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....... 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...

Nicotine stimulates pancreatic cancer xenografts by systemic increase in stress neurotransmitters and suppression of the inhibitory neurotransmitter gamma-aminobutyric acid.

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Al-Wadei, Hussein A N; Plummer, Howard K; Schuller, Hildegard M

2009-03-01

Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer mortality in Western countries. We have shown previously that four representative human PDAC cell lines were regulated by beta-adrenoreceptors via cyclic adenosine 3',5'-monophosphate (cAMP)-dependent signaling. In the current study, we have tested the hypothesis that nicotine stimulates the growth of PDAC xenografts in nude mice by increasing the systemic levels of the stress neurotransmitters adrenaline and noradrenaline, which are the physiological agonists for beta-adrenoreceptors and that inhibition by gamma-aminobutyric acid (GABA) of the adenylyl cyclase-dependent pathway downstream of adrenoreceptors blocks this effect. The size of xenografts from PDAC cell line Panc-1 was determined 30 days after inoculation of the cancer cells. Stress neurotransmitters in serum as well as cAMP in the cellular fraction of blood and in tumor tissue were assessed by immunoassays. Levels of GABA, its synthesizing enzymes GAD65 and GAD67 and beta-adrenergic signaling proteins in the tumor tissue were determined by western blotting. Nicotine significantly increased the systemic levels of adrenaline, noradrenaline and cAMP while increasing xenograft size and protein levels of cAMP, cyclic AMP response element-binding protein and p-extracellular signal-regulated kinase 1/2 in the tumor tissue. Nicotine additionally reduced the protein levels of both GAD isozymes and GABA in tumor tissue. Treatment with GABA abolished these responses to nicotine and blocked the development of xenografts in mice not exposed to nicotine. These findings suggest that the development and progression of PDAC is subject to significant modulation by stimulatory stress neurotransmitters and inhibitory GABA and that treatment with GABA may be useful for marker-guided cancer intervention of PDAC.

Expression Profiles of Neuropeptides, Neurotransmitters, and Their Receptors in Human Keratocytes In Vitro and In Situ.

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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

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

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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.

Neurotransmitter receptors as signaling platforms in anterior pituitary cells

Czech Academy of Sciences Publication Activity Database

Zemková, Hana; Stojilkovic, S. S.

2018-01-01

Roč. 463, C (2018), s. 49-64 ISSN 0303-7207 R&D Projects: GA ČR(CZ) GA16-12695S; GA ČR(CZ) GBP304/12/G069; GA MŠk(CZ) LQ1604; GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:67985823 Keywords : pituitary * ligand-gated receptor channels * G protein -coupled receptors * neurotransmitters * action potentials * calcium signaling * hormone secretion Subject RIV: FH - Neurology OBOR OECD: Neurosciences (including psychophysiology Impact factor: 3.754, year: 2016

Development of the mouse neuromuscular junction in the absence of regulated secretion

NARCIS (Netherlands)

Heeroma, J.H.; Plomp, J.J.; Roubos, E.W.; Verhage, M.

2003-01-01

To investigate the role of neurotransmitter secretion in the development and stabilization of synapses, the innervation of the diaphragm and intercostal muscles was studied in munc18-1 null mutant mice, which lack regulated secretion. We found that this mutant is completely devoid of both

Modulation of electrogenic transport processes in the porcine proximal colon by enteric neurotransmitters.

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Pfannkuche, H; Mauksch, A; Gäbel, G

2012-06-01

The aim of our study was to evaluate the involvement of essential pro- and antisecretory neurotransmitters in regulation of secretion in porcine proximal colon. Choline acetyltransferase (ChAT), nitric oxide synthase (NOS), vasoactive intestinal peptide (VIP), substance P (SP), somatostatin (SOM) and neuropeptide Y (NPY) were located immunohistochemically in the epithelium and subepithelial layer. Modulation of epithelial secretion was studied in Ussing chambers. Application of carbachol (CA), sodium nitroprussid (SNP), VIP and SP but not of NPY or SOM resulted in a chloride dependent increase in short circuit current (I(sc) ). I(sc) increase induced by CA, VIP or SNP was not altered by preincubation with tetrodotoxin or indomethacin. In contrast, SP-induced I(sc) increase was diminished by preincubation with tetrodotoxin, indomethacin, L-nitro-arginin-methyl-ester, and atropine but not hexamethonium. Simultaneous application of CA and VIP, or CA and SNP increased the I(sc) stronger as expected. Applying SP/CA led to a smaller increase in I(sc) as calculated. It is concluded that mainly prosecretory neurotransmitters are involved in regulation of colonic secretion. Cross-potentiations of acetylcholine and nitric oxide and acetylcholine and VIP suggest activation of different intracellular cascades. Similar intracellular pathways may be stimulated by acetylcholine and SP, thus preventing an additive effect of the transmitters. © 2011 Blackwell Verlag GmbH.

Perivascular neurotransmitters

DEFF Research Database (Denmark)

Frederiksen, Simona D; Haanes, Kristian A; Warfvinge, Karin

2018-01-01

In order to understand the nature of the relationship between cerebral blood flow (CBF) and primary headaches, we have conducted a literature review with particular emphasis on the role of perivascular neurotransmitters. Primary headaches are in general considered complex polygenic disorders...... (located outside the blood-brain barrier) are variably activated and sensitized which gives rise to vasoactive neurotransmitter release. Sympathetic, parasympathetic and sensory nerves to the cerebral vasculature are activated. During migraine attacks, altered CBF has been observed in brain regions...... such as the somatosensory cortex, brainstem and thalamus. In regulation of CBF, the individual roles of neurotransmitters are partly known, but much needs to be unraveled with respect to headache disorders....

Unconventional secretion of tissue transglutaminase involves phospholipid-dependent delivery into recycling endosomes.

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Evgeny A Zemskov

2011-04-01

Full Text Available Although endosomal compartments have been suggested to play a role in unconventional protein secretion, there is scarce experimental evidence for such involvement. Here we report that recycling endosomes are essential for externalization of cytoplasmic secretory protein tissue transglutaminase (tTG. The de novo synthesized cytoplasmic tTG does not follow the classical ER/Golgi-dependent secretion pathway, but is targeted to perinuclear recycling endosomes, and is delivered inside these vesicles prior to externalization. On its route to the cell surface tTG interacts with internalized β1 integrins inside the recycling endosomes and is secreted as a complex with recycled β1 integrins. Inactivation of recycling endosomes, blocking endosome fusion with the plasma membrane, or downregulation of Rab11 GTPase that controls outbound trafficking of perinuclear recycling endosomes, all abrogate tTG secretion. The initial recruitment of cytoplasmic tTG to recycling endosomes and subsequent externalization depend on its binding to phosphoinositides on endosomal membranes. These findings begin to unravel the unconventional mechanism of tTG secretion which utilizes the long loop of endosomal recycling pathway and indicate involvement of endosomal trafficking in non-classical protein secretion.

Detection and monitoring of neurotransmitters--a spectroscopic analysis.

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Manciu, Felicia S; Lee, Kendall H; Durrer, William G; Bennet, Kevin E

2013-01-01

We demonstrate that confocal Raman mapping spectroscopy provides rapid, detailed, and accurate neurotransmitter analysis, enabling millisecond time resolution monitoring of biochemical dynamics. As a prototypical demonstration of the power of the method, we present real-time in vitro serotonin, adenosine, and dopamine detection, and dopamine diffusion in an inhomogeneous organic gel, which was used as a substitute for neurologic tissue.  Dopamine, adenosine, and serotonin were used to prepare neurotransmitter solutions in distilled water. The solutions were applied to the surfaces of glass slides, where they interdiffused. Raman mapping was achieved by detecting nonoverlapping spectral signatures characteristic of the neurotransmitters with an alpha 300 WITec confocal Raman system, using 532 nm neodymium-doped yttrium aluminum garnet laser excitation. Every local Raman spectrum was recorded in milliseconds and complete Raman mapping in a few seconds.  Without damage, dyeing, or preferential sample preparation, confocal Raman mapping provided positive detection of each neurotransmitter, allowing association of the high-resolution spectra with specific microscale image regions. Such information is particularly important for complex, heterogeneous samples, where changes in composition can influence neurotransmission processes. We also report an estimated dopamine diffusion coefficient two orders of magnitude smaller than that calculated by the flow-injection method.  Accurate nondestructive characterization for real-time detection of neurotransmitters in inhomogeneous environments without the requirement of sample labeling is a key issue in neuroscience. Our work demonstrates the capabilities of Raman spectroscopy in biological applications, possibly providing a new tool for elucidating the mechanism and kinetics of deep brain stimulation. © 2012 International Neuromodulation Society.

Nanosensors for neurotransmitters.

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Polo, Elena; Kruss, Sebastian

2016-04-01

Neurotransmitters are an important class of messenger molecules. They govern chemical communication between cells for example in the brain. The spatiotemporal propagation of these chemical signals is a crucial part of communication between cells. Thus, the spatial aspect of neurotransmitter release is equally important as the mere time-resolved measurement of these substances. In conclusion, without tools that provide the necessary spatiotemporal resolution, chemical signaling via neurotransmitters cannot be studied in greater detail. In this review article we provide a critical overview about sensors/probes that are able to monitor neurotransmitters. Our focus are sensing concepts that provide or could in the future provide the spatiotemporal resolution that is necessary to 'image' dynamic changes of neurotransmitter concentrations around cells. These requirements set the bar for the type of sensors we discuss. The sensor must be small enough (if possible on the nanoscale) to provide the envisioned spatial resolution and it should allow parallel (spatial) detection. In this article we discuss both optical and electrochemical concepts that meet these criteria. We cover techniques that are based on fluorescent building blocks such as nanomaterials, proteins and organic dyes. Additionally, we review electrochemical array techniques and assess limitations and possible future directions.

Turning off neurotransmitters.

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Snyder, Solomon H

2006-04-07

The historic discovery that the catecholamine neurotransmitters of the sympathetic nervous system, norepinephrine and epinephrine, are inactivated through their reuptake by presynaptic nerve terminals provided new insights into neurotransmitter action and paved the way for the development of modern antidepressant drugs.

Benzodiazepine receptor and neurotransmitter studies in the brain of suicides

Energy Technology Data Exchange (ETDEWEB)

Manchon, M.; Kopp, N.; Rouzioux, J.J.; Lecestre, D.; Deluermoz, S.; Miachon, S.

1987-12-14

The characteristics of benzodiazepine binding sites were studied on frozen sections of hippocampus of 7 suicides and 5 controls subjects, using biochemical and autoradiographic techniques. /sup 3/H flunitrazepam was used as ligand, clonazepam and CL 218,872 as displacing agents. Some neurotransmitters or their derivatives were evaluated quantitatively in parallel in the hippocampal tissue by liquid chromatography. The authors observed mainly an increase in the Ki of CL 218,872 subtype I binding sites in suicides, and an increase in % of type I binding sites. Among neurotransmitters, only norepinephrine differed significantly between controls and suicides. 36 references, 3 figures, 1 table.

Benzodiazepine receptor and neurotransmitter studies in the brain of suicides

International Nuclear Information System (INIS)

Manchon, M.; Kopp, N.; Rouzioux, J.J.; Lecestre, D.; Deluermoz, S.; Miachon, S.

1987-01-01

The characteristics of benzodiazepine binding sites were studied on frozen sections of hippocampus of 7 suicides and 5 controls subjects, using biochemical and autoradiographic techniques. 3 H flunitrazepam was used as ligand, clonazepam and CL 218,872 as displacing agents. Some neurotransmitters or their derivatives were evaluated quantitatively in parallel in the hippocampal tissue by liquid chromatography. The authors observed mainly an increase in the Ki of CL 218,872 subtype I binding sites in suicides, and an increase in % of type I binding sites. Among neurotransmitters, only norepinephrine differed significantly between controls and suicides. 36 references, 3 figures, 1 table

Histaminergic regulation of prolactin secretion

DEFF Research Database (Denmark)

Knigge, U P

1990-01-01

Histamine (HA), which acts as a neurotransmitter in the central nervous system, participates in the neuroendocrine regulation of prolactin (PRL) secretion. HA has a predominant stimulatory effect which is mediated via H2-receptors following central administration and via H1-receptors following...... systemic infusion of the amine. In addition, HA seems to exert a minor inhibitory effect on PRL secretion, an effect unmasked only during blockade of the receptor mediating the stimulatory effect. Following central administration the inhibitory effect is mediated via H1-receptors, while following systemic...... administration this effect is mediated via H2-receptors. In accordance with these findings, the H2-receptor antagonist cimetidine (CIM) has an inhibitory (following central administration) or stimulatory (following systemic administration) effect on PRL secretion. However, high doses of CIM possess an additional...

Nanomaterial-based electrochemical sensing of neurological drugs and neurotransmitters

International Nuclear Information System (INIS)

Sanghavi, Bankim J.; Swami, Nathan S.; Wolfbeis, Otto S.; Hirsch, Thomas

2015-01-01

Nanomaterial-modified detection systems represent a chief driver towards the adoption of electrochemical methods, since nanomaterials enable functional tunability, ability to self-assemble, and novel electrical, optical and catalytic properties that emerge at this scale. This results in tremendous gains in terms of sensitivity, selectivity and versatility. We review the electrochemical methods and mechanisms that may be applied to the detection of neurological drugs. We focus on understanding how specific nano-sized modifiers may be applied to influence the electron transfer event to result in gains in sensitivity, selectivity and versatility of the detection system. This critical review is structured on the basis of the Anatomical Therapeutic Chemical (ATC) Classification System, specifically ATC Code N (neurotransmitters). Specific sections are dedicated to the widely used electrodes based on the carbon materials, supporting electrolytes, and on electrochemical detection paradigms for neurological drugs and neurotransmitters within the groups referred to as ATC codes N01 to N07. We finally discuss emerging trends and future challenges such as the development of strategies for simultaneous detection of multiple targets with high spatial and temporal resolutions, the integration of microfluidic strategies for selective and localized analyte pre-concentration, the real-time monitoring of neurotransmitter secretions from active cell cultures under electro- and chemotactic cues, aptamer-based biosensors, and the miniaturization of the sensing system for detection in small sample volumes and for enabling cost savings due to manufacturing scale-up. The Electronic Supporting Material (ESM) includes review articles dealing with the review topic in last 40 years, as well as key properties of the analytes, viz., pK a values, half-life of drugs and their electrochemical mechanisms. The ESM also defines analytical figures of merit of the drugs and neurotransmitters. The

Estimation of in-vivo neurotransmitter release by brain microdialysis: the issue of validity.

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Di Chiara, G.; Tanda, G.; Carboni, E.

1996-11-01

Although microdialysis is commonly understood as a method of sampling low molecular weight compounds in the extracellular compartment of tissues, this definition appears insufficient to specifically describe brain microdialysis of neurotransmitters. In fact, transmitter overflow from the brain into dialysates is critically dependent upon the composition of the perfusing Ringer. Therefore, the dialysing Ringer not only recovers the transmitter from the extracellular brain fluid but is a main determinant of its in-vivo release. Two types of brain microdialysis are distinguished: quantitative micro-dialysis and conventional microdialysis. Quantitative microdialysis provides an estimate of neurotransmitter concentrations in the extracellular fluid in contact with the probe. However, this information might poorly reflect the kinetics of neurotransmitter release in vivo. Conventional microdialysis involves perfusion at a constant rate with a transmitter-free Ringer, resulting in the formation of a steep neurotransmitter concentration gradient extending from the Ringer into the extracellular fluid. This artificial gradient might be critical for the ability of conventional microdialysis to detect and resolve phasic changes in neurotransmitter release taking place in the implanted area. On the basis of these characteristics, conventional microdialysis of neurotransmitters can be conceptualized as a model of the in-vivo release of neurotransmitters in the brain. As such, the criteria of face-validity, construct-validity and predictive-validity should be applied to select the most appropriate experimental conditions for estimating neurotransmitter release in specific brain areas in relation to behaviour.

Atrial natriuretic peptide stimulates salt secretion by shark rectal gland by releasing VIP

Energy Technology Data Exchange (ETDEWEB)

Silva, P.; Stoff, J.S.; Solomon, R.J.; Lear, S.; Kniaz, D.; Greger, R.; Epstein, F.H.

1987-01-01

Salt secretion by the isolated perfused rectal gland of the spiny dogfish shark, Squalus acanthias, is stimulated by synthetic rat atrial natriuretic peptide (ANP II) as well as extracts of shark heart, but not by 8-bromo-cyclic guanosine 5'-monophosphate. Cardiac peptides have no effect on isolated rectal gland cells or perfused tubules, suggesting that stimulation requires an intact gland. The stimulation of secretion by ANP II is eliminated by maneuvers that block neurotransmitter release. Cardiac peptides stimulate the release of vasoactive intestinal peptide (VIP), known to be present in rectal glands nerves, into the venous effluent of perfused glands in parallel with their stimulation of salt secretion, but the release of VIP induced by ANP II is prevented by perfusion with procaine. VIP was measured by radioimmunoassay. Cardiac peptides thus appear to regulate rectal gland secretion by releasing VIP from neural stores within the gland. It is possible that other physiological effects of these hormones might be explained by an action to enhanced local release of neurotransmitters.

Atrial natriuretic peptide stimulates salt secretion by shark rectal gland by releasing VIP

International Nuclear Information System (INIS)

Silva, P.; Stoff, J.S.; Solomon, R.J.; Lear, S.; Kniaz, D.; Greger, R.; Epstein, F.H.

1987-01-01

Salt secretion by the isolated perfused rectal gland of the spiny dogfish shark, Squalus acanthias, is stimulated by synthetic rat atrial natriuretic peptide (ANP II) as well as extracts of shark heart, but not by 8-bromo-cyclic guanosine 5'-monophosphate. Cardiac peptides have no effect on isolated rectal gland cells or perfused tubules, suggesting that stimulation requires an intact gland. The stimulation of secretion by ANP II is eliminated by maneuvers that block neurotransmitter release. Cardiac peptides stimulate the release of vasoactive intestinal peptide (VIP), known to be present in rectal glands nerves, into the venous effluent of perfused glands in parallel with their stimulation of salt secretion, but the release of VIP induced by ANP II is prevented by perfusion with procaine. VIP was measured by radioimmunoassay. Cardiac peptides thus appear to regulate rectal gland secretion by releasing VIP from neural stores within the gland. It is possible that other physiological effects of these hormones might be explained by an action to enhanced local release of neurotransmitters

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, and third trimesters of human pregnancy. Results support the recommendation that pregnant women should abstain from drinking—even small quantities—as effects of ethanol on neurotransmitter systems have been detected at low levels of exposure. Recent studies have elucidated new mechanisms and/or consequences of the actions of ethanol on amino acid and biogenic amine neurotransmitter systems. Alterations in these neurotransmitter systems could, in part, be responsible for many of the conditions associated with FASD, including (1) learning, memory, and attention deficits; (2) motor coordination impairments; (3) abnormal responsiveness to stress; and (4) increased susceptibility to neuropsychiatric disorders, such as substance abuse and depression, and also neurological disorders, such as epilepsy and sudden infant death syndrome. However, future research is needed to conclusively establish a causal relationship between these conditions and developmental dysfunctions in neurotransmitter systems. PMID:23580048

Neurotransmitter-Triggered Transfer of Exosomes Mediates Oligodendrocyte–Neuron Communication

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Kuo, Wen Ping; Amphornrat, Jesa; Thilemann, Sebastian; Saab, Aiman S.; Kirchhoff, Frank; Möbius, Wiebke; Goebbels, Sandra; Nave, Klaus-Armin; Schneider, Anja; Simons, Mikael; Klugmann, Matthias; Trotter, Jacqueline; Krämer-Albers, Eva-Maria

2013-01-01

Reciprocal interactions between neurons and oligodendrocytes are not only crucial for myelination, but also for long-term survival of axons. Degeneration of axons occurs in several human myelin diseases, however the molecular mechanisms of axon-glia communication maintaining axon integrity are poorly understood. Here, we describe the signal-mediated transfer of exosomes from oligodendrocytes to neurons. These endosome-derived vesicles are secreted by oligodendrocytes and carry specific protein and RNA cargo. We show that activity-dependent release of the neurotransmitter glutamate triggers oligodendroglial exosome secretion mediated by Ca2+ entry through oligodendroglial NMDA and AMPA receptors. In turn, neurons internalize the released exosomes by endocytosis. Injection of oligodendroglia-derived exosomes into the mouse brain results in functional retrieval of exosome cargo in neurons. Supply of cultured neurons with oligodendroglial exosomes improves neuronal viability under conditions of cell stress. These findings indicate that oligodendroglial exosomes participate in a novel mode of bidirectional neuron-glia communication contributing to neuronal integrity. PMID:23874151

Neurotransmitter-triggered transfer of exosomes mediates oligodendrocyte-neuron communication.

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Frühbeis, Carsten; Fröhlich, Dominik; Kuo, Wen Ping; Amphornrat, Jesa; Thilemann, Sebastian; Saab, Aiman S; Kirchhoff, Frank; Möbius, Wiebke; Goebbels, Sandra; Nave, Klaus-Armin; Schneider, Anja; Simons, Mikael; Klugmann, Matthias; Trotter, Jacqueline; Krämer-Albers, Eva-Maria

2013-07-01

Reciprocal interactions between neurons and oligodendrocytes are not only crucial for myelination, but also for long-term survival of axons. Degeneration of axons occurs in several human myelin diseases, however the molecular mechanisms of axon-glia communication maintaining axon integrity are poorly understood. Here, we describe the signal-mediated transfer of exosomes from oligodendrocytes to neurons. These endosome-derived vesicles are secreted by oligodendrocytes and carry specific protein and RNA cargo. We show that activity-dependent release of the neurotransmitter glutamate triggers oligodendroglial exosome secretion mediated by Ca²⁺ entry through oligodendroglial NMDA and AMPA receptors. In turn, neurons internalize the released exosomes by endocytosis. Injection of oligodendroglia-derived exosomes into the mouse brain results in functional retrieval of exosome cargo in neurons. Supply of cultured neurons with oligodendroglial exosomes improves neuronal viability under conditions of cell stress. These findings indicate that oligodendroglial exosomes participate in a novel mode of bidirectional neuron-glia communication contributing to neuronal integrity.

Neurotransmitter synthesis from CNS glutamine for central control of breathing

International Nuclear Information System (INIS)

Hoop, B.; Systrom, D.; Chiang, C.H.; Shih, V.E.; Kazemi, H.

1986-01-01

The maximum rate at which CNS glutamine (GLN) derived from glutamate (GLU) can be sequestered for synthesis of neurotransmitter GLU and/or γ-aminobutyric acid (GABA) has been determined in pentobarbital-anesthetized dogs. A total of 57 animals were studied under normal, hypoxic (Pa/sub O2/ greater than or equal to 20 mmHg), or hypercapnic (Pa/sub CO2/ less than or equal to 71 mm Hg) conditions. Thirteen of these were bilaterally vagotomized and carotid body denervated and studied only under normoxic or hypoxic conditions. In 5 animals cerebrospinal fluid GLN transfer rate constant k was measured using 13 N-ammonia tracer. Measured cerebral cortical (CC) and medullary (MED) GLN concentrations c are found to vary with GLU metabolic rate r according to c-C/sub m/r/(r+R), where r, the product of k and corresponding tissue GLU concentration, is assumed equal to the maximum GLN metabolic rate via pathways other than for neurotransmitter synthesis. The constants C/sub m/ and R are the predicted maximum GLN concentration and its maximum rate of sequestration for neurotransmitter synthesis, respectively. For both CNS tissue types in all animals, C/sub m/ = 20.9 +- 7.4 (SD) mmoles/kg wet wt(mM) and R = 6.2 +- 2.3 mM/min. These values are consistent with results obtained in anesthetized rats

Effect of adjuvant acupuncture therapy on serum cytokines and neurotransmitters in patients with post-stroke depression

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Wan Feng

2017-07-01

Full Text Available Objective: To study the effect of adjuvant acupuncture therapy on serum cytokines and neurotransmitters in patients with post-stroke depression. Methods: Patients with poststroke depression who were treated in Traditional Chinese Medicine Hospital of Yuyang District Yulin City between May 2014 and February 2017 were selected as the research subjects and divided into two groups by random number table, control group of patients received neurotrophy, rehabilitation exercise, antidepressant drugs and other symptomatic treatment, and the acupuncture group received auxiliary acupuncture treatment on the basis of symptomatic treatment. The serum levels of nerve cytokines, inflammatory cytokines and neurotransmitters were detected before treatment as well as 2 weeks and 4 weeks after treatment. Results: 2 weeks and 4 weeks after treatment, serum BDNF, NGF, IGF-1, FGF-2, NE, DA and 5-HT levels of both groups of patients were higher than those before treatment while HCY, IL- 1β, IL-2, sIL-2R, TNF-α levels were lower than those before treatment, and serum BDNF, NGF, IGF-1, FGF-2, NE, DA and 5-HT levels of acupuncture group were higher than those of control group while HCY, IL-1β, IL-2, sIL-2R, TNF-α levels were lower than those of control group. Conclusion: Adjuvant acupuncture therapy for post-stroke depression can increase the secretion of nerve cytokines, reduce the secretion of inflammatory cytokines and regulate the function of monoamine neurotransmitters.

Distribution of Interleukin-22-secreting Immune Cells in Conjunctival Associated Lymphoid Tissue.

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Yoon, Chang Ho; Lee, Daeseung; Jeong, Hyun Jeong; Ryu, Jin Suk; Kim, Mee Kum

2018-04-01

Interleukin (IL)-22 is a cytokine involved in epithelial cell regeneration. Currently, no research studies have analyzed the distribution of the three distinct IL-22-secreting cell populations in human or mouse conjunctiva. This study investigated the distribution of the three main populations of IL-22-secreting immune cells, αβ Th cells, γδ T cells, or innate cells (innate lymphoid cells [ILCs] or natural killer cells), in conjunctival associated lymphoid tissues (CALTs) in human and mouse models. We collected discarded cadaveric bulbar conjunctival tissue specimens after preservation of the corneo-limbal tissue for keratoplasty from four enucleated eyes of the domestic donor. The bulbar conjunctiva tissue, including the cornea from normal (n = 27) or abraded (n = 4) B6 mice, were excised and pooled in RPMI 1640 media. After the lymphoid cells were gated in forward and side scattering, the αβ Th cells, γδ T cells, or innate lymphoid cells were positively or negatively gated using anti-CD3, anti-γδ TCR, and anti-IL-22 antibodies, with a FACSCanto flow cytometer. In normal human conjunctiva, the percentage and number of cells were highest in αβ Th cells, followed by γδ T cells and CD3- γδ TCR- IL-22+ innate cells (presumed ILCs, pILCs) (Kruskal-Wallis test, p = 0.012). In normal mice keratoconjunctiva, the percentage and total number were highest in γδ T cells, followed by αβ Th cells and pILCs (Kruskal-Wallis test, p = 0.0004); in corneal abraded mice, the population of αβ Th cells and pILCs tended to increase. This study suggests that three distinctive populations of IL-22-secreting immune cells are present in CALTs of both humans and mice, and the proportions of IL-22+αβ Th cells, γδ T cells, and pILCs in CALTs in humans might be differently distributed from those in normal mice. © 2018 The Korean Ophthalmological Society.

Neurotransmitter signaling in white matter.

Science.gov (United States)

Butt, Arthur M; Fern, Robert F; Matute, Carlos

2014-11-01

White matter (WM) tracts are bundles of myelinated axons that provide for rapid communication throughout the CNS and integration in grey matter (GM). The main cells in myelinated tracts are oligodendrocytes and astrocytes, with small populations of microglia and oligodendrocyte precursor cells. The prominence of neurotransmitter signaling in WM, which largely exclude neuronal cell bodies, indicates it must have physiological functions other than neuron-to-neuron communication. A surprising aspect is the diversity of neurotransmitter signaling in WM, with evidence for glutamatergic, purinergic (ATP and adenosine), GABAergic, glycinergic, adrenergic, cholinergic, dopaminergic and serotonergic signaling, acting via a wide range of ionotropic and metabotropic receptors. Both axons and glia are potential sources of neurotransmitters and may express the respective receptors. The physiological functions of neurotransmitter signaling in WM are subject to debate, but glutamate and ATP-mediated signaling have been shown to evoke Ca(2+) signals in glia and modulate axonal conduction. Experimental findings support a model of neurotransmitters being released from axons during action potential propagation acting on glial receptors to regulate the homeostatic functions of astrocytes and myelination by oligodendrocytes. Astrocytes also release neurotransmitters, which act on axonal receptors to strengthen action potential propagation, maintaining signaling along potentially long axon tracts. The co-existence of multiple neurotransmitters in WM tracts suggests they may have diverse functions that are important for information processing. Furthermore, the neurotransmitter signaling phenomena described in WM most likely apply to myelinated axons of the cerebral cortex and GM areas, where they are doubtless important for higher cognitive function. © 2014 Wiley Periodicals, Inc.

Unconventional neurotransmitters, neurodegeneration and neuroprotection

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M. Leonelli

2009-01-01

Full Text Available Neurotransmitters are also involved in functions other than conventional signal transfer between nerve cells, such as development, plasticity, neurodegeneration, and neuroprotection. For example, there is a considerable amount of data indicating developmental roles for the glutamatergic, cholinergic, dopaminergic, GABA-ergic, and ATP/adenosine systems. In this review, we discuss the existing literature on these "new" functions of neurotransmitters in relation to some unconventional neurotransmitters, such as the endocannabinoids and nitric oxide. Data indicating both transcriptional and post-transcriptional modulation of endocannabinoid and nitrinergic systems after neural lesions are discussed in relation to the non-conventional roles of these neurotransmitters. Knowledge of the roles of neurotransmitters in brain functions other than information transfer is critical for a more complete understanding of the functional organization of the brain and to provide more opportunities for the development of therapeutical tools aimed at minimizing neuronal death.

Electrochemical Analysis of Neurotransmitters

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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.

Neurotransmitter receptor imaging

International Nuclear Information System (INIS)

Cordes, M.; Hierholzer, J.; Nikolai-Beyer, K.

1993-01-01

The importance of neuroreceptor imaging in vivo using single photon emission tomography (SPECT) and positron emission tomography (PET) has increased enormously. The principal neurotransmitters, such as dopamine, GABA/benzodiazepine, acetylcholine, and serotonin, are presented with reference to anatomical, biochemical, and physiological features. The main radioligands for SPECT and PET are introduced, and methodological characteristics of both PET and SPECT presented. Finally, the results of neurotransmitter receptor imaging obtained so far will be discussed. (orig.) [de

Altered neurotransmitter expression profile in the ganglionic bowel in Hirschsprung's disease.

Science.gov (United States)

Coyle, David; O'Donnell, Anne Marie; Gillick, John; Puri, Prem

2016-05-01

Despite having optimal pull-through (PT) surgery for Hirschsprung's disease (HSCR), many patients experience persistent bowel symptoms with no mechanical/histopathological cause. Murine models of HSCR suggest that expression of key neurotransmitters is unbalanced proximal to the aganglionic colonic segment. We aimed to investigate expression of key enteric neurotransmitters in the colon of children with HSCR. Full-length PT specimens were collected fresh from children with HSCR (n=10). Control specimens were collected at colostomy closure from children with anorectal malformation (n=8). The distributions of neuronal nitric oxide synthase (nNOS), choline acetyltransferase (ChAT), vasoactive intestinal peptide (VIP), and substance P (SP) were evaluated using immunofluorescence and confocal microscopy. Neurotransmitter quantification was with Western blot analysis. ChAT expression was high in aganglionic bowel and transition zone but reduced in ganglionic bowel in HSCR relative to controls. Conversely, nNOS expression was markedly reduced in aganglionic bowel but high in ganglionic bowel in HSCR relative to controls. VIP expression was similar in ganglionic HSCR and control colon. SP expression was similar in all tissue types. Imbalance of key excitatory and inhibitory neurotransmitters in the ganglionic bowel in HSCR may explain the basis of bowel dysmotility after an optimal pull-through operation in some patients. Copyright © 2016 Elsevier Inc. All rights reserved.

Quantitative-profiling of neurotransmitter abnormalities in the disease progression of experimental diabetic encephalopathy rat.

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Zhou, Xueyan; Zhu, Qiuxiang; Han, Xiaowen; Chen, Renguo; Liu, Yaowu; Fan, Hongbin; Yin, Xiaoxing

2015-11-01

Diabetic encephalopathy (DE) is one of the most prevalent chronic complications of diabetes mellitus (DM), with neither effective prevention nor proven therapeutic regimen. This study aims to uncover the potential dysregulation pattern of the neurotransmitters in a rat model of streptozotocin (STZ)-induced experimental DE. For that purpose, male Sprague-Dawley (SD) rats were treated with a single intraperitoneal injection of STZ. Cognitive performance was detected with the Morris water maze (MWM) test. Serum, cerebrospinal fluid (CSF), and brain tissues were collected to measure the levels of neurotransmitters. Compared with the control rats, the acetylcholine (ACh) levels in serum, CSF, hippocampus, and cortex were all significantly down-regulated as early as 6 weeks in the STZ treatment group. In contrast, the glutamate (Glu) levels were decreased in CSF and the hippocampus, but unaffected in the serum and cortex of STZ-treated rats. As for γ-aminobutyric acid (GABA), it was down-regulated in serum, but up-regulated in CSF, hippocampus, and the cortex in the STZ-treated group. The mRNA expressions of neurotransmitter-related rate limiting enzymes (including AChE, GAD1, and GAD2) and pro-inflammatory cytokines (including IL-1β and TNF-α) were all increased in the DE rats. Our data suggest that DM induces isoform-dependent and tissue-specific neurotransmitter abnormalities, and that neuroinflammation may underlay the nervous system dysfunction observed in the progression of DE.

Secretion of autoimmune antibodies in the human subcutaneous adipose tissue.

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Frasca, Daniela; Diaz, Alain; Romero, Maria; Thaller, Seth; Blomberg, Bonnie B

2018-01-01

The adipose tissue (AT) contributes to systemic and B cell intrinsic inflammation, reduced B cell responses and secretion of autoimmune antibodies. In this study we show that adipocytes in the human obese subcutaneous AT (SAT) secrete several pro-inflammatory cytokines and chemokines, which contribute to the establishment and maintenance of local and systemic inflammation, and consequent suboptimal immune responses in obese individuals, as we have previously shown. We also show that pro-inflammatory chemokines recruit immune cells expressing the corresponding receptors to the SAT, where they also contribute to local and systemic inflammation, secreting additional pro-inflammatory mediators. Moreover, we show that the SAT generates autoimmune antibodies. During the development of obesity, reduced oxygen and consequent hypoxia and cell death lead to further release of pro-inflammatory cytokines, "self" protein antigens, cell-free DNA and lipids. All these stimulate class switch and the production of autoimmune IgG antibodies which have been described to be pathogenic. In addition to hypoxia, we have measured cell cytotoxicity and DNA damage mechanisms, which may also contribute to the release of "self" antigens in the SAT. All these processes are significantly elevated in the SAT as compared to the blood. We definitively found that fat-specific IgG antibodies are secreted by B cells in the SAT and that B cells express mRNA for the transcription factor T-bet and the membrane marker CD11c, both involved in the production of autoimmune IgG antibodies. Finally, the SAT also expresses RNA for cytokines known to promote Germinal Center formation, isotype class switch, and plasma cell differentiation. Our results show novel mechanisms for the generation of autoimmune antibody responses in the human SAT and allow the identification of new pathways to possibly manipulate in order to reduce systemic inflammation and autoantibody production in obese individuals.

Neurotransmitters and Neuropeptides: New Players in the Control of Islet of Langerhans' Cell Mass and Function.

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Di Cairano, Eliana S; Moretti, Stefania; Marciani, Paola; Sacchi, Vellea Franca; Castagna, Michela; Davalli, Alberto; Folli, Franco; Perego, Carla

2016-04-01

Islets of Langerhans control whole body glucose homeostasis, as they respond, releasing hormones, to changes in nutrient concentrations in the blood stream. The regulation of hormone secretion has been the focus of attention for a long time because it is related to many metabolic disorders, including diabetes mellitus. Endocrine cells of the islet use a sophisticate system of endocrine, paracrine and autocrine signals to synchronize their activities. These signals provide a fast and accurate control not only for hormone release but also for cell differentiation and survival, key aspects in islet physiology and pathology. Among the different categories of paracrine/autocrine signals, this review highlights the role of neurotransmitters and neuropeptides. In a manner similar to neurons, endocrine cells synthesize, accumulate, release neurotransmitters in the islet milieu, and possess receptors able to decode these signals. In this review, we provide a comprehensive description of neurotransmitter/neuropetide signaling pathways present within the islet. Then, we focus on evidence supporting the concept that neurotransmitters/neuropeptides and their receptors are interesting new targets to preserve β-cell function and mass. A greater understanding of how this network of signals works in physiological and pathological conditions would advance our knowledge of islet biology and physiology and uncover potentially new areas of pharmacological intervention. J. Cell. Physiol. 231: 756-767, 2016. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

Therapeutics of Neurotransmitters in Alzheimer's Disease.

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Kandimalla, Ramesh; Reddy, P Hemachandra

2017-01-01

Alzheimer's disease (AD) is a progressive neurodegenerative disease, characterized by the loss of memory, multiple cognitive impairments and changes in the personality and behavior. Several decades of intense research have revealed that multiple cellular changes are involved in disease process, including synaptic damage, mitochondrial abnormalities and inflammatory responses, in addition to formation and accumulation of amyloid-β (Aβ) and phosphorylated tau. Although tremendous progress has been made in understanding the impact of neurotransmitters in the progression and pathogenesis of AD, we still do not have a drug molecule associated with neurotransmitter(s) that can delay disease process in elderly individuals and/or restore cognitive functions in AD patients. The purpose of our article is to assess the latest developments in neurotransmitters research using cell and mouse models of AD. We also updated the current status of clinical trials using neurotransmitters' agonists/antagonists in AD.

Effect of LH and prolactin on steroid secretion by perifused luteal tissue from pregnant gilts with induced hypoprolactinemia or after passive immunoneutralization of LH

International Nuclear Information System (INIS)

Szafranska, B.; Przala, J.; Grazul-Bilska, A.

1992-01-01

The study was performed using luteal tissue obtained from 24 pregnant gilts. Group 1 was treated with bromocriptine (BR) from 37th to 42nd day of day of pregnancy. Group 2 was treated with homologous anti-pLH serum from 37th to 42nd day of pregnancy. Group 3 was given BR from 67th to 72nd day of gestation. Group 4 received anti-pLH serum from 67th to 72nd day of pregnancy. The effect of exogenous LH or prolactin (100 ng/ml) on secretion of progesterone (P 4 ) and estradiol (E 2 ) by luteal tissue was studied using perfusion technique. Prolactin caused a significant (P 4 secretion by luteal tissue from gilts in groups 1 and 4. Both LH and prolactin decreased (P 4 and E 2 secretion by luteal tissue from gilts from groups 4 and 2, respectively. The results demonstrate that both LH and prolactin have a regulatory role in steroid secretion by luteal tissue of gilts in the mid- and late period of pregnancy. (author). 28 refs, 2 figs

The amino acid transporters of the glutamate/GABA-glutamine cycle and their impact on insulin and glucagon secretion

Directory of Open Access Journals (Sweden)

Monica eJenstad

2013-12-01

Full Text Available Intercellular communication is pivotal in optimising and synchronising cellular responses to keep internal homeostasis and to respond adequately to external stimuli. In the central nervous system (CNS, glutamatergic and GABAergic signals are postulated to be dependent on the glutamate/GABA-glutamine (GGG cycle for vesicular loading of neurotransmitters, for inactivating the signal and for the replenishment of the neurotransmitters. Islets of Langerhans release the hormones insulin and glucagon, but share similarities with CNS cells in for example transcriptional control of development and differentiation, and chromatin methylation. Interestingly, proteins involved in the CNS in secretion of the neurotransmitters and emitting their responses as well as the regulation of these processes, are also found in islet cells. Moreover, high levels of glutamate, GABA and glutamine and their respective vesicular and plasma membrane transporters have been shown in the islet cells and there is emerging support for these amino acids and their transporters playing important roles in the maturation and secretion of insulin and glucagon. In this review, we will discuss the feasibility of recent data in the field in relation to the biophysical properties of the transporters (Slc1, Slc17, Slc32 and Slc38 and physiology of hormone secretion in islets of Langerhans.

Redifferentiation of insulin-secreting cells after in vitro expansion of adult human pancreatic islet tissue

International Nuclear Information System (INIS)

Lechner, Andreas; Nolan, Anna L.; Blacken, Robyn A.; Habener, Joel F.

2005-01-01

Cellular replacement therapy holds promise for the treatment of diabetes mellitus but donor tissue is severely limited. Therefore, we investigated whether insulin-secreting cells could be differentiated in vitro from a monolayer of cells expanded from human donor pancreatic islets. We describe a three-step culture protocol that allows for the efficient generation of insulin-producing cell clusters from in vitro expanded, hormone-negative cells. These clusters express insulin at levels of up to 34% that of average freshly isolated human islets and secrete C-peptide upon membrane depolarization. They also contain cells expressing the other major islet hormones (glucagon, somatostatin, and pancreatic polypeptide). The source of the newly differentiated endocrine cells could either be indigenous stem/progenitor cells or the proliferation-associated dedifferentiation and subsequent redifferentiation of mature endocrine cells. The in vitro generated cell clusters may be efficacious in providing islet-like tissue for transplantation into diabetic recipients

Neuronal calcium sensor synaptotagmin-9 is not involved in the regulation of glucose homeostasis or insulin secretion

DEFF Research Database (Denmark)

Gustavsson, Natalia; Wang, Xiaorui; Wang, Yue

2010-01-01

the identities of proteins that are responsible for sensing calcium changes and for transmitting the calcium signal to release machineries. Synaptotagmins are primarily expressed in brain and endocrine cells and exhibit diverse calcium binding properties. Synaptotagmin-1, -2 and -9 are calcium sensors for fast......BACKGROUND: Insulin secretion is a complex and highly regulated process. It is well established that cytoplasmic calcium is a key regulator of insulin secretion, but how elevated intracellular calcium triggers insulin granule exocytosis remains unclear, and we have only begun to define...... neurotransmitter release in respective brain regions, while synaptotagmin-7 is a positive regulator of calcium-dependent insulin release. Unlike the three neuronal calcium sensors, whose deletion abolished fast neurotransmitter release, synaptotagmin-7 deletion resulted in only partial loss of calcium...

Porters and neurotransmitter transporters.

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Nelson, N; Lill, H

1994-11-01

Uptake of neurotransmitters involves multiple transporters acting in different brain locations under different physiological conditions. The vesicular transporters are driven by a proton-motive force generated by a V-ATPase and their substrates are taken up via proton/substrate exchange. The plasma membrane transporters are driven by an electrochemical gradient of sodium generated by a Na+/K(+)-ATPase. Two distinct families of transporters were identified in this group. One cotransports sodium with glutamate and other amino acids and requires additionally an outwardly directed potassium gradient. The second cotransports sodium, chloride and a variety of neurotransmitters, including gamma-aminobutyric acid (GABA), glycine and monoamines. Genes and cDNA encoding several members of the latter family have been cloned and studied in detail. The structure and function as well as the evolutionary relationships among these neurotransmitter transporters are discussed.

Planar Diamond-Based Multiarrays to Monitor Neurotransmitter Release and Action Potential Firing: New Perspectives in Cellular Neuroscience.

Science.gov (United States)

Carabelli, Valentina; Marcantoni, Andrea; Picollo, Federico; Battiato, Alfio; Bernardi, Ettore; Pasquarelli, Alberto; Olivero, Paolo; Carbone, Emilio

2017-02-15

High biocompatibility, outstanding electrochemical responsiveness, inertness, and transparency make diamond-based multiarrays (DBMs) first-rate biosensors for in vitro detection of electrochemical and electrical signals from excitable cells together, with potential for in vivo applications as neural interfaces and prostheses. Here, we will review the electrochemical and physical properties of various DBMs and how these devices have been employed for recording released neurotransmitter molecules and all-or-none action potentials from living cells. Specifically, we will overview how DBMs can resolve localized exocytotic events from subcellular compartments using high-density microelectrode arrays (MEAs), or monitoring oxidizable neurotransmitter release from populations of cells in culture and tissue slices using low-density MEAs. Interfacing DBMs with excitable cells is currently leading to the promising opportunity of recording electrical signals as well as creating neuronal interfaces through the same device. Given the recent increasingly growing development of newly available DBMs of various geometries to monitor electrical activity and neurotransmitter release in a variety of excitable and neuronal tissues, the discussion will be limited to planar DBMs.

Developmental vitamin D deficiency alters multiple neurotransmitter systems in the neonatal rat brain.

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Kesby, James P; Turner, Karly M; Alexander, Suzanne; Eyles, Darryl W; McGrath, John J; Burne, Thomas H J

2017-11-01

Epidemiological evidence suggests that developmental vitamin D (DVD) deficiency is a risk factor for neuropsychiatric disorders, such as schizophrenia. DVD deficiency in rats is associated with altered brain structure and adult behaviours indicating alterations in dopamine and glutamate signalling. Developmental alterations in dopamine neurotransmission have also been observed in DVD-deficient rats but a comprehensive assessment of brain neurochemistry has not been undertaken. Thus, the current study determined the regional concentrations of dopamine, noradrenaline, serotonin, glutamine, glutamate and γ-aminobutyric acid (GABA), and associated metabolites, in DVD-deficient neonates. Sprague-Dawley rats were fed a vitamin D deficient diet or control diet six weeks prior to mating until birth and housed under UVB-free lighting conditions. Neurotransmitter concentration was assessed by high-performance liquid chromatography on post-mortem neonatal brain tissue. Ubiquitous reductions in the levels of glutamine (12-24%) were observed in DVD-deficient neonates compared with control neonates. Similarly, in multiple brain regions DVD-deficient neonates had increased levels of noradrenaline and serine compared with control neonates. In contrast, increased levels of dopamine and decreased levels of serotonin in DVD-deficient neonates were limited to striatal subregions compared with controls. Our results confirm that DVD deficiency leads to changes in multiple neurotransmitter systems in the neonate brain. Importantly, this regionally-based assessment in DVD-deficient neonates identified both widespread neurotransmitter changes (glutamine/noradrenaline) and regionally selective neurotransmitter changes (dopamine/serotonin). Thus, vitamin D may have both general and local actions depending on the neurotransmitter system being investigated. Taken together, these data suggest that DVD deficiency alters neurotransmitter systems relevant to schizophrenia in the developing rat

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 monoamine neurotransmitters serotonin (5-hydroxytryptamine), dopamine, and norepinephrine, and the amino acid neurotransmitters GABA and glycine. The SLC6 NTTs are widely expressed in the mammalian brain and play an essential role in regulating neurotransmitter signaling and homeostasis by mediating uptake...... of released neurotransmitters from the extracellular space into neurons and glial cells. The transporters are targets for a wide range of therapeutic drugs used in treatment of psychiatric diseases, including major depression, anxiety disorders, attention deficit hyperactivity disorder and epilepsy...

Unsupported platinum nanoparticles as effective sensors of neurotransmitters and possible drug curriers

Science.gov (United States)

Tąta, Agnieszka; Gralec, Barbara; Proniewicz, Edyta

2018-03-01

Herein, surface-enhanced Raman scattering (SERS) activity of positively charged unsupported platinum nanoparticles (PtNPs) with ∼12 nm size and narrow size distribution, in an aqueous solution, towards neurotransmitters was monitored at 785 nm excitation wavelength. The pure PtNPs were synthetized by polyol method. Their morphology and structure were checked by scanning electron microscopy (SEM) and X-ray diffraction spectroscopy (XRD) measurements. As a neurotransmitter bombesin (BN), which exhibits autocrine effect on the growth of normal and tumour tissues, and its fragments from the C-terminal end: BN13-14, BN12-14, BN11-14, BN10-14, BN9-14, and BN8-14 (X-14 fragments of the BN amino acid sequence) were chosen. The collected spectra were interpreted and discussed. This is to determine the adsorption mode of bombesin onto the PtNPs surface and changes in this mode as a result of the bombesin backbone shortening from the N-terminal end. This is important from the point of using PtNPs as potential BN carrier into the cancerous tissue and antitumor drug.

Tissue-specific expression of transgenic secreted ACE in vasculature can restore normal kidney functions, but not blood pressure, of Ace-/- mice.

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Saurabh Chattopadhyay

Full Text Available Angiotensin-converting enzyme (ACE regulates normal blood pressure and fluid homeostasis through its action in the renin-angiotensin-system (RAS. Ace-/- mice are smaller in size, have low blood pressure and defective kidney structure and functions. All of these defects are cured by transgenic expression of somatic ACE (sACE in vascular endothelial cells of Ace-/- mice. sACE is expressed on the surface of vascular endothelial cells and undergoes a natural cleavage secretion process to generate a soluble form in the body fluids. Both the tissue-bound and the soluble forms of ACE are enzymatically active, and generate the vasoactive octapeptide Angiotensin II (Ang II with equal efficiency. To assess the relative physiological roles of the secreted and the cell-bound forms of ACE, we expressed, in the vascular endothelial cells of Ace-/- mice, the ectodomain of sACE, which corresponded to only the secreted form of ACE. Our results demonstrated that the secreted form of ACE could normalize kidney functions and RAS integrity, growth and development of Ace-/- mice, but not their blood pressure. This study clearly demonstrates that the secreted form of ACE cannot replace the tissue-bound ACE for maintaining normal blood pressure; a suitable balance between the tissue-bound and the soluble forms of ACE is essential for maintaining all physiological functions of ACE.

Tissue-specific expression of transgenic secreted ACE in vasculature can restore normal kidney functions, but not blood pressure, of Ace-/- mice.

Science.gov (United States)

Chattopadhyay, Saurabh; Kessler, Sean P; Colucci, Juliana Almada; Yamashita, Michifumi; Senanayake, Preenie deS; Sen, Ganes C

2014-01-01

Angiotensin-converting enzyme (ACE) regulates normal blood pressure and fluid homeostasis through its action in the renin-angiotensin-system (RAS). Ace-/- mice are smaller in size, have low blood pressure and defective kidney structure and functions. All of these defects are cured by transgenic expression of somatic ACE (sACE) in vascular endothelial cells of Ace-/- mice. sACE is expressed on the surface of vascular endothelial cells and undergoes a natural cleavage secretion process to generate a soluble form in the body fluids. Both the tissue-bound and the soluble forms of ACE are enzymatically active, and generate the vasoactive octapeptide Angiotensin II (Ang II) with equal efficiency. To assess the relative physiological roles of the secreted and the cell-bound forms of ACE, we expressed, in the vascular endothelial cells of Ace-/- mice, the ectodomain of sACE, which corresponded to only the secreted form of ACE. Our results demonstrated that the secreted form of ACE could normalize kidney functions and RAS integrity, growth and development of Ace-/- mice, but not their blood pressure. This study clearly demonstrates that the secreted form of ACE cannot replace the tissue-bound ACE for maintaining normal blood pressure; a suitable balance between the tissue-bound and the soluble forms of ACE is essential for maintaining all physiological functions of ACE.

Neural regulation of duodenal alkali secretion: Effects of electrical field stimulation

International Nuclear Information System (INIS)

Crampton, J.R.; Gibbons, L.G.; Rees, W.D.W.

1988-01-01

The role of transmitters released from enteric neurons in regulating bicarbonate secretion by the proximal duodenum has been studied using electrical field stimulation (EFS). Stripped duodenal mucosa from Rana catesbeiana was mounted as an intact tube over circular platinum electrode,s and luminal alkalinization was measured by pH stat titration before, during, and after EFS. Transmucosal potential difference (PD) was simultaneously measured before and after EFS by paired electrodes. Square-wave pulses 50 V, 2 ms in duration, at 10 Hz were delivered in trains of 0.5 s at 1 Hz for periods of 15 min after stable basal secretion. This resulted in a 63 ± 27% increase in alkalinization that returned to basal values after cessation of the stimulus, without change in transmucosal PD. Serosal-to-lumen [ 3 H]mannitol flux was not affected. Repetition of the stimulus resulted in a similar responses for as long as the tissue remained viable. The response to EFS was abolished by tetrodotoxin and veratrine indicating that intrinsic neurons were responsible for mediating the effect. In addition, the effect was blocked by serosal dinitrophenol, indicating that the secretory response occurred by a metabolically dependent process. These results indicate that alkalinization by proximal duodenum may be controlled by neurotransmitter release from local enteric neurons

Zn2+ modulation of neurotransmitter transporters

DEFF Research Database (Denmark)

Nørgaard-Nielsen, K.; Gether, U.

2006-01-01

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...

Antibody-secreting cells in respiratory tract tissues in the absence of eosinophils as supportive partners.

Science.gov (United States)

Sealy, Robert E; Surman, Sherri L; Vogel, Peter; Hurwitz, Julia L

2016-11-01

Antibody-secreting cells (ASCs) in respiratory tract tissues provide a first line of defense against invading pathogens. These cells often secrete IgA that is efficiently transcytosed across epithelial barriers into the airway lumen where pathogens can be blocked at their point of entry. Previous literature has reported that in the bone marrow, eosinophils are required for the maintenance of ASCs, and that eosinophils co-localize with ASCs as nearest neighbors. To determine if these rules similarly apply to the maintenance of ASCs in respiratory tract tissues, we evaluated virus-specific responses 1 month and 4 months following an intranasal virus infection of eosinophil-null (∆dblGATA-1) mice. Results showed that ASCs were fractionally reduced, but were nonetheless observed in respiratory tract tissues in the absence of eosinophils. Virus-specific antibodies were similarly observed in the airways of eosinophil-deficient mice. Respiratory tract ASCs were also present in mice lacking neutrophils (Mcl1 ∆M ). The staining of tissue sections from the upper respiratory tract of wild-type mice following viral infections demonstrated that virus-specific ASCs were most frequently situated adjacent to epithelial cells rather than eosinophils or neutrophils. Taken together, these data emphasize that rules for cell maintenance are not absolute and that ASCs can survive in the respiratory tract without eosinophils or neutrophils as their nearest neighbors. © The Japanese Society for Immunology. 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

OXIDATIVE STRESS: ITS ROLE IN INSULIN SECRETION, HORMONE RECEPTION BY ADIPOCYTES AND LIPOLYSIS IN ADIPOSE TISSUE

Directory of Open Access Journals (Sweden)

V. V. Ivanov

2014-01-01

Full Text Available Oxidative stress is one of the pathogenetic components of many diseases during which generation of reactive oxigen species increases and the capacity of the antioxidant protection system diminishes. In the research of the last decades special attention has been given to adipose tissue, production of adipokines by it and their role in development of immunoresistance associated with formation of the metabolic syndrome and diabetes.Search for methods of therapeutic correction of adipokine secretion disorders, their influence on metabolism of separate cells and the organism on the whole as well as development of new approaches to correction of disorders in cell sensitivity to insulin are extremely topical nowadays. Systematization and consolidation of accumulated data allow to determine the strategies of further research more accurately; as a result, we have attempted to summarize and analyze the accumulated data on the role of adipose tissue in oxidative stress development.On the basis of literature data and the results of the personal investigations, the role of adipose tissue in forming oxidative stress in diabetes has been analyzed in the article. Brief description of adipose tissue was given as a secretory organ regulating metabolic processes in adipocytes and influencing functions of various organs and systems of the body. Mechanisms of disorder in insulin secretion as well as development of insulin sesistance in type I diabetes were described along with the contribution of lipolysis in adipose tissue to these processes.

Aging rather than aneuploidy affects monoamine neurotransmitters in brain regions of Down syndrome mouse models

NARCIS (Netherlands)

Dekker, Alain D; Vermeiren, Yannick; Albac, Christelle; Lana-Elola, Eva; Watson-Scales, Sheona; Gibbins, Dorota; Aerts, Tony; Van Dam, Debby; Fisher, Elizabeth M C; Tybulewicz, Victor L J; Potier, Marie-Claude; De Deyn, Peter P

Altered concentrations of monoamine neurotransmitters and metabolites have been repeatedly found in people with Down syndrome (DS, trisomy 21). Because of the limited availability of human post-mortem tissue, DS mouse models are of great interest to study these changes and the underlying

Analysis of drug effects on neurotransmitter release

International Nuclear Information System (INIS)

Rowell, P.; Garner, A.

1986-01-01

The release of neurotransmitter is routinely studied in a superfusion system in which serial samples are collected and the effects of drugs or other treatments on the amount of material in the superfusate is determined. With frequent sampling interval, this procedure provides a mechanism for dynamically characterizing the release process itself. Using automated data collection in conjunction with polyexponential computer analysis, the equation which describes the release process in each experiment is determined. Analysis of the data during the nontreated phase of the experiment allows an internal control to be used for accurately assessing any changes in neurotransmitter release which may occur during a subsequent treatment phase. The use of internal controls greatly improves the signal to noise ratio and allows determinations of very low concentrations of drugs on small amounts of tissue to be made. In this presentation, the effects of 10 μM nicotine on 3 H-dopamine release in rat nucleus accumbens is described. The time course, potency and efficacy of the drug treatment is characterized using this system. Determinations of the exponential order of the release as well as the rate constants allow one to study the mechanism of the release process. A description of 3 H-dopamine release in normal as well as Ca ++ -free medium is presented

A Critical Assessment of Research on Neurotransmitters in Alzheimer's Disease.

Science.gov (United States)

Reddy, P Hemachandra

2017-01-01

The purpose of this mini-forum, "Neurotransmitters and Alzheimer's Disease", is to critically assess the current status of neurotransmitters in Alzheimer's disease. Neurotransmitters are essential neurochemicals that maintain synaptic and cognitive functions in mammals, including humans, by sending signals across pre- to post-synaptic neurons. Authorities in the fields of synapses and neurotransmitters of Alzheimer's disease summarize the current status of basic biology of synapses and neurotransmitters, and also update the current status of clinical trials of neurotransmitters in Alzheimer's disease. This article discusses the prevalence, economic impact, and stages of Alzheimer's dementia in humans.

Clinical features and pharmacotherapy of childhood monoamine neurotransmitter disorders.

Science.gov (United States)

Ng, J; Heales, S J R; Kurian, M A

2014-08-01

Childhood neurotransmitter disorders are increasingly recognised as an expanding group of inherited neurometabolic syndromes. They are caused by disturbance in synthesis, metabolism, and homeostasis of the monoamine neurotransmitters, including the catecholamines (dopamine, norepinephrine, and epinephrine) and serotonin. Disturbances in monoamine neurotransmission will lead to neurological symptoms that often overlap with clinical features of other childhood neurological disorders (such as hypoxic ischaemic encephalopathy, cerebral palsy, other movement disorders, and paroxysmal conditions); consequently, neurotransmitter disorders are frequently misdiagnosed. The diagnosis of neurotransmitter disorders is made through detailed clinical assessment, analysis of cerebrospinal fluid neurotransmitters, and further supportive diagnostic investigations. Early and accurate diagnosis of neurotransmitter disorders is important, as many are amenable to therapeutic intervention. The principles of treatment for monoamine neurotransmitter disorders are mainly directly derived from understanding these metabolic pathways. In disorders characterized by enzyme deficiency, we aim to increase monoamine substrate availability, boost enzyme co-factor levels, reduce monoamine breakdown, and replace depleted levels of monoamines with pharmacological analogs as clinically indicated. Most monoamine neurotransmitter disorders lead to reduced levels of central dopamine and/or serotonin. Complete amelioration of motor symptoms is achievable in some disorders, such as Segawa's syndrome, and, in other conditions, significant improvement in quality of life can be attained with pharmacotherapy. In this review, we provide an overview of the clinical features and current treatment strategies for childhood monoamine neurotransmitter disorders.

Quantitative densitometry of neurotransmitter receptors

International Nuclear Information System (INIS)

Rainbow, T.C.; Bleisch, W.V.; Biegon, A.; McEwen, B.S.

1982-01-01

An autoradiographic procedure is described that allows the quantitative measurement of neurotransmitter receptors by optical density readings. Frozen brain sections are labeled in vitro with [ 3 H]ligands under conditions that maximize specific binding to neurotransmitter receptors. The labeled sections are then placed against the 3 H-sensitive LKB Ultrofilm to produce the autoradiograms. These autoradiograms resemble those produced by [ 14 C]deoxyglucose autoradiography and are suitable for quantitative analysis with a densitometer. Muscarinic cholinergic receptors in rat and zebra finch brain and 5-HT receptors in rat brain were visualized by this method. When the proper combination of ligand concentration and exposure time are used, the method provides quantitative information about the amount and affinity of neurotransmitter receptors in brain sections. This was established by comparisons of densitometric readings with parallel measurements made by scintillation counting of sections. (Auth.)

Spinal cord regeneration by modulating bone marrow with neurotransmitters and Citicholine: Analysis at micromolecular level.

Science.gov (United States)

Paulose, Cheramadathukudiyil Skaria; John, Ponnezhathu Sebastian; Chinthu, Romeo; Akhilraj, Puthenveetil Raju; Anju, Thoppil Raveendran

2017-04-01

Spinal cord injury results in disruption of brain-spinal cord fibre connectivity, leading to progressive tissue damage at the site of injury and resultant paralysis of varying degrees. The current study investigated the role of autologous bone marrow modulated with neurotransmitters and neurotransmitter stimulating agent, Citicholine, in spinal cord of spinal cord injured rats. Radioreceptor assay using [3H] ligand was carried out to quantify muscarinic receptor. Gene expression studies were done using Real Time PCR analysis. Scatchard analysis of muscarinic M1 receptor showed significantly decreased B max (p neurotransmitters combination along with bone marrow or Citicholine with bone marrow can reverse the muscarinic receptor alterations in the spinal cord of spinal cord injured rats, which is a promising step towards a better therapeutic intervention for spinal cord injury because of the positive role of cholinergic system in regulation of both locomotor activity and synaptic plasticity. Copyright © 2017 Chang Gung University. Published by Elsevier B.V. All rights reserved.

[Preliminary research on multi-neurotransmitters' change regulation in 120 depression patients' brains].

Science.gov (United States)

Chi, Ming; Qing, Xue-Mei; Pan, Yan-Shu; Xu, Feng-Quan; Liu, Chao; Zhang, Cheng; Xu, Zhen-Hua

2014-04-01

In view of the effective traditional Chinese medicine (TCM) in the treatment of clinical depression, the mechanism is not clear, this study attempts to research the cause of depression in a complex situation to lay the foundation for the next step of TCM curative effect evaluation. Based on the brain wave of 120 depression patients and 40 ordinary person, the change regulation of acetylcholine, dopamine, norepinephrine, depression neurotransmitters and excited neurotransmitters in the whole and various encephalic regions' multi-neurotransmitters of depression patients-serotonin are analysed by search of encephalo-telex (SET) system, which lays the foundation for the diagnosis of depression. The result showed that: contrased with the normal person group, the mean value of the six neurotransmitters in depression patients group are: (1) in the whole encephalic region of depression patients group the dopamine fall (P neurotransmitters and neurotransmitters: (1) the three antagonizing pairs of neurotransmitters-serotonin and dopamine, acetylcholine and norepinephrine, depression neurotransmitters and excited neurotransmitters, in ordinary person group and depression patients group are characterizeed by middle or strong negative correlation. Serotonin and dopamine, which are characterized by weak negative correlation in the right rear temporal region of ordinary person group, are characterized by strong negative correlation in the other encephalic regions and the whole encephalic (ordinary person group except the right rear temporal region: the range of [r] is [0.82, 0.92], P neurotransmitters and excited neurotransmitters are characterized by middle strong negative correlation (ordinary person group: the range of [r] is [0.57, 0.80], P neurotransmitters which are not antagonizing pairs of neurotransmitters, serotonin and excited neurotransmitters, or acetylcholine and depression neurotra-nsmitters, or dopamine and depression neurotransmitters in the various encephalic

Electroactive biodegradable polyurethane significantly enhanced Schwann cells myelin gene expression and neurotrophin secretion for peripheral nerve tissue engineering.

Science.gov (United States)

Wu, Yaobin; Wang, Ling; Guo, Baolin; Shao, Yongpin; Ma, Peter X

2016-05-01

Myelination of Schwann cells (SCs) is critical for the success of peripheral nerve regeneration, and biomaterials that can promote SCs' neurotrophin secretion as scaffolds are beneficial for nerve repair. Here we present a biomaterials-approach, specifically, a highly tunable conductive biodegradable flexible polyurethane by polycondensation of poly(glycerol sebacate) and aniline pentamer, to significantly enhance SCs' myelin gene expression and neurotrophin secretion for peripheral nerve tissue engineering. SCs are cultured on these conductive polymer films, and the biocompatibility of these films and their ability to enhance myelin gene expressions and sustained neurotrophin secretion are successfully demonstrated. The mechanism of SCs' neurotrophin secretion on conductive films is demonstrated by investigating the relationship between intracellular Ca(2+) level and SCs' myelination. Furthermore, the neurite growth and elongation of PC12 cells are induced by adding the neurotrophin medium suspension produced from SCs-laden conductive films. These data suggest that these conductive degradable polyurethanes that enhance SCs' myelin gene expressions and sustained neurotrophin secretion perform great potential for nerve regeneration applications. Copyright © 2016 Elsevier Ltd. All rights reserved.

Dynamic regulation of neurotransmitter specification: Relevance to nervous system homeostasis

Science.gov (United States)

Borodinsky, Laura N.; Belgacem, Yesser Hadj; Swapna, Immani; Sequerra, Eduardo Bouth

2013-01-01

During nervous system development the neurotransmitter identity changes and coexpression of several neurotransmitters is a rather generalized feature of developing neurons. In the mature nervous system, different physiological and pathological circumstances recreate this phenomenon. The rules of neurotransmitter respecification are multiple. Among them, the goal of assuring balanced excitability appears as an important driving force for the modifications in neurotransmitter phenotype expression. The functional consequences of these dynamic revisions in neurotransmitter identity span a varied range, from fine-tuning the developing neural circuit to modifications in addictive and locomotor behaviors. Current challenges include determining the mechanisms underlying neurotransmitter phenotype respecification and how they intersect with genetic programs of neuronal specialization. PMID:23270605

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...

Therapeutics of Neurotransmitters in Alzheimer’s Disease

Science.gov (United States)

Kandimalla, Ramesh; Reddy, P. Hemachandra

2018-01-01

Alzheimer’s disease (AD) is a progressive neurodegenerative disease, characterized by the loss of memory, multiple cognitive impairments and changes in the personality and behavior. Several decades of intense research have revealed that multiple cellular changes are involved in disease process, including synaptic damage, mitochondrial abnormalities and inflammatory responses, in addition to formation and accumulation of amyloid-β (Aβ) and phosphorylated tau. Although tremendous progress has been made in understanding the impact of neurotransmitters in the progression and pathogenesis of AD, we still do not have a drug molecule associated with neurotransmitter(s) that can delay disease process in elderly individuals and/or restore cognitive functions in AD patients. The purpose of our article is to assess the latest developments in neurotransmitters research using cell and mouse models of AD. We also updated the current status of clinical trials using neurotransmitters’ agonists/antagonists in AD. PMID:28211810

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...

A Critical Assessment of Research on Neurotransmitters in Alzheimer’s Disease

Science.gov (United States)

Reddy, P. Hemachandra

2018-01-01

The purpose of this mini-forum, “Neurotransmitters and Alzheimer’s Disease”, is to critically assess the current status of neurotransmitters in Alzheimer’s disease. Neurotransmitters are essential neurochemicals that maintain synaptic and cognitive functions in mammals, including humans, by sending signals across pre- to post-synaptic neurons. Authorities in the fields of synapses and neurotransmitters of Alzheimer’s disease summarize the current status of basic biology of synapses and neurotransmitters, and also update the current status of clinical trials of neurotransmitters in Alzheimer’s disease. This article discusses the prevalence, economic impact, and stages of Alzheimer’s dementia in humans. PMID:28409748

Effect of taurine on the insuline secretion isolated by the pancreatic tissue of intact and irradiated rats

International Nuclear Information System (INIS)

Dokshina, G.A.; Silaeva, T.Yu.

1976-01-01

The whole-body irradiation of rats (700 rads) inhibits the secretory activity of insular pancreatic tissue. Administration of taurine (200 mg/kg), on the fifth day after irradiation, five times every second day normalizes the secretory function of pancreatic islands. In the experiments in vitro, taurine (1.5 and 3.0 mg/ml) stimulated hormone secretion. The stimulating action of the amino acid manifests itself when β-receptors are blocked by obsidane (0.5 μg/ml). It is suggested that insuline secretion by β-cells of pancreas is restored and enhanced by taurine not merely through the adenylatecyclase system; other ways are also possible

Effect of taurine on the insuline secretion isolated by the pancreatic tissue of intact and irradiated rats

Energy Technology Data Exchange (ETDEWEB)

Dokshina, G A; Silaeva, T Yu [Tomskij Gosudarstvennyj Univ. (USSR). Nauchno-Issledovatel' skij Inst. Biologii i Biofiziki

1976-05-01

The whole-body irradiation of rats (700 rads) inhibits the secretory activity of insular pancreatic tissue. Administration of taurine (200 mg/kg), on the fifth day after irradiation, five times every second day normalizes the secretory function of pancreatic islands. In the experiments in vitro, taurine (1.5 and 3.0 mg/ml) stimulated hormone secretion. The stimulating action of the amino acid manifests itself when ..beta..-receptors are blocked by obsidane (0.5 ..mu..g/ml). It is suggested that insuline secretion by ..beta..-cells of pancreas is restored and enhanced by taurine not merely through the adenylatecyclase system; other ways are also possible.

Gefarnate stimulates mucin-like glycoprotein secretion in conjunctival tissue and ameliorates corneal epithelial damage in animal dry-eye models

Directory of Open Access Journals (Sweden)

Dota A

2013-01-01

Full Text Available Atsuyoshi Dota, Yuko Takaoka-Shichijo, Masatsugu NakamuraOphthalmic Research and Development Center, Santen Pharmaceutical Co, Ltd, Ikoma-shi, Nara, JapanPurpose: The aim of this study was to evaluate the effect of gefarnate on mucin-like glycoprotein secretion in isolated rabbit conjunctival tissue, and on corneal epithelial damage in rabbit and cat dry-eye models.Methods: Conjunctival tissue isolated from rabbits was treated with gefarnate. Mucin-like glycoprotein was detected in the culture supernatant by an enzyme-linked lectin assay. Gefarnate ointment was topically applied to eyes once daily for 7 days in the rabbit dry-eye model, in which the lacrimal glands, Harderian gland, and nictitating membrane were removed, or for 4 weeks in the cat dry-eye model, in which the lacrimal gland and nictitating membrane were removed. Corneal epithelial damage was evaluated by measurement of corneal permeability by rose bengal in the rabbit model or by fluorescein staining in the cat model.Results: Gefarnate stimulated mucin-like glycoprotein secretion in conjunctival tissue in a dose-dependent manner. In the rabbit dry-eye model, application of gefarnate ointment to the eyes resulted in a dose-dependent decrease in rose bengal permeability in the cornea, with the effect being significant at concentrations of ≥0.3%. In the cat dry-eye model, application of gefarnate ointment resulted in a significant decrease in the corneal fluorescein staining score.Conclusion: These results suggest that gefarnate stimulates in vitro secretion of mucin-like glycoprotein in conjunctival tissue and ameliorates corneal epithelial damage in animal dry-eye models. Gefarnate may therefore be effective for treating dry eye.Keywords: gefarnate, fluorescein staining, rose bengal permeability, rabbit, cat, dry eye

Metabolic Profiling and Quantification of Neurotransmitters in Mouse Brain by Gas Chromatography-Mass Spectrometry.

Science.gov (United States)

Jäger, Christian; Hiller, Karsten; Buttini, Manuel

2016-09-01

Metabolites are key mediators of cellular functions, and have emerged as important modulators in a variety of diseases. Recent developments in translational biomedicine have highlighted the importance of not looking at just one disease marker or disease inducing molecule, but at populations thereof to gain a global understanding of cellular function in health and disease. The goal of metabolomics is the systematic identification and quantification of metabolite populations. One of the most pressing issues of our times is the understanding of normal and diseased nervous tissue functions. To ensure high quality data, proper sample processing is crucial. Here, we present a method for the extraction of metabolites from brain tissue, their subsequent preparation for non-targeted gas chromatography-mass spectrometry (GC-MS) measurement, as well as giving some guidelines for processing of raw data. In addition, we present a sensitive screening method for neurotransmitters based on GC-MS in selected ion monitoring mode. The precise multi-analyte detection and quantification of amino acid and monoamine neurotransmitters can be used for further studies such as metabolic modeling. Our protocol can be applied to shed light on nervous tissue function in health, as well as neurodegenerative disease mechanisms and the effect of experimental therapeutics at the metabolic level. © 2016 by John Wiley & Sons, Inc. Copyright © 2016 John Wiley & Sons, Inc.

Relationship of neurotransmitters to the symptoms of major depressive disorder.

Science.gov (United States)

Nutt, David J

2008-01-01

A relationship appears to exist between the 3 main monoamine neurotransmitters in the brain (i.e., dopamine, norepinephrine, and serotonin) and specific symptoms of major depressive disorder. Specific symptoms are associated with the increase or decrease of specific neurotransmitters, which suggests that specific symptoms of depression could be assigned to specific neurochemical mechanisms, and subsequently specific antidepressant drugs could target symptom-specific neurotransmitters. Research on electroconvulsive therapy has supported a correlation between neurotransmitters and depression symptoms. A 2-dimensional model of neurotransmitter functions is discussed that describes depression as a mixture of 2 separate components--negative affect and the loss of positive affect--that can be considered in relation to the 3 amine neurotransmitters. Owing to the different methods of action of available antidepressant agents and the depression symptoms thought to be associated with dopamine, serotonin, and norepinephrine, current treatments can be targeted toward patients' specific symptoms.

Carbon Nanotube-based microelectrodes for enhanced detection of neurotransmitters

Science.gov (United States)

Jacobs, Christopher B.

Fast-scan cyclic voltammetry (FSCV) is one of the common techniques used for rapid measurement of neurotransmitters in vivo. Carbon-fiber microelectrodes (CFMEs) are typically used for neurotransmitter detection because of sub-second measurement capabilities, ability to measure changes in neurotransmitter concentration during neurotransmission, and the small size electrode diameter, which limits the amount of damage caused to tissue. Cylinder CFMEs, typically 50 -- 100 microm long, are commonly used for in vivo experiments because the electrode sensitivity is directly related to the electrode surface area. However the length of the electrode can limit the spatial resolution of neurotransmitter detection, which can restrict experiments in Drosophila and other small model systems. In addition, the electrode sensitivity toward dopamine and serotonin detection drops significantly for measurements at rates faster than 10 Hz, limiting the temporal resolution of CFMEs. While the use of FSCV at carbon-fiber microelectrodes has led to substantial strides in our understanding of neurotransmission, techniques that expand the capabilities of CFMEs are crucial to fully maximize the potential uses of FSCV. This dissertation introduces new methods to integrate carbon nanotubes (CNT) into microelectrodes and discusses the electrochemical enhancements of these CNT-microelectrodes. The electrodes are specifically designed with simple fabrication procedures so that highly specialized equipment is not necessary, and they utilize commercially available materials so that the electrodes could be easily integrated into existing systems. The electrochemical properties of CNT modified CFMEs are characterized using FSCV and the effect of CNT functionalization on these properties is explored in Chapter 2. For example, CFME modification using carboxylic acid functionalized CNTs yield about a 6-fold increase in dopamine oxidation current, but modification with octadecylamine CNTs results in a

Isthmin 1 Is a Secreted Protein Expressed in Skin, Mucosal Tissues, and NK, NKT, and Th17 Cells

OpenAIRE

Valle-Rios, Ricardo; Maravillas-Montero, José L.; Burkhardt, Amanda M.; Martinez, Cynthia; Buhren, Bettina Alexandra; Homey, Bernhard; Gerber, Peter Arne; Robinson, Octavio; Hevezi, Peter; Zlotnik, Albert

2014-01-01

Using a comprehensive microarray database of human gene expression, we identified that in mammals, a secreted protein known as isthmin 1 (ISM1) is expressed in skin, mucosal tissues, and selected lymphocyte populations. ISM1 was originally identified in Xenopus brain during development, and it encodes a predicted ∼50-kDa protein containing a signal peptide, a thrombospondin domain, and an adhesion-associated domain. We confirmed the pattern of expression of ISM1 in both human and mouse tissue...

Onchocerca volvulus-neurotransmitter tyramine is a biomarker for river blindness.

Science.gov (United States)

Globisch, Daniel; Moreno, Amira Y; Hixon, Mark S; Nunes, Ashlee A K; Denery, Judith R; Specht, Sabine; Hoerauf, Achim; Janda, Kim D

2013-03-12

Onchocerciasis, also known as "river blindness", is a neglected tropical disease infecting millions of people mainly in Africa and the Middle East but also in South America and Central America. Disease infectivity initiates from the filarial parasitic nematode Onchocerca volvulus, which is transmitted by the blackfly vector Simulium sp. carrying infectious third-stage larvae. Ivermectin has controlled transmission of microfilariae, with an African Program elimination target date of 2025. However, there is currently no point-of-care diagnostic that can distinguish the burden of infection--including active and/or past infection--and enable the elimination program to be effectively monitored. Here, we describe how liquid chromatography-MS-based urine metabolome analysis can be exploited for the identification of a unique biomarker, N-acetyltyramine-O,β-glucuronide (NATOG), a neurotransmitter-derived secretion metabolite from O. volvulus. The regulation of this tyramine neurotransmitter was found to be linked to patient disease infection, including the controversial antibiotic doxycycline treatment that has been shown to both sterilize and kill adult female worms. Further clues to its regulation have been elucidated through biosynthetic pathway determination within the nematode and its human host. Our results demonstrate that NATOG tracks O. volvulus metabolism in both worms and humans, and thus can be considered a host-specific biomarker for onchocerciasis progression. Liquid chromatography-MS-based urine metabolome analysis discovery of NATOG not only has broad implications for a noninvasive host-specific onchocerciasis diagnostic but provides a basis for the metabolome mining of other neglected tropical diseases for the discovery of distinct biomarkers and monitoring of disease progression.

In vitro labelled neurotransmitters release for the study of neuro toxins

International Nuclear Information System (INIS)

Camillo, Maria A.P.; Rogero, Jose R.; Troncone, Lanfranco R.P.

1995-01-01

There is an increasing concern in the replacement of in vivo by in vitro methods in Pharmacology. Looking for a method which involves the most of the physiological aspects related to neural functions, a super fusion system designed to evaluate in vitro neurotransmitter release from brain striatal tissue is here described. The method is based on the basal and stimulated release of pre-loaded tritium-labelled neurotransmitters. This procedure bears an active uptake/release function which is fairly changed by membrane polarisation state, ion channel activation and enzymatic activity, as well as other still unknown steps involved in neurotransmission. Calcium dependency of dopamine and acetylcholine release induced by high potassium depolarization or glutamate (Glu) stimulation was demonstrated employing calcium-free (+EGTA) super fusion or lanthanum/cadmium addition. Glutamate stimulation involved NMDA receptors since magnesium or MK801 blocks stimulated release. Uptake of DA and Ach was evidenced by using bupropione or hemicolinium-3. presynaptic inhibition of Ach release was evidenced by physostigmine-induced inhibitions of acetylcholinesterase. (author). 3 refs., 6 figs

Impaired CD23 and CD62L expression and tissue inhibitors of metalloproteinases secretion by eosinophils in adults with atopic dermatitis.

Science.gov (United States)

de Oliveira Titz, T; Orfali, R L; de Lollo, C; Dos Santos, V G; da Silva Duarte, A J; Sato, M N; Aoki, V

2016-12-01

Eosinophils are multifunctional, polymorphonuclear leucocytes that secrete proteins within cytoplasmic granules, such as cytokines, chemokines, metalloproteinases (MMPs) and metalloproteinases tissue inhibitors (TIMPs). Although eosinophilia is a hallmark of atopic dermatitis (AD), several functional aspects of eosinophils remain unknown. We aimed to evaluate the phenotype and functional response of eosinophils under staphylococcal enterotoxin B (SEB) and Toll-like receptor (TLR)-2/6 (FSL-1) stimulation in the secretion of CCL5, MMPs and TIMPs in adults with AD. Forty-one adult patients with AD and 45 healthy controls enrolled for the study. Phenotype of eosinophils from granulocytes of peripheral blood was analysed by flow cytometry. We performed evaluation of CCL5 (cytometric bead array), MMP and TIMP (ELISA) secretion, in culture supernatants of purified eosinophils stimulated with SEB or TLR2/6 agonist (FSL-1). We found a higher frequency of LIN1 - CCR3 + eosinophils, and decreased expression of CD23 and CD62L receptors in eosinophils of AD patients. There was no difference in MMP and TIMP serum levels between the evaluated groups. However, we detected decreased basal levels of TIMP-1, TIMP-2 and CCL5 in culture supernatants from purified, unstimulated eosinophils from AD patients. In adults with AD, phenotypical features of eosinophils reveal decreased expression of early activation and L-selectin receptors. Regarding the functional profile of purified eosinophils related to tissue remodelling in atopic dermatitis, innate immune stimulation (TLR2/6 agonist and SEB) did not affect the ratio of MMP/TIMPs secretion in AD. Our findings reinforce the potential breakdown in tissue remodelling process mediated by eosinophils in AD. © 2016 European Academy of Dermatology and Venereology.

Tuning Selectivity of Fluorescent Carbon Nanotube-Based Neurotransmitter Sensors.

Science.gov (United States)

Mann, Florian A; Herrmann, Niklas; Meyer, Daniel; Kruss, Sebastian

2017-06-28

Detection of neurotransmitters is an analytical challenge and essential to understand neuronal networks in the brain and associated diseases. However, most methods do not provide sufficient spatial, temporal, or chemical resolution. Near-infrared (NIR) fluorescent single-walled carbon nanotubes (SWCNTs) have been used as building blocks for sensors/probes that detect catecholamine neurotransmitters, including dopamine. This approach provides a high spatial and temporal resolution, but it is not understood if these sensors are able to distinguish dopamine from similar catecholamine neurotransmitters, such as epinephrine or norepinephrine. In this work, the organic phase (DNA sequence) around SWCNTs was varied to create sensors with different selectivity and sensitivity for catecholamine neurotransmitters. Most DNA-functionalized SWCNTs responded to catecholamine neurotransmitters, but both dissociation constants ( K d ) and limits of detection were highly dependent on functionalization (sequence). K d values span a range of 2.3 nM (SWCNT-(GC) 15 + norepinephrine) to 9.4 μM (SWCNT-(AT) 15 + dopamine) and limits of detection are mostly in the single-digit nM regime. Additionally, sensors of different SWCNT chirality show different fluorescence increases. Moreover, certain sensors (e.g., SWCNT-(GT) 10 ) distinguish between different catecholamines, such as dopamine and norepinephrine at low concentrations (50 nM). These results show that SWCNTs functionalized with certain DNA sequences are able to discriminate between catecholamine neurotransmitters or to detect them in the presence of interfering substances of similar structure. Such sensors will be useful to measure and study neurotransmitter signaling in complex biological settings.

Two Classes of Secreted Synaptic Organizers in the Central Nervous System.

Science.gov (United States)

Yuzaki, Michisuke

2018-02-10

Research in the last two decades has identified many synaptic organizers in the central nervous system that directly regulate the assembly of pre- and/or postsynaptic molecules, such as synaptic vesicles, active zone proteins, and neurotransmitter receptors. They are classified into secreted factors and cell adhesion molecules, such as neurexins and neuroligins. Certain secreted factors are termed extracellular scaffolding proteins (ESPs) because they are components of the synaptic extracellular matrix and serve as a scaffold at the synaptic cleft. These include Lgi1, Cbln1, neuronal pentraxins, Hevin, thrombospondins, and glypicans. Diffusible secreted factors, such as Wnts, fibroblast growth factors, and semaphorins, tend to act from a distance. In contrast, ESPs remain at the synaptic cleft and often help synaptic adhesion and/or accumulation of postsynaptic receptors. Many fundamental questions remain about when, how, and why various synaptic organizers establish and modify the vast numbers of connections during development and throughout life.

Atypical Neurotransmitters and the Neurobiology of Depression.

Science.gov (United States)

Joca, Samia Regiane; Moreira, Fabricio Araujo; Wegener, Gregers

2015-01-01

Since the first report that the mechanism of action of antidepressants involves the facilitation of monoaminergic neurotransmission in the brain in the 1960s, the leading hypothesis about the neurobiology of depression has been the so called "monoaminergic hypothesis". However, a growing body of evidence from the last two decades also supports important involvement of non-monoaminergic mechanisms in the neurobiology of depression and antidepressant action. The discovery of nitric oxide (NO) and endocannabinoid signaling in the brain during the 1990s challenged the wellestablished criteria of classical neurotransmission. These transmitters are synthesized and released on demand by the postsynaptic neurons, and may act as a retrograde messenger on the presynaptic terminal, modulating neurotransmitter release. These unconventional signaling mechanisms and the important role as neural messengers have classified NO and endocannabinoids as atypical neurotransmitters. They are able to modulate neural signaling mediated by the main conventional neurotransmitters systems in the brain, including the monoaminergic, glutamatergic and GABAergic signaling systems. This review aims at discussing the fundamental aspects of NO- and endocannabinoid-mediated signaling in the brain, and how they can be related to the neurobiology of depression. Both preclinical and clinical evidence supporting the involvement of these atypical neurotransmitters in the neurobiology of depression, and in the antidepressant effects are presented here. The evidence is discussed on basis of their ability to modulate different neurotransmitter systems in the brain, including monoaminergic and glutamatergic ones. A better comprehension of NO and endocannabinoid signaling mechanisms in the neurobiology depression could provide new avenues for the development of novel non-monoamine based antidepressants.

Monitoring the electrochemical responses of neurotransmitters through localized surface plasmon resonance using nanohole array.

Science.gov (United States)

Li, Nantao; Lu, Yanli; Li, Shuang; Zhang, Qian; Wu, Jiajia; Jiang, Jing; Liu, Gang Logan; Liu, Qingjun

2017-07-15

In this study, a novel spectroelectrochemical method was proposed for neurotransmitters detection. The central sensing device was a hybrid structure of nanohole array and gold nanoparticles, which demonstrated good conductivity and high localized surface plasmon resonance (LSPR) sensitivity. By utilizing such specially-designed nanoplasmonic sensor as working electrode, both electrical and spectral responses on the surface of the sensor could be simultaneously detected during the electrochemical process. Cyclic voltammetry was implemented to activate the oxidation and recovery of dopamine and serotonin, while transmission spectrum measurement was carried out to synchronously record to LSPR responses of the nanoplasmonic sensor. Coupling with electrochemistry, LSPR results indicated good integrity and linearity, along with promising accuracy in qualitative and quantitative detection even for mixed solution and in brain tissue homogenates. Also, the detection results of other negatively-charged neurotransmitters like acetylcholine demonstrated the selectivity of our detection method for transmitters with positive charge. When compared with traditional electrochemical signals, LSPR signals provided better signal-to-noise ratio and lower detection limits, along with immunity against interference factors like ascorbic acid. Taking the advantages of such robustness, the coupled detection method was proved to be a promising platform for point-of-care testing for neurotransmitters. Copyright © 2016 Elsevier B.V. All rights reserved.

Role of adipose secreted factors and kisspeptin in the metabolic control of gonadotropin secretion and puberty

Science.gov (United States)

Factors secreted by adipose tissue continue to be discovered. Evidence indicates a strong link between neural influences and adipocyte expression and secretion of a wide array of cytokines, neurotrophic factors, growth factors, binding proteins, and neuropeptides. These “adipokines” are linked to im...

Zebrafish neurotransmitter systems as potential pharmacological and toxicological targets.

Science.gov (United States)

Rico, E P; Rosemberg, D B; Seibt, K J; Capiotti, K M; Da Silva, R S; Bonan, C D

2011-01-01

Recent advances in neurobiology have emphasized the study of brain structure and function and its association with numerous pathological and toxicological events. Neurotransmitters are substances that relay, amplify, and modulate electrical signals between neurons and other cells. Neurotransmitter signaling mediates rapid intercellular communication by interacting with cell surface receptors, activating second messenger systems and regulating the activity of ion channels. Changes in the functional balance of neurotransmitters have been implicated in the failure of central nervous system function. In addition, abnormalities in neurotransmitter production or functioning can be induced by several toxicological compounds, many of which are found in the environment. The zebrafish has been increasingly used as an animal model for biomedical research, primarily due to its genetic tractability and ease of maintenance. These features make this species a versatile tool for pre-clinical drug discovery and toxicological investigations. Here, we present a review regarding the role of different excitatory and inhibitory neurotransmitter systems in zebrafish, such as dopaminergic, serotoninergic, cholinergic, purinergic, histaminergic, nitrergic, glutamatergic, glycinergic, and GABAergic systems, and emphasizing their features as pharmacological and toxicological targets. The increase in the global knowledge of neurotransmitter systems in zebrafish and the elucidation of their pharmacological and toxicological aspects may lead to new strategies and appropriate research priorities to offer insights for biomedical and environmental research. Copyright © 2011 Elsevier Inc. All rights reserved.

Anaplerotic roles of pyruvate carboxylase in mammalian tissues.

Science.gov (United States)

Jitrapakdee, S; Vidal-Puig, A; Wallace, J C

2006-04-01

Pyruvate carboxylase (PC) catalyzes the ATP-dependent carboxylation of pyruvate to oxaloacetate. PC serves an anaplerotic role for the tricarboxylic acid cycle, when intermediates are removed for different biosynthetic purposes. In liver and kidney, PC provides oxaloacetate for gluconeogenesis. In adipocytes PC is involved in de novo fatty acid synthesis and glyceroneogenesis, and is regulated by the peroxisome proliferator-activated receptor-gamma, suggesting that PC is involved in the metabolic switch controlling fuel partitioning toward lipogenesis. In islets, PC is necessary for glucose-induced insulin secretion by providing oxaloacetate to form malate that participates in the 'pyruvate/malate cycle' to shuttle 3C or 4C between mitochondria and cytoplasm. Hyperglycemia and hyperlipidemia impair this cycle and affect glucose-stimulated insulin release. In astrocytes, PC is important for de novo synthesis of glutamate, an important excitatory neurotransmitter supplied to neurons. Transcriptional studies of the PC gene pinpoint some transcription factors that determine tissue-specific expression.

Affinity of four polar neurotransmitters for lipid bilayer membranes

DEFF Research Database (Denmark)

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

2011-01-01

. The simulations suggest that this attraction mainly relies on electrostatic interactions of the amino group of the neurotransmitter and the lipid phosphate. We conclude that moderate attraction to lipid membranes occurs for some polar neurotransmitters and hence that one premise for a theory of bilayer-mediated......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...

Simultaneous imaging of multiple neurotransmitters and neuroactive substances in the brain by desorption electrospray ionization mass spectrometry.

Science.gov (United States)

Shariatgorji, Mohammadreza; Strittmatter, Nicole; Nilsson, Anna; Källback, Patrik; Alvarsson, Alexandra; Zhang, Xiaoqun; Vallianatou, Theodosia; Svenningsson, Per; Goodwin, Richard J A; Andren, Per E

2016-08-01

With neurological processes involving multiple neurotransmitters and neuromodulators, it is important to have the ability to directly map and quantify multiple signaling molecules simultaneously in a single analysis. By utilizing a molecular-specific approach, namely desorption electrospray ionization mass spectrometry imaging (DESI-MSI), we demonstrated that the technique can be used to image multiple neurotransmitters and their metabolites (dopamine, dihydroxyphenylacetic acid, 3-methoxytyramine, serotonin, glutamate, glutamine, aspartate, γ-aminobutyric acid, adenosine) as well as neuroactive drugs (amphetamine, sibutramine, fluvoxamine) and drug metabolites in situ directly in brain tissue sections. The use of both positive and negative ionization modes increased the number of identified molecular targets. Chemical derivatization by charge-tagging the primary amines of molecules significantly increased the sensitivity, enabling the detection of low abundant neurotransmitters and other neuroactive substances previously undetectable by MSI. The sensitivity of the imaging approach of neurochemicals has a great potential in many diverse applications in fields such as neuroscience, pharmacology, drug discovery, neurochemistry, and medicine. Copyright © 2016 Elsevier Inc. All rights reserved.

Role of perisynaptic parameters in neurotransmitter homeostasis - computational study of a general synapse

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Pendyam, Sandeep; Mohan, Ashwin; Kalivas, Peter W.; Nair, Satish S.

2015-01-01

Extracellular neurotransmitter concentrations vary over a wide range depending on the type of neurotransmitter and location in the brain. Neurotransmitter homeostasis near a synapse is achieved by a balance of several mechanisms including vesicular release from the presynapse, diffusion, uptake by transporters, non-synaptic production, and regulation of release by autoreceptors. These mechanisms are also affected by the glia surrounding the synapse. However, the role of these mechanisms in achieving neurotransmitter homeostasis is not well understood. A biophysical modeling framework was proposed to reverse engineer glial configurations and parameters related to homeostasis for synapses that support a range of neurotransmitter gradients. Model experiments reveal that synapses with extracellular neurotransmitter concentrations in the micromolar range require non-synaptic neurotransmitter sources and tight synaptic isolation by extracellular glial formations. The model was used to identify the role of perisynaptic parameters on neurotransmitter homeostasis, and to propose glial configurations that could support different levels of extracellular neurotransmitter concentrations. Ranking the parameters based on their effect on neurotransmitter homeostasis, non-synaptic sources were found to be the most important followed by transporter concentration and diffusion coefficient. PMID:22460547

Porters and neurotransmitter transporters

NARCIS (Netherlands)

Nelson, Nathan; Lill, H

1994-01-01

Uptake of neurotransmitters involves multiple transporters acting in different brain locations under different physiological conditions. The vesicular transporters are driven by a proton-motive force generated by a V-ATPase and their substrates are taken up via proton/substrate exchange. The plasma

Anxiolytic action of neuromedin-U and neurotransmitters involved in mice.

Science.gov (United States)

Telegdy, G; Adamik, A

2013-09-10

Peptide Neuromedin-U (NmU) is widely distributed in the central nervous system and the peripheral tissues. Its physiological effects include the regulation of blood pressure, heart rate, and body temperature, and the inhibition of gastric acid secretion. The action of NmU in rats is mediated by two G-protein-coupled receptors, NmU-1R and NmU-2R. NmU-2R is present mainly in the brain, and NmU-1R mainly in the periphery. Despite the great variety of the physiological action of NmU, little is known about its possible effects in different forms of behavior, such as anxiety. In the present work, NmU-23 (the rodent form of the peptide) was tested for its effect on anxiety in elevated plus maze test in mice. For detection of the possible involvement of neurotransmitters, the mice were pretreated with receptor blockers: haloperidol (a D2, dopamine receptor antagonist), propranolol (a β-adrenergic receptor antagonist), atropine (a nonselective muscarinic acetylcholine receptor antagonist), phenoxybenzamine (a nonselective α-adrenergic receptor antagonist) or nitro-l-arginine (a nitric oxide synthase inhibitor). The peptide and nitro-l-arginine were administered into the lateral brain ventricle, while the receptor blockers were applied intraperitoneally. An NmU-23 dose 0.5μg elicited anxiolytic action, whereas this action is faded away when the dose was increased. For further testing therefore 0.5μg i.c.v. was used. Propranolol and atropine fully blocked the NmU-induced anxiolytic action, while haloperidol, phenoxybenzamine and nitro-l-arginine were ineffective. The results suggest that β-adrenergic and cholinergic mechanisms are involved in the anxiolytic action of NmU. © 2013.

Validity of urinary monoamine assay sales under the "spot baseline urinary neurotransmitter testing marketing model".

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Hinz, Marty; Stein, Alvin; Uncini, Thomas

2011-01-01

Spot baseline urinary monoamine assays have been used in medicine for over 50 years as a screening test for monoamine-secreting tumors, such as pheochromocytoma and carcinoid syndrome. In these disease states, when the result of a spot baseline monoamine assay is above the specific value set by the laboratory, it is an indication to obtain a 24-hour urine sample to make a definitive diagnosis. There are no defined applications where spot baseline urinary monoamine assays can be used to diagnose disease or other states directly. No peer-reviewed published original research exists which demonstrates that these assays are valid in the treatment of individual patients in the clinical setting. Since 2001, urinary monoamine assay sales have been promoted for numerous applications under the "spot baseline urinary neurotransmitter testing marketing model". There is no published peer-reviewed original research that defines the scientific foundation upon which the claims for these assays are made. On the contrary, several articles have been published that discredit various aspects of the model. To fill the void, this manuscript is a comprehensive review of the scientific foundation and claims put forth by laboratories selling urinary monoamine assays under the spot baseline urinary neurotransmitter testing marketing model.

Classical neurotransmitters and neuropeptides involved in generalized epilepsy in a multi-neurotransmitter system: How to improve the antiepileptic effect?

Science.gov (United States)

Werner, Felix-Martin; Coveñas, Rafael

2017-06-01

Here, we describe in generalized epilepsies the alterations of classical neurotransmitters and neuropeptides acting at specific subreceptors. In order to consider a network context rather than one based on focal substrates and in order to make the interaction between neurotransmitters and neuropeptides and their specific subreceptors comprehensible, neural networks in the hippocampus, thalamus, and cerebral cortex are described. In this disease, a neurotransmitter imbalance between dopaminergic and serotonergic neurons and between presynaptic GABAergic neurons (hypoactivity) and glutaminergic neurons (hyperactivity) occurs. Consequently, combined GABA A agonists and NMDA antagonists could furthermore stabilize the neural networks in a multimodal pharmacotherapy. The antiepileptic effect and the mechanisms of action of conventional and recently developed antiepileptic drugs are reviewed. The GASH:Sal animal model can contribute to examine the efficacy of antiepileptic drugs. The issues of whether the interaction of classical neurotransmitters with other subreceptors (5-HT 7 , metabotropic 5 glutaminergic, A 2A adenosine, and alpha nicotinic 7 cholinergic receptors) or whether the administration of agonists/antagonists of neuropeptides might improve the therapeutic effect of antiepileptic drugs should be addressed. This article is part of a Special Issue entitled "Genetic and Reflex Epilepsies, Audiogenic Seizures and Strains: From Experimental Models to the Clinic". Copyright © 2015 Elsevier Inc. All rights reserved.

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. Copyright © 2014 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

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 neurotransmitte...

Analysis of Secreted Proteins Using SILAC

DEFF Research Database (Denmark)

Henningsen, Jeanette; Blagoev, Blagoy; Kratchmarova, Irina

2014-01-01

Secreted proteins serve a crucial role in the communication between cells, tissues, and organs. Proteins released to the extracellular environment exert their function either locally or at distant points of the organism. Proteins are secreted in a highly dynamic fashion by cells and tissues...... in the body responding to the stimuli and requirements presented by the extracellular milieu. Characterization of secretomes derived from various cell types has been performed using different quantitative mass spectrometry-based proteomics strategies, several of them taking advantage of labeling with stable...

Neuronal calcium sensor synaptotagmin-9 is not involved in the regulation of glucose homeostasis or insulin secretion.

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Natalia Gustavsson

Full Text Available BACKGROUND: Insulin secretion is a complex and highly regulated process. It is well established that cytoplasmic calcium is a key regulator of insulin secretion, but how elevated intracellular calcium triggers insulin granule exocytosis remains unclear, and we have only begun to define the identities of proteins that are responsible for sensing calcium changes and for transmitting the calcium signal to release machineries. Synaptotagmins are primarily expressed in brain and endocrine cells and exhibit diverse calcium binding properties. Synaptotagmin-1, -2 and -9 are calcium sensors for fast neurotransmitter release in respective brain regions, while synaptotagmin-7 is a positive regulator of calcium-dependent insulin release. Unlike the three neuronal calcium sensors, whose deletion abolished fast neurotransmitter release, synaptotagmin-7 deletion resulted in only partial loss of calcium-dependent insulin secretion, thus suggesting that other calcium-sensors must participate in the regulation of insulin secretion. Of the other synaptotagmin isoforms that are present in pancreatic islets, the neuronal calcium sensor synaptotagmin-9 is expressed at the highest level after synaptotagmin-7. METHODOLOGY/PRINCIPAL FINDINGS: In this study we tested whether synaptotagmin-9 participates in the regulation of glucose-stimulated insulin release by using pancreas-specific synaptotagmin-9 knockout (p-S9X mice. Deletion of synaptotagmin-9 in the pancreas resulted in no changes in glucose homeostasis or body weight. Glucose tolerance, and insulin secretion in vivo and from isolated islets were not affected in the p-S9X mice. Single-cell capacitance measurements showed no difference in insulin granule exocytosis between p-S9X and control mice. CONCLUSIONS: Thus, synaptotagmin-9, although a major calcium sensor in the brain, is not involved in the regulation of glucose-stimulated insulin release from pancreatic β-cells.

Neuronal calcium sensor synaptotagmin-9 is not involved in the regulation of glucose homeostasis or insulin secretion.

Science.gov (United States)

Gustavsson, Natalia; Wang, Xiaorui; Wang, Yue; Seah, Tingting; Xu, Jun; Radda, George K; Südhof, Thomas C; Han, Weiping

2010-11-09

Insulin secretion is a complex and highly regulated process. It is well established that cytoplasmic calcium is a key regulator of insulin secretion, but how elevated intracellular calcium triggers insulin granule exocytosis remains unclear, and we have only begun to define the identities of proteins that are responsible for sensing calcium changes and for transmitting the calcium signal to release machineries. Synaptotagmins are primarily expressed in brain and endocrine cells and exhibit diverse calcium binding properties. Synaptotagmin-1, -2 and -9 are calcium sensors for fast neurotransmitter release in respective brain regions, while synaptotagmin-7 is a positive regulator of calcium-dependent insulin release. Unlike the three neuronal calcium sensors, whose deletion abolished fast neurotransmitter release, synaptotagmin-7 deletion resulted in only partial loss of calcium-dependent insulin secretion, thus suggesting that other calcium-sensors must participate in the regulation of insulin secretion. Of the other synaptotagmin isoforms that are present in pancreatic islets, the neuronal calcium sensor synaptotagmin-9 is expressed at the highest level after synaptotagmin-7. In this study we tested whether synaptotagmin-9 participates in the regulation of glucose-stimulated insulin release by using pancreas-specific synaptotagmin-9 knockout (p-S9X) mice. Deletion of synaptotagmin-9 in the pancreas resulted in no changes in glucose homeostasis or body weight. Glucose tolerance, and insulin secretion in vivo and from isolated islets were not affected in the p-S9X mice. Single-cell capacitance measurements showed no difference in insulin granule exocytosis between p-S9X and control mice. Thus, synaptotagmin-9, although a major calcium sensor in the brain, is not involved in the regulation of glucose-stimulated insulin release from pancreatic β-cells.

Vitis vinifera juice ameliorates depression-like behavior in mice by modulating biogenic amine neurotransmitters

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Muhammad Aslam

2015-12-01

Full Text Available The advantageous effects of Vitis vinifera juice on depressive model mice were examined utilizing a blend of behavioral evaluations and biogenic amine neurotransmitter estimations. During the behavioral evaluations, immobility time on the forced swimming test and tail suspension test were measured in unstressed and immobilization-induced stressed mice. V. vinifera juice (4 mL/kg and 8 mL/kg and fluoxetine (20 mg/kg produced a significant decrease in immobility time of both unstressed and stressed mice when compared with their respective saline-treated control groups in both paradigms. Neurotransmitters were measured using high-performance liquid chromatography with electrochemical detector. V. vinifera juice raised the levels of both serotonin (p<0.001 and noradrenalin (p<0.001 in brain tissue. These outcomes give significant mechanistic insights into the protective effect of V. vinifera juice against depressive disorders. Our results showed that V. vinifera juice could relieve depressive manifestations in the rodent model of depression.

MRI sensing of neurotransmitters with a crown ether appended Gd(3+) complex.

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Oukhatar, Fatima; Même, Sandra; Même, William; Szeremeta, Frédéric; Logothetis, Nikos K; Angelovski, Goran; Tóth, Éva

2015-02-18

Molecular magnetic resonance imaging (MRI) approaches that detect biomarkers associated with neural activity would allow more direct observation of brain function than current functional MRI based on blood-oxygen-level-dependent contrast. Our objective was to create a synthetic molecular platform with appropriate recognition moieties for zwitterionic neurotransmitters that generate an MR signal change upon neurotransmitter binding. The gadolinium complex (GdL) we report offers ditopic binding for zwitterionic amino acid neurotransmitters, via interactions (i) between the positively charged and coordinatively unsaturated metal center and the carboxylate function and (ii) between a triazacrown ether and the amine group of the neurotransmitters. GdL discriminates zwitterionic neurotransmitters from monoamines. Neurotransmitter binding leads to a remarkable relaxivity change, related to a decrease in hydration number. GdL was successfully used to monitor neural activity in ex vivo mouse brain slices by MRI.

Genetic susceptibility and neurotransmitters in Tourette syndrome.

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Paschou, Peristera; Fernandez, Thomas V; Sharp, Frank; Heiman, Gary A; Hoekstra, Pieter J

2013-01-01

Family studies have consistently shown that Tourette syndrome (TS) is a familial disorder and twin studies have clearly indicated a genetic contribution in the etiology of TS. Whereas early segregation studies of TS suggested a single-gene autosomal dominant disorder, later studies have pointed to more complex models including additive and multifactorial inheritance and likely interaction with genetic factors. While the exact cellular and molecular base of TS is as yet elusive, neuroanatomical and neurophysiological studies have pointed to the involvement of cortico-striato-thalamocortical circuits and abnormalities in dopamine, glutamate, gamma-aminobutyric acid, and serotonin neurotransmitter systems, with the most consistent evidence being available for involvement of dopamine-related abnormalities, that is, a reduction in tonic extracellular dopamine levels along with hyperresponsive spike-dependent dopamine release, following stimulation. Genetic and gene expression findings are very much supportive of involvement of these neurotransmitter systems. Moreover, intriguingly, genetic work on a two-generation pedigree has opened new research pointing to a role for histamine, a so far rather neglected neurotransmitter, with the potential of the development of new treatment options. Future studies should be aimed at directly linking neurotransmitter-related genetic and gene expression findings to imaging studies (imaging genetics), which enables a better understanding of the pathways and mechanisms through which the dynamic interplay of genes, brain, and environment shapes the TS phenotype. © 2013 Elsevier Inc. All rights reserved.

Secondary Abnormalities of Neurotransmitters in Infants with Neurological Disorders

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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…

Adipose Tissue-Derived Stem Cell Secreted IGF-1 Protects Myoblasts from the Negative Effect of Myostatin

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Sebastian Gehmert

2014-01-01

Full Text Available Myostatin, a TGF-β family member, is associated with inhibition of muscle growth and differentiation and might interact with the IGF-1 signaling pathway. Since IGF-1 is secreted at a bioactive level by adipose tissue-derived mesenchymal stem cells (ASCs, these cells (ASCs provide a therapeutic option for Duchenne Muscular Dystrophy (DMD. But the protective effect of stem cell secreted IGF-1 on myoblast under high level of myostatin remains unclear. In the present study murine myoblasts were exposed to myostatin under presence of ASCs conditioned medium and investigated for proliferation and apoptosis. The protective effect of IGF-1 was further examined by using IGF-1 neutralizing and receptor antibodies as well as gene silencing RNAi technology. MyoD expression was detected to identify impact of IGF-1 on myoblasts differentiation when exposed to myostatin. IGF-1 was accountable for 43.6% of the antiapoptotic impact and 48.8% for the proliferative effect of ASCs conditioned medium. Furthermore, IGF-1 restored mRNA and protein MyoD expression of myoblasts under risk. Beside fusion and transdifferentiation the beneficial effect of ASCs is mediated by paracrine secreted cytokines, particularly IGF-1. The present study underlines the potential of ASCs as a therapeutic option for Duchenne muscular dystrophy and other dystrophic muscle diseases.

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.

Communication networks in the brain: neurons, receptors, neurotransmitters, and alcohol.

Science.gov (United States)

Lovinger, David M

2008-01-01

Nerve cells (i.e., neurons) communicate via a combination of electrical and chemical signals. Within the neuron, electrical signals driven by charged particles allow rapid conduction from one end of the cell to the other. Communication between neurons occurs at tiny gaps called synapses, where specialized parts of the two cells (i.e., the presynaptic and postsynaptic neurons) come within nanometers of one another to allow for chemical transmission. The presynaptic neuron releases a chemical (i.e., a neurotransmitter) that is received by the postsynaptic neuron's specialized proteins called neurotransmitter receptors. The neurotransmitter molecules bind to the receptor proteins and alter postsynaptic neuronal function. Two types of neurotransmitter receptors exist-ligand-gated ion channels, which permit rapid ion flow directly across the outer cell membrane, and G-protein-coupled receptors, which set into motion chemical signaling events within the cell. Hundreds of molecules are known to act as neurotransmitters in the brain. Neuronal development and function also are affected by peptides known as neurotrophins and by steroid hormones. This article reviews the chemical nature, neuronal actions, receptor subtypes, and therapeutic roles of several transmitters, neurotrophins, and hormones. It focuses on neurotransmitters with important roles in acute and chronic alcohol effects on the brain, such as those that contribute to intoxication, tolerance, dependence, and neurotoxicity, as well as maintained alcohol drinking and addiction.

High-level secretion of tissue factor-rich extracellular vesicles from ovarian cancer cells mediated by filamin-A and protease-activated receptors.

Science.gov (United States)

Koizume, Shiro; Ito, Shin; Yoshioka, Yusuke; Kanayama, Tomohiko; Nakamura, Yoshiyasu; Yoshihara, Mitsuyo; Yamada, Roppei; Ochiya, Takahiro; Ruf, Wolfram; Miyagi, Etsuko; Hirahara, Fumiki; Miyagi, Yohei

2016-01-01

Thromboembolic events occur frequently in ovarian cancer patients. Tissue factor (TF) is often overexpressed in tumours, including ovarian clear-cell carcinoma (CCC), a subtype with a generally poor prognosis. TF-coagulation factor VII (fVII) complexes on the cell surface activate downstream coagulation mechanisms. Moreover, cancer cells secrete extracellular vesicles (EVs), which act as vehicles for TF. We therefore examined the characteristics of EVs produced by ovarian cancer cells of various histological subtypes. CCC cells secreted high levels of TF within EVs, while the high-TF expressing breast cancer cell line MDA-MB-231 shed fewer TF-positive EVs. We also found that CCC tumours with hypoxic tissue areas synthesised TF and fVII in vivo, rendering the blood of xenograft mice bearing these tumours hypercoagulable compared with mice bearing MDA-MB-231 tumours. Incorporation of TF into EVs and secretion of EVs from CCC cells exposed to hypoxia were both dependent on the actin-binding protein, filamin-A (filA). Furthermore, production of these EVs was dependent on different protease-activated receptors (PARs) on the cell surface. These results show that CCC cells could produce large numbers of TF-positive EVs dependent upon filA and PARs. This phenomenon may be the mechanism underlying the increased incidence of venous thromboembolism in ovarian cancer patients.

Postvagotomy acid secretion and mucosal blood flow during beta-adrenoceptor stimulation and universal chemical sympathectomy in dogs

DEFF Research Database (Denmark)

Hovendal, C P

1983-01-01

The aim of the present study was to examine the effect of beta-adrenoceptor stimulation, alpha blockade, and elimination of the adrenergic nerve function on mucosal blood flow and acid secretion in parietal-cell-vagotomized (PCV) gastric fistula dogs. Isoprenaline inhibited pentagastrin-stimulate......The aim of the present study was to examine the effect of beta-adrenoceptor stimulation, alpha blockade, and elimination of the adrenergic nerve function on mucosal blood flow and acid secretion in parietal-cell-vagotomized (PCV) gastric fistula dogs. Isoprenaline inhibited pentagastrin...... to chemical sympathectomy with 6-hydroxy-dopamine, a false neurotransmitter that selectively destroys the adrenergic nerve terminals. Chemical sympathectomy increased the pentagastrin-stimulated gastric acid secretion and stabilized the mucosal blood flow at the level before vagotomy, but with an increased...... ratio between blood flow and acid secretion. One may conclude that the sympathetic nerve system influences gastric function after vagotomy....

Regulation of nonsmall-cell lung cancer stem cell like cells by neurotransmitters and opioid peptides.

Science.gov (United States)

Banerjee, Jheelam; Papu John, Arokya M S; Schuller, Hildegard M

2015-12-15

Nonsmall-cell lung cancer (NSCLC) is the leading type of lung cancer and has a poor prognosis. We have shown that chronic stress promoted NSCLC xenografts in mice via stress neurotransmitter-activated cAMP signaling downstream of beta-adrenergic receptors and incidental beta-blocker therapy was reported to improve clinical outcomes in NSCLC patients. These findings suggest that psychological stress promotes NSCLC whereas pharmacologically or psychologically induced decreases in cAMP may inhibit NSCLC. Cancer stem cells are thought to drive the development, progression and resistance to therapy of NSCLC. However, their potential regulation by stress neurotransmitters has not been investigated. In the current study, epinephrine increased the number of cancer stem cell like cells (CSCs) from three NSCLC cell lines in spheroid formation assays while enhancing intracellular cAMP and the stem cell markers sonic hedgehog (SHH), aldehyde dehydrogenase-1 (ALDH-1) and Gli1, effects reversed by GABA or dynorphin B via Gαi -mediated inhibition of cAMP formation. The growth of NSCLC xenografts in a mouse model of stress reduction was significantly reduced as compared with mice maintained under standard conditions. Stress reduction reduced serum levels of corticosterone, norepinephrine and epinephrine while the inhibitory neurotransmitter γ-aminobutyric acid (GABA) and opioid peptides increased. Stress reduction significantly reduced cAMP, VEGF, p-ERK, p-AKT, p-CREB, p-SRc, SHH, ALDH-1 and Gli1 in xenograft tissues whereas cleaved caspase-3 and p53 were induced. We conclude that stress neurotransmitters activate CSCs in NSCLC via multiple cAMP-mediated pathways and that pharmacologically or psychologically induced decreases in cAMP signaling may improve clinical outcomes in NSCLC patients. © 2015 UICC.

Pattern recognition of neurotransmitters using multimode sensing.

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Stefan-van Staden, Raluca-Ioana; Moldoveanu, Iuliana; van Staden, Jacobus Frederick

2014-05-30

Pattern recognition is essential in chemical analysis of biological fluids. Reliable and sensitive methods for neurotransmitters analysis are needed. Therefore, we developed for pattern recognition of neurotransmitters: dopamine, epinephrine, norepinephrine a method based on multimode sensing. Multimode sensing was performed using microsensors based on diamond paste modified with 5,10,15,20-tetraphenyl-21H,23H-porphyrine, hemin and protoporphyrin IX in stochastic and differential pulse voltammetry modes. Optimized working conditions: phosphate buffer solution of pH 3.01 and KCl 0.1mol/L (as electrolyte support), were determined using cyclic voltammetry and used in all measurements. The lowest limits of quantification were: 10(-10)mol/L for dopamine and epinephrine, and 10(-11)mol/L for norepinephrine. The multimode microsensors were selective over ascorbic and uric acids and the method facilitated reliable assay of neurotransmitters in urine samples, and therefore, the pattern recognition showed high reliability (RSDneurotransmitters on biological fluids at a lower determination level than chromatographic methods. The sampling of the biological fluids referees only to the buffering (1:1, v/v) with a phosphate buffer pH 3.01, while for chromatographic methods the sampling is laborious. Accordingly with the statistic evaluation of the results at 99.00% confidence level, both modes can be used for pattern recognition and quantification of neurotransmitters with high reliability. The best multimode microsensor was the one based on diamond paste modified with protoporphyrin IX. Copyright © 2014 Elsevier B.V. All rights reserved.

Secretion of pancreastatins from the porcine digestive tract

International Nuclear Information System (INIS)

Boerglum Jensen, T.D.; Holst, J.J.; Fahrenkrug, J.

1994-01-01

Pancreastatin, a 49-amino acid peptide with a COOH-terminal glycine amide, was originally isolated from porcine pancreas, but pancreastatin immunoreactivity has been found in several neuroendocrine tissues. There are strong indications that pancreastatin is derived from chromogranin A, since the amino acid sequence 240-288 in porcine chromogranin A corresponds to pancreastatin flanked by typical signals for proteolytic processing. The authors studied the effect of electric stimulation of the nervous supply to perfused porcine pancreas, antrum, nonantral stomach, and small intestine on the release of immunoreactive pancreastatin, and they have characterized the molecular nature of the secreted immunoreactivity by using a radioimmunoassay specific for the COOH-terminal glycine amide of porcine pancreastatin in combination with chromatography. In all tissues nerve stimulation significantly increased the release of immunoreactive pancreastatin. The secreted immunoreactive pancreastatin was heterogeneous, consisting of pancreastatin itself, a COOH-terminal pancreastatin fragment, and NH 2 -terminally extended pancreastatin forms. Pancreastatin predominated in the perfusate from pancreas and antrum, whereas mainly NH 2 -terminally extended molecular forms were secreted from the antrectomized stomach and small intestine. The different molecular forms of pancreastatin were secreted from the perfused organs in the same molar ratio as they occur in extracts of the corresponding tissues. Thus, pancreastatin and other chromogranin A-derived peptides in organ-specific proportions regularly accompany the secretion of the peptide hormones from the gastrointestinal tissues on appropriate stimulation. 40 refs., 5 figs

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.

Role of taurine on acid secretion in the rat stomach

Science.gov (United States)

2011-01-01

Background Taurine has chemical structure similar to an inhibitory neurotransmitter, γ-aminobutyric acid (GABA). Previous studies on GABA in the stomach suggest GABAergic neuron is involved in acid secretion, but the effects of taurine are poor understood. Methods The effects of taurine on acid secretion, signal transduction, and localization of taurinergic neurons were determined in the rat stomach using everted whole stomach, RIA kit and immunohistochemical methods. Results We used antibodies against taurine-synthesizing enzyme, cysteine sulfuric acid decarboxylase (CSAD), and taurine. CSAD- and taurine-positive cells were found in the muscle and mucosal layers. Distributions of CSAD- and taurine-positive cells in both mucosal and muscle layers were heterogeneous in the stomach. Taurine at 10-9~10-4 M induced acid secretion, and the maximum secretion was at 10-5 M, 1.6-fold higher than the spontaneous secretion. Taurine-induced acid secretion was completely inhibited by bicuculline and atropine but not by cimetidine, proglumide, or strychnine. Atropine and tetrodotoxin (TTX) completely inhibited the acid secretion induced by low concentrations of taurine and partially inhibited induced by high concentrations. Verapamil, a calcium blocker agent, inhibited acid output elicited by taurine. We assumed all Ca2+ channels involved in the response to these secretagogues were equally affected by verapamil. Intracellular cAMP (adenosine 3', 5'-monophosphat) in the stomach significantly increased with taurine treatment in a dose-dependent manner. High correlation (r=0.859, p taurine concentrations with cAMP was observed. Conclusions Our results demonstrated for the first time in taurine-induced acid secretion due to increase intracellular calcium may act through the A type of GABA receptors, which are mainly located on cholinergic neurons though cAMP pathway and partially on nonneuronal cells in the rat stomach. PMID:21294907

Role of taurine on acid secretion in the rat stomach

Directory of Open Access Journals (Sweden)

Ho Jau-Der

2011-02-01

Full Text Available Abstract Background Taurine has chemical structure similar to an inhibitory neurotransmitter, γ-aminobutyric acid (GABA. Previous studies on GABA in the stomach suggest GABAergic neuron is involved in acid secretion, but the effects of taurine are poor understood. Methods The effects of taurine on acid secretion, signal transduction, and localization of taurinergic neurons were determined in the rat stomach using everted whole stomach, RIA kit and immunohistochemical methods. Results We used antibodies against taurine-synthesizing enzyme, cysteine sulfuric acid decarboxylase (CSAD, and taurine. CSAD- and taurine-positive cells were found in the muscle and mucosal layers. Distributions of CSAD- and taurine-positive cells in both mucosal and muscle layers were heterogeneous in the stomach. Taurine at 10-9~10-4 M induced acid secretion, and the maximum secretion was at 10-5 M, 1.6-fold higher than the spontaneous secretion. Taurine-induced acid secretion was completely inhibited by bicuculline and atropine but not by cimetidine, proglumide, or strychnine. Atropine and tetrodotoxin (TTX completely inhibited the acid secretion induced by low concentrations of taurine and partially inhibited induced by high concentrations. Verapamil, a calcium blocker agent, inhibited acid output elicited by taurine. We assumed all Ca2+ channels involved in the response to these secretagogues were equally affected by verapamil. Intracellular cAMP (adenosine 3', 5'-monophosphat in the stomach significantly increased with taurine treatment in a dose-dependent manner. High correlation (r=0.859, p Conclusions Our results demonstrated for the first time in taurine-induced acid secretion due to increase intracellular calcium may act through the A type of GABA receptors, which are mainly located on cholinergic neurons though cAMP pathway and partially on nonneuronal cells in the rat stomach.

Effect of physical training on insulin secretion and action in skeletal muscle and adipose tissue of first-degree relatives of type 2 diabetic patients

DEFF Research Database (Denmark)

Dela, Flemming; Stallknecht, Bente Merete

2010-01-01

in CON but not in FDR, whereas glucose-mediated GU increased (P groups. Adipose tissue GU was not affected by training, but it was higher (abdominal, P Training increased skeletal muscle lipolysis (P ...- to sevenfold. We conclude that insulin-secretory capacity is lower in FDR than in CON and that there is dissociation between training-induced changes in insulin secretion and insulin-mediated GU. Maximal GU rates are similar between groups and increases with physical training.......Physical training affects insulin secretion and action, but there is a paucity of data on the direct effects in skeletal muscle and adipose tissue and on the effect of training in first-degree relatives (FDR) of patients with type 2 diabetes. We studied insulin action at the whole body level...

Development of clinical study and application on dopaminergic neurotransmitters and neuroreceptor imaging

International Nuclear Information System (INIS)

Wang Rongfu

2000-01-01

In recent years, the neurotransmitter mapping has been rapidly developed from a lot of fundamental researches to the studies of clinical applications. At present, the dopaminergic neurotransmitter and receptor imaging in the central neurotransmitter mapping study are the most active area including dopaminergic receptor, dopaminergic neurotransmitter and dopaminergic transporter imaging, etc,. The nuclear medicine functional imaging technique with positron emission tomography and single photon emission computed tomography possesses potential advantages in the diagnosis and distinguished diagnosis of neuropsychiatric disorders and movement disorders, and in the study of recognition function

Human renin biosynthesis and secretion in normal and ischemic kidneys

International Nuclear Information System (INIS)

Pratt, R.E.; Carleton, J.E.; Richie, J.P.; Heusser, C.; Dzau, V.J.

1987-01-01

The pathway of renin biosynthesis and secretion in normal and ischemic human kidneys has been investigated by pulse-labeling experiments. The results indicate that in normal human kidney, preprorenin is rapidly processed to 47-kDa prorenin. Microradiosequencing showed that this molecule was generated by cleavage between Gly-23 and Leu-24, yielding a 43-amino acid proregion. Analysis of prorenin secreted by the kidney tissue yielded an identical sequence, indicating that prorenin is secreted without any further proteolysis. An examination of the kinetics of processing and secretion suggested that a majority of the newly synthesized prorenin is quickly secreted, while only a small fraction is processed intracellularly to the mature renin. The differences in secretion kinetics between prorenin and mature renin and the selective inhibition of prorenin secretion by monensin suggest that they are secreted independently via two pathways: a constitutive pathway probably from the Golgi or protogranules that rapidly release prorenin and a regulated pathway that secretes mature renin from the mature granules. A comparison of the kinetics of processing between normal and ischemic tissues suggests that renal ischemia leads to an overall increase in the rate of processing or prorenin to mature renin. In addition, prolonged biosynthetic labeling of renin in the ischemic kidney yielded two smaller molecular weight immunoreactive forms suggestive of renin fragments that may be degradative products. These fragments were not detected in normal kidney tissue labeled for similar lengths of time

Functional relevance of neurotransmitter receptor heteromers in the central nervous system.

Science.gov (United States)

Ferré, Sergi; Ciruela, Francisco; Woods, Amina S; Lluis, Carme; Franco, Rafael

2007-09-01

The existence of neurotransmitter receptor heteromers is becoming broadly accepted and their functional significance is being revealed. Heteromerization of neurotransmitter receptors produces functional entities that possess different biochemical characteristics with respect to the individual components of the heteromer. Neurotransmitter receptor heteromers can function as processors of computations that modulate cell signaling. Thus, the quantitative or qualitative aspects of the signaling generated by stimulation of any of the individual receptor units in the heteromer are different from those obtained during coactivation. Furthermore, recent studies demonstrate that some neurotransmitter receptor heteromers can exert an effect as processors of computations that directly modulate both pre- and postsynaptic neurotransmission. This is illustrated by the analysis of striatal receptor heteromers that control striatal glutamatergic neurotransmission.

Challenges and recent advances in mass spectrometric imaging of neurotransmitters

Science.gov (United States)

Gemperline, Erin; Chen, Bingming; Li, Lingjun

2014-01-01

Mass spectrometric imaging (MSI) is a powerful tool that grants the ability to investigate a broad mass range of molecules, from small molecules to large proteins, by creating detailed distribution maps of selected compounds. To date, MSI has demonstrated its versatility in the study of neurotransmitters and neuropeptides of different classes toward investigation of neurobiological functions and diseases. These studies have provided significant insight in neurobiology over the years and current technical advances are facilitating further improvements in this field. neurotransmitters, focusing specifically on the challenges and recent Herein, we advances of MSI of neurotransmitters. PMID:24568355

Regulation of neurosteroid biosynthesis by neurotransmitters and neuropeptides

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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

NEUROTRANSMITTER ABNORMALITIES AND RESPONSE TO SUPPLEMENTATION IN SPG11

Science.gov (United States)

Vanderver, Adeline; Tonduti, Davide; Auerbach, Sarah; Schmidt, Johanna L.; Parikh, Sumit; Gowans, Gordon C.; Jackson, Kelly E.; Brock, Pamela L.; Patterson, Marc; Nehrebecky, Michelle; Godfrey, Rena; Zein, Wadih M.; Gahl, William; Toro, Camilo

2012-01-01

Objective To report the detection of secondary neurotransmitter abnormalities in a group of SPG11 patients and describe treatment with L-dopa/carbidopa and sapropterin. Design Case reports Setting National Institutes of Health in the context of the Undiagnosed Disease Program; Children’s National Medical Center in the context of Myelin Disorders Bioregistry Program Patients Four SPG11 patients with a clinical picture of progressive spastic paraparesis complicated by extrapyramidal symptoms and maculopathy Interventions L-dopa/carbidopa and sapropterin Results 3/4 patients presented secondary neurotransmitter abnormalities; 4/4 partially responded to L-dopa as well as sapropterin Conclusions In the SPG11 patient with extrapyramidal symptoms, a trial of L-dopa/carbidopa and sapropterin and/or evaluation of cerebrospinal fluid neurotransmitters should be considered. PMID:22749184

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

OpenAIRE

Uutela, Päivi

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...

Tunable Molecular Logic Gates Designed for Imaging Released Neurotransmitters.

Science.gov (United States)

Klockow, Jessica L; Hettie, Kenneth S; Secor, Kristen E; Barman, Dipti N; Glass, Timothy E

2015-08-03

Tunable dual-analyte fluorescent molecular logic gates (ExoSensors) were designed for the purpose of imaging select vesicular primary-amine neurotransmitters that are released from secretory vesicles upon exocytosis. ExoSensors are based on the coumarin-3-aldehyde scaffold and rely on both neurotransmitter binding and the change in environmental pH associated with exocytosis to afford a unique turn-on fluorescence output. A pH-functionality was directly integrated into the fluorophore π-system of the scaffold, thereby allowing for an enhanced fluorescence output upon the release of labeled neurotransmitters. By altering the pH-sensitive unit with various electron-donating and -withdrawing sulfonamide substituents, we identified a correlation between the pKa of the pH-sensitive group and the fluorescence output from the activated fluorophore. In doing so, we achieved a twelvefold fluorescence enhancement upon evaluating the ExoSensors under conditions that mimic exocytosis. ExoSensors are aptly suited to serve as molecular imaging tools that allow for the direct visualization of only the neurotransmitters that are released from secretory vesicles upon exocytosis. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Palmitoylation as a Functional Regulator of Neurotransmitter Receptors

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Vladimir S. Naumenko

2018-01-01

Full Text Available The majority of neuronal proteins involved in cellular signaling undergo different posttranslational modifications significantly affecting their functions. One of these modifications is a covalent attachment of a 16-C palmitic acid to one or more cysteine residues (S-palmitoylation within the target protein. Palmitoylation is a reversible modification, and repeated cycles of palmitoylation/depalmitoylation might be critically involved in the regulation of multiple signaling processes. Palmitoylation also represents a common posttranslational modification of the neurotransmitter receptors, including G protein-coupled receptors (GPCRs and ligand-gated ion channels (LICs. From the functional point of view, palmitoylation affects a wide span of neurotransmitter receptors activities including their trafficking, sorting, stability, residence lifetime at the cell surface, endocytosis, recycling, and synaptic clustering. This review summarizes the current knowledge on the palmitoylation of neurotransmitter receptors and its role in the regulation of receptors functions as well as in the control of different kinds of physiological and pathological behavior.

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.

Pituitary tumour causing gigantism. Morphology and in vitro hormone secretion.

Science.gov (United States)

Anniko, M; Ritzén, E M

1986-01-01

True gigantism with overproduction of growth hormone (GH) and prolactin (PRL) was diagnosed in a 13-year-old boy. The clinical history indicated that the tumour had caused an oversecretion of GH since the age of 4-5 years. At diagnosis, the sella turcica was markedly enlarged. No infiltrative growth was noted at surgery. Endocrine investigations showed elevated GH and PRL secretion. Light and electron microscopy of tumour tissue revealed densely packed pleomorphic cells of both GH and PRL type. In addition, oncocyte-like cells were observed. Organ culture of pieces of tumour tissue demonstrated continued secretion of GH and PRL into the medium for more than 5 days in vitro. Addition of bromocriptine to the medium caused a rapid decline in PRL secretion while GH secretion remained the same. X-ray irradiation in vitro also caused a decrease in PRL secretion. These effects of bromocriptine and X-ray on hormone secretion in vitro mirrored the corresponding effect of treatment, when the patient showed signs of tumour recurrence after pituitary surgery. It is concluded that also in childhood, the in vitro response of tumour tissue to various treatments may be explored as a possible way to predict the efficacy of pharmacological or irradiation treatment of pituitary tumours.

General principles of neurotransmitter detection. Problems and application to catecholamines

International Nuclear Information System (INIS)

Taxi, Jacques

1976-01-01

The use of radioautography for neurotransmitter studies requires two preliminary conditions (in addition to the availability of tritiated molecules): there must be a selective uptake of the neurotransmitter itself, or of a related substance (precursor or false transmitter); the labelled substance must be preserved in situ by fixation and must not be removed by further treatments. Since the putative neurotransmitters are generally small, hydrosoluble molecules, they can be maintained in situ only if they are bound to structure made insoluble by the fixative. The technical indications are summarized so that the successive stages of experimentation can be considered in an attempt to answer the major questions posed by the experimenter

Macrocyclic Gd(3+) complexes with pendant crown ethers designed for binding zwitterionic neurotransmitters.

Science.gov (United States)

Oukhatar, Fatima; Meudal, Hervé; Landon, Céline; Logothetis, Nikos K; Platas-Iglesias, Carlos; Angelovski, Goran; Tóth, Éva

2015-07-27

A series of Gd(3+) complexes exhibiting a relaxometric response to zwitterionic amino acid neurotransmitters was synthesized. The design concept involves ditopic interactions 1) between a positively charged and coordinatively unsaturated Gd(3+) chelate and the carboxylate group of the neurotransmitters and 2) between an azacrown ether appended to the chelate and the amino group of the neurotransmitters. The chelates differ in the nature and length of the linker connecting the cyclen-type macrocycle that binds the Ln(3+) ion and the crown ether. The complexes are monohydrated, but they exhibit high proton relaxivities (up to 7.7 mM(-1)  s(-1) at 60 MHz, 310 K) due to slow molecular tumbling. The formation of ternary complexes with neurotransmitters was monitored by (1) H relaxometric titrations of the Gd(3+) complexes and by luminescence measurements on the Eu(3+) and Tb(3+) analogues at pH 7.4. The remarkable relaxivity decrease (≈80 %) observed on neurotransmitter binding is related to the decrease in the hydration number, as evidenced by luminescence lifetime measurements on the Eu(3+) complexes. These complexes show affinity for amino acid neurotransmitters in the millimolar range, which can be suited to imaging concentrations of synaptically released neurotransmitters. They display good selectivity over non-amino acid neurotransmitters (acetylcholine, serotonin, and noradrenaline) and hydrogenphosphate, but selectivity over hydrogencarbonate was not achieved. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Functional and phenotypical analysis of IL-6-secreting CD4+ T cells in human adipose tissue.

Science.gov (United States)

de Jong, Anja J; Pollastro, Sabrina; Kwekkeboom, Joanneke C; Andersen, Stefan N; Dorjée, Annemarie L; Bakker, Aleida M; Alzaid, Fawaz; Soprani, Antoine; Nelissen, Rob G H H; Mullers, Jan B; Venteclef, Nicolas; de Vries, Niek; Kloppenburg, Margreet; Toes, René E M; Ioan-Facsinay, Andreea

2018-03-01

Emerging evidence indicates that a dynamic interplay between the immune system and adipocytes contributes to the disturbed homeostasis in adipose tissue of obese subjects. Recently, we observed IL-6-secretion by CD4 + T cells from the stromal vascular fraction (SVF) of the infrapatellar fat pad (IFP) of knee osteoarthritis patients directly ex vivo. Here we show that human IL-6 + CD4 + T cells from SVF display a more activated phenotype than the IL-6 - T cells, as evidenced by the expression of the activation marker CD69. Analysis of cytokines secretion, as well as expression of chemokine receptors and transcription factors associated with different Th subsets (Treg, Th1, Th2, Th17 and Tfh) revealed that IL-6-secreting CD4 + T cells cannot be assigned to a conventional Th subset. TCRβ gene analysis revealed that IL-6 + and IL-6 - CD4 + T cells appear clonally unrelated to each other, suggesting a different specificity of these cells. In line with these observations, adipocytes are capable of enhancing IL-6 production by CD4 + T cells. Thus, IL-6 + CD4 + T cells are TCRαβ T cells expressing an activated phenotype potentially resulting from an interplay with adipocytes that could be involved in the inflammatory processes in the OA joint. © 2017 The Authors. European Journal of Immunology published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Dynamic neurotransmitter interactions measured with PET

International Nuclear Information System (INIS)

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

2001-01-01

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

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

Concise Review: Mesenchymal Stem Cells Ameliorate Tissue Injury via Secretion of Tumor Necrosis Factor-α Stimulated Protein/Gene 6

Directory of Open Access Journals (Sweden)

Zhigang He

2014-01-01

Full Text Available Numerous reports have described therapeutic benefits in various disease models after administration of the adult stem/progenitor cells from bone marrow or other tissues referred to as mesenchymal stem cells/multipotent mesenchymal stromal cells (MSCs. They all showed that one of the important effects of MSCs is to act against excessive inflammatory responses and repair the damaged tissues. The therapeutic benefits of MSCs were initially interpreted by their migration, engraftment, and differentiation into target tissues. However, remarkable anatomical structural repairs and functional improvements were increasingly observed with a small number of or even no MSCs in the injured tissues. This suggests that most beneficial effects are largely due to paracrine secretions or cell-to-cell contacts that have multiple effects involving modulation of inflammatory and immune responses. Currently, the therapeutic benefits of MSCs are in part explained by the cells being activated by signals from injured tissues to express an anti-inflammatory protein, tumor-necrosis-factor-α-induced protein 6. This important mechanism of action has attracted increasing attention, and therefore we conducted this review to summarize the latest research.

Neurotransmitter transporters in schistosomes: structure, function and prospects for drug discovery.

Science.gov (United States)

Ribeiro, Paula; Patocka, Nicholas

2013-12-01

Neurotransmitter transporters (NTTs) play a fundamental role in the control of neurotransmitter signaling and homeostasis. Sodium symporters of the plasma membrane mediate the cellular uptake of neurotransmitter from the synaptic cleft, whereas proton-driven vesicular transporters sequester the neurotransmitter into synaptic vesicles for subsequent release. Together these transporters control how much transmitter is released and how long it remains in the synaptic cleft, thereby regulating the intensity and duration of signaling. NTTs have been the subject of much research in mammals and there is growing interest in their activities among invertebrates as well. In this review we will focus our attention on NTTs of the parasitic flatworm Schistosoma mansoni. Bloodflukes of the genus Schistosoma are the causative agents of human schistosomiasis, a devastating disease that afflicts over 200 million people worldwide. Schistosomes have a well-developed nervous system and a rich diversity of neurotransmitters, including many of the small-molecule ("classical") neurotransmitters that normally employ NTTs in their mechanism of signaling. Recent advances in schistosome genomics have unveiled numerous NTTs in this parasite, some of which have now been cloned and characterized in vitro. Moreover new genetic and pharmacological evidence suggests that NTTs are required for proper control of neuromuscular signaling and movement of the worm. Among these carriers are proteins that have been successfully targeted for drug discovery in other organisms, in particular sodium symporters for biogenic amine neurotransmitters such as serotonin and dopamine. Our goal in this chapter is to review the current status of research on schistosome NTTs, with emphasis on biogenic amine sodium symporters, and to evaluate their potential for anti-schistosomal drug targeting. Through this discussion we hope to draw attention to this important superfamily of parasite proteins and to identify new

Selectivity of phenothiazine cholinesterase inhibitors for neurotransmitter systems.

Science.gov (United States)

Darvesh, Sultan; Macdonald, Ian R; Martin, Earl

2013-07-01

Synthetic derivatives of phenothiazine have been used for over a century as well-tolerated drugs against a variety of human ailments from psychosis to cancer. This implies a considerable diversity in the mechanisms of action produced by structural changes to the phenothiazine scaffold. For example, chlorpromazine treatment of psychosis is related to its interaction with dopaminergic receptors. On the other hand, antagonistic action of such drugs on cholinergic receptor systems would be counter-productive for treatment of Alzheimer's disease. In a search for phenothiazines that are inhibitors of cholinesterases, especially butyrylcholinesterase, with potential to treat Alzheimer's disease, we wished to ascertain that such molecules could be devoid of neurotransmitter receptor interactions. To that end, a number of our synthetic N-10-carbonyl phenothiazine derivatives, with cholinesterase inhibitory activity, were tested for interaction with a variety of neurotransmitter receptor systems. We demonstrate that phenothiazines can be prepared without significant neurotransmitter receptor interactions while retaining high potency as cholinesterase ligands for treatment of Alzheimer's disease. Copyright © 2013 Elsevier Ltd. All rights reserved.

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

Pharmacological approaches for Alzheimer's disease: neurotransmitter as drug targets.

Science.gov (United States)

Prakash, Atish; Kalra, Jaspreet; Mani, Vasudevan; Ramasamy, Kalavathy; Majeed, Abu Bakar Abdul

2015-01-01

Alzheimer's disease (AD) is the most common CNS disorder occurring worldwide. There is neither proven effective prevention for AD nor a cure for patients with this disorder. Hence, there is an urgent need to develop safer and more efficacious drugs to help combat the tremendous increase in disease progression. The present review is an attempt at discussing the treatment strategies and drugs under clinical trials governing the modulation of neurotransmitter. Therefore, looking at neurotransmitter abnormalities, there is an urge for developing the pharmacological approaches aimed at correcting those abnormalities and dysfunctioning. In addition, this review also discusses the drugs that are in Phase III trials for the treatment of AD. Despite advances in treatment strategies aimed at correcting neurotransmitter abnormalities, there exists a need for the development of drug therapies focusing on the attempts to remove the pathogenomic protein deposits, thus combating the disease progression.

Leptine: an hormone secreted by adipose tissue. First study in Uruguayan population sample

International Nuclear Information System (INIS)

Pisabarro, Raul; Irrazabal, Ernesto; Recalde, Alicia; Barrios, Enrique; Arocena, Beatriz; Garcia Loriente, Jose Maria; Lorenzo Bonifazio, Juan

1999-01-01

The recent discovery of leptine, an hormone secreted by adipose tissue which modulates the energetic expenditure has signified a gigantic advance in studying obesity facts. In spite of a recent description of absence of leptine in humans, the obesity human model answers to leptine resistance. In this paper, we revise the actual concepts and show leptine values of a sample of 101 middle aged uruguayans, male and female, of normal weight and over weighted (table 1), correlated with corporal mass index (CMI) as an indirect measure of total body fat and waist diameter as an indirect measure of visceral fat, and hips (periferical fat). Bioimpedance studies were carried out to get the corporal composition. Results: good correlation between corporal fat and leptine, but fat distribution was not found representative. All in all, this data set confirms the correlation between leptine and total body fat mass

A neurotransmitter transporter encoded by the Drosophila inebriated gene

Science.gov (United States)

Soehnge, Holly; Huang, Xi; Becker, Marie; Whitley, Penn; Conover, Diana; Stern, Michael

1996-01-01

Behavioral and electrophysiological studies on mutants defective in the Drosophila inebriated (ine) gene demonstrated increased excitability of the motor neuron. In this paper, we describe the cloning and sequence analysis of ine. Mutations in ine were localized on cloned DNA by restriction mapping and restriction fragment length polymorphism (RFLP) mapping of ine mutants. DNA from the ine region was then used to isolate an ine cDNA. In situ hybridization of ine transcripts to developing embryos revealed expression of this gene in several cell types, including the posterior hindgut, Malpighian tubules, anal plate, garland cells, and a subset of cells in the central nervous system. The ine cDNA contains an open reading frame of 658 amino acids with a high degree of sequence similarity to members of the Na+/Cl−-dependent neurotransmitter transporter family. Members of this family catalyze the rapid reuptake of neurotransmitters released into the synapse and thereby play key roles in controlling neuronal function. We conclude that ine mutations cause increased excitability of the Drosophila motor neuron by causing the defective reuptake of the substrate neurotransmitter of the ine transporter and thus overstimulation of the motor neuron by this neurotransmitter. From this observation comes a unique opportunity to perform a genetic dissection of the regulation of excitability of the Drosophila motor neuron. PMID:8917579

Changes in Neurotransmitter Profiles during Early Zebrafish (Danio rerio) Development and after Pesticide Exposure.

Science.gov (United States)

Tufi, Sara; Leonards, Pim; Lamoree, Marja; de Boer, Jacob; Legler, Juliette; Legradi, Jessica

2016-03-15

During early development, neurotransmitters are important stimulants for the development of the central nervous system. Although the development of different neuronal cell types during early zebrafish (Danio rerio) development is well-studied, little is known of the levels of neurotransmitters, their precursors and metabolites during development, and how these levels are affected by exposure to environmental contaminants. A method based on hydrophilic interaction liquid chromatography coupled to tandem mass spectrometry has been applied for the first time to zebrafish embryos and larvae to study five neurotransmitter systems in parallel, including the dopaminergic-andrenergic, glutaminergic-GABAnergic, serotoninergic, histaminergic, and cholinergic systems. Our method enables the quantification of neurotransmitters and their precursors and metabolites in whole zebrafish from the period of zygote to free-swimming larvae 6 days postfertilization (dpf). We observed a developmental stage-dependent pattern with clear differences between the first 2 days of development and the following days. Whereas the neurotransmitter levels steadily increased, the precursors showed a peak at 3 dpf. After exposure to several pesticides, significant differences in concentrations of neurotransmitters and precursors were observed. Our study revealed new insights about neurotransmitter systems during early zebrafish development and showed the usefulness of our approach for environmental neurotoxicity studies.

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.

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.

Psychotropic and neurotropic drugs and neurotransmitter receptors

International Nuclear Information System (INIS)

Takahashi, Ryo

1986-01-01

Neurotransmitters are important in nervous and mental diseases because of their part in the pathogenesis of such diseases; at the same time, they play significant roles in the actions of effective therapeutic drugs. Studies of the mechanisms involved in the actions of such drugs not only generate useful methods to elucidate the pathogenesis of nervous and mental disorders but also serve as indispensable means of developing new drugs. In this field, investigations using both animal models of certain diseases and healthy animals are essential. Development of these animal models is urgently required. In this workshop, studies were presented of the mechanisms of action of major neuropsychotropic drugs such as anxiolytics, antidepressants, and antipsychotics, assessed in terms of the parts played by neurotransmitters and receptors. (Auth.)

[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 occupational stress degree groups, multiple comparison showed high. occupational stress group was higher than those of low occupational stress group. Multivariate correlation analysis showed that the occupational stress and sleep quality component scores correlated positively with the 5-HT, NE and SP (P Occupational stress in petroleum workers is correlated with serum monoamine and neuropeptides neurotransmitters, and it may affect serum levels of monoamine and neuropeptides neurotransmitters.

EFFECTS OF SECRETABLE PLACENTAL FACTORS UPON SECRETION OF CYTOKINES BY THP-1 MONOCYTE-LIKE CELLS

Directory of Open Access Journals (Sweden)

Ya. S. Onokhina

2013-01-01

Full Text Available Abstract. Мonocytes in feto-placental circulation are exposed to factors secreted by placental tissue. These factors influence monocyte functions in pregnancy. In present study, an in vitro model (monocyte-like THP-1 cells was used for assessing effects of soluble placental factors obtained from women with physiological pregnancies, or preeclampsia cases. The following effects of placental factors were revealed: increased secretion of VEGF by THP-1 cells along with decreased secretion of IL-6, IL-8 and MCP-1 under the influence of placental factors from the I. trimester of pregnancy in comparison with III. trimester. Secretion of IL-6 and MCP-1 by THP-1 cells was increased, and secretion of soluble TNFRII was decreased upon co-cultivation with soluble placental factors from the women with preeclampsia, as compared with placental products from physiological pregnancies.The work is supported by grants ГК № 02.740.11.0711 from Ministry of Education and Science, and НШ-3594.2010.7 grant from the President of Russian Federation.

Ethylbenzene-induced hearing loss, neurobehavioral function, and neurotransmitter alterations in petrochemical workers.

Science.gov (United States)

Zhang, Ming; Wang, Yanrang; Wang, Qian; Yang, Deyi; Zhang, Jingshu; Wang, Fengshan; Gu, Qing

2013-09-01

To estimate hearing loss, neurobehavioral function, and neurotransmitter alteration induced by ethylbenzene in petrochemical workers. From two petrochemical plants, 246 and 307 workers exposed to both ethylbenzene and noise were recruited-290 workers exposed to noise only from a power station plant and 327 office personnel as control group, respectively. Hearing and neurobehavioral functions were evaluated. Serum neurotransmitters were also determined. The prevalence of hearing loss was much higher in petrochemical groups than that in power station and control groups (P workers (P hearing loss, neurobehavioral function impairment, and imbalance of neurotransmitters.

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

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...

A Life of Neurotransmitters.

Science.gov (United States)

Snyder, Solomon H

2017-01-06

Development of scientific creativity is often tied closely to mentorship. In my case, two years with Julius Axelrod, the sum total of my research training, was transformative. My mentoring generations of graduate students and postdoctoral fellows has been as nurturing for me as it has been for them. Work in our lab over fifty years has covered the breadth of neurotransmitters and related substances, focusing on the discovery and characterization of novel messenger molecules. I can't conceptualize a more rewarding professional life.

[Brain repair after ischemic stroke: role of neurotransmitters in post-ischemic neurogenesis].

Science.gov (United States)

Sánchez-Mendoza, Eduardo; Bellver-Landete, Víctor; González, María Pilar; Merino, José Joaquín; Martínez-Murillo, Ricardo; Oset-Gasque, María Jesús

2012-11-01

Brain ischemia and reperfusion produce alterations in the microenvironment of the parenchyma, including ATP depletion, ionic homeostasis alterations, inflammation, release of multiple cytokines and abnormal release of neurotransmitters. As a consequence, the induction of proliferation and migration of neural stem cells towards the peri-infarct region occurs. The success of new neurorestorative treatments for damaged brain implies the need to know, with greater accuracy, the mechanisms in charge of regulating adult neurogenesis, both under physiological and pathological conditions. Recent evidence demonstrates that many neurotransmitters, glutamate in particular, control the subventricular zone, thus being part of the complex signalling network that influences the production of new neurons. Neurotransmitters provide a link between brain activity and subventricular zone neurogenesis. Therefore, a deeper knowledge of the role of neurotransmitters systems, such as glutamate and its transporters, in adult neurogenesis, may provide a valuable tool to be used as a neurorestorative therapy in this pathology.

Neurosteroid biosynthesis: enzymatic pathways and neuroendocrine regulation by neurotransmitters and neuropeptides.

Science.gov (United States)

Do Rego, Jean Luc; Seong, Jae Young; Burel, Delphine; Leprince, Jerôme; Luu-The, Van; Tsutsui, Kazuyoshi; Tonon, Marie-Christine; Pelletier, Georges; Vaudry, Hubert

2009-08-01

Neuroactive steroids synthesized in neuronal tissue, referred to as neurosteroids, are implicated in proliferation, differentiation, activity and survival of nerve cells. Neurosteroids are also involved in the control of a number of behavioral, neuroendocrine and metabolic processes such as regulation of food intake, locomotor activity, sexual activity, aggressiveness, anxiety, depression, body temperature and blood pressure. In this article, we summarize the current knowledge regarding the existence, neuroanatomical distribution and biological activity of the enzymes responsible for the biosynthesis of neurosteroids in the brain of vertebrates, and we review the neuronal mechanisms that control the activity of these enzymes. The observation that the activity of key steroidogenic enzymes is finely tuned by various neurotransmitters and neuropeptides strongly suggests that some of the central effects of these neuromodulators may be mediated via the regulation of neurosteroid production.

Neurotransmitter alteration in a testosterone propionate-induced polycystic ovarian syndrome rat model.

Science.gov (United States)

Chaudhari, Nirja K; Nampoothiri, Laxmipriya P

2017-02-01

Polycystic ovarian syndrome (PCOS), one of the leading causes of infertility seen in women, is characterized by anovulation and hyperandrogenism, resulting in ovarian dysfunction. In addition, associations of several metabolic complications like insulin resistance, obesity, dyslipidemia and psychological co-morbidities are well known in PCOS. One of the major factors influencing mood and the emotional state of mind is neurotransmitters. Also, these neurotransmitters are very crucial for GnRH release. Hence, the current study investigates the status of neurotransmitters in PCOS. A PCOS rat model was developed using testosterone. Twenty-one-day-old rats were subcutaneously injected with 10 mg/kg body weight of testosterone propionate (TP) for 35 days. The animals were validated for PCOS characteristics by monitoring estrus cyclicity, serum testosterone and estradiol levels and by histological examination of ovarian sections. Neurotransmitter estimation was carried out using fluorometric and spectrophotometric methods. TP-treated animals demonstrated increased serum testosterone levels with unaltered estradiol content, disturbed estrus cyclicity and many peripheral cysts in the ovary compared to control rats mimicking human PCOS. Norepinephrine (NE), dopamine, serotonin, γ-amino butyric acid (GABA) and epinephrine levels were significantly low in TP-induced PCOS rats compared to control ones, whereas the activity of acetylcholinesterase in the PCOS brain was markedly elevated. Neurotransmitter alteration could be one of the reasons for disturbed gonadotropin-releasing hormone (GnRH) release, consequently directing the ovarian dysfunction in PCOS. Also, decrease in neurotransmitters, mainly NE, serotonin and dopamine (DA) attributes to mood disorders like depression and anxiety in PCOS.

Unraveling the Wnt secretion pathway

NARCIS (Netherlands)

Harterink, M.

2011-01-01

The Wnt family of signaling proteins has essential functions in development and adult tissue homeostasis throughout the animal kingdom. Although signaling cascades triggered by Wnt proteins have been extensively studied, much remains to be learned about how Wnts are produced and secreted and how

Chapter 54: the discovery of neurotransmitters, and applications to neurology.

Science.gov (United States)

Sourkes, Theodore L

2010-01-01

The theory of chemical transmission has proved to be a powerful tool in the analysis of many aspects of neurological function, and its implications loom large on the horizon of neurology and psychiatry. Neurotransmitters are released at neuronal endings, diffuse rapidly across the synaptic cleft, and then act upon receptor proteins embedded in the membrane of the post-synaptic neuron or gland. Drugs are evaluated for their ability to stimulate or to block specific receptors, and in that way modify activity of the postsynaptic organ in order to achieve some desirable therapeutic effect. This chapter is concerned with our knowledge of some of the principal neurotransmitters, namely the primary amines: dopamine, noradrenaline, and serotonin; the quaternary amine: acetylcholine; and the aminoacids: gamma-aminobutyric acid, glutamic acid and glycine. The historical background to the discovery of these molecules as physiological neurotransmitters is presented, and their relation to various clinical states is discussed.

Proton MR Spectroscopy—Detectable Major Neurotransmitters of the Brain: Biology and Possible Clinical Applications

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Agarwal, N.; Renshaw, P.F.

2015-01-01

SUMMARY Neurotransmitters are chemical substances that, by definition, allow communication between neurons and permit most neuronal-glial interactions in the CNS. Approximately 80% of all neurons use glutamate, and almost all interneurons use GABA. A third neurotransmitter, NAAG, modulates glutamatergic neurotransmission. Concentration changes in these molecules due to defective synthetic machinery, receptor expression, or errors in their degradation and metabolism are accepted causes of several neurologic disorders. Knowledge of changes in neurotransmitter concentrations in the brain can add useful information in making a diagnosis, helping to pick the right drug of treatment, and monitoring patient response to drugs in a more objective manner. Recent advances in 1H-MR spectroscopy hold promise in providing a more reliable in vivo detection of these neurotransmitters. In this article, we summarize the essential biology of 3 major neurotransmitters: glutamate, GABA, and NAAG. Finally we illustrate possible applications of 1H-MR spectroscopy in neuroscience research. PMID:22207303

Human placenta secretes apolipoprotein B-100-containing lipoproteins

DEFF Research Database (Denmark)

Munk-Madsen, Eva; Lindegaard, Marie Louise Skakkebæk; Andersen, Claus B

2004-01-01

Supply of lipids from the mother is essential for fetal growth and development. In mice, disruption of yolk sac cell secretion of apolipoprotein (apo) B-containing lipoproteins results in embryonic lethality. In humans, the yolk sac is vestigial. Nutritional functions are instead established very...... lipoproteins secreted from placental tissue showed spherical particles with a diameter of 47 +/- 10 nm. These results demonstrate that human placenta expresses both apoB and MTP and consequently synthesize and secrete apoB-100-containing lipoproteins. Placental lipoprotein formation constitutes a novel pathway...

Identification of small secreted peptides (SSPs) in maize and expression analysis of partial SSP genes in reproductive tissues.

Science.gov (United States)

Li, Ye Long; Dai, Xin Ren; Yue, Xun; Gao, Xin-Qi; Zhang, Xian Sheng

2014-10-01

Maize 1,491 small secreted peptides were identified, which were classified according to the character of peptide sequences. Partial SSP gene expressions in reproductive tissues were determined by qRT-PCR. Small secreted peptides (SSPs) are important cell-cell communication messengers in plants. Most information on plant SSPs come from Arabidopsis thaliana and Oryza sativa, while little is known about the SSPs of other grass species such as maize (Zea mays). In this study, we identified 1,491 SSP genes from maize genomic sequences. These putative SSP genes were distributed throughout the ten maize chromosomes. Among them, 611 SSPs were classified into 198 superfamilies according to their conserved domains, and 725 SSPs with four or more cysteines at their C-termini shared similar cysteine arrangements with their counterparts in other plant species. Moreover, the SSPs requiring post-translational modification, as well as defensin-like (DEFL) proteins, were identified. Further, the expression levels of 110 SSP genes were analyzed in reproductive tissues, including male flower, pollen, silk, and ovary. Most of the genes encoding basal-layer antifungal peptide-like, small coat proteins-like, thioredoxin-like proteins, γ-thionins-like, and DEFL proteins showed high expression levels in the ovary and male flower compared with their levels in silk and mature pollen. The rapid alkalinization factor-like genes were highly expressed only in the mature ovary and mature pollen, and pollen Ole e 1-like genes showed low expression in silk. The results of this study provide basic information for further analysis of SSP functions in the reproductive process of maize.

Radiopharmaceuticals for neurotransmitter imaging

Energy Technology Data Exchange (ETDEWEB)

Oh, Seung Jun [Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of)

2007-04-15

Neurotransmitter imaging with radiopharmaceuticals plays major role for understanding of neurological and psychiatric disorders such as Parkinson's disease and depression. Radiopharmaceuticals for neurotransmitter imaging can be divided to dopamine transporter imaging radiopharmaceuticals and serotonin transporter imaging radiopharmaceuticals. Many kinds of new dopamine transporter imaging radiopharmaceuticals has a tropane ring and they showed different biological properties according to the substituted functional group on tropane ring. After the first clinical trials with [{sup 123}I] {beta} -CIT, alkyl chain substituent introduced to tropane ring amine to decrease time for imaging acquisition and to increase selectivity. From these results, [{sup 123}I]PE2I, [18F]FE-CNT, [{sup 123}I]FP-CIT and [{sup 18}F]FP-CIT were developed and they showed high uptake on the dopamine transporter rich regions and fast peak uptake equilibrium time within 4 hours after injection. [{sup 11}C]McN 5652 was developed for serotonin transporter imaging but this compound showed slow kinetics and high background radioactivity. To overcome these problems, new diarylsulfide backbone derivatives such as ADAM, ODAM, AFM, and DASB were developed. In these candidates, [{sup 11}C]AFM and [{sup 11}C]DASB showed high binding affinity to serotonin transporter and fast in vivo kinetics. This paper gives an overview of current status on dopamine and serotonin transporter imaging radiopharmaceuticals and the development of new lead compounds as potential radiopharmaceuticals by medicinal chemistry.

Neurobeachin regulates neurotransmitter receptor trafficking to synapses

NARCIS (Netherlands)

Nair, R.; Lauks, J.; Jung, S; Cooke, N.E.; de Wit, H.; Brose, N.; Kilimann, M.W.; Verhage, M.; Rhee, J.

2013-01-01

The surface density of neurotransmitter receptors at synapses is a key determinant of synaptic efficacy. Synaptic receptor accumulation is regulated by the transport, postsynaptic anchoring, and turnover of receptors, involving multiple trafficking, sorting, motor, and scaffold proteins. We found

Neurotransmitter measures in the cerebrospinal fluid of patients with Alzheimer's disease: a review.

Science.gov (United States)

Strac, Dubravka Svob; Muck-Seler, Dorotea; Pivac, Nela

2015-03-01

Alzheimer's disease (AD) is a severe neurodegenerative disorder characterized by progressive cognitive and functional decline, as well as by a variety of neuropsychiatric and psychological symptoms and behavioral dysfunctions. Various studies proposed the role of different neurotransmitter systems not only in AD-related cognitive, but also psychotic symptoms and behavioral and emotional deficits. Due to the close proximity, pathological neurochemical changes in brain occurring in AD are likely to be reflected in the cerebrospinal fluid (CSF). The purpose of this review is to provide a summary of the CSF neurotransmitter correlates of AD in order to get further insights into the potential role of altered neurotransmitters in the pathophysiology of AD and to offer novel AD biomarkers. PubMed and MEDLINE data bases were searched for English-language articles by using "Alzheimer's disease", "CSF" and "neurotransmitter" as primary terms. No time or article type constraints were applied. Moreover, the lists of references were searched manually for additional articles. Changes in various correlates of cholinergic, monoaminergic and amino acid neurotransmitter systems, as well as neuropeptides, have been observed in CSF of AD patients. However, as the results of these studies have been controversial, the importance of CSF neurotransmitter parameters as potential biomarkers in AD remains quite unclear. The observed discrepancies could be bypassed by implementation of new sensitive methods, such as novel proteomics approaches that include protein separation techniques, mass spectroscopy and targeted multiplex panels of specific analytes. Although no individual CSF neurotransmitter correlate was demonstrated as suitable biomarker of AD, a combined profile of several CSF neurochemical parameters might show enhanced sensitivity and specificity and thus contribute to earlier and more accurate diagnosis of AD, crucial for application of effective treatments.

Effect of anxiety and depression on serum neurotransmitters and immune function in patients with cervical cancer chemotherapy

Institute of Scientific and Technical Information of China (English)

Yi-Qun He; Fa-Qun He; Shao-Long Wang

2017-01-01

Objective:To study the effect of anxiety and depression on serum neurotransmitters and immune function in patients with cervical cancer chemotherapy.Methods:Patients with advanced cervical cancer who received chemotherapy in the First Affiliated Hospital of Chengdu Medical College between May 2014 and June 2016 were selected, HAMA scores and HAMD scores were used to assess anxiety and depression and divide the patients into control group, depression group, anxiety group and depression + anxiety group. The contents of monoamine neurotransmitters and immune cytokines in serum as well as the expression of immune transcription factors in peripheral blood mononuclear cells were detected.Results:Serum NE, E, 5-HT, 5-HIAA and DOPAC contents of depression group and depression + anxiety group were significantly lower than those of control group, and serum NE, E, 5-HT, 5-HIAA and DOPAC contents of anxiety group were significantly higher than those of control group; peripheral blood T-bet mRNA expression as well as serum IFN-γ and TNF-α contents of depression group, anxiety group and depression + anxiety group were significantly lower than those of control group while GATA3, Foxp3 and RORγt mRNA expression as well as serum IL-4, TGF-β and IL-17 contents were significantly higher than those of control group; peripheral blood T-bet mRNA expression as well as serum IFN-γ and TNF-α contents of depression + anxiety group were significantly lower than those of depression group and anxiety group while GATA3, Foxp3 and RORγt mRNA expression as well as serum IL-4, TGF-β and IL-17 contents were significantly higher than those of depression group and anxiety group. Conclusion: Anxiety and depression in patients with cervical cancer chemotherapy can affect the secretion of monoamine neurotransmitters, the differentiation of CD4+T cell subsets and the antitumor immune response mediated by them.

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...

Effect of Omega-3 Fatty Acids on Neurotransmitters Level in the Brain of Male Albino Rats Exposed to Gamma Irradiation

International Nuclear Information System (INIS)

Saada, H.N.; Said, U.Z.; Shedid, S.M.; Mahdy, E.M.E.; Elmezayen, H.E.

2014-01-01

The omega-3 fatty acids are essential dietary nutrients, and one of their important roles is providing docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) for growth and function of nervous tissue. Reduced level of DHA in the brain induce dramatic changes in brain function including changes in size of neurons as well as changes in learning and memory. The objective of this study was to evaluate the role of fish oil rich in omega-3 fatty acids on γ-radiation-induced physiological changes in the brain cerebral hemispheres. Omega-3 fatty acids was supplemented daily by gavages to rats at a dose of 400 mg/ kg body wt for 7 days pre- and 21 days post-exposure to whole body fractionated gamma rays at doses of 2 Gy/week up to a total dose of 8 Gy. The results demonstrated that whole body γ-irradiation induced oxidative stress, de - creased the main polyunsaturated fatty acids; DHA and EPA, and induced neurotransmitters alteration in brain tissues. Oxidative stress was manifested by a significant increase in lipid peroxidation product malondialdehyde (MDA) and decrease in the activity of antioxidant enzymes, superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px). Oxidative stress was accompanied by alterations in the level of the neurotransmitters manifested by a significant increase of glutamic and aspartic and a significant decrease of serotonin (5-HT) levels in brain cerebral hemispheres. Rats receiving fish oil 7 days before and 21 days after exposure to γ-radiation showed significant improvement in the levels of EPA and DHA associated with significant amelioration of oxidative stress and neurotransmitters alteration. It is concluded that fish oil protect the brain from radiation-induced physiological changes by protecting brain cellular membranes through counteracting the decrease of omega-3 fatty acids and minimizing oxidative stress

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...... and conductive polymer microelectrodes made of Pedot:Pss were also fabricated and used successfully to measure transmitter release from cells. The use of different thin film electrodes for low-noise amperometric measurements of single events of transmitter release from neuronal cells was studied....... For this application a very low current noise is needed together with a large temporal resolution. It was shown, that resistive and capacitive properties of thin film electrode materials are determining their usefulness in low-noise amperometric measurements. An analytical expression for the noise was derived...

The role of laserpuncture exposure on gonad maturation mechanism of catfish (Clarias sp. through Ca2+, PKC and GABA neurotransmitter

Directory of Open Access Journals (Sweden)

Pungky Slamet Wisnu Kusuma

2017-12-01

Full Text Available Laser puncture exposure at reproduction acupoint is proven to increase cellular activity like Ca2+ in the skin tissues. The aim of the study is to determine the role of laserpuncture exposure on gonad maturation by evaluating Ca2+ stimulation and PKC activity in skin tissue and the release of GABA from GABAergic neurons of the brain tissue of catfish (Clarias sp.. A total of 36 females and 36 males of 8–9-month old of F1 catfish broodstock Sangkuriang (female and Paiton (male. This study used Completely Randomized Design (CDR experimental method. Expression analysis was conducted using immunohistochemical staining with a streptavidinbiotin method with calcineurin kit, PKC kit, and GABA kit. The results showed that laserpuncture can stimulate calcineurin and PKC expression in skin tissue, and GABA expression in the brain tissue on the condition pre-spawn, spawn, and post-spawn (P < .05. It can be concluded that laserpuncture stimulates gonad maturation through Ca2+, PKC, and GABA neurotransmitter.

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. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Outside-out "sniffer-patch" clamp technique for in situ measures of neurotransmitter release.

Science.gov (United States)

Muller-Chrétien, Emilie

2014-01-01

The mechanism underlying neurotransmitter release is a critical research domain for the understanding of neuronal network function; however, few techniques are available for the direct detection and measurement of neurotransmitter release. To date, the sniffer-patch clamp technique is mainly used to investigate these mechanisms from individual cultured cells. In this study, we propose to adapt the sniffer-patch clamp technique to in situ detection of neurosecretion. Using outside-out patches from donor cells as specific biosensors plunged in acute cerebral slices, this technique allows for proper detection and quantification of neurotransmitter release at the level of the neuronal network.

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...... 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 1.7 pmol 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...

Urinary Neurotransmitters Are Selectively Altered in Children With Obstructive Sleep Apnea and Predict Cognitive Morbidity

Science.gov (United States)

Kheirandish-Gozal, Leila; McManus, Corena J. T.; Kellermann, Gottfried H.; Samiei, Arash

2013-01-01

Background: Pediatric obstructive sleep apnea (OSA) is associated with cognitive dysfunction, suggesting altered neurotransmitter function. We explored overnight changes in neurotransmitters in the urine of children with and without OSA. Methods: Urine samples were collected from children with OSA and from control subjects before and after sleep studies. A neurocognitive battery assessing general cognitive ability (GCA) was administered to a subset of children with OSA. Samples were subjected to multiple enzyme-linked immunosorbent assays for 12 neurotransmitters, and adjusted for creatinine concentrations. Results: The study comprised 50 children with OSA and 20 control subjects. Of the children with OSA, 20 had normal GCA score (mean ± SD) (101.2 ± 14.5) and 16 had a reduced GCA score (87.3 ± 13.9; P neurotransmitters enabled prediction of OSA (area under the curve [AUC]: 0.923; P neurotransmitters in urine may not only predict OSA but also the presence of cognitive deficits. Larger cohort studies appear warranted to confirm these findings. PMID:23306904

Autoreceptor Control of Peptide/Neurotransmitter Corelease from PDF Neurons Determines Allocation of Circadian Activity in Drosophila

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Charles Choi

2012-08-01

Full Text Available Drosophila melanogaster flies concentrate behavioral activity around dawn and dusk. This organization of daily activity is controlled by central circadian clock neurons, including the lateral-ventral pacemaker neurons (LNvs that secrete the neuropeptide PDF (pigment dispersing factor. Previous studies have demonstrated the requirement for PDF signaling to PDF receptor (PDFR-expressing dorsal clock neurons in organizing circadian activity. Although LNvs also express functional PDFR, the role of these autoreceptors has remained enigmatic. Here, we show that (1 PDFR activation in LNvs shifts the balance of circadian activity from evening to morning, similar to behavioral responses to summer-like environmental conditions, and (2 this shift is mediated by stimulation of the Gα,s-cAMP pathway and a consequent change in PDF/neurotransmitter corelease from the LNvs. These results suggest another mechanism for environmental control of the allocation of circadian activity and provide new general insight into the role of neuropeptide autoreceptors in behavioral control circuits.

Brain neurotransmitters and hippocampal proteome in pigs under stress and environmental enrichment

Directory of Open Access Journals (Sweden)

Laura Arroyo

2017-06-01

Full Text Available Stress and wellbeing are psychological conditions that are mediated by the central nervous system. In the brain, stress is mediated mainly by the hypothalamus, which will activate the hypothalamic-pituitary-adrenal (HPA axis, leading to the secretion of cortisol, the paradigmatic stress hormone. Other brain areas as the amygdala, the hippocampus or the prefrontal cortex (PFC are involved in emotions such as happiness, anxiety and fear. Communication between brain areas is achieved by chemical neurotransmitters (NTs, which are secreted by presynaptic neurons to reach postsynaptic neurons, where they will cause a variation in membrane polarization and other cell signaling actions, leading to physiological responses. Amongst these NTs, catecholamines (noradrenaline and dopamine and serotonin play an important role. On the other hand, the adverse effects of stress may be counteracted by housing the individuals under environmental enrichment conditions. This long-term situation should have an effect, not only on NTs, but also on the brain proteome. Under the hypothesis that different stress situations will lead to changes in NT composition that will be specific for crucial brain areas, we have tested the effects of transport stress, handling stress at the slaughterhouse, and the stress-susceptible genotype (Ryr1 on the amine NT concentration in amygdala, hippocampus, PFC and hypothalamus of pigs. The effects of living under environmentally enriched or control conditions on the NT concentration in several brain regions and on the hippocampus proteome has been also analyzed. In conclusion, genetic factors as well as management conditions related to housing, transport and slaughterhouse alter in different degree the catecholaminergic and the serotoninergic neurotransmission in the brain, and give clues about how different individual types are able to react to external challenges. Likewise, environmental enrichment leads to changes in the proteome

Generation of Dopamine-Secreting Cells from Human Adipose Tissue-Derived Stem Cells In Vitro.

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Soheilifar, Mohammad Hasan; Javeri, Arash; Amini, Hossein; Taha, Masoumeh Fakhr

2018-03-12

Several studies have demonstrated the differentiation of human adipose tissue-derived stem cells (hADSCs) to neuronal and glial phenotypes, but directing the fate of these cells toward dopaminergic neurons has not been frequently reported. The aim of this study was to investigate dopaminergic specification of hADSCs in vitro. ADSCs were isolated from subcutaneous abdominal adipose tissue and were characterized. For dopaminergic differentiation, a cocktail of sonic hedgehog, fibroblast growth factor 8, basic fibroblast growth factor, and brain-derived neurotrophic factor were used under a low serum condition. As the control group, the ADSCs were cultured under the same low serum condition without the dopaminergic cocktail. At the end of differentiation period, the cells expressed neuron-specific markers, NES, NSE, and NEFL, and dopaminergic markers, EN1, NURR1, PITX3, VMAT2, TH, and GIRK2 genes. TH, NURR1, and EN1 mRNAs were upregulated in the dopaminergic group compared with the control group. NEFL and TH proteins were also expressed in the differentiated cells. A total of 27.9% of the cells differentiated in dopaminergic induction medium showed positive staining for TH protein. Based on reversed-phase high-performance liquid chromatography analysis, the differentiated cells released a significant amount of dopamine in response to KCl-induced depolarization. In conclusion, results of this study indicate that hADSCs can be induced by a growth factor cocktail to produce dopamine secreting cells with possible applications for future cell replacement therapy of Parkinson's disease.

The role of jasmonates in floral nectar secretion.

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Venkatesan Radhika

Full Text Available Plants produce nectar in their flowers as a reward for their pollinators and most of our crops depend on insect pollination, but little is known on the physiological control of nectar secretion. Jasmonates are well-known for their effects on senescence, the development and opening of flowers and on plant defences such as extrafloral nectar. Their role in floral nectar secretion has, however, not been explored so far. We investigated whether jasmonates have an influence on floral nectar secretion in oil-seed rape, Brassica napus. The floral tissues of this plant produced jasmonic acid (JA endogenously, and JA concentrations peaked shortly before nectar secretion was highest. Exogenous application of JA to flowers induced nectar secretion, which was suppressed by treatment with phenidone, an inhibitor of JA synthesis. This effect could be reversed by additional application of JA. Jasmonoyl-isoleucine and its structural mimic coronalon also increased nectar secretion. Herbivory or addition of JA to the leaves did not have an effect on floral nectar secretion, demonstrating a functional separation of systemic defence signalling from reproductive nectar secretion. Jasmonates, which have been intensively studied in the context of herbivore defences and flower development, have a profound effect on floral nectar secretion and, thus, pollination efficiency in B. napus. Our results link floral nectar secretion to jasmonate signalling and thereby integrate the floral nectar secretion into the complex network of oxylipid-mediated developmental processes of plants.

Autoradiographic localization of drug and neurotransmitter receptors in the brain

International Nuclear Information System (INIS)

Kuhar, M.J.

1981-01-01

By combining and adapting various methodologies, it is possible to develop radiohistochemical methods for the light microscopic localization of drug and neurotransmitter receptors in the brain. These methods are valuable complements to other histochemical methods for mapping neurotransmitters; they provide a unique view of neuroanatomy and they can be used to provide valuable new hypotheses about how drugs produce various effects. Interesting 'hot spots' of receptor localizations have been observed in some sensory and limbic areas of the brain. Because most available methods are light microscopic, the development of ultrastructural methods will be a necessary and important extension of this field. (Auth.)

Insertion of Neurotransmitters into a Lipid Bilayer Membrane and Its Implication on Membrane Stability: A Molecular Dynamics Study.

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Shen, Chun; Xue, Minmin; Qiu, Hu; Guo, Wanlin

2017-03-17

The signaling molecules in neurons, called neurotransmitters, play an essential role in the transportation of neural signals, during which the neurotransmitters interact with not only specific receptors, but also cytomembranes, such as synaptic vesicle membranes and postsynaptic membranes. Through extensive molecular dynamics simulations, the atomic-scale insertion dynamics of typical neurotransmitters, including methionine enkephalin (ME), leucine enkephalin (LE), dopamine (DA), acetylcholine (ACh), and aspartic acid (ASP), into lipid bilayers is investigated. The results show that the first three neurotransmitters (ME, LE, and DA) are able to diffuse freely into both 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine (POPE) membranes, and are guided by the aromatic residues Tyr and Phe. Only a limited number of these neurotransmitters are allowed to penetrate into the membrane, which suggests an intrinsic mechanism by which the membrane is protected from being destroyed by excessive inserted neurotransmitters. After spontaneous insertion, the neurotransmitters disturb the surrounding phospholipids in the membrane, as indicated by the altered distribution of components in lipid leaflets and the disordered lipid tails. In contrast, the last two neurotransmitters (ACh and ASP) cannot enter the membrane, but instead always diffuse freely in solution. These findings provide an understanding at the atomic level of how neurotransmitters interact with the surrounding cytomembrane, as well as their impact on membrane behavior. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Multi-metal, Multi-wavelength Surface-Enhanced Raman Spectroscopy Detection of Neurotransmitters.

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Moody, Amber S; Sharma, Bhavya

2018-04-05

The development of a sensor for the rapid and sensitive detection of neurotransmitters could provide a pathway for the diagnosis of neurological diseases, leading to the discovery of more effective treatment methods. We investigate the use of surface enhanced Raman spectroscopy (SERS) based sensors for the rapid detection of melatonin, serotonin, glutamate, dopamine, GABA, norepinephrine, and epinephrine. Previous studies have demonstrated SERS detection of neurotransmitters; however, there has been no comprehensive study on the effect of the metal used as the SERS substrate or the excitation wavelength used for detection. Here, we present the detection of 7 neurotransmitters using both silver and gold nanoparticles at excitation wavelengths of 532, 633, and 785 nm. Over the range of wavelengths investigated, the SERS enhancement on the silver and gold nanoparticles varies, with an average enhancement factor of 10 5 -10 6 . The maximum SERS enhancement occurs at an excitation wavelength of 785 nm for the gold nanoparticles and at 633 nm for the silver nanoparticles.

Adrenergic effects on secretion of epidermal growth factor from Brunner's glands

DEFF Research Database (Denmark)

Poulsen, Steen Seier

1985-01-01

The influence of the sympathetic nervous system and adrenergic agonists on flow rate and secretion of epidermal growth factor (EGF) from Brunner's glands has been investigated in the rat. Chemical sympathectomy by administration of 6-hydroxydopamine increased volume secretion and output of EGF from...... Brunner's glands but depleted the glands of EGF. Infusion of noradrenaline, an alpha-adrenergic agonist, inhibited basal and vasoactive intestinal polypeptide (VIP) stimulated flow rate and output of EGF from Brunner's glands and increased the amount of EGF in the tissue. Vasoactive intestinal polypeptide...... also increased the amount of EGF in Brunner's gland tissue and this was unchanged after simultaneous infusion of VIP and noradrenaline as well as VIP and isoproterenol, a beta-adrenergic agonist. Isoproterenol had no effect on basal and VIP stimulated secretion of EGF from Brunner's glands...

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

DEFF Research Database (Denmark)

Sinning, Steffen; Said, Saida; Malinauskaite, Lina

The monoamine transporter family consists of dopamine (DAT), norepinephrine (NET) and serotonin transporters (SERT) that mediate the reuptake of the monoamine neurotransmitters after their release during neurotransmission. These transporters play prominent roles in psychiatric disorders and are t......The monoamine transporter family consists of dopamine (DAT), norepinephrine (NET) and serotonin transporters (SERT) that mediate the reuptake of the monoamine neurotransmitters after their release during neurotransmission. These transporters play prominent roles in psychiatric disorders...... 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...

Artificial neural network and classical least-squares methods for neurotransmitter mixture analysis.

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Schulze, H G; Greek, L S; Gorzalka, B B; Bree, A V; Blades, M W; Turner, R F

1995-02-01

Identification of individual components in biological mixtures can be a difficult problem regardless of the analytical method employed. In this work, Raman spectroscopy was chosen as a prototype analytical method due to its inherent versatility and applicability to aqueous media, making it useful for the study of biological samples. Artificial neural networks (ANNs) and the classical least-squares (CLS) method were used to identify and quantify the Raman spectra of the small-molecule neurotransmitters and mixtures of such molecules. The transfer functions used by a network, as well as the architecture of a network, played an important role in the ability of the network to identify the Raman spectra of individual neurotransmitters and the Raman spectra of neurotransmitter mixtures. Specifically, networks using sigmoid and hyperbolic tangent transfer functions generalized better from the mixtures in the training data set to those in the testing data sets than networks using sine functions. Networks with connections that permit the local processing of inputs generally performed better than other networks on all the testing data sets. and better than the CLS method of curve fitting, on novel spectra of some neurotransmitters. The CLS method was found to perform well on noisy, shifted, and difference spectra.

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.

Mimicking Neurotransmitter Release in Chemical Synapses via Hysteresis Engineering in MoS2 Transistors.

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Arnold, Andrew J; Razavieh, Ali; Nasr, Joseph R; Schulman, Daniel S; Eichfeld, Chad M; Das, Saptarshi

2017-03-28

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 MoS 2 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 MoS 2 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.

Isthmin 1 is a secreted protein expressed in skin, mucosal tissues, and NK, NKT, and th17 cells.

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Valle-Rios, Ricardo; Maravillas-Montero, José L; Burkhardt, Amanda M; Martinez, Cynthia; Buhren, Bettina Alexandra; Homey, Bernhard; Gerber, Peter Arne; Robinson, Octavio; Hevezi, Peter; Zlotnik, Albert

2014-10-01

Using a comprehensive microarray database of human gene expression, we identified that in mammals, a secreted protein known as isthmin 1 (ISM1) is expressed in skin, mucosal tissues, and selected lymphocyte populations. ISM1 was originally identified in Xenopus brain during development, and it encodes a predicted ∼50-kDa protein containing a signal peptide, a thrombospondin domain, and an adhesion-associated domain. We confirmed the pattern of expression of ISM1 in both human and mouse tissues. ISM1 is expressed by DX5(+) lung lymphocytes that include NK and NKT-like cells, and is also expressed by some CD4(+) T cells upon activation but its expression increases significantly when CD4(+) T cells were polarized to the Th17 lineage in vitro. The presence of IFN-γ during CD4(+) T cell polarization inhibits ISM1 expression. Given that ISM1 has been reported to have anti-angiogenic properties, these observations suggest that ISM1 is a mediator of lymphocyte effector functions and may participate in both innate and acquired immune responses.

Autoreceptor Modulation of Peptide/Neurotransmitter Co-release from PDF Neurons Determines Allocation of Circadian Activity in Drosophila

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Choi, Charles; Cao, Guan; Tanenhaus, Anne K.; McCarthy, Ellena v.; Jung, Misun; Schleyer, William; Shang, Yuhua; Rosbash, Michael; Yin, Jerry C.P.; Nitabach, Michael N.

2012-01-01

Drosophila melanogaster flies concentrate behavioral activity around dawn and dusk. This organization of daily activity is controlled by central circadian clock neurons, including the lateral ventral pacemaker neurons (LNvs) that secrete the neuropeptide PDF (Pigment Dispersing Factor). Previous studies have demonstrated the requirement for PDF signaling to PDF receptor (PDFR)-expressing dorsal clock neurons in organizing circadian activity. While LNvs also express functional PDFR, the role of these autoreceptors has remained enigmatic. Here we show that (1) PDFR activation in LNvs shifts the balance of circadian activity from evening to morning, similar to behavioral responses to summer-like environmental conditions and (2) this shift is mediated by stimulation of the Ga,s-cAMP pathway and a consequent change in PDF/neurotransmitter co-release from the LNvs. These results suggest a novel mechanism for environmental control of the allocation of circadian activity and provide new general insight into the role of neuropeptide autoreceptors in behavioral control circuits. PMID:22938867

Wireless Instantaneous Neurotransmitter Concentration Sensing System (WINCS) for intraoperative neurochemical monitoring.

Science.gov (United States)

Kimble, Christopher J; Johnson, David M; Winter, Bruce A; Whitlock, Sidney V; Kressin, Kenneth R; Horne, April E; Robinson, Justin C; Bledsoe, Jonathan M; Tye, Susannah J; Chang, Su-Youne; Agnesi, Filippo; Griessenauer, Christoph J; Covey, Daniel; Shon, Young-Min; Bennet, Kevin E; Garris, Paul A; Lee, Kendall H

2009-01-01

The Wireless Instantaneous Neurotransmitter Concentration Sensing System (WINCS) measures extracellular neurotransmitter concentration in vivo and displays the data graphically in nearly real time. WINCS implements two electroanalytical methods, fast-scan cyclic voltammetry (FSCV) and fixed-potential amperometry (FPA), to measure neurotransmitter concentrations at an electrochemical sensor, typically a carbon-fiber microelectrode. WINCS comprises a battery-powered patient module and a custom software application (WINCSware) running on a nearby personal computer. The patient module impresses upon the electrochemical sensor either a constant potential (for FPA) or a time-varying waveform (for FSCV). A transimpedance amplifier converts the resulting current to a signal that is digitized and transmitted to the base station via a Bluetooth radio link. WINCSware controls the operational parameters for FPA or FSCV, and records the transmitted data stream. Filtered data is displayed in various formats, including a background-subtracted plot of sequential FSCV scans - a representation that enables users to distinguish the signatures of various analytes with considerable specificity. Dopamine, glutamate, adenosine and serotonin were selected as analytes for test trials. Proof-of-principle tests included in vitro flow-injection measurements and in vivo measurements in rat and pig. Further testing demonstrated basic functionality in a 3-Tesla MRI unit. WINCS was designed in compliance with consensus standards for medical electrical device safety, and it is anticipated that its capability for real-time intraoperative monitoring of neurotransmitter release at an implanted sensor will prove useful for advancing functional neurosurgery.

Article Neurotransmitters – A biochemical view | Shalayel | Sudan ...

African Journals Online (AJOL)

The neurotransmission at most if not all synapses is chemical and is of great biochemical, physiological and pharmacological importance. Neurons communicate with each other at synapses by a process called synaptic transmission in which the release of small quantities of chemical messengers, called neurotransmitters ...

A role for SPARC in the moderation of human insulin secretion.

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Lorna W Harries

Full Text Available AIMS/HYPOTHESIS: We have previously shown the implication of the multifunctional protein SPARC (Secreted protein acidic and rich in cysteine/osteonectin in insulin resistance but potential effects on beta-cell function have not been assessed. We therefore aimed to characterise the effect of SPARC on beta-cell function and features of diabetes. METHODS: We measured SPARC expression by qRT-PCR in human primary pancreatic islets, adipose tissue, liver and muscle. We then examined the relation of SPARC with glucose stimulated insulin secretion (GSIS in primary human islets and the effect of SPARC overexpression on GSIS in beta cell lines. RESULTS: SPARC was expressed at measurable levels in human islets, adipose tissue, liver and skeletal muscle, and demonstrated reduced expression in primary islets from subjects with diabetes compared with controls (p< = 0.05. SPARC levels were positively correlated with GSIS in islets from control donors (p< = 0.01. Overexpression of SPARC in cultured beta-cells resulted in a 2.4-fold increase in insulin secretion in high glucose conditions (p< = 0.01. CONCLUSIONS: Our data suggest that levels of SPARC are reduced in islets from donors with diabetes and that it has a role in insulin secretion, an effect which appears independent of SPARC's modulation of obesity-induced insulin resistance in adipose tissue.

Tyrosine 402 Phosphorylation of Pyk2 Is Involved in Ionomycin-Induced Neurotransmitter Release

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Zhang, Zhao; Zhang, Yun; Mou, Zheng; Chu, Shifeng; Chen, Xiaoyu; He, Wenbin; Guo, Xiaofeng; Yuan, Yuhe; Takahashi, Masami; Chen, Naihong

2014-01-01

Protein tyrosine kinases, which are highly expressed in the central nervous system, are implicated in many neural processes. However, the relationship between protein tyrosine kinases and neurotransmitter release remains unknown. In this study, we found that ionomycin, a Ca2+ ionophore, concurrently induced asynchronous neurotransmitter release and phosphorylation of a non-receptor protein tyrosine kinase, proline-rich tyrosine kinase 2 (Pyk2), in clonal rat pheochromocytoma PC12 cells and cerebellar granule cells, whereas introduction of Pyk2 siRNA dramatically suppressed ionomycin-induced neurotransmitter release. Further study indicated that Tyr-402 (Y402) in Pyk2, instead of other tyrosine sites, underwent rapid phosphorylation after ionomycin induction in 1 min to 2 min. We demonstrated that the mutant of Pyk2 Y402 could abolish ionomycin-induced dopamine (DA) release by transfecting cells with recombinant Pyk2 and its mutants (Y402F, Y579F, Y580F, and Y881F). In addition, Src inhibition could prolong phosphorylation of Pyk2 Y402 and increase DA release. These findings suggested that Pyk2 was involved in ionomycin-induced neurotransmitter release through phosphorylation of Y402. PMID:24718602

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.

Optimization of Methods for Articular Cartilage Surface Tissue Engineering: Cell Density and Transforming Growth Factor Beta Are Critical for Self-Assembly and Lubricin Secretion.

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Iwasa, Kenjiro; Reddi, A Hari

2017-07-01

Lubricin/superficial zone protein (SZP)/proteoglycan4 (PRG4) plays an important role in boundary lubrication in articular cartilage. Lubricin is secreted by superficial zone chondrocytes and synoviocytes of the synovium. The specific objective of this investigation is to optimize the methods for tissue engineering of articular cartilage surface. The aim of this study is to investigate the effect of cell density on the self-assembly of superficial zone chondrocytes and lubricin secretion as a functional assessment. Superficial zone chondrocytes were cultivated as a monolayer at low, medium, and high densities. Chondrocytes at the three different densities were treated with transforming growth factor beta (TGF-β)1 twice a week or daily, and the accumulated lubricin in the culture medium was analyzed by immunoblots and quantitated by enzyme-linked immunosorbent assay (ELISA). Cell numbers in low and medium densities were increased by TGF-β1; whereas cell numbers in high-density cell cultures were decreased by twice-a-week treatment of TGF-β1. On the other hand, the cell numbers were maintained by daily TGF-β treatment. Immunoblots and quantitation of lubricin by ELISA analysis indicated that TGF-β1 stimulated lubricin secretion by superficial zone chondrocytes at all densities with twice-a-week TGF-β treatment. It is noteworthy that the daily treatment of TGF-β1 increased lubricin much higher compared with twice-a-week treatment. These data demonstrate that daily treatment is optimal for the TGF-β1 response in a higher density of monolayer cultures. These findings have implications for self-assembly of surface zone chondrocytes of articular cartilage for application in tissue engineering of articular cartilage surface.

Glycine receptors support excitatory neurotransmitter release in developing mouse visual cortex

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Kunz, Portia A; Burette, Alain C; Weinberg, Richard J; Philpot, Benjamin D

2012-01-01

Glycine receptors (GlyRs) are found in most areas of the brain, and their dysfunction can cause severe neurological disorders. While traditionally thought of as inhibitory receptors, presynaptic-acting GlyRs (preGlyRs) can also facilitate glutamate release under certain circumstances, although the underlying molecular mechanisms are unknown. In the current study, we sought to better understand the role of GlyRs in the facilitation of excitatory neurotransmitter release in mouse visual cortex. Using whole-cell recordings, we found that preGlyRs facilitate glutamate release in developing, but not adult, visual cortex. The glycinergic enhancement of neurotransmitter release in early development depends on the high intracellular to extracellular Cl− gradient maintained by the Na+–K+–2Cl− cotransporter and requires Ca2+ entry through voltage-gated Ca2+ channels. The glycine transporter 1, localized to glial cells, regulates extracellular glycine concentration and the activation of these preGlyRs. Our findings demonstrate a developmentally regulated mechanism for controlling excitatory neurotransmitter release in the neocortex. PMID:22988142

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

Detection and Monitoring of Neurotransmitters - a Spectroscopic Analysis

Science.gov (United States)

Manciu, Felicia; Lee, Kendall; Durrer, William; Bennet, Kevin

2012-10-01

In this work we demonstrate the capability of confocal Raman mapping spectroscopy for simultaneously and locally detecting important compounds in neuroscience such as dopamine, serotonin, and adenosine. The Raman results show shifting of the characteristic vibrations of the compounds, observations consistent with previous spectroscopic studies. Although some vibrations are common in these neurotransmitters, Raman mapping was achieved by detecting non-overlapping characteristic spectral signatures of the compounds, as follows: for dopamine the vibration attributed to C-O stretching, for serotonin the indole ring stretching vibration, and for adenosine the adenine ring vibrations. Without damage, dyeing, or preferential sample preparation, confocal Raman mapping provided positive detection of each neurotransmitter, allowing association of the high-resolution spectra with specific micro-scale image regions. Such information is particularly important for complex, heterogeneous samples, where modification of the chemical or physical composition can influence the neurotransmission processes. We also report an estimated dopamine diffusion coefficient two orders of magnitude smaller than that calculated by the flow-injection method.

GnRH dysregulation in polycystic ovarian syndrome (PCOS) is a manifestation of an altered neurotransmitter profile.

Science.gov (United States)

Chaudhari, Nirja; Dawalbhakta, Mitali; Nampoothiri, Laxmipriya

2018-04-11

GnRH is the master molecule of reproduction that is influenced by several intrinsic and extrinsic factors such as neurotransmitters and neuropeptides. Any alteration in these regulatory loops may result in reproductive-endocrine dysfunction such as the polycystic ovarian syndrome (PCOS). Although low dopaminergic tone has been associated with PCOS, the role of neurotransmitters in PCOS remains unknown. The present study was therefore aimed at understanding the status of GnRH regulatory neurotransmitters to decipher the neuroendocrine pathology in PCOS. PCOS was induced in rats by oral administration of letrozole (aromatase inhibitor). Following PCOS validation, animals were assessed for gonadotropin levels and their mRNA expression. Neurotrasnmitter status was evaluated by estimating their levels, their metabolism and their receptor expression in hypothalamus, pituitary, hippocampus and frontal cortex of PCOS rat model. We demonstrate that GnRH and LH inhibitory neurotransmitters - serotonin, dopamine, GABA and acetylcholine - are reduced while glutamate, a major stimulator of GnRH and LH release, is increased in the PCOS condition. Concomitant changes were observed for neurotransmitter metabolising enzymes and their receptors as well. Our results reveal that increased GnRH and LH pulsatility in PCOS condition likely result from the cumulative effect of altered GnRH stimulatory and inhibitory neurotransmitters in hypothalamic-pituitary centre. This, we hypothesise, is responsible for the depression and anxiety-like mood disorders commonly seen in PCOS women.

Neurotransmitter signaling pathways required for normal development in Xenopus laevis embryos: a pharmacological survey screen.

Science.gov (United States)

Sullivan, Kelly G; Levin, Michael

2016-10-01

Neurotransmitters are not only involved in brain function but are also important signaling molecules for many diverse cell types. Neurotransmitters are widely conserved, from evolutionarily ancient organisms lacking nervous systems through man. Here, results are reported from a loss- and gain-of-function survey, using pharmacological modulators of several neurotransmitter pathways to examine possible roles for these pathways in normal embryogenesis. Applying reagents targeting the glutamatergic, adrenergic and dopaminergic pathways to embryos of Xenopus laevis from gastrulation to organogenesis stages, we observed and quantified numerous malformations, including craniofacial defects, hyperpigmentation, muscle mispatterning and miscoiling of the gut. These data implicate several key neurotransmitters in new embryonic patterning roles, reveal novel earlier stages for processes involved in eye development, suggest new targets for subsequent molecular-genetic investigation, and highlight the necessity for in-depth toxicology studies of psychoactive compounds to which human embryos might be exposed during pregnancy. © 2016 Anatomical Society.

Neurotrophin Signaling Is Required for Glucose-Induced Insulin Secretion.

Science.gov (United States)

Houtz, Jessica; Borden, Philip; Ceasrine, Alexis; Minichiello, Liliana; Kuruvilla, Rejji

2016-11-07

Insulin secretion by pancreatic islet β cells is critical for glucose homeostasis, and a blunted β cell secretory response is an early deficit in type 2 diabetes. Here, we uncover a regulatory mechanism by which glucose recruits vascular-derived neurotrophins to control insulin secretion. Nerve growth factor (NGF), a classical trophic factor for nerve cells, is expressed in pancreatic vasculature while its TrkA receptor is localized to islet β cells. High glucose rapidly enhances NGF secretion and increases TrkA phosphorylation in mouse and human islets. Tissue-specific deletion of NGF or TrkA, or acute disruption of TrkA signaling, impairs glucose tolerance and insulin secretion in mice. We show that internalized TrkA receptors promote insulin granule exocytosis via F-actin reorganization. Furthermore, NGF treatment augments glucose-induced insulin secretion in human islets. These findings reveal a non-neuronal role for neurotrophins and identify a new regulatory pathway in insulin secretion that can be targeted to ameliorate β cell dysfunction. Copyright © 2016 Elsevier Inc. All rights reserved.

[Influence of 1, 2-dichloroethane on open field behavior and levels of neurotransmitters in brain of mice].

Science.gov (United States)

Qi, Ying; Shi, Lei; Gao, Lan-Yue; Wang, Gao-Yang; Li, Ge-Xin; Lv, Xiu-Qiang; Jin, Ya-Ping

2011-06-01

To explore the effects of 1,2-dichloroethane (1,2-DCE) on the behavior and the brain neurotransmitter levels in mice. Thirty mice were randomly divided into four groups, which were control group and groups of low, middle and high exposure (225, 450 and 900 mg/m3) to 1,2-DCE for 10 days (3.5 h a day) by inhalation. After the last exposure, the open field test was performed immediately. After exposure all mice were killed and the brain tissues were taken up rapidly. The levels of aspartate (Asp), glutamate (Glu) and gamma-aminobutyric acid (GABA) in the brain were detected by high performance liquid chromatography (HPLC). Levels of Asp and Glu in all exposure groups increased with doses. As compared to the control group, levels of Glu in all exposure groups increased significantly (P open field test showed that effect of low exposure to 1,2-DCE on the behavior was stimulant, but the high exposure to 1,2-DCE inhibited behavior of exploration, excitement and sport. Subacute exposure to 1,2-DCE could result in the change of amino acid neurotransmitter content and ratio in the brain, thereby change the behavior of mice appeared, which might be the mechanism of neurotoxicity caused by 1,2-DCE in part.

Autoreceptor control of peptide/neurotransmitter corelease from PDF neurons determines allocation of circadian activity in drosophila.

Science.gov (United States)

Choi, Charles; Cao, Guan; Tanenhaus, Anne K; McCarthy, Ellena V; Jung, Misun; Schleyer, William; Shang, Yuhua; Rosbash, Michael; Yin, Jerry C P; Nitabach, Michael N

2012-08-30

Drosophila melanogaster flies concentrate behavioral activity around dawn and dusk. This organization of daily activity is controlled by central circadian clock neurons, including the lateral-ventral pacemaker neurons (LN(v)s) that secrete the neuropeptide PDF (pigment dispersing factor). Previous studies have demonstrated the requirement for PDF signaling to PDF receptor (PDFR)-expressing dorsal clock neurons in organizing circadian activity. Although LN(v)s also express functional PDFR, the role of these autoreceptors has remained enigmatic. Here, we show that (1) PDFR activation in LN(v)s shifts the balance of circadian activity from evening to morning, similar to behavioral responses to summer-like environmental conditions, and (2) this shift is mediated by stimulation of the Gα,s-cAMP pathway and a consequent change in PDF/neurotransmitter corelease from the LN(v)s. These results suggest another mechanism for environmental control of the allocation of circadian activity and provide new general insight into the role of neuropeptide autoreceptors in behavioral control circuits. Copyright © 2012 The Authors. Published by Elsevier Inc. All rights reserved.

ISSUES OF THE ACCOUNTING OF A WEAK NEUROTRANSMITTER COMPONENT IN THE PHARMACOTHERAPY OF POSTCOMATOSE STATES

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O. S. Zaitsev

2016-01-01

Full Text Available The principle in the accounting of a weak neurotransmitter component is considered as one of the most specific and promising ones for the study and practical introduction of therapy for postcomatous states. The paper outlines problems in the accurate determination of the lack and excess of neurotransmitters by up-to-date techniques (biochemical and neurophysiological tests, magnetic resonance spectroscopy. It gives the reasons for clinical doubts and difficulties in the practical use of ideas about the relationship of the clinical picture to one or another disorder of neurotransmitter metabolism and to the feasibilities of its effective correction. It is concluded that the main method for the individualized therapy of postcomatous states is the clinical analysis of neurological and psychiatric symptoms, only upon its completion, the consideration of a weak neurotransmitter component can be taken into account. The main possible and currently preferable ways to correct cholinergic and GABAergic deficiency and redundancy and deficiency in glutamate and dopamine are considered.

Simultaneous quantification of seven hippocampal neurotransmitters in depression mice by LC-MS/MS.

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Huang, Fei; Li, Jia; Shi, Hai-Lian; Wang, Ting-ting; Muhtar, Wahaf; Du, Min; Zhang, Bei-bei; Wu, Hui; Yang, Li; Hu, Zhi-bi; Wu, Xiao-jun

2014-05-30

There is no method available to simultaneously detect GABA, Glu, Epi, NE, DA, 5-HT and 5-HIAA in mouse hippocampus. A rapid and sensitive LC-MS/MS method has been developed for simultaneously measuring seven neurotransmitters in mouse hippocampus. The analytes were detected in positive mode with multiple reaction monitoring (MRM) and the procedure was completed in less than 9min. This method exhibited excellent linearity for all of the analytes with regression coefficients higher than 0.99, and showed good intra- and inter-day precisions (RSDneurotransmitters in a mouse depression model induced by successive methylprednisolone injections. The results indicated that this depression model was closely associated with the decreased level of Epi (p=0.002) and elevated ratio of 5-HIAA/5-HT (p=0.01), which has never been reported elsewhere. Compared with previous methods, current approach is more convenient without any pre-column derivatization of the analytes but enhances detectability with incremental neurotransmitter profile and shortens detection time. This work represents the first accurate simultaneous determination of seven neurotransmitters in the mouse depression model induced by methylprednisolone. The reliable method will benefit the research of neurological diseases with the altered neurotransmitter profile in brain. Copyright © 2014 Elsevier B.V. All rights reserved.

Regulation of hormone release by cultured cells from a thyrotropin-growth hormone-secreting pituitary tumor. Direct inhibiting effects of 3,5,3'-triiodothyronine and dexamethasone on thyrotropin secretion.

Science.gov (United States)

Lamberts, S W; Oosterom, R; Verleun, T; Krenning, E P; Assies, H

1984-08-01

The regulation of TSH and GH secretion was investigated in cultured tumor cells prepared from a mixed TSH/GH secreting pituitary tumor. The tumor tissue had been removed transsphenoidally from a patient with hyperthyroidism and inappropriately high serum TSH levels and acromegaly. TSH and GH secretion by cultured cells were stimulated in a parallel way by TRH (300 nM) and LHRH (50 nM), but were unaffected by bromocriptine (10 nM). Exposure of the tumor cells to dexamethasone (0.1 microM) or T3 (50 nM) had differential effects on hormone secretion. GH secretion was greatly stimulated by dexamethasone, but unaffected by T3. TSH secretion was inhibited both by T3 and by dexamethasone. So, T3 and glucocorticoids inhibit TSH release by the human pituitary tumor cells studied at least partly by means of a direct effect.

Radiotracers for per studies of neurotransmitter binding sites: Design considerations

International Nuclear Information System (INIS)

Kilbourn, M.R.

1991-01-01

Neurotransmitter binding sites, such as receptors, neuronal uptake systems, and vesicular uptake systems, are important targets for new radiopharmaceutical design. Selection of potential radioligands can be guided by in vitro laboratory data including such characteristics as selectivity and affinity for specific binding sites. However, development of PET radiotracers for use in vivo must include considerations of in vivo pharmacokinetics and metabolism. Introduction of potential radioligands is further narrowed by the demands of the radiochemical synthesis, which must produce radioligands of high chemical and radiochemical purity and of high specific activity. This paper will review examples of previous and current attempts by radiopharmaceutical chemists to meet these demands for new positron emitter-labeled radioligands for PET studies of a wide array of neurotransmitter binding sites

Probe-pin device for optical neurotransmitter sensing in the brain

Science.gov (United States)

Kim, Min Hyuck; Song, Kyo D.; Yoon, Hargsoon; Park, Yeonjoon; Choi, Sang H.; Lee, Dae-Sung; Shin, Kyu-Sik; Hwang, Hak-In; Lee, Uhn

2015-04-01

Development of an optical neurotransmitter sensing device using nano-plasmonic probes and a micro-spectrometer for real time monitoring of neural signals in the brain is underway. Clinical application of this device technology is to provide autonomous closed-loop feedback control to a deep brain stimulation (DBS) system and enhance the accuracy and efficacy of DBS treatment. By far, we have developed an implantable probe-pin device based on localized field enhancement of surface plasmonic resonance on a nanostructured sensing domain which can amplify neurochemical signals from evoked neural activity in the brain. In this paper, we will introduce the details of design and sensing performance of a proto-typed microspectrometer and nanostructured probing devices for real time measurement of neurotransmitter concentrations.

Compartmental modeling alternatives for kinetic analysis of pet neurotransmitter receptor studies

International Nuclear Information System (INIS)

Koeppe, R.A.

1991-01-01

With the increased interest in studying neurotransmitter and receptor function in vivo, imaging procedures using positron emission tomography have presented new challenges for kinetic modeling and analysis of data. The in vivo behavior of radiolabeled markers for examining these neurotransmitter systems can be quite complex and, therefore, the implementation of compartmental models for data analysis is similarly complex. Often, the variability in the estimates of model parameters representing neurotransmitter or receptor densities, association and dissociation rates, or rates of incorporation or turnover does not permit reliable interpretation of the data. When less complex analyses are used, these model parameters may be biased and thus also do not yield the information being sought. Examination of trade-offs between uncertainty and bias in the parameters of interest may be used to select a compartmental model configuration with an appropriate level of complexity. Modeling alternatives will be discussed for radioligands with varying kinetic properties, such as those that bind reversibly and rapidly and others that bind nearly irreversibly. Specific problems, such as those occurring when a radioligand is open-quotes flow limitedclose quotes also will be discussed

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...

Integrative network analysis highlights biological processes underlying GLP-1 stimulated insulin secretion: A DIRECT study.

Directory of Open Access Journals (Sweden)

Valborg Gudmundsdottir

Full Text Available Glucagon-like peptide 1 (GLP-1 stimulated insulin secretion has a considerable heritable component as estimated from twin studies, yet few genetic variants influencing this phenotype have been identified. We performed the first genome-wide association study (GWAS of GLP-1 stimulated insulin secretion in non-diabetic individuals from the Netherlands Twin register (n = 126. This GWAS was enhanced using a tissue-specific protein-protein interaction network approach. We identified a beta-cell protein-protein interaction module that was significantly enriched for low gene scores based on the GWAS P-values and found support at the network level in an independent cohort from Tübingen, Germany (n = 100. Additionally, a polygenic risk score based on SNPs prioritized from the network was associated (P < 0.05 with glucose-stimulated insulin secretion phenotypes in up to 5,318 individuals in MAGIC cohorts. The network contains both known and novel genes in the context of insulin secretion and is enriched for members of the focal adhesion, extracellular-matrix receptor interaction, actin cytoskeleton regulation, Rap1 and PI3K-Akt signaling pathways. Adipose tissue is, like the beta-cell, one of the target tissues of GLP-1 and we thus hypothesized that similar networks might be functional in both tissues. In order to verify peripheral effects of GLP-1 stimulation, we compared the transcriptome profiling of ob/ob mice treated with liraglutide, a clinically used GLP-1 receptor agonist, versus baseline controls. Some of the upstream regulators of differentially expressed genes in the white adipose tissue of ob/ob mice were also detected in the human beta-cell network of genes associated with GLP-1 stimulated insulin secretion. The findings provide biological insight into the mechanisms through which the effects of GLP-1 may be modulated and highlight a potential role of the beta-cell expressed genes RYR2, GDI2, KIAA0232, COL4A1 and COL4A2 in GLP-1 stimulated

Methylenetetrahydrofolate reductase deficiency alters levels of glutamate and γ-aminobutyric acid in brain tissue

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N.M. Jadavji

2015-06-01

Full Text Available Methylenetetrahydrofolate reductase (MTHFR is an enzyme key regulator in folate metabolism. Deficiencies in MTHFR result in increased levels of homocysteine, which leads to reduced levels of S-adenosylmethionine (SAM. In the brain, SAM donates methyl groups to catechol-O-methyltransferase (COMT, which is involved in neurotransmitter analysis. Using the MTHFR-deficient mouse model the purpose of this study was to investigate levels of monoamine neurotransmitters and amino acid levels in brain tissue. MTHFR deficiency affected levels of both glutamate and γ-aminobutyric acid in within the cerebellum and hippocampus. Mthfr−/− mice had reduced levels of glutamate in the amygdala and γ-aminobutyric acid in the thalamus. The excitatory mechanisms of homocysteine through activation of the N-methyl-d-aspartate receptor in brain tissue might alter levels of glutamate and γ-aminobutyric acid.

The Top 5 Neurotransmitters from a Clinical Neurologist's Perspective

DEFF Research Database (Denmark)

Kondziella, Daniel

2017-01-01

that we routinely prescribe. Most of us can hardly come up with more than a handful of relevant neurochemicals. From our point of view the most important neurotransmitters are, in alphabetical order, acetylcholine (associated with Alzheimer's disease and myasthenia gravis), dopamine (Parkinson's disease...

A linear model for estimation of neurotransmitter response profiles from dynamic PET data

OpenAIRE

Normandin, M.D.; Schiffer, W.K.; Morris, E.D.

2011-01-01

The parametric ntPET model (p-ntPET) estimates the kinetics of neurotransmitter release from dynamic PET data with receptor-ligand radiotracers. Here we introduce a linearization (lp-ntPET) that is computationally efficient and can be applied to single-scan data. lp-ntPET employs a non-invasive reference region input function and extends the LSRRM of Alpert et al. (2003) using basis functions to characterize the time course of neurotransmitter activation. In simulation studies, the temporal p...

Neurotransmitters Drive Combinatorial Multistate Postsynaptic Density Networks

OpenAIRE

Coba, Marcelo P; Pocklington, Andrew J; Collins, Mark O; Kopanitsa, Maksym V; Uren, Rachel T; Swamy, Sajani; Croning, Mike D R; Choudhary, Jyoti S; Grant, Seth G N

2009-01-01

The mammalian postsynaptic density (PSD) comprises a complex collection of approximately 1100 proteins. Despite extensive knowledge of individual proteins, the overall organization of the PSD is poorly understood. Here, we define maps of molecular circuitry within the PSD based on phosphorylation of postsynaptic proteins. Activation of a single neurotransmitter receptor, the N-methyl-D-aspartate receptor (NMDAR), changed the phosphorylation status of 127 proteins. Stimulation of ionotropic an...

Functional imaging of neurotransmitter systems in movement disorders

Energy Technology Data Exchange (ETDEWEB)

Ilgin, N. [Ankara, Gazi Univ. Medical School (Turkey). Dept. of Nuclear Medicine

1998-09-01

PET and SPECT enable the direct measurement of components of the dopaminergic and other systems in the living human brain and offer unique opportunity for the in vivo quantification on the dopaminergic function in PD and other movement disorders. The need to establish the early and differential diagnosis of PD is increasingly important given the recent evidence that early pharmacologic intervention may slow progression of this progressive degenerative disease. Accordingly, imaging with PET and SPECT using specific neuro markers has been increasingly important to biochemically identify the loss of specific neurotransmitters, their synthesizing enzymes and their receptors in movement disorders. Through the parallel development of new radiotracers, kinetic models and better instruments, PET and SPECT technology is enabling investigation of increasingly more complex aspects of the human brain neurotransmitter systems. This paper summarizes the results of different PET-SPECT studies used to evaluate the various elements of the dopamine system in the human brain with PET and intends to introduce the newly emerging specific tracers and their applications to clinical research in movement disorders.

Functional imaging of neurotransmitter systems in movement disorders

International Nuclear Information System (INIS)

Ilgin, N.

1998-01-01

PET and SPECT enable the direct measurement of components of the dopaminergic and other systems in the living human brain and offer unique opportunity for the in vivo quantification on the dopaminergic function in PD and other movement disorders. The need to establish the early and differential diagnosis of PD is increasingly important given the recent evidence that early pharmacologic intervention may slow progression of this progressive degenerative disease. Accordingly, imaging with PET and SPECT using specific neuro markers has been increasingly important to biochemically identify the loss of specific neurotransmitters, their synthesizing enzymes and their receptors in movement disorders. Through the parallel development of new radiotracers, kinetic models and better instruments, PET and SPECT technology is enabling investigation of increasingly more complex aspects of the human brain neurotransmitter systems. This paper summarizes the results of different PET-SPECT studies used to evaluate the various elements of the dopamine system in the human brain with PET and intends to introduce the newly emerging specific tracers and their applications to clinical research in movement disorders

LKB1 Regulates Mitochondria-Dependent Presynaptic Calcium Clearance and Neurotransmitter Release Properties at Excitatory Synapses along Cortical Axons.

Science.gov (United States)

Kwon, Seok-Kyu; Sando, Richard; Lewis, Tommy L; Hirabayashi, Yusuke; Maximov, Anton; Polleux, Franck

2016-07-01

Individual synapses vary significantly in their neurotransmitter release properties, which underlie complex information processing in neural circuits. Presynaptic Ca2+ homeostasis plays a critical role in specifying neurotransmitter release properties, but the mechanisms regulating synapse-specific Ca2+ homeostasis in the mammalian brain are still poorly understood. Using electrophysiology and genetically encoded Ca2+ sensors targeted to the mitochondrial matrix or to presynaptic boutons of cortical pyramidal neurons, we demonstrate that the presence or absence of mitochondria at presynaptic boutons dictates neurotransmitter release properties through Mitochondrial Calcium Uniporter (MCU)-dependent Ca2+ clearance. We demonstrate that the serine/threonine kinase LKB1 regulates MCU expression, mitochondria-dependent Ca2+ clearance, and thereby, presynaptic release properties. Re-establishment of MCU-dependent mitochondrial Ca2+ uptake at glutamatergic synapses rescues the altered neurotransmitter release properties characterizing LKB1-null cortical axons. Our results provide novel insights into the cellular and molecular mechanisms whereby mitochondria control neurotransmitter release properties in a bouton-specific way through presynaptic Ca2+ clearance.

The Dynamics of Autism Spectrum Disorders: How Neurotoxic Compounds and Neurotransmitters Interact

Directory of Open Access Journals (Sweden)

Margot Van de Bor

2013-08-01

Full Text Available In recent years concern has risen about the increasing prevalence of Autism Spectrum Disorders (ASD. Accumulating evidence shows that exposure to neurotoxic compounds is related to ASD. Neurotransmitters might play a key role, as research has indicated a connection between neurotoxic compounds, neurotransmitters and ASD. In the current review a literature overview with respect to neurotoxic exposure and the effects on neurotransmitter systems is presented. The aim was to identify mechanisms and related factors which together might result in ASD. The literature reported in the current review supports the hypothesis that exposure to neurotoxic compounds can lead to alterations in the GABAergic, glutamatergic, serotonergic and dopaminergic system which have been related to ASD in previous work. However, in several studies findings were reported that are not supportive of this hypothesis. Other factors also might be related, possibly altering the mechanisms at work, such as time and length of exposure as well as dose of the compound. Future research should focus on identifying the pathway through which these factors interact with exposure to neurotoxic compounds making use of human studies.

Constitutive protein secretion from the exocrine pancreas of fetal rats

International Nuclear Information System (INIS)

Arvan, P.; Chang, A.

1987-01-01

Two general kinds of exocytotic secretion of proteins are known: that which is stimulated by secretagogues; and constitutive exocytosis, which is unable to be stimulated. The exocrine pancreas has often been cited as a model system for the first kind of secretion. However, the release of digestive enzymes from the exocrine pancreas of 1-day prenatal rats cannot be stimulated by secretagogues; therefore, its secretion is constitutive. To gain insight into the intracellular pathways which mediate secretion in the fetal gland, we examined the kinetics of release of newly synthesized proteins. We find that fetal pancreas in a steady state of secretion releases pulse-labeled secretory proteins in two kinetically distinct phases. The first phase occurring during 0-6.5 h of chase comprises approximately 12% of total incorporated radioactivity, the second phase beginning at greater than 7 h of chase comprises the remainder. Based on analysis by electron microscope autoradiography, radiolabel is localized during the first phase of secretion in immature granules/condensing vacuoles, Golgi compartments, and few mature granules. The second phase of secretion occurs when radiolabel is predominantly in mature granules. We propose that secretion occurs via (at least) 2 exocytotic routes, both of which are constitutive in fetal pancreatic tissue

Novel perspectives of neural stem cell differentiation: from neurotransmitters to therapeutics.

Science.gov (United States)

Trujillo, Cleber A; Schwindt, Telma T; Martins, Antonio H; Alves, Janaína M; Mello, Luiz Eugênio; Ulrich, Henning

2009-01-01

In the past years, many reports have described the existence of neural progenitor and stem cells in the adult central nervous system capable of generating new neurons, astrocytes, and oligodendrocytes. This discovery has overturned the central assumption in the neuroscience field, of no new neurons being originated in the brain after birth and provided the fundaments to understand the molecular basis of neural differentiation and to develop new therapies for neural tissue repair. Although the mechanisms underlying cell fate during neural development are not yet understood, the importance of intrinsic and extrinsic factors and of an appropriate microenvironment is well known. In this context, emerging evidence strongly suggests that glial cells play a key role in controlling multiple steps of neurogenesis. Those cells, of particular radial glia, are important for migration, cell specification, and integration of neurons into a functional neural network. This review aims to present an update in the neurogenesis area and highlight the modulation of neural stem cell differentiation by neurotransmitters, growth factors, and their receptors, with possible applications for cell therapy strategies of neurological disorders.

Interaction of differentiated human adipocytes with macrophages leads to trogocytosis and selective IL-6 secretion.

Science.gov (United States)

Sárvári, A K; Doan-Xuan, Q-M; Bacsó, Z; Csomós, I; Balajthy, Z; Fésüs, L

2015-01-22

Obesity leads to adipose tissue inflammation that is characterized by increased release of proinflammatory molecules and the recruitment of activated immune cells. Although macrophages are present in the highest number among the immune cells in obese adipose tissue, not much is known about their direct interaction with adipocytes. We have introduced an ex vivo experimental system to characterize the cellular interactions and the profile of secreted cytokines in cocultures of macrophages and human adipocytes differentiated from either mesenchymal stem cells or a preadipocyte cell line. As observed by time-lapse microscopy, flow, and laser-scanning cytometry, macrophages phagocytosed bites of adipocytes (trogocytosis), which led to their de novo, phagocytosis and NF-κB-dependent synthesis, then release of interleukin (IL)-6 and monocyte chemoattractant protein (MCP)-1. IL-6 secretion was not accompanied by secretion of other proinflammatory cytokines, such as tumor necrosis factor (TNF)-α and IL-8, except MCP-1. LPS-induced release of TNF-α, IL-8 and MCP-1 was decreased in the presence of the differentiated adipocytes but the IL-6 level did not subside suggesting that phagocytosis-dependent IL-6 secretion may have significant regulatory function in the inflamed adipose tissue.

Selected regulation of gastrointestinal acid-base secretion and tissue metabolism for the diamondback water snake and Burmese python.

Science.gov (United States)

Secor, Stephen M; Taylor, Josi R; Grosell, Martin

2012-01-01

Snakes exhibit an apparent dichotomy in the regulation of gastrointestinal (GI) performance with feeding and fasting; frequently feeding species modestly regulate intestinal function whereas infrequently feeding species rapidly upregulate and downregulate intestinal function with the start and completion of each meal, respectively. The downregulatory response with fasting for infrequently feeding snakes is hypothesized to be a selective attribute that reduces energy expenditure between meals. To ascertain the links between feeding habit, whole-animal metabolism, and GI function and metabolism, we measured preprandial and postprandial metabolic rates and gastric and intestinal acid-base secretion, epithelial conductance and oxygen consumption for the frequently feeding diamondback water snake (Nerodia rhombifer) and the infrequently feeding Burmese python (Python molurus). Independent of body mass, Burmese pythons possess a significantly lower standard metabolic rate and respond to feeding with a much larger metabolic response compared with water snakes. While fasting, pythons cease gastric acid and intestinal base secretion, both of which are stimulated with feeding. In contrast, fasted water snakes secreted gastric acid and intestinal base at rates similar to those of digesting snakes. We observed no difference between fasted and fed individuals for either species in gastric or intestinal transepithelial potential and conductance, with the exception of a significantly greater gastric transepithelial potential for fed pythons at the start of titration. Water snakes experienced no significant change in gastric or intestinal metabolism with feeding. Fed pythons, in contrast, experienced a near-doubling of gastric metabolism and a tripling of intestinal metabolic rate. For fasted individuals, the metabolic rate of the stomach and small intestine was significantly lower for pythons than for water snakes. The fasting downregulation of digestive function for pythons is

Simultaneous determination of 8 neurotransmitters and their metabolite levels in rat brain using liquid chromatography in tandem with mass spectrometry: Application to the murine Nrf2 model of depression.

Science.gov (United States)

Wojnicz, Aneta; Avendaño Ortiz, José; Casas, Ana I; Freitas, Andiara E; G López, Manuela; Ruiz-Nuño, Ana

2016-01-30

Analysis of neurotransmitters and their metabolites is useful for the diagnosis of central nervous system diseases. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method with protein precipitation was developed to monitor levels of adrenaline (AD), noradrenaline (NA), glutamic acid (Glu), γ-aminobutyric acid (GABA), dopamine (DA), 5-hydroxytryptamine (5-HT), 5-hydroxyindole acetic acid (5-HIAA), and 3-methoxy-4-hydroxyphenylglycol (MHPG) in rat brain tissue. Isoprenaline was used as an internal standard (IS). Neurotransmitters and metabolites were eluted with a reverse phase column under gradient conditions through a mobile phase consisting of 0.2% formic acid water solution/acetonitrile. The compounds were detected and quantified by LC-MS/MS with positive or negative electrospray ionization, which operates in multiple-reaction monitoring mode. The method was linear or polynomial (R(2)>0.99) for AD, NA, Glu, GABA, DA, 5-HT, 5-HIAA, and MHPG in the range of 0.25-200, 0.5-200, 250-20,000, 250-20,000, 0.25-200, 10-3000, 1-50, and 1-50ng/mL, respectively. The validation assays for accuracy and precision, matrix effect, extraction recovery, stability and carry-over of the samples for neurotransmitters and metabolites were consistent with the requirements of regulatory agencies. The method enables rapid quantification of neurotransmitters and their metabolites and has been applied in the nuclear factor (erythroid 2-derived)-like 2 (Nrf2) knockout mouse model of depression. Copyright © 2015 Elsevier B.V. All rights reserved.

Effect of serotonin infusions on the mean plasma concentrations of ...

African Journals Online (AJOL)

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hhazali@hotmail.com, tabeshyarnoor@yahoo.com. neurotransmitters. It has been shown that neurons secreting serotonin may be co-locolized with neurons secreting GHRH and TRH (Bujatti et al., 1976; Bulsa et al., 1998; Savard et al., 1986; Savard et al., 1983). This indicate that serotonin as a neurotransmitter may control.

Tissue Engineering Using Transfected Growth-Factor Genes

Science.gov (United States)

Madry, Henning; Langer, Robert S.; Freed, Lisa E.; Trippel, Stephen; Vunjak-Novakovic, Gordana

2005-01-01

A method of growing bioengineered tissues includes, as a major component, the use of mammalian cells that have been transfected with genes for secretion of regulator and growth-factor substances. In a typical application, one either seeds the cells onto an artificial matrix made of a synthetic or natural biocompatible material, or else one cultures the cells until they secrete a desired amount of an extracellular matrix. If such a bioengineered tissue construct is to be used for surgical replacement of injured tissue, then the cells should preferably be the patient s own cells or, if not, at least cells matched to the patient s cells according to a human-leucocyteantigen (HLA) test. The bioengineered tissue construct is typically implanted in the patient's injured natural tissue, wherein the growth-factor genes enhance metabolic functions that promote the in vitro development of functional tissue constructs and their integration with native tissues. If the matrix is biodegradable, then one of the results of metabolism could be absorption of the matrix and replacement of the matrix with tissue formed at least partly by the transfected cells. The method was developed for articular chondrocytes but can (at least in principle) be extended to a variety of cell types and biocompatible matrix materials, including ones that have been exploited in prior tissue-engineering methods. Examples of cell types include chondrocytes, hepatocytes, islet cells, nerve cells, muscle cells, other organ cells, bone- and cartilage-forming cells, epithelial and endothelial cells, connective- tissue stem cells, mesodermal stem cells, and cells of the liver and the pancreas. Cells can be obtained from cell-line cultures, biopsies, and tissue banks. Genes, molecules, or nucleic acids that secrete factors that influence the growth of cells, the production of extracellular matrix material, and other cell functions can be inserted in cells by any of a variety of standard transfection techniques.

Table S1 Basic characteristics of 32 SNPs of neurotransmitter ...

Indian Academy of Sciences (India)

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Basic characteristics of 32 SNPs in neurotransmitter-related genes. Gene .... rs45435444, rs80837467 and rs80980072, significant differences (P. *** * ... At the same age and environments, skin lesion scores on the ears (P < 0.001), front (P <.

Recent progress and challenges in nanotechnology for biomedical applications: an insight into the analysis of neurotransmitters.

Science.gov (United States)

Shankaran, Dhesingh Ravi; Miura, Norio

2007-01-01

Nanotechnology offers exciting opportunities and unprecedented compatibilities in manipulating chemical and biological materials at the atomic or molecular scale for the development of novel functional materials with enhanced capabilities. It plays a central role in the recent technological advances in biomedical technology, especially in the areas of disease diagnosis, drug design and drug delivery. In this review, we present the recent trend and challenges in the development of nanomaterials for biomedical applications with a special emphasis on the analysis of neurotransmitters. Neurotransmitters are the chemical messengers which transform information and signals all over the body. They play prime role in functioning of the central nervous system (CNS) and governs most of the metabolic functions including movement, pleasure, pain, mood, emotion, thinking, digestion, sleep, addiction, fear, anxiety and depression. Thus, development of high-performance and user-friendly analytical methods for ultra-sensitive detection of neurotransmitters remain a major challenge in modern biomedical analysis. Nanostructured materials are emerging as a powerful mean for diagnosis of CNS disorders because of their unique optical, size and surface characteristics. This review provides a brief outline on the basic concepts and recent advancements of nanotechnology for biomedical applications, especially in the analysis of neurotransmitters. A brief introduction to the nanomaterials, bionanotechnology and neurotransmitters is also included along with discussions on most of the patents published in these areas.

[Subcutaneous transplants of juvenile rat testicular tissues continue to develop and secret androgen in adult rats].

Science.gov (United States)

Yu, Zhou; Wang, Tong; Cui, Jiangbo; Song, Yajuan; Ma, Xianjie; Su, Yingjun; Peng, Pai

2017-12-01

Objective To explore the effects of subcutaneous microenvironment of adult rats on survival, development and androgen secretion of Leydig cells of transplanted juvenile rat testis. Methods Healthy adult SD rats were randomly divided into control group, sham group, castrated group and non-castrated group. Rats in the control group were kept intact, no testis was transplanted subcutaneously after adult recipients were castrated in the sham group; 5-7-day juvenile rat testes were transplanted subcutaneously in the castrated group, with one testis per side; Testes resected from juvenile rats were directly transplanted subcutaneously on both sides of the recipients in the non-castrated group. The grafts were obtained and weighed 4 weeks later. Then the histological features of the grafts were examined by HE staining; the expression and distribution of hydroxysteroid 17-beta dehydrogenase 1 (HSD-17β1) were investigated by immunohistochemistry; and the serum androgen level was determined by ELISA. Results The average mass of grafts obtained from the castrated group was significantly higher than that of the non-castrated group. Immunohistochemistry indicated that Leydig cells were visible in the tissues from both the castrated and non-castrated groups, but the number of HSD-17β1-posotive cells in the castrated group was larger than that in the non-castrated group. ELISA results showed that the serum androgen level was higher in the control group and non-castrated group than in the sham group and castrated group, and compared with the sham group, the serum androgen level in the castrated group was significantly higher. Conclusion The juvenile rat testis subcutaneously transplanted could further develop under the adult recipient rat skin, and the Leydig cells of grafts harbored the ability to produce and secret androgen.

Regulation of the secretion of immunoregulatory factors of mesenchymal stem cells (MSCs) by collagen-based scaffolds during chondrogenesis

Energy Technology Data Exchange (ETDEWEB)

Yang, Jingyu; Chen, Xuening, E-mail: xchen6@scu.edu.cn; Yuan, Tun, E-mail: Stalight@163.com; Yang, Xiao; Fan, Yujiang; Zhang, Xingdong

2017-01-01

In the latest decade, mesenchymal stem cells (MSCs) have wildly considered as a source of seeded cells in tissue engineering, not only because of its multi-differentiation potentials, but also due to its immunoregulation ability. The main immunoregulatory features of MSCs could be divided into low self-immunogenicity and secretion of soluble factors. In this study, we explored how scaffold structures modulated the secretion of soluble immunoregulatory factors in MSCs under an allogeneic cartilage tissue engineering background. MSCs were seeded in four different collagen-based scaffolds. Their proliferation, differentiation, and secretion of various soluble factors associated with the immunosuppressive effects were evaluated. In this study, qRT-PCR, ELISA and immunoregulation results showed a great variability of the factor secretion by MSCs seeded in scaffolds with different structures. Compared with two-dimensional (2D) monolayer culture condition, three-dimensional (3D) groups (hydrogels and sponge) could effectively promote the mRNA expression and the protein production of soluble immune-related factors. Also, the supernatants collected from 3D groups obviously showed inhibition on allogeneic lymphocyte activating. These results suggested that scaffold structures might modulate MSCs' secretion of soluble immunoregulatory factors, and our study might enlighten the scaffold designs for desired tissue regeneration to control the host immune rejection through immune-regulation reaction. - Highlights: • 3D collagen-based hydrogels and sponge could promote the chondrogenic differentiation of MSCs in vitro. • In accordance with the tendency of chondrogenic differentiation, MSCs in 3D scaffolds could secrete various immunoregulatory factors. • Scaffold structure could regulate the secretion of soluble immunoregulatory factors to inhibited the activity of allogeneic lymphocytes in a paracrine way. • Scaffolds could modulate the immunological properties of

Impact of aspartame consumption on neurotransmitters in rat brain ...

African Journals Online (AJOL)

Background: Aspartame (APM), a common artificial sweetener, has been used for diabetic subjects and body weight control for a long time. The goal of the present study was to evaluate the impact of APM consumption on neurotransmitters and oxidative stress in rat's brain. Materials and Methods: Four groups of male ...

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

DEFF Research Database (Denmark)

Larsen, Philip J; Holst, Jens Juul

2005-01-01

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...

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.

The Acid-Secreting Parietal Cell as an Endocrine Source of Sonic Hedgehog During Gastric Repair

Science.gov (United States)

Engevik, Amy C.; Feng, Rui; Yang, Li

2013-01-01

Sonic Hedgehog (Shh) has been shown to regulate wound healing in various tissues. Despite its known function in tissue regeneration, the role of Shh secreted from the gastric epithelium during tissue repair in the stomach remains unknown. Here we tested the hypothesis that Shh secreted from the acid-secreting parietal cell is a fundamental circulating factor that drives gastric repair. A mouse model expressing a parietal cell-specific deletion of Shh (PC-ShhKO) was generated using animals bearing loxP sites flanking exon 2 of the Shh gene (Shhflx/flx) and mice expressing a Cre transgene under the control of the H+,K+-ATPase β-subunit promoter. Shhflx/flx, the H+,K+-ATPase β-subunit promoter, and C57BL/6 mice served as controls. Ulcers were induced via acetic acid injury. At 1, 2, 3, 4, 5, and 7 days after the ulcer induction, gastric tissue and blood samples were collected. Parabiosis experiments were used to establish the effect of circulating Shh on ulcer repair. Control mice exhibited an increased expression of Shh in the gastric tissue and plasma that correlated with the repair of injury within 7 days after surgery. PC-ShhKO mice showed a loss of ulcer repair and reduced Shh tissue and plasma concentrations. In a parabiosis experiment whereby a control mouse was paired with a PC-ShhKO littermate and both animals subjected to gastric injury, a significant increase in the circulating Shh was measured in both parabionts. Elevated circulating Shh concentrations correlated with the repair of gastric ulcers in the PC-ShhKO parabionts. Therefore, the acid-secreting parietal cell within the stomach acts as an endocrine source of Shh during repair. PMID:24092639

Hypoxia enhances the interaction between pancreatic stellate cells and cancer cells via increased secretion of connective tissue growth factor.

Science.gov (United States)

Eguchi, Daiki; Ikenaga, Naoki; Ohuchida, Kenoki; Kozono, Shingo; Cui, Lin; Fujiwara, Kenji; Fujino, Minoru; Ohtsuka, Takao; Mizumoto, Kazuhiro; Tanaka, Masao

2013-05-01

Pancreatic cancer (PC), a hypovascular tumor, thrives under hypoxic conditions. Pancreatic stellate cells (PSCs) promote PC progression by secreting soluble factors, but their functions in hypoxia are poorly understood. This study aimed to clarify the effects of hypoxic conditions on the interaction between PC cells and PSCs. We isolated human PSCs from fresh pancreatic ductal adenocarcinomas and analyzed functional differences in PSCs between normoxia (21% O2) and hypoxia (1% O2), including expression of various factors related to tumor-stromal interactions. We particularly analyzed effects on PC invasiveness of an overexpressed molecule-connective tissue growth factor (CTGF)-in PSCs under hypoxic conditions, using RNA interference techniques. Conditioned media from hypoxic PSCs enhanced PC cell invasiveness more intensely than that from normoxic PSCs (P cancer. Copyright © 2013 Elsevier Inc. All rights reserved.

Imaging neurotransmitter release by drugs of abuse.

Science.gov (United States)

Martinez, Diana; Narendran, Rajesh

2010-01-01

Previous studies have shown that imaging with positron emission tomography (PET) and single photon emission computed tomography (SPECT) radiotracers that are specific for brain dopamine receptors can be used to indirectly image the change in the levels of neurotransmitters within the brain. Most of the studies in addiction have focused on dopamine, since the dopamine neurons that project to the striatum have been shown to play a critical role in mediating addictive behavior. These imaging studies have shown that increased extracellular dopamine produced by psychostimulants can be measured with PET and SPECT. However, there are some technical issues associated with imaging changes in dopamine, and these are reviewed in this chapter. Among these are the loss of sensitivity, the time course of dopamine pulse relative to PET and SPECT imaging, and the question of affinity state of the receptor. In addition, animal studies have shown that most drugs of abuse increase extracellular dopamine in the striatum, yet not all produce a change in neurotransmitter that can be measured. As a result, imaging with a psychostimulant has become the preferred method for imaging presynaptic dopamine transmission, and this method has been used in studies of addiction. The results of these studies suggest that cocaine and alcohol addiction are associated with a loss of dopamine transmission, and a number of studies show that this loss correlates with severity of disease.

Co-infusion of autologous adipose tissue derived insulin-secreting mesenchymal stem cells and bone marrow derived hematopoietic stem cells: Viable therapy for type III.C. a diabetes mellitus

Directory of Open Access Journals (Sweden)

Umang G Thakkar

2014-12-01

Full Text Available Transition from acute pancreatitis to insulin-dependent diabetes mellitus (IDDM is a rare manifestation of primary hyperparathyroidism caused by parathyroid adenoma because of impaired glucose tolerance and suppresses insulin secretion. We report the case of a 26-year-old male with pancreatic diabetes caused by parathyroid adenoma induced chronic pancreatitis. He had serum C-peptide 0.12 ng/ml, glutamic acid decarboxylase antibody 5.0 IU/ml, and glycosylated hemoglobin (HbA1C 8.9%, and required 72 IU/day of biphasic-isophane insulin injection for uncontrolled hyperglycemia. We treated him with his own adipose tissue derived insulin-secreting mesenchymal stem-cells (IS-ADMSC along with his bone marrow derived hematopoietic stem cells (BM-HSC. Autologous IS-ADMSC + BM-HSC were infused into subcutaneous tissue, portal and thymic circulation without any conditioning. Over a follow-up of 27 months, the patient is maintaining fasting and postprandial blood sugar levels of 132 and 165 mg/dl, respectively, with HbA1C 6.8% and requiring 36 IU/day of biphasic-isophane insulin. Co-infusion of IS-ADMSC + BM-HSC offers a safe and viable therapy for type III.C.a Diabetes Mellitus.

Low intraprostatic DHT promotes the infiltration of CD8+ T cells in BPH tissues via modulation of CCL5 secretion.

Science.gov (United States)

Fan, Yu; Hu, Shuai; Liu, Jie; Xiao, Fei; Li, Xin; Yu, Wei; Cui, Yun; Sun, Mengkui; Lv, Tianjing; He, Qun; Jin, Jie

2014-01-01

Clinical studies suggested thatandrogen might be associated with infiltrating T cells in prostate of benign prostatic hyperplasia (BPH) patients, but detail of T-cell subset and mechanism still remained unclear. The present study tested the hypothesis that intraprostatic 5 α -dihydrotestosterone (DHT) exerts effects on T cells recruitment by BPH epithelial cells. Prostate tissues from 64 cases of BPH patients after transurethral resection of prostate (TURP) were divided into 2 groups: (1) no medication history; (2) administration of 5 α -reductase type II inhibitor-finasteride 5 mg daily for at least 6 months before surgery. Group 2 presented significantly higher CD8+ T cells infiltration than group 1, but no changes in CD4+ T cells (immunohistochemistry and flow cytometry). In vitro study more CD8+ T cell migrated to the prostate tissue lysates from group 2 and BPH-1 cells in low DHT condition. Transcription of chemokine (C-C motif) Ligand 5 (CCL5) mRNA in BPH-1 cells and chemokine (C-C motif) receptor 5 (CCR5) mRNA in CD8+ T cells were upregulated in low DHT condition (q-PCR). CCL5 expression was also identified to be higher in group 2 prostate tissues by IHC. This study suggested that intraprostatic DHT may participate in regulating inflammatory response which was induced by human prostatic epithelial cell, via modulating CCL5 secretion.

Low Intraprostatic DHT Promotes the Infiltration of CD8+ T Cells in BPH Tissues via Modulation of CCL5 Secretion

Directory of Open Access Journals (Sweden)

Yu Fan

2014-01-01

Full Text Available Clinical studies suggested thatandrogen might be associated with infiltrating T cells in prostate of benign prostatic hyperplasia (BPH patients, but detail of T-cell subset and mechanism still remained unclear. The present study tested the hypothesis that intraprostatic 5α-dihydrotestosterone (DHT exerts effects on T cells recruitment by BPH epithelial cells. Prostate tissues from 64 cases of BPH patients after transurethral resection of prostate (TURP were divided into 2 groups: (1 no medication history; (2 administration of 5α-reductase type II inhibitor-finasteride 5 mg daily for at least 6 months before surgery. Group 2 presented significantly higher CD8+ T cells infiltration than group 1, but no changes in CD4+ T cells (immunohistochemistry and flow cytometry. In vitro study more CD8+ T cell migrated to the prostate tissue lysates from group 2 and BPH-1 cells in low DHT condition. Transcription of chemokine (C-C motif Ligand 5 (CCL5 mRNA in BPH-1 cells and chemokine (C-C motif receptor 5 (CCR5 mRNA in CD8+ T cells were upregulated in low DHT condition (q-PCR. CCL5 expression was also identified to be higher in group 2 prostate tissues by IHC. This study suggested that intraprostatic DHT may participate in regulating inflammatory response which was induced by human prostatic epithelial cell, via modulating CCL5 secretion.

Direct Visualization of Neurotransmitters in Rat Brain Slices by Desorption Electrospray Ionization Mass Spectrometry Imaging (DESI - MS)

Science.gov (United States)

Fernandes, Anna Maria A. P.; Vendramini, Pedro H.; Galaverna, Renan; Schwab, Nicolas V.; Alberici, Luciane C.; Augusti, Rodinei; Castilho, Roger F.; Eberlin, Marcos N.

2016-12-01

Mass spectrometry imaging (MSI) of neurotransmitters has so far been mainly performed by matrix-assisted laser desorption/ionization (MALDI) where derivatization reagents, deuterated matrix and/or high resolution, or tandem MS have been applied to circumvent problems with interfering ion peaks from matrix and from isobaric species. We herein describe the application of desorption electrospray ionization mass spectrometry imaging (DESI)-MSI in rat brain coronal and sagittal slices for direct spatial monitoring of neurotransmitters and choline with no need of derivatization reagents and/or deuterated materials. The amino acids γ-aminobutyric (GABA), glutamate, aspartate, serine, as well as acetylcholine, dopamine, and choline were successfully imaged using a commercial DESI source coupled to a hybrid quadrupole-Orbitrap mass spectrometer. The spatial distribution of the analyzed compounds in different brain regions was determined. We conclude that the ambient matrix-free DESI-MSI is suitable for neurotransmitter imaging and could be applied in studies that involve evaluation of imbalances in neurotransmitters levels.

Spectroscopic Analysis of Neurotransmitters: A Theoretical and Experimental Raman Study

Science.gov (United States)

Alonzo, Matthew

Surface-enhanced Raman spectroscopy (SERS) was applied to investigate the feasibility in the detection and monitoring of the dopamine (DA) neurotransmitter adsorbed onto silver nanoparticles (Ag NPs) at 10-11 molar, a concentration far below physiological levels. In addition, density functional theory (DFT) calculations were obtained with the Gaussian-09 analytical suite software to generate the theoretical molecular configuration of DA in its neutral, cationic, anionic, and dopaminequinone states for the conversion of computer-simulated Raman spectra. Comparison of theoretical and experimental results show good agreement and imply the presence of dopamine in all of its molecular forms in the experimental setting. The dominant dopamine Raman bands at 750 cm-1 and 795 cm-1 suggest the adsorption of dopaminequinone onto the silver nanoparticle surface. The results of this experiment give good insight into the applicability of using Raman spectroscopy for the biodetection of neurotransmitters.

Contributions to the field of neurotransmitters by Japanese scientists, and reflections on my own research

OpenAIRE

Otsuka, Masanori

2007-01-01

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 ...

Proteomes of the barley aleurone layer: A model system for plant signalling and protein secretion

DEFF Research Database (Denmark)

Finnie, Christine; Andersen, Birgit; Shahpiri, Azar

2011-01-01

molecules in an isolated system. These properties have led to its use as a model system for the study of plant signalling and germination. More recently, proteome analysis of the aleurone layer has provided new insight into this unique tissue including identification of plasma membrane proteins and targeted...... analysis of germination-related changes and the thioredoxin system. Here, analysis of intracellular and secreted proteomes reveals features of the aleurone layer system that makes it promising for investigations of plant protein secretion mechanisms....... to gibberellic acid produced by the embryo, the aleurone layer synthesises hydrolases that are secreted to the endosperm for the degradation of storage products. The barley aleurone layer can be separated from the other seed tissues and maintained in culture, allowing the study of the effect of added signalling...

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. Copyright © 2011 Elsevier B.V. All rights reserved.

What is the role of neurotransmitter systems in cortical seizures?

Czech Academy of Sciences Publication Activity Database

Mareš, Pavel; Kubová, Hana

2008-01-01

Roč. 57, Suppl.3 (2008), S111-S120 ISSN 0862-8408 R&D Projects: GA MŠk(CZ) LC554 Institutional research plan: CEZ:AV0Z50110509 Keywords : neurotransmitters * cerebral cortex * seizures Subject RIV: FH - Neurology Impact factor: 1.653, year: 2008

Fetal growth-retardation and brain-sparing by malnutrition are associated to changes in neurotransmitters profile.

Science.gov (United States)

García-Contreras, C; Valent, D; Vázquez-Gómez, M; Arroyo, L; Isabel, B; Astiz, S; Bassols, A; Gonzalez-Bulnes, A

2017-04-01

The present study assesses possible changes in the levels of different neurotransmitters (catecholamines and indoleamines) in fetuses affected by nutrient shortage. Hence, we determined the concentration of catecholamines and indoleamines at the hypothalamus of 56 swine fetuses obtained at both 70 and 90days of pregnancy (n=33 and 23 fetuses, respectively). The degree of fetal development and the fetal sex affected the neurotransmitters profile at both stages. At Day 70, there were found higher mean concentrations of l-DOPA in both female and male fetuses with severe IUGR; male fetuses with severe IUGR also showed higher concentrations of TRP than normal male littermates. At Day 90 of pregnancy, the differences between sexes were more evident. There were no significant effects from either severe IUGR on the neurotransmitter profile in male fetuses. However, in the females, a lower body-weight was related to lower concentrations of l-DOPA and TRP and those female fetuses affected by severe IUGR evidenced lower HVA concentration. In conclusion, the fetal synthesis and use of neurotransmitters increase with time of pregnancy but, in case of IUGR, both catecholamines and indoleamines pathways are affected by sex-related effects. Copyright © 2017 ISDN. Published by Elsevier Ltd. All rights reserved.

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

Open Secrets

OpenAIRE

Madison, Michael

2017-01-01

The law of trade secrets is often conceptualized in bilateral terms, as creating and enforcing rights between trade secret owners, on the one hand, and misappropriators on the other hand. This paper, a chapter in a forthcoming collection on the law of trade secrets, argues that trade secrets and the law that guards them can serve structural and insitutional roles as well. Somewhat surprisingly, given the law’s focus on secrecy, among the institutional products of trade secrets law are commons...

Neuroglobin in the rat brain (II): co-localisation with neurotransmitters

DEFF Research Database (Denmark)

Hundahl, Christian Ansgar; Kelsen, Jesper; Dewilde, Sylvia

2008-01-01

In an accompanying article, we found that neuroglobin (Ngb) was expressed in a few well-defined nuclei in the rat brain. Here, we show by use of immunohistochemistry and in situ hybridisation (ISH) that Ngb co-localise with several specific neurotransmitters. Ngb co-localise consistently with tyr...

Proteomic identification of secreted proteins of Propionibacterium acnes

Directory of Open Access Journals (Sweden)

Holland Carsten

2010-08-01

Full Text Available Abstract Background The anaerobic Gram-positive bacterium Propionibacterium acnes is a human skin commensal that resides preferentially within sebaceous follicles; however, it also exhibits many traits of an opportunistic pathogen, playing roles in a variety of inflammatory diseases such as acne vulgaris. To date, the underlying disease-causing mechanisms remain ill-defined and knowledge of P. acnes virulence factors remains scarce. Here, we identified proteins secreted during anaerobic cultivation of a range of skin and clinical P. acnes isolates, spanning the four known phylogenetic groups. Results Culture supernatant proteins of P. acnes were separated by two-dimensional electrophoresis (2-DE and all Coomassie-stained spots were subsequently identified by MALDI mass spectrometry (MALDI-MS. A set of 20 proteins was secreted in the mid-exponential growth phase by the majority of strains tested. Functional annotation revealed that many of these common proteins possess degrading activities, including glycoside hydrolases with similarities to endoglycoceramidase, β-N-acetylglucosaminidase and muramidase; esterases such as lysophospholipase and triacylglycerol lipase; and several proteases. Other secreted factors included Christie-Atkins-Munch-Petersen (CAMP factors, glyceraldehyde 3-phosphate dehydrogenase (GAPDH, and several hypothetical proteins, a few of which are unique to P. acnes. Strain-specific differences were apparent, mostly in the secretion of putative adhesins, whose genes exhibit variable phase variation-like sequence signatures. Conclusions Our proteomic investigations have revealed that the P. acnes secretome harbors several proteins likely to play a role in host-tissue degradation and inflammation. Despite a large overlap between the secretomes of all four P. acnes phylotypes, distinct differences between predicted host-tissue interacting proteins were identified, providing potential insight into the differential virulence

Oxygen-Sensitive K+ Channels Modulate Human Chorionic Gonadotropin Secretion from Human Placental Trophoblast

Science.gov (United States)

Díaz, Paula; Sibley, Colin P.; Greenwood, Susan L.

2016-01-01

Human chorionic gonadotropin (hCG) is a key autocrine/paracrine regulator of placental syncytiotrophoblast, the transport epithelium of the human placenta. Syncytiotrophoblast hCG secretion is modulated by the partial pressure of oxygen (pO2), reactive oxygen species (ROS) and potassium (K+) channels. Here we test the hypothesis that K+ channels mediate the effects of pO2 and ROS on hCG secretion. Placental villous explants from normal term pregnancies were cultured for 6 days at 6% (normoxia), 21% (hyperoxia) or 1% (hypoxia) pO2. On days 3–5, explants were treated with 5mM 4-aminopyridine (4-AP) or tetraethylammonium (TEA), blockers of pO2-sensitive voltage-gated K+ (KV) channels, or ROS (10–1000μM H2O2). hCG secretion and lactate dehydrogenase (LDH) release, a marker of necrosis, were determined daily. At day 6, hCG and LDH were measured in tissue lysate and 86Rb (K+) efflux assessed to estimate syncytiotrophoblast K+ permeability. hCG secretion and 86Rb efflux were significantly greater in explants maintained in 21% pO2 than normoxia. 4-AP/TEA inhibited hCG secretion to a greater extent at 21% than 6% and 1% pO2, and reduced 86Rb efflux at 21% but not 6% pO2. LDH release and tissue LDH/hCG were similar in 6%, 21% and 1% pO2 and unaffected by 4-AP/TEA. H2O2 stimulated 86Rb efflux and hCG secretion at normoxia but decreased 86Rb efflux, without affecting hCG secretion, at 21% pO2. 4-AP/TEA-sensitive K+ channels participate in pO2-sensitive hCG secretion from syncytiotrophoblast. ROS effects on both hCG secretion and 86Rb efflux are pO2-dependent but causal links between the two remain to be established. PMID:26863525

Adrenocortical Secreting Mass in a Patient with Gardner's Syndrome: A Case Report

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Nabila Mejdoub Rekik

2010-01-01

Full Text Available Gardner's syndrome (GS is a dysplasia characterized by neoformations of the intestine, soft tissue, and osseous tissue. Endocrine neoplasms have occasionally been reported in association with GS. Adrenal masses in GS are rare, and few have displayed clinical manifestations. In the current paper, The authors report a 37-year-old male patient with GS including familial adenomatous polyposis (FAP and mandible osteoma who presented with an incidental adrenal mass. Computerized tomography adrenal scan identified bilateral masses. Functional analyses showed a hormonal secretion pattern consistent with pre-Cushing's syndrome. Other extraintestinal manifestations were hypertrophy of the pigmented layer of the retina and histiocytofibroma in the right leg. This paper describes a rare association of adrenocortical secreting mass in an old male patient with Gardner syndrome.

The Preferential Infection of Astrocytes by Enterovirus 71 Plays a Key Role in the Viral Neurogenic Pathogenesis.

Science.gov (United States)

Feng, Min; Guo, Sujie; Fan, Shengtao; Zeng, Xiaofeng; Zhang, Ying; Liao, Yun; Wang, Jianbin; Zhao, Ting; Wang, Lichun; Che, Yanchun; Wang, Jingjing; Ma, Na; Liu, Longding; Yue, Lei; Li, Qihan

2016-01-01

The pathological manifestations of fatal cases of human hand, foot, and mouth disease (HFMD) caused by enterovirus 71 (EV71) are characterized by inflammatory damage to the central nervous system (CNS). Here, the dynamic distribution of EV71 in the CNS and the subsequent pathological characteristics within different regions of neonatal rhesus macaque brain tissue were studied using a chimeric EV71 expressing green fluorescence protein. The results were compared with brain tissue obtained from the autopsies of deceased EV71-infected HFMD patients. These observations suggested that the virus was prevalent in areas around the blood vessels and nerve nuclei in the brain stem and showed a preference for astrocytes in the CNS. Interestingly, infected astrocytes within the in vivo and in vitro human and macaque systems exhibited increased expression of excitatory neurotransmitters and cytokines that also stimulated the neuronal secretion of the excitatory neurotransmitters noradrenalin and adrenalin, and this process most likely plays a role in the pathophysiological events that occur during EV71 infection.

New mechanisms of the TCM spleen-based treatment of immune thrombocytopenia purpura from the perspective of blood neurotransmitters

Directory of Open Access Journals (Sweden)

Ke Chen

2017-04-01

Conclusions: The JYS prescription may regulate the expression levels of blood neurotransmitters via the brain-gut axis in patients with “spleen deficiency” ITP and thus activate hemostatic mechanisms to promote hemostasis. β-EP and VIP are key neurotransmitters of the JYS-induced functional regulation.

Common spectrum of polypeptides occurs in secretion granule membranes of different exocrine glands

International Nuclear Information System (INIS)

Cameron, R.S.; Cameron, P.L.; Castle, J.D.

1986-01-01

A highly purified membrane preparation from rat parotid secretion granules has been used as a comparative probe to examine the extent of compositional overlap in granule membranes of three other exocrine secretory tissues - pancreatic, lacrimal, and submandibular - from several standpoints. First, indirect immunofluorescent studies using a polyclonal polyspecific anti-parotid granule membrane antiserum has indicated a selective staining of granule membrane profiles in all acinar cells of all tissues. Second, highly purified granule membrane subfractions have been isolated from each exocrine tissue; comparative two-dimensional (isoelectric focusing; SDS) PAGE of radioiodinated granule membranes has identified 10-15 polypeptides of identical pI and apparent molecular mass. These species are likely to be integral membrane components since they are not extracted by either saponin-sodium sulfate or sodium carbonate (pH 11.5) treatments, and they do not have counterparts in the granule content. Finally, the identity among selected parotid and pancreatic radioiodinated granule membrane polypeptides has been documented using two-dimensional peptide mapping of chymotryptic and tryptic digests. These findings clearly indicate that exocrine secretory granules, irrespective of the nature of stored secretion, comprise a type of vesicular carrier with a common (and probably refined) membrane composition. Conceivably, the polypeptides identified carry out general functions related to exocrine secretion

Correlation of secreted protein acidic and rich in cysteine with diabetic nephropathy

OpenAIRE

Li, Lei; Song, Hai-Yan; Liu, Kai; An, Meng-Meng

2015-01-01

To detect the serum concentrations of secreted protein acidic and rich in cysteine (SPARC) in patients with diabetic nephropathy and SPARC mRNA and protein expressions in renal tissue of db/db mice (C57BL/KsJ, diabetic nephropathy mice), thus preliminary exploration on the role of secreted protein acidic riches in cysteine in the development of diabetic nephropathy were carried out. Serum SPARC levels in normal subjects, patients with type 2 diabetes mellitus (without diabetic nephropathy), c...

High rates of intestinal bicarbonate secretion in seawater tilapia (Oreochromis mossambicus).

Science.gov (United States)

Ruiz-Jarabo, I; Gregório, S F; Gaetano, P; Trischitta, F; Fuentes, J

2017-05-01

Osmoregulation in fish is a complex process that requires the orchestrated cooperation of many tissues. In fish facing hyperosmotic environments, the intestinal absorption of some monovalent ions and the secretion of bicarbonate are key processes to favor water absorption. In the present study, we showed that bicarbonate levels in the intestinal fluid are several fold higher in seawater than in freshwater acclimated tilapia (Oreochromis mossambicus). In addition, we analyzed gene expression of the main molecular mechanisms involved in HCO 3 - movements i.e. slc26a6, slc26a3, slc4a4 and v-type H-ATPase sub C in the intestine of tilapia acclimated to both seawater and freshwater. Our results show an anterior/posterior functional regionalization of the intestine in tilapia in terms of expression patterns, which is affected by environmental salinity mostly in the anterior and mid intestine. Analysis of bicarbonate secretion using pH-Stat in tissues mounted in Ussing chambers reveals high rates of bicarbonate secretion in tilapia acclimated to seawater from anterior intestine to rectum ranging between ~900 and ~1700nmolHCO 3 - cm -2 h -1 . However, a relationship between the expression of slc26a6, slc26a3, slc4a4 and the rate of bicarbonate secretion seems to be compromised in the rectum. In this region, the low expression of the bicarbonate transporters could not explain the high bicarbonate secretion rates here described. However, we postulate that the elevated v-type H-ATPase mRNA expression in the rectum could be involved in this process. Copyright © 2017 Elsevier Inc. All rights reserved.

[Investigations on the physiology of the glands of carnivorous plants : IV. The kinetics of chloride secretion by the gland tissue of Nepenthes].

Science.gov (United States)

Lüttge, U

1966-03-01

The transport of chloride in isolated tissue from Nepenthes pitchers was investigated using (36)Cl(-), an Aminco-Cotlove chloride-titrator for the determinations of Cl(-) concentrations, and KCN and AsO 4 (-) -as metabolic inhibitors.The tissue was brought in contact with different experimental solutions (=medium). The surface corresponding to the outside of the pitchers was cut with a razor blade to remove the cutinized epidermal layer. At this surface the Cl(-) uptake from the medium is a metabolic process which depends on the Cl(-)-concentration of the medium in a manner that corresponds to the MICHAELIS-MENTEN kinetics. The Michaelis-constant of this transport step was 3×10(-2)M. The Cl(-)-efflux into the medium, however, is a passive process.The opposite surface of the tissue slices (corresponding to the inside of the pitchers) carries the glands. The chloride secretion taking place here is also dependent on metabolism. In vitro it occurs even when a high gradient of chloride concentration has been set up between the medium and the solution which is in contact with the glands. In vivo the Cl(-)-concentration of the pitcher fluid and the amount of Cl(-) per gram of tissue water are almost equal.The rôle of chloride in the physiology of Nepenthes is still under investigation, A correlation between the chloride content of the pitcher fluid and its enzymatic activity (Casein-test), however, could already be demonstrated.

Convergent and reciprocal modulation of a leak K+ current and Ih by an inhalational anaesthetic and neurotransmitters in rat brainstem motoneurones

Science.gov (United States)

Sirois, Jay E; Lynch, Carl; Bayliss, Douglas A

2002-01-01

Neurotransmitters and volatile anaesthetics have opposing effects on motoneuronal excitability which appear to reflect contrasting modulation of two types of subthreshold currents. Neurotransmitters increase motoneuronal excitability by inhibiting TWIK-related acid-sensitive K+ channels (TASK) and shifting activation of a hyperpolarization-activated cationic current (Ih) to more depolarized potentials; on the other hand, anaesthetics decrease excitability by activating a TASK-like current and inducing a hyperpolarizing shift in Ih activation. Here, we used whole-cell recording from motoneurones in brainstem slices to test if neurotransmitters (serotonin (5-HT) and noradrenaline (NA)) and an anaesthetic (halothane) indeed compete for modulation of the same ion channels - and we determined which prevails. When applied together under current clamp conditions, 5-HT reversed anaesthetic-induced membrane hyperpolarization and increased motoneuronal excitability. Under voltage clamp conditions, 5-HT and NA overcame most, but not all, of the halothane-induced current. When Ih was blocked with ZD 7288, the neurotransmitters completely inhibited the K+ current activated by halothane; the halothane-sensitive neurotransmitter current reversed at the equilibrium potential for potassium (EK) and displayed properties expected of acid-sensitive, open-rectifier TASK channels. To characterize modulation of Ih in relative isolation, effects of 5-HT and halothane were examined in acidified bath solutions that blocked TASK channels. Under these conditions, 5-HT and halothane each caused their characteristic shift in voltage-dependent gating of Ih. When tested concurrently, however, halothane decreased the neurotransmitter-induced depolarizing shift in Ih activation. Thus, halothane and neurotransmitters converge on TASK and Ih channels with opposite effects; transmitter action prevailed over anaesthetic effects on TASK channels, but not over effects on Ih. These data suggest that

Sites of production of sex steroids: secretion of steroids from x-irradiated and polycystic ovaries of rats

International Nuclear Information System (INIS)

Sawada, T.; Ichikawa, S.

1978-01-01

Ovaries of immature rats and PMS-induced pregnant rats were unilaterally x-irradiated. Ten days later, the concentrations of pregnane compounds in the ovarian venous plasma were measured. LH (2 μg) was injected iv 30 min before bleeding. A comparison of steroid levels in the ovarian venous effluent of rats with and without destruction of selected tissue components by irradiation of the ovaries suggests that the follicles contribute to the secretion of 5α-pregnane-3,20-dione and 3α-hydroxy-5α-pregnan-20-one in the presence of interstitial gland tissue. Because it is known that follicular tissue is involved in the production of estrogens, we studied the interrelationship between the secretion of the two progesterone metabolites and estrogens in follicular polycystic ovaries of androgen-sterilized rats. Normal ovaries of diestrus-2 rats were used as controls for the polycystic ovaries. The injection of LH greatly increased the secretion of 5α-pregnane-3,20-dione and 3α-hydroxy-5α-pregnan-20-one within 1 h in normal ovaries, but the response of polycystic ovaries was low, suggesting low 5α-reductase activity in the cystic ovary. The polycystic ovaries exhibited a marked increase in the secretion of estrogens in response to LH, whereas normal ovaries showed no significant change. These results suggest that low 5α-reductase activity may be causally related to the high level of estrogen secretion in polycystic ovaries of androgen-sterilized rats

Simultaneous imaging of multiple neurotransmitters and neuroactive substances in the brain by desorption electrospray ionization mass spectrometry

OpenAIRE

Shariatgorji, Mohammadreza; Strittmatter, Nicole; Nilsson, Anna; Kallbäck, Patrik; Alvarsson, Alexandra; Zhang, Xiaoqun; Vallianatou, Theodosia; Svenningsson, Per; Goodwin, Richard J. A.; Andrén, Per E.

2016-01-01

With neurological processes involving multiple neurotransmitters and neuromodulators, it is important to have the ability to directly map and quantify multiple signaling molecules simultaneously in a single analysis. By utilizing a molecular-specific approach, namely desorption electrospray ionization mass spectrometry imaging (DESI-MSI), we demonstrated that the technique can be used to image multiple neurotransmitters and their metabolites (dopamine, dihydroxyphenylacetic acid, 3-methoxytyr...

Endoplasmic reticulum stress is increased in adipose tissue of women with gestational diabetes.

Directory of Open Access Journals (Sweden)

Stella Liong

Full Text Available Maternal obesity and gestational diabetes mellitus (GDM are two increasingly common and important obstetric complications that are associated with severe long-term health risks to mothers and babies. IL-1β, which is increased in obese and GDM pregnancies, plays an important role in the pathophysiology of these two pregnancy complications. In non-pregnant tissues, endoplasmic (ER stress is increased in diabetes and can induce IL-1β via inflammasome activation. The aim of this study was to determine whether ER stress is increased in omental adipose tissue of women with GDM, and if ER stress can also upregulate inflammasome-dependent secretion of IL-1β. ER stress markers IRE1α, GRP78 and XBP-1s were significantly increased in adipose tissue of obese compared to lean pregnant women. ER stress was also increased in adipose tissue of women with GDM compared to BMI-matched normal glucose tolerant (NGT women. Thapsigargin, an ER stress activator, induced upregulated secretion of mature IL-1α and IL-1β in human omental adipose tissue explants primed with bacterial endotoxin LPS, the viral dsRNA analogue poly(I:C or the pro-inflammatory cytokine TNF-α. Inhibition of capase-1 with Ac-YVAD-CHO resulted in decreased IL-1α and IL-1β secretion, whereas inhibition of pannexin-1 with carbenoxolone suppressed IL-1β secretion only. Treatment with anti-diabetic drugs metformin and glibenclamide also reduced IL-1α and IL-1β secretion in infection and cytokine-primed adipose tissue. In conclusion, this study has demonstrated ER stress to activate the inflammasome in pregnant adipose tissue. Therefore, increased ER stress may contribute towards the pathophysiology of obesity in pregnancy and GDM.

Next Generation Sequencing Identifies Five Major Classes of Potentially Therapeutic Enzymes Secreted by Lucilia sericata Medical Maggots.

Science.gov (United States)

Franta, Zdeněk; Vogel, Heiko; Lehmann, Rüdiger; Rupp, Oliver; Goesmann, Alexander; Vilcinskas, Andreas

2016-01-01

Lucilia sericata larvae are used as an alternative treatment for recalcitrant and chronic wounds. Their excretions/secretions contain molecules that facilitate tissue debridement, disinfect, or accelerate wound healing and have therefore been recognized as a potential source of novel therapeutic compounds. Among the substances present in excretions/secretions various peptidase activities promoting the wound healing processes have been detected but the peptidases responsible for these activities remain mostly unidentified. To explore these enzymes we applied next generation sequencing to analyze the transcriptomes of different maggot tissues (salivary glands, gut, and crop) associated with the production of excretions/secretions and/or with digestion as well as the rest of the larval body. As a result we obtained more than 123.8 million paired-end reads, which were assembled de novo using Trinity and Oases assemblers, yielding 41,421 contigs with an N50 contig length of 2.22 kb and a total length of 67.79 Mb. BLASTp analysis against the MEROPS database identified 1729 contigs in 577 clusters encoding five peptidase classes (serine, cysteine, aspartic, threonine, and metallopeptidases), which were assigned to 26 clans, 48 families, and 185 peptidase species. The individual enzymes were differentially expressed among maggot tissues and included peptidase activities related to the therapeutic effects of maggot excretions/secretions.

[The association between plasma neurotransmitters levels and depression in acute hemorrhagic stroke].

Science.gov (United States)

Yuan, Huai-wu; Zhang, Ning; Wang, Chun-xue; Shi, Yu-zhi; Qi, Dong; Luo, Ben-yan; Wang, Yong-jun

2013-08-01

To explore the relation between plasma neurotransmitters (Glutamic acid, GAA; γ-aminobutyric acid, GABA; 5-hydroxytryptamine, 5-HT; and noradrenaline, NE) and depression in acute hemorrhagic stroke. Objectives were screened from consecutive hospitalized patients with acute stroke. Fasting blood samples were taken on the day next to hospital admission, and neurotransmitters were examined by the liquid chromatography-high resolution mass spectrometry (LC-HRMS). The fourth edition of Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) was used to diagnose depression at two weeks after onset of stroke. The modified Ranking Scale (mRS) was followed up at 1 year. Pearson test was used to analyse the correlation between serum concentration of neurotransmitters and the Hamilton Depression scale-17-items (HAMD-17) score. Logistic regression was used to analyse the relation of serum concentration of neurotransmitters and depression and outcome of stroke. One hundred and eighty-one patients were included in this study. GABA significantly decreased [6.1(5.0-8.2) µg/L vs 8.1(6.3-14.7) µg/L, P depression in hemorrhagic stroke, and there was no significant difference in GAA, 5-HT, or NE. GABA concentration was negatively correlated with HAMD-17 score (r = -0.131, P depression in acute phase of hemorrhagic stroke was reduced by 5.6% (OR 0.944, 95%CI 0.893-0.997). While concentration of serum GAA rose by 1 µg/L, risk of worse outcome at 1 year was raised by 0.1%, although a statistic level was on marginal status (OR 1.001, 95%CI 1.000-1.002). In patients with depression in the acute phase of hemorrhagic stroke, there was a significant reduction in plasma GABA concentration. GABA may have a protective effect on depression in acute phase of hemorrhagic stroke. Increased concentrations of serum GAA may increase the risk of worse outcomes at 1 year after stroke.

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

The discovery of chemical neurotransmitters.

Science.gov (United States)

Valenstein, Elliot S

2002-06-01

Neurotransmitters have become such an intrinsic part of our theories about brain function that many today are unaware of how difficult it was to prove their existence or the protracted dispute over the nature of synaptic transmission. The story is important not only because it is fascinating science history, but also because it exemplifies much of what is best in science and deserving to be emulated. The friendships formed among such major figures in this history as Henry Dale, Otto Loewi, Wilhelm Feldberg, Walter Cannon, and others extended over two world wars, enriching their lives and facilitating their research. Even the dispute-the "war of the sparks and the soups"--between neurophysiologists and pharmacologists over whether synaptic transmission is electrical or chemical played a positive role in stimulating the research needed to provide convincing proof. Copyright 2002 Elsevier Science (USA).

"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.

On Converting Secret Sharing Scheme to Visual Secret Sharing Scheme

Directory of Open Access Journals (Sweden)

Wang Daoshun

2010-01-01

Full Text Available Abstract Traditional Secret Sharing (SS schemes reconstruct secret exactly the same as the original one but involve complex computation. Visual Secret Sharing (VSS schemes decode the secret without computation, but each share is m times as big as the original and the quality of the reconstructed secret image is reduced. Probabilistic visual secret sharing (Prob.VSS schemes for a binary image use only one subpixel to share the secret image; however the probability of white pixels in a white area is higher than that in a black area in the reconstructed secret image. SS schemes, VSS schemes, and Prob. VSS schemes have various construction methods and advantages. This paper first presents an approach to convert (transform a -SS scheme to a -VSS scheme for greyscale images. The generation of the shadow images (shares is based on Boolean XOR operation. The secret image can be reconstructed directly by performing Boolean OR operation, as in most conventional VSS schemes. Its pixel expansion is significantly smaller than that of VSS schemes. The quality of the reconstructed images, measured by average contrast, is the same as VSS schemes. Then a novel matrix-concatenation approach is used to extend the greyscale -SS scheme to a more general case of greyscale -VSS scheme.

Authentication Without Secrets

Energy Technology Data Exchange (ETDEWEB)

Pierson, Lyndon G. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Robertson, Perry J. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

2015-11-01

This work examines a new approach to authentication, which is the most fundamental security primitive that underpins all cyber security protections. Current Internet authentication techniques require the protection of one or more secret keys along with the integrity protection of the algorithms/computations designed to prove possession of the secret without actually revealing it. Protecting a secret requires physical barriers or encryption with yet another secret key. The reason to strive for "Authentication without Secret Keys" is that protecting secrets (even small ones only kept in a small corner of a component or device) is much harder than protecting the integrity of information that is not secret. Promising methods are examined for authentication of components, data, programs, network transactions, and/or individuals. The successful development of authentication without secret keys will enable far more tractable system security engineering for high exposure, high consequence systems by eliminating the need for brittle protection mechanisms to protect secret keys (such as are now protected in smart cards, etc.). This paper is a re-release of SAND2009-7032 with new figures numerous edits.

Sensitive determination of neurotransmitters in urine by microchip electrophoresis with multiple-concentration approaches combining field-amplified and reversed-field stacking.

Science.gov (United States)

Zhang, Yan; Zhang, Yi; Wang, Guan; Chen, Wujuan; Li, Yi; Zhang, Yating; He, Pingang; Wang, Qingjiang

2016-07-01

Microchip electrophoresis (MCE) is particularly attractive as it provides high sensitivity and selectivity, short analysis time and low sample consumption. An on-line preconcentration strategy combining field-amplified stacking (FASS) and reversed-field stacking (RFS) was developed for efficient and sensitive analysis of neurotransmitters in real urine samples by MCE with laser induced fluorescence (LIF) detection. In this study, the multiple-preconcentration strategy greatly improves the sensitivity enhancement and surpass other conventional analytical methods for neurotransmitters detection. Under optimal conditions, the separation of three neurotransmitters (dopamine, norepinephrine and serotonin), was achieved within 3min with limits of detection (S/N=3) of 1.69, 2.35, and 2.73nM, respectively. The detection sensitivities were improved by 201-, 182-, and 292-fold enhancement, for the three neurotransmitters respectively. Other evaluation parameters such as linear correlation coefficients were considered as satisfactory. A real urine sample was analyzed with recoveries of 101.8-106.4%. The proposed FASS-RFS-MCE method was characterized in terms of precision, linearity, accuracy and successfully applied for rapid and sensitive determination of three neurotransmitters in human urine. Copyright © 2016 Elsevier B.V. All rights reserved.

Macrophage-secreted factors induce adipocyte inflammation and insulin resistance

International Nuclear Information System (INIS)

Permana, Paska A.; Menge, Christopher; Reaven, Peter D.

2006-01-01

Macrophage infiltration into adipose tissue increases with obesity, a condition associated with low-grade inflammation and insulin resistance. We investigated the direct effects of macrophage-secreted factors on adipocyte inflammation and insulin resistance. 3T3-L1 adipocytes incubated with media conditioned by RAW264.7 macrophages (RAW-CM) showed dramatically increased transcription of several inflammation-related genes, greater nuclear factor kappa B (NF-κB) activity, and enhanced binding of U937 monocytes. All of these effects were prevented by co-incubation with pyrrolidinedithiocarbamate, an NF-κB inhibitor. Adipocytes incubated with RAW-CM also released more non-esterified fatty acids and this increased lipolysis was not suppressed by insulin. In addition, RAW-CM treatment decreased insulin-stimulated glucose uptake in adipocytes. Taken together, these results indicate that macrophage-secreted factors induce inflammatory responses and reduce insulin responsiveness in adipocytes. These effects of macrophage-secreted factors on adipocytes may contribute significantly to the systemic inflammation and insulin resistance associated with obesity

[A case of GH and TSH secreting pituitary macroadenoma].

Science.gov (United States)

Gołkowski, Filip; Buziak-Bereza, Monika; Stefańska, Agnieszka; Trofimiuk, Małgorzata; Pantofliński, Jacek; Huszno, Bohdan; Czepko, Ryszard; Adamek, Dariusz

2006-01-01

A case of GH and TSH secreting pituitary macroadenoma is reported. A 45-year-old female presented clinical features of acromegaly (the abnormal growth of the hands and feet, with lower jaw protrusion), diabetes mellitus, hypertension, nodular goiter and hyperthyroidism of unclear origin. NMR pituitary imaging revealed intra and extrasellar tumor. The laboratory examinations showed very high plasma levels of GH and IGF-1 and normal level of TSH coexisting with high plasma levels of free thyroid hormones. Pharmacological pretreatment with somatostatin analogues caused the substantial reduction of GH and TSH plasma levels. Histological and immunohistochemical examination of the tissue obtained at transsphenoidal surgery showed GH and TSH secreting adenoma. The laboratory examinations after surgery showed normal GH and IGF-1 plasma levels and reduced insulin requirement, what indicates radical operation. The very low plasma levels of TSH and free thyroid hormones after surgery and immunohistochemical examination suggest central hyperthyroidism due to TSH secreting pituitary tumor (thyrotropinoma).

A genome-wide RNAi screen identifies regulators of cholesterol-modified hedgehog secretion in Drosophila.

Directory of Open Access Journals (Sweden)

Reid Aikin

Full Text Available Hedgehog (Hh proteins are secreted molecules that function as organizers in animal development. In addition to being palmitoylated, Hh is the only metazoan protein known to possess a covalently-linked cholesterol moiety. The absence of either modification severely disrupts the organization of numerous tissues during development. It is currently not known how lipid-modified Hh is secreted and released from producing cells. We have performed a genome-wide RNAi screen in Drosophila melanogaster cells to identify regulators of Hh secretion. We found that cholesterol-modified Hh secretion is strongly dependent on coat protein complex I (COPI but not COPII vesicles, suggesting that cholesterol modification alters the movement of Hh through the early secretory pathway. We provide evidence that both proteolysis and cholesterol modification are necessary for the efficient trafficking of Hh through the ER and Golgi. Finally, we identified several putative regulators of protein secretion and demonstrate a role for some of these genes in Hh and Wingless (Wg morphogen secretion in vivo. These data open new perspectives for studying how morphogen secretion is regulated, as well as provide insight into regulation of lipid-modified protein secretion.

Secreted Clusterin protein inhibits osteoblast differentiation of bone marrow mesenchymal stem cells by suppressing ERK1/2 signaling pathway

DEFF Research Database (Denmark)

Abdallah, Basem; Alzahrani, Abdullah M; Kassem, Moustapha

2018-01-01

Secreted Clusterin (sCLU, also known as Apolipoprotein J) is an anti-apoptotic glycoprotein involved in the regulation of cell proliferation, lipid transport, extracellular tissue remodeling and apoptosis. sCLU is expressed and secreted by mouse bone marrow-derived skeletal (stromal or mesenchyma...

The primary mechanism of attenuation of bacillus Calmette–Guérin is a loss of secreted lytic function required for invasion of lung interstitial tissue

Science.gov (United States)

Hsu, Tsungda; Hingley-Wilson, Suzanne M.; Chen, Bing; Chen, Mei; Dai, Annie Z.; Morin, Paul M.; Marks, Carolyn B.; Padiyar, Jeevan; Goulding, Celia; Gingery, Mari; Eisenberg, David; Russell, Robert G.; Derrick, Steven C.; Collins, Frank M.; Morris, Sheldon L.; King, C. Harold; Jacobs, William R.

2003-01-01

Tuberculosis remains a leading cause of death worldwide, despite the availability of effective chemotherapy and a vaccine. Bacillus Calmette–Guérin (BCG), the tuberculosis vaccine, is an attenuated mutant of Mycobacterium bovis that was isolated after serial subcultures, yet the functional basis for this attenuation has never been elucidated. A single region (RD1), which is absent in all BCG substrains, was deleted from virulent M. bovis and Mycobacterium tuberculosis strains, and the resulting ΔRD1 mutants were significantly attenuated for virulence in both immunocompromised and immunocompetent mice. The M. tuberculosis ΔRD1 mutants were also shown to protect mice against aerosol challenge, in a similar manner to BCG. Interestingly, the ΔRD1 mutants failed to cause cytolysis of pneumocytes, a phenotype that had been previously used to distinguish virulent M. tuberculosis from BCG. A specific transposon mutation, which disrupts the Rv3874 Rv3875 (cfp-10 esat-6) operon of RD1, also caused loss of the cytolytic phenotype in both pneumocytes and macrophages. This mutation resulted in the attenuation of virulence in mice, as the result of reduced tissue invasiveness. Moreover, specific deletion of each transcriptional unit of RD1 revealed that three independent transcriptional units are required for virulence, two of which are involved in the secretion of ESAT-6 (6-kDa early secretory antigenic target). We conclude that the primary attenuating mechanism of bacillus Calmette–Guérin is the loss of cytolytic activity mediated by secreted ESAT-6, which results in reduced tissue invasiveness. PMID:14557547

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

Protein kinase A mediates adenosine A2a receptor modulation of neurotransmitter release via synapsin I phosphorylation in cultured cells from medulla oblongata.

Science.gov (United States)

Matsumoto, Joao Paulo Pontes; Almeida, Marina Gomes; Castilho-Martins, Emerson Augusto; Costa, Maisa Aparecida; Fior-Chadi, Debora Rejane

2014-08-01

Synaptic transmission is an essential process for neuron physiology. Such process is enabled in part due to modulation of neurotransmitter release. Adenosine is a synaptic modulator of neurotransmitter release in the Central Nervous System, including neurons of medulla oblongata, where several nuclei are involved with neurovegetative reflexes. Adenosine modulates different neurotransmitter systems in medulla oblongata, specially glutamate and noradrenaline in the nucleus tractussolitarii, which are involved in hypotensive responses. However, the intracellular mechanisms involved in this modulation remain unknown. The adenosine A2a receptor modulates neurotransmitter release by activating two cAMP protein effectors, the protein kinase A and the exchange protein activated by cAMP. Therefore, an in vitro approach (cultured cells) was carried out to evaluate modulation of neurotransmission by adenosine A2a receptor and the signaling intracellular pathway involved. Results show that the adenosine A2a receptor agonist, CGS 21680, increases neurotransmitter release, in particular, glutamate and noradrenaline and such response is mediated by protein kinase A activation, which in turn increased synapsin I phosphorylation. This suggests a mechanism of A2aR modulation of neurotransmitter release in cultured cells from medulla oblongata of Wistar rats and suggest that protein kinase A mediates this modulation of neurotransmitter release via synapsin I phosphorylation. Copyright © 2014 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

Secreted microvesicular miR-31 inhibits osteogenic differentiation of mesenchymal stem cells

DEFF Research Database (Denmark)

Weilner, Sylvia; Schraml, Elisabeth; Wieser, Matthias

2016-01-01

Damage to cells and tissues is one of the driving forces of aging and age-related diseases. Various repair systems are in place to counteract this functional decline. In particular, the property of adult stem cells to self-renew and differentiate is essential for tissue homeostasis and regeneration....... However, their functionality declines with age (Rando, 2006). One organ that is notably affected by the reduced differentiation capacity of stem cells with age is the skeleton. Here, we found that circulating microvesicles impact on the osteogenic differentiation capacity of mesenchymal stem cells....... As a potential source of its secretion, we identified senescent endothelial cells, which are known to increase during aging in vivo (Erusalimsky, 2009). Endothelial miR-31 is secreted within senescent cell-derived microvesicles and taken up by mesenchymal stem cells where it inhibits osteogenic differentiation...

Efficacy of supermacroporous poly(ethylene glycol)–gelatin cryogel matrix for soft tissue engineering applications

Energy Technology Data Exchange (ETDEWEB)

Sharma, Archana [Department of Biological Sciences, Birla Institute of Technology and Science, Pilani-K.K Birla Goa Campus, 403726 Goa (India); Bhat, Sumrita [Department of Biological Sciences and Bioengineering, Indian Institute of Technology Kanpur, Kanpur, 208016 UP (India); Nayak, Vijayashree, E-mail: vijayashree@goa.bits-pilani.ac.in [Department of Biological Sciences, Birla Institute of Technology and Science, Pilani-K.K Birla Goa Campus, 403726 Goa (India); Kumar, Ashok, E-mail: ashokkum@iitk.ac.in [Department of Biological Sciences and Bioengineering, Indian Institute of Technology Kanpur, Kanpur, 208016 UP (India)

2015-02-01

Three dimensional scaffolds synthesized using natural or synthetic polymers act as an artificial niche for cell adherence and proliferation. In this study, we have fabricated cryogels employing blend of poly (ethylene glycol) (PEG) and gelatin using two different crosslinkers like, glutaraldehyde and EDC-NHS by cryogelation technique. Synthesized matrices possessed interconnected porous structure in the range of 60–100 μm diameter and regained their original length after 90% compression without deformation. Visco-elastic behavior was studied by rheology and unconfined compression analysis, elastic modulus of these cryogels was observed to be > 10{sup 5} Pa which showed their elasticity and mechanical strength. TGA and DSC also showed the stability of these cryogels at different temperatures. In vitro degradation capacity was analyzed for 4 weeks at 37 °C. IMR-32, C2C12 and Cos-7 cells proliferation and ECM secretion on PEG–gelatin cryogels were observed by SEM and fluorescent analysis. In vitro biocompatibility was analyzed by MTT assay for the period of 15 days. Furthermore, cell proliferation efficiency, metabolic activity and functionality of IMR-32 cells were analyzed by neurotransmitter assay and DNA quantification. The cell–matrix interaction, elasticity, mechanical strength, stability at different temperatures, biocompatible, degradable nature showed the potentiality of these cryogels towards soft tissue engineering such as neural, cardiac and skin. - Highlights: • PEG–gelatin cryogel matrices were produced by cryogelation technology. • Matrices showed suitable properties for tissue engineering applications. • Polymeric cryogels supported growth of IMR-32, C2C12 and Cos-7 cells in vitro.

Sex and intrauterine growth restriction modify brain neurotransmitters profile of newborn piglets.

Science.gov (United States)

Vázquez-Gómez, M; Valent, D; García-Contreras, C; Arroyo, L; Óvilo, C; Isabel, B; Bassols, A; González-Bulnes, A

2016-12-01

The current study aimed to determine, using a swine model of intrauterine growth restriction (IUGR), whether short- and long-term neurological deficiencies and interactive dysfunctions of Low Birth-Weight (LBW) offspring might be related to altered pattern of neurotransmitters. Hence, we compared the quantities of different neurotransmitters (catecholamines and indoleamines), which were determined by HPLC, at brain structures related to the limbic system (hippocampus and amygdala) in 14 LBW and 10 Normal Body-Weight (NBW) newborn piglets. The results showed, firstly, significant effects of sex on the NBW newborns, with females having higher dopamine (DA) concentrations than males. The IUGR processes affected DA metabolism, with LBW piglets having lower concentrations of noradrenaline at the hippocampus and higher concentrations of the DA metabolites, homovanillic acid (HVA), at both the hippocampus and the amygdala than NBW neonates. The effects of IUGR were modulated by sex; there were no significant differences between LBW and NBW females, but LBW males had higher HVA concentration at the amygdala and higher concentration of 5-hydroxyindoleacetic acid, the serotonin metabolite, at the hippocampus than NBW males. In conclusion, the present study shows that IUGR is mainly related to changes, modulated by sex, in the concentrations of catecholamine neurotransmitters, which are related to adaptation to physical activity and to essential cognitive functions such as learning, memory, reward-motivated behavior and stress. Copyright © 2016 ISDN. Published by Elsevier Ltd. All rights reserved.

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...... related to oxidative metabolism when the amino acids are used as energy substrates. This, in turn, is influenced by the extent to which the cycling of the amino acids between neurons and astrocytes may occur. This cycling is brought about by the glutamate/GABA - glutamine cycle the operation of which...

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

Primary cultures of GABAergic cerebral cortex neurons and glutamatergic cerebellar granule cells were used to study the expression of synaptophysin, a synaptic vesicle marker protein, along with the ability of each cell type to release neurotransmitter upon stimulation. The synaptophysin expression...... 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...

Self-assembly of SiO2 nanoparticles for the potentiometric detection of neurotransmitter acetylcholine and its inhibitor.

Science.gov (United States)

Arruda, Izabela G; Guimarães, Francisco E G; Ramos, Romildo J; Vieira, Nirton C S

2014-09-01

The detection and quantification of neurotransmitter acetylcholine (ACh) are relevant because modifications in the ACh levels constitute a threat to human health. The biological regulator of this neurotransmitter is acetylcholinesterase (AChE), an enzyme that catalyzes the hydrolysis of ACh to choline and acetic acid. However, its activity is inhibited in the presence of organophosphate and carbamate pesticides, compromising the degradation of the neurotransmitter. There has been a growing interest in faster and more sensitive detection systems that include new methods and materials for the determination of the ACh concentration. This paper proposes a potentiometric biosensor for the detection of neurotransmitter ACh and its inhibitors, specifically organophosphate pesticide methamidophos. The biosensor is based on a self-assembled platform formed by poly(allylamine) hydrochloride (PAH) and silicon dioxide nanoparticles (SiO2-Np) that contains the immobilized enzyme AChE. First, the responses of the biosensor were investigated for different concentrations of ACh in buffer solutions. After quantifying ACh, the inhibition of AChE in the presence of methamidophos was determined, enabling the quantification of methamidophos expressed as the percentage of enzyme inhibition. The potential advantages of this biosensor include simplicity in building the electrode, possible production on an industrial scale, limited need for qualified personnel to operate the device and low processing cost.

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.

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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. Copyright © 2016 Elsevier B.V. All rights reserved.

Adipose tissue macrophages impair preadipocyte differentiation in humans.

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Li Fen Liu

Full Text Available The physiologic mechanisms underlying the relationship between obesity and insulin resistance are not fully understood. Impaired adipocyte differentiation and localized inflammation characterize adipose tissue from obese, insulin-resistant humans. The directionality of this relationship is not known, however. The aim of the current study was to investigate whether adipose tissue inflammation is causally-related to impaired adipocyte differentiation.Abdominal subcutaneous(SAT and visceral(VAT adipose tissue was obtained from 20 human participants undergoing bariatric surgery. Preadipocytes were isolated, and cultured in the presence or absence of CD14+ macrophages obtained from the same adipose tissue sample. Adipocyte differentiation was quantified after 14 days via immunofluorescence, Oil-Red O, and adipogenic gene expression. Cytokine secretion by mature adipocytes cultured with or without CD14+macrophages was quantified.Adipocyte differentiation was significantly lower in VAT than SAT by all measures (p<0.001. With macrophage removal, SAT preadipocyte differentiation increased significantly as measured by immunofluorescence and gene expression, whereas VAT preadipocyte differentiation was unchanged. Adipocyte-secreted proinflammatory cytokines were higher and adiponectin lower in media from VAT vs SAT: macrophage removal reduced inflammatory cytokine and increased adiponectin secretion from both SAT and VAT adipocytes. Differentiation of preadipocytes from SAT but not VAT correlated inversely with systemic insulin resistance.The current results reveal that proinflammatory immune cells in human SAT are causally-related to impaired preadipocyte differentiation, which in turn is associated with systemic insulin resistance. In VAT, preadipocyte differentiation is poor even in the absence of tissue macrophages, pointing to inherent differences in fat storage potential between the two depots.

Effects of focal brain cooling on extracellular concentrations of neurotransmitters in patients with epilepsy.

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Nomura, Sadahiro; Inoue, Takao; Imoto, Hirochika; Suehiro, Eiichi; Maruta, Yuichi; Hirayama, Yuya; Suzuki, Michiyasu

2017-04-01

Brain hypothermia controls epileptic discharge and reduces extracellular concentrations of glutamate (Glu), an excitatory neurotransmitter. We aimed to determine the effects of focal brain cooling (FBC) on levels of γ-aminobutyric acid (GABA), which is a major inhibitory neurotransmitter. The relationship between Glu or GABA concentrations and the severity of epileptic symptoms was also analyzed. Patients with intractable epilepsy underwent FBC at lesionectomized (n = 11) or hippocampectomized (n = 8) regions at 15°C for 30 min using custom-made cooling devices. Concentrations of Glu (n = 18) and GABA (n = 12) were measured in extracellular fluid obtained through microdialysis using high-performance liquid chromatography (HPLC). The reduction rate of neurotransmitter levels and its relationship with electrocorticography (ECoG) signal changes in response to FBC were measured. We found no relationship between the concentrations of Glu or GABA and seizure severity. There was a significant decrease in the concentration of Glu to 66.3% of control levels during the cooling period (p = 0.001). This rate of reduction correlated with ECoG power (r 2 = 0.68). Cortical and hippocampal GABA levels significantly (p = 0.02) and nonsignificantly decreased to 47.7% and 32.4% of control levels, respectively. However, the rate of this reduction did not correlate with ECoG (r 2 = 0.11). Although the decrease in hippocampal GABA levels was not significant due to wide variations in its concentration, the levels of cortical GABA and Glu were decreased following FBC. FBC suppresses epileptic discharge and the release of both excitatory and inhibitory neurotransmitters. The reduction in Glu levels further contributes to the reduction in epileptic discharge. However, the reduction in the levels of GABA has no impact on ECoG. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

Effect of single-dose radiation on cell survival and growth hormone secretion by rat anterior pituitary cells

International Nuclear Information System (INIS)

Hochberg, Z.; Kuten, A.; Hertz, P.; Tatcher, M.; Kedar, A.; Benderly, A.

1983-01-01

Cranial irradiation has been shown to impair growth hormone secretion in children. In this study a cell culture of dispersed rat anterior pituitary cells was exposed to single doses of radiation in the range of 100 to 1500 rad. Survival curves were obtained for the different anterior pituitary cell lines, and growth hormone secretion was measured in the tissue culture medium. Both survival and growth hormone secretion curves showed an initial shoulder in the range of 0 to 300 rad, followed by a decline between 300 to 750 rad. It is concluded that growth hormone secreting acidophilic pituicytes are sensitive to radiation at single doses greater than 300 rad

Autophagy Mediates Interleukin-1β Secretion in Human Neutrophils

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Leonardo Iula

2018-02-01

Full Text Available Interleukin-1β (IL-1β, a major pro-inflammatory cytokine, is a leaderless cytosolic protein whose secretion does not follow the classical endoplasmic reticulum-to-Golgi pathway, and for which a canonical mechanism of secretion remains to be established. Neutrophils are essential players against bacterial and fungi infections. These cells are rapidly and massively recruited from the circulation into infected tissues and, beyond of displaying an impressive arsenal of toxic weapons effective to kill pathogens, are also an important source of IL-1β in infectious conditions. Here, we analyzed if an unconventional secretory autophagy mechanism is involved in the exportation of IL-1β by these cells. Our findings indicated that inhibition of autophagy with 3-methyladenine and Wortmannin markedly reduced IL-1β secretion induced by LPS + ATP, as did the disruption of the autophagic flux with Bafilomycin A1 and E64d. These compounds did not noticeable affect neutrophil viability ruling out that the effects on IL-1β secretion were due to cell death. Furthermore, VPS34IN-1, a specific autophagy inhibitor, was still able to reduce IL-1β secretion when added after it was synthesized. Moreover, siRNA-mediated knockdown of ATG5 markedly reduced IL-1β secretion in neutrophil-differentiated PLB985 cells. Upon LPS + ATP stimulation, IL-1β was incorporated to an autophagic compartment, as was revealed by its colocalization with LC3B by confocal microscopy. Overlapping of IL-1β-LC3B in a vesicular compartment peaked before IL-1β increased in culture supernatants. On the other hand, stimulation of autophagy by cell starvation augmented the colocalization of IL-1β and LC3B and then promoted neutrophil IL-1β secretion. In addition, specific ELISAs indicated that although both IL-1β and pro-IL-1β are released to culture supernatants upon neutrophil stimulation, autophagy only promotes IL-1β secretion. Furthermore, the serine proteases inhibitor

A reduced, yet functional, nectary disk integrates a complex system of floral nectar secretion in the genus Zeyheria (Bignoniaceae

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Silvia Rodrigues Machado

Full Text Available ABSTRACT The genus Zeyheria (Bignoniaceae comprises only two species, both of which have been described as possessing a reduced and non-functional nectary disk. Despite the importance of this evolutionary change in the floral nectary, these functional assumptions have been based on disk size and on the distribution, abundance and histochemistry of corolla-borne trichomes. By combining methods on light and electron microscopy, here we investigated the functionality of the reduced nectary disk and describe all of the tissues and structures of the nectar chamber in order to determine the sites of floral nectar secretion in both Zeyheria species. . Our data find the floral nectary traits of both species to be very similar, although differing in their cellular contents. Subcellular evidence in both species indicated that disk, stipe and petal axils were, predominantly, involved in hydrophilic secretion, while capitate glandular trichomes produced lipophilic secretion and papillae produced mixed secretion. Our study shows that in spite of its reduced size, the reduced disk functions in nectar secretion in both species of Zeyheria. This kind of nectary system is a novelty for Bignoniaceae, since it comprises several tissues and structures functioning in an integrated fashion.

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

Simultaneous Measurement of Etravirine, Maraviroc and Raltegravir in Pigtail Macaque Plasma, Vaginal Secretions and Vaginal Tissue using a LC-MS/MS Assay

Science.gov (United States)

Blakney, Anna K.; Jiang, Yonghou; Whittington, Dale; Woodrow, Kim A.

2016-01-01

Etravirine (ETR), maraviroc (MVC) and raltegravir (RAL) are promising antiretroviral drugs being used in HIV treatment and may be interesting for prevention applications such as oral or topical pre-exposure prophylaxis. Here we describe a sensitive and accurate method for the simultaneous detection of ETR, MVC and RAL from pigtail macaque plasma, vaginal secretions, and vaginal tissue. This method is characterized by a straightforward precipitation extraction method, a limit of quantification 94% in all cases. We also show that extracted biological samples are stable after storage at room temperature or 4 °C and after three freeze/thaw cycles. This is the first analytical method capable of quantifying ETR, MVC and RAL in biological matrices relevant for pre-clinical testing of oral or topical HIV prevention methods in pigtailed macaques. PMID:27236000

The dependence of neuronal encoding efficiency on Hebbian plasticity and homeostatic regulation of neurotransmitter release

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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.

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.

LcrG secretion is not required for blocking of Yops secretion in Yersinia pestis

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Matson Jyl S

2008-02-01

Full Text Available Abstract Background LcrG, a negative regulator of the Yersinia type III secretion apparatus has been shown to be primarily a cytoplasmic protein, but is secreted at least in Y. pestis. LcrG secretion has not been functionally analyzed and the relevance of LcrG secretion on LcrG function is unknown. Results An LcrG-GAL4AD chimera, originally constructed for two-hybrid analyses to analyze LcrG protein interactions, appeared to be not secreted but the LcrG-GAL4AD chimera retained the ability to regulate Yops secretion. This result led to further investigation to determine the significance of LcrG secretion on LcrG function. Additional analyses including deletion and substitution mutations of amino acids 2–6 in the N-terminus of LcrG were constructed to analyze LcrG secretion and LcrG's ability to control secretion. Some changes to the N-terminus of LcrG were found to not affect LcrG's secretion or LcrG's secretion-controlling activity. However, substitution of poly-isoleucine in the N-terminus of LcrG did eliminate LcrG secretion but did not affect LcrG's secretion controlling activity. Conclusion These results indicate that secretion of LcrG, while observable and T3SS mediated, is not relevant for LcrG's ability to control secretion.

Tamper-proof secret image-sharing scheme for identifying cheated secret keys and shared images

Science.gov (United States)

Chen, Chien-Chang; Liu, Chong-An

2013-01-01

A (t,n) secret image-sharing scheme shares a secret image to n participants, and the t users recover the image. During the recovery procedure of a conventional secret image-sharing scheme, cheaters may use counterfeit secret keys or modified shared images to cheat other users' secret keys and shared images. A cheated secret key or shared image leads to an incorrect secret image. Unfortunately, the cheater cannot be identified. We present an exponent and modulus-based scheme to provide a tamper-proof secret image-sharing scheme for identifying cheaters on secret keys or shared images. The proposed scheme allows users to securely select their secret key. This assignment can be performed over networks. Modulus results of each shared image is calculated to recognize cheaters of a shared image. Experimental results indicate that the proposed scheme is excellent at identifying cheated secret keys and shared images.

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.

Detection of neurotransmitters by a light scattering technique based on seed-mediated growth of gold nanoparticles

International Nuclear Information System (INIS)

Shang Li; Dong Shaojun

2008-01-01

A simple light scattering detection method for neurotransmitters has been developed, based on the growth of gold nanoparticles. Neurotransmitters (dopamine, L-dopa, noradrenaline and adrenaline) can effectively function as active reducing agents for generating gold nanoparticles, which result in enhanced light scattering signals. The strong light scattering of gold nanoparticles then allows the quantitative detection of the neurotransmitters simply by using a common spectrofluorometer. In particular, Au-nanoparticle seeds were added to facilitate the growth of nanoparticles, which was found to enhance the sensing performance greatly. Using this light scattering technique based on the seed-mediated growth of gold nanoparticles, detection limits of 4.4 x 10 -7 M, 3.5 x 10 -7 M, 4.1 x 10 -7 M, and 7.7 x 10 -7 M were achieved for dopamine, L-dopa, noradrenaline and adrenaline, respectively. The present strategy can be extended to detect other biologically important molecules in a very fast, simple and sensitive way, and may have potential applications in a wide range of fields

Detection of neurotransmitters by a light scattering technique based on seed-mediated growth of gold nanoparticles

Energy Technology Data Exchange (ETDEWEB)

Shang Li; Dong Shaojun [State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Graduate School of the Chinese Academy of Sciences, Chinese Academy of Sciences, Changchun 130022 (China)], E-mail: dongsj@ciac.jl.cn

2008-03-05

A simple light scattering detection method for neurotransmitters has been developed, based on the growth of gold nanoparticles. Neurotransmitters (dopamine, L-dopa, noradrenaline and adrenaline) can effectively function as active reducing agents for generating gold nanoparticles, which result in enhanced light scattering signals. The strong light scattering of gold nanoparticles then allows the quantitative detection of the neurotransmitters simply by using a common spectrofluorometer. In particular, Au-nanoparticle seeds were added to facilitate the growth of nanoparticles, which was found to enhance the sensing performance greatly. Using this light scattering technique based on the seed-mediated growth of gold nanoparticles, detection limits of 4.4 x 10{sup -7} M, 3.5 x 10{sup -7} M, 4.1 x 10{sup -7} M, and 7.7 x 10{sup -7} M were achieved for dopamine, L-dopa, noradrenaline and adrenaline, respectively. The present strategy can be extended to detect other biologically important molecules in a very fast, simple and sensitive way, and may have potential applications in a wide range of fields.

Evidence for inhibition of steroid hormone secretion by arginine vasotocin (AVT) in tissue culture of isolated ovarian follicular cells

International Nuclear Information System (INIS)

Stoklosowa, S.; Gregoraszczuk, E.; Galas, J.; Rzasa, J.

1994-01-01

Two follicular compartments, granulosa (G) and theca interna (T) cells isolated from porcine ovaries were cultured alone or in co-culture (GT). Cells were grown as monolayers in a control medium without hormone and in a media supplemented with arginine-vasotocin (AVT) at a concentration of either 10 -7 M or 2x10 -7 M. Progesterone (P4), estrogen (E2) and androgen (A) concentrations in the culture media were taken as measures of the effect of AVT on the function of follicular cells. Steroids were analyzed by radioimmunoassay. AVT action in this culture system was expressed as a decrease in progesterone secretion by cultures of granulosa cells alone, and specially as a change in the pattern of estradiol and androgen secretion by co-cultures. Control T and G cells cultured alone secreted small amounts of A (238.0 pg/10 5 cells, respectively), and E2 272.5 pg/10 5 cells, 10.6 pg/10 5 cells, respectively) while in co-culture these two cell types interacted and the result of this positive interaction was a significant increase in secretion of these two steroids (941.0 pg/10 5 cell androgen secretion and 854.1 pg/10 5 cells estradiol secretion). This phenomenon is similar to that observed in the intact follicle 'in vivo'. AVT introduced to the culture medium impaired the effect of this positive interaction of mixed G and T cells on the production of high levels of E2 and A by untreated co-cultures. (author). 37 refs, 9 figs, 1 tab

Wrapped up in Covers: Preschoolers' Secrets and Secret Hiding Places

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Corson, Kimberly; Colwell, Malinda J.; Bell, Nancy J.; Trejos-Castillo, Elizabeth

2014-01-01

In this qualitative study, interviews about children's secret hiding places were conducted with 3-5-year-olds (n?=?17) in a university sponsored preschool programme using art narratives. Since prior studies indicate that children understand the concept of a secret as early as five and that they associate secrets with hiding places, the purpose of…

Use of neurotransmitter regulators in functional gastrointestinal disorders based on symptom analysis.

Science.gov (United States)

Luo, Qing Qing; Chen, Sheng Liang

2017-04-01

It has been a great challenge for gastroenterologists to cope with functional gastrointestinal disorders (FGIDs) in clinical practice due to the contemporary increase in stressful events. A growing body of evidence has shown that neuroregulators such as anti-anxiety agents and antidepressants function well on FGIDs, particularly in cases that are refractory to classical gastrointestinal (GI) medications. Among these central-acting agents, small individualized doses of tricyclic antidepressants and selective serotonin reuptake inhibitors are usually recommended as a complement to routine GI management. When these drugs are chosen to treat FGIDs, both their central effects and the modulation of peripheral neurotransmitters should be taken into consideration. In this article we recommend strategies for choosing drugs based on an analysis of psychosomatic GI symptoms. The variety and dosage of the neurotransmitter regulators are also discussed. © 2017 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.

Versatile electrochemial sensor for tissue culturing and sample handling

DEFF Research Database (Denmark)

Bakmand, Tanya; Kwasny, Dorota; Al Atraktchi, Fatima Al-Zahraa

2014-01-01

Culturing of organtypic brain tissues is a routine procedure in neural research. The visual inspection of the medium is the only way of determining the state of the tissue. At the end of culturing, post-processing techniques such as HPLC can be used to measure the concentration of the secreted...

Salmonella-secreted Virulence Factors

Energy Technology Data Exchange (ETDEWEB)

Heffron, Fred; Niemann, George; Yoon, Hyunjin; Kidwai, Afshan S.; Brown, Roslyn N.; McDermott, Jason E.; Smith, Richard D.; Adkins, Joshua N.

2011-05-01

In this short review we discuss secreted virulence factors of Salmonella, which directly affect Salmonella interaction with its host. Salmonella secretes protein to subvert host defenses but also, as discussed, to reduce virulence thereby permitting the bacteria to persist longer and more successfully disperse. The type III secretion system (TTSS) is the best known and well studied of the mechanisms that enable secretion from the bacterial cytoplasm to the host cell cytoplasm. Other secretion systems include outer membrane vesicles, which are present in all Gram-negative bacteria examined to date, two-partner secretion, and type VI secretion will also be addressed. Excellent reviews of Salmonella secreted effectors have focused on themes such as actin rearrangements, vesicular trafficking, ubiquitination, and the activities of the virulence factors themselves. This short review is based on S. Typhimurium infection of mice because it is a model of typhoid like disease in humans. We have organized effectors in terms of events that happen during the infection cycle and how secreted effectors may be involved.

Effect of rehabilitation training combined with hyperbaric oxygen therapy on the nerve cytokine secretion and oxidative stress in rehabilitation period of patients with cerebral infarction

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Ling Kong

2017-11-01

Full Text Available Objective: To discuss the influence of rehabilitation training combined with hyperbaric oxygen therapy on the nerve cytokine secretion and oxidative stress in rehabilitation period of patients with cerebral infarction. Methods: A total of 110 patients with cerebral infarction who received rehabilitation therapy in the hospital between January 2015 and May 2017 were divided into routine group (n=55 and hyperbaric oxygen group (n=55 according to random number table. Routine group received regular rehabilitation training, and hyperbaric oxygen group underwent rehabilitation training combined with hyperbaric oxygen therapy. The differences in the serum contents of nerve factors, neurotransmitters and oxidative stress indexes were compared between the two groups at immediately after admission (T0 and after 14 d of treatment (T1. Results: At T0, there was no statistically significant difference in the serum contents of nerve factors, neurotransmitters and oxidative stress indexes between the two groups. At T1, serum nerve factors MBP and NSE contents of hyperbaric oxygen group were lower than those of routine group while NGF content was higher than that of routine group; serum neurotransmitter Glu content was lower than that of routine group while GABA content was higher than that of routine group; serum oxidative stress indexes ROS and LHP contents were lower than those of routine group while CAT and SOD contents were higher than those of routine group. Conclusion: Rehabilitation training combined with hyperbaric oxygen therapy can effectively optimize the nerve function and inhibit the systemic oxidative stress response in rehabilitation period of patients with cerebral infarction.

Mucus glycoprotein secretion by tracheal explants: effects of pollutants

International Nuclear Information System (INIS)

Last, J.A.; Kaizu, T.

1980-01-01

Tracheal slices incubated with radioactive precursors in tissue culture medium secrete labeled mucus glycoproteins into the culture medium. We have used an in vivtro approach, a combined method utilizing exposure to pneumotoxins in vivo coupled with quantitation of mucus secretion rates in vitro, to study the effects of inhaled pollutants on mucus biosynthesis by rat airways. In addition, we have purified the mucus glycoproteins secreted by rat tracheal explants in order to determine putative structural changes that might by the basis for the observed augmented secretion rates after exposure of rats to H2SO4 aerosols in combination with high ambient levels of ozone. After digestion with papain, mucus glycoproteins secreted by tracheal explants may be separated into five fractions by ion-exchange chromatography, with recovery in high yield, on columns of DEAE-cellulose. Each of these five fractions, one neutral and four acidic, migrates as a single unique spot upon cellulose acetate electrophoresis at pH values of 8.6 and 1.2. The neutral fraction, which is labeled with [3H] glucosamine, does not contain radioactivity when Na2 35SO4 is used as the precursor. Acidic fractions I to IV are all labeled with either 3H-glucosamine or Na2 35SO4 as precursor. Acidic fraction II contains sialic acid as the terminal sugar on its oligosaccharide side chains, based upon its chromatographic behavior on columns of wheat-germ agglutinin-Agarose. Treatment of this fraction with neuraminidase shifts its elution position in the gradient to a lower salt concentration, coincident with acidic fraction I. After removal of terminal sialic acid residues with either neuraminidase or low pH treatment, the resultant terminal sugar on the oligosaccharide side chains is fucose. These results are identical with those observed with mucus glycoproteins secreted by cultured human tracheal explants and purified by these same techniques

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...... (NSS). Due to their important role, dysfunctions are associated with several psychiatric and neurological diseases and they also serve as targets for a wide range of therapeutic and illicit drugs. Despite the central physiological and pharmacological importance, direct evidence on structure......–function relationships on mammalian NSS proteins has so far been unsuccessful. The crystal structure of the bacterial NSS protein, LeuT, has been a turning point in structural investigations. Scope of review: To provide an update on what is known about the binding sites for substrates and inhibitors in the Leu...

Evidence for inhibition of steroid hormone secretion by arginine vasotocin (AVT) in tissue culture of isolated ovarian follicular cells

Energy Technology Data Exchange (ETDEWEB)

Stoklosowa, S.; Gregoraszczuk, E.; Galas, J. [Uniwersytet Jagiellonski, Cracow (Poland); Rzasa, J. [Akademia Rolnicza, Cracow (Poland)

1994-12-31

Two follicular compartments, granulosa (G) and theca interna (T) cells isolated from porcine ovaries were cultured alone or in co-culture (GT). Cells were grown as monolayers in a control medium without hormone and in a media supplemented with arginine-vasotocin (AVT) at a concentration of either 10{sup -7} M or 2x10{sup -7} M. Progesterone (P4), estrogen (E2) and androgen (A) concentrations in the culture media were taken as measures of the effect of AVT on the function of follicular cells. Steroids were analyzed by radioimmunoassay. AVT action in this culture system was expressed as a decrease in progesterone secretion by cultures of granulosa cells alone, and specially as a change in the pattern of estradiol and androgen secretion by co-cultures. Control T and G cells cultured alone secreted small amounts of A (238.0 pg/10{sup 5} cells, respectively), and E2 (272.5 pg/10{sup 5} cells, 10.6 pg/10{sup 5} cells, respectively) while in co-culture these two cell types interacted and the result of this positive interaction was a significant increase in secretion of these two steroids (941.0 pg/10{sup 5} cell androgen secretion and 854.1 pg/10{sup 5} cells estradiol secretion). This phenomenon is similar to that observed in the intact follicle `in vivo`. AVT introduced to the culture medium impaired the effect of this positive interaction of mixed G and T cells on the production of high levels of E2 and A by untreated co-cultures. (author). 37 refs, 9 figs, 1 tab.

Screening for Identification of Personalized Food to Promote Adiponectin Secretion in Patients with Cancer.

Science.gov (United States)

Sakaue, Miki; Maeda, Kazuhisa; Ohno, Satoshi; Ito, Toshinori

2016-07-01

Adiponectin is secreted specifically from adipose tissue. Low serum adiponectin levels may cause metabolic syndrome, which is also a risk factor for carcinogenesis. Several studies have suggested a negative correlation between adiponectin and risk of cancers. This study examined the adiponectin secretion-promoting effect of food ingredients in adipose-derived stem cells (ADSCs) obtained from patients with cancer. ADSCs from 7 lifestyle disease cancer patients were differentiated into adipocytes. Subsequently, the adipocytes were treated with 49 food constituents. The adiponectin levels in cell culture supernatants were measured after 48 and 96 h. Soy genistein extract, lychee low-molecular-weight polyphenol, olive extract and turmeric promoted adiponectin secretion. Food constituents that promoted adiponectin secretion were identified using ADSCs derived from patients. This study suggested the possibility of a new treatment approach to prevent cancer recurrence. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

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

Science.gov (United States)

Muschter, Dominique; Schäfer, Nicole; Stangl, Hubert; Straub, Rainer H.; Grässel, Susanne

2015-01-01

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, 10-6M 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. PMID:26431344

Determination of amino acid neurotransmitters in rat hippocampi by HPLC-UV using NBD-F as a derivative.

Science.gov (United States)

Wu, Xiaomeng; Wang, Rui; Jiang, Qingqing; Wang, Shue; Yao, Yao; Shao, Lihua

2014-04-01

A simple, rapid and accurate high-performance liquid chromatography method with ultraviolet-visible detection was developed for the determination of five amino acid neurotransmitters - aspartate, glutamic acid, glycine, taurine and γ-aminobutyric acid - in rat hippocampi with pre-column derivatization with 4-fluoro-7-nitrobenzofurazan. Several conditions which influenced derivatization and separation, such as pH, temperature, acetonitrile percentage mobile phase and flow rate, were optimized to obtain a suitable protocol for amino acids quantification in samples. The separation of the five neurotransmitter derivatives was performed on a C18 column using a mobile phase consisting of phosphate buffer (0.02 mol/L, pH 6.0)-acetonitrile (84:16, v/v) at a flow rate of 1.0 mL/min with the column temperature at 30°C. The detection wavelength was 472 nm. Without gradient elution, the five neurotransmitter derivatives were completely separated within 15 min. The linear relation was good in the range from 0.50 to 500 µmol/L, and the correlation coefficients were ≥0.999. Intra-day precision was between 1.8 and 3.2%, and inter-day precision was between 2.4 and 4.7%. The limits of detection (signal-to-noise ratio 3) were from 0.02 to 0.15 µmol/L. The established method was used to determine amino acid neurotransmitters in rat hippocampi with satisfactory recoveries varying from 94.9 to 105.2%. Copyright © 2013 John Wiley & Sons, Ltd.

Iodine-131 saliva secretion in ablation treatment for thyroid cancer patients

International Nuclear Information System (INIS)

Nascimento, Ana C.H.; Brandao, Luis E.; Candeiro, Ricardo E.; Rebelo, Ana M.O.; Corbo, Rossana; Dutra, Janaina

2008-01-01

In general, well-differentiated thyroid cancer treatment consists in Na 131 I administration following total or a near total thyroidectomy. The activity of a single administration in the majority of nuclear centers ranges from 1 to 4 GBq for residual thyroid tissue elimination and ranges from 4 to 8 GBq for residual thyroid tissue as well as metastases elimination. The high magnitude of 131 I activities administered for thyroid cancer treatment can lead to side effects, where salivary gland dysfunctions are the most common observed. In the absence of thyroid gland, secondary tissues - iodide specific uptake, mainly the salivary glands, rise at the element body retention process. In addition, among nuclear medicine professionals, there is no consensus about suitable restrictions that must be observed by the hospital released patient to avoid 131 I contamination by saliva. The aim of this study is to evaluate qualitatively the secretion of 131 I by salivary glands after the administration of the radionuclide to thyroid cancer patients for ablation purposes. Well-differentiated thyroid cancer patients from Clementino Fraga Filho University Hospital (HUCFF) of Federal University of Rio de Janeiro (UFRJ) followed-up in the present study are female, adult and without additional health diseases detected. After 131 I administration for ablation purposes, saliva samples were collected systematically and counting rate was assessed using a NaI(Tl) scintillator detector. As the study is at an early stage, the preliminary results concern the possibility of conducting an evaluation of 131 I secreted in saliva using the proposed protocol. It can be seen that many factors have potential to influence the behaviour of 1 31 I secretion in saliva, for example the use of Na 131 I in solution or in capsules. It was observed two standards that can be defined according to these variables. (author)

Clinical hyperthyroidism due to non-neoplastic inappropriate thyrotrophin secretion.

OpenAIRE

Chan, A. W.; MacFarlane, I. A.; van Heyningen, C.; Foy, P. M.

1990-01-01

We report a case of hyperthyroidism due to inappropriate thyrotrophin (TSH) secretion in a patient with selective pituitary resistance to thyroid hormone action. Symptoms of hyperthyroidism in patients with this disorder are usually mild, implying some peripheral tissue resistance to the metabolic effects of thyroid hormone. Our patient had unusually severe symptoms, including marked weight loss and cardiac arrythmias which required carbimazole and beta-blocker therapy for control. Somatostat...

Cholecystokinin-From Local Gut Hormone to Ubiquitous Messenger

DEFF Research Database (Denmark)

Rehfeld, Jens F

2017-01-01

pancreatic enzyme secretion and growth, gallbladder contraction, and gut motility, satiety and inhibit acid secretion from the stomach. Moreover, they are major neurotransmitters in the brain and the periphery. CCK peptides also stimulate calcitonin, insulin, and glucagon secretion, and they may act...

Estrogen inhibits chloride secretion caused by cholera and Escherichia coli enterotoxins in female rat distal colon.

LENUS (Irish Health Repository)

Alzamora, Rodrigo

2011-05-08

Excessive Cl(-) secretion is the driving force for secretory diarrhea. 17β-Estradiol has been shown to inhibit Cl(-) secretion in rat distal colon through a nongenomic pathway. We examined whether 17β-estradiol inhibits Cl(-) secretion in an animal model of secretory diarrhea and the downstream effectors involved. The effect of 17β-estradiol on cholera toxin and heat-stable enterotoxin induced Cl(-) secretion in rat colonic mucosal sheets was studied by current-voltage clamping. Selective permeabilization of apical or basolateral membranes with amphotericin B or nystatin was used to isolate basolateral K(+) channel and apical Cl(-) channel activity, respectively. 17β-Estradiol dose-dependently inhibited secretory responses to both toxins with IC(50) values of approximately 1nM. This effect was female-gender specific, with no inhibition observed in male tissues. 17β-Estradiol responses were insensitive to the pure anti-estrogen ICI 182,720. 17β-Estradiol exerted its effects downstream of enterotoxin-induced production of second messengers (cAMP and cGMP) but was dependent on PKCδ activation. In nystatin-permeabilized tissues, apical Cl(-) currents were unaffected by 17β-estradiol treatment while basolateral K(+) current was profoundly inhibited by the hormone. This current was sensitive to the specific KCNQ1 channel inhibitors chromanol 293B and HMR-1556. In conclusion, 17β-estradiol inhibits enterotoxin-induced Cl(-) secretion via a PKCδ-dependent mechanism involving inhibition of basolateral KCNQ1 channels. These data elucidate mechanisms of 17β-estradiol inhibition of Cl(-) secretion induced by enterotoxins in intestinal epithelia, which may be relevant for the treatment of diarrheal diseases.

Estrogen inhibits chloride secretion caused by cholera and Escherichia coli enterotoxins in female rat distal colon.

LENUS (Irish Health Repository)

Alzamora, Rodrigo

2012-02-01

Excessive Cl(-) secretion is the driving force for secretory diarrhea. 17beta-Estradiol has been shown to inhibit Cl(-) secretion in rat distal colon through a nongenomic pathway. We examined whether 17beta-estradiol inhibits Cl(-) secretion in an animal model of secretory diarrhea and the downstream effectors involved. The effect of 17beta-estradiol on cholera toxin and heat-stable enterotoxin induced Cl(-) secretion in rat colonic mucosal sheets was studied by current-voltage clamping. Selective permeabilization of apical or basolateral membranes with amphotericin B or nystatin was used to isolate basolateral K(+) channel and apical Cl(-) channel activity, respectively. 17beta-Estradiol dose-dependently inhibited secretory responses to both toxins with IC(50) values of approximately 1nM. This effect was female-gender specific, with no inhibition observed in male tissues. 17beta-Estradiol responses were insensitive to the pure anti-estrogen ICI 182,720. 17beta-Estradiol exerted its effects downstream of enterotoxin-induced production of second messengers (cAMP and cGMP) but was dependent on PKCdelta activation. In nystatin-permeabilized tissues, apical Cl(-) currents were unaffected by 17beta-estradiol treatment while basolateral K(+) current was profoundly inhibited by the hormone. This current was sensitive to the specific KCNQ1 channel inhibitors chromanol 293B and HMR-1556. In conclusion, 17beta-estradiol inhibits enterotoxin-induced Cl(-) secretion via a PKCdelta-dependent mechanism involving inhibition of basolateral KCNQ1 channels. These data elucidate mechanisms of 17beta-estradiol inhibition of Cl(-) secretion induced by enterotoxins in intestinal epithelia, which may be relevant for the treatment of diarrheal diseases.

Effect of ligustrazine on levels of amino acid neurotransmitters in rat striatum after cerebral ischemia-reperfusion injury.

Science.gov (United States)

Han, Jin; Wan, Hai-Tong; Yang, Jie-Hong; Zhang, Yu-Yan; Ge, Li-Jun; Bie, Xiao-Dong

2014-01-01

This study aimed to evaluate the effect of ligustrazine on levels of amino acid transmitters in the extracellular fluid of striatum following cerebral ischemia/reperfusion (I/R) in male Sprague-Dawley rats. A microdialysis cannula guide was implanted into the right striatum. After recovery, animals underwent a sham operation or middle cerebral artery occlusion (MCAO). Those that developed cerebral ischemia after MCAO were randomized to receive propylene glycol salt water and ligustrazine respectively. Striatal fluid samples were collected from all animals at 15-min intervals after treatment and were subjected to HPLC analysis of aspartic acid, glutamic acid, taurine, and γ-amino butyric acid. Upon the last sample collection, animals were sacrificed and brain tissue specimens were collected for triphenyltetrazolium chloride staining and NeuN staining. Compared with the sham operation, MCAO induced significant neurological deficits and increased striatal concentrations of the four neurotransmitters assessed in a time-dependent manner (P cerebral infarction-protective agent may have potential clinical implications for I/R-related brain damage.

Pomegranate Alleviates Oxidative Damage and Neurotransmitter Alterations in Rats Brain Exposed to Aluminum Chloride and/or Gamma Radiation

International Nuclear Information System (INIS)

Said, U.Z.; EL-Tahawey, N.A.; Elassal, A.A.; Elsayed, E.M.; Shousha, W.Gh.

2013-01-01

Aluminum and gamma radiation, both are potent neurotoxins and have been implicated in many human neuro degenerative diseases. The present study was designed to investigate the role of pomegranate in alleviating oxidative damage and alteration of neurotransmitters in the brain of rats exposed to aluminum chloride (AlCl 3 ), and/or gamma radiation (IR). The results revealed that rats whole body exposed to γ- rays, (1 Gy/week up to 4 Gy), and/or administered aluminum chloride (35 mg/kg body weight), via gavages for 4 weeks, resulted in brain tissue damage, featuring by significant increase of the level of thiobarbituric acid reactive substances (TBARS), and advanced oxidation protein products (AOPP), associated with significant decrease of superoxide dismutase (SOD) and catalase (CAT) activities, as well as glutathione (GSH) content indicating occurrence of oxidative stress. A significant decrease of serotonin (5-HT) level associated with a significant increase of 5-hydroxyindole acetic acid (5-HIAA), in addition to a significant decrease in dopamine (DA), norepinephrine (NE) and epinephrine (EPI) contents recorded at the 1st, 7th and 14th day post-irradiation, indicating alterations in the metabolism of brain monoamines. On the other hand, the results exhibited that, supplementation of rats with pomegranate, via gavages, at a dose of 3 ml /kg body weight/ day, for 4 weeks along with AlCl 3 with or without radiation has significantly ameliorated the changes occurred in the mentioned parameters and the values returned close to the normal ones. It could be concluded that pomegranate, by its antioxidant constituents might antagonize brain oxidative damage and minimize the severity of aluminum (Al), and/or radiation-induced neurotransmitters disorders

Meaningful Share Generation for Increased Number of Secrets in Visual Secret-Sharing Scheme

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Mustafa Ulutas

2010-01-01

Full Text Available This paper presents a new scheme for hiding two halftone secret images into two meaningful shares created from halftone cover images. Meaningful shares are more desirable than noise-like (meaningless shares in Visual Secret Sharing because they look natural and do not attract eavesdroppers' attention. Previous works in the field focus on either increasing number of secrets or creating meaningful shares for one secret image. The method outlined in this paper both increases the number of secrets and creates meaningful shares at the same time. While the contrast ratio of shares is equal to that of Extended Visual Cryptography, two secrets are encoded into two shares as opposed to one secret in the Extended Visual Cryptography. Any two natural-looking images can be used as cover unlike the Halftone Visual Cryptography method where one cover should be the negative of the other cover image and can only encode one secret. Effectiveness of the proposed method is verified by an experiment.

ECRG4 expression in normal rat tissues: expression study and literature review

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A. Porzionato

2015-05-01

Full Text Available The Esophageal Cancer Related Gene 4 (ECRG4 is a highly conserved tumour suppressor gene encoding various peptides (augurin, CΔ16 augurin, ecilin, argilin, CΔ16 argilin which can be processed and secreted. In the present work, we examined ECRG4 expression and location in a wide range of rat organs and reviewed the available literature. ECRG4 mRNA was identified in all examined tissues by quantitative PCR (qPCR. ECRG4 immunoreaction was mainly cytoplasmic, and was detected in heart and skeletal muscles, smooth muscle cells showing only weak reactions. In the digestive system, ECRG4 immunostaining was stronger in the esophageal epithelium, bases of gastric glands, hepatocytes and pancreatic acinar epithelium. In the lymphatic system, immunoreactive cells were detectable in the thymus cortex, lymph node medulla and splenic red pulp. In the central and peripheral nervous systems, different neuronal groups showed different reaction intensities. In the endocrine system, ECRG4 immunoreaction was detected in the hypothalamic paraventricular and supraoptic nuclei, hypophysis, thyroid and parathyroid glands, adrenal zona glomerularis and medulla and Leydig cells, as well as in follicular and luteal cells of the ovary. In the literature, ECRG4 has been reported to inhibit cell proliferation and increase apoptosis in various cell types. It is down-regulated, frequently due to hypermethylation, in esophageal, prostate, breast and colon cancers, together with glioma (oncosuppressor function, although it is up-regulated in papillary thyroid cancer (oncogenic role. ECRG4 expression is also higher in non-proliferating cells of the lymphatic system. In conclusion, our identification of ECRG4 in many structures suggests the involvement of ECRG4 in the tumorigenesis of other organs and also the need for further research. In addition, on the basis of the location of ECRG4 in neurons and endocrine cells and the fact that it can be secreted, its role as a

High expression of cystine-glutamate antiporter xCT (SLC7A11) is an independent biomarker for epileptic seizures at diagnosis in glioma

DEFF Research Database (Denmark)

Sørensen, Mai Froberg; Heimisdóttir, Sólborg Berglind; Sørensen, Mia Dahl

2018-01-01

Epileptic seizures are an important cause of morbidity in glioma patients. Substantial lines of evidence support the concept of the excitatory neurotransmitter glutamate being a crucial mediator of glioma-associated seizures. In gliomas, non-vesicular secretion of glutamate via the cystine...... tumor using tissue microarrays. In addition to histological grading of the tumors, isocitrate dehydrogenase 1 (IDH1) R132H mutational status was determined by immunohistochemistry. 215 consecutive glioma patients were included in the study (7.4% grade II, 7.0% grade III, 85.6% grade IV). High x...

Effect of fenspiride, a non-steroidal antiinflammatory agent, on neurogenic mucus secretion in ferret trachea in vitro.

Science.gov (United States)

Khawaja, A M; Liu, Y C; Rogers, D F

1999-01-01

Neural mechanisms contribute to control of mucus secretion in the airways. Fenspiride is a non-steroidal antiinflammatory agent which has a variety of actions, including inhibition of neurogenic bronchoconstriction. The effect of fenspiride on neurally-mediated mucus secretion was investigated in vitro in electrically-stimulated ferret trachea, using(35)SO(4)as a mucus marker. Cholinergic secretory responses were isolated using adrenoceptor and tachykinin receptor antagonists. Tachykinin responses were isolated using cholinoceptor and adrenoceptor antagonists. Electrical stimulation increased cholinergic secretion by;90% and tachykininergic secretion by;40%. Fenspiride (1 microM-1 mM) tended to inhibit cholinergic secretion in a concentration-dependent manner, although only at 1 mM was inhibition (by 87%) significant. Inhibition by fenspiride of tachykininergic secretion was not concentration-dependent, and again significant inhibition (by 85%) was only at 1 mM. Inhibition was not due to loss of tissue viability, as assessed by restitution of secretory response after washout. Fenspiride also inhibited secretion induced by acetylcholine, but did not inhibit substance P-induced secretion. Histamine receptor antagonists increased basal secretion by 164%, whereas fenspiride did not affect basal secretion. We conclude that, in ferret trachea in vitro, fenspiride inhibits neurally-mediated mucus secretion, with antimuscarinic action the most plausible mechanism of action, but not necessarily the only mechanism. Copyright 1999 Academic Press.

Analysis of in vitro secretion profiles from adipose-derived cell populations

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Blaber Sinead P

2012-08-01

Full Text Available Abstract Background Adipose tissue is an attractive source of cells for therapeutic purposes because of the ease of harvest and the high frequency of mesenchymal stem cells (MSCs. Whilst it is clear that MSCs have significant therapeutic potential via their ability to secrete immuno-modulatory and trophic cytokines, the therapeutic use of mixed cell populations from the adipose stromal vascular fraction (SVF is becoming increasingly common. Methods In this study we have measured a panel of 27 cytokines and growth factors secreted by various combinations of human adipose-derived cell populations. These were 1. co-culture of freshly isolated SVF with adipocytes, 2. freshly isolated SVF cultured alone, 3. freshly isolated adipocytes alone and 4. adherent adipose-derived mesenchymal stem cells (ADSCs at passage 2. In addition, we produced an ‘in silico’ dataset by combining the individual secretion profiles obtained from culturing the SVF with that of the adipocytes. This was compared to the secretion profile of co-cultured SVF and adipocytes. Two-tailed t-tests were performed on the secretion profiles obtained from the SVF, adipocytes, ADSCs and the ‘in silico’ dataset and compared to the secretion profiles obtained from the co-culture of the SVF with adipocytes. A p-value of  Results A co-culture of SVF and adipocytes results in a distinct secretion profile when compared to all other adipose-derived cell populations studied. This illustrates that cellular crosstalk during co-culture of the SVF with adipocytes modulates the production of cytokines by one or more cell types. No biologically relevant differences were detected in the proteomes of SVF cultured alone or co-cultured with adipocytes. Conclusions The use of mixed adipose cell populations does not appear to induce cellular stress and results in enhanced secretion profiles. Given the importance of secreted cytokines in cell therapy, the use of a mixed cell population such as the

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

Monoamine neurotransmitters play an important role in the modulation of sensory, motor and autonomic functions in the spinal cord. Although traditionally it is believed that in mammalian spinal cord, monoamine neurotransmitters mainly originate from the brain, accumulating evidence indicates...... 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...... that dopamine and serotonin could be synthesized sequentially in two monoenzymatic cells in the spinal cord via a TH-AADC and a TPH-AADC cascade respectively. The monoamines synthesized through this pathway may compensate for lost neurotransmitters following spinal cord injury and also may play specific roles...

A FSH-Secreting Pituitary Macroadenoma Causing A Testosterone Deficiency Syndrome

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Xiong Wang

2014-03-01

Full Text Available FSH-secreting pituitary adenomas can affect sexual and reproductive function. In this article, we have reported the case of a 32-year-old male with secondary infertility. The patient had sexual and reproductive disturbances. The test results of the blood samples indicated obviously decreased testosterone (T and estradiol (E2 levels. Based on previous hormonal results, the patient received pituitary stimulation and human chorionic gonadotropin (hCG tests. Both follicle stimulating hormone (FSH and luteinizing hormone (LH showed low response during the pituitary stimulation test. The results of the hCG test indicated that T/E2 could recover to a normal level. In addition, this patient was diagnosed with pituitary macroadenoma, which was supported by the pituitary MRI. The man’s sexual and reproductive functions recovered following surgery. The pathological results confirmed that the tumor tissue was an FSH-secreting pituitary adenoma by immunohistochemical staining. The purpose of this report was to review the relative literature and discuss the influence of FSH-secreting pituitary adenomas on hormones through the hypothalamus-pituitary-testis axis.

Glutamatergic and GABAergic neurotransmitter cycling and energy metabolism in rat cerebral cortex during postnatal development.

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Chowdhury, Golam M I; Patel, Anant B; Mason, Graeme F; Rothman, Douglas L; Behar, Kevin L

2007-12-01

The contribution of glutamatergic and gamma-aminobutyric acid (GABA)ergic neurons to oxidative energy metabolism and neurotransmission in the developing brain is not known. Glutamatergic and GABAergic fluxes were assessed in neocortex of postnatal day 10 (P10) and 30 (P30) urethane-anesthetized rats infused intravenously with [1,6-(13)C(2)]glucose for different time intervals (time course) or with [2-(13)C]acetate for 2 to 3 h (steady state). Amino acid levels and (13)C enrichments were determined in tissue extracts ex vivo using (1)H-[(13)C]-NMR spectroscopy. Metabolic fluxes were estimated from the best fits of a three-compartment metabolic model (glutamatergic neurons, GABAergic neurons, and astroglia) to the (13)C-enrichment time courses of amino acids from [1,6-(13)C(2)]glucose, constrained by the ratios of neurotransmitter cycling (V(cyc))-to-tricarboxylic acid (TCA) cycle flux (V(TCAn)) calculated from the steady-state [2-(13)C]acetate enrichment data. From P10 to P30 increases in total neuronal (glutamate plus GABA) TCA cycle flux (3 x ; 0.24+/-0.05 versus 0.71+/-0.07 micromol per g per min, Pcycling flux (3.1 to 5 x ; 0.07 to 0.11 (+/-0.03) versus 0.34+/-0.03 micromol per g per min, Pcycling (DeltaV(cyc(tot))) and neuronal TCA cycle flux (DeltaV(TCAn(tot))) between P10 and P30 were 0.23 to 0.27 and 0.47 micromol per g per min, respectively, similar to the approximately 1:2 relationship previously reported for adult cortex. For the individual neurons, increases in V(TCAn) and V(cyc) were similar in magnitude (glutamatergic neurons, 2.7 x versus 2.8 to 4.6 x ; GABAergic neurons, approximately 5 x versus approximately 7 x), although GABAergic flux changes were larger. The findings show that glutamate and GABA neurons undergo large and approximately proportional increases in neurotransmitter cycling and oxidative energy metabolism during this major postnatal growth spurt.

Adipose stem cells can secrete angiogenic factors that inhibit hyaline cartilage regeneration.

Science.gov (United States)

Lee, Christopher Sd; Burnsed, Olivia A; Raghuram, Vineeth; Kalisvaart, Jonathan; Boyan, Barbara D; Schwartz, Zvi

2012-08-24

Adipose stem cells (ASCs) secrete many trophic factors that can stimulate tissue repair, including angiogenic factors, but little is known about how ASCs and their secreted factors influence cartilage regeneration. Therefore, the aim of this study was to determine the effects ASC-secreted factors have in repairing chondral defects. ASCs isolated from male Sprague Dawley rats were cultured in monolayer or alginate microbeads supplemented with growth (GM) or chondrogenic medium (CM). Subsequent co-culture, conditioned media, and in vivo cartilage defect studies were performed. ASC monolayers and microbeads cultured in CM had decreased FGF-2 gene expression and VEGF-A secretion compared to ASCs cultured in GM. Chondrocytes co-cultured with GM-cultured ASCs for 7 days had decreased mRNAs for col2, comp, and runx2. Chondrocytes treated for 12 or 24 hours with conditioned medium from GM-cultured ASCs had reduced sox9, acan, and col2 mRNAs; reduced proliferation and proteoglycan synthesis; and increased apoptosis. ASC-conditioned medium also increased endothelial cell tube lengthening whereas conditioned medium from CM-cultured ASCs had no effect. Treating ASCs with CM reduced or abolished these deleterious effects while adding a neutralizing antibody for VEGF-A eliminated ASC-conditioned medium induced chondrocyte apoptosis and restored proteoglycan synthesis. FGF-2 also mitigated the deleterious effects VEGF-A had on chondrocyte apoptosis and phenotype. When GM-grown ASC pellets were implanted in 1 mm non-critical hyaline cartilage defects in vivo, cartilage regeneration was inhibited as evaluated by radiographic and equilibrium partitioning of an ionic contrast agent via microCT imaging. Histology revealed that defects with GM-cultured ASCs had no tissue ingrowth from the edges of the defect whereas empty defects and defects with CM-grown ASCs had similar amounts of neocartilage formation. ASCs must be treated to reduce the secretion of VEGF-A and other factors that

Downregulation of lncRNA TUG1 Affects Apoptosis and Insulin Secretion in Mouse Pancreatic β Cells

Directory of Open Access Journals (Sweden)

Dan-dan Yin

2015-03-01

Full Text Available Background: Increasing evidence indicates that long noncoding RNAs (IncRNAs perform specific biological functions in diverse processes. Recent studies have reported that IncRNAs may be involved in β cell function. The aim of this study was to characterize the role of IncRNA TUG1 in mouse pancreatic β cell functioning both in vitro and in vivo. Methods: qRT-PCR analyses were performed to detect the expression of lncRNA TUG1 in different tissues. RNAi, MTT, TUNEL and Annexin V-FITC assays and western blot, GSIS, ELISA and immunochemistry analyses were performed to detect the effect of lncRNA TUG1 on cell apoptosis and insulin secretion in vitro and in vivo. Results: lncRNA TUG1 was highly expressed in pancreatic tissue compared with other organ tissues, and expression was dynamically regulated by glucose in Nit-1 cells. Knockdown of lncRNA TUG1 expression resulted in an increased apoptosis ratio and decreased insulin secretion in β cells both in vitro and in vivo . Immunochemistry analyses suggested decreased relative islet area after treatment with lncRNA TUG1 siRNA. Conclusion: Downregulation of lncRNA TUG1 expression affected apoptosis and insulin secretion in pancreatic β cells in vitro and in vivo. lncRNA TUG1 may represent a factor that regulates the function of pancreatic β cells.

Downregulation of lncRNA TUG1 affects apoptosis and insulin secretion in mouse pancreatic β cells.

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Yin, Dan-dan; Zhang, Er-bao; You, Liang-hui; Wang, Ning; Wang, Lin-tao; Jin, Fei-yan; Zhu, Ya-nan; Cao, Li-hua; Yuan, Qing-xin; De, Wei; Tang, Wei

2015-01-01

Increasing evidence indicates that long noncoding RNAs (IncRNAs) perform specific biological functions in diverse processes. Recent studies have reported that IncRNAs may be involved in β cell function. The aim of this study was to characterize the role of IncRNA TUG1 in mouse pancreatic β cell functioning both in vitro and in vivo. qRT-PCR analyses were performed to detect the expression of lncRNA TUG1 in different tissues. RNAi, MTT, TUNEL and Annexin V-FITC assays and western blot, GSIS, ELISA and immunochemistry analyses were performed to detect the effect of lncRNA TUG1 on cell apoptosis and insulin secretion in vitro and in vivo. lncRNA TUG1 was highly expressed in pancreatic tissue compared with other organ tissues, and expression was dynamically regulated by glucose in Nit-1 cells. Knockdown of lncRNA TUG1 expression resulted in an increased apoptosis ratio and decreased insulin secretion in β cells both in vitro and in vivo . Immunochemistry analyses suggested decreased relative islet area after treatment with lncRNA TUG1 siRNA. Downregulation of lncRNA TUG1 expression affected apoptosis and insulin secretion in pancreatic β cells in vitro and in vivo. lncRNA TUG1 may represent a factor that regulates the function of pancreatic β cells. © 2015 S. Karger AG, Basel.

LPS-Enhanced Glucose-Stimulated Insulin Secretion Is Normalized by Resveratrol

DEFF Research Database (Denmark)

Nøhr, Mark K; Dudele, Anete; Poulsen, Morten M

2016-01-01

we test the effect of LPS and the anti-inflammatory compound resveratrol on glucose homeostasis, insulin levels and inflammation. Mice were subcutaneously implanted with osmotic mini pumps infusing either low-dose LPS or saline for 28 days. Half of the mice were treated with resveratrol delivered...... through the diet. LPS caused increased inflammation of the liver and adipose tissue (epididymal and subcutaneous) together with enlarged spleens and increased number of leukocytes in the blood. Resveratrol specifically reduced the inflammatory status in epididymal fat (reduced expression of TNFa and Il1b......, whereas the increased macrophage infiltration was unaltered) without affecting the other tissues investigated. By LC-MS, we were able to quantitate resveratrol metabolites in epididymal but not subcutaneous adipose tissue. LPS induced insulin resistance as the glucose-stimulated insulin secretion during...

Impact of Perturbed Pancreatic β-Cell Cholesterol Homeostasis on Adipose Tissue and Skeletal Muscle Metabolism

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Cochran, Blake J.; Hou, Liming; Manavalan, Anil Paul Chirackal; Moore, Benjamin M.; Tabet, Fatiha; Sultana, Afroza; Cuesta Torres, Luisa; Tang, Shudi; Shrestha, Sudichhya; Senanayake, Praween; Patel, Mili; Ryder, William J.; Bongers, Andre; Maraninchi, Marie; Wasinger, Valerie C.; Westerterp, Marit; Tall, Alan R.; Barter, Philip J.

2016-01-01

Elevated pancreatic β-cell cholesterol levels impair insulin secretion and reduce plasma insulin levels. This study establishes that low plasma insulin levels have a detrimental effect on two major insulin target tissues: adipose tissue and skeletal muscle. Mice with increased β-cell cholesterol levels were generated by conditional deletion of the ATP-binding cassette transporters, ABCA1 and ABCG1, in β-cells (β-DKO mice). Insulin secretion was impaired in these mice under basal and high-glucose conditions, and glucose disposal was shifted from skeletal muscle to adipose tissue. The β-DKO mice also had increased body fat and adipose tissue macrophage content, elevated plasma interleukin-6 and MCP-1 levels, and decreased skeletal muscle mass. They were not, however, insulin resistant. The adipose tissue expansion and reduced skeletal muscle mass, but not the systemic inflammation or increased adipose tissue macrophage content, were reversed when plasma insulin levels were normalized by insulin supplementation. These studies identify a mechanism by which perturbation of β-cell cholesterol homeostasis and impaired insulin secretion increase adiposity, reduce skeletal muscle mass, and cause systemic inflammation. They further identify β-cell dysfunction as a potential therapeutic target in people at increased risk of developing type 2 diabetes. PMID:27702832

Metabolomics reveals the heterogeneous secretome of two entomopathogenic fungi to ex vivo cultured insect tissues.

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Charissa de Bekker

Full Text Available Fungal entomopathogens rely on cellular heterogeneity during the different stages of insect host infection. Their pathogenicity is exhibited through the secretion of secondary metabolites, which implies that the infection life history of this group of environmentally important fungi can be revealed using metabolomics. Here metabolomic analysis in combination with ex vivo insect tissue culturing shows that two generalist isolates of the genus Metarhizium and Beauveria, commonly used as biological pesticides, employ significantly different arrays of secondary metabolites during infectious and saprophytic growth. It also reveals that both fungi exhibit tissue specific strategies by a distinguishable metabolite secretion on the insect tissues tested in this study. In addition to showing the important heterogeneous nature of these two entomopathogens, this study also resulted in the discovery of several novel destruxins and beauverolides that have not been described before, most likely because previous surveys did not use insect tissues as a culturing system. While Beauveria secreted these cyclic depsipeptides when encountering live insect tissues, Metarhizium employed them primarily on dead tissue. This implies that, while these fungi employ comparable strategies when it comes to entomopathogenesis, there are most certainly significant differences at the molecular level that deserve to be studied.

Cholecystokinin inhibits gastrin secretion independently of paracrine somatostatin secretion in the pig

DEFF Research Database (Denmark)

Schmidt, P T; Hansen, L; Hilsted, L

2004-01-01

BACKGROUND: Cholecystokinin inhibits the secretion of gastrin from antral G cells, an effect that is speculated to be mediated by D cells secreting somatostatin. The aim of the study was to test directly whether cholecystokinin inhibition of antral gastrin secretion is mediated by somatostatin....... METHODS: The effects of CCK on gastrin and somatostatin secretion were studied in isolated vascularly perfused preparations of pig antrum before and after immunoneutralization brought about by infusion of large amounts of a high affinity monoclonal antibody against somatostatin. RESULTS: CCK infusion...... at 10(-9) M and 10(-8) M decreased gastrin output to 70.5% +/- 7.6% (n = 8) and 76.3% +/- 3.6% (n = 7) of basal output, respectively. CCK at 10(-10) M had no effect (n = 6). Somatostatin secretion was dose-dependently increased by CCK infusion and increased to 268 +/- 38.2% (n = 7) of basal secretion...

Dynamic quantum secret sharing

International Nuclear Information System (INIS)

Jia, Heng-Yue; Wen, Qiao-Yan; Gao, Fei; Qin, Su-Juan; Guo, Fen-Zhuo

2012-01-01

In this Letter we consider quantum secret sharing (QSS) between a sender and a dynamic agent group, called dynamic quantum secret sharing (DQSS). In the DQSS, the change of the agent group is allowable during the procedure of sharing classical and quantum information. Two DQSS schemes are proposed based on a special kind of entangled state, starlike cluster states. Without redistributing all the shares, the changed agent group can reconstruct the sender's secret by their cooperation. Compared with the previous quantum secret sharing scheme, our schemes are more flexible and suitable for practical applications. -- Highlights: ► We consider quantum secret sharing between a sender and a dynamic agent group, called dynamic quantum secret sharing (DQSS). ► In the DQSS, the change of the agent group is allowable during the procedure of sharing classical and quantum information. ► Two DQSS schemes are proposed based on a special kind of entangled state, starlike cluster states. ► Without redistributing all the shares, the changed agent group can reconstruct the sender's secret by their cooperation. ► Compared with the previous quantum secret sharing scheme, our schemes are more flexible and suitable for practical applications.

Miniaturized and Wireless Optical Neurotransmitter Sensor for Real-Time Monitoring of Dopamine in the Brain.

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Kim, Min H; Yoon, Hargsoon; Choi, Sang H; Zhao, Fei; Kim, Jongsung; Song, Kyo D; Lee, Uhn

2016-11-10

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).

Adipose tissue remodeling: its role in energy metabolism and metabolic disorders

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Sung Sik eChoe

2016-04-01

Full Text Available The adipose tissue is a central metabolic organ in the regulation of whole-body energy homeostasis. The white adipose tissue (WAT functions as a key energy reservoir for other organs, whereas the brown adipose tissue (BAT accumulates lipids for cold-induced adaptive thermogenesis. Adipose tissues secret various hormones, cytokines, and metabolites (termed as adipokines that control systemic energy balance by regulating appetitive signals from the central nerve system as well as metabolic activity in peripheral tissues. In response to changes in the nutritional status, the adipose tissue undergoes dynamic remodeling, including quantitative and qualitative alterations in adipose tissue resident cells. A growing body of evidence indicates that adipose tissue remodeling in obesity is closely associated with adipose tissue function. Changes in the number and size of the adipocytes affect the microenvironment of expanded fat tissues, accompanied by alterations in adipokine secretion, adipocyte death, local hypoxia, and fatty acid fluxes. Concurrently, stromal vascular cells in the adipose tissue, including immune cells, are involved in numerous adaptive processes, such as dead adipocyte clearance, adipogenesis, and angiogenesis, all of which are dysregulated in obese adipose tissue remodeling. Chronic over-nutrition triggers uncontrolled inflammatory responses, leading to systemic low-grade inflammation and metabolic disorders, such as insulin resistance. This review will discuss current mechanistic understandings of adipose tissue remodeling processes in adaptive energy homeostasis and pathological remodeling of adipose tissue in connection with immune response.

[Hormones and osteoporosis update. Regulation of bone remodeling by neuropeptides and neurotransmitters].

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Takeda, Shu

2009-07-01

From the discovery of the regulation of bone remodelling by leptin, much attention has been focused on neurogenic control of bone remodelling. Various hypothalamic neuropeptides, which are involved in appetite regulation, are now revealed to be important regulators of bone remodelling. More recently, neurotransmitters, such as serotonin or catecholamines, are proven to be bone remodelling regulators.

Tributyltin alters secretion of interleukin 1 beta from human immune cells.

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Brown, Shyretha; Whalen, Margaret

2015-08-01

Tributyltin (TBT) has been used as a biocide in industrial applications such as wood preservation, antifouling paint and antifungal agents. Owing to its many uses, it contaminates the environment and has been found in human blood samples. Interleukin-1 beta (IL-1β) is a pro-inflammatory cytokine that promotes cell growth, tissue repair and immune response regulation. Produced predominately by both monocytes and macrophages, IL-1β appears to increase the invasiveness of certain tumors. This study shows that TBT modifies the secretion of IL-1β from increasingly reconstituted preparations of human immune cells. IL-1β secretion was examined after 24-, 48-h or 6-day exposures to TBT in highly enriched human natural killer (NK) cells, monocyte-depleted peripheral blood mononuclear cells (MD-PBMCs), PBMCs, granulocytes and a preparation combining both PBMCs and granulocytes (PBMCs+granulocytes). TBT altered IL-1β secretion from all of the cell preparations. The 200 nM concentration of TBT normally blocked the secretion of IL-1β, whereas lower concentrations (usually 5-50 nM) elevated secretion of IL-1β. Examination of the signaling pathway(s) responsible for the elevated secretion of IL-1β was carried out in MD-PBMCs. Pathways examined were IL-1β processing (Caspase-1), mitogen-activated protein kinases (MAPKs) and nuclear factor kappa B (NFκB). Results indicated that MAPK pathways (p44/42 and p38) appear to be the targets of TBT that lead to increased IL-1β secretion from immune cells. These results from human immune cells show IL-1β dysregulation by TBT is occurring ex vivo. Thus, the potential for in vivo effects on pro-inflammatory cytokine levels may possibly be a consequence of TBT exposures. Copyright © 2014 John Wiley & Sons, Ltd.

Qing-Hua Granule induces GLP-1 secretion via bitter taste receptor in db/db mice.

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Li, Junyan; Xu, Jie; Hou, Ruifang; Jin, Xin; Wang, Jingyi; Yang, Na; Yang, Li; Liu, Li; Tao, Feng; Lu, Hao

2017-05-01

Qing-Hua Granule (QHG), the modified formulation of a classical Chinese prescription named Gegen Qinlian Decoction, was clinically employed to treat type 2 diabetes mellitus (T2DM) through regulation of glucagon-like peptide-1 (GLP-1). However, the potential mechanism is unknown. We investigate whether QHG induces GLP-1 secretion via activation of bitter taste receptor (TAS2R) pathway in the gastrointestinal tract of db/db mice. The db/db mice were intragastrically (i.g.) administered QHG (low/medium/high dose) once daily for 8 weeks. GLP-1 secretion was evaluated. The bitter receptor signaling pathway, which regulates GLP-1 secretion, including TAS2R5 (a subtype of TAS2R), α-gustducin (Gαgust), 1-phosphatidylinositol-4, 5-bisphosphate phosphodiesterase beta-2 (PLCβ2), transient receptor potential cation channel subfamily M member 5 (TRPM5), was assessed by quantitative real-time polymerase chain reaction (qRT-PCR), Western blot and immunohistochemistry (IHC). The biochemical observations of ileum and pancreas tissue were detected histopathologically. Acquity Ultra Performance LCTM - Micromass ZQ 2000 (UPLC-MS) was used for the phytochemical analysis. QHG exhibited significant and dose-dependent effect on GLP-1 secretion in db/db mice, along with significant up-regulation of TAS2R5 mRNA level and activation of TAS2R pathway (p<0.05). In addition, QHG improved the histopathological structure of ileum and pancreatic tissue. Seventeen compounds were identified in QHG. In conclusion, QHG induces GLP-1 secretion in db/db mice, most likely through the bitter taste receptor pathway. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Histochemical and structural analysis of mucous glycoprotein secreted by the gill of Mytilus edulis

International Nuclear Information System (INIS)

Ahn, Hae-Young.

1988-01-01

Studies were carried out to characterized various mucous cells in the gill filament, to ascertain structural characteristics of the secreted mucous glycoproteins, and to determine the ability of the gill epithelium to incorporate [ 14 C]glucosamine as a precursor in the biosynthesis and secretion of mucous glycoproteins. Using histochemical staining techniques, mucous cells containing neutral and acidic mucins were found in the lateral region, whereas mucous cells containing primarily neutral or sulfated mucins were found in the postlateral region. Serotonin, but not dopamine, stimulated the mucous secretion. In tissues pretreated with [ 14 C]glucosamine, the secreted glycoproteins contain incorporated radiolabel. Analysis by column chromatography using Bio-Gel P-2 and P-6 shows that the secretion contains two glycoprotein populations. Glycoprotein II has a molecular weight of 2.3 x 10 4 daltons. Upon alkaline reductive borohydride cleavage of the O-glycosidic linkages of glycoprotein I, about 70% of the radiolabel was removed from the protein. Gas chromatographic analysis of the carbohydrate composition shows that the glycoproteins contains N-acetylglucosamine (GluNAc), N-acetylgalactosamine (GalNAc), and galactose, fucose and mannose. Amino acid analysis shows that the glycoproteins are rich in serine, threonine and proline

GABA and glycine as neurotransmitters: a brief history.

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Bowery, N G; Smart, T G

2006-01-01

gamma-Aminobutyric acid (GABA) emerged as a potentially important brain chemical just over 50 years ago, but its significance as a neurotransmitter was not fully realized until over 16 years later. We now know that at least 40% of inhibitory synaptic processing in the mammalian brain uses GABA. Establishing its role as a transmitter was a lengthy process and it seems hard to believe with our current knowledge that there was ever any dispute about its role in the mammalian brain. The detailed information that we now have about the receptors for GABA together with the wealth of agents which facilitate or reduce GABA receptor mechanisms make the prospects for further research very exciting. The emergence of glycine as a transmitter seems relatively painless by comparison to GABA. Perhaps this is appropriate for the simplest of transmitter structures! Its discovery within the spinal cord and brainstem approximately 40 years ago was followed only 2 years later by the proposal that it be conferred with 'neurotransmitter' status. It was another 16 years before the receptor was biochemically isolated. Now it is readily accepted as a vital spinal and supraspinal inhibitory transmitter and we know many details regarding its molecular structure and trafficking around neurones. The pharmacology of these receptors has lagged behind that of GABA. There is not the rich variety of allosteric modulators that we have come to readily associate with GABA receptors and which has provided us with a virtual treasure trove of important drugs used in anxiety, insomnia, epilepsy, anaesthesia, and spasticity, all stemming from the actions of the simple neutral amino acid GABA. Nevertheless, the realization that glycine receptors are involved in motor reflexes and nociceptive pathways together with the more recent advent of drugs that exhibit some subtype selectivity make the goal of designing selective therapeutic ligands for the glycine receptor that much closer.

The subpopulation of microglia sensitive to neurotransmitters/neurohormones is modulated by stimulation with LPS, interferon-γ, and IL-4.

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Pannell, Maria; Szulzewsky, Frank; Matyash, Vitali; Wolf, Susanne A; Kettenmann, Helmut

2014-05-01

Recently, neurotransmitters/neurohormones have been identified as factors controlling the function of microglia, the immune competent cells of the central nervous system. In this study, we compared the responsiveness of microglia to neurotransmitters/neurohormones. We freshly isolated microglia from healthy adult C57Bl/6 mice and found that only a small fraction (1-20%) responded to the application of endothelin, histamine, substance P, serotonin, galanin, somatostatin, angiotensin II, vasopressin, neurotensin, dopamine, or nicotine. In cultured microglia from neonatal and adult mice, a similarly small population of cells responded to these neurotransmitters/neurohormones. To induce a proinflammatory phenotype, we applied lipopolysaccaride (LPS) or interferon-gamma (IFN-γ) to the cultures for 24 h. Several of the responding populations increased; however, there was no uniform pattern when comparing adult with neonatal microglia or LPS with IFN-γ treatment. IL-4 as an anti-inflammatory substance increased the histamine-, substance P-, and somatostatin-sensitive populations only in microglia from adult, but not in neonatal cells. We also found that the expression of different receptors was not strongly correlated, indicating that there are many different populations of microglia with a distinct set of receptors. Our results demonstrate that microglial cells are a heterogeneous population with respect to their sensitivity to neurotransmitters/neurohormones and that they are more responsive in defined activation states. Copyright © 2014 Wiley Periodicals, Inc.

High dose sapropterin dihydrochloride therapy improves monoamine neurotransmitter turnover in murine phenylketonuria (PKU).

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Winn, Shelley R; Scherer, Tanja; Thöny, Beat; Harding, Cary O

2016-01-01

Central nervous system (CNS) deficiencies of the monoamine neurotransmitters, dopamine and serotonin, have been implicated in the pathophysiology of neuropsychiatric dysfunction in phenylketonuria (PKU). Increased brain phenylalanine concentration likely competitively inhibits the activities of tyrosine hydroxylase (TH) and tryptophan hydroxylase (TPH), the rate limiting steps in dopamine and serotonin synthesis respectively. Tetrahydrobiopterin (BH4) is a required cofactor for TH and TPH activity. Our hypothesis was that treatment of hyperphenylalaninemic Pah(enu2/enu2) mice, a model of human PKU, with sapropterin dihydrochloride, a synthetic form of BH4, would stimulate TH and TPH activities leading to improved dopamine and serotonin synthesis despite persistently elevated brain phenylalanine. Sapropterin (20, 40, or 100mg/kg body weight in 1% ascorbic acid) was administered daily for 4 days by oral gavage to Pah(enu2/enu2) mice followed by measurement of brain biopterin, phenylalanine, tyrosine, tryptophan and monoamine neurotransmitter content. A significant increase in brain biopterin content was detected only in mice that had received the highest sapropterin dose, 100mg/kg. Blood and brain phenylalanine concentrations were unchanged by sapropterin therapy. Sapropterin therapy also did not alter the absolute amounts of dopamine and serotonin in brain but was associated with increased homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA), dopamine and serotonin metabolites respectively, in both wild type and Pah(enu2/enu2) mice. Oral sapropterin therapy likely does not directly affect central nervous system monoamine synthesis in either wild type or hyperphenylalaninemic mice but may stimulate synaptic neurotransmitter release and subsequent metabolism. Copyright © 2015 Elsevier Inc. All rights reserved.

Harmane: an atypical neurotransmitter?

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Abu Ghazaleh, Haya; Lalies, Maggie D; Nutt, David J; Hudson, Alan L

2015-03-17

Harmane is an active component of clonidine displacing substance and a candidate endogenous ligand for imidazoline binding sites. The neurochemistry of tritiated harmane was investigated in the present study examining its uptake and release properties in the rat brain central nervous system (CNS) in vitro. At physiological temperature, [(3)H]harmane was shown to be taken up in rat brain cortex. Further investigations demonstrated that treatment with monoamine uptake blockers (citalopram, nomifensine and nisoxetine) did not alter [(3)H]harmane uptake implicating that the route of [(3)H]harmane transport was distinct from the monoamine uptake systems. Furthermore, imidazoline ligands (rilmenidine, efaroxan, 2-BFI and idazoxan) showed no prominent effect on [(3)H]harmane uptake suggesting the lack of involvement of imidazoline binding sites. Subsequent analyses showed that disruption of the Na(+) gradient using ouabain or choline chloride did not block [(3)H]harmane uptake suggesting a Na(+)-independent transport mechanism. Moreover, higher temperatures (50°C) failed to impede [(3)H]harmane uptake implying a non-physiological transporter. The failure of potassium to evoke the release of preloaded [(3)H]harmane from rat brain cortex indicates that the properties of this putative endogenous ligand for imidazoline binding sites do not resemble that of a conventional neurotransmitter. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Stimulatory effect of Coca-Cola on gastroduodenal HCO3- secretion in rats.

Science.gov (United States)

Sasaki, Y; Aihara, E; Ise, F; Kita, K; Takeuchi, K

2007-10-01

We examined the effect of various carbonated beverages, especially Coca-Cola, on the HCO3- secretion in the rat stomach and duodenum. Under urethane anaesthesia, a chambered stomach or a proximal duodenal loop was perfused with saline, and HCO3- secretion was measured at pH 7.0 using a pH-stat method and by adding 2 mM HCl. The amount of CO2 contained in these beverages was about 4-7 g/mL. Coca-Cola topically applied to the mucosa for 10 min significantly increased the HCO3- secretion in both the stomach and the duodenum. The HCO3- response in the duodenum was totally abolished by indomethacin and also partially inhibited by acetazolamide, an inhibitor of carbonic anhydrase. Likewise, the response in the stomach was also markedly inhibited by either acetazolamide or indomethacin. The mucosal application of Coca-Cola increased the PGE2 contents in both the stomach and the duodenum. Other carbonated beverages, such as sparkling water, Fanta Grape or cider, also increased the HCO3- secretion in these tissues. These results suggest that Coca-Cola induces HCO3- secretion in both the stomach and the duodenum, and these responses may be attributable to both the intracellular supply of HCO3- generated via carbonic anhydrase, and endogenous PGs, probably related to the acidic pH of the solution.

Sugary secretions of wasp galls: a want-to-be extrafloral nectar?

Science.gov (United States)

Aranda-Rickert, Adriana; Rothen, Carolina; Diez, Patricia; González, Ana María; Marazzi, Brigitte

2017-11-10

The most widespread form of protective mutualisms is represented by plants bearing extrafloral nectaries (EFNs) that attract ants and other arthropods for indirect defence. Another, but less common, form of sugary secretion for indirect defence occurs in galls induced by cynipid wasps. Until now, such galls have been reported only for cynipid wasps that infest oak trees in the northern hemisphere. This study provides the first evidence of galls that exude sugary secretions in the southern hemisphere and asks whether they can be considered as analogues of plants' EFNs. The ecology and anatomy of galls and the chemical composition of the secretion were investigated in north-western Argentina, in natural populations of the host trees Prosopis chilensis and P. flexuosa . To examine whether ants protect the galls from natural enemies, ant exclusion experiments were conducted in the field. The galls produce large amounts of sucrose-rich, nectar-like secretions. No typical nectary and sub-nectary parenchymatic tissues or secretory trichomes can be observed; instead there is a dense vascularization with phloem elements reaching the gall periphery. At least six species of ants, but also vespid wasps, Diptera and Coleoptera, consumed the gall secretions. The ant exclusion experiment showed that when ants tended galls, no differences were found in the rate of successful emergence of gall wasps or in the rate of parasitism and inquiline infestation compared with ant-excluded galls. The gall sugary secretion is not analogous to extrafloral nectar because no nectar-producing structure is associated with it, but is functionally equivalent to arthropod honeydew because it provides indirect defence to the plant parasite. As in other facultative mutualisms mediated by sugary secretions, the gall secretion triggers a complex multispecies interaction, in which the outcome of individual pair-wise interactions depends on the ecological context in which they take place. © The Author

Assessment of post-implantation integration of engineered tissues using fluorescence lifetime spectroscopy

Science.gov (United States)

Elahi, Sakib F.; Lee, Seung Y.; Lloyd, William R.; Chen, Leng-Chun; Kuo, Shiuhyang; Zhou, Ying; Kim, Hyungjin M.; Kennedy, Robert; Marcelo, Cynthia; Feinberg, Stephen E.; Mycek, Mary-Ann

2018-02-01

Clinical translation of engineered tissue constructs requires noninvasive methods to assess construct health and viability after implantation in patients. However, current practices to monitor post-implantation construct integration are either qualitative (visual assessment) or destructive (tissue histology). As label-free fluorescence lifetime sensing can noninvasively characterize pre-implantation construct viability, we employed a handheld fluorescence lifetime spectroscopy probe to quantitatively and noninvasively assess tissue constructs that were implanted in a murine model. We designed the system to be suitable for intravital measurements: portability, localization with precise maneuverability, and rapid data acquisition. Our model tissue constructs were manufactured from primary human cells to simulate patient variability and were stressed to create a range of health states. Secreted amounts of three cytokines that relate to cellular viability were measured in vitro to assess pre-implantation construct health. In vivo optical sensing assessed tissue integration of constructs at one-week and three-weeks post-implantation. At one-week post-implantation, optical parameters correlated with in vitro pre-implantation secretion levels of all three cytokines (p clinical optical diagnostic tools based on label-free fluorescence lifetime sensing of endogenous tissue fluorophores could noninvasively monitor post-implantation integration of engineered tissues.

Synthesis on accumulation of putative neurotransmitters by cultured neural crest cells

International Nuclear Information System (INIS)

Maxwell, G.D.; Sietz, P.D.; Rafford, C.E.

1982-01-01

The events mediating the differentiation of embryonic neural crest cells into several types of neurons are incompletely understood. In order to probe one aspect of this differentiation, we have examined the capacity of cultured quail trunk neural crest cells to synthesize, from radioactive precursors, and store several putative neurotransmitter compounds. These neural crest cultures develop the capacity to synthesize and accumulate acetylcholine and the catecholamines norepinephrine and dopamine. In contrast, detectable but relatively little synthesis and accumulation of 5-hydroxytryptamine gamma-aminobutyric acid, or octopamine from the appropriate radiolabeled precursors were observed. The capacity for synthesis and accumulation of radiolabeled acetylcholine and catecholamines is very low or absent at 2 days in vitro. Between 3 and 7 days in vitro, there is a marked rise in both catecholamine and acetylcholine accumulation in the cultures. These findings suggest that, under the particular conditions used in these experiments, the development of neurotransmitter biosynthesis in trunk neural crest cells ijs restricted and resembles, at least partially, the pattern observed in vivo. The development of this capacity to synthesize and store radiolabeled acetylcholine and catecholamines from the appropriate radioactive precursors coincides closely with the development of the activities of the synthetic enzymes choline acetyltransferase and dopamine beta-hydroxylase reported by others

Determination of neurotransmitters and their metabolites using one- and two-dimensional liquid chromatography with acidic potassium permanganate chemiluminescence detection.

Science.gov (United States)

Holland, Brendan J; Conlan, Xavier A; Stevenson, Paul G; Tye, Susannah; Reker, Ashlie; Barnett, Neil W; Adcock, Jacqui L; Francis, Paul S

2014-09-01

High-performance liquid chromatography with chemiluminescence detection based on the reaction with acidic potassium permanganate and formaldehyde was explored for the determination of neurotransmitters and their metabolites. The neurotransmitters norepinephrine and dopamine were quantified in the left and right hemispheres of rat hippocampus, nucleus accumbens and prefrontal cortex, and the metabolites vanillylmandelic acid, 3,4-dihydrophenylacetic acid, 5-hydroxyindole-3-acetic acid and homovanillic acid were identified in human urine. Under optimised chemiluminescence reagent conditions, the limits of detection for these analytes ranged from 2.5 × 10(-8) to 2.5 × 10(-7) M. For the determination of neurotransmitter metabolites in urine, a two-dimensional high-performance liquid chromatography (2D-HPLC) separation operated in heart-cutting mode was developed to overcome the peak capacity limitations of the one-dimensional separation. This approach provided the greater separation power of 2D-HPLC with analysis times comparable to conventional one-dimensional separations.

p53- and ERK7-dependent ribosome surveillance response regulates Drosophila insulin-like peptide secretion.

Directory of Open Access Journals (Sweden)

Kiran Hasygar

2014-11-01

Full Text Available Insulin-like signalling is a conserved mechanism that coordinates animal growth and metabolism with nutrient status. In Drosophila, insulin-producing median neurosecretory cells (IPCs regulate larval growth by secreting insulin-like peptides (dILPs in a diet-dependent manner. Previous studies have shown that nutrition affects dILP secretion through humoral signals derived from the fat body. Here we uncover a novel mechanism that operates cell autonomously in the IPCs to regulate dILP secretion. We observed that impairment of ribosome biogenesis specifically in the IPCs strongly inhibits dILP secretion, which consequently leads to reduced body size and a delay in larval development. This response is dependent on p53, a known surveillance factor for ribosome biogenesis. A downstream effector of this growth inhibitory response is an atypical MAP kinase ERK7 (ERK8/MAPK15, which is upregulated in the IPCs following impaired ribosome biogenesis as well as starvation. We show that ERK7 is sufficient and essential to inhibit dILP secretion upon impaired ribosome biogenesis, and it acts epistatically to p53. Moreover, we provide evidence that p53 and ERK7 contribute to the inhibition of dILP secretion upon starvation. Thus, we conclude that a cell autonomous ribosome surveillance response, which leads to upregulation of ERK7, inhibits dILP secretion to impede tissue growth under limiting dietary conditions.

Modulation of pumping rate by two species of marine bivalve molluscs in response to neurotransmitters: Comparison of in vitro and in vivo results.

Science.gov (United States)

Frank, Dana M; Deaton, Lewis; Shumway, Sandra E; Holohan, Bridget A; Ward, J Evan

2015-07-01

Most studies regarding the neuroanatomy and neurophysiology of molluscan ctenidia have focused on isolated ctenidial tissue preparations. This study investigated how bivalve molluscs modulate their feeding rates by examining the effects of a variety of neurotransmitters, including serotonin, dopamine, and the dopamine agonist apomorphine on both isolated ctenidial tissue and in intact members of two commercially important bivalve species: the blue mussel, Mytilus edulis; and the bay scallop Argopecten irradians. In particular, we examined the effect of changes in: 1) beat of the lateral cilia (in vitro), 2) distance between ctenidial filaments and/or plicae (in vivo), and 3) diameter of the siphonal openings (in vivo) on alteration of bulk water flow through the mantle cavity. Important differences were found between isolated tissue and whole animals, and between species. Drugs that stimulated ciliary beat in vitro did not increase water processing rate in vivo. None of the treatments increased water flow through the mantle cavity of intact animals. Results suggest that A. irradians was primarily modulating lateral ciliary activity, while M. edulis appeared to have a number of ways to control water processing activity, signifying that the two species may have different compensatory and regulatory mechanisms controlling feeding activity. Copyright © 2015 Elsevier Inc. All rights reserved.

The emerging role of senescent cells in tissue homeostasis and pathophysiology

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Kaoru Tominaga

2015-05-01

Full Text Available Cellular senescence is a state of permanent growth arrest and is thought to play a pivotal role in tumor suppression. Cellular senescence may play an important role in tumor suppression, wound healing, and protection against tissue fibrosis in physiological conditions in vivo. However, accumulating evidence that senescent cells may have harmful effects in vivo and may contribute to tissue remodeling, organismal aging, and many age-related diseases also exists. Cellular senescence can be induced by various intrinsic and extrinsic factors. Both p53/p21 and p16/RB pathways are important for irreversible growth arrest in senescent cells. Senescent cells secret numerous biologically active factors. This specific secretion phenotype by senescent cells may largely contribute to physiological and pathological consequences in organisms. Here I review the molecular basis of cell cycle arrest and the specific secretion phenotype in cellular senescence. I also summarize the current knowledge of the role of cellular senescence in vivo in physiological and pathological settings.

Sebaceous lipid profiling of bat integumentary tissues: quantitative analysis of free Fatty acids, monoacylglycerides, squalene, and sterols.

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Pannkuk, Evan L; Gilmore, David F; Fuller, Nathan W; Savary, Brett J; Risch, Thomas S

2013-12-01

White-nose syndrome (WNS) is a fungal disease caused by Pseudogymnoascus destructans and is devastating North American bat populations. Sebaceous lipids secreted from host integumentary tissues are implicated in the initial attachment and recognition of host tissues by pathogenic fungi. We are interested in determining if ratios of lipid classes in sebum can be used as biomarkers to diagnose severity of fungal infection in bats. To first establish lipid compositions in bats, we isolated secreted and integral lipid fractions from the hair and wing tissues of three species: big brown bats (Eptesicus fuscus), Eastern red bats (Lasiurus borealis), and evening bats (Nycticeius humeralis). Sterols, FFAs, MAGs, and squalene were derivatized as trimethylsilyl esters, separated by gas chromatography, and identified by mass spectrometry. Ratios of sterol to squalene in different tissues were determined, and cholesterol as a disease biomarker was assessed. Free sterol was the dominant lipid class of bat integument. Squalene/sterol ratio is highest in wing sebum. Secreted wing lipid contained higher proportions of saturated FFAs and MAGs than integral wing or secreted hair lipid. These compounds are targets for investigating responses of P. destructans to specific host lipid compounds and as biomarkers to diagnose WNS. Copyright © 2013 Verlag Helvetica Chimica Acta AG, Zürich.

Interaction of differentiated human adipocytes with macrophages leads to trogocytosis and selective IL-6 secretion

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Sárvári, Anitta Kinga; Doan-Xuan, Quang-Minh; Bacsó, Zsolt; Csomós, István; Balajthy, Zoltán; Fésüs, László

2015-01-01

Obesity leads to adipose tissue inflammation that is characterized by increased release of proinflammatory molecules and the recruitment of activated immune cells. Although macrophages are present in the highest number among the immune cells in obese adipose tissue, not much is known about their direct interaction with adipocytes. We have introduced an ex vivo experimental system to characterize the cellular interactions and the profile of secreted cytokines in cocultures of macrophages and h...

Classical neurotransmitters and neuropeptides involved in major depression in a multi-neurotransmitter system: a focus on antidepressant drugs.

Science.gov (United States)

Werner, Felix-Martin; Coveñas, R

2013-01-01

We summarize the alterations of classical neurotransmitters and neuropeptides and the corresponding subreceptors involved in major depression. Neuronal circuits in the brainstem, hippocampus and hypothalamus are developed, since they can be used to derive a multimodal pharmacotherapy. In this sense, serotonin hypoactivity could occur through a strong presynaptic inhibition of glutaminergic neurons via the subtype 5 of metabotropic glutaminergic receptors, and noradrenaline hypoactivity could be due to an enhanced presynaptic inhibition of GABAergic neurons via GABAB receptors. In the hippocampus, dopamine hypoactivity leads to a decreased positive effect. In clinical trials, the antidepressant effect of drugs interfering with the mentioned subreceptors, for example the triple reuptake inhibitor amitifadine, is being investigated. Moreover, the alterations of neuropeptides, such as corticotropin-releasing hormone, neuropeptide Y and galanin are pointed out. The additional antidepressant effect of analogs, agonists and antagonists of the mentioned neuropeptides should be examined.

Vesicular and Plasma Membrane Transporters for Neurotransmitters

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Blakely, Randy D.; Edwards, Robert H.

2012-01-01

The regulated exocytosis that mediates chemical signaling at synapses requires mechanisms to coordinate the immediate response to stimulation with the recycling needed to sustain release. Two general classes of transporter contribute to release, one located on synaptic vesicles that loads them with transmitter, and a second at the plasma membrane that both terminates signaling and serves to recycle transmitter for subsequent rounds of release. Originally identified as the target of psychoactive drugs, these transport systems have important roles in transmitter release, but we are only beginning to understand their contribution to synaptic transmission, plasticity, behavior, and disease. Recent work has started to provide a structural basis for their activity, to characterize their trafficking and potential for regulation. The results indicate that far from the passive target of psychoactive drugs, neurotransmitter transporters undergo regulation that contributes to synaptic plasticity. PMID:22199021

The Effect of Scalp Point Cluster-Needling on Learning and Memory Function and Neurotransmitter Levels in Rats with Vascular Dementia

OpenAIRE

Yang, Junli; Litscher, Gerhard; Li, Haitao; Guo, Wenhai; Liang, Zhang; Zhang, Ting; Wang, Weihua; Li, Xiaoyan; Zhou, Yao; Zhao, Bing; Rong, Qi; Sheng, Zemin; Gaischek, Ingrid; Litscher, Daniela; Wang, Lu

2014-01-01

We observed the effect of scalp point cluster-needling treatment on learning and memory function and neurotransmitter levels in rats with vascular dementia (VD). Permanent ligation of the bilateral carotid arteries was used to create the VD rat model. A Morris water maze was used to measure the rats' learning and memory function, and the changes in neurotransmitter levels in the rats' hippocampus were analyzed. The results show that scalp point cluster-needling can increase the VD rat model's...

Adipose Tissue Dysfunction in Nascent Metabolic Syndrome

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Andrew A. Bremer

2013-01-01

Full Text Available The metabolic syndrome (MetS confers an increased risk for both type 2 diabetes mellitus (T2DM and cardiovascular disease (CVD. Moreover, studies on adipose tissue biology in nascent MetS uncomplicated by T2DM and/or CVD are scanty. Recently, we demonstrated that adipose tissue dysregulation and aberrant adipokine secretion contribute towards the syndrome’s low-grade chronic proinflammatory state and insulin resistance. Specifically, we have made the novel observation that subcutaneous adipose tissue (SAT in subjects with nascent MetS has increased macrophage recruitment with cardinal crown-like structures. We have also shown that subjects with nascent MetS have increased the levels of SAT-secreted adipokines (IL-1, IL-6, IL-8, leptin, RBP-4, CRP, SAA, PAI-1, MCP-1, and chemerin and plasma adipokines (IL-1, IL-6, leptin, RBP-4, CRP, SAA, and chemerin, as well as decreased levels of plasma adiponectin and both plasma and SAT omentin-1. The majority of these abnormalities persisted following correction for increased adiposity. Our data, as well as data from other investigators, thus, highlight the importance of subcutaneous adipose tissue dysfunction in subjects with MetS and its contribution to the proinflammatory state and insulin resistance. This adipokine profile may contribute to increased insulin resistance and low-grade inflammation, promoting the increased risk of T2DM and CVD.

Rapid labeling of amino acid neurotransmitters with a fluorescent thiol in the presence of o-phthalaldehyde.

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Maddukuri, Naveen; Zhang, Qiyang; Zhang, Ning; Gong, Maojun

2017-02-01

LIF detection often requires labeling of analytes with fluorophores; and fast fluorescent derivatization is valuable for high-throughput analysis with flow-gated CE. Here, we report a fast fluorescein-labeling scheme for amino acid neurotransmitters, which were then rapidly separated and detected in flow-gated CE. This scheme was based on the reaction between primary amines and o-phthalaldehyde in the presence of a fluorescent thiol, 2-((5-fluoresceinyl)aminocarbonyl)ethyl mercaptan (FACE-SH). The short reaction time (neurotransmitters by coupling in vitro microdialysis with online derivatization and flow-gated CE. It is also anticipated that this fluorophore tagging scheme would be valuable for on-chip labeling of proteins retained on support in SPE. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Quantum strongly secure ramp secret sharing

DEFF Research Database (Denmark)

Zhang, Paul; Matsumoto, Rytaro Yamashita

2015-01-01

Quantum secret sharing is a scheme for encoding a quantum state (the secret) into multiple shares and distributing them among several participants. If a sufficient number of shares are put together, then the secret can be fully reconstructed. If an insufficient number of shares are put together...... however, no information about the secret can be revealed. In quantum ramp secret sharing, partial information about the secret is allowed to leak to a set of participants, called an unqualified set, that cannot fully reconstruct the secret. By allowing this, the size of a share can be drastically reduced....... This paper introduces a quantum analog of classical strong security in ramp secret sharing schemes. While the ramp secret sharing scheme still leaks partial information about the secret to unqualified sets of participants, the strong security condition ensures that qudits with critical information can...

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

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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. Copyright © 2015 Elsevier B.V. All rights reserved.

Neurotransmitter implications in descending motility of longitudinal and circular muscles in rat colon

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Zornitsa V. Gorcheva

2018-03-01

Full Text Available Introduction. The role of neurotransmitter systems in the motor activity of longitudinal or circular muscles in autonomic regulation of the motility of the colon by the nervous system is unclear. The aim of the study was to investigate the neurotransmitter implications in descending motility of longitudinal and circular muscles in rat colon. Methods. Electrically-induced (2, 5 or 10 Hz, 0.8 ms, 40 V, 20 s local or descending motor responses of longitudinal and circular muscles in isolated preparations and drugs were used to define the neurotransmitters’ role in colonic motility. Results. The spontaneous activity of the distal part of preparations manifested as high-amplitude irregular contractions more expressed in the longitudinal muscles. The electrically-induced local responses differed considerably in the two muscles: in longitudinal muscle there were frequency-dependent contractions, while initial relaxation followed by contraction was observed in circular muscle. The descending motor response resembled the pattern of the local responses, but the amplitudes were significantly less expressed, as compared to the respective local responses.

Highly selective and sensitive detection of neurotransmitters using receptor-modified single-walled carbon nanotube sensors

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Kim, Byeongju; Song, Hyun Seok; Jin, Hye Jun; Park, Eun Jin; Lee, Sang Hun; Lee, Byung Yang; Park, Tai Hyun; Hong, Seunghun

2013-07-01

We present receptor-modified carbon nanotube sensors for the highly selective and sensitive detection of acetylcholine (ACh), one kind of neurotransmitter. Here, we successfully expressed the M1 muscarinic acetylcholine receptor (M1 mAChR), a family of G protein-coupled receptors (GPCRs), in E. coli and coated single-walled carbon nanotube (swCNT)-field effect transistors (FETs) with lipid membrane including the receptor, enabling highly selective and sensitive ACh detection. Using this sensor, we could detect ACh at 100 pM concentration. Moreover, we showed that this sensor could selectively detect ACh among other neurotransmitters. This is the first demonstration of the real-time detection of ACh using specific binding between ACh and M1 mAChR, and it may lead to breakthroughs for various applications such as disease diagnosis and drug screening.

Highly selective and sensitive detection of neurotransmitters using receptor-modified single-walled carbon nanotube sensors

International Nuclear Information System (INIS)

Kim, Byeongju; Jin, Hye Jun; Park, Eun Jin; Hong, Seunghun; Song, Hyun Seok; Lee, Sang Hun; Park, Tai Hyun; Lee, Byung Yang

2013-01-01

We present receptor-modified carbon nanotube sensors for the highly selective and sensitive detection of acetylcholine (ACh), one kind of neurotransmitter. Here, we successfully expressed the M1 muscarinic acetylcholine receptor (M1 mAChR), a family of G protein-coupled receptors (GPCRs), in E. coli and coated single-walled carbon nanotube (swCNT)-field effect transistors (FETs) with lipid membrane including the receptor, enabling highly selective and sensitive ACh detection. Using this sensor, we could detect ACh at 100 pM concentration. Moreover, we showed that this sensor could selectively detect ACh among other neurotransmitters. This is the first demonstration of the real-time detection of ACh using specific binding between ACh and M1 mAChR, and it may lead to breakthroughs for various applications such as disease diagnosis and drug screening. (paper)

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

2014-07-01

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. © The Author(s) 2014.

Dynamic secrets in communication security

CERN Document Server

Xiao, Sheng; Towsley, Donald

2013-01-01

Dynamic secrets are constantly generated and updated from messages exchanged between two communication users. When dynamic secrets are used as a complement to existing secure communication systems, a stolen key or password can be quickly and automatically reverted to its secret status without disrupting communication. 'Dynamic Secrets in Communication Security' presents unique security properties and application studies for this technology. Password theft and key theft no longer pose serious security threats when parties frequently use dynamic secrets. This book also illustrates that a dynamic

Scaffold-free 3D bio-printed human liver tissue stably maintains metabolic functions useful for drug discovery.

Science.gov (United States)

Kizawa, Hideki; Nagao, Eri; Shimamura, Mitsuru; Zhang, Guangyuan; Torii, Hitoshi

2017-07-01

The liver plays a central role in metabolism. Although many studies have described in vitro liver models for drug discovery, to date, no model has been described that can stably maintain liver function. Here, we used a unique, scaffold-free 3D bio-printing technology to construct a small portion of liver tissue that could stably maintain drug, glucose, and lipid metabolism, in addition to bile acid secretion. This bio-printed normal human liver tissue maintained expression of several kinds of hepatic drug transporters and metabolic enzymes that functioned for several weeks. The bio-printed liver tissue displayed glucose production via cAMP/protein kinase A signaling, which could be suppressed with insulin. Bile acid secretion was also observed from the printed liver tissue, and it accumulated in the culture medium over time. We observed both bile duct and sinusoid-like structures in the bio-printed liver tissue, which suggested that bile acid secretion occurred via a sinusoid-hepatocyte-bile duct route. These results demonstrated that our bio-printed liver tissue was unique, because it exerted diverse liver metabolic functions for several weeks. In future, we expect our bio-printed liver tissue to be applied to developing new models that can be used to improve preclinical predictions of long-term toxicity in humans, generate novel targets for metabolic liver disease, and evaluate biliary excretion in drug development.

[Single and combining effects of Calculus Bovis and zolpidem on inhibitive neurotransmitter of rat striatum corpora].

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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.

Development and validation of a simple, rapid and sensitive LC-MS/MS method for the measurement of urinary neurotransmitters and their metabolites.

Science.gov (United States)

Yan, Jingya; Kuzhiumparambil, Unnikrishnan; Bandodkar, Sushil; Solowij, Nadia; Fu, Shanlin

2017-12-01

Neurotransmitters play crucial roles in physiological functions and their imbalances have demonstrated association in the pathology of several diseases. The measurement of neurotransmitters possesses a great potential as a significant clinical tool. This study presents the development and validation of an LC-MS/MS method for simultaneous quantification of multi-class neurotransmitters associated with dopamine, tryptophan and glutamate-γ-aminobutyric acid pathways. A total of ten neurotransmitters and their metabolites (dopamine, epinephrine, metanephrine, tryptophan, serotonin, kynurenic acid, kynurenine, anthranilic acid, GABA, glutamic acid) were determined based on a simple and rapid 'dilute and shoot' method using minimal urine volume. The chromatographic separation was achieved using a Poroshell 120 Bonus-RP LC Column in combination with a gradient elution within an 8.5-min time frame. The method exhibited good sensitivity as the limits of quantification ranged between 0.025 and 0.075 μg/mL with acceptable matrix effects ( 0.98). The accuracy and precision for all analytes were within tolerances, at neurotransmitter concentrations in urine of healthy donors. Furthermore, the undertaken stability experiments indicated that acidified urine specimens allowed the analytes to be stable for prolonged durations in comparison to those untreated. The study also reveals the performance of the method is unaffected by the absence of expensive deuterated reference standards under the experimental conditions employed which further simplifies the analytical procedures and provides a significant cost saving for running the assay. Graphical abstract The quantification of multi-class neurotransitters associated with the dopamine, tryptophan and GABA-glutamate pathways using a simple 'dilute and shoot' LC-MS/MS method.

Regulation of Bicarbonate Secretion in Marine Fish Intestine by the Calcium-Sensing Receptor

Directory of Open Access Journals (Sweden)

Sílvia F. Gregório

2018-04-01

Full Text Available In marine fish, high epithelial intestinal HCO3− secretion generates luminal carbonate precipitates of divalent cations that play a key role in water and ion homeostasis. The present study was designed to expose the putative role for calcium and the calcium-sensing receptor (CaSR in the regulation of HCO3− secretion in the intestine of the sea bream (Sparus aurata L.. Effects on the expression of the CaSR in the intestine were evaluated by qPCR and an increase was observed in the anterior intestine in fed fish compared with unfed fish and with different regions of intestine. CaSR expression reflected intestinal fluid calcium concentration. In addition, anterior intestine tissue was mounted in Ussing chambers to test the putative regulation of HCO3− secretion in vitro using the anterior intestine. HCO3− secretion was sensitive to varying calcium levels in luminal saline and to calcimimetic compounds known to activate/block the CaSR i.e., R 568 and NPS-2143. Subsequent experiments were performed in intestinal sacs to measure water absorption and the sensitivity of water absorption to varying luminal levels of calcium and calcimimetics were exposed as well. It appears, that CaSR mediates HCO3− secretion and water absorption in marine fish as shown by responsiveness to calcium levels and calcimimetic compounds.

Insulin Regulates Hepatic Triglyceride Secretion and Lipid Content via Signaling in the Brain.

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Scherer, Thomas; Lindtner, Claudia; O'Hare, James; Hackl, Martina; Zielinski, Elizabeth; Freudenthaler, Angelika; Baumgartner-Parzer, Sabina; Tödter, Klaus; Heeren, Joerg; Krššák, Martin; Scheja, Ludger; Fürnsinn, Clemens; Buettner, Christoph

2016-06-01

Hepatic steatosis is common in obesity and insulin resistance and results from a net retention of lipids in the liver. A key mechanism to prevent steatosis is to increase secretion of triglycerides (TG) packaged as VLDLs. Insulin controls nutrient partitioning via signaling through its cognate receptor in peripheral target organs such as liver, muscle, and adipose tissue and via signaling in the central nervous system (CNS) to orchestrate organ cross talk. While hepatic insulin signaling is known to suppress VLDL production from the liver, it is unknown whether brain insulin signaling independently regulates hepatic VLDL secretion. Here, we show that in conscious, unrestrained male Sprague Dawley rats the infusion of insulin into the third ventricle acutely increased hepatic TG secretion. Chronic infusion of insulin into the CNS via osmotic minipumps reduced the hepatic lipid content as assessed by noninvasive (1)H-MRS and lipid profiling independent of changes in hepatic de novo lipogenesis and food intake. In mice that lack the insulin receptor in the brain, hepatic TG secretion was reduced compared with wild-type littermate controls. These studies identify brain insulin as an important permissive factor in hepatic VLDL secretion that protects against hepatic steatosis. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Prevention of iron- and copper-mediated DNA damage by catecholamine and amino acid neurotransmitters, L-DOPA, and curcumin: metal binding as a general antioxidant mechanism.

Science.gov (United States)

García, Carla R; Angelé-Martínez, Carlos; Wilkes, Jenna A; Wang, Hsiao C; Battin, Erin E; Brumaghim, Julia L

2012-06-07

Concentrations of labile iron and copper are elevated in patients with neurological disorders, causing interest in metal-neurotransmitter interactions. Catecholamine (dopamine, epinephrine, and norepinephrine) and amino acid (glycine, glutamate, and 4-aminobutyrate) neurotransmitters are antioxidants also known to bind metal ions. To investigate the role of metal binding as an antioxidant mechanism for these neurotransmitters, L-dihydroxyphenylalanine (L-DOPA), and curcumin, their abilities to prevent iron- and copper-mediated DNA damage were quantified, cyclic voltammetry was used to determine the relationship between their redox potentials and DNA damage prevention, and UV-vis studies were conducted to determine iron and copper binding as well as iron oxidation rates. In contrast to amino acid neurotransmitters, catecholamine neurotransmitters, L-DOPA, and curcumin prevent significant iron-mediated DNA damage (IC(50) values of 3.2 to 18 μM) and are electrochemically active. However, glycine and glutamate are more effective at preventing copper-mediated DNA damage (IC(50) values of 35 and 12.9 μM, respectively) than L-DOPA, the only catecholamine to prevent this damage (IC(50) = 73 μM). This metal-mediated DNA damage prevention is directly related to the metal-binding behaviour of these compounds. When bound to iron or copper, the catecholamines, amino acids, and curcumin significantly shift iron oxidation potentials and stabilize Fe(3+) over Fe(2+) and Cu(2+) over Cu(+), a factor that may prevent metal redox cycling in vivo. These results highlight the disparate antioxidant activities of neurotransmitters, drugs, and supplements and highlight the importance of considering metal binding when identifying antioxidants to treat and prevent neurodegenerative disorders.

YghJ, the secreted metalloprotease of pathogenic E. coli induces hemorrhagic fluid accumulation in mouse ileal loop.

Science.gov (United States)

Tapader, Rima; Bose, Dipro; Pal, Amit

2017-04-01

YghJ, also known as SslE (Secreted and surface associated lipoprotein) is a cell surface associated and secreted lipoprotein harbouring M60 metalloprotease domain. Though the gene is known to be conserved among both pathogenic and commensal Escherichia coli isolates, the expression and secretion of YghJ was found to be higher among diverse E. coli pathotypes. YghJ, secreted from intestinal pathogens such as enterotoxigenic E. coli (ETEC) and enteropathogenic E. coli (EPEC) has been demonstrated to possess mucinase activity and hence facilitates colonization of these enteric pathogens to intestinal epithelial cells. Importantly, YghJ is also reported to be secreted from extraintestinal pathogenic E. coli isolates. In our previous study we have shown that YghJ, purified from a neonatal septicemic E. coli isolate could trigger induction of various proinflammatory cytokines in vitro. This led us to investigate the role of YghJ in causing in vivo tissue hemorrhage. In the present study, we validate the earlier in vitro finding and have showed that YghJ can cause extensive tissue damage in mouse ileum and is also able to induce significant fluid accumulation in a dose dependent manner in a mouse ileal loop (MIL) assay. Hence, our present study not only confirms the pathogenic potential of YghJ in sepsis pathophysiology but also indicates the enterotoxic ability of YghJ which makes it an important virulence determinant of intestinal pathogenic E. coli. Copyright © 2017 Elsevier Ltd. All rights reserved.

Cerebellar level of neurotransmitters in rats exposed to paracetamol during development.

Science.gov (United States)

Blecharz-Klin, Kamilla; Joniec-Maciejak, Ilona; Jawna-Zboińska, Katarzyna; Pyrzanowska, Justyna; Piechal, Agnieszka; Wawer, Adriana; Widy-Tyszkiewicz, Ewa

2016-12-01

The present study was designed to clarify the effect of prenatal and postnatal paracetamol administration on the neurotransmitter level and balance of amino acids in the cerebellum. Biochemical analysis to determine the concentration of neurotransmitters in this brain structure was performed on two-month-old Wistar male rats previously exposed to paracetamol in doses of 5 (P5, n=10) or 15mg/kg (P15, n=10) throughout the entire prenatal period, lactation and until the completion of the second month of life, when the experiment was terminated. Control animals were given tapped water (Con, n=10). The cerebellar concentration of monoamines, their metabolites and amino acids were assayed using High Performance Liquid Chromatography (HPLC). The present experiment demonstrates that prenatal and postnatal paracetamol exposure results in modulation of cerebellar neurotransmission with changes concerning mainly 5-HIAA and MHPG levels. The effect of paracetamol on monoaminergic neurotransmission in the cerebellum is reflected by changes in the level of catabolic end-products of serotonin (5-HIAA) and noradrenaline (MHPG) degradation. Further work is required to define the mechanism of action and impact of prenatal and postnatal exposure to paracetamol in the cerebellum and other structures of the central nervous system (CNS). Copyright © 2016 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Decrease of glucose-induced insulin secretion of rat pancreatic islets after irradiation in vitro

Energy Technology Data Exchange (ETDEWEB)

Heinzmann, D; Nadrowitz, R; Besch, W; Schmidt, W; Hahn, H J [Zentralinstitut fuer Diabetes, Karlsburg (German Democratic Republic); Ernst-Moritz-Arndt-Universitaet, Greifswald (German Democratic Republic). Radiologische Klinik)

1983-01-01

In vitro irradiation of rat pancreatic islets up to a dose of 2.5 Gy did neither alter glucose- nor isobutylmethyl xanthine (IBMX)-induced insulin secretion. Insulin as well as glucagon content of irradiated islets corresponded to that of the control tissue. So it was in islets irradiated with 25 Gy which were characterized by a decreased insulin secretion in the presence of glucose and IBMX, respectively. There was no indication of an enhanced hormone output in the radiation medium and it is to be suggested that higher radiation doses affect the insulin release of pancreatic islets in vitro. This must be taken into consideration for radioimmunosuppression experiments.

Mining secreted proteins that function in pepper fruit development and ripening using a yeast secretion trap (YST)

Energy Technology Data Exchange (ETDEWEB)

Lee, Je Min, E-mail: jemin@knu.ac.kr [Department of Plant Science, College of Agriculture and Life Sciences, Seoul National University, Seoul (Korea, Republic of); Department of Horticultural Science, Kyungpook National University, Daegu (Korea, Republic of); Lee, Sang-Jik [Biotechnology Institute, Nongwoo Bio Co, Ltd, Yeoju (Korea, Republic of); Department of Plant Biology, Cornell University, Ithaca, NY (United States); Rose, Jocelyn K.C. [Department of Plant Biology, Cornell University, Ithaca, NY (United States); Yeam, Inhwa [Department of Horticulture and Breeding, Andong National University, Andong (Korea, Republic of); Kim, Byung-Dong [Department of Plant Science, College of Agriculture and Life Sciences, Seoul National University, Seoul (Korea, Republic of)

2014-04-18

Highlights: • Yeast secretion trap (YST) is a valuable tool for mining secretome. • A total of 80 secreted proteins are newly identified via YST in pepper fruits. • The secreted proteins are differentially regulated during pepper development and ripening. • Transient GFP-fusion assay and in planta secretion trap can effectively validate the secretion of proteins. - Abstract: Plant cells secrete diverse sets of constitutively- and conditionally-expressed proteins under various environmental and developmental states. Secreted protein populations, or secretomes have multiple functions, including defense responses, signaling, metabolic processes, and developmental regulation. To identify genes encoding secreted proteins that function in fruit development and ripening, a yeast secretion trap (YST) screen was employed using pepper (Capsicum annuum) fruit cDNAs. The YST screen revealed 80 pepper fruit-related genes (CaPFRs) encoding secreted proteins including cell wall proteins, several of which have not been previously described. Transient GFP-fusion assay and an in planta secretion trap were used to validate the secretion of proteins encoded by selected YST clones. In addition, RNA gel blot analyses provided further insights into their expression and regulation during fruit development and ripening. Integrating our data, we conclude that the YST provides a valuable functional genomics tool for the identification of substantial numbers of novel secreted plant proteins that are associated with biological processes, including fruit development and ripening.

Mining secreted proteins that function in pepper fruit development and ripening using a yeast secretion trap (YST)

International Nuclear Information System (INIS)

Lee, Je Min; Lee, Sang-Jik; Rose, Jocelyn K.C.; Yeam, Inhwa; Kim, Byung-Dong

2014-01-01

Highlights: • Yeast secretion trap (YST) is a valuable tool for mining secretome. • A total of 80 secreted proteins are newly identified via YST in pepper fruits. • The secreted proteins are differentially regulated during pepper development and ripening. • Transient GFP-fusion assay and in planta secretion trap can effectively validate the secretion of proteins. - Abstract: Plant cells secrete diverse sets of constitutively- and conditionally-expressed proteins under various environmental and developmental states. Secreted protein populations, or secretomes have multiple functions, including defense responses, signaling, metabolic processes, and developmental regulation. To identify genes encoding secreted proteins that function in fruit development and ripening, a yeast secretion trap (YST) screen was employed using pepper (Capsicum annuum) fruit cDNAs. The YST screen revealed 80 pepper fruit-related genes (CaPFRs) encoding secreted proteins including cell wall proteins, several of which have not been previously described. Transient GFP-fusion assay and an in planta secretion trap were used to validate the secretion of proteins encoded by selected YST clones. In addition, RNA gel blot analyses provided further insights into their expression and regulation during fruit development and ripening. Integrating our data, we conclude that the YST provides a valuable functional genomics tool for the identification of substantial numbers of novel secreted plant proteins that are associated with biological processes, including fruit development and ripening

Paecilomyces tenuipes extract prevents depression-like behaviors in chronic unpredictable mild stress-induced rat model via modulation of neurotransmitters.

Science.gov (United States)

Liu, Chungang; Wang, Juan; Xu, Shiqi; An, Shengshu; Tang, Siying; He, Jian; Liu, Yang; Lee, Robert J; Wang, Di

2017-08-01

The medicinal fungus Paecilomyces tenuipes exhibits a variety of pharmacological effects, including antidepressive effects. The chronic unpredictable mild stress (CUMS)‑induced rat model has served an important role in studies involving antidepressants screening. The aim of the present study was to evaluate the antidepressant‑like activity of P. tenuipes N45 aqueous extract (PTNE) in a CUMS‑induced rat model of behavioral despair depression. Following 4 weeks of PTNE treatment, behavioral tests were conducted to investigate the antidepressant‑like activities, and the levels of neurotransmitters and hormones in blood and hypothalamus were measured. The results demonstrated that PTNE treatment significantly increased movement in the forced running test, whereas the immobility time was reduced in the hotplate test and the forced swim test in depression‑model rats. PTNE treatment was able to normalize the levels of hormones and neurotransmitters in serum and hypothalamus of CUMS rats. The data demonstrated that PTNE treatment may be a potential pharmaceutical agent in treatment‑resistant depression, and the effects of PTNE may be partly mediated through normalizing the levels of neurotransmitters.

Immunoglobins in mammary secretions

DEFF Research Database (Denmark)

Hurley, W L; Theil, Peter Kappel

2013-01-01

Immunoglobulins secreted in colostrum and milk by the lactating mammal are major factors providing immune protection to the newborn. Immunoglobulins in mammary secretions represent the cumulative immune response of the lactating animal to exposure to antigenic stimulation that occurs through...... the immunoglobulins found in mammary secretions in the context of their diversity of structure, origin, mechanisms of transfer, and function....

A simple LC-MS/MS method for quantitative analysis of underivatized neurotransmitters in rats urine: assay development, validation and application in the CUMS rat model.

Science.gov (United States)

Zhai, Xue-jia; Chen, Fen; Zhu, Chao-ran; Lu, Yong-ning

2015-11-01

Many amino acid neurotransmitters in urine are associated with chronic stress as well as major depressive disorders. To better understand depression, an analytical LC-MS/MS method for the simultaneous determination of 11 underivatized neurotransmitters (4-aminohippurate, 5-HIAA, glutamate, glutamine, hippurate, pimelate, proline, tryptophan, tyramine, tyrosine and valine) in a single analytical run was developed. The advantage of this method is the simple preparation in that there is no need to deconjugate the urine samples. The quantification range was 25-12,800 ng mL(-1) with >85.8% recovery for all analytes. The nocturnal urine concentrations of the 11 neurotransmitters in chronic unpredictable mild stress (CUMS) model rats and control group (n = 12) were analyzed. A series of significant changes in urinary excretion of neurotransmitters could be detected: the urinary glutamate, glutamine, hippurate and tyramine concentrations were significantly lower in the CUMS group. In addition, the urinary concentrations of tryptophan as well as tyrosine were significantly higher in chronically stressed rats. This method allows the assessment of the neurotransmitters associated with CUMS in rat urine in a single analytical run, making it suitable for implementation as a routine technique in depression research. Copyright © 2015 John Wiley & Sons, Ltd.

Dissecting the Wnt secretion pathway: key questions on the modification and intracellular trafficking of Wnt proteins

NARCIS (Netherlands)

Harterink, M.; Korswagen, H.C.

2012-01-01

The Wnt family of signalling proteins has essential functions in development and adult tissue homoeostasis throughout the animal kingdom. Although signalling cascades triggered by Wnt proteins have been extensively studied, much remains to be learned about how Wnts are produced and secreted. Over

In vitro cholesteatoma growth and secretion of cytokines.

Science.gov (United States)

Helgaland, Tore; Engelen, Bart; Olsnes, Carla; Aarstad, Hans Jørgen; Vassbotn, Flemming S

2010-07-01

Our results show a significant difference between skin and cholesteatoma biology in vitro. Cholesteatoma disease is a process of destruction characterized by uncontrolled growth of squamous epithelial cells in the middle ear or temporal bone. The pathophysiology behind the cholesteatoma development is controversial, and the mechanisms driving the cholesteatoma growth, migration and destructive properties is still unclear. We aimed to provide a method to study the effect of various compounds on cholesteatoma and skin tissue growth, as well as to further investigate the biological differences between normal skin and cholesteatoma tissue. We have established a method to study cholesteatoma biopsy tissue in vitro. Cholesteatoma tissues from patients undergoing surgery for chronic otitis were grown in culture medium and compared to growth patterns and behaviour of normal retroauricular skin. Conditioned medium was analysed for various secreted cytokines. We found a radial outgrowth of keratinocyte epithelium from the circular biopsies. After 5 days of culture we found a significant growth of both cholesteatoma and skin-derived cells. Cholesteatoma samples showed higher growth rate as compared with skin control cultures from the same patient. Moreover, the cholesteatoma cells showed higher production of monocyte chemoattractant protein-1 (MCP-1) and interleukin (IL)-6 as compared with normal skin.

Matroids and quantum-secret-sharing schemes

International Nuclear Information System (INIS)

Sarvepalli, Pradeep; Raussendorf, Robert

2010-01-01

A secret-sharing scheme is a cryptographic protocol to distribute a secret state in an encoded form among a group of players such that only authorized subsets of the players can reconstruct the secret. Classically, efficient secret-sharing schemes have been shown to be induced by matroids. Furthermore, access structures of such schemes can be characterized by an excluded minor relation. No such relations are known for quantum secret-sharing schemes. In this paper we take the first steps toward a matroidal characterization of quantum-secret-sharing schemes. In addition to providing a new perspective on quantum-secret-sharing schemes, this characterization has important benefits. While previous work has shown how to construct quantum-secret-sharing schemes for general access structures, these schemes are not claimed to be efficient. In this context the present results prove to be useful; they enable us to construct efficient quantum-secret-sharing schemes for many general access structures. More precisely, we show that an identically self-dual matroid that is representable over a finite field induces a pure-state quantum-secret-sharing scheme with information rate 1.

Extracellular secretion of recombinant proteins

Science.gov (United States)

Linger, Jeffrey G.; Darzins, Aldis

2014-07-22

Nucleic acids encoding secretion signals, expression vectors containing the nucleic acids, and host cells containing the expression vectors are disclosed. Also disclosed are polypeptides that contain the secretion signals and methods of producing polypeptides, including methods of directing the extracellular secretion of the polypeptides. Exemplary embodiments include cellulase proteins fused to secretion signals, methods to produce and isolate these polypeptides, and methods to degrade lignocellulosic biomass.

Euglycemia Restoration by Central Leptin in Type 1 Diabetes Requires STAT3 Signaling but Not Fast-Acting Neurotransmitter Release.

Science.gov (United States)

Xu, Yuanzhong; Chang, Jeffrey T; Myers, Martin G; Xu, Yong; Tong, Qingchun

2016-04-01

Central leptin action is sufficient to restore euglycemia in insulinopenic type 1 diabetes (T1D); however, the underlying mechanism remains poorly understood. To examine the role of intracellular signal transducer and activator of transcription 3 (STAT3) pathways, we used LepRs/s mice with disrupted leptin-phosphorylated STAT3 signaling to test the effect of central leptin on euglycemia restoration. These mice developed streptozocin-induced T1D, which was surprisingly not associated with hyperglucagonemia, a typical manifestation in T1D. Further, leptin action on euglycemia restoration was abrogated in these mice, which was associated with refractory hypercorticosteronemia. To examine the role of fast-acting neurotransmitters glutamate and γ-aminobutyric acid (GABA), two major neurotransmitters in the brain, from leptin receptor (LepR) neurons, we used mice with disrupted release of glutamate, GABA, or both from LepR neurons. Surprisingly, all mice responded normally to leptin-mediated euglycemia restoration, which was associated with expected correction from hyperglucagonemia and hyperphagia. In contrast, mice with loss of glutamate and GABA appeared to develop an additive obesity effect over those with loss of single neurotransmitter release. Thus, our study reveals that STAT3 signaling, but not fast-acting neurotransmitter release, is required for leptin action on euglycemia restoration and that hyperglucagonemia is not required for T1D. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

RESTRAIN OF FEAR: PARTICIPATION OF GABA NEUROTRANSMITTER SYSTEM

Directory of Open Access Journals (Sweden)

Galina I. Shulgina

2013-07-01

Full Text Available In experiences on rats in the conditions of free behavior at development of a conditioned of passive avoidanсe reflex (the first series and a defensive reflex and a conditional inhibition (the second series it is revealed, and elaboration of internal inhibition and Phenibut – a nonspecific agonist of GAMKA and GAMKB receptors cause in experimental animals weakening of freezing arising in a dangerous situation, and a disinhibition of research behavior. Results of experiences in the accounting of data of the literature allow to assume that both factors, and elaboration of internal inhibition, and Phenibut weaken freezing – the phenomenon used in experiments as a biological analog of fear, owing to increase of level of activity of the GABA neurotransmitter system of a brain.

Pituitary-hormone secretion by thyrotropinomas.

Science.gov (United States)

Roelfsema, Ferdinand; Kok, Simon; Kok, Petra; Pereira, Alberto M; Biermasz, Nienke R; Smit, Jan W; Frolich, Marijke; Keenan, Daniel M; Veldhuis, Johannes D; Romijn, Johannes A

2009-01-01

Hormone secretion by somatotropinomas, corticotropinomas and prolactinomas exhibits increased pulse frequency, basal and pulsatile secretion, accompanied by greater disorderliness. Increased concentrations of growth hormone (GH) or prolactin (PRL) are observed in about 30% of thyrotropinomas leading to acromegaly or disturbed sexual functions beyond thyrotropin (TSH)-induced hyperthyroidism. Regulation of non-TSH pituitary hormones in this context is not well understood. We there therefore evaluated TSH, GH and PRL secretion in 6 patients with up-to-date analytical and mathematical tools by 24-h blood sampling at 10-min intervals in a clinical research laboratory. The profiles were analyzed with a new deconvolution method, approximate entropy, cross-approximate entropy, cross-correlation and cosinor regression. TSH burst frequency and basal and pulsatile secretion were increased in patients compared with controls. TSH secretion patterns in patients were more irregular, but the diurnal rhythm was preserved at a higher mean with a 2.5 h phase delay. Although only one patient had clinical acromegaly, GH secretion and IGF-I levels were increased in two other patients and all three had a significant cross-correlation between the GH and TSH. PRL secretion was increased in one patient, but all patients had a significant cross-correlation with TSH and showed decreased PRL regularity. Cross-ApEn synchrony between TSH and GH did not differ between patients and controls, but TSH and PRL synchrony was reduced in patients. We conclude that TSH secretion by thyrotropinomas shares many characteristics of other pituitary hormone-secreting adenomas. In addition, abnormalities in GH and PRL secretion exist ranging from decreased (joint) regularity to overt hypersecretion, although not always clinically obvious, suggesting tumoral transformation of thyrotrope lineage cells.

A novel surface modification on calcium polyphosphate scaffold for articular cartilage tissue engineering

International Nuclear Information System (INIS)

Lien, S.-M.; Liu, C.-K.; Huang, T.-J.

2007-01-01

The surface of porous three-dimensional (3D) calcium polyphosphate (CPP) scaffold was modified by treatment of quenching-after-sintering in the fabrication process. Scanning electron microscopic examination and degradation tests confirmed a new type of surface modification. A rotary-shaking culture was compared to that of a stationary culture and the results showed that rotary shaking led to enhanced extracellular matrices (ECM) secretion of both proteoglycans and collagen. Rotary-shaking cultured results showed that the quenching-treated CPP scaffold produced a better cartilage tissue, with both proteoglycans and collagen secretions enhanced, than the air-cooled-after-sintering scaffolds. Moreover, β-CPP scaffolds were better for the ECM secretion of both proteoglycans and collagen than the β-CPP + γ-CPP multiphase scaffold. However, the multiphase scaffold led to higher growth rate than that of β-CPP scaffold; the quenching-after-sintering treatment reversed this. In addition, the ECM secretions of both proteoglycans and collagen in the quenching-treated β-CPP scaffold were higher than those in the air-cooled one. Thus, the novel treatment of quenching-after-sintering has shown merits to the porous 3D CPP scaffolds for articular cartilage tissue engineering

In vitro and in vivo assessment of oral autologous artificial connective tissue characteristics that influence its performance as a graft.

Science.gov (United States)

Fontanilla, Marta Raquel; Espinosa, Lady Giovanna

2012-09-01

Several studies have evaluated proteins secreted by fibroblasts comprising skin substitutes, finding that they are secreted in combinations and concentrations that promote wound healing. However, assessment of proteins secreted by oral fibroblasts forming a part of oral substitutes is scarce. In our previous work, collagen type-I scaffolds (CSs) and autologous artificial connective tissue (AACT) were produced and implanted in rabbit oral lesions, evidencing that AACT outperforms CS. The present work determined the secreted factor profile of AACT in the time of grafting as well as that of the AACT embedded in the clot. It also evaluated the proliferation and viability of AACT fibroblasts to establish the dwell time of these cells in the grafted area. Finally, it assessed whether CS, AACT, and clot-embedded AACT increase fibroblast recruitment induced by a fibrin clot, because the cell migratory response has been associated with the wound-healing outcome. We found that some of the factors secreted by AACT fibroblasts are significantly different from those secreted by clot-embedded AACT fibroblasts. Also, that the profile of proteins secreted by AACT fibroblasts and clot-embedded AACT fibroblasts is different from already reported protein secretion profiles of other engineered tissues used in treating oral mucosa wounds. It was also found that AACT fibroblasts are viable when grafted and remain in the treated area for almost 2 weeks, and that the migratory response of fibroblasts to tissue-substitute stimulus is significantly less than the migratory response induced by the clot alone. Overall, data suggest that AACT secretion of proteins is modulated by three-dimensionality and environment factors. This bioactivity and the fact that AACT does not increase fibroblast migration can be held accountable for AACT's good performance as a graft.

Semiquantum secret sharing using entangled states

International Nuclear Information System (INIS)

Li Qin; Chan, W. H.; Long Dongyang

2010-01-01

Secret sharing is a procedure for sharing a secret among a number of participants such that only the qualified subsets of participants have the ability to reconstruct the secret. Even in the presence of eavesdropping, secret sharing can be achieved when all the members are quantum. So what happens if not all the members are quantum? In this paper, we propose two semiquantum secret sharing protocols by using maximally entangled Greenberger-Horne-Zeilinger-type states in which quantum Alice shares a secret with two classical parties, Bob and Charlie, in a way that both parties are sufficient to obtain the secret, but one of them cannot. The presented protocols are also shown to be secure against eavesdropping.

The Nitric Oxide Donor SNAP-Induced Amino Acid Neurotransmitter Release in Cortical Neurons. Effects of Blockers of Voltage-Dependent Sodium and Calcium Channels

Science.gov (United States)

Merino, José Joaquín; Arce, Carmen; Naddaf, Ahmad; Bellver-Landete, Victor; Oset-Gasque, Maria Jesús; González, María Pilar

2014-01-01

Background The discovery that nitric oxide (NO) functions as a signalling molecule in the nervous system has radically changed the concept of neuronal communication. NO induces the release of amino acid neurotransmitters but the underlying mechanisms remain to be elucidated. Findings The aim of this work was to study the effect of NO on amino acid neurotransmitter release (Asp, Glu, Gly and GABA) in cortical neurons as well as the mechanism underlying the release of these neurotransmitters. Cortical neurons were stimulated with SNAP, a NO donor, and the release of different amino acid neurotransmitters was measured by HPLC. The involvement of voltage dependent Na+ and Ca2+ channels as well as cGMP in its mechanism of action was evaluated. Conclusions Our results indicate that NO induces release of aspartate, glutamate, glycine and GABA in cortical neurons and that this release is inhibited by ODQ, an inhibitor of soluble guanylate cyclase. Thus, the NO effect on amino acid neurotransmission could be mediated by cGMP formation in cortical neurons. Our data also demonstrate that the Na+ and Ca2+ voltage- dependent calcium channels are involved in the NO effects on cortical neurons. PMID:24598811

The nitric oxide donor SNAP-induced amino acid neurotransmitter release in cortical neurons. Effects of blockers of voltage-dependent sodium and calcium channels.

Science.gov (United States)

Merino, José Joaquín; Arce, Carmen; Naddaf, Ahmad; Bellver-Landete, Victor; Oset-Gasque, Maria Jesús; González, María Pilar

2014-01-01

The discovery that nitric oxide (NO) functions as a signalling molecule in the nervous system has radically changed the concept of neuronal communication. NO induces the release of amino acid neurotransmitters but the underlying mechanisms remain to be elucidated. The aim of this work was to study the effect of NO on amino acid neurotransmitter release (Asp, Glu, Gly and GABA) in cortical neurons as well as the mechanism underlying the release of these neurotransmitters. Cortical neurons were stimulated with SNAP, a NO donor, and the release of different amino acid neurotransmitters was measured by HPLC. The involvement of voltage dependent Na+ and Ca2+ channels as well as cGMP in its mechanism of action was evaluated. Our results indicate that NO induces release of aspartate, glutamate, glycine and GABA in cortical neurons and that this release is inhibited by ODQ, an inhibitor of soluble guanylate cyclase. Thus, the NO effect on amino acid neurotransmission could be mediated by cGMP formation in cortical neurons. Our data also demonstrate that the Na+ and Ca2+ voltage- dependent calcium channels are involved in the NO effects on cortical neurons.

The nitric oxide donor SNAP-induced amino acid neurotransmitter release in cortical neurons. Effects of blockers of voltage-dependent sodium and calcium channels.

Directory of Open Access Journals (Sweden)

José Joaquín Merino

Full Text Available The discovery that nitric oxide (NO functions as a signalling molecule in the nervous system has radically changed the concept of neuronal communication. NO induces the release of amino acid neurotransmitters but the underlying mechanisms remain to be elucidated.The aim of this work was to study the effect of NO on amino acid neurotransmitter release (Asp, Glu, Gly and GABA in cortical neurons as well as the mechanism underlying the release of these neurotransmitters. Cortical neurons were stimulated with SNAP, a NO donor, and the release of different amino acid neurotransmitters was measured by HPLC. The involvement of voltage dependent Na+ and Ca2+ channels as well as cGMP in its mechanism of action was evaluated.Our results indicate that NO induces release of aspartate, glutamate, glycine and GABA in cortical neurons and that this release is inhibited by ODQ, an inhibitor of soluble guanylate cyclase. Thus, the NO effect on amino acid neurotransmission could be mediated by cGMP formation in cortical neurons. Our data also demonstrate that the Na+ and Ca2+ voltage- dependent calcium channels are involved in the NO effects on cortical neurons.

Three Gaseous Neurotransmitters, Nitric oxide, Carbon Monoxide, and Hydrogen Sulfide, Are Involved in the Neurogenic Relaxation Responses of the Porcine Internal Anal Sphincter.

Science.gov (United States)

Folasire, Oladayo; Mills, Kylie A; Sellers, Donna J; Chess-Williams, Russ

2016-01-31

The internal anal sphincter (IAS) plays an important role in maintaining continence and a number of neurotransmitters are known to regulate IAS tone. The aim of this study was to determine the relative importance of the neurotransmitters involved in the relaxant and contractile responses of the porcine IAS. Responses of isolated strips of IAS to electrical field stimulation (EFS) were obtained in the absence and presence of inhibitors of neurotransmitter systems. Contractile responses of the sphincter to EFS were unaffected by the muscarinic receptor antagonist, atropine (1 μM), but were almost completely abolished by the adrenergic neuron blocker guanethidine (10 μM). Contractile responses were also reduced (by 45% at 5 Hz, P 40-50% reduction), zinc protoprophyrin IX (10 μM), an inhibitor of carbon monoxide synthesis (20-40% reduction), and also propargylglycine (30 μM) and aminooxyacetic acid (30 μM), inhibitors of hydrogen sulphide synthesis (15-20% reduction). Stimulation of IAS efferent nerves releases excitatory and inhibitory neurotransmitters: noradrenaline is the predominant contractile transmitter with a smaller component from ATP, whilst 3 gases mediate relaxation responses to EFS, with the combined contributions being nitric oxide > carbon monoxide > hydrogen sulfide.

Probabilistic Infinite Secret Sharing

OpenAIRE

Csirmaz, László

2013-01-01

The study of probabilistic secret sharing schemes using arbitrary probability spaces and possibly infinite number of participants lets us investigate abstract properties of such schemes. It highlights important properties, explains why certain definitions work better than others, connects this topic to other branches of mathematics, and might yield new design paradigms. A probabilistic secret sharing scheme is a joint probability distribution of the shares and the secret together with a colle...

The 'sniffer-patch' technique for detection of neurotransmitter release.

Science.gov (United States)

Allen, T G

1997-05-01

A wide variety of techniques have been employed for the detection and measurement of neurotransmitter release from biological preparations. Whilst many of these methods offer impressive levels of sensitivity, few are able to combine sensitivity with the necessary temporal and spatial resolution required to study quantal release from single cells. One detection method that is seeing a revival of interest and has the potential to fill this niche is the so-called 'sniffer-patch' technique. In this article, specific examples of the practical aspects of using this technique are discussed along with the procedures involved in calibrating these biosensors to extend their applications to provide quantitative, in addition to simple qualitative, measurements of quantal transmitter release.

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 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....

Polymorphisms of genes in neurotransmitter systems were associated with alcohol use disorders in a Tibetan population.

Directory of Open Access Journals (Sweden)

Yan Xu

Full Text Available Studies of linkage and association in various ethnic populations have revealed many predisposing genes of multiple neurotransmitter systems for alcohol use disorders (AUD. However, evidence often is contradictory regarding the contribution of most candidate genes to the susceptibility of AUD. We, therefore, performed a case-control study to investigate the possible associations of genes selected from multiple neurotransmitter systems with AUD in a homogeneous Tibetan community population in China. AUD cases (N = 281 with an alcohol use disorder identification test (AUDIT score ≥10, as well as healthy controls (N = 277 with an AUDIT score ≤5, were recruited. All participants were genotyped for 366 single nucleotide polymorphisms (SNPs of 34 genes selected from those involved in neurotransmitter systems. Association analyses were performed using PLINK version 1.07 software. Allelic analyses before adjustment for multiple tests showed that 15 polymorphisms within seven genes were associated with AUD (p<0.05. After adjustment for the number of SNPs genotyped within each gene, only the association of a single marker (rs10044881 in HTR4 remained statistically significant. Haplotype analysis for two SNPs in HTR4 (rs17777298 and rs10044881 showed that the haplotype AG was significantly associated with the protective effect for AUD. In conclusion, the present study discovered that the HTR4 gene may play a marked role in the pathogenesis of AUD. In addition, this Tibetan population sample marginally replicated previous evidence regarding the associations of six genes in AUD.

Predator Exposure/Psychosocial Stress Animal Model of Post-Traumatic Stress Disorder Modulates Neurotransmitters in the Rat Hippocampus and Prefrontal Cortex

Science.gov (United States)

Wilson, C. Brad; Ebenezer, Philip J.; McLaughlin, Leslie D.; Francis, Joseph

2014-01-01

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 cause a

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

Measurement of neurotransmitters with positron emission tomography

Energy Technology Data Exchange (ETDEWEB)

Laruelle, M.; Erritzoe, D.; Abi-Dargham, A.; Huang, Y. [Columbia Univ., Coll. of Physicians and Surgeons, Dept. of Psychiatry and Radiology, New York, NY (United States)

2003-09-01

Over the last decade several groups have provided evidence that PET and SPECT neuro-receptor imaging techniques might be applied to measure fluctuations of dopamine (DA) synaptic concentrations in the living human brain. It is generally believed that changes in the in vivo binding of radioligands following acute changes in transmitter levels are driven by binding competition. These techniques have been very successful in giving dynamic information regarding DA transmission. However, the development of similar techniques to study other neurotransmitter systems has proven difficult. This review paper first summarizes endogenous competition studies performed in animals and humans. The validity of the model underlying the interpretation of these data is critically assessed. Emerging data suggest that simple binding competition might not be the only phenomenon involved in these interactions; receptor trafficking might play an important role. A better understanding of the radioligand properties that determine sensitivity to endogenous molecules might facilitate the selective development of this type of radiotracer. (authors)

Neuronal uptake and metabolism of 2- and 6-fluorodopamine: false neurotransmitters for positron emission tomographic imaging of sympathetically innervated tissues

Energy Technology Data Exchange (ETDEWEB)

Eisenhofer, G.; Hovevey-Sion, D.; Kopin, I.J.; Miletich, R.; Kirk, K.L.; Finn, R.; Goldstein, D.S.

1989-01-01

The neuronal uptake and metabolism of 2-fluorodopamine (2F-dopamine), 6-fluorodopamine (6F-dopamine) and tritium-labeled dopamine were compared in heart, submaxillary gland and spleen of rats to assess the utility of 18F-labeled 2F- or 6F-dopamine for positron emission tomographic imaging of sympathetically innervated tissues. Tritiated dopamine with and without 2F- or 6F-dopamine, or tritiated 2F-dopamine alone, were injected i.v. into rats that were or were not pretreated with desipramine to block catecholamine neuronal uptake or with reserpine to block vesicular translocation of catecholamines. Tissue and plasma samples were obtained at intervals up to 1 hr after injections. At 1 hr after injection of tritiated dopamine, tritium-labeled norepinephrine, dopamine, dihydroxyphenylacetic acid and dihydroxyphenylglucol accounted for less than 2% of the tritium in plasma but up to 92% of that in tissues; tritiated norepinephrine accounted for 70% or more of the tritium in tissues. In contrast, at 1 hr after injection of tritiated 2F-dopamine, tritiated 2F-norepinephrine accounted for 30 to 46% of the tritium in tissues. Desipramine and reserpine pretreatment blocked the tissue accumulation of tritiated and fluorinated dopamine as well as their dihydroxy-metabolites, indicating that accumulation of exogenous norepinephrine and dopamine analogs was within sympathetic storage vesicles. Relative to the doses of dopamine precursors, less 2F- and 6F-norepinephrine accumulated in tissues than tritiated norepinephrine, due largely to inefficient beta-hydroxylation of fluorinated dopamine.

Neuronal uptake and metabolism of 2- and 6-fluorodopamine: false neurotransmitters for positron emission tomographic imaging of sympathetically innervated tissues

International Nuclear Information System (INIS)

Eisenhofer, G.; Hovevey-Sion, D.; Kopin, I.J.; Miletich, R.; Kirk, K.L.; Finn, R.; Goldstein, D.S.

1989-01-01

The neuronal uptake and metabolism of 2-fluorodopamine (2F-dopamine), 6-fluorodopamine (6F-dopamine) and tritium-labeled dopamine were compared in heart, submaxillary gland and spleen of rats to assess the utility of 18F-labeled 2F- or 6F-dopamine for positron emission tomographic imaging of sympathetically innervated tissues. Tritiated dopamine with and without 2F- or 6F-dopamine, or tritiated 2F-dopamine alone, were injected i.v. into rats that were or were not pretreated with desipramine to block catecholamine neuronal uptake or with reserpine to block vesicular translocation of catecholamines. Tissue and plasma samples were obtained at intervals up to 1 hr after injections. At 1 hr after injection of tritiated dopamine, tritium-labeled norepinephrine, dopamine, dihydroxyphenylacetic acid and dihydroxyphenylglucol accounted for less than 2% of the tritium in plasma but up to 92% of that in tissues; tritiated norepinephrine accounted for 70% or more of the tritium in tissues. In contrast, at 1 hr after injection of tritiated 2F-dopamine, tritiated 2F-norepinephrine accounted for 30 to 46% of the tritium in tissues. Desipramine and reserpine pretreatment blocked the tissue accumulation of tritiated and fluorinated dopamine as well as their dihydroxy-metabolites, indicating that accumulation of exogenous norepinephrine and dopamine analogs was within sympathetic storage vesicles. Relative to the doses of dopamine precursors, less 2F- and 6F-norepinephrine accumulated in tissues than tritiated norepinephrine, due largely to inefficient beta-hydroxylation of fluorinated dopamine

The transcription factor ERG increases expression of neurotransmitter receptors on prostate cancer cells

International Nuclear Information System (INIS)

Kissick, Haydn T.; On, Seung T.; Dunn, Laura K.; Sanda, Martin G.; Asara, John M.; Pellegrini, Kathryn L.; Noel, Jonathan K.; Arredouani, Mohamed S.

2015-01-01

The TMPRSS2-ERG gene fusion occurs in about half of prostate cancer (PCa) cases and results in overexpression of the transcription factor ERG. Overexpression of ERG has many effects on cellular function. However, how these changes enhance cell growth and promote tumor development is unclear. To investigate the role of ERG, LNCaP and PC3 cells were transfected with ERG and gene expression and metabolic profile were analyzed. Our data show that expression of ERG induces overexpression of many nicotinicacetylcholine receptors (nAChRs). In addition, metabolic profiling by LC-MS/MS revealed elevated production of several neurotransmitters in cells expressing ERG. Consistently, treatment of ERG-expressing cells with nicotine induced elevated calcium influx, GSK3β (Ser9) phosphorylation and cell proliferation. Finally, we show that PCa patientswho are smokers have larger tumors if their tumors are TMPRSS2-ERG gene fusion positive. Collectively, our data suggest that ERG sensitizes prostate tumor cells to neurotransmitter receptor agonists like nicotine. The online version of this article (doi:10.1186/s12885-015-1612-3) contains supplementary material, which is available to authorized users

Effects of occupational exposure to polychlorinated biphenyls on urinary metabolites of neurotransmitters: A cross-sectional and longitudinal perspective.

Science.gov (United States)

Putschögl, Franziska Maria; Gaum, Petra Maria; Schettgen, Thomas; Kraus, Thomas; Gube, Monika; Lang, Jessica

2015-07-01

Polychlorinated biphenyls (PCBs) are chemicals which were used for industrial purposes and are known to induce various adverse health effects. They are also known to be neurotoxic and numerous targets within the central nervous system have been identified in previous studies. Specifically, the neurotransmitters dopamine (DA) and norepinephrine (NE) are influenced by PCBs as indicated in studies involving animals. However, limited evidence has been published documenting PCB induced changes in the neurotransmitter system in humans. In the present study, we examined the association between a higher PCB body burden following occupational exposure and possible changes in human neurotransmitter metabolites. Within a medical surveillance programme called HELPcB (Health Effects in High-Level Exposure to PCB) that monitors adverse health effects of occupational PCB exposure, urine samples were obtained (n(T1) = 166; n(T2) = 177 and n(T3) = 141). The urinary concentrations of the metabolites homovanillic acid (HVA; for DA) and vanillylmandelic acid (VMA; for NE) were analyzed. Blood samples were obtained by vena puncture in order to determine the internal exposure to PCBs with human biomonitoring. A cross-sectional analysis indicated a significant negative effect of PCB exposure on HVA and VMA. Longitudinally, an initially higher exposure to higher chlorinated PCBs was followed by constant reduced HVA level over three consecutive years. Exploratory analyses show different long-term effects for different PCBs according to their chlorination degree. A higher exposure with lower chlorinated PCBs leads to an increase of VMA and HVA. Conversely, a higher exposure to all PCBs results in a reduction of HVA. This study, to our knowledge, is the first to document changes in neurotransmitter metabolites after occupational PCB exposure in humans. This finding advances evidence obtained from past research, and identifies one potential pathomechanism in the central dopaminergic system of

Nicotinic receptor-associated modulation of stimulatory and inhibitory neurotransmitters in NNK-induced adenocarcinoma of the lungs and pancreas

Science.gov (United States)

Al-Wadei, Hussein A. N.; Schuller, Hildegard M.

2012-01-01

Small airway-derived pulmonary adenocarcinoma (PAC) and pancreatic ductal adenocarcinoma (PDAC) are among the most common human cancers and smoking is a risk factor for both. Emerging research has identified cAMP signaling stimulated by the stress neurotransmitters adrenaline and noradrenaline as important stimulators of several adenocarcinomas, including PAC and PDAC. The nicotine-derived nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is a potent mutagen and the most powerful tobacco carcinogen. NNK is also an agonist for nicotinic acetylcholine receptors (nAChRs). Using hamster models of NNK-induced PAC and PDAC, we have tested the hypothesis that in analogy to chronic effects of nicotine in the brain, NNK may modulate the α7- and α4β2nAChRs, causing an increase in stress neurotransmitters and decrease in the inhibitory neurotransmitter γ-aminobutyric acid (GABA). In support of our hypothesis, immunoassays showed a significant increase in serum adrenaline/noradrenaline and increased intracellular cAMP in the cellular fraction of blood of NNK treated hamsters. Western blots were done with cells harvested by laser capture microcopy from control small airway epithelia, alveolar epithelia, pancreatic islet and pancreatic duct epithelia and from NNK-induced PACs and PDACs. The GABA synthesizing enzyme glutamate decarboxylase 65 (GAD65) and GABA were suppressed in NNK-induced PACs and PDACs whereas protein expression of the α7nAChR, α4nAChR as well as p-CREB and p-ERK1/2 were upregulated. These findings suggest, for the first time, that NNK-induced alterations in regulatory nAChRs may contribute to the development of smoking-associated PAC and PDAC by disturbing the balance between cancer stimulating and inhibiting neurotransmitters. PMID:19274673

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

International Nuclear Information System (INIS)

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

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

Differential effects of ethanol on regional glutamatergic and GABAergic neurotransmitter pathways in mouse brain.

Science.gov (United States)

Tiwari, Vivek; Veeraiah, Pandichelvam; Subramaniam, Vaidyanathan; Patel, Anant Bahadur

2014-03-01

This study investigates the effects of ethanol on neuronal and astroglial metabolism using (1)H-[(13)C]-NMR spectroscopy in conjunction with infusion of [1,6-(13)C2]/[1-(13)C]glucose or [2-(13)C]acetate, respectively. A three-compartment metabolic model was fitted to the (13)C turnover of GluC3 , GluC4, GABAC 2, GABAC 3, AspC3 , and GlnC4 from [1,6-(13)C2 ]glucose to determine the rates of tricarboxylic acid (TCA) and neurotransmitter cycle associated with glutamatergic and GABAergic neurons. The ratio of neurotransmitter cycle to TCA cycle fluxes for glutamatergic and GABAegic neurons was obtained from the steady-state [2-(13)C]acetate experiment and used as constraints during the metabolic model fitting. (1)H MRS measurement suggests that depletion of ethanol from cerebral cortex follows zero order kinetics with rate 0.18 ± 0.04 μmol/g/min. Acute exposure of ethanol reduces the level of glutamate and aspartate in cortical region. GlnC4 labeling was found to be unchanged from a 15 min infusion of [2-(13)C]acetate suggesting that acute ethanol exposure does not affect astroglial metabolism in naive mice. Rates of TCA and neurotransmitter cycle associated with glutamatergic and GABAergic neurons were found to be significantly reduced in cortical and subcortical regions. Acute exposure of ethanol perturbs the level of neurometabolites and decreases the excitatory and inhibitory activity differentially across the regions of brain. Depletion of ethanol and its effect on brain functions were measured using (1)H and (1)H-[(13)C]-NMR spectroscopy in conjunction with infusion of (13)C-labeled substrates. Ethanol depletion from brain follows zero order kinetics. Ethanol perturbs level of glutamate, and the excitatory and inhibitory activity in mice brain. © 2013 International Society for Neurochemistry.

RSA-Based Secret Handshakes

OpenAIRE

Vergnaud , Damien

2006-01-01

A secret handshake mechanism allows two entities, members of a same group, to authenticate each other secretly. This primitive was introduced recently by Balfanz, Durfee, Shankar, Smetters, Staddon and Wong and, so far, all the schemes proposed are based on discrete log systems. This paper proposes three new secret handshake protocols secure against active impersonator and detector adversaries. Inspired by two RSA-based key agreement protocols introduced by Okamoto and Tanaka in 1989 and Gira...

Differential effect of combined lipase deficiency (cld/cld) on human hepatic lipase and lipoprotein lipase secretion.

Science.gov (United States)

Boedeker, J C; Doolittle, M H; White, A L

2001-11-01

Combined lipase deficiency (cld) is a recessively inherited disorder in mice associated with a deficiency of LPL and hepatic lipase (HL) activity. LPL is synthesized in cld tissues but is retained in the endoplasmic reticulum (ER), whereas mouse HL (mHL) is secreted but inactive. In this study we investigated the effect of cld on the secretion of human HL (hHL) protein mass and activity. Differentiated liver cell lines were derived from cld mice and their normal heterozygous (het) littermates by transformation of hepatocytes with SV40 large T antigen. After transient transfection with lipase expression constructs, secretion of hLPL activity from cld cells was only 12% of that from het cells. In contrast, the rate of secretion of hHL activity and protein mass per unit of expressed hHL mRNA was identical for the two cell lines. An intermediate effect was observed for mHL, with a 46% reduction in secretion of activity from cld cells. The ER glucosidase inhibitor, castanospermine, decreased secretion of both hLPL and hHL from het cells by approximately 70%, but by only approximately 45% from cld cells. This is consistent with data suggesting that cld may result from a reduced concentration of the ER chaperone calnexin. In conclusion, our results demonstrate a differential effect of cld on hLPL, mHL, and hHL secretion, suggesting differential requirements for activation and exit of the enzymes from the ER.

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.

Cross Talk between Adipose Tissue and Placenta in Obese and Gestational Diabetes Mellitus Pregnancies via Exosomes.

Science.gov (United States)

Jayabalan, Nanthini; Nair, Soumyalekshmi; Nuzhat, Zarin; Rice, Gregory E; Zuñiga, Felipe A; Sobrevia, Luis; Leiva, Andrea; Sanhueza, Carlos; Gutiérrez, Jaime Agustín; Lappas, Martha; Freeman, Dilys Jane; Salomon, Carlos

2017-01-01

Obesity is an important public health issue worldwide, where it is commonly associated with the development of metabolic disorders, especially insulin resistance (IR). Maternal obesity is associated with an increased risk of pregnancy complications, especially gestational diabetes mellitus (GDM). Metabolism is a vital process for energy production and the maintenance of essential cellular functions. Excess energy storage is predominantly regulated by the adipose tissue. Primarily made up of adipocytes, adipose tissue acts as the body's major energy reservoir. The role of adipose tissue, however, is not restricted to a "bag of fat." The adipose tissue is an endocrine organ, secreting various adipokines, enzymes, growth factors, and hormones that take part in glucose and lipid metabolism. In obesity, the greater portion of the adipose tissue comprises fat, and there is increased pro-inflammatory cytokine secretion, macrophage infiltration, and reduced insulin sensitivity. Obesity contributes to systemic IR and its associated metabolic complications. Similar to adipose tissue, the placenta is also an endocrine organ. During pregnancy, the placenta secretes various molecules to maintain pregnancy physiology. In addition, the placenta plays an important role in metabolism and exchange of nutrients between mother and fetus. Inflammation at the placenta may contribute to the severity of maternal IR and her likelihood of developing GDM and may also mediate the adverse consequences of obesity and GDM on the fetus. Interestingly, studies on maternal insulin sensitivity and secretion of placental hormones have not shown a positive correlation between these phenomena. Recently, a great interest in the field of extracellular vesicles (EVs) has been observed in the literature. EVs are produced by a wide range of cells and are present in all biological fluids. EVs are involved in cell-to-cell communication. Recent evidence points to an association between adipose tissue

Cross Talk between Adipose Tissue and Placenta in Obese and Gestational Diabetes Mellitus Pregnancies via Exosomes

Directory of Open Access Journals (Sweden)

Nanthini Jayabalan

2017-09-01

Full Text Available Obesity is an important public health issue worldwide, where it is commonly associated with the development of metabolic disorders, especially insulin resistance (IR. Maternal obesity is associated with an increased risk of pregnancy complications, especially gestational diabetes mellitus (GDM. Metabolism is a vital process for energy production and the maintenance of essential cellular functions. Excess energy storage is predominantly regulated by the adipose tissue. Primarily made up of adipocytes, adipose tissue acts as the body’s major energy reservoir. The role of adipose tissue, however, is not restricted to a “bag of fat.” The adipose tissue is an endocrine organ, secreting various adipokines, enzymes, growth factors, and hormones that take part in glucose and lipid metabolism. In obesity, the greater portion of the adipose tissue comprises fat, and there is increased pro-inflammatory cytokine secretion, macrophage infiltration, and reduced insulin sensitivity. Obesity contributes to systemic IR and its associated metabolic complications. Similar to adipose tissue, the placenta is also an endocrine organ. During pregnancy, the placenta secretes various molecules to maintain pregnancy physiology. In addition, the placenta plays an important role in metabolism and exchange of nutrients between mother and fetus. Inflammation at the placenta may contribute to the severity of maternal IR and her likelihood of developing GDM and may also mediate the adverse consequences of obesity and GDM on the fetus. Interestingly, studies on maternal insulin sensitivity and secretion of placental hormones have not shown a positive correlation between these phenomena. Recently, a great interest in the field of extracellular vesicles (EVs has been observed in the literature. EVs are produced by a wide range of cells and are present in all biological fluids. EVs are involved in cell-to-cell communication. Recent evidence points to an association between

Effect of Human Myotubes-Derived Media on Glucose-Stimulated Insulin Secretion

Directory of Open Access Journals (Sweden)

Maria L. Mizgier

2017-01-01

Full Text Available Fasting to postprandial transition requires a tight adjustment of insulin secretion to its demand, so tissue (e.g., skeletal muscle glucose supply is assured while hypo-/hyperglycemia are prevented. High muscle glucose disposal after meals is pivotal for adapting to increased glycemia and might drive insulin secretion through muscle-released factors (e.g., myokines. We hypothesized that insulin influences myokine secretion and then increases glucose-stimulated insulin secretion (GSIS. In conditioned media from human myotubes incubated with/without insulin (100 nmol/L for 24 h, myokines were qualitatively and quantitatively characterized using an antibody-based array and ELISA-based technology, respectively. C57BL6/J mice islets and Wistar rat beta cells were incubated for 24 h with control and conditioned media from noninsulin- and insulin-treated myotubes prior to GSIS determination. Conditioned media from insulin-treated versus nontreated myotubes had higher RANTES but lower IL6, IL8, and MCP1 concentration. Qualitative analyses revealed that conditioned media from noninsulin- and insulin-treated myotubes expressed 32 and 23 out of 80 myokines, respectively. Islets incubated with conditioned media from noninsulin-treated myotubes had higher GSIS versus control islets (p<0.05. Meanwhile, conditioned media from insulin-treated myotubes did not influence GSIS. In beta cells, GSIS was similar across conditions. In conclusion, factors being present in noninsulin-stimulated muscle cell-derived media appear to influence GSIS in mice islets.

Decrease of glucose-induced insulin secretion of pancreatic rat islets after irradiation in vitro

Energy Technology Data Exchange (ETDEWEB)

Heinzmann, D; Nadrowitz, R; Besch, W; Schmidt, W; Hahn, H J

1983-01-01

Irradiation of pancreatic rat islets up to a dose of 2.5 Gy did neither alter glucose-nor IBMX-induced insulin secretion studied in vitro. The insulin as well as glucagon content of irradiated islets were similar as in the control tissue. This was also true in islets irradiated with 25 Gy which were characterized by a decreased insulin secretion in the presence of glucose and IBMX, respectively. Since we did not find indications of an enhanced hormone output in the radiation medium, we want to suggest that higher irradiation doses affect insulin release of pancreatic islets in vitro. This observation has to be taken into account for application of radioimmunosuppression for transplantation.

Reversal of Type 1 Diabetes in Mice by Brown Adipose Tissue Transplant

OpenAIRE

Gunawardana, Subhadra C.; Piston, David W.

2012-01-01

Current therapies for type 1 diabetes (T1D) involve insulin replacement or transplantation of insulin-secreting tissue, both of which suffer from numerous limitations and complications. Here, we show that subcutaneous transplants of embryonic brown adipose tissue (BAT) can correct T1D in streptozotocin-treated mice (both immune competent and immune deficient) with severely impaired glucose tolerance and significant loss of adipose tissue. BAT transplants result in euglycemia, normalized gluco...

Diagnostic approach to neurotransmitter monoamine disorders: experience from clinical, biochemical, and genetic profiles.

Science.gov (United States)

Kuster, Alice; Arnoux, Jean-Baptiste; Barth, Magalie; Lamireau, Delphine; Houcinat, Nada; Goizet, Cyril; Doray, Bérénice; Gobin, Stéphanie; Schiff, Manuel; Cano, Aline; Amsallem, Daniel; Barnerias, Christine; Chaumette, Boris; Plaze, Marion; Slama, Abdelhamid; Ioos, Christine; Desguerre, Isabelle; Lebre, Anne-Sophie; de Lonlay, Pascale; Christa, Laurence

2018-01-01

To improve the diagnostic work-up of patients with diverse neurological diseases, we have elaborated specific clinical and CSF neurotransmitter patterns. Neurotransmitter determinations in CSF from 1200 patients revealed abnormal values in 228 (19%) cases. In 54/228 (24%) patients, a final diagnosis was identified. We have reported primary (30/54, 56%) and secondary (24/54, 44%) monoamine neurotransmitter disorders. For primary deficiencies, the most frequently mutated gene was DDC (n = 9), and the others included PAH with neuropsychiatric features (n = 4), PTS (n = 5), QDPR (n = 3), SR (n = 1), and TH (n = 1). We have also identified mutations in SLC6A3, FOXG1 (n = 1 of each), MTHFR (n = 3), FOLR1, and MTHFD (n = 1 of each), for dopamine transporter, neuronal development, and folate metabolism disorders, respectively. For secondary deficiencies, we have identified POLG (n = 3), ACSF3 (n = 1), NFU1, and SDHD (n = 1 of each), playing a role in mitochondrial function. Other mutated genes included: ADAR, RNASEH2B, RNASET2, SLC7A2-IT1 A/B lncRNA, and EXOSC3 involved in nuclear and cytoplasmic metabolism; RanBP2 and CASK implicated in post-traductional and scaffolding modifications; SLC6A19 regulating amino acid transport; MTM1, KCNQ2 (n = 2), and ATP1A3 playing a role in nerve cell electrophysiological state. Chromosome abnormalities, del(8)(p23)/dup(12) (p23) (n = 1), del(6)(q21) (n = 1), dup(17)(p13.3) (n = 1), and non-genetic etiologies (n = 3) were also identified. We have classified the final 54 diagnoses in 11 distinctive biochemical profiles and described them through 20 clinical features. To identify the specific molecular cause of abnormal NT profiles, (targeted) genomics might be used, to improve diagnosis and allow early treatment of complex and rare neurological genetic diseases.

Failure of rabbit neutrophils to secrete endogenous pyrogen when stimulated with staphylococci

OpenAIRE

1980-01-01

Cells obtained from acute peritoneal exudates in rabbits were separated into neutrophil and mononuclear populations by centrifugation on colloidal silica gradients. When these populations were separately incubated in tissue culture medium in the presence of opsonized Staphylococcus epidermidis, endogenous pyrogen was secreted only by the adherent cells of the mononuclear population. Pyrogen production by neutrophils could not have amounted to as much as 1% of the pyrogen produced by macrophag...

11C-labeled and 18F-labeled PET ligands for subtype-specific imaging of histamine receptors in the brain

NARCIS (Netherlands)

Funke, U.; Vugts, D.J.; Janssen, B.; Spaans, A.; Kruijer, P.S.; Lammertsma, A.A.; Perk, L.R.; Windhorst, A.D.

2013-01-01

The signaling molecule histamine plays a key role in the mediation of immune reactions, in gastric secretion, and in the sensory system. In addition, it has an important function as a neurotransmitter in the central nervous system, acting in pituitary hormone secretion, wakefulness, motor and

Efficient multiparty quantum-secret-sharing schemes

International Nuclear Information System (INIS)

Xiao Li; Deng Fuguo; Long Guilu; Pan Jianwei

2004-01-01

In this work, we generalize the quantum-secret-sharing scheme of Hillery, Buzek, and Berthiaume [Phys. Rev. A 59, 1829 (1999)] into arbitrary multiparties. Explicit expressions for the shared secret bit is given. It is shown that in the Hillery-Buzek-Berthiaume quantum-secret-sharing scheme the secret information is shared in the parity of binary strings formed by the measured outcomes of the participants. In addition, we have increased the efficiency of the quantum-secret-sharing scheme by generalizing two techniques from quantum key distribution. The favored-measuring-basis quantum-secret-sharing scheme is developed from the Lo-Chau-Ardehali technique [H. K. Lo, H. F. Chau, and M. Ardehali, e-print quant-ph/0011056] where all the participants choose their measuring-basis asymmetrically, and the measuring-basis-encrypted quantum-secret-sharing scheme is developed from the Hwang-Koh-Han technique [W. Y. Hwang, I. G. Koh, and Y. D. Han, Phys. Lett. A 244, 489 (1998)] where all participants choose their measuring basis according to a control key. Both schemes are asymptotically 100% in efficiency, hence nearly all the Greenberger-Horne-Zeilinger states in a quantum-secret-sharing process are used to generate shared secret information

Neurotransmitters as food supplements: the effects of GABA on brain and behavior

OpenAIRE

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 studie...

Characterization of pituitary function with emphasis on GH secretion in the chronic fatigue syndrome.

Science.gov (United States)

Moorkens, G; Berwaerts, J; Wynants, H; Abs, R

2000-07-01

TSH levels (1.6 +/- 1.0 mU/l vs. 1.0 +/- 0.4 mU/l; P = 0.011) were found in CFS patients. Serum free thyroxine was comparable in both groups. Visceral fat mass was significantly higher in CFS patients (86.6 +/- 34.9 cm2 vs. 51.5 +/- 15.7 cm2; P < 0.001). We observed a significant impairment of GH response during insulin-induced hypoglycaemia and a low nocturnal GH secretion in CFS patients. These changes did, however, not lead to different concentrations in serum IGF-I. The clinical expression of this inadequate GH secretion can thus be questioned, although the alteration in body composition may be related to this relative GH deficiency. Significantly increased prolactin and TSH levels were found when compared to controls. These findings give support to the hypothesis of a decreased dopaminergic tone in CFS. Further investigations are required in order to identify specific adaptations within the neurotransmitter system in CFS and to determine the clinical importance of the impaired GH homeostasis.

Identification of catecholamine neurotransmitters using fluorescence sensor array.

Science.gov (United States)

Ghasemi, Forough; Hormozi-Nezhad, M Reza; Mahmoudi, Morteza

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(-1). Finally, we found that the sensor had capability to identify the various catecholamines in urine sample. Copyright © 2016 Elsevier B.V. All rights reserved.

Antidepressant Binding Site in a Bacterial Homologue of Neurotransmitter Transporters

International Nuclear Information System (INIS)

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 rational

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

Calcium-Activated Cl- Channel: Insights on the Molecular Identity in Epithelial Tissues.

Science.gov (United States)

Rottgen, Trey S; Nickerson, Andrew J; Rajendran, Vazhaikkurichi M

2018-05-10

Calcium-activated chloride secretion in epithelial tissues has been described for many years. However, the molecular identity of the channel responsible for the Ca 2+ -activated Cl − secretion in epithelial tissues has remained a mystery. More recently, TMEM16A has been identified as a new putative Ca 2+ -activated Cl − channel (CaCC). The primary goal of this article will be to review the characterization of TMEM16A, as it relates to the physical structure of the channel, as well as important residues that confer voltage and Ca 2+ -sensitivity of the channel. This review will also discuss the role of TMEM16A in epithelial physiology and potential associated-pathophysiology. This will include discussion of developed knockout models that have provided much needed insight on the functional localization of TMEM16A in several epithelial tissues. Finally, this review will examine the implications of the identification of TMEM16A as it pertains to potential novel therapies in several pathologies.

Functions of tissue-resident eosinophils.

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Weller, Peter F; Spencer, Lisa A

2017-12-01

Eosinophils are a prominent cell type in particular host responses such as the response to helminth infection and allergic disease. Their effector functions have been attributed to their capacity to release cationic proteins stored in cytoplasmic granules by degranulation. However, eosinophils are now being recognized for more varied functions in previously underappreciated diverse tissue sites, based on the ability of eosinophils to release cytokines (often preformed) that mediate a broad range of activities into the local environment. In this Review, we consider evolving insights into the tissue distribution of eosinophils and their functional immunobiology, which enable eosinophils to secrete in a selective manner cytokines and other mediators that have diverse, 'non-effector' functions in health and disease.

Unexpected visitor on FDG PET/CT--brown adipose tissue (BAT) in mesentery in a case of retroperitoneal extra-adrenal pheochromocytoma: is the BAT activation secondary to catecholamine-secreting pheochromocytoma?

Science.gov (United States)

Joshi, Prathamesh Vijay; Lele, Vikram Ramchandra

2012-05-01

Fused positron emission tomography-computed tomography (PET/CT) technology has enabled the determination that nonmalignant fluorodeoxyglucose (FDG) uptake is observed in brown adipose tissue (BAT). FDG uptake in BAT is a known potential source of false-positive interpretations for PET. The typical locations of BAT include neck, supraclavicular area, mediastinum, and paravertebral intercostal spaces. Examples of atypical locations for BAT include posterior neck, left paratracheal area, axillae, perirenal area, and retrocrural area. We report PET/CT findings in a young male patient with malignant retroperitoneal extra-adrenal pheochromocytoma, who demonstrated FDG uptake in BAT at multiple locations including mesenteric BAT. We also propose catecholamine-secreting pheochromocytoma as a possible cause of BAT activation in our case.

Tachykinin: recent developments and novel roles in health and disease.

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Onaga, Takenori

2014-06-01

Over 80 years has passed since the discovery of substance P (SP), and a variety of peptides of the tachykinin (TK) family have been found and investigated. SP, neurokinin A (NKA), and neurokinin B (NKB) are representative peptides in mammalian species. SP and NKA are major excitatory neurotransmitters in the peripheral nervous system, while NKB is primarily involved in the central nervous system (CNS). Moreover, TK peptides play roles not only as neurotransmitters but also as local factors and are involved in almost all aspects of the regulation of physiological functions and pathophysiological processes. The role of SP as a mediator of pain processing and inflammation in peripheral tissues in coordination with transient receptor potential channels is well established, while novel aspects of TKs in relation to hematopoiesis, venous thromboembolism, tendinopathy, and taste perception have been clarified. In the CNS, the NKB signaling system in the hypothalamus has been shown to play a crucial role in the regulation of gonadotropin hormone secretion and the onset of puberty, and molecular biological studies have elucidated novel prophylaxic activities of TKs against neurogenic movement disorders based on their molecular structure. This review provides an overview of the novel aspects of TKs reported around the world in the last 5 years, with particular focus on nociception, inflammation, hemopoiesis, gonadotropin secretion, and CNS diseases.

Opposite Effects of Soluble Factors Secreted by Adipose Tissue on Proliferating and Quiescent Osteosarcoma Cells.

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Avril, Pierre; Duteille, Franck; Ridel, Perrine; Heymann, Marie-Françoise; De Pinieux, Gonzague; Rédini, Françoise; Blanchard, Frédéric; Heymann, Dominique; Trichet, Valérie; Perrot, Pierre

2016-03-01

Autologous adipose tissue transfer may be performed for aesthetic needs following resection of osteosarcoma, the most frequent primary malignant tumor of bone, excluding myeloma. The safety of autologous adipose tissue transfer regarding the potential risk of cancer recurrence must be addressed. Adipose tissue injection was tested in a human osteosarcoma preclinical model induced by MNNG-HOS cells. Culture media without growth factors from fetal bovine serum were conditioned with adipose tissue samples and added to two osteosarcoma cell lines (MNNG-HOS and MG-63) that were cultured in monolayer or maintained in nonadherent spheres, favoring a proliferation or quiescent stage, respectively. Proliferation and cell cycle were analyzed. Adipose tissue injection increased local growth of osteosarcoma in mice but was not associated with aggravation of lung metastasis or osteolysis. Adipose tissue-derived soluble factors increased the in vitro proliferation of osteosarcoma cells up to 180 percent. Interleukin-6 and leptin were measured in higher concentrations in adipose tissue-conditioned medium than in osteosarcoma cell-conditioned medium, but the authors' results indicated that they were not implicated alone. Furthermore, adipose tissue-derived soluble factors did not favor a G0-to-G1 phase transition of MNNG-HOS cells in nonadherent oncospheres. This study indicates that adipose tissue-soluble factors activate osteosarcoma cell cycle from G1 to mitosis phases, but do not promote the transition from quiescent G0 to G1 phases. Autologous adipose tissue transfer may not be involved in the activation of dormant tumor cells or cancer stem cells.

Application of cross-species PET imaging to assess neurotransmitter release in brain.

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Finnema, Sjoerd J; Scheinin, Mika; Shahid, Mohammed; Lehto, Jussi; Borroni, Edilio; Bang-Andersen, Benny; Sallinen, Jukka; Wong, Erik; Farde, Lars; Halldin, Christer; Grimwood, Sarah

2015-11-01

This review attempts to summarize the current status in relation to the use of positron emission tomography (PET) imaging in the assessment of synaptic concentrations of endogenous mediators in the living brain. Although PET radioligands are now available for more than 40 CNS targets, at the initiation of the Innovative Medicines Initiative (IMI) "Novel Methods leading to New Medications in Depression and Schizophrenia" (NEWMEDS) in 2009, PET radioligands sensitive to an endogenous neurotransmitter were only validated for dopamine. NEWMEDS work-package 5, "Cross-species and neurochemical imaging (PET) methods for drug discovery", commenced with a focus on developing methods enabling assessment of changes in extracellular concentrations of serotonin and noradrenaline in the brain. Sharing the workload across institutions, we utilized in vitro techniques with cells and tissues, in vivo receptor binding and microdialysis techniques in rodents, and in vivo PET imaging in non-human primates and humans. Here, we discuss these efforts and review other recently published reports on the use of radioligands to assess changes in endogenous levels of dopamine, serotonin, noradrenaline, γ-aminobutyric acid, glutamate, acetylcholine, and opioid peptides. The emphasis is on assessment of the availability of appropriate translational tools (PET radioligands, pharmacological challenge agents) and on studies in non-human primates and human subjects, as well as current challenges and future directions. PET imaging directed at investigating changes in endogenous neurochemicals, including the work done in NEWMEDS, have highlighted an opportunity to further extend the capability and application of this technology in drug development.

Investigation on the pancreatic and stomach secretion in pigs by means of continuous infusion of 14C-amino acids

International Nuclear Information System (INIS)

Simon, O.; Bergner, H.; Muenchmeyer, R.; Zebrowska, T.

1983-01-01

2 pigs received a barley-soya bean meal diet and another 2 a casein-wheat starch diet. The specific radioactivity (SR = dpm/μmol) of leucine and phenylalanine in the TCA soluble fraction of plasma and in the TCA soluble and TCA precipitable fractions of pancreatic juice and of digesta leaving the stomach was determined during 6 hours of intravenous infusion of 14 C-leucine and 14 C-phenylalanine. At the end of the infusion the SR of both amino acids in both fractions of several tissues was measured and used for calculations of the rate of tissue protein synthesis. The results are that mainly amino acids derived from the extracellular space were used for synthesis that the process of synthesis, concentration and secretion of secretory proteins requires in pigs 120 to 180 minutes, and that TCA soluble amino acids in pancreatic juice are not free amino acids per se, but originate from processing of presecretory proteins. In the duodenal digesta labelled proteins appeared 3 to 4 hours after the beginning of the infusion. Both, secretion of proteins by the pancreas and by the stomach seemed to be more stimulated after feeding the barley-soya diet than the casein-starch diet. Of all tissues, the SR of amino acids in proteins was highest in the pancreas. However, proteins secreted by the pancreas were 3 to 4 times higher labelled than those retained in the tissue. The range of the fractional rate of protein synthesis was calculated for the sections of the gastrointestinal tract, the liver and skeletal muscles and discussed with other findings. (author)

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. Copyright © 2014 Elsevier B.V. All rights reserved.

The effects of ecstasy on neurotransmitter systems: a review on the findings of molecular imaging studies.

Science.gov (United States)

Vegting, Yosta; Reneman, Liesbeth; Booij, Jan

2016-10-01

Ecstasy is a commonly used psychoactive drug with 3,4-methylenedioxymethamphetamine (MDMA) as the main content. Importantly, it has been suggested that use of MDMA may be neurotoxic particularly for serotonergic (5-hydroxytryptamine (5-HT)) neurons. In the past decades, several molecular imaging studies examined directly in vivo the effects of ecstasy/MDMA on neurotransmitter systems. The objective of the present study is to review the effects of ecstasy/MDMA on neurotransmitter systems as assessed by molecular imaging studies in small animals, non-human primates and humans. A search in PubMed was performed. Eighty-eight articles were found on which inclusion and exclusion criteria were applied. Thirty-three studies met the inclusion criteria; all were focused on the 5-HT or dopamine (DA) system. Importantly, 9 out of 11 of the animal studies that examined the effects of MDMA on 5-HT transporter (SERT) availability showed a significant loss of binding potential. In human studies, this was the case for 14 out of 16 studies, particularly in heavy users. In abstinent users, significant recovery of SERT binding was found over time. Most imaging studies in humans that focused on the DA system did not find any significant effect of ecstasy/MDMA use. Preclinical and clinical molecular imaging studies on the effects of ecstasy/MDMA use/administration on neurotransmitter systems show quite consistent alterations of the 5-HT system. Particularly, in human studies, loss of SERT binding was observed in heavy ecstasy users, which might reflect 5-HT neurotoxicity, although alternative explanations (e.g. down-regulation of the SERT) cannot be excluded.

High mobility group box-1 is phosphorylated by protein kinase C zeta and secreted in colon cancer cells

International Nuclear Information System (INIS)

Lee, Hanna; Park, Minhee; Shin, Nara; Kim, Gamin; Kim, Yun Gi; Shin, Jeon-Soo; Kim, Hoguen

2012-01-01

Highlights: ► Specific enzyme for HMGB1 phosphorylation and its secretion is proposed. ► Inhibition of PKC-ζ leads to significant reduction of the secreted HMGB1. ► Phosphorylation of specific site of HMGB1 redirects its secretion in cancer cells. ► Activation of PKC-ζ in cancers explains the enhanced HMGB1 secretion. -- Abstract: High mobility group box-1 (HMGB1), a nuclear protein, is overexpressed and secreted in cancer cells. Phosphorylation on two different nuclear localization signal regions are known to be important for the nuclear-to-cytoplasmic transport and secretion of HMGB1. However, little is known about the biochemical mechanism of HMGB1 modifications and its subsequent secretion from cancer cells. To identify the specific enzyme and important sites for HMGB1 phosphorylation, we screened the protein kinase C (PKC) family in a colon cancer cell line (HCT116) for HMGB1 binding by pull-down experiments using a 3XFLAG-HMGB1 construct. Strong interactions between atypical PKCs (PKC-ζ, λ, and ι) and cytoplasmic HMGB1 were observed in HCT116 cells. We further identified the most critical PKC isotype that regulates HMGB1 secretion is PKC-ζ by using PKC inhibitors and siRNA experiments. The serine residues at S39, S53 and S181 of HMGB1 were related to enhancing HMGB1 secretion. We also demonstrated overexpression and activation of PKC-ζ in colon cancer tissues. Our findings suggest that PKC-ζ is involved in the phosphorylation of HMGB1, and the phosphorylation of specific serine residues in the nuclear localization signal regions is related to enhanced HMGB1 secretion in colon cancer cells.

Roles of Organic Acid Anion Secretion in Aluminium Tolerance of Higher Plants

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Yang, Lin-Tong; Qi, Yi-Ping; Jiang, Huan-Xin; Chen, Li-Song

2013-01-01

Approximately 30% of the world's total land area and over 50% of the world's potential arable lands are acidic. Furthermore, the acidity of the soils is gradually increasing as a result of the environmental problems including some farming practices and acid rain. At mildly acidic or neutral soils, aluminium(Al) occurs primarily as insoluble deposits and is essentially biologically inactive. However, in many acidic soils throughout the tropics and subtropics, Al toxicity is a major factor limiting crop productivity. The Al-induced secretion of organic acid (OA) anions, mainly citrate, oxalate, and malate, from roots is the best documented mechanism of Al tolerance in higher plants. Increasing evidence shows that the Al-induced secretion of OA anions may be related to the following several factors, including (a) anion channels or transporters, (b) internal concentrations of OA anions in plant tissues, (d) temperature, (e) root plasma membrane (PM) H+-ATPase, (f) magnesium (Mg), and (e) phosphorus (P). Genetically modified plants and cells with higher Al tolerance by overexpressing genes for the secretion and the biosynthesis of OA anions have been obtained. In addition, some aspects needed to be further studied are also discussed. PMID:23509687

Mechanical Regulation in Cell Division and in Neurotransmitter Release

Science.gov (United States)

Thiyagarajan, Sathish

During their lifecycle, cells must produce forces which play important roles in several subcellular processes. Force-producing components are organized into macromolecular assemblies of proteins that are often dynamic, and are constructed or disassembled in response to various signals. The forces themselves may directly be involved in subcellular mechanics, or they may influence mechanosensing proteins either within or outside these structures. These proteins play different roles: they may ensure the stability of the force-producing structure, or they may send signals to a coupled process. The generation and sensing of subcellular forces is an active research topic, and this thesis focusses on the roles of these forces in two key areas: cell division and neurotransmitter release. The first part of the thesis deals with the effect of force on cell wall growth regulation during division in the fission yeast Schizosaccharomyces pombe, a cigar-shaped, unicellular organism. During cytokinesis, the last stage of cell division in which the cell physically divides into two, a tense cytokinetic ring anchored to the cellular membrane assembles and constricts, accompanied by the inward centripetal growth of new cell wall, called septum, in the wake of the inward-moving membrane. The contour of the septum hole maintains its circularity as it reduces in size--an indication of regulated growth. To characterize the cell wall growth process, we performed image analysis on contours of the leading edge of the septum obtained via fluorescence microscopy in the labs of our collaborators. We quantified the deviations from circularity using the edge roughness. The roughness was spatially correlated, suggestive of regulated growth. We hypothesized that the cell wall growers are mechanosensitive and respond to the force exerted by the ring. A mathematical model based on this hypothesis then showed that this leads to corrections of roughness in a curvature-dependent fashion. Thus, one of

Secretion management in the mechanically ventilated patient.

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Branson, Richard D

2007-10-01

Secretion management in the mechanically ventilated patient includes routine methods for maintaining mucociliary function, as well as techniques for secretion removal. Humidification, mobilization of the patient, and airway suctioning are all routine procedures for managing secretions in the ventilated patient. Early ambulation of the post-surgical patient and routine turning of the ventilated patient are common secretion-management techniques that have little supporting evidence of efficacy. Humidification is a standard of care and a requisite for secretion management. Both active and passive humidification can be used. The humidifier selected and the level of humidification required depend on the patient's condition and the expected duration of intubation. In patients with thick, copious secretions, heated humidification is superior to a heat and moisture exchanger. Airway suctioning is the most important secretion removal technique. Open-circuit and closed-circuit suctioning have similar efficacy. Instilling saline prior to suctioning, to thin the secretions or stimulate a cough, is not supported by the literature. Adequate humidification and as-needed suctioning are the foundation of secretion management in the mechanically ventilated patient. Intermittent therapy for secretion removal includes techniques either to simulate a cough, to mechanically loosen secretions, or both. Patient positioning for secretion drainage is also widely used. Percussion and postural drainage have been widely employed for mechanically ventilated patients but have not been shown to reduce ventilator-associated pneumonia or atelectasis. Manual hyperinflation and insufflation-exsufflation, which attempt to improve secretion removal by simulating a cough, have been described in mechanically ventilated patients, but neither has been studied sufficiently to support routine use. Continuous lateral rotation with a specialized bed reduces atelectasis in some patients, but has not been shown

Incretin secretion: direct mechanisms

DEFF Research Database (Denmark)

Balk-Møller, Emilie; Holst, Jens Juul; Kuhre, Rune Ehrenreich

2014-01-01

The incretin hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) are secreted from gastro-intestinal K- and L-cells, respectively, and play an important role in post-prandial blood glucose regulation. They do this by direct stimulation of the pancreatic β...... enzyme responsible for incretin degradation (dipeptidyl peptidase-4) is inhibited (drugs are already on the market) while the secretion of endogenous GLP-1 secretion is stimulated at the same time may prove particularly rewarding. In this section we review current knowledge on the mechanisms for direct...

Effect of alcohol on insulin secretion and viability of human pancreatic islets

Directory of Open Access Journals (Sweden)

Nikolić Dragan

2017-01-01

Full Text Available Introduction/Objective. There are controversial data in the literature on the topic of effects of alcohol on insulin secretion, apoptosis, and necrosis of the endocrine and exocrine pancreas. The goal of this research was to determine how alcohol affects the insulin secretion and viability of human adult pancreatic islets in vitro during a seven-day incubation. Methods. Human pancreatic tissue was digested with Collagenase XI, using a non-automated method. Cultures were incubated in Roswell Park Memorial Institute (RPMI medium containing alcohol (10 μl of alcohol in 100 ml of medium. Insulin stimulation index (SI and viability of the islets were determined on the first, third, and seventh day of cultivation. Results. Analysis of the viability of the islets showed that there wasn’t significant difference between the control and the test group. In the test group, viability of the cultures declined with the time of incubation. SI of the test group was higher compared to the control group, by 50% and 25% on the first and third day of cultivation, respectively. On the seventh day, insulin secretion was reduced by 25%. The difference was not statistically significant (p > 0.05. In the test group, significant decline in insulin secretion was found on the third and seventh day of incubation (p ≤ 0.05. Conclusion. Alcohol can increase or decrease insulin secretion of islets cultures, which may result in an inadequate response of pancreatic β-cells to blood glucose, leading to insulin resistance, and increased risk of developing type 2 diabetes. [Project of the Serbian Ministry of Education, Science and Technological Development, Grant no. 41002

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.

Near-future carbon dioxide levels alter fish behaviour by interfering with neurotransmitter function

Science.gov (United States)

Nilsson, Göran E.; Dixson, Danielle L.; Domenici, Paolo; McCormick, Mark I.; Sørensen, Christina; Watson, Sue-Ann; Munday, Philip L.

2012-03-01

Predicted future CO2 levels have been found to alter sensory responses and behaviour of marine fishes. Changes include increased boldness and activity, loss of behavioural lateralization, altered auditory preferences and impaired olfactory function. Impaired olfactory function makes larval fish attracted to odours they normally avoid, including ones from predators and unfavourable habitats. These behavioural alterations have significant effects on mortality that may have far-reaching implications for population replenishment, community structure and ecosystem function. However, the underlying mechanism linking high CO2 to these diverse responses has been unknown. Here we show that abnormal olfactory preferences and loss of behavioural lateralization exhibited by two species of larval coral reef fish exposed to high CO2 can be rapidly and effectively reversed by treatment with an antagonist of the GABA-A receptor. GABA-A is a major neurotransmitter receptor in the vertebrate brain. Thus, our results indicate that high CO2 interferes with neurotransmitter function, a hitherto unrecognized threat to marine populations and ecosystems. Given the ubiquity and conserved function of GABA-A receptors, we predict that rising CO2 levels could cause sensory and behavioural impairment in a wide range of marine species, especially those that tightly control their acid-base balance through regulatory changes in HCO3- and Cl- levels.

Neuromodulatory neurotransmitters influence LTP-like plasticity in human cortex: a pharmaco-TMS study.

Science.gov (United States)

Korchounov, Alexei; Ziemann, Ulf

2011-08-01

Long-term potentiation (LTP) of synaptic efficacy is considered a fundamental mechanism of learning and memory. At the cellular level a large body of evidence demonstrated that the major neuromodulatory neurotransmitters dopamine (DA), norepinephrine (NE), and acetylcholine (ACh) influence LTP magnitude. Noninvasive brain stimulation protocols provide the opportunity to study LTP-like plasticity at the systems level of human cortex. Here we applied paired associative stimulation (PAS) to induce LTP-like plasticity in the primary motor cortex of eight healthy subjects. In a double-blind, randomized, placebo-controlled, crossover design, the acute effects of a single oral dose of the neuromodulatory drugs cabergoline (DA agonist), haloperidol (DA antagonist), methylphenidate (indirect NE agonist), prazosine (NE antagonist), tacrine (ACh agonist), and biperiden (ACh antagonist) on PAS-induced LTP-like plasticity were examined. The antagonists haloperidol, prazosine, and biperiden depressed significantly the PAS-induced LTP-like plasticity observed under placebo, whereas the agonists cabergoline, methylphenidate, and tacrine had no effect. Findings demonstrate that antagonists in major neuromodulatory neurotransmitter systems suppress LTP-like plasticity at the systems level of human cortex, in accord with evidence of their modulating action of LTP at the cellular level. This provides further supportive evidence for the known detrimental effects of these drugs on LTP-dependent mechanisms such as learning and memory.

Identification of pro-opiomelanocortin and secretion of its peptide fragments in bovine adrenals

Energy Technology Data Exchange (ETDEWEB)

Tennov, A.V.; Dmitriev, A.D.; Kizim, E.A.; Ustinova, E.E.

1986-01-01

This paper describes the results of an investigation to show that biosynthesis of POMC, its proteolytic processing, an secretion of the peptide products of that processing take place in the bovine adrenals. Rabbit antisera against endorphins were obtained and used for radioimmunoassay of peptides. I 125-labeled peptides were obtained by the chloramine method and purified from free I 125 on Sephadex G-10 (0.7 x 5 cm, centrifugation for 10 min at 1500 g). To detect secretion of peptide fragments of POMC in the adrenals experiments were undertaken to determine the beta-endorphin content in perfusates obtained during retrograde perfusion of the bovine adrenals. It was found that immunoreactive compounds, indistinguishable in their immunochemical properties from beta-endorphin, are present in the perfusates, just as in the tissue extracts.

Tissue-Engineered Skeletal Muscle Organoids for Reversible Gene Therapy

Science.gov (United States)

Vandenburgh, Herman; DelTatto, Michael; Shansky, Janet; Lemaire, Julie; Chang, Albert; Payumo, Francis; Lee, Peter; Goodyear, Amy; Raven, Latasha

1996-01-01

Genetically modified murine skeletal myoblasts were tissue engineered in vitro into organ-like structures (organoids) containing only postmitotic myofibers secreting pharmacological levels of recombinant human growth hormone (rhGH). Subcutaneous organoid Implantation under tension led to the rapid and stable appearance of physiological sera levels of rhGH for up to 12 weeks, whereas surgical removal led to its rapid disappearance. Reversible delivery of bioactive compounds from postimtotic cells in tissue engineered organs has several advantages over other forms of muscle gene therapy.

Mammalian protein secretion without signal peptide removal. Biosynthesis of plasminogen activator inhibitor-2 in U-937 cells

International Nuclear Information System (INIS)

Ye, R.D.; Wun, T.C.; Sadler, J.E.

1988-01-01

Plasminogen activator inhibitor-2 (PAI-2) is a serine protease inhibitor that regulates plasmin generation by inhibiting urokinase and tissue plasminogen activator. The primary structure of PAI-2 suggests that it may be secreted without cleavage of a single peptide. To confirm this hypothesis we have studied the glycosylation and secretion of PAI-2 in human monocytic U-937 cells by metabolic labeling, immunoprecipitation, glycosidase digestion, and protein sequencing. PAI-2 is variably glycosylated on asparagine residues to yield intracellular intermediates with zero, one, two, or three high mannose-type oligosaccharide units. Secretion of the N-glycosylated species began by 1 h of chase and the secreted molecules contained both complex-type N-linked and O-linked oligosaccharides. Enzymatically deglycosylated PAI-2 had an electrophoretic mobility identical to that of the nonglycosylated precursor and also to that of PAI-2 synthesized in vitro in a rabbit reticulocyte lysate from synthetic mRNA derived from full length PAI-2 cDNA. The amino-terminal protein sequence of secreted PAI-2 began with the initiator methionine residue. These results indicate that PAI-2 is glycosylated and secreted efficiently without the cleavage of a signal peptide. PAI-2 shares this property with its nearest homologue in the serine protease inhibitor family, chicken ovalbumin, and appears to be the first well characterized example of this phenomenon among natural mammalian proteins

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.

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.

Molecular cloning and expression analysis of the synaptotagmin-1 gene in the hypothalamus and pituitary of Huoyan goose during different stages of the egg-laying cycle.

Science.gov (United States)

Luan, Xinhong; Luo, Lina; Cao, Zhongzan; Li, Rongrong; Liu, Dawei; Gao, Ming; Liu, Mei; Wang, Laiyou

2014-08-21

Synaptotagmin-1 (Syt1) is an abundant, evolutionarily conserved integral membrane protein that plays essential roles in neurotransmitter release and hormone secretion. Neurotransmitters secreted by hypothalamic neurons can alter GnRH (gonadotropin-releasing hormones) neuronal activity by binding to and activating specific membrane receptors in pituitary cells and, in turn, control the release of gonadotropin hormones from the pituitary gland. To reveal the influence of Syt1 on the process of goose egg-laying, we cloned and characterized the cDNA of goose Syt1 originating from hypothalamus and pituitary tissues of Huoyan goose and investigated the mRNA expression profiles during different stages of the egg-laying cycle. Hypothalamus and pituitary tissues were obtained from 36 Huoyan geese in the pre-laying period, early laying period, peak-laying period, and ceased period. The cDNA sequences of goose Syt1 were cloned and characterized from Huoyan goose tissues using 5'-RACE and 3'-RACE methods. Multiple alignments and phylogenetic analyses of the deduced Syt1 amino acid sequence were conducted using bioinformatics tools. The expression profiles of the Syt1 mRNA in the hypothalamus and pituitary during pre-laying, early laying, peak-laying and ceased period were examined using real-time PCR (qRT-PCR). The cDNA of Syt1 consisted of a 274 bp 5' UTR, a 1266 bp open reading frame (ORF) encoding 421 amino acids, and a 519 bp 3' UTR. The deduced amino acid sequence of goose Syt1 is highly conserved with the sequence from other species, especially with birds (more than 98%), and contains two protein kinase C2 conserved regions (C2 domain) from amino acids residue 157 to 259 and 288 to 402. The results of qRT-PCR demonstrated that the expression of Syt1 mRNA increased from the pre-laying period to the peak-laying period, reached its peak in the peak-laying period, and then decreased in the ceased period. To the best of our knowledge, this study is the first to obtain full

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......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 investigated. Cultured cerebellar (primarily glutamatergic) neurons were superfused in medium containing [U-13C]glucose (2.5 mmol/L) and lactate (1 or 5 mmol/L) or glucose (2.5 mmol/L) and [U-13C]lactate (1 mmol/L), and exposed to pulses of N-methyl-D-aspartate (300 micromol/L), leading to synaptic activity...... significantly during induced depolarization. In contrast, at both concentrations of extracellular lactate, the metabolism of [U-13C]glucose was increased during neuronal depolarization. The role of glucose and lactate as energy substrates during vesicular release as well as transporter-mediated influx...

Nonlinear secret image sharing scheme.

Science.gov (United States)

Shin, Sang-Ho; Lee, Gil-Je; Yoo, Kee-Young

2014-01-01

Over the past decade, most of secret image sharing schemes have been proposed by using Shamir's technique. It is based on a linear combination polynomial arithmetic. Although Shamir's technique based secret image sharing schemes are efficient and scalable for various environments, there exists a security threat such as Tompa-Woll attack. Renvall and Ding proposed a new secret sharing technique based on nonlinear combination polynomial arithmetic in order to solve this threat. It is hard to apply to the secret image sharing. In this paper, we propose a (t, n)-threshold nonlinear secret image sharing scheme with steganography concept. In order to achieve a suitable and secure secret image sharing scheme, we adapt a modified LSB embedding technique with XOR Boolean algebra operation, define a new variable m, and change a range of prime p in sharing procedure. In order to evaluate efficiency and security of proposed scheme, we use the embedding capacity and PSNR. As a result of it, average value of PSNR and embedding capacity are 44.78 (dB) and 1.74t⌈log2 m⌉ bit-per-pixel (bpp), respectively.

Current concepts on the physiology and genetics of neurotransmitters-mediating enzyme-aromatic L-amino acid decarboxylase

International Nuclear Information System (INIS)

Rahman, M.K.

1993-03-01

Two most important neurotransmitters, dopamine and serotonin are mediated by the enzyme aromatic L-amino acid decarboxylase (AADC). Because of their importance in the regulation of neuronal functions, behaviour and emotion of higher animals, many researchers are working on this enzyme to elucidate its physiological properties, structure and genetic aspects. We have discovered this enzyme in the mammalian blood, we established sensitive assay methods for the assay of the activities of this enzyme. We have made systematic studies on this enzyme in the tissues and brains of rats, and human subjects. We have found an endogenous inhibitor of this enzyme in the monkey's blood. The amino acid sequences of human AADC has been compared to rat or bovine. A full-length cDNA clone encoding human AADC has been isolated. Very recently the structure of human AADC gene including 5'-flaking region has been characterized and the transcriptional starting point has been determined. The human AADC gene assigned to chromosome 7. Up-to-date research data have shown that AADC is encoded by a single gene. Recently two patients with AADC deficiency were reported. This paper describes the systematic up-to-date review studies on AADC. (author). 62 refs, 5 figs, 8 tabs

Single cells from human primary colorectal tumors exhibit polyfunctional heterogeneity in secretions of ELR+ CXC chemokines.

Science.gov (United States)

Adalsteinsson, Viktor A; Tahirova, Narmin; Tallapragada, Naren; Yao, Xiaosai; Campion, Liam; Angelini, Alessandro; Douce, Thomas B; Huang, Cindy; Bowman, Brittany; Williamson, Christina A; Kwon, Douglas S; Wittrup, K Dane; Love, J Christopher

2013-10-01

Cancer is an inflammatory disease of tissue that is largely influenced by the interactions between multiple cell types, secreted factors, and signal transduction pathways. While single-cell sequencing continues to refine our understanding of the clonotypic heterogeneity within tumors, the complex interplay between genetic variations and non-genetic factors ultimately affects therapeutic outcome. Much has been learned through bulk studies of secreted factors in the tumor microenvironment, but the secretory behavior of single cells has been largely uncharacterized. Here we directly profiled the secretions of ELR+ CXC chemokines from thousands of single colorectal tumor and stromal cells, using an array of subnanoliter wells and a technique called microengraving to characterize both the rates of secretion of several factors at once and the numbers of cells secreting each chemokine. The ELR+ CXC chemokines are highly redundant, pro-angiogenic cytokines that signal via the CXCR1 and CXCR2 receptors, influencing tumor growth and progression. We find that human primary colorectal tumor and stromal cells exhibit polyfunctional heterogeneity in the combinations and magnitudes of secretions for these chemokines. In cell lines, we observe similar variance: phenotypes observed in bulk can be largely absent among the majority of single cells, and discordances exist between secretory states measured and gene expression for these chemokines among single cells. Together, these measures suggest secretory states among tumor cells are complex and can evolve dynamically. Most importantly, this study reveals new insight into the intratumoral phenotypic heterogeneity of human primary tumors.

Shared Secrets versus Secrets Kept Private Are Linked to Better Adolescent Adjustment

Science.gov (United States)

Frijns, Tom; Finkenauer, Catrin; Keijsers, Loes

2013-01-01

It is a household notion that secrecy is bad while sharing is good. But what about shared secrets? The present research adopts a functional analysis of sharing secrets, arguing that it should negate harmful consequences generally associated with secrecy and serves important interpersonal functions in adolescence. A survey study among 790 Dutch…

Investigation on the pancreatic and stomach secretion in pigs by means of continuous infusion of /sup 14/C-amino acids

Energy Technology Data Exchange (ETDEWEB)

Simon, O; Bergner, H; Muenchmeyer, R [Humboldt-Universitaet, Berlin (German Democratic Republic). Sektion Tierproduktion und Veterinaermedizin; Zebrowska, T [Polska Akademia Nauk, Warsaw

1983-01-01

2 pigs received a barley-soya bean meal diet and another 2 a casein-wheat starch diet. The specific radioactivity (SR = dpm/..mu..mol) of leucine and phenylalanine in the TCA soluble fraction of plasma and in the TCA soluble and TCA precipitable fractions of pancreatic juice and of digesta leaving the stomach was determined during 6 hours of intravenous infusion of /sup 14/C-leucine and /sup 14/C-phenylalanine. At the end of the infusion the SR of both amino acids in both fractions of several tissues was measured and used for calculations of the rate of tissue protein synthesis. The results are that mainly amino acids derived from the extracellular space were used for synthesis that the process of synthesis, concentration and secretion of secretory proteins requires in pigs 120 to 180 minutes, and that TCA soluble amino acids in pancreatic juice are not free amino acids per se, but originate from processing of presecretory proteins. In the duodenal digesta labelled proteins appeared 3 to 4 hours after the beginning of the infusion. Both, secretion of proteins by the pancreas and by the stomach seemed to be more stimulated after feeding the barley-soya diet than the casein-starch diet. Of all tissues, the SR of amino acids in proteins was highest in the pancreas. However, proteins secreted by the pancreas were 3 to 4 times higher labelled than those retained in the tissue. The range of the fractional rate of protein synthesis was calculated for the sections of the gastrointestinal tract, the liver and skeletal muscles and discussed with other findings.

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

2009-10-01

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. 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 mum) 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 approximately 100 microm. 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. 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); 2

Development, regulation, metabolism and function of bone marrow adipose tissues.

Science.gov (United States)

Li, Ziru; Hardij, Julie; Bagchi, Devika P; Scheller, Erica L; MacDougald, Ormond A

2018-05-01

Most adipocytes exist in discrete depots throughout the body, notably in well-defined white and brown adipose tissues. However, adipocytes also reside within specialized niches, of which the most abundant is within bone marrow. Whereas bone marrow adipose tissue (BMAT) shares many properties in common with white adipose tissue, the distinct functions of BMAT are reflected by its development, regulation, protein secretion, and lipid composition. In addition to its potential role as a local energy reservoir, BMAT also secretes proteins, including adiponectin, RANK ligand, dipeptidyl peptidase-4, and stem cell factor, which contribute to local marrow niche functions and which may also influence global metabolism. The characteristics of BMAT are also distinct depending on whether marrow adipocytes are contained within yellow or red marrow, as these can be thought of as 'constitutive' and 'regulated', respectively. The rBMAT for instance can be expanded or depleted by myriad factors, including age, nutrition, endocrine status and pharmaceuticals. Herein we review the site specificity, age-related development, regulation and metabolic characteristics of BMAT under various metabolic conditions, including the functional interactions with bone and hematopoietic cells. Copyright © 2018 Elsevier Inc. All rights reserved.

On alternative approach for verifiable secret sharing

OpenAIRE

Kulesza, Kamil; Kotulski, Zbigniew; Pieprzyk, Joseph

2002-01-01

Secret sharing allows split/distributed control over the secret (e.g. master key). Verifiable secret sharing (VSS) is the secret sharing extended by verification capacity. Usually verification comes at the price. We propose "free lunch", the approach that allows to overcome this inconvenience.

High mobility group box-1 is phosphorylated by protein kinase C zeta and secreted in colon cancer cells

Energy Technology Data Exchange (ETDEWEB)

Lee, Hanna; Park, Minhee; Shin, Nara; Kim, Gamin [Department of Pathology, Yonsei University College of Medicine, 134 Shinchon-Dong, Seodaemoon-Ku, Seoul (Korea, Republic of); Brain Korea 21 Project for Medical Sciences, Yonsei University College of Medicine, 134 Shinchon-Dong, Seodaemoon-Ku, Seoul (Korea, Republic of); Kim, Yun Gi [Department of Internal Medicine, Seoul National University College of Medicine, 28 Yongon-dong, Chongno-gu, Seoul 110-744 (Korea, Republic of); Shin, Jeon-Soo [Department of Microbiology, Yonsei University College of Medicine, 134 Shinchon-Dong, Seodaemoon-Ku, Seoul (Korea, Republic of); Kim, Hoguen, E-mail: hkyonsei@yuhs.ac [Department of Pathology, Yonsei University College of Medicine, 134 Shinchon-Dong, Seodaemoon-Ku, Seoul (Korea, Republic of); Brain Korea 21 Project for Medical Sciences, Yonsei University College of Medicine, 134 Shinchon-Dong, Seodaemoon-Ku, Seoul (Korea, Republic of)

2012-07-27

Highlights: Black-Right-Pointing-Pointer Specific enzyme for HMGB1 phosphorylation and its secretion is proposed. Black-Right-Pointing-Pointer Inhibition of PKC-{zeta} leads to significant reduction of the secreted HMGB1. Black-Right-Pointing-Pointer Phosphorylation of specific site of HMGB1 redirects its secretion in cancer cells. Black-Right-Pointing-Pointer Activation of PKC-{zeta} in cancers explains the enhanced HMGB1 secretion. -- Abstract: High mobility group box-1 (HMGB1), a nuclear protein, is overexpressed and secreted in cancer cells. Phosphorylation on two different nuclear localization signal regions are known to be important for the nuclear-to-cytoplasmic transport and secretion of HMGB1. However, little is known about the biochemical mechanism of HMGB1 modifications and its subsequent secretion from cancer cells. To identify the specific enzyme and important sites for HMGB1 phosphorylation, we screened the protein kinase C (PKC) family in a colon cancer cell line (HCT116) for HMGB1 binding by pull-down experiments using a 3XFLAG-HMGB1 construct. Strong interactions between atypical PKCs (PKC-{zeta}, {lambda}, and {iota}) and cytoplasmic HMGB1 were observed in HCT116 cells. We further identified the most critical PKC isotype that regulates HMGB1 secretion is PKC-{zeta} by using PKC inhibitors and siRNA experiments. The serine residues at S39, S53 and S181 of HMGB1 were related to enhancing HMGB1 secretion. We also demonstrated overexpression and activation of PKC-{zeta} in colon cancer tissues. Our findings suggest that PKC-{zeta} is involved in the phosphorylation of HMGB1, and the phosphorylation of specific serine residues in the nuclear localization signal regions is related to enhanced HMGB1 secretion in colon cancer cells.

Assessment of Energy Metabolic Changes in Adipose Tissue-Derived Stem Cells

NARCIS (Netherlands)

Hajmousa, Ghazaleh; Harmsen, Martin C; Di Nardo, Paolo; Dhingra, Sanjiv; Singla, Dinender K.

2017-01-01

Adipose tissue-derived stem cells (ADSC) are promising candidates for therapeutic applications in cardiovascular regenerative medicine. By definition, the phenotype ADSCs, e.g., the ubiquitous secretion of growth factors, cytokines, and extracellular matrix components is not met in vivo, which

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.

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

International Nuclear Information System (INIS)

Martyniuk, Christopher J.; Sanchez, Brian C.; Szabo, Nancy J.; Denslow, Nancy D.; Sepulveda, Maria S.

2009-01-01

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 (μg/g): atrazine (0.3 and 3.0), toxaphene (10 and 100), cadmium (CdCl 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 μg/g) significantly increased cGnRH-II mRNA while PCB 126 (0.25 μg/g) decreased GAD65 mRNA. Phenanthrene decreased GAD65 and tyrosine hydroxylase mRNA levels at the highest dose (50 μg/g) but increased cGnRH-II mRNA at the lowest dose (5 μg/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.

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

Science.gov (United States)

Martyniuk, Christopher J; Sanchez, Brian C; Szabo, Nancy J; Denslow, Nancy D; Sepúlveda, Maria S

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 (microg/g): atrazine (0.3 and 3.0), toxaphene (10 and 100), cadmium (CdCl(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 microg/g) significantly increased cGnRH-II mRNA while PCB 126 (0.25 microg/g) decreased GAD65 mRNA. Phenanthrene decreased GAD65 and tyrosine hydroxylase mRNA levels at the highest dose (50 microg/g) but increased cGnRH-II mRNA at the lowest dose (5 microg/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.

Trade Secrets in Life Science and Pharmaceutical Companies

Science.gov (United States)

Nealey, Tara; Daignault, Ronald M.; Cai, Yu

2015-01-01

Trade secret protection arises under state common law and state statutes. In general, a trade secret is information that is not generally known to the public and is maintained as a secret, and it provides a competitive advantage or economic benefit to the trade secret holder. Trade secrets can be worth tens or hundreds of millions of dollars, and damage awards in trade secret litigation have been high; often, there is a lot at stake. Obtaining a trade secret through “improper means” is misappropriation. If the alleged trade secret, however, was developed independently, known publicly, or not maintained as a secret, then those defenses may successfully overcome a claim for trade secret misappropriation. With today’s interconnectedness in the biotechnology and pharmaceutical fields, more collaborations, joint ventures, and outsourcing arrangements among firms, and increased mobility of employees’ careers, life science companies need to not only understand how to protect their trade secrets, but also know how to defend against a claim for trade secret theft. PMID:25414378

Trade secrets in life science and pharmaceutical companies.

Science.gov (United States)

Nealey, Tara; Daignault, Ronald M; Cai, Yu

2014-11-20

Trade secret protection arises under state common law and state statutes. In general, a trade secret is information that is not generally known to the public and is maintained as a secret, and it provides a competitive advantage or economic benefit to the trade secret holder. Trade secrets can be worth tens or hundreds of millions of dollars, and damage awards in trade secret litigation have been high; often, there is a lot at stake. Obtaining a trade secret through "improper means" is misappropriation. If the alleged trade secret, however, was developed independently, known publicly, or not maintained as a secret, then those defenses may successfully overcome a claim for trade secret misappropriation. With today's interconnectedness in the biotechnology and pharmaceutical fields, more collaborations, joint ventures, and outsourcing arrangements among firms, and increased mobility of employees' careers, life science companies need to not only understand how to protect their trade secrets, but also know how to defend against a claim for trade secret theft. Copyright © 2015 Cold Spring Harbor Laboratory Press; all rights reserved.

Two-party secret key distribution via a modified quantum secret sharing protocol.

Science.gov (United States)

Grice, W P; Evans, P G; Lawrie, B; Legré, M; Lougovski, P; Ray, W; Williams, B P; Qi, B; Smith, A M

2015-03-23

We present and demonstrate a novel protocol for distributing secret keys between two and only two parties based on N-party single-qubit Quantum Secret Sharing (QSS). We demonstrate our new protocol with N = 3 parties using phase-encoded photons. We show that any two out of N parties can build a secret key based on partial information from each other and with collaboration from the remaining N - 2 parties. Our implementation allows for an accessible transition between N-party QSS and arbitrary two party QKD without modification of hardware. In addition, our approach significantly reduces the number of resources such as single photon detectors, lasers and dark fiber connections needed to implement QKD.

Brain structures and neurotransmitters regulating aggression in cats: implications for human aggression.

Science.gov (United States)

Gregg, T R; Siegel, A

2001-01-01

1. Violence and aggression are major public health problems. 2. The authors have used techniques of electrical brain stimulation, anatomical-immunohistochemical techniques, and behavioral pharmacology to investigate the neural systems and circuits underlying aggressive behavior in the cat. 3. The medial hypothalamus and midbrain periaqueductal gray are the most important structures mediating defensive rage behavior, and the perifornical lateral hypothalamus clearly mediates predatory attack behavior. The hippocampus, amygdala, bed nucleus of the stria terminalis, septal area, cingulate gyrus, and prefrontal cortex project to these structures directly or indirectly and thus can modulate the intensity of attack and rage. 4. Evidence suggests that several neurotransmitters facilitate defensive rage within the PAG and medial hypothalamus, including glutamate, Substance P, and cholecystokinin, and that opioid peptides suppress it; these effects usually depend on the subtype of receptor that is activated. 5. A key recent discovery was a GABAergic projection that may underlie the often-observed reciprocally inhibitory relationship between these two forms of aggression. 6. Recently, Substance P has come under scrutiny as a possible key neurotransmitter involved in defensive rage, and the mechanism by which it plays a role in aggression and rage is under investigation. 7. It is hoped that this line of research will provide a better understanding of the neural mechanisms and substrates regulating aggression and rage and thus establish a rational basis for treatment of disorders associated with these forms of aggression.

Trefoil factors in saliva and gingival tissues of patients with chronic periodontitis

DEFF Research Database (Denmark)

Chaiyarit, Ponlatham; Chayasadom, Anek; Wara-Aswapati, Nawarat

2012-01-01

BACKGROUND: Trefoil factors (TFFs) are secreted molecules that are involved in cytoprotection against tissue damage and the immune response. TFFs have been detected in saliva and oral tissues, but their clinical significance has never been investigated in patients with chronic periodontitis....... The objective of this study is to determine whether TFF expression in saliva and gingival tissues is associated with periodontal pathology. METHODS: Saliva and gingival tissue samples were collected from 25 non-periodontitis individuals and 25 patients with chronic periodontitis (CP). Enzyme...... observed in patients with CP (P = 0.003 and P periodontal pathology and number of Porphyromonas gingivalis...

Subfractions of enamel matrix derivative differentially influence cytokine secretion from human oral fibroblasts

Directory of Open Access Journals (Sweden)

Oscar Villa

2015-03-01

Full Text Available Enamel matrix derivative is used to promote periodontal regeneration during the corrective phase of the treatment of periodontal defects. Our main goal was to analyze the bioactivity of different molecular weight fractions of enamel matrix derivative. Enamel matrix derivative, a complex mixture of proteins, was separated into 13 fractions using size-exclusion chromatography and characterized by sodium dodecyl sulfate–polyacrylamide gel electrophoresis and liquid chromatography–electrospray ionization–tandem mass spectrometry. Human periodontal ligament fibroblasts were treated with either enamel matrix derivative or the different fractions. Proliferation and cytokine secretion to the cell culture medium were measured and compared to untreated cells. The liquid chromatography–electrospray ionization–tandem mass spectrometry analyses revealed that the most abundant peptides were amelogenin and leucine-rich amelogenin peptide related. The fractions containing proteins above 20 kDa induced an increase in vascular endothelial growth factor and interleukin-6 secretion, whereas lower molecular weight fractions enhanced proliferation and secretion of interleukin-8 and monocyte chemoattractant protein-1 and reduced interleukin-4 release. The various molecular components in the enamel matrix derivative formulation might contribute to reported effects on tissue regeneration through their influence on vascularization, the immune response, and chemotaxis.

Pegvisomant treatment in gigantism caused by a growth hormone-secreting giant pituitary adenoma.

Science.gov (United States)

Müssig, K; Gallwitz, B; Honegger, J; Strasburger, C J; Bidlingmaier, M; Machicao, F; Bornemann, A; Ranke, M B; Häring, H-U; Petersenn, S

2007-03-01

Gigantism is rare with the majority of cases caused by a growth hormone (GH)-secreting pituitary adenoma. Treatment options for GH-secreting pituitary adenomas have been widened with the availability of long-acting dopamine agonists, depot preparations of somatostatin analogues, and recently the GH receptor antagonist pegvisomant. A 23-year-old male patient presented with continuous increase in height during the past 6 years due to a GH-secreting giant pituitary adenoma. Because of major intracranial extension and failure of octreotide treatment to shrink the tumour, the tumour was partially resected by a trans-frontal surgical approach. At immunohistochemistry, the tumour showed a marked expression of GH and a sparsely focal expression of prolactin. Somatostatin receptors (sst) 1-5 were not detected. Tumour tissue weakly expressed dopamine receptor type 2. The Gs alpha subunit was intact. Conversion from somatostatin analogue to pegvisomant normalized insulin-like-growth-factor-I (IGF-I) levels and markedly improved glucose tolerance. Pegvisomant is a potent treatment option in patients with pituitary gigantism. In patients who do not respond to somatostatin analogues, knowledge of the SST receptor status may shorten the time to initiation of pegvisomant treatment.

5 CFR 1312.27 - Top secret control.

Science.gov (United States)

2010-01-01

... 5 Administrative Personnel 3 2010-01-01 2010-01-01 false Top secret control. 1312.27 Section 1312... Classified Information § 1312.27 Top secret control. The EOP Security Officer serves as the Top Secret... Top Secret material. The ATSCOs will be responsible for the accountability and custodianship of Top...

Effect of adrenal hormones on thyroid secretion and thyroid hormones on adrenal secretion in the sheep.