotype of PWS, including insistence on sameness and ,just right' behaviours, and uncover a surprising overlap with those seen in children with autism. Clinical management for children with PWS should include advice and education regarding management of repetitive and rigid behaviour. Future research should investigate whether the repetitive behaviours that form part of the behavioural phenotype of both PWS and autism are associated with a common neuropsychological, neurotransmitter or genetic origin. [source]