Measuring the serotonin uptake site using [3H]paroxetine--a new serotonin uptake inhibitor

International Nuclear Information System (INIS)

Gleiter, C.H.; Nutt, D.J.

1988-01-01

Serotonin is an important neurotransmitter that may be involved in ethanol preference and dependence. It is possible to label the serotonin uptake site in brain using the tricyclic antidepressant imipramine, but this also binds to other sites. We have used the new high-affinity uptake blocker paroxetine to define binding to this site and report it to have advantages over imipramine as a ligand

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...

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

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

Effects of x-irradiation induced loss of cerebellar granule cells on the synaptosomal levels and the high affinity uptake of amino acids

International Nuclear Information System (INIS)

Rohde, B.H.; Rea, M.A.; Simon, J.R.; McBride, W.J.

1979-01-01

Crude synaptosomal (P 2 ) preparations were obtained from the cerebella of rats in which the granule cell population had been selectively reduced by X-irradiation treatment and from the cerebella of control animals. In the P 2 fraction form control cerebella, the level of glutamate was greater than any other of the 5 amino acids measured and was 2-fold higher than taurine. The content of taurine, GABA, glycine, and alanine were not changed by the X-irradiation treatment. The uptake of 1.0 micrometers-L-[ 3 H]glutamate and L-[ 3 H]aspartate was reduced approx 20% by X-irradiation treatment, whereas the uptake of 1.0 micrometers-[ 3 H]GABA and [ 3 H]taurine was unchanged. In a second study, the uptake of L-[ 3 H]glutamate, L-[ 3 H]aspartate and [ 3 H]GABA was measured using P 2 fractions obtained from the cerebella of rats in which the population of granule, stellate and basket cells had been reduced by X-irradiation treatment. The uptake of 1.0 micrometers-L-[ 3 H]glutamate, L-[ 3 H]aspartate and [ 3 H]GABA was significantly (P < 0.05) reduced to 57.68 and 59% respectively, of control values. The data are discussed in terms of glutamate being the excitatory neurotransmitter released from granule cells and GABA being the inhibitory neurotransmitter released from basket cells. (author)

Silicate reduces cadmium uptake into cells of wheat

International Nuclear Information System (INIS)

Greger, Maria; Kabir, Ahmad H.; Landberg, Tommy; Maity, Pooja J.; Lindberg, Sylvia

2016-01-01

Cadmium (Cd) is a health threat all over the world and high Cd content in wheat causes high Cd intake. Silicon (Si) decreases cadmium content in wheat grains and shoot. This work investigates whether and how silicate (Si) influences cadmium (Cd) uptake at the cellular level in wheat. Wheat seedlings were grown in the presence or absence of Si with or without Cd. Cadmium, Si, and iron (Fe) accumulation in roots and shoots was analysed. Leaf protoplasts from plants grown without Cd were investigated for Cd uptake in the presence or absence of Si using the fluorescent dye, Leadmium Green AM. Roots and shoots of plants subjected to all four treatments were investigated regarding the expression of genes involved in the Cd uptake across the plasma membrane (i.e. LCT1) and efflux of Cd into apoplasm or vacuole from the cytosol (i.e. HMA2). In addition, phytochelatin (PC) content and PC gene (PCS1) expression were analysed. Expression of iron and metal transporter genes (IRT1 and NRAMP1) were also analysed. Results indicated that Si reduced Cd accumulation in plants, especially in shoot. Si reduced Cd transport into the cytoplasm when Si was added both directly during the uptake measurements and to the growth medium. Silicate downregulated LCT1 and HMA2 and upregulated PCS1. In addition, Si enhanced PC formation when Cd was present. The IRT1 gene, which was downregulated by Cd was upregulated by Si in root and shoot facilitating Fe transport in wheat. NRAMP1 was similarly expressed, though the effect was limited to roots. This work is the first to show how Si influences Cd uptake on the cellular level. - Highlights: • Si decreases accumulation and translocation of Cd in plants at tissue level. • This work is the first to show how Si influences Cd uptake. • Si decreases Cd uptake into cell and downregulates heavy metal transporter LCT1. • Si downregulates HMA2 transporter, which regulates Cd transport from root to shoot. • Si increases phytochelatin formation

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....

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

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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.

Nanosensors for neurotransmitters.

Science.gov (United States)

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.

Science.gov (United States)

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.

Positron emission tomography shows high specific uptake of racemic carbon-11 labelled norepinephrine in the primate heart

International Nuclear Information System (INIS)

Farde, L.; Halldin, C.; Naagren, K.; Suhara, Tetsuya; Karlsson, P.; Schoeps, K.O.; Swahn, C.G.; Bone, D.

1994-01-01

(-)-Norepinephrine is the predominant neurotransmitter of the sympathetic innervation of the heart. Racemic norepinephrine was labelled with carbon-11 and injected i.v. into Cynomolgus monkeys. Five minutes after injection there was a more than tenfold higher radioactivity in the heart than in adjacent tissue. Pretreatment with the norepinephrine reuptake inhibitor desipramine reduced the uptake by more than 80%. The high specific uptake of racemic [ 11 C]norepinephrine indicates that enatiomerically pure(-)-[ 11 C]norepinephrine has promising potential for detailed mapping of the sympathetic innervation of the human myocardium. (orig.)

Positron emission tomography shows high specific uptake of racemic carbon-11 labelled norepinephrine in the primate heart

Energy Technology Data Exchange (ETDEWEB)

Farde, L [Dept. of Clinical Neuroscience, Karolinska Inst., Stockholm (Sweden); Halldin, C [Dept. of Clinical Neuroscience, Karolinska Inst., Stockholm (Sweden); Naagren, K [Turku Univ., Cyclotron/PET Center (Finland); Suhara, Tetsuya [Dept. of Clinical Neuroscience, Karolinska Inst., Stockholm (Sweden); Karlsson, P [Dept. of Clinical Neuroscience, Karolinska Inst., Stockholm (Sweden); Schoeps, K O [Dept. of Clinical Neuroscience, Karolinska Inst., Stockholm (Sweden); Swahn, C G [Dept. of Clinical Neuroscience, Karolinska Inst., Stockholm (Sweden); Bone, D [Dept. of Clinical Neuroscience, Karolinska Inst., Stockholm (Sweden)

1994-04-01

(-)-Norepinephrine is the predominant neurotransmitter of the sympathetic innervation of the heart. Racemic norepinephrine was labelled with carbon-11 and injected i.v. into Cynomolgus monkeys. Five minutes after injection there was a more than tenfold higher radioactivity in the heart than in adjacent tissue. Pretreatment with the norepinephrine reuptake inhibitor desipramine reduced the uptake by more than 80%. The high specific uptake of racemic [[sup 11]C]norepinephrine indicates that enatiomerically pure(-)-[[sup 11]C]norepinephrine has promising potential for detailed mapping of the sympathetic innervation of the human myocardium. (orig.)

Focus On: Neurotransmitter Systems

Science.gov (United States)

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

Albumin-derived peptides efficiently reduce renal uptake of radiolabelled peptides

International Nuclear Information System (INIS)

Vegt, Erik; Eek, Annemarie; Oyen, Wim J.G.; Gotthardt, Martin; Boerman, Otto C.; Jong, Marion de

2010-01-01

In peptide-receptor radionuclide therapy (PRRT), the maximum activity dose that can safely be administered is limited by high renal uptake and retention of radiolabelled peptides. The kidney radiation dose can be reduced by coinfusion of agents that competitively inhibit the reabsorption of radiolabelled peptides, such as positively charged amino acids, Gelofusine, or trypsinised albumin. The aim of this study was to identify more specific and potent inhibitors of the kidney reabsorption of radiolabelled peptides, based on albumin. Albumin was fragmented using cyanogen bromide and six albumin-derived peptides with different numbers of electric charges were selected and synthesised. The effect of albumin fragments (FRALB-C) and selected albumin-derived peptides on the internalisation of 111 In-albumin, 111 In-minigastrin, 111 In-exendin and 111 In-octreotide by megalin-expressing cells was assessed. In rats, the effect of Gelofusine and albumin-derived peptides on the renal uptake and biodistribution of 111 In-minigastrin, 111 In-exendin and 111 In-octreotide was determined. FRALB-C significantly reduced the uptake of all radiolabelled peptides in vitro. The albumin-derived peptides showed different potencies in reducing the uptake of 111 In-albumin, 111 In-exendin and 111 In-minigastrin in vitro. The most efficient albumin-derived peptide (peptide 6), was selected for in vivo testing. In rats, 5 mg of peptide 6 very efficiently inhibited the renal uptake of 111 In-minigastrin, by 88%. Uptake of 111 In-exendin and 111 In-octreotide was reduced by 26 and 33%, respectively. The albumin-derived peptide 6 efficiently inhibited the renal reabsorption of 111 In-minigastrin, 111 In-exendin and 111 In-octreotide and is a promising candidate for kidney protection in PRRT. (orig.)

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....

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.

Neurotransmitters, more than meets the eye--neurotransmitters and their perspectives in cancer development and therapy.

Science.gov (United States)

Li, Zhi Jie; Cho, Chi Hin

2011-09-30

The neurotransmitter/receptor system has been shown to modulate various aspects of tumor development including cell proliferation, angiogenesis, invasion, migration and metastasis. It has been found that tumor tissues can not only synthesize and release a wide range of neurotransmitters but also produce different biological effects via respective receptors. These tissues are also innervated by nerve fibers but the biological significance is unknown. Nevertheless neurotransmitters can produce either stimulatory or inhibitory effect in normal and tumor tissues. These effects are dependent on the types of tissues and the kinds of neurotransmitter as well as the subtypes of corresponding receptors being involved. These findings clearly extend the conventional role of neurotransmitters in nervous system to the actions in oncogenesis. In this regard, intervention or stimulation of these neuronal pathways in different cancer diseases would have significant clinical implications in cancer treatments. Here, we summarize the influences of various well-characterized neurotransmitters and their receptors on tumor growth and further discuss the respective possible strategies and perspectives for cancer therapy in the future. Copyright © 2011. Published by Elsevier B.V.

Unconventional neurotransmitters, neurodegeneration and neuroprotection

Directory of Open Access Journals (Sweden)

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

Science.gov (United States)

Bucher, Elizabeth S.; Wightman, R. Mark

2015-07-01

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

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.

Therapeutics of Neurotransmitters in Alzheimer's Disease.

Science.gov (United States)

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.

Risk-reducing mastectomy and salpingo-oophorectomy in unaffected BRCA mutation carriers: uptake and timing

DEFF Research Database (Denmark)

Skytte, A-B; Gerdes, Anne-Marie Axø; Andersen, M K

2010-01-01

from 306 healthy BRCA carriers with no personal history of ovarian or breast cancer. We found a 10-year uptake of 75% for risk-reducing salpingo-oophorectomy and 50% for risk-reducing mastectomy by time to event analysis. Age and childbirth influenced this decision. The uptake rate has not changed......Once female carriers of a BRCA mutation are identified they have to make decisions on risk management. The aim of this study is to outline the uptake of risk-reducing surgery in the Danish population of BRCA mutation positive women and to search for factors affecting this decision. We analysed data...

The emergence of neurotransmitters as immune modulators.

Science.gov (United States)

Franco, Rafael; Pacheco, Rodrigo; Lluis, Carmen; Ahern, Gerard P; O'Connell, Peta J

2007-09-01

Initially, the idea that neurotransmitters could serve as immunomodulators emerged with the discovery that their release and diffusion from nervous tissue could lead to signaling through lymphocyte cell-surface receptors and the modulation of immune function. It is now evident that neurotransmitters can also be released from leukocytes and act as autocrine or paracrine modulators. Here, we review the data indicating that leukocytes synthesize and release 'neurotransmitters' and we also discuss the diverse effects that these compounds exert in a variety of immune cells. The role of neurotransmitters in immune-related diseases is also reviewed succinctly. Current and future developments in understanding the cross-talk between the immune and nervous systems will probably identify new avenues for treating immune-mediated diseases using agonists or antagonists of neurotransmitter receptors.

Dynamic SERS nanosensor for neurotransmitter sensing near neurons.

Science.gov (United States)

Lussier, Félix; Brulé, Thibault; Bourque, Marie-Josée; Ducrot, Charles; Trudeau, Louis-Éric; Masson, Jean-François

2017-12-04

Current electrophysiology and electrochemistry techniques have provided unprecedented understanding of neuronal activity. However, these techniques are suited to a small, albeit important, panel of neurotransmitters such as glutamate, GABA and dopamine, and these constitute only a subset of the broader range of neurotransmitters involved in brain chemistry. Surface-enhanced Raman scattering (SERS) provides a unique opportunity to detect a broader range of neurotransmitters in close proximity to neurons. Dynamic SERS (D-SERS) nanosensors based on patch-clamp-like nanopipettes decorated with gold nanoraspberries can be located accurately under a microscope using techniques analogous to those used in current electrophysiology or electrochemistry experiments. In this manuscript, we demonstrate that D-SERS can measure in a single experiment ATP, glutamate (glu), acetylcholine (ACh), GABA and dopamine (DA), among other neurotransmitters, with the potential for detecting a greater number of neurotransmitters. The SERS spectra of these neurotransmitters were identified with a barcoding data processing method and time series of the neurotransmitter levels were constructed. The D-SERS nanosensor was then located near cultured mouse dopaminergic neurons. The detection of neurotransmitters was performed in response to a series of K + depolarisations, and allowed the detection of elevated levels of both ATP and dopamine. Control experiments were also performed near glial cells, showing only very low basal detection neurotransmitter events. This paper demonstrates the potential of D-SERS to detect neurotransmitter secretion events near living neurons, but also constitutes a strong proof-of-concept for the broad application of SERS to the detection of secretion events by neurons or other cell types in order to study normal or pathological cell functions.

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...

Arrhythmia causes lipid accumulation and reduced glucose uptake.

Science.gov (United States)

Lenski, Matthias; Schleider, Gregor; Kohlhaas, Michael; Adrian, Lucas; Adam, Oliver; Tian, Qinghai; Kaestner, Lars; Lipp, Peter; Lehrke, Michael; Maack, Christoph; Böhm, Michael; Laufs, Ulrich

2015-01-01

Atrial fibrillation (AF) is characterized by irregular contractions of atrial cardiomyocytes and increased energy demand. The aim of this study was to characterize the influence of arrhythmia on glucose and fatty acid (FA) metabolism in cardiomyocytes, mice and human left atrial myocardium. Compared to regular pacing, irregular (pseudo-random variation at the same number of contractions/min) pacing of neonatal rat cardiomyocytes induced shorter action potential durations and effective refractory periods and increased diastolic [Ca(2+)]c. This was associated with the activation of Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) and AMP-activated protein kinase (AMPK). Membrane expression of fatty acid translocase (FAT/CD36) and (14)C-palmitic acid uptake were augmented while membrane expression of glucose transporter subtype 4 (GLUT-4) as well as (3)H-glucose uptake were reduced. Inhibition of AMPK and CaMKII prevented these arrhythmia-induced metabolic changes. Similar alterations of FA metabolism were observed in a transgenic mouse model (RacET) for spontaneous AF. Consistent with these findings samples of left atrial myocardium of patients with AF compared to matched samples of patients with sinus rhythm showed up-regulation of CaMKII and AMPK and increased membrane expression of FAT/CD36, resulting in lipid accumulation. These changes of FA metabolism were accompanied by decreased membrane expression of GLUT-4, increased glycogen content and increased expression of the pro-apoptotic protein bax. Irregular pacing of cardiomyocytes increases diastolic [Ca(2+)]c and activation of CaMKII and AMPK resulting in lipid accumulation, reduced glucose uptake and increased glycogen synthesis. These metabolic changes are accompanied by an activation of pro-apoptotic signalling pathways.

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

Reduced folate carrier polymorphism determines methotrexate uptake by B cells and CD4+ T cells

DEFF Research Database (Denmark)

Baslund, B; Gregers, J; Nielsen, Claus Henrik

2008-01-01

To examine if polymorphism 80G --> A in the Reduced Folate Carrier (RFC) affects uptake of MTX in B- and CD4+ T-cells.......To examine if polymorphism 80G --> A in the Reduced Folate Carrier (RFC) affects uptake of MTX in B- and CD4+ T-cells....

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.

Reducing Renal Uptake of {sup 177}Lu Labeled CCK Derivative using Basic Amino Acids

Energy Technology Data Exchange (ETDEWEB)

Lee, Soyoung; Lim, Jaecheong; Joh, Eunha [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

2014-05-15

Radiolabeled peptides have been designed to target the relative receptors overespressed in tumor cells, such as integrin αvβ3, gastrin-releasing peptide receptor (GRPR), melanocortin-1 receptor (MC1-R), glucagon-like peptide-a receptor (GLP-1R), and cholecystokinin (CCK) receptor. Most of these peptides are eliminated from the body via the kidney and are partly reabsorbed in the proximal tubular cells. However, the high renal uptake of the radiolabeled peptides may lead to renal toxicity. In this study we investigated various amino acid solutions to reduce the renal uptake of {sup 177}Lu-DOTA-CCK derivative. Renal uptake of {sup 177}Lu-DOTA-CCK derivative is effectively reduced by the administration of positively charged amino acids. The administration of 12 mg of L-lysine was as effective in reducing the renal uptake as 6 mg of lysine and 6 mg of arginine combinations. Further studies will be performed to identify the most potent inhibitor of renal reuptake of radiolabeled peptides and minimize the chance of unwanted side effects.

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.)

Elevated CO2 plus chronic warming reduce nitrogen uptake and levels or activities of nitrogen-uptake and -assimilatory proteins in tomato roots.

Science.gov (United States)

Jayawardena, Dileepa M; Heckathorn, Scott A; Bista, Deepesh R; Mishra, Sasmita; Boldt, Jennifer K; Krause, Charles R

2017-03-01

Atmospheric CO 2 enrichment is expected to often benefit plant growth, despite causing global warming and nitrogen (N) dilution in plants. Most plants primarily procure N as inorganic nitrate (NO 3 - ) or ammonium (NH 4 + ), using membrane-localized transport proteins in roots, which are key targets for improving N use. Although interactive effects of elevated CO 2 , chronic warming and N form on N relations are expected, these have not been studied. In this study, tomato (Solanum lycopersicum) plants were grown at two levels of CO 2 (400 or 700 ppm) and two temperature regimes (30 or 37°C), with NO 3 - or NH 4 + as the N source. Elevated CO 2 plus chronic warming severely inhibited plant growth, regardless of N form, while individually they had smaller effects on growth. Although %N in roots was similar among all treatments, elevated CO 2 plus warming decreased (1) N-uptake rate by roots, (2) total protein concentration in roots, indicating an inhibition of N assimilation and (3) shoot %N, indicating a potential inhibition of N translocation from roots to shoots. Under elevated CO 2 plus warming, reduced NO 3 - -uptake rate per g root was correlated with a decrease in the concentration of NO 3 - -uptake proteins per g root, reduced NH 4 + uptake was correlated with decreased activity of NH 4 + -uptake proteins and reduced N assimilation was correlated with decreased concentration of N-assimilatory proteins. These results indicate that elevated CO 2 and chronic warming can act synergistically to decrease plant N uptake and assimilation; hence, future global warming may decrease both plant growth and food quality (%N). © 2016 Scandinavian Plant Physiology Society.

Evaluating and reducing a model of radiocaesium soil-plant uptake

Energy Technology Data Exchange (ETDEWEB)

Tarsitano, D.; Young, S.D. [School of Biosciences, University of Nottingham, University Park, Nottingham, NG7 2RD (United Kingdom); Crout, N.M.J., E-mail: neil.crout@nottingham.ac.u [School of Biosciences, University of Nottingham, University Park, Nottingham, NG7 2RD (United Kingdom)

2011-03-15

An existing model of radiocaesium transfer to grasses was extended to include wheat and barley and parameterised using data from a wide range of soils and contact times. The model structure was revised and evaluated using a subset of the available data which was not used for model parameterisation. The resulting model was then used as a basis for systematic model reduction to test the utility of the model components. This analysis suggested that the use of 4 model variables (relating to radiocaesium adsorption on organic matter and the pH sensitivity of soil solution potassium concentration) and 1 model input (pH) are not required. The results of this analysis were used to develop a reduced model which was further evaluated in terms of comparisons to observations. The reduced model had an improved empirical performance and fewer adjustable parameters and soil characteristic inputs. - Research highlights: {yields} A model of plant radiocesium uptake is evaluated and re-parameterised. {yields} The representation of time dependent changes in plant uptake is improved. {yields} Model reduction is applied to evaluate the model structure. {yields} A reduced model is identified which outperforms the previously reported model. {yields} The reduced model requires fewer soil specific inputs.

[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

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

GABA and glutamate uptake and metabolism in retinal glial (Müller cells

Directory of Open Access Journals (Sweden)

Andreas eBringmann

2013-04-01

Full Text Available Müller cells, the principal glial cells of the retina, support the synaptic activity by the uptake and metabolization of extracellular neurotransmitters. Müller cells express uptake and exchange systems for various neurotransmitters including glutamate and -aminobutyric acid (GABA. Müller cells remove the bulk of extracellular glutamate in the inner retina and contribute to the glutamate clearance around photoreceptor terminals. By the uptake of glutamate, Müller cells are involved in the shaping and termination of the synaptic activity, particularly in the inner retina. Reactive Müller cells are neuroprotective, e.g., by the clearance of excess extracellular glutamate, but may also contribute to neuronal degeneration by a malfunctioning or even reversal of glial glutamate transporters, or by a downregulation of the key enzyme, glutamine synthetase. This review summarizes the present knowledge about the role of Müller cells in the clearance and metabolization of extracellular glutamate and GABA. Some major pathways of GABA and glutamate metabolism in Müller cells are described; these pathways are involved in the glutamate-glutamine cycle of the retina, in the defense against oxidative stress via the production of glutathione, and in the production of substrates for the neuronal energy metabolism.

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.

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.

Strategies for sensing neurotransmitters with responsive MRI contrast agents.

Science.gov (United States)

Angelovski, Goran; Tóth, Éva

2017-01-23

A great deal of research involving multidisciplinary approaches is currently dedicated to the understanding of brain function. The complexity of physiological processes that underlie neural activity is the greatest hurdle to faster advances. Among imaging techniques, MRI has great potential to enable mapping of neural events with excellent specificity, spatiotemporal resolution and unlimited tissue penetration depth. To this end, molecular imaging approaches using neurotransmitter-sensitive MRI agents have appeared recently to study neuronal activity, along with the first successful in vivo MRI studies. Here, we review the pioneering steps in the development of molecular MRI methods that could allow functional imaging of the brain by sensing the neurotransmitter activity directly. We provide a brief overview of other imaging and analytical methods to detect neurotransmitter activity, and describe the approaches to sense neurotransmitters by means of molecular MRI agents. Based on these initial steps, further progress in probe chemistry and the emergence of innovative imaging methods to directly monitor neurotransmitters can be envisaged.

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.

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.

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.

Calcium-sensing beyond neurotransmitters

DEFF Research Database (Denmark)

Gustavsson, Natalia; Han, Weiping

2009-01-01

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

Beta-amyloid peptides undergo regulated co-secretion with neuropeptide and catecholamine neurotransmitters.

Science.gov (United States)

Toneff, Thomas; Funkelstein, Lydiane; Mosier, Charles; Abagyan, Armen; Ziegler, Michael; Hook, Vivian

2013-08-01

Beta-amyloid (Aβ) peptides are secreted from neurons, resulting in extracellular accumulation of Aβ and neurodegeneration of Alzheimer's disease. Because neuronal secretion is fundamental for the release of neurotransmitters, this study assessed the hypothesis that Aβ undergoes co-release with neurotransmitters. Model neuronal-like chromaffin cells were investigated, and results illustrate regulated, co-secretion of Aβ(1-40) and Aβ(1-42) with peptide neurotransmitters (galanin, enkephalin, and NPY) and catecholamine neurotransmitters (dopamine, norepinephrine, and epinephrine). Regulated secretion from chromaffin cells was stimulated by KCl depolarization and nicotine. Forskolin, stimulating cAMP, also induced co-secretion of Aβ peptides with peptide and catecholamine neurotransmitters. These data suggested the co-localization of Aβ with neurotransmitters in dense core secretory vesicles (DCSV) that store and secrete such chemical messengers. Indeed, Aβ was demonstrated to be present in DCSV with neuropeptide and catecholamine transmitters. Furthermore, the DCSV organelle contains APP and its processing proteases, β- and γ-secretases, that are necessary for production of Aβ. Thus, Aβ can be generated in neurotransmitter-containing DCSV. Human IMR32 neuroblastoma cells also displayed regulated secretion of Aβ(1-40) and Aβ(1-42) with the galanin neurotransmitter. These findings illustrate that Aβ peptides are present in neurotransmitter-containing DCSV, and undergo co-secretion with neuropeptide and catecholamine neurotransmitters that regulate brain functions. Copyright © 2013 Elsevier Inc. All rights reserved.

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.

The use of ice-cream to reduce inferior and liver uptake of 99mTc Sestamibi

International Nuclear Information System (INIS)

Williams, R.C.; Jost, G.M.

2002-01-01

Aim: To determine if ice-cream has any role in reducing the main drawback of sestamibi imaging namely inferior and liver uptake of sestamibi in myocardial imaging. This inferior uptake from, Stomach, Loops of Bowel and Left Lobe of liver can make interpretation difficult Can obscure a defect in the inferior margin of the heart and Hot inferior uptake can produce false adjacent cold defect when using a Fourier kernel. Material and Methods: To remove the confounding factor of various 'stress' regimes adenosine exercise and Dobutamine, only resting Sestamibi scans were examined. Patients where Given ice cream on a stick (ice covered) just prior to injection Imaged at 90 mins post injection of 500 Mbq Tc99m Sestamibi with > 90% purity, using eccentric non-elliptical non circular orbit to maximise resolution, for 18 mins with 2 heads. Processing: Reconstruct (for this purpose) with a butterworth filter of 0.4 and a power factor of 2. Sum all coronal views: Make a rectangular ROI covering the inferior 1/2 or the myocardium. Duplicate this ROI and place at same vertical position over highest activity region of liver. Duplicate region and place immediately underneath cardiac region. Create a BGD region of interest between heart and liver. Data: Ratios of heart to liver and inferior to heart are created with and without background correction. Results: Summary: Ice cream reduces the inferior uptake of Sestamibi by 30%. Ice cream reduces the liver uptake by 14%. Conclusion: Given: The low risk of an ice cream intervention. The high acceptance by patients. The low cost. The effect on inferior uptake. The possible effect on liver uptake. I would recommend the use of Ice Cream for all Myocardial Sestamibi Imaging

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...

Effects of surgical and chemical lesions on neurotransmitter candidates in the nucleus accumbens of the rat

Energy Technology Data Exchange (ETDEWEB)

Walaas, I; Fonnum, F

1979-01-01

The origin of fibers containing different neurotransmitter candidates in the nucleus accumbens of rat brain has been studied with surgical and chemical lesion techniques. Destruction of the medial forebrain bundle decreased the activity of aromatic amino acid decarboxylase by 80% in the nucleus. Cutting of the fornix or a hemitransection decreased the high affinity uptake of glutamate by 45% and the endogenous level of glutamate by 33%. The high affinity uptake of glutamate was concentrated in the synaptosomal fraction and the decrease after the lesion was most pronounced in this fraction. Restricted lesions indicated that fibers in the fimbria/fornix coming from the subiculum were responsible for this part of the glutamate uptake in the nucleus. Local injection of kainic acid into the nucleus was accompanied by a 75% decrease in choline acetyltransferase and a 35% decrease in acetylcholineserase activities, a 70% decrease in glutamate decarboxylase activity and a 60% decrease in the high affinity uptake of ..gamma..-aminobutyrate, a 45% decrease in high affinity glutamate uptake, and no change in aromatic amino acid decarboxylase activity. Performing a lesion of the fornix after kainic acid injection led to an 85% decrease in high affinity glutamate uptake, without further affecting the other neuronal markers. The results indicate that all aminergic fibers to the nucleus accumbens are ascending in the medial forebrain bundle, that the subiculum-accumbens fibers are glutamergic and the nucleus also contains intrinsic glutamergic or aspartergic cells. Cholinergic and ..gamma..-aminobutyrate-containing cells are wholly intrinsic to the nucleus.

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

Science.gov (United States)

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.

Synthetic nanoparticles camouflaged with biomimetic erythrocyte membranes for reduced reticuloendothelial system uptake

International Nuclear Information System (INIS)

Rao, Lang; Xu, Jun-Hua; Cai, Bo; Liu, Huiqin; Li, Ming; Jia, Yan; Xiao, Liang; Guo, Shi-Shang; Liu, Wei; Zhao, Xing-Zhong

2016-01-01

Suppression of the reticuloendothelial system (RES) uptake is one of the most challenging tasks in nanomedicine. Coating stratagems using polymers, such as poly(ethylene glycol) (PEG), have led to great success in this respect. Nevertheless, recent observations of immunological response toward these synthetic polymers have triggered a search for better alternatives. In this work, natural red blood cell (RBC) membranes are camouflaged on the surface of Fe 3 O 4 nanoparticles for reducing the RES uptake. In vitro macrophage uptake, in vivo biodistribution and pharmacokinetic studies demonstrate that the RBC membrane is a superior alternative to the current gold standard PEG for nanoparticle ‘stealth’. Furthermore, we systematically investigate the in vivo potential toxicity of RBC membrane-coated nanoparticles by blood biochemistry, whole blood panel examination and histology analysis based on animal models. The combination of synthetic nanoparticles and natural cell membranes embodies a novel and biomimetic nanomaterial design strategy and presents a compelling property of functional materials for a broad range of biomedical applications. (paper)

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.

Vesicular GABA Uptake Can Be Rate Limiting for Recovery of IPSCs from Synaptic Depression

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Manami Yamashita

2018-03-01

Full Text Available Summary: Synaptic efficacy plays crucial roles in neuronal circuit operation and synaptic plasticity. Presynaptic determinants of synaptic efficacy are neurotransmitter content in synaptic vesicles and the number of vesicles undergoing exocytosis at a time. Bursts of presynaptic firings depress synaptic efficacy, mainly due to depletion of releasable vesicles, whereas recovery from strong depression is initiated by endocytic vesicle retrieval followed by refilling of vesicles with neurotransmitter. We washed out presynaptic cytosolic GABA to induce a rundown of IPSCs at cerebellar inhibitory cell pairs in slices from rats and then allowed fast recovery by elevating GABA concentration using photo-uncaging. The time course of this recovery coincided with that of IPSCs from activity-dependent depression induced by a train of high-frequency stimulation. We conclude that vesicular GABA uptake can be a limiting step for the recovery of inhibitory neurotransmission from synaptic depression. : Recovery of inhibitory synaptic transmission from activity-dependent depression requires refilling of vesicles with GABA. Yamashita et al. find that vesicular uptake rate of GABA is a slow process, limiting the recovery rate of IPSCs from depression.

Gallium-67-labeled lactam bridge-cyclized alpha-MSH peptides with enhanced melanoma uptake and reduced renal uptake.

Science.gov (United States)

Guo, Haixun; Gallazzi, Fabio; Miao, Yubin

2012-06-20

The purpose of this study was to examine the melanoma targeting and pharmacokinetic properties of (67)Ga-DOTA-GGNle-CycMSHhex {(67)Ga-1,4,7,10-tetraazacyclononane-1,4,7,10-tetraacetic acid-Gly-Gly-Nle-c[Asp-His-DPhe-Arg-Trp-Lys]-CONH2} and (67)Ga-NOTA-GGNle-CycMSHhex {(67)Ga-1,4,7-triazacyclononane-1,4,7-triacetic acid-Gly-Gly-Nle-c[Asp-His-DPhe-Arg-Trp-Lys]-CONH2} and compare with (67)Ga-DOTA-GlyGlu-CycMSH {(67)Ga-DOTA-Gly-Glu-c[Lys-Nle-Glu-His-DPhe-Arg-Trp-Gly-Arg-Pro-Val-Asp]} we previously reported. DOTA-GGNle-CycMSHhex and NOTA-GGNle-CycMSHhex were synthesized using fluorenylmethyloxy carbonyl (Fmoc) chemistry. The melanocortin-1 (MC1) receptor binding affinity of NOTA-GGNle-CycMSHhex was determined in B16/F1 melanoma cells and compared with DOTA-GGNle-CycMSHhex. The melanoma targeting and pharmacokinetic properties of (67)Ga-NOTA-GGNle-CycMSHhex and (67)Ga-DOTA-GGNle-CycMSHhex were determined in B16/F1 melanoma-bearing C57 mice. NOTA-GGNle-CycMSHhex and DOTA-GGNle-CycMSHhex displayed comparable MC1 receptor binding affinities (1.6 vs 2.1 nM) in B16/F1 melanoma cells. Both (67)Ga-NOTA-GGNle-CycMSHhex and (67)Ga-DOTA-GGNle-CycMSHhex exhibited dramatically enhanced melanoma uptake and reduced renal uptake than (67)Ga-DOTA-GlyGlu-CycMSH in B16/F1 melanoma-bearing C57 mice. Furthermore, (67)Ga-NOTA-GGNle-CycMSHhex exhibited more favorable radiolabeling conditions (>85% radiolabeling yields started at 37 °C), as well as higher tumor/kidney uptake ratios than (67)Ga-DOTA-GGNle-CycMSHhex at 0.5, 2, and 24 h postinjection. High melanoma uptake coupled with low renal uptake highlighted the potential of (67)Ga-NOTA-GGNle-CycMSHhex for melanoma imaging and therapy.

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

Directory of Open Access Journals (Sweden)

Joeri eVan Liefferinge

2013-08-01

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

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...

Submaximal oxygen uptake kinetics, functional mobility, and physical activity in older adults with heart failure and reduced ejection fraction.

Science.gov (United States)

Hummel, Scott L; Herald, John; Alpert, Craig; Gretebeck, Kimberlee A; Champoux, Wendy S; Dengel, Donald R; Vaitkevicius, Peter V; Alexander, Neil B

2016-07-01

Submaximal oxygen uptake measures are more feasible and may better predict clinical cardiac outcomes than maximal tests in older adults with heart failure (HF). We examined relationships between maximal oxygen uptake, submaximal oxygen kinetics, functional mobility, and physical activity in older adults with HF and reduced ejection fraction. Older adults with HF and reduced ejection fraction (n = 25, age 75 ± 7 years) were compared to 25 healthy age- and gender-matched controls. Assessments included a maximal treadmill test for peak oxygen uptake (VO2peak), oxygen uptake kinetics at onset of and on recovery from a submaximal treadmill test, functional mobility testing [Get Up and Go (GUG), Comfortable Gait Speed (CGS), Unipedal Stance (US)], and self-reported physical activity (PA). Compared to controls, HF had worse performance on GUG, CGS, and US, greater delays in submaximal oxygen uptake kinetics, and lower PA. In controls, VO2peak was more strongly associated with functional mobility and PA than submaximal oxygen uptake kinetics. In HF patients, submaximal oxygen uptake kinetics were similarly associated with GUG and CGS as VO2peak, but weakly associated with PA. Based on their mobility performance, older HF patients with reduced ejection fraction are at risk for adverse functional outcomes. In this population, submaximal oxygen uptake measures may be equivalent to VO2 peak in predicting functional mobility, and in addition to being more feasible, may provide better insight into how aerobic function relates to mobility in older adults with HF.

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

Science.gov (United States)

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.

Science.gov (United States)

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

Science.gov (United States)

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

2007-01-01

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

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.

Detection and monitoring of neurotransmitters--a spectroscopic analysis.

Science.gov (United States)

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.

Phytoremediation of arsenic contaminated paddy soils with Pteris vittata markedly reduces arsenic uptake by rice

International Nuclear Information System (INIS)

Ye Wenling; Khan, M. Asaduzzaman; McGrath, Steve P.; Zhao Fangjie

2011-01-01

Arsenic (As) accumulation in food crops such as rice is of major concern. To investigate whether phytoremediation can reduce As uptake by rice, the As hyperaccumulator Pteris vittata was grown in five contaminated paddy soils in a pot experiment. Over a 9-month period P. vittata removed 3.5-11.4% of the total soil As, and decreased phosphate-extractable As and soil pore water As by 11-38% and 18-77%, respectively. Rice grown following P. vittata had significantly lower As concentrations in straw and grain, being 17-82% and 22-58% of those in the control, respectively. Phytoremediation also resulted in significant changes in As speciation in rice grain by greatly decreasing the concentration of dimethylarsinic acid (DMA). In two soils the concentration of inorganic As in rice grain was decreased by 50-58%. The results demonstrate an effective stripping of bioavailable As from contaminated paddy soils thus reducing As uptake by rice. - Highlights: → Pteris vittata removed 3.5-11.4% of the total As from five contaminated paddy soils. → P. vittata decreased phosphate-extractable and soil solution As to a greater extent. → P. vittata reduced As concentration in rice grain by 18-83%. → P. vittata decreased methylated As in rice grain more than inorganic As. - Phytoremediation with P. vittata significantly reduced arsenic uptake by rice from contaminated paddy soils.

Phytoremediation of arsenic contaminated paddy soils with Pteris vittata markedly reduces arsenic uptake by rice

Energy Technology Data Exchange (ETDEWEB)

Ye Wenling [Rothamsted Research, Harpenden, Hertfordshire AL5 2JQ (United Kingdom); School of Earth and Space Sciences, University of Science and Technology of China, Hefei, Anhui 230026 (China); Khan, M. Asaduzzaman [Rothamsted Research, Harpenden, Hertfordshire AL5 2JQ (United Kingdom); Sher-e-Bangla Agricultural University, Sher-e-Bangla Nagar, Dhaka-1207 (Bangladesh); McGrath, Steve P. [Rothamsted Research, Harpenden, Hertfordshire AL5 2JQ (United Kingdom); Zhao Fangjie, E-mail: Fangjie.Zhao@bbsrc.ac.uk [Rothamsted Research, Harpenden, Hertfordshire AL5 2JQ (United Kingdom)

2011-12-15

Arsenic (As) accumulation in food crops such as rice is of major concern. To investigate whether phytoremediation can reduce As uptake by rice, the As hyperaccumulator Pteris vittata was grown in five contaminated paddy soils in a pot experiment. Over a 9-month period P. vittata removed 3.5-11.4% of the total soil As, and decreased phosphate-extractable As and soil pore water As by 11-38% and 18-77%, respectively. Rice grown following P. vittata had significantly lower As concentrations in straw and grain, being 17-82% and 22-58% of those in the control, respectively. Phytoremediation also resulted in significant changes in As speciation in rice grain by greatly decreasing the concentration of dimethylarsinic acid (DMA). In two soils the concentration of inorganic As in rice grain was decreased by 50-58%. The results demonstrate an effective stripping of bioavailable As from contaminated paddy soils thus reducing As uptake by rice. - Highlights: > Pteris vittata removed 3.5-11.4% of the total As from five contaminated paddy soils. > P. vittata decreased phosphate-extractable and soil solution As to a greater extent. > P. vittata reduced As concentration in rice grain by 18-83%. > P. vittata decreased methylated As in rice grain more than inorganic As. - Phytoremediation with P. vittata significantly reduced arsenic uptake by rice from contaminated paddy soils.

Selenium reduces cadmium uptake and mitigates cadmium toxicity in rice

Energy Technology Data Exchange (ETDEWEB)

Lin, Li; Zhou, Weihui; Dai, Huaxin; Cao, Fangbin; Zhang, Guoping [Department of Agronomy, College of Agriculture and Biotechnology, Zijingang Campus, Zhejiang University, Hangzhou, 310058 (China); Wu, Feibo, E-mail: wufeibo@zju.edu.cn [Department of Agronomy, College of Agriculture and Biotechnology, Zijingang Campus, Zhejiang University, Hangzhou, 310058 (China)

2012-10-15

Highlights: Black-Right-Pointing-Pointer Se alleviated Cd-toxicity, reduced Cd content and O{sub 2}{center_dot}{sup -}, H{sub 2}O{sub 2}, MDA in rice plants. Black-Right-Pointing-Pointer Se counteracted Cd-induced alterations of antioxidant enzymes. Black-Right-Pointing-Pointer Se suppressed Cd-induced increase in SOD, APX, but elevated depressed CAT activity. Black-Right-Pointing-Pointer Se markedly increased H{sup +}-ATPase, Ca{sup 2+}-ATPase activities in roots under Cd exposure. - Abstract: Hydroponic experiments were performed to investigate physiological mechanisms of selenium (Se) mitigation of Cd toxicity in rice. Exogenous Se markedly reduced Cd concentration in leaves, roots, and stems. Addition or pretreatment of 3 {mu}M Se in 50 {mu}M Cd solution significantly addressed Cd-induced growth inhibition, recovered root cell viability, and dramatically depressed O{sub 2}{center_dot}{sup -}, H{sub 2}O{sub 2}, and malondialdehyde (MDA) accumulation. Supplemental Se counteracted 50 {mu}M Cd-induced alterations of certain antioxidant enzymes, and uptake of nutrients, e.g. depressed Cd-induced increase in leaf and root superoxide dismutase (SOD) and leaf peroxidase (POD) activities, but elevated depressed catalase (CAT) activity; decreased Cd-induced high S and Cu concentrations in both leaves and roots. External Se counteracted the pattern of alterations in ATPase activities induced by Cd, e.g. significantly elevated the depressed root H{sup +}- and Ca{sup 2+}-ATPase activities, but decreased the ascent root Na{sup +}K{sup +}-ATP activity. Results indicate that alleviated Cd toxicity by Se application is related to reduced Cd uptake and ROS accumulation, balanced nutrients, and increased H{sup +}- and Ca{sup 2+}-ATPase activities in rice.

Reduced uptake of mass treatment for schistosomiasis control in absence of food

DEFF Research Database (Denmark)

Muhumuza, Simon; Olsen, Annette; Katahoire, Anne

2015-01-01

the other, in addition to the education messages, received a pre-treatment snack shortly before mass treatment. The uptake of praziquantel in the snack schools was 94 % compared to 79 % in the non-snack schools. During mass treatment in 2014, no snack was provided. We compared the uptake of praziquantel....... mansoni infection. RESULTS: Uptake of praziquantel reduced from 93.9 to 78.0 % (p = 0.002) in the snack schools but was unchanged in the non-schools 78.7 and 70.4 % (p = 0.176). The occurence of side-effects attributable to praziquantel increased from 34.4 to 61.2 % (p = 0.001) in the snack schools...... but was unchanged in the non-snack schools; 46.9 and 53.2 % (p = 0.443). Although the prevalence of S. mansoni infection increased in both the snack and non-snack schools, the differences did not reach statistical significance;1.3 and 7.5 % (p = 0.051) and 14.1 and 22.0 % (p = 0.141), respectively. Similarly...

Reduced 123I-BMIPP uptake implies decreased myocardial flow reserve in patients with chronic stable angina.

Science.gov (United States)

Kageyama, Hiroyuki; Morita, Koichi; Katoh, Chietsugu; Tsukamoto, Takahiro; Noriyasu, Kazuyuki; Mabuchi, Megumi; Naya, Masanao; Kawai, Yuko; Tamaki, Nagara

2006-01-01

Long-chain fatty acid (LCFA) is the main energy source for normal myocardium at rest, but in ischemic myocardium, the main energy substrate shifts from LCFA to glucose. 123I-BMIPP is a radiolabeled LCFA analog. In chronic stable angina without previous infarction, we suppose that reduced 123I-BMIPP uptake is related to the substrate shift in myocardium with decreased myocardial flow reserve (MFR). The purpose of this study was to relate 123I-BMIPP uptake to rest myocardial blood flow (MBF), hyperemic MBF, and MFR assessed with 15O-water positron emission tomography (PET). We enrolled 21 patients with chronic stable angina without previous infarction, all of whom underwent 123I-BMIPP single-photon emission computed tomography (SPECT) and 15O-water PET. The left ventricle was divided into 13 segments. In each segment, rest MBF and hyperemic MBF were measured by PET. 123I-BMIPP uptake was evaluated as follows: score 0=normal, 1=slightly decreased uptake, 2=moderately decreased uptake, 3=severely decreased uptake, and 4=complete defect. 123I-BMIPP uptake was compared with rest MBF, hyperemic MBF, and MFR. The numbers of segments with 123I-BMIPP scores 0, 1, 2, 3, and 4 were 178, 40, 25, 24, and 0, respectively. The rest MBFs for scores 0, 1, 2, and 3 were 0.93+/-0.25, 0.86+/-0.21, 0.97+/-0.30, and 0.99+/-0.37 ml/min/g, respectively. The hyperemic MBFs for scores 0, 1, 2, and 3 were 2.76+/-1.29, 1.84+/-0.74, 1.37+/-0.39, and 1.08+/-0.40 ml/min/g, respectively. The MFRs for scores 0, 1, 2, and 3 were 3.01+/-1.38, 2.20+/-0.95, 1.44+/-0.22, and 1.10+/-0.26, respectively. As 123I-BMIPP uptake declined, hyperemic MBF and MFR decreased. In chronic stable angina without previous infarction, reduced 123I-BMIPP uptake implies decreased MFR.

Reduced 123I-BMIPP uptake implies decreased myocardial flow reserve in patients with chronic stable angina

International Nuclear Information System (INIS)

Kageyama, Hiroyuki; Morita, Koichi; Katoh, Chietsugu; Mabuchi, Megumi; Tamaki, Nagara; Tsukamoto, Takahiro; Noriyasu, Kazuyuki; Naya, Masanao; Kawai, Yuko

2006-01-01

Long-chain fatty acid (LCFA) is the main energy source for normal myocardium at rest, but in ischemic myocardium, the main energy substrate shifts from LCFA to glucose. 123 I-BMIPP is a radiolabeled LCFA analog. In chronic stable angina without previous infarction, we suppose that reduced 123 I-BMIPP uptake is related to the substrate shift in myocardium with decreased myocardial flow reserve (MFR). The purpose of this study was to relate 123 I-BMIPP uptake to rest myocardial blood flow (MBF), hyperemic MBF, and MFR assessed with 15 O-water positron emission tomography (PET). We enrolled 21 patients with chronic stable angina without previous infarction, all of whom underwent 123 I-BMIPP single-photon emission computed tomography (SPECT) and 15 O-water PET. The left ventricle was divided into 13 segments. In each segment, rest MBF and hyperemic MBF were measured by PET. 123 I-BMIPP uptake was evaluated as follows: score 0=normal, 1=slightly decreased uptake, 2=moderately decreased uptake, 3=severely decreased uptake, and 4=complete defect. 123 I-BMIPP uptake was compared with rest MBF, hyperemic MBF, and MFR. The numbers of segments with 123 I-BMIPP scores 0, 1, 2, 3, and 4 were 178, 40, 25, 24, and 0, respectively. The rest MBFs for scores 0, 1, 2, and 3 were 0.93±0.25, 0.86±0.21, 0.97±0.30, and 0.99±0.37 ml/min/g, respectively. The hyperemic MBFs for scores 0, 1, 2, and 3 were 2.76±1.29, 1.84±0.74, 1.37±0.39, and 1.08±0.40 ml/min/g, respectively. The MFRs for scores 0, 1, 2, and 3 were 3.01±1.38, 2.20±0.95, 1.44±0.22, and 1.10±0.26, respectively. As 123 I-BMIPP uptake declined, hyperemic MBF and MFR decreased. In chronic stable angina without previous infarction, reduced 123 I-BMIPP uptake implies decreased MFR. (orig.)

Pattern recognition of neurotransmitters using multimode sensing.

Science.gov (United States)

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.

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

Neurotransmitter Transporter-Like: a male germline-specific SLC6 transporter required for Drosophila spermiogenesis.

Directory of Open Access Journals (Sweden)

Nabanita Chatterjee

2011-01-01

Full Text Available The SLC6 class of membrane transporters, known primarily as neurotransmitter transporters, is increasingly appreciated for its roles in nutritional uptake of amino acids and other developmentally specific functions. A Drosophila SLC6 gene, Neurotransmitter transporter-like (Ntl, is expressed only in the male germline. Mobilization of a transposon inserted near the 3' end of the Ntl coding region yields male-sterile mutants defining a single complementation group. Germline transformation with Ntl cDNAs under control of male germline-specific control elements restores Ntl/Ntl homozygotes to normal fertility, indicating that Ntl is required only in the germ cells. In mutant males, sperm morphogenesis appears normal, with elongated, individualized and coiled spermiogenic cysts accumulating at the base of the testes. However, no sperm are transferred to the seminal vesicle. The level of polyglycylation of Ntl mutant sperm tubulin appears to be significantly lower than that of wild type controls. Glycine transporters are the most closely related SLC6 transporters to Ntl, suggesting that Ntl functions as a glycine transporter in developing sperm, where augmentation of the cytosolic pool of glycine may be required for the polyglycylation of the massive amounts of tubulin in the fly's giant sperm. The male-sterile phenotype of Ntl mutants may provide a powerful genetic system for studying the function of an SLC6 transporter family in a model organism.

Siderophores mediate reduced and increased uptake of cadmium by Streptomyces tendae F4 and sunflower (Helianthus annuus), respectively.

Science.gov (United States)

Dimkpa, C O; Merten, D; Svatos, A; Büchel, G; Kothe, E

2009-11-01

As a toxic metal, cadmium (Cd) affects microbial and plant metabolic processes, thereby potentially reducing the efficiency of microbe or plant-mediated remediation of Cd-polluted soil. The role of siderophores produced by Streptomyces tendae F4 in the uptake of Cd by bacteria and plant was investigated to gain insight into the influence of siderophores on Cd availability to micro-organisms and plants. The bacterium was cultured under siderophore-inducing conditions in the presence of Cd. The kinetics of siderophore production and identification of the siderophores and their metal-bound forms were performed using electrospray ionization mass spectrometry. Inductively coupled plasma spectroscopy was used to measure iron (Fe) and Cd contents in the bacterium and in sunflower plant grown in Cd-amended soil. Siderophores significantly reduced the Cd uptake by the bacterium, while supplying it with iron. Bacterial culture filtrates containing three hydroxamate siderophores secreted by S. tendae F4 significantly promoted plant growth and enhanced uptake of Cd and Fe by the plant, relative to the control. Furthermore, application of siderophores caused slightly more Cd, but similar Fe uptake, compared with EDTA. Bioinoculation with Streptomyces caused a dramatic increase in plant Fe content, but resulted only in slight increase in plant Cd content. It is concluded that siderophores can help reduce toxic metal uptake in bacteria, while simultaneously facilitating the uptake of such metals by plants. Also, EDTA is not superior to hydroxamate siderophores in terms of metal solubilization for plant uptake. The study showed that microbial processes could indirectly influence the availability and amount of toxic metals taken up from the rhizosphere of plants. Furthermore, although EDTA is used for chelator-enhanced phytoremediation, microbial siderophores would be ideal for this purpose.

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

Directory of Open Access Journals (Sweden)

Jean-Luc eDo-Rego

2012-01-01

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

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.

Cardiac retention of PET neuronal imaging agent LMI1195 in different species: Impact of norepinephrine uptake-1 and -2 transporters

International Nuclear Information System (INIS)

Yu, Ming; Bozek, Jody; Kagan, Mikhail; Guaraldi, Mary; Silva, Paula; Azure, Michael; Onthank, David; Robinson, Simon P.

2013-01-01

Introduction: Released sympathetic neurotransmitter norepinephrine (NE) in the heart is cleared by neuronal uptake-1 and extraneuronal uptake-2 transporters. Cardiac uptake-1 and -2 expression varies among species, but the uptake-1 is the primary transporter in humans. LMI1195 is an NE analog labeled with 18 F for PET evaluation of cardiac neuronal function. This study investigated the impact of cardiac neuronal uptake-1 associated with different species on LMI1195 heart uptake. Methods: Cardiac uptake-1 was blocked by desipramine, a selective uptake-1 inhibitor, and sympathetic neuronal denervation was induced by 6-hydroxydopamine, a neurotoxin, in rats, rabbits and nonhuman primates (NHP). Tissue biodistribution and cardiac imaging of LMI1195 and 123 I-metaiodobenzylguanidine (MIBG) were performed. Results: In rats, uptake-1 blockade did not alter LMI1195 heart uptake compared to the control at 60-min post injection [1.41 ± 0.07 vs. 1.47 ± 0.23 % injected dose per gram tissue (%ID/g)]. In contrast, LMI1195 heart uptake was reduced by 80% in uptake-1 blocked rabbits. In sympathetically denervated rats, LMI1195 heart uptake was similar to the control (2.18 ± 0.40 vs. 2.58 ± 0.76 %ID/g). However, the uptake decreased by 79% in denervated rabbits. Similar results were found in MIBG heart uptake in rats and rabbits with uptake-1 blockade. Consistently, LMI1195 cardiac imaging showed comparable myocardial activity in uptake-1 blocked or sympathetically denervated rats to the control, but marked activity reduction in uptake-1 blocked or denervated rabbits and NHPs. Conclusions: LMI1195 is retained in the heart of rabbits and NHPs primarily via the neuronal uptake-1 with high selectivity and can be used for evaluation of cardiac sympathetic denervation. Similar to the human, the neuronal uptake-1 is the dominant transporter for cardiac retention of NE analogs in rabbits and NHPs, but not in rats

Reduced {sup 123}I-BMIPP uptake implies decreased myocardial flow reserve in patients with chronic stable angina

Energy Technology Data Exchange (ETDEWEB)

Kageyama, Hiroyuki; Morita, Koichi; Katoh, Chietsugu; Mabuchi, Megumi; Tamaki, Nagara [Hokkaido University Graduate School of Medicine, Department of Nuclear Medicine, Sapporo (Japan); Tsukamoto, Takahiro; Noriyasu, Kazuyuki; Naya, Masanao [Hokkaido University, Department of Cardiovascular Medicine, Sapporo (Japan); Hokkaido University Graduate School of Medicine, Department of Nuclear Medicine, Sapporo (Japan); Kawai, Yuko [Hokko Memorial Hospital, Department of Cardiovascular Medicine, Sapporo (Japan)

2006-01-01

Long-chain fatty acid (LCFA) is the main energy source for normal myocardium at rest, but in ischemic myocardium, the main energy substrate shifts from LCFA to glucose. {sup 123}I-BMIPP is a radiolabeled LCFA analog. In chronic stable angina without previous infarction, we suppose that reduced {sup 123}I-BMIPP uptake is related to the substrate shift in myocardium with decreased myocardial flow reserve (MFR). The purpose of this study was to relate {sup 123}I-BMIPP uptake to rest myocardial blood flow (MBF), hyperemic MBF, and MFR assessed with {sup 15}O-water positron emission tomography (PET). We enrolled 21 patients with chronic stable angina without previous infarction, all of whom underwent {sup 123}I-BMIPP single-photon emission computed tomography (SPECT) and {sup 15}O-water PET. The left ventricle was divided into 13 segments. In each segment, rest MBF and hyperemic MBF were measured by PET. {sup 123}I-BMIPP uptake was evaluated as follows: score 0=normal, 1=slightly decreased uptake, 2=moderately decreased uptake, 3=severely decreased uptake, and 4=complete defect. {sup 123}I-BMIPP uptake was compared with rest MBF, hyperemic MBF, and MFR. The numbers of segments with {sup 123}I-BMIPP scores 0, 1, 2, 3, and 4 were 178, 40, 25, 24, and 0, respectively. The rest MBFs for scores 0, 1, 2, and 3 were 0.93{+-}0.25, 0.86{+-}0.21, 0.97{+-}0.30, and 0.99{+-}0.37 ml/min/g, respectively. The hyperemic MBFs for scores 0, 1, 2, and 3 were 2.76{+-}1.29, 1.84{+-}0.74, 1.37{+-}0.39, and 1.08{+-}0.40 ml/min/g, respectively. The MFRs for scores 0, 1, 2, and 3 were 3.01{+-}1.38, 2.20{+-}0.95, 1.44{+-}0.22, and 1.10{+-}0.26, respectively. As {sup 123}I-BMIPP uptake declined, hyperemic MBF and MFR decreased. In chronic stable angina without previous infarction, reduced {sup 123}I-BMIPP uptake implies decreased MFR. (orig.)

Palmitoylation as a Functional Regulator of Neurotransmitter Receptors

Directory of Open Access Journals (Sweden)

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.

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

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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.

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

Science.gov (United States)

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.

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

Submaximal oxygen uptake kinetics, functional mobility, and physical activity in older adults with heart failure and reduced ejection fraction

OpenAIRE

Hummel, Scott L; Herald, John; Alpert, Craig; Gretebeck, Kimberlee A; Champoux, Wendy S; Dengel, Donald R; Vaitkevicius, Peter V; Alexander, Neil B

2016-01-01

Background Submaximal oxygen uptake measures are more feasible and may better predict clinical cardiac outcomes than maximal tests in older adults with heart failure (HF). We examined relationships between maximal oxygen uptake, submaximal oxygen kinetics, functional mobility, and physical activity in older adults with HF and reduced ejection fraction. Methods Older adults with HF and reduced ejection fraction (n = 25, age 75 ? 7 years) were compared to 25 healthy age- and gender-matched cont...

Low carbohydrate diet before 18F-FDG tumor imaging contributes to reduce myocardial 18F-FDG uptake

International Nuclear Information System (INIS)

Miao Weibing; Chen Shaoming; Zheng Shan; Wu Jing; Peng Jiequan; Jiang Zhihong

2014-01-01

Objective: To evaluate whether low carbohydrate diet before 18 F-FDG tumor imaging could reduce myocardial 18 F-FDG uptake. Methods: From April 2011 to January 2012, 70 patients were enrolled in this study.They were randomly divided into control group (34 cases) and test group (36 cases). Patients in control group were on regular diet, while those in test group had low carbohydrate diet in the evening before imaging. Blood samples were taken before injection of 18 F-FDG for the measurement of serum glucose, free fatty acid,insulin and ketone body. Whole body 18 F-FDG tomography was performed with dual-head coincidence SPECT. The myocardial uptake of FDG was assessed visually and scored as 0 for no uptake, 1 for uptake lower than liver, 2 for uptake similar to liver, 3 for uptake higher than liver, and 4 for remarkable uptake.The ratio of myocardium to liver (H/L) was calculated. Two-sample t test, Wilcoxon rank sum test and linear correlation analysis were performed. Results: The myocardial uptake in test group was significantly lower than that in control group with H/L ratios of 0.94±0.57 and 1.50±1.04, respectively (t=-2.75, P<0.05). The concentrations of serum free fatty acid and ketone body in test group were significantly higher than those in control group: (0.671±0.229) mmol/L vs (0.547±0.207) mmol/L and (0.88±0.60) mmol/L vs (0.57±0.32) mmol/L, t=2.38 and 2.67, both P<0.05. The concentrations of glucose and insulin were (5.28±1.06) mmol/L and (35.16±33.70) pmol/L in test group, which showed no significant difference with those in control group ((5.19±0.78) mmol/L and (41.64±35.13) pmol/L, t=0.39 and-0.79, both P>0.05). A negative correlation was found between the myocardial uptake of 18 F-FDG and serum free fatty acid/ketone body concentration (r=-0.40, -0.33, both P<0.01), respectively. There was no correlation between the myocardial uptake of 18 F-FDG and glucose/insulin (r=-0.02, 0.13, both P>0.05), respectively. Conclusion: Low carbohydrate

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.

Limited energy supply in Müller cells alters glutamate uptake

DEFF Research Database (Denmark)

Toft-Kehler, Anne Katrine; Skytt, Dorte Marie; Poulsen, Kristian Arild

2014-01-01

The viability of retinal ganglion cells (RGC) is essential for the maintenance of visual function. RGC homeostasis is maintained by the surrounding retinal glial cells, the Müller cells, which buffer the extracellular concentration of neurotransmitters and provide the RGCs with energy. This study...... evaluates if glucose-deprivation of Müller cells interferes with their ability to remove glutamate from the extracellular space. The human Müller glial cell line, Moorfields/Institute of Ophthalmology-Müller 1, was used to study changes in glutamate uptake. Excitatory amino acid transporter (EAAT) proteins...... were up-regulated in glucose-deprived Müller cells and glutamate uptake was significantly increased in the absence of glucose. The present findings revealed an up-regulation of EAAT1 and EAAT2 in glucose-deprived Müller cells as well as an increased ability to take up glutamate. Hence, glucose...

Sniffer patch laser uncaging response (SPLURgE): an assay of regional differences in allosteric receptor modulation and neurotransmitter clearance.

Science.gov (United States)

Christian, Catherine A; Huguenard, John R

2013-10-01

Allosteric modulators exert actions on neurotransmitter receptors by positively or negatively altering the effective response of these receptors to their respective neurotransmitter. γ-Aminobutyric acid (GABA) type A ionotropic receptors (GABAARs) are major targets for allosteric modulators such as benzodiazepines, neurosteroids, and barbiturates. Analysis of substances that produce similar effects has been hampered by the lack of techniques to assess the localization and function of such agents in brain slices. Here we describe measurement of the sniffer patch laser uncaging response (SPLURgE), which combines the sniffer patch recording configuration with laser photolysis of caged GABA. This methodology enables the detection of allosteric GABAAR modulators endogenously present in discrete areas of the brain slice and allows for the application of exogenous GABA with spatiotemporal control without altering the release and localization of endogenous modulators within the slice. Here we demonstrate the development and use of this technique for the measurement of allosteric modulation in different areas of the thalamus. Application of this technique will be useful in determining whether a lack of modulatory effect on a particular category of neurons or receptors is due to insensitivity to allosteric modulation or a lack of local release of endogenous ligand. We also demonstrate that this technique can be used to investigate GABA diffusion and uptake. This method thus provides a biosensor assay for rapid detection of endogenous GABAAR modulators and has the potential to aid studies of allosteric modulators that exert effects on other classes of neurotransmitter receptors, such as glutamate, acetylcholine, or glycine receptors.

Rain events decrease boreal peatland net CO2 uptake through reduced light availability.

Science.gov (United States)

Nijp, Jelmer J; Limpens, Juul; Metselaar, Klaas; Peichl, Matthias; Nilsson, Mats B; van der Zee, Sjoerd E A T M; Berendse, Frank

2015-06-01

Boreal peatlands store large amounts of carbon, reflecting their important role in the global carbon cycle. The short-term exchange and the long-term storage of atmospheric carbon dioxide (CO2 ) in these ecosystems are closely associated with the permanently wet surface conditions and are susceptible to drought. Especially, the single most important peat forming plant genus, Sphagnum, depends heavily on surface wetness for its primary production. Changes in rainfall patterns are expected to affect surface wetness, but how this transient rewetting affects net ecosystem exchange of CO2 (NEE) remains unknown. This study explores how the timing and characteristics of rain events during photosynthetic active periods, that is daytime, affect peatland NEE and whether rain event associated changes in environmental conditions modify this response (e.g. water table, radiation, vapour pressure deficit, temperature). We analysed an 11-year time series of half-hourly eddy covariance and meteorological measurements from Degerö Stormyr, a boreal peatland in northern Sweden. Our results show that daytime rain events systematically decreased the sink strength of peatlands for atmospheric CO2 . The decrease was best explained by rain associated reduction in light, rather than by rain characteristics or drought length. An average daytime growing season rain event reduced net ecosystem CO2 uptake by 0.23-0.54 gC m(-2) . On an annual basis, this reduction of net CO2 uptake corresponds to 24% of the annual net CO2 uptake (NEE) of the study site, equivalent to a 4.4% reduction of gross primary production (GPP) during the growing season. We conclude that reduced light availability associated with rain events is more important in explaining the NEE response to rain events than rain characteristics and changes in water availability. This suggests that peatland CO2 uptake is highly sensitive to changes in cloud cover formation and to altered rainfall regimes, a process hitherto largely

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.

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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.

Diphenyl diselenide ameliorates monosodium glutamate induced anxiety-like behavior in rats by modulating hippocampal BDNF-Akt pathway and uptake of GABA and serotonin neurotransmitters.

Science.gov (United States)

Rosa, Suzan Gonçalves; Quines, Caroline Brandão; Stangherlin, Eluza Curte; Nogueira, Cristina Wayne

2016-03-01

Monosodium glutamate (MSG), a flavor enhancer used in food, administered to neonatal rats causes neuronal lesions and leads to anxiety when adulthood. We investigated the anxiolytic-like effect of diphenyl diselenide (PhSe)2 and its mechanisms on anxiety induced by MSG. Neonatal male and female Wistar rats received a subcutaneous injection of saline (0.9%) or MSG (4 g/kg/day) from the 1st to 10th postnatal day. At 60 days of life, the rats received (PhSe)2 (1mg/kg/day) or vehicle by the intragastric route for 7 days. The spontaneous locomotor activity (LAM), elevated plus maze test (EPM) and contextual fear conditioning test (CFC) as well as neurochemical ([(3)H]GABA and [(3)H]5-HT uptake) and molecular analyses (Akt and p-Akt and BDNF levels) were carried out after treatment with (PhSe)2. Neonatal exposure to MSG increased all anxiogenic parameters in LAM, EPM and CFC tests. MSG increased GABA and 5-HT uptake in hippocampus of rats, without changing uptake in cerebral cortex. The levels of BDNF and p-Akt were reduced in hippocampus of rats treated with MSG. The administration of (PhSe)2 to rats reversed all behavioral anxiogenic parameters altered by MSG. The increase in hippocampal GABA and 5-HT uptake induced by MSG was reversed by (PhSe)2. (PhSe)2 reversed the reduction in hippocampal BDNF and p-Akt levels induced by MSG. In conclusion, the anxiolytic-like action of (PhSe)2 in rats exposed to MSG during their neonatal period is related to its modulation of hippocampal GABA and 5-HT uptake as well as the BDNF-Akt pathway. Copyright © 2015 Elsevier Inc. All rights reserved.

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

Effects of antibiotics on uptake of calcium into isolated nerve terminals

International Nuclear Information System (INIS)

Atchison, W.D.; Adgate, L.; Beaman, C.M.

1988-01-01

The goal of the present study was to determine whether several antibiotics which are known to block neuromuscular transmission would impair depolarization-dependent and/or -independent uptake of calcium into isolated nerve terminals prepared from forebrain synaptosomes of rats by conventional methods. Antibiotics tested for potential block of Ca++ uptake included the aminoglycosides neomycin and streptomycin, the lincosamide clindamycin, oxytetracycline and polymyxin B. Drugs were applied in concentrations ranging from 1 to 1000 microM. Uptake of 45Ca was determined during depolarization induced by an elevated K+ concentration (77.5 mM). Influxes of 45Ca during 1 and 10 sec of depolarization were used to assess Ca++ uptake via a fast, inactivating path and total uptake, respectively. Uptake of 45Ca during 10 sec of depolarization into synaptosomes which were previously depolarized for 10 sec in the presence of 77.5 mM K+ but in the absence of external Ca++ was used to measure uptake during a slow, noninactivating path. Total depolarization-dependent uptake of 45Ca was depressed significantly by all antibiotics tested except oxytetracycline; however, the various agents differed with respect to their efficacy and potency as blockers of Ca influx. The fast component of uptake, which is thought to be associated with neurotransmitter release, was decreased significantly by all antibiotics. Neomycin and polymyxin were the most potent and most effective at lowering fast phase 45Ca influx; streptomycin, was intermediate in effectiveness whereas clindamycin and oxytetracycline were only effective at concentrations greater than or equal to 100 microM. Only clindamycin, streptomycin and polymyxin B caused significant reductions in the slow phase of 45Ca uptake

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.)

[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.

[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.

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...

Phytoremediation of arsenic contaminated paddy soils with Pteris vittata markedly reduces arsenic uptake by rice.

Science.gov (United States)

Ye, Wen-Ling; Khan, M Asaduzzaman; McGrath, Steve P; Zhao, Fang-Jie

2011-12-01

Arsenic (As) accumulation in food crops such as rice is of major concern. To investigate whether phytoremediation can reduce As uptake by rice, the As hyperaccumulator Pteris vittata was grown in five contaminated paddy soils in a pot experiment. Over a 9-month period P. vittata removed 3.5-11.4% of the total soil As, and decreased phosphate-extractable As and soil pore water As by 11-38% and 18-77%, respectively. Rice grown following P. vittata had significantly lower As concentrations in straw and grain, being 17-82% and 22-58% of those in the control, respectively. Phytoremediation also resulted in significant changes in As speciation in rice grain by greatly decreasing the concentration of dimethylarsinic acid (DMA). In two soils the concentration of inorganic As in rice grain was decreased by 50-58%. The results demonstrate an effective stripping of bioavailable As from contaminated paddy soils thus reducing As uptake by rice. Copyright © 2011 Elsevier Ltd. All rights reserved.

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.

Studies on the hepatic uptake of In-111 labeled monoclonal antibodies and the method to reduce the hepatic uptake

International Nuclear Information System (INIS)

Kinuya, Seigo

1990-01-01

Prolonged retention of In-111 labeled monoclonal antibody (In-111 MoAb) in the liver poses problems in radioimmunoscintigraphy. Therefore, subcellular kinetics of In-111 MoAb was investigated. In a study with In-111 225.28S in normal SD rats, the supernatant was found to be a predominant fraction of In-111 radioactivity (61% at 3 hr), with the activity decreasing with time to 21% at 72 hr; however, activity of the mitochondrial fraction was found to increase from 11% to 44%. High performance liquid chromatography for the supernatant revealed that In-111 activity at the earlier time was mainly eluted with the intact IgG peak, and that the major peak activity was thereafter reduced with associated activity peaks found in smaller moistly fractions. Such a sequential distribution change of In-111 225.28S was not found when labeled with I-125. A study with In-111 ZCE025 in mice bearing human colon cancer revealed that activity of the supernatant fraction decreased with time, but the lysosomal activity increased from 14% to 29%, as found in the experiment using normal rats. In tumors, the subcellular distribution of In-111 radioactivity almost remained unchanged throughout the study. The lysosomal fraction was not a predominant fraction of In-111 radioactivity in tumors. When 4 mg of ferric ion (Fe) was administered 48 hr before the injection of In-111 ZCE025, liver uptake of In-111 decreased as compared with the non-Fe group, but tumor uptake was unchanged. Intrahepatic lysosomal radioactivity was smaller in the Fe group than the non-Fe group. These results indicated the involvement of lysosomes in hepatic retention of In-111 MoAb. Once taken up by the liver, the MoAb was metabolized in the supernatant and In-111 ion was transchelated from DTPA onto the lysosomal substances resulting in prolonged retention in the liver. The lysosome in the liver could be saturated by Fe, resulting in a decrease of hepatic uptake without a decrease of tumor uptake. (N.K.) 53 refs

Intramolecular cross-linking in a bacterial homolog of mammalian SLC6 neurotransmitter transporters suggests an evolutionary conserved role of transmembrane segments 7 and 8

DEFF Research Database (Denmark)

Kniazeff, Julie; Loland, Claus Juul; Goldberg, Naomi

2005-01-01

The extracellular concentration of the neurotransmitters dopamine, serotonin, norepinephrine, GABA and glycine is tightly controlled by plasma membrane transporters belonging to the SLC6 gene family. A very large number of putative transport proteins with a remarkable homology to the SLC6...... proximity between TM 7 and 8 in the tertiary structure of TnaT as previously suggested for the mammalian counterparts. Furthermore, the inhibition of uptake upon cross-linking the two cysteines provides indirect support for a conserved conformational role of these transmembrane domains in the transport...

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.

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

Science.gov (United States)

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.

Extracellular Vesicles from Hypoxic Adipocytes and Obese Subjects Reduce Insulin‐Stimulated Glucose Uptake

Science.gov (United States)

Mleczko, Justyna; Ortega, Francisco J.; Falcon‐Perez, Juan Manuel; Wabitsch, Martin; Fernandez‐Real, Jose Manuel

2018-01-01

Scope We investigate the effects of extracellular vesicles (EVs) obtained from in vitro adipocyte cell models and from obese subjects on glucose transport and insulin responsiveness. Methods and results EVs are isolated from the culture supernatant of adipocytes cultured under normoxia, hypoxia (1% oxygen), or exposed to macrophage conditioned media (15% v/v). EVs are isolated from the plasma of lean individuals and subjects with obesity. Cultured adipocytes are incubated with EVs and activation of insulin signalling cascades and insulin‐stimulated glucose transport are measured. EVs released from hypoxic adipocytes impair insulin‐stimulated 2‐deoxyglucose uptake and reduce insulin mediated phosphorylation of AKT. Insulin‐mediated phosphorylation of extracellular regulated kinases (ERK1/2) is not affected. EVs from individuals with obesity decrease insulin stimulated 2‐deoxyglucose uptake in adipocytes (p = 0.0159). Conclusion EVs released by stressed adipocytes impair insulin action in neighboring adipocytes. PMID:29292863

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.

Method to reduce contamination and uptake of lead by plants from car exhaust gases

Energy Technology Data Exchange (ETDEWEB)

Isermann, K.

1977-03-01

Splashing and/or washing plants with aqueous solutions of the chelates CaEDTA (max. 5 mM/litre) or Na-polyphosphate (max. 0.5 percent) is an effective way of reducing contamination and uptake of lead by plants within regions where lead is emitted at significant levels. By chelating lead it first becomes unloaded or even negatively charged (for instance with EDTA as Pb/sub 2/EDTA or PbHEDTA/sup 1 -/ and PbEDTA/sup 2 -/). Therefore chelated lead, in contrast to normal Pb/sup 2 +/, is not absorbed, either on negatively charged surfaces of the plants (cuticula) or within the plant-tissue (mesophyll, on negatively charged cell-walls or membranes). Also, Pb-chelate has a larger diameter than bivalent Pb/sup 2 +/, resulting in a restricted lead uptake by the plant roots.

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

Science.gov (United States)

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

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

Reduced malonyl-CoA content in recovery from exercise correlates with improved insulin-stimulated glucose uptake in human skeletal muscle

DEFF Research Database (Denmark)

Frøsig, Christian; Roepstorff, Carsten; Brandt, Nina

2009-01-01

This study evaluated whether improved insulin-stimulated glucose uptake in recovery from acute exercise coincides with reduced malonyl-CoA (MCoA) content in human muscle. Furthermore, we investigated whether a high-fat diet [65 energy-% (Fat)] would alter the content of MCoA and insulin action...... to be compromised, although to a minor extent, by the Fat diet. Collectively, this study indicates that reduced muscle MCoA content in recovery from exercise may be part of the adaptive response leading to improved insulin action on glucose uptake after exercise in human muscle....

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

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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.

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...

Depolarization-dependent 45Ca uptake by synaptosomes of rat cerebral cortex is enhanced by L-triiodothyronine

International Nuclear Information System (INIS)

Mason, G.A.; Walker, C.H.; Prange, A.J. Jr.

1990-01-01

Depolarization-induced release of neurotransmitters and other secretions from nerve endings is triggered by the rapid entry of Ca++ through voltage-sensitive channels. Calcium entry is thought to occur in two distinct phases or processes: a fast-phase response to an action potential, which initiates release; and a slow phase associated with extended stimulation of the neuron. Thyroid hormones are sequestered by nerve terminals and can produce changes in behaviour and mood. They may therefore be involved in modulating central synaptic transmission. We studied the effects of L-triiodothyronine (T3), L-thyroxine (T4), reverse T3 (rT3) and D-T3 on depolarization-induced uptake of 45Ca by synaptosomes from euthyroid and hypothyroid rats. T3, but not T4, rT3, or D-T3 significantly enhanced depolarization-induced 45Ca uptake at physiologically relevant (1 to 10 nmol/L) concentrations. The stimulatory effect of 10 nmol/L T3 on depolarization-induced uptake after 2 seconds (21%) was greater than after 5 (10%) or 30 (8%) seconds, indicating that T3 enhanced primarily the fast-phase process. There was no effect of T3 or other hormones tested on nondepolarization-induced 45Ca uptake. Preincubation of synaptosomes with T3 prior to depolarization did not enhance the effect of T3; in fact, preincubations of 30 seconds or more resulted in diminished T3 effects. Preincubation of synaptosomes for 15 seconds with D-T3 or the addition of D-T3 and T3 together reduced the effect of T3. We found no difference in the effect of T3 on 45Ca uptake by synaptosomes from euthyroid and hypothyroid rats. These results suggest a novel mechanism of action of thyroid hormones in the brain

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...

Thyroid uptake test

International Nuclear Information System (INIS)

Ganatra, R.D.

1992-01-01

The uptake of radioiodine by the thyroid gland is altered by the iodine content of diet or drugs. American diet has a high iodine content because each slice of the white bread contains nearly 150μg of iodine due to the bleaching process employed in the production of the bread. This carrier content of iodine reduces the uptake so much, that the normal American uptakes are usually three to four times lower than the uptakes in the developing countries. The other drawback of the thyroid uptake test is that it is affected by the iodine containing drugs. Anti-diarrhoea medications are quire common in the developing countries and many of them contain iodine moiety. Without a reliable drug history, a low thyroid uptake value may lead to a misleading conclusion

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.

The building of the neocortex with non-hyperpolarizing neurotransmitters.

Science.gov (United States)

Ascenzi, Matteo; Bony, Guillaume

2017-09-01

The development of the neocortex requires the synergic action of several secreted molecules to achieve the right amount of proliferation, differentiation, and migration of neural cells. Neurons are well known to release neurotransmitters (NTs) in adult and a growing body of evidences describes the presence of NTs already in the embryonic brain, long before the generation of synapses. NTs are classified as inhibitory or excitatory based on the physiological responses of the target neuron. However, this view is challenged by the fact that glycine and GABA NTs are excitatory during development. Many reviews have described the role of nonhyperpolarizing GABA at this stage. Nevertheless, a global consideration of the inhibitory neurotransmitters and their downstream signaling during the embryonic cortical development is still needed. For example, taurine, the most abundant neurotransmitter during development is poorly studied regarding its role during cortical development. In the light of recent discoveries, we will discuss the functions of glycine, GABA, and taurine during embryonic cortical development with an emphasis on their downstream signaling. © 2017 Wiley Periodicals, Inc. Develop Neurobiol 77: 1023-1037, 2017. © 2017 Wiley Periodicals, Inc.

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.

Depolarization-dependent sup 45 Ca uptake by synaptosomes of rat cerebral cortex is enhanced by L-triiodothyronine

Energy Technology Data Exchange (ETDEWEB)

Mason, G.A.; Walker, C.H.; Prange, A.J. Jr. (Univ. of North Carolina, Chapel Hill (USA))

1990-08-01

Depolarization-induced release of neurotransmitters and other secretions from nerve endings is triggered by the rapid entry of Ca++ through voltage-sensitive channels. Calcium entry is thought to occur in two distinct phases or processes: a fast-phase response to an action potential, which initiates release; and a slow phase associated with extended stimulation of the neuron. Thyroid hormones are sequestered by nerve terminals and can produce changes in behaviour and mood. They may therefore be involved in modulating central synaptic transmission. We studied the effects of L-triiodothyronine (T3), L-thyroxine (T4), reverse T3 (rT3) and D-T3 on depolarization-induced uptake of 45Ca by synaptosomes from euthyroid and hypothyroid rats. T3, but not T4, rT3, or D-T3 significantly enhanced depolarization-induced 45Ca uptake at physiologically relevant (1 to 10 nmol/L) concentrations. The stimulatory effect of 10 nmol/L T3 on depolarization-induced uptake after 2 seconds (21%) was greater than after 5 (10%) or 30 (8%) seconds, indicating that T3 enhanced primarily the fast-phase process. There was no effect of T3 or other hormones tested on nondepolarization-induced 45Ca uptake. Preincubation of synaptosomes with T3 prior to depolarization did not enhance the effect of T3; in fact, preincubations of 30 seconds or more resulted in diminished T3 effects. Preincubation of synaptosomes for 15 seconds with D-T3 or the addition of D-T3 and T3 together reduced the effect of T3. We found no difference in the effect of T3 on 45Ca uptake by synaptosomes from euthyroid and hypothyroid rats. These results suggest a novel mechanism of action of thyroid hormones in the brain.

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

Science.gov (United States)

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

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

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.

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.)

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

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

Science.gov (United States)

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.

GABA and glycine as neurotransmitters: a brief history.

Science.gov (United States)

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.

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.

Enhancing soil infiltration reduces gaseous emissions and improves N uptake from applied dairy slurry.

Science.gov (United States)

Bhandral, R; Bittman, S; Kowalenko, G; Buckley, K; Chantigny, M H; Hunt, D E; Bounaix, F; Friesen, A

2009-01-01

Rapid infiltration of liquid manure into the soil reduces emissions of ammonia (NH(3)) into the atmosphere. This study was undertaken to assess the effects of two low-cost methods of assisting infiltration of applied dairy slurry on emissions of NH(3), nitrous oxide (N(2)O), and on crop N uptake. The two methods were removing of solids by settling-decantation to make the manure less viscous and mechanically aerating the soil. Ammonia emissions were measured with wind tunnels as percentage of applied total ammoniacal nitrogen (TAN) while emissions of N(2)O were measured with vented chambers. Mechanically aerating the soil before manure application significantly reduced emissions of NH(3) relative to the nonaerated soil in spring (38.6 to 20.3% of applied TAN), summer (41.1 to 26.4% of applied TAN) and fall (27.7 to 13.6% of applied TAN) trials. Decantation of manure had no effect on NH(3) emissions in spring, tended to increase emissions in summer and significantly decreased emissions in fall (30.3 to 11.1% of applied TAN). Combining the two abatement techniques reduced NH(3) emission by 82% in fall, under cool weather conditions typical of manure spreading. The two abatement techniques generally did not significantly affect N(2)O emissions. Uptake of applied N by Italian ryegrass (Lolium multiflorum Lam.) was generally significantly greater with decanted than from whole manure but the effect of aeration was generally small and not significant. The study shows that low cost methods that assist manure infiltration into the soil may be used to greatly reduce ammonia loss without increasing N(2)O emissions, but efficacy of abatement methods is affected by weather conditions.

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

Science.gov (United States)

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.

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...

Glutamine synthetase activity and glutamate uptake in hippocampus and frontal cortex in portal hypertensive rats

Science.gov (United States)

Acosta, Gabriela Beatriz; Fernández, María Alejandra; Roselló, Diego Martín; Tomaro, María Luján; Balestrasse, Karina; Lemberg, Abraham

2009-01-01

AIM: To study glutamine synthetase (GS) activity and glutamate uptake in the hippocampus and frontal cortex (FC) from rats with prehepatic portal vein hypertension. METHODS: Male Wistar rats were divided into sham-operated group and a portal hypertension (PH) group with a regulated stricture of the portal vein. Animals were sacrificed by decapitation 14 d after portal vein stricture. GS activity was determined in the hippocampus and FC. Specific uptake of radiolabeled L-glutamate was studied using synaptosome-enriched fractions that were freshly prepared from both brain areas. RESULTS: We observed that the activity of GS increased in the hippocampus of PH rats, as compared to control animals, and decreased in the FC. A significant decrease in glutamate uptake was found in both brain areas, and was more marked in the hippocampus. The decrease in glutamate uptake might have been caused by a deficient transport function, significantly and persistent increase in this excitatory neurotransmitter activity. CONCLUSION: The presence of moderate ammonia blood levels may add to the toxicity of excitotoxic glutamate in the brain, which causes alterations in brain function. Portal vein stricture that causes portal hypertension modifies the normal function in some brain regions. PMID:19533812

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

Science.gov (United States)

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.

ATP Synthase β-Chain Overexpression in SR-BI Knockout Mice Increases HDL Uptake and Reduces Plasma HDL Level

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Kexiu Song

2014-01-01

Full Text Available HDL cholesterol is known to be inversely correlated with cardiovascular disease due to its diverse antiatherogenic functions. SR-BI mediates the selective uptake of HDL-C. SR-BI knockout diminishes but does not completely block the transport of HDL; other receptors may be involved. Ectopic ATP synthase β-chain in hepatocytes has been previously characterized as an apoA-I receptor, triggering HDL internalization. This study was undertaken to identify the overexpression of ectopic ATP synthase β-chain on DIL-HDL uptake in primary hepatocytes in vitro and on plasma HDL levels in SR-BI knockout mice. Human ATP synthase β-chain cDNA was delivered to the mouse liver by adenovirus and GFP adenovirus as control. The adenovirus-mediated overexpression of β-chain was identified at both mRNA and protein levels on mice liver and validated by its increasing of DiL-HDL uptake in primary hepatocytes. In response to hepatic overexpression of β-chain, plasma HDL-C levels and cholesterol were reduced in SR-BI knockout mice, compared with the control. The present data suggest that ATP synthase β-chain can serve as the endocytic receptor of HDL, and its overexpression can reduce plasma HDL-C.

Reduced isotope uptake restricted to the motor area in patients with amyotrophic lateral sclerosis

International Nuclear Information System (INIS)

Abe, K.; Yorifuji, S.; Nishikawa, Y.

1993-01-01

To study degeneration in the central nervous system in amyotrophic lateral sclerosis (ALS), we studied four patients using single photon emission tomography (SPECT) and magnetic resonance imaging (MRI). MRI demonstrated high intensity along the pyramidal tract on T2-weighted images in two. SPECT demonstrated reduced isotope uptake restricted to the motor area. While the cause of degeneration of the cortical neurons in the motor area is unknown, SPECT is useful for detecting the degeneration in patients with ALS. (orig.)

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.

Reduced 125I-meta-iodobenzylguanidine uptake and norepinephrine transporter density in the hearts of mice with MPTP-induced parkinsonism

International Nuclear Information System (INIS)

Fukumitsu, Nobuyoshi; Suzuki, Masahiko; Fukuda, Takahiro; Kiyono, Yasushi; Kajiyama, Satomi; Saji, Hideo

2006-01-01

Uptake of 123 I-meta-iodobenzylguanidine ( 123 I-MIBG) is markedly reduced in the hearts of patients with Parkinson's disease. Although the mechanism of this reduction is unclear, 12 5 I-MIBG uptake is similarly reduced in the hearts of mice with 1-methyl-4-phenyl-1,2,3,6-tetrahydroxypyridine (MPTP)-induced parkinsonism. Three groups of ten 15-week-old C57BL6 mice received intraperitoneal injections of (1) saline (control) (2) 10 mg/kg MPTP or (3) 40 mg/kg MPTP. After 0.185 MBq of 125 I-MIBG was injected, the percent injected dose of 125 I-MIBG per gram of tissue (%ID/g) was determined and cardiac concentrations of norepinephrine were measured. Cardiac concentrations of norepinephrine transporter (NET) were measured in three groups of twenty 15-week-old C57BL6 mice receiving these same treatments. The %ID/g in mice receiving 10 or 40 mg/kg MPTP (5.7±1.1 and 4.4±1.2%/g) was significantly lower than that in control mice (11.3±2.2%/g; P 5 and 7.50±0.89x10 5 pg/wet g) was significantly lower than that in control mice (9.21±0.97x10 5 pg/wet g; P 125 I-MIBG and NET density decreased as the dose of MPTP increased. This study clearly shows that reduced cardiac 12 5 I-MIBG uptake in mice with MPTP-induced parkinsonism is closely related to the reduced NET density in postganglionic cardiac sympathetic nerve terminals

Dopamine receptors on adrenal chromaffin cells modulate calcium uptake and catecholamine release

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Bigornia, L; Suozzo, M; Ryan, K A; Napp, D; Schneider, A S

1988-10-01

The presence of dopamine-containing cells in sympathetic ganglia, i.e., small, intensely fluorescent cells, has been known for some time. However, the role of dopamine as a peripheral neurotransmitter and its mechanism of action are not well understood. Previous studies have demonstrated the presence of D2 dopamine receptors on the surface of bovine adrenal chromaffin cells using radioligand binding methods and dopamine receptor inhibition of catecholamine release from perfused adrenal glands. In the present study, we provide evidence confirming a role of dopamine receptors as inhibitory modulators of adrenal catecholamine release from bovine chromaffin cell cultures and further show that the mechanism of modulation involves inhibition of stimulated calcium uptake. Apomorphine gave a dose-dependent inhibition (IC50 = 1 microM) of 45Ca2+ uptake stimulated by either nicotine (10 microM) or membrane depolarization with an elevated K+ level (60 mM). This inhibition was reversed by a series of specific (including stereospecific) dopamine receptor antagonists: haloperidol, spiperone, sulpiride, and (+)-butaclamol, but not (-)-butaclamol. In addition, the calcium channel agonist Bay K 8644 was used to stimulate uptake of 45Ca2+ into chromaffin cells, and this uptake was also inhibited by the dopamine receptor agonist apomorphine. The combined results suggest that dopamine receptors on adrenal chromaffin cells alter Ca2+ channel conductance, which, in turn, modulates catecholamine release.

Peripheral Nerve Fibers and Their Neurotransmitters in Osteoarthritis Pathology.

Science.gov (United States)

Grässel, Susanne; Muschter, Dominique

2017-04-28

The importance of the nociceptive nervous system for maintaining tissue homeostasis has been known for some time, and it has also been suggested that organogenesis and tissue repair are under neuronal control. Changes in peripheral joint innervation are supposed to be partly responsible for degenerative alterations in joint tissues which contribute to development of osteoarthritis. Various resident cell types of the musculoskeletal system express receptors for sensory and sympathetic neurotransmitters, allowing response to peripheral neuronal stimuli. Among them are mesenchymal stem cells, synovial fibroblasts, bone cells and chondrocytes of different origin, which express distinct subtypes of adrenoceptors (AR), receptors for vasoactive intestinal peptide (VIP), substance P (SP) and calcitonin gene-related peptide (CGRP). Some of these cell types synthesize and secrete neuropeptides such as SP, and they are positive for tyrosine-hydroxylase (TH), the rate limiting enzyme for biosynthesis of catecholamines. Sensory and sympathetic neurotransmitters are involved in the pathology of inflammatory diseases such as rheumatoid arthritis (RA) which manifests mainly in the joints. In addition, they seem to play a role in pathogenesis of priori degenerative joint disorders such as osteoarthritis (OA). Altogether it is evident that sensory and sympathetic neurotransmitters have crucial trophic effects which are critical for joint tissue and bone homeostasis. They modulate articular cartilage, subchondral bone and synovial tissue properties in physiological and pathophysiological conditions, in addition to their classical neurological features.

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 ...

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

Science.gov (United States)

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

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.

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.

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

SNT-1 functions as the Ca2+ sensor for tonic and evoked neurotransmitter release in C. elegans.

Science.gov (United States)

Li, Lei; Liu, Haowen; Wang, Wei; Chandra, Mintu; Collins, Brett M; Hu, Zhitao

2018-05-14

Synaptotagmin-1 (Syt1) binds Ca 2+ through its tandem C2 domains (C2A and C2B) and triggers Ca 2+ -dependent neurotransmitter release. Here we show that snt-1 , the homolog of mammalian Syt1, functions as the Ca 2+ sensor for both tonic and evoked neurotransmitter release at the C. elegans neuromuscular junction. Mutations that disrupt Ca 2+ binding in double C2 domains of SNT-1 significantly impaired tonic release, whereas disrupting Ca 2+ binding in a single C2 domain had no effect, indicating that the Ca 2+ binding of the two C2 domains is functionally redundant for tonic release. Stimulus-evoked release was significantly reduced in snt-1 mutants, with prolonged release latency as well as faster rise and decay kinetics. Unlike tonic release, evoked release was triggered by Ca 2+ binding solely to the C2B domain. Moreover, we showed that SNT-1 plays an essential role in the priming process in different subpopulations of synaptic vesicles with tight or loose coupling to Ca 2+ entry. SIGNIFICANCE STATEMENT We showed that SNT-1 in C. elegans regulates evoked neurotransmitter release through Ca 2+ binding to its C2B domain, a similar way to Syt1 in the mouse CNS and the fly NMJ. However, the largely decreased tonic release in snt-1 mutants argues SNT-1 has a clamping function. Indeed, Ca 2+ -binding mutations in the C2 domains in SNT-1 significantly reduced the frequency of the miniature excitatory postsynaptic current (mEPSC), indicating that SNT-1 also acts as a Ca 2+ sensor for tonic release. Therefore, revealing the differential mechanisms between invertebrates and vertebrates will provide significant insights into our understanding how synaptic vesicle fusion is regulated. Copyright © 2018 the authors.

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.

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.

Optimization of a blanching process to reduce the furan level of potato crisps without increasing their oil uptake

DEFF Research Database (Denmark)

Mariotti, Salomé; Granby, Kit

, the objective of this work was to reduce the level of furan in crisps without increasing their oil uptake. To accomplish this purpose a central composite design was used to study the effect of blanching time and temperature on the reduction of reducing sugars, one of furan precursors, in potato slices. After...... levels of both reducing sugar and furan, crisps pre-treated under these conditions presented a significant increasing in their oil content. On the other hand, blanching at temperature of 65° for 10 min was a 30% more efficient (30 %) in the extraction of reducing sugars compared to blanching at lower...

Distribution of 3H-GABA uptake sites in the nematode Ascaris

International Nuclear Information System (INIS)

Guastella, J.; Stretton, A.O.

1991-01-01

The distribution of uptake sites for the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) in the nematode Ascaris suum was examined by autoradiography of 3H-GABA uptake. Single neural processes in both the ventral and dorsal nerve cords were labeled with 3H-GABA. Serial section analysis identified the cells of origin of these processes as the RMEV-like and RMED-like neurons. These cells belong to a set of four neurons in the nerve ring, all of which are labeled by 3H-GABA. 3H-GABA labeling of at least two other sets of cephalic neurons was seen. One of these pairs consists of medium-sized lateral ganglia neurons, located at the level of the amphid commissure bundle. A second pair is located in the lateral ganglia at the level of the deirid commissure bundle. The position and size of these lateral ganglia cells suggest that they are the GABA-immunoreactive lateral ganglia cells frequently seen in whole-mount immunocytochemical preparations. Four neuronal cell bodies located in the retrovesicular ganglion were also labeled with 3H-GABA. These cells, which are probably cholinergic excitatory motor neurons, do not contain detectable GABA-like immunoreactivity. Heavy labeling of muscle cells was also observed. The ventral and dorsal nerve cord inhibitory motor neurons, which are known to contain GABA-like immunoreactivity, were not labeled above background with 3H-GABA. Together with the experiments reported previously, these results define three classes of GABA-associated neurons in Ascaris: (1) neurons that contain endogenous GABA and possess a GABA uptake system; (2) neurons that contain endogenous GABA, but that either lack a GABA uptake system or possess a GABA uptake system of low activity; (3) neurons that possess a GABA uptake system, but that lack endogenous GABA

Neuromodulatory properties of fluorescent carbon dots: effect on exocytotic release, uptake and ambient level of glutamate and GABA in brain nerve terminals.

Science.gov (United States)

Borisova, Tatiana; Nazarova, Anastasia; Dekaliuk, Mariia; Krisanova, Natalia; Pozdnyakova, Natalia; Borysov, Arsenii; Sivko, Roman; Demchenko, Alexander P

2015-02-01

Carbon dots (C-dots), a recently discovered class of fluorescent nano-sized particles with pure carbon core, have great bioanalytical potential. Neuroactive properties of fluorescent C-dots obtained from β-alanine by microwave heating were assessed based on the analysis of their effects on the key characteristics of GABA- and glutamatergic neurotransmission in isolated rat brain nerve terminals. It was found that C-dots (40-800 μg/ml) in dose-dependent manner: (1) decreased exocytotic release of [(3)H]GABA and L-[(14)C]glutamate; (2) reduced acidification of synaptic vesicles; (3) attenuated the initial velocity of Na(+)-dependent transporter-mediated uptake of [(3)H]GABA and L-[(14)C]glutamate; (4) increased the ambient level of the neurotransmitters, nevertheless (5) did not change significantly the potential of the plasma membrane of nerve terminals. Almost complete suppression of exocytotic release of the neurotransmitters was caused by C-dots at a concentration of 800 μg/ml. Fluorescent and neuromodulatory features combined in C-dots create base for their potential usage for labeling and visualization of key processes in nerve terminals, and also in theranostics. In addition, natural presence of carbon-containing nanoparticles in the human food chain and in the air may provoke the development of neurologic consequences. Copyright © 2014 Elsevier Ltd. 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.

Science.gov (United States)

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.

Increased brain uptake of gamma-aminobutyric acid in a rabbit model of hepatic encephalopathy

International Nuclear Information System (INIS)

Bassett, M.L.; Mullen, K.D.; Scholz, B.; Fenstermacher, J.D.; Jones, E.A.

1990-01-01

Transfer of the inhibitory neurotransmitter gamma-aminobutyric acid across the normal blood-brain barrier is minimal. One prerequisite for gamma-aminobutyric acid in plasma contributing to the neural inhibition of hepatic encephalopathy would be that increased transfer of gamma-aminobutyric acid across the blood-brain barrier occurs in liver failure. The aim of the present study was to determine if brain gamma-aminobutyric acid uptake is increased in rabbits with stage II-III (precoma) hepatic encephalopathy due to galactosamine-induced fulminant hepatic failure. A modification of the Oldendorf intracarotid artery-injection technique was applied. [3H] gamma-aminobutyric acid, [14C] butanol, and 113mIn-labeled serum protein (transferrin) were injected simultaneously 4 s before decapitation. The ipsilateral brain uptake index of gamma-aminobutyric acid was determined from measurements of the 3 isotopes in 5 brain regions. Uncorrected or simple brain uptake indices of [3H] gamma-aminobutyric acid and [113mIn] transferrin were calculated using [14C] butanol as the highly extracted reference compound. The [113mIn] transferrin data were also used to correct the brain uptake index of [3H] gamma-aminobutyric acid for intravascular retention of [3H] gamma-aminobutyric acid. The methodology adopted minimized problems attributable to rapid [3H] gamma-aminobutyric acid metabolism, and slow brain washout and recirculation of the radiolabeled tracers. Both the uncorrected and corrected brain uptake indices of gamma-aminobutyric acid as well as the simple brain uptake index of transferrin were significantly increased in both stage II and III hepatic encephalopathy in all brain regions studied. Moreover, these brain uptake indices were significantly greater in stage III hepatic encephalopathy than in stage II hepatic encephalopathy

A novel Trojan-horse targeting strategy to reduce the non-specific uptake of nanocarriers by non-cancerous cells.

Science.gov (United States)

Shen, Zheyu; Wu, Hao; Yang, Sugeun; Ma, Xuehua; Li, Zihou; Tan, Mingqian; Wu, Aiguo

2015-11-01

One big challenge with active targeting of nanocarriers is non-specific binding between targeting molecules and non-target moieties expressed on non-cancerous cells, which leads to non-specific uptake of nanocarriers by non-cancerous cells. Here, we propose a novel Trojan-horse targeting strategy to hide or expose the targeting molecules of nanocarriers on-demand. The non-specific uptake by non-cancerous cells can be reduced because the targeting molecules are hidden in hydrophilic polymers. The nanocarriers are still actively targetable to cancer cells because the targeting molecules can be exposed on-demand at tumor regions. Typically, Fe3O4 nanocrystals (FN) as magnetic resonance imaging (MRI) contrast agents were encapsulated into albumin nanoparticles (AN), and then folic acid (FA) and pH-sensitive polymers (PP) were grafted onto the surface of AN-FN to construct PP-FA-AN-FN nanoparticles. Fourier transform infrared spectroscopy (FT-IR), dynamic light scattering (DLS), transmission electron microscope (TEM) and gel permeation chromatography (GPC) results confirm successful construction of PP-FA-AN-FN. According to difference of nanoparticle-cellular uptake between pH 7.4 and 5.5, the weight ratio of conjugated PP to nanoparticle FA-AN-FN (i.e. graft density) and the molecular weight of PP (i.e. graft length) are optimized to be 1.32 and 5.7 kDa, respectively. In vitro studies confirm that the PP can hide ligand FA to prevent it from binding to cells with FRα at pH 7.4 and shrink to expose FA at pH 5.5. In vivo studies demonstrate that our Trojan-horse targeting strategy can reduce the non-specific uptake of the PP-FA-AN-FN by non-cancerous cells. Therefore, our PP-FA-AN-FN might be used as an accurately targeted MRI contrast agent. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

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

High affinity (3H) β-Alanine uptake by scar margins of ferric chloride-induced epileptogenic foci in rat isocortex

International Nuclear Information System (INIS)

Robitaille, Y.; Sherwin, A.

1984-01-01

Cortical astrocytes of normal mammalian brain are endowed with a high affinity uptake system for β-Alanine which is competitively inhibited by gamma aminobutyric acid (GABA), a neurotransmitter strongly implicated in epileptogenesis. The authors evaluated ( 3 H) β-Alanine uptake by reactive astrocytes proliferating within scar of epileptogenic foci induced in rat motor cortex by microinjections of 100 mM ferric chloride. Following in vitro incubation of scar tissue with ( 3 H) β-Alanine, ultrastructural morphometry of grain patterns at 5, 30 and 120 days post injection revealed early and significant grain count increases over astroglial processes, predominantly those related to perivascular glial end-feet. Astrocytic cell body and endothelial cell counts showed a more gradual and stepwise increase. Similar data were obtained by comparing visual and edited mean astrocytic grain counts. These results suggest that the enhanced uptake of reactive astrocytes may reflect a marked decrease of inhibitory GABAergic neurons within ferric chloride-induced scars. 7 figures, 1 table

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

Reducing renal uptake of 9Y- and 177Lu-labeled alpha-melanocyte stimulating hormone peptide analogues

International Nuclear Information System (INIS)

Miao Yubin; Fisher, Darrell R.; Quinn, Thomas P.

2006-01-01

Objective: The purpose of this study was to improve the tumor-to-kidney uptake ratios of 9 Y- and 177 Lu-[1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-Re-Cys 3,4,1 , D-Phe 7 , Arg 11 ]α-melanocyte stimulating hormone 3-13 {DOTA-Re(Arg 11 )CCMSH} through coupling a negatively charged glutamic acid (Glu) to the peptide sequence. Methods: A new peptide of DOTA-Re(Glu 2 , Arg 11 )CCMSH was designed, synthesized and labeled with 9 Y and 177 Lu. Pharmacokinetics of 9 Y- and 177 Lu-DOTA-Re(Glu 2 , Arg 11 )CCMSH was determined in B16/F1 murine melanoma-bearing C57 mice. Results: 9 Y- and 177 Lu-DOTA-Re(Glu 2 , Arg 11 )CCMSH exhibited significantly (P 9 Y- and 177 Lu-DOTA-Re(Arg 11 )CCMSH at 30 min and at 2, 4 and 24 h after dose administration. The renal uptake values of 9 Y- and 177 Lu-DOTA-Re(Glu 2 , Arg 11 )CCMSH were 28.16% and 28.81% of those of 9 Y- and 177 Lu-DOTA-Re(Arg 11 )CCMSH, respectively, at 4 h postinjection. 9 Y- and 177 Lu-DOTA-Re(Glu 2 , Arg 11 )CCMSH displayed higher tumor-to-kidney uptake ratios than 9 Y- and 177 Lu-DOTA-Re(Arg 11 )CCMSH at 30 min and at 2, 4 and 24 h after dose administration. The tumor-to-kidney uptake ratio of 9 Y- and 177 Lu-DOTA-Re(Glu 2 , Arg 11 )CCMSH was 2.28 and 1.69 times of 9 Y- and 177 Lu-DOTA-Re(Arg 11 )CCMSH, respectively, at 4 h postinjection. The 9 Y- and 177 Lu-DOTA-Re(Glu 2 , Arg 11 )CCMSH activity accumulation was low in normal organs except for kidney. Conclusions: Coupling a negatively charged amino acid (Glu) to the CCMSH peptide sequence dramatically reduced the renal uptake values and increased the tumor-to-kidney uptake ratios of 9 Y- and 177 Lu-DOTA-Re(Glu 2 , Arg 11 )CCMSH, facilitating their potential applications as radiopharmaceuticals for targeted radionuclide therapy of melanoma

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...

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

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

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.

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

Dopamine in the Auditory Brainstem and Midbrain: Co-localization with Amino Acid Neurotransmitters and Gene Expression following Cochlear Trauma

Directory of Open Access Journals (Sweden)

Avril Genene eHolt

2015-07-01

Full Text Available Dopamine (DA modulates the effects of amino acid neurotransmitters, including GABA and glutamate, in motor, visual, olfactory and reward systems (Hnasko et al., 2010; Stuber et al., 2010; Hnasko and Edwards, 2012. The results suggest that DA may play a similar modulatory role in the auditory pathways. Previous studies have shown that deafness results in decreased GABA release, changes in excitatory neurotransmitter levels, and increased spontaneous neuronal activity within brainstem regions related to auditory function. Modulation of the expression and localization of tyrosine hydroxylase (TH; the rate limiting enzyme in the production of DA in the IC following cochlear trauma has been previously reported (Tong et al., 2005. In the current study the possibility of co-localization of TH with amino acid neurotransmitters (AANs was examined. Changes in the gene expression of TH were compared with changes in the gene expression of markers for AANs in the cochlear nucleus (CN and IC to determine whether those deafness related changes occur concurrently. The results indicate that bilateral cochlear ablation significantly reduced TH gene expression in the CN after two months while in the IC the reduction in TH was observed at both three days and two months following ablation. Furthermore, in the CN, glycine transporter 2 (GlyT2 and the GABA transporter (GABAtp were also significantly reduced only after two months. However, in the IC, DA receptor 1 (DRDA1, vesicular glutamate transporters 2 and 3 (vGluT2, vGluT3, GABAtp and GAD67 were reduced in expression both at the three day and two month time points. A close relationship between the distribution of TH and several of the AANs was determined in both the CN and the IC. In addition, GlyT2 and vGluT3 each co-localized with TH within IC somata and dendrites. Therefore, the results of the current study suggest that DA is spatially well positioned to influence the effects of AANs on auditory neurons.

Static magnetic field reduced exogenous oligonucleotide uptake by spermatozoa using magnetic nanoparticle gene delivery system

International Nuclear Information System (INIS)

Katebi, Samira; Esmaeili, Abolghasem; Ghaedi, Kamran

2016-01-01

Spermatozoa could introduce exogenous oligonucleotides of interest to the oocyte. The most important reason of low efficiency of sperm mediated gene transfer (SMGT) is low uptake of exogenous DNA by spermatozoa. The aim of this study was to evaluate the effects of static magnetic field on exogenous oligonucleotide uptake of spermatozoa using magnetofection method. Magnetic nanoparticles (MNPs) associated with the labeled oligonucleotides were used to increase the efficiency of exogenous oligonucleotide uptake by rooster spermatozoa. We used high-field/high-gradient magnet (NdFeB) to enhance and accelerate exogenous DNA sedimentation at the spermatozoa surface. Flow cytometry analysis was performed to measure viability and percentage of exogenous oligonucleotide uptake by sperm. Flow cytometry analysis showed a significant increase in exogenous oligonucleotide uptake by rooster spermatozoa (P<0.001) when spermatozoa were incubated in exogenous oligonucleotide solution and MNPs. However, by applying static magnetic field during magnetofection method, a significant decrease in exogenous oligonucleotide uptake was observed (P<0.05). Findings of this study showed that MNPs were effective to increase exogenous oligonucleotide uptake by rooster spermatozoa; however unlike others studies, static magnetic field, was not only ineffective to enhance exogenous oligonucleotide uptake by rooster spermatozoa but also led to reduction in efficiency of magnetic nanoparticles in gene transfer. - Highlights: • Core/shell type Iron oxide nanoparticles were used as a novel and efficient method. • This method increases exogenous DNA uptake by rooster spermatozoa. • Static magnetic field decreased DNA uptake by rooster spermatozoa.

Static magnetic field reduced exogenous oligonucleotide uptake by spermatozoa using magnetic nanoparticle gene delivery system

Energy Technology Data Exchange (ETDEWEB)

Katebi, Samira; Esmaeili, Abolghasem, E-mail: aesmaeili@sci.ui.ac.ir; Ghaedi, Kamran

2016-03-15

Spermatozoa could introduce exogenous oligonucleotides of interest to the oocyte. The most important reason of low efficiency of sperm mediated gene transfer (SMGT) is low uptake of exogenous DNA by spermatozoa. The aim of this study was to evaluate the effects of static magnetic field on exogenous oligonucleotide uptake of spermatozoa using magnetofection method. Magnetic nanoparticles (MNPs) associated with the labeled oligonucleotides were used to increase the efficiency of exogenous oligonucleotide uptake by rooster spermatozoa. We used high-field/high-gradient magnet (NdFeB) to enhance and accelerate exogenous DNA sedimentation at the spermatozoa surface. Flow cytometry analysis was performed to measure viability and percentage of exogenous oligonucleotide uptake by sperm. Flow cytometry analysis showed a significant increase in exogenous oligonucleotide uptake by rooster spermatozoa (P<0.001) when spermatozoa were incubated in exogenous oligonucleotide solution and MNPs. However, by applying static magnetic field during magnetofection method, a significant decrease in exogenous oligonucleotide uptake was observed (P<0.05). Findings of this study showed that MNPs were effective to increase exogenous oligonucleotide uptake by rooster spermatozoa; however unlike others studies, static magnetic field, was not only ineffective to enhance exogenous oligonucleotide uptake by rooster spermatozoa but also led to reduction in efficiency of magnetic nanoparticles in gene transfer. - Highlights: • Core/shell type Iron oxide nanoparticles were used as a novel and efficient method. • This method increases exogenous DNA uptake by rooster spermatozoa. • Static magnetic field decreased DNA uptake by rooster spermatozoa.

The 'glial' glutamate transporter, EAAT2 (Glt-1) accounts for high affinity glutamate uptake into adult rodent nerve endings.

Science.gov (United States)

Suchak, Sachin K; Baloyianni, Nicoletta V; Perkinton, Michael S; Williams, Robert J; Meldrum, Brian S; Rattray, Marcus

2003-02-01

The excitatory amino acid transporters (EAAT) removes neurotransmitters glutamate and aspartate from the synaptic cleft. Most CNS glutamate uptake is mediated by EAAT2 into glia, though nerve terminals show evidence for uptake, through an unknown transporter. Reverse-transcriptase PCR identified the expression of EAAT1, EAAT2, EAAT3 and EAAT4 mRNAs in primary cultures of mouse cortical or striatal neurones. We have used synaptosomes and glial plasmalemmal vesicles (GPV) from adult mouse and rat CNS to identify the nerve terminal transporter. Western blotting showed detectable levels of the transporters EAAT1 (GLAST) and EAAT2 (Glt-1) in both synaptosomes and GPVs. Uptake of [3H]D-aspartate or [3H]L-glutamate into these preparations revealed sodium-dependent uptake in GPV and synaptosomes which was inhibited by a range of EAAT blockers: dihydrokainate, serine-o-sulfate, l-trans-2,4-pyrrolidine dicarboxylate (PDC) (+/-)-threo-3-methylglutamate and (2S,4R )-4-methylglutamate. The IC50 values found for these compounds suggested functional expression of the 'glial, transporter, EAAT2 in nerve terminals. Additionally blockade of the majority EAAT2 uptake sites with 100 micro m dihydrokainate, failed to unmask any functional non-EAAT2 uptake sites. The data presented in this study indicate that EAAT2 is the predominant nerve terminal glutamate transporter in the adult rodent CNS.

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

Indian Academy of Sciences (India)

微软用户

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.

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.

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.

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.

Active uptake of substance P carboxy-terminal heptapeptide (5-11) into rat brain and rabbit spinal cord slices

Energy Technology Data Exchange (ETDEWEB)

Nakata, Y; Kusaka, Y; Yajima, H; Segawa, T

1981-12-01

We previously reported that nerve terminals and glial cells lack an active uptake system capable of terminating transmitter action of substance P (SP). In the present study, we demonstrated the existence of an active uptake system for SP carboxy-terminal heptapeptide, (5-11)SP. When the slices from either rat brain or rabbit spinal cord were incubated with (3H)(5-11)SP, the uptake of (5-11)SP into slices was observed. The uptake system has the properties of an active transport mechanism: it is dependent on temperature and sensitive to hypoosmotic treatment and is inhibited by ouabain and dinitrophenol (DNP). In the brain, (5-11)SP was accumulated by means of a high-affinity and a low-affinity uptake system. The Km and the Vmax values for the high-affinity system were 4.20 x 10(-8) M and 7.59 fmol/10 mg wet weight/min, respectively, whereas these values for the low-affinity system were 1.00 x 10(-6) M and 100 fmol/10 mg wet weight/min, respectively. In the spinal cord, there was only one uptake system, with a Km value of 2.16 x 10(-7) M and Vmax value of 26.2 fmol/10 mg wet weight/min. These results suggest that when SP is released from nerve terminals, it is hydrolysed into (5-11)SP before or after acting as a neurotransmitter, which is in turn accumulated into nerve terminals. Therefore, the uptake system may represent a possible mechanism for the inactivation of SP.

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 ...

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.

Static magnetic field reduced exogenous oligonucleotide uptake by spermatozoa using magnetic nanoparticle gene delivery system

Science.gov (United States)

Katebi, Samira; Esmaeili, Abolghasem; Ghaedi, Kamran

2016-03-01

Spermatozoa could introduce exogenous oligonucleotides of interest to the oocyte. The most important reason of low efficiency of sperm mediated gene transfer (SMGT) is low uptake of exogenous DNA by spermatozoa. The aim of this study was to evaluate the effects of static magnetic field on exogenous oligonucleotide uptake of spermatozoa using magnetofection method. Magnetic nanoparticles (MNPs) associated with the labeled oligonucleotides were used to increase the efficiency of exogenous oligonucleotide uptake by rooster spermatozoa. We used high-field/high-gradient magnet (NdFeB) to enhance and accelerate exogenous DNA sedimentation at the spermatozoa surface. Flow cytometry analysis was performed to measure viability and percentage of exogenous oligonucleotide uptake by sperm. Flow cytometry analysis showed a significant increase in exogenous oligonucleotide uptake by rooster spermatozoa (Prooster spermatozoa; however unlike others studies, static magnetic field, was not only ineffective to enhance exogenous oligonucleotide uptake by rooster spermatozoa but also led to reduction in efficiency of magnetic nanoparticles in gene transfer.

Seasonal variation in the effect of constant ambient temperature of 24 C in reducing FDG uptake by brown adipose tissue in children

International Nuclear Information System (INIS)

Zukotynski, Katherine A.; Fahey, Frederic H.; Laffin, Stephen; Davis, Royal; Treves, S. Ted; Grant, Frederick D.; Drubach, Laura A.

2010-01-01

It has been shown that warming patients prior to and during 18 F-FDG uptake by controlling the room temperature can decrease uptake by brown adipose tissue (BAT). The aim of this study is to determine if this effect is subject to seasonal variation. A retrospective review was conducted of all patients referred for whole-body 18 F-FDG PET between December 2006 and December 2008. After December 2007, all patients were kept in the PET injection room at a constant 24 C for 30 min before and until 1 h following FDG administration. Patients over 22 years of age and those who received pre-medication known to reduce FDG uptake by BAT were excluded. One hundred and three patients were warmed to 24 C prior to scanning. The number of patients showing uptake by BAT in this group was compared to a control group of 99 patients who underwent PET prior to December 2007 when the injection room temperature was 21 C. Uptake by BAT occurred in 9% of studies performed after patient warming (24 C), compared to 27% of studies performed on the control group (21 C) (p 0.05). Maintaining room temperature at a constant 24 C for 30 min prior to and 1 h after IV tracer administration significantly decreases FDG uptake by BAT in children. This effect is greatest in the summer and winter. (orig.)

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

Diabetter"T"M Reduces Post Meal Hyperglycemia Via Enhancement of Glucose Uptake Into Adipocytes and Muscles Cells

International Nuclear Information System (INIS)

Zainah Adam; Mohd Hishamudin Mohd Jinal; Alqarni Bader Ayed; Shafii Khamis

2014-01-01

There are lots of herbal products for diabetes mellitus treatment available in local market. Most of these products are not standardized and lack of efficacy and safety data. DiaBetter"T"M is one of the herbal products that have been used for diabetes treatment. This study was carried out to determine the efficacy of DiaBetter"T"M in reducing hyperglycemia and to elucidate the mechanisms by which hyperglycemia is reduced. The results showed that DiaBetter"T"M significantly reduced post meal hyperglycemia in normal and diabetic rats, and improved glucose tolerance activity in diabetic rats particularly after 4 and 6 hours of administration. Antihyperglycemic mechanisms elucidation revealed that the DiaBetter"T"M significantly enhanced insulin-stimulated glucose uptake into adipocytes and muscle cells, with the highest magnitude of enhancement were 1.54 fold (p<0.01) and 1.46 fold (p<0.001), respectively. Molecular mechanisms that responsible for this enhancement were the increment of insulin sensitivity at cells membrane. Cytotoxic evaluation was also done and confirmed that DiaBetter"T"M was toxicologically safe against muscle and adipocytes cells. In conclusion, post-meal antihyperglycemic and glucose tolerance activity of DiaBetter"T"M was mediated through the enhancement of glucose uptake into adipocytes and muscle cells. Insulin sensitizing activity showed by DiaBetter"T"M suggests that this product has the potential to ameliorate insulin resistance condition. Therefore, it is suggested that the DiaBetter"T"M can be used as dietary adjunct for the management of type 2 diabetes mellitus which related to insulin resistance. (Author)

Endogenous opioid peptides as neurotransmitters in the rat hippocampus

International Nuclear Information System (INIS)

Neumaier, J.F.

1989-01-01

The role of endogenous opioid peptides as neurotransmitters in the rat hippocampus was investigated by using extracellular recording and radioligand binding techniques in the hippocampal slice preparation. Synaptic conductances from endogenously released opioid peptides have been difficult to detect. This problem was approach by designing a novel assay of opioid peptide release, in which release was detected by measuring binding competition between endogenous opioids and added radioligand. Membrane depolarization displaced [ 3 H]-diprenorphine binding in a transient, calcium-dependent, and peptidase-sensitive manner. Autoradiographic localization of the sites of [ 3 H]-diprenorphine binding displacement showed that significant opioid peptide release and receptor occupancy occurred in each major subregion of the hippocampal slices. This assay method can not be used to define optimal electrical stimulation conditions for releasing endogenous opioids. The binding displacement method was extended to the study of the sigma receptor. Depolarization of hippocampal slices was found to reduce the binding of the sigma-selective radioligand [ 3 H]-ditolylguanidine in a transient and calcium-dependent manner with no apparent direct effects on sigma receptor affinity

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...

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

Science.gov (United States)

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.

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.

DiabetterTM Reduces Post Meal Hyperglycemia Via Enhancement Of Glucose Uptake Into Adipocytes And Muscles Cells

International Nuclear Information System (INIS)

Zainah Adam; Shafii Khamis

2014-01-01

Currently, there are lots of herbal products available in local markets that are used for treatment of diabetes mellitus. Most of these products are not standardized and lack of efficacy and safety data. DiaBetterTM is one of the local herbal products that have been used for treatment of diabetes. This study was carried out to determine the efficacy of DiaBetterTM in reducing hyperglycemia and to elucidate the mechanisms by which hyperglycemia is reduced. Antihyperglycemic evaluation was done in normal and streptozotocin-induced diabetic rats at different prandial states and the antihyperglycemic mechanisms elucidation was carried out in muscle and adipocytes cells using glucose tracer method (2-deoxy-[1-3H]-glucose). The results showed that DiaBetterTM significantly reduced post meal hyperglycemia in normal and diabetic rats, and improved glucose tolerance activity in diabetic rats particularly after 4 and 6 hours of administration. Antihyperglycemic mechanisms elucidation revealed that the DiaBetterTM significantly enhanced insulin-stimulated glucose uptake into adipocytes and muscle cells, with the highest magnitude of enhancement were 1.54-fold (p<0.01) and 1.46-fold (p<0.001), respectively. Molecular mechanisms that responsible for this enhancement were the increment of insulin sensitivity at cells membrane. Cytotoxic evaluation was also done and confirmed that DiaBetterTM was toxicologically safe against muscle and adipocytes cells. In conclusion, post-meal antihyperglycemic and glucose tolerance activity activity of DiaBetterTM was mediated through the enhancement of glucose uptake into adipocytes and muscle cells. Insulin sensitizing activity showed by DiaBetterTM suggests that this product has the potential to ameliorate insulin resistance condition. Therefore, it is suggested that DiaBetterTM can be used as dietary adjunct for the treatment of type 2 diabetes mellitus which related to insulin resistance. (author)

Neurotransmitter positron emission tomographic-studies in adults with phenylketonuria, a pilot study

NARCIS (Netherlands)

Paans, AMJ; Pruim, J; Smit, GPA; Visser, G; Willemsen, ATM; Ullrich, K

Patients with phenylketonuria (PKU) may suffer from cognitive and neurological deficits which are related to reduced intracerebral concentrations of catecholamines. The function of phenylalanine (Phe) as an inhibitor of the uptake of the precursor amino acid tyrosine (Tyr) through the blood-brain

Molecular imaging of reduced renal uptake of radiolabelled [DOTA{sup 0},Tyr{sup 3}]octreotate by the combination of lysine and Gelofusine in rats

Energy Technology Data Exchange (ETDEWEB)

Rolleman, E.J.; Bernard, B.F.; Breeman, W.A.P.; Forrer, F.; Blois, E. de; Krenning, E.P.; Jong, M. de [Dept. of Nuclear Medicine, Erasmus MC Rotterdam, Nijmegen (Netherlands); Hoppin, J. [Bioscan Inc., Washington, DC (United States); Gotthardt, M.; Boerman, O.C. [Dept. of Nuclear Medicine, Radboud Univ. Hospital, Nijmegen (Netherlands)

2008-07-01

Aim: in peptide receptor radionuclide therapy (PRRT) using radiolabelled somatostatin analogues, kidney uptake of radiolabelled compound is the major dose-limiting factor. We studied the effects of Gelofusine (20 mg) and lysine (100 mg) and the combination of both after injection of therapeutic doses of radiolabelled [DOTA{sup 0},Tyr{sup 3}]octreotate (60 MBq {sup 111}In or 555 MBq {sup 177}Lu labelled to 15 {mu}g peptide) in male Lewis rats. Methods: kidney uptake was measured by single photon emission computed tomography (SPECT) scans with a four-headed multi-pinhole camera (NanoSPECT) at 24 h, 5 and 7 days p. i. and was quantified by volume of interest analysis. For validation the activity concentration in the dissected kidneys was also determined ex vivo using a gamma counter and a dose calibrator. Results: Gelofusine and lysine both reduced kidney uptake of [{sup 177}Lu-DOTA{sup 0},Tyr{sup 3}]octreotate significantly by about 40% at all time points. The combination of Gelofusine and lysine resulted in a 62% inhibition of kidney uptake (p < 0.01 vs. lysine alone). A weak but significant dose-response relationship for Gelofusine, but not for lysine, was found. In a study with [{sup 111}In-DOTA{sup 0},Tyr{sup 3}]octreotate, conclusions drawn from NanoSPECT data were confirmed by biodistribution data. Conclusions: we conclude that rat kidney uptake of radiolabelled somatostatin analogues can be monitored for a longer period in the same animal using animal SPECT. Gelofusine and lysine had equal potential to reduce kidney uptake of therapeutic doses of [{sup 177}Lu-DOTA{sup 0},Tyr{sup 3}]octreotate. The combination of these compounds caused a significantly larger reduction than lysine or Gelofusine alone and may therefore offer new possibilities in PRRT. The NanoSPECT data were validated by standard biodistribution experiments. (orig.)

Brain neurotransmitters in an animal model with postpartum depressive-like behavior.

Science.gov (United States)

Avraham, Y; Hants, Y; Vorobeiv, L; Staum, M; Abu Ahmad, Wiessam; Mankuta, D; Galun, E; Arbel-Alon, S

2017-05-30

Post-Partum Depression (PPD) occurs in 15% of pregnancies and its patho-physiology is not known. We studied female BALB/c ("depressive") and C57BL/6 (control) mice as a model for PPD and assessed their behavior and correlates with brain neurotransmitters (NTs) - norepinephrine, dopamine, serotonin and intermediates, during the pre-pregnancy (PREP), pregnancy (PREG) and post-partum (PP) periods. Depressive-like behavior was evaluated by the Open Field (OFT), Tail Suspension (TST) and Forced Swim (FST) tests. Neurotransmitters (NTs) were determined in the striatum (care-giving), hippocampus (cognitive function) and hypothalamus (maternal care & eating behavior). In the BALB/c mice, while their performance in all behavioral tests was significantly reduced during pregnancy and P-P indicative of the development of depressive-like responses, no changes were observed in the C57BL/6 mice. Changes in NTs in BALB/C were as follows: PREP, all NTs in the three brain areas were decreased, although an increase in dopamine release was observed in the hippocampus. PREG: No changes were observed in the NTs except for a decrease in 5-HT in the striatum. P-P: striatum, low 5-HT, NE and dopamine; Hippocampus: low 5-HT, NE and high Dopamine; hypothalamus: all NTs increased, especially NE. Following pregnancy and delivery, the BALB/c mice developed depressive-like behavior associated with a significant decrease in 5-HT, dopamine and NE in the striatum and 5-HT and NE in the hippocampus. Dopamine increased in the latter together with a significant increase in all NTs in the hypothalamus. These findings suggest that the development of PPD may be associated with NT changes. Normalization of these alterations may have a role in the treatment of PPD. Copyright © 2017 Elsevier B.V. All rights reserved.

Development and preclinical characterisation of 99mTc-labelled Affibody molecules with reduced renal uptake

International Nuclear Information System (INIS)

Ekblad, Torun; Karlstroem, Amelie Eriksson; Tran, Thuy; Orlova, Anna; Feldwisch, Joachim; Widstroem, Charles; Abrahmsen, Lars; Wennborg, Anders; Tolmachev, Vladimir

2008-01-01

Affibody molecules are low molecular weight proteins (7 kDa), which can be selected to bind to tumour-associated target proteins with subnanomolar affinity. Because of rapid tumour localisation and clearance from nonspecific compartments, Affibody molecules are promising tracers for molecular imaging. Earlier, 99m Tc-labelled Affibody molecules demonstrated specific targeting of tumour xenografts. However, the biodistribution was suboptimal either because of hepatobiliary excretion or high renal uptake of the radioactivity. The goal of this study was to optimise the biodistribution of Affibody molecules by chelator engineering. Anti-HER2 Z HER2:342 Affibody molecules, carrying the mercaptoacetyl-glutamyl-seryl-glutamyl (maESE), mercaptoacetyl-glutamyl-glutamyl-seryl (maEES) and mercaptoacetyl-seryl-glutamyl-glutamyl (maSEE) chelators, were prepared by peptide synthesis and labelled with 99m Tc. The tumour-targeting capacity of these conjugates was compared with each other and with the best previously available conjugate, 99m Tc-maEEE-Z HER2:342, in nude mice bearing SKOV-3 xenografts. The tumour-targeting capacity of the most promising conjugate, 99m Tc-maESE-Z HER2:342, was compared with radioiodinated Z HER2:342 . All novel conjugates demonstrated successful tumour targeting and a low degree of hepatobiliary excretion. The renal uptakes of serine-containing conjugates, 33±5, 68±21 and 71±10%IA/g, for 99m Tc-maESE-Z HER2:342 , 99m Tc-maEES-Z HER2:342 and 99m Tc-maSEE-Z HER2:342 , respectively, were significantly reduced in comparison with 99m Tc-maEEE-Z HER2:342 (102 ± 13%IA/g). For 99m Tc-maESE-Z HER2:342 , a tumour uptake of 9.6±1.8%IA/g and a tumour-to-blood ratio of 58±6 were reached at 4 h p.i. A combination of serine and glutamic acid residues in the chelator sequence confers increased renal excretion and relatively low renal uptake of 99m Tc-labelled Affibody molecules. In combination with preserved targeting capacity, this improved imaging of targets

Cellular Origin of [18F]FDG-PET Imaging Signals During Ceftriaxone-Stimulated Glutamate Uptake: Astrocytes and Neurons.

Science.gov (United States)

Dienel, Gerald A; Behar, Kevin L; Rothman, Douglas L

2017-12-01

Ceftriaxone stimulates astrocytic uptake of the excitatory neurotransmitter glutamate, and it is used to treat glutamatergic excitotoxicity that becomes manifest during many brain diseases. Ceftriaxone-stimulated glutamate transport was reported to drive signals underlying [ 18 F]fluorodeoxyglucose-positron emission tomographic ([ 18 F]FDG-PET) metabolic images of brain glucose utilization and interpreted as supportive of the notion of lactate shuttling from astrocytes to neurons. This study draws attention to critical roles of astrocytes in the energetics and imaging of brain activity, but the results are provocative because (1) the method does not have cellular resolution or provide information about downstream pathways of glucose metabolism, (2) neuronal and astrocytic [ 18 F]FDG uptake were not separately measured, and (3) strong evidence against lactate shuttling was not discussed. Evaluation of potential metabolic responses to ceftriaxone suggests lack of astrocytic specificity and significant contributions by pre- and postsynaptic neuronal compartments. Indeed, astrocytic glycolysis may not make a strong contribution to the [ 18 F]FDG-PET signal because partial or complete oxidation of one glutamate molecule on its uptake generates enough ATP to fuel uptake of 3 to 10 more glutamate molecules, diminishing reliance on glycolysis. The influence of ceftriaxone on energetics of glutamate-glutamine cycling must be determined in astrocytes and neurons to elucidate its roles in excitotoxicity treatment.

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

Evidence for cysteine sulfinate as a neurotransmitter

International Nuclear Information System (INIS)

Recasens, M.; Varga, V.; Nanopoulos, D.; Saadoun, F.; Vincendon, G.; Benavides, J.

1982-01-01

The Na + -independent binding of L-[ 3 H]cysteine sulfinate and L-[ 3 H]cysteine sulfinate uptake were investigated in rat brain membranes and vesicles. Specific binding of L-[ 3 H]cysteine sulfinate was saturable and occurred by a single high affinity process with a Ksub(b) of 100 nM +- 9 and a capacity (Bsub(max)) of 2.4 +- 0.22 pmol/mg protein. The regional distribution of the binding of L-[ 3 H]cysteine sulfinate in the brain was found to be heterogeneous. The rate of L-[ 3 H]cysteine sulfinate uptake shows a biphasic dependence on the concentration of L-cysteine sulfinate, corresponding to a high affinity (27.2 μM) and a low affinity (398 μM) transport system. The maximum L-[ 3 H]cysteine sulfinate uptake is reached at 2min and the uptake increases as a function of the sodium concentration. Chloride and potassium ions stimulate the uptake. (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.

Fife, a Drosophila Piccolo-RIM Homolog, Promotes Active Zone Organization and Neurotransmitter Release

Science.gov (United States)

Bruckner, Joseph J.; Gratz, Scott J.; Slind, Jessica K.; Geske, Richard R.; Cummings, Alexander M.; Galindo, Samantha E.; Donohue, Laura K.; O'Connor-Giles, Kate M.

2012-01-01

Neuronal communication depends on the precisely orchestrated release of neurotransmitter at specialized sites called active zones (AZs). A small number of scaffolding and cytoskeletal proteins comprising the cytomatrix of the active zone (CAZ) are thought to organize the architecture and functional properties of AZs. The majority of CAZ proteins are evolutionarily conserved, underscoring the fundamental similarities in neurotransmission at all synapses. However, core CAZ proteins Piccolo and Bassoon have long been believed exclusive to vertebrates, raising intriguing questions about the conservation of the molecular mechanisms that regulate presynaptic properties. Here, we present the identification of a piccolo-rim-related gene in invertebrates, together with molecular phylogenetic analyses that indicate the encoded proteins may represent Piccolo orthologs. In accordance, we find that the Drosophila homolog, Fife, is neuronal and localizes to presynaptic AZs. To investigate the in vivo function of Fife, we generated a deletion of the fife locus. We find that evoked neurotransmitter release is substantially decreased in fife mutants and loss of fife results in motor deficits. Through morphological analysis of fife synapses, we identify underlying AZ abnormalities including pervasive presynaptic membrane detachments and reduced synaptic vesicle clustering. Our data demonstrate the conservation of a Piccolo-related protein in invertebrates and identify critical roles for Fife in regulating AZ structure and function. These findings suggest the CAZ is more conserved than previously thought, and open the door to a more complete understanding of how CAZ proteins regulate presynaptic structure and function through genetic studies in simpler model systems. PMID:23197698

Loud Noise Exposure Produces DNA, Neurotransmitter and Morphological Damage within Specific Brain Areas

Directory of Open Access Journals (Sweden)

Giada Frenzilli

2017-06-01

Full Text Available Exposure to loud noise is a major environmental threat to public health. Loud noise exposure, apart from affecting the inner ear, is deleterious for cardiovascular, endocrine and nervous systems and it is associated with neuropsychiatric disorders. In this study we investigated DNA, neurotransmitters and immune-histochemical alterations induced by exposure to loud noise in three major brain areas (cerebellum, hippocampus, striatum of Wistar rats. Rats were exposed to loud noise (100 dBA for 12 h. The effects of noise on DNA integrity in all three brain areas were evaluated by using Comet assay. In parallel studies, brain monoamine levels and morphology of nigrostriatal pathways, hippocampus and cerebellum were analyzed at different time intervals (24 h and 7 days after noise exposure. Loud noise produced a sudden increase in DNA damage in all the brain areas under investigation. Monoamine levels detected at 7 days following exposure were differently affected depending on the specific brain area. Namely, striatal but not hippocampal dopamine (DA significantly decreased, whereas hippocampal and cerebellar noradrenaline (NA was significantly reduced. This is in line with pathological findings within striatum and hippocampus consisting of a decrease in striatal tyrosine hydroxylase (TH combined with increased Bax and glial fibrillary acidic protein (GFAP. Loud noise exposure lasting 12 h causes immediate DNA, and long-lasting neurotransmitter and immune-histochemical alterations within specific brain areas of the rat. These alterations may suggest an anatomical and functional link to explain the neurobiology of diseases which prevail in human subjects exposed to environmental noise.

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...

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

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

) Bluetooth transceiver; 3) microprocessor; and 4) direct-current battery. A Windows-XP laptop computer running custom software and equipped with a Universal Serial Bus-connected Bluetooth transceiver served as the base station. Computer software directed wireless data acquisition at 100 kilosamples/second and remote control of FSCV operation and adjustable waveform parameters. The WINCS provided reliable, high-fidelity measurements of dopamine and other neurochemicals such as serotonin, norepinephrine, and ascorbic acid by using FSCV at CFM and by flow injection analysis. In rats, the WINCS detected subsecond striatal dopamine release at the implanted sensor during high-frequency stimulation of ascending dopaminergic fibers. Overall, in vitro and in vivo testing demonstrated comparable signals to a conventional hardwired electrochemical system for FSCV. Importantly, the WINCS reduced susceptibility to electromagnetic noise typically found in an operating room setting. Taken together, these results demonstrate that the WINCS is well suited for intraoperative neurochemical monitoring. It is anticipated that neurotransmitter measurements at an implanted chemical sensor will prove useful for advancing functional neurosurgery.

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.

Plant Growth and Phosphorus Uptake of Three Riparian Grass Species

Science.gov (United States)

Riparian buffers can significantly reduce sediment-bound phosphorus (P) entering surface water, but control of dissolved P inputs is more challenging. Because plant roots remove P from soil solution, it follows that plant uptake will reduce dissolved P losses. We evaluated P uptake of smooth bromegr...

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.

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

Citrate and succinate uptake by potato mitochondria

International Nuclear Information System (INIS)

Jung, D.W.; Laties, G.G.

1979-01-01

Potato mitochondria, in the absence of respiration, have a very low capacity for uptake by exchange with endogenous anions, taking up only 2.4 nanomoles citrate and 2.0 nanomoles succinate per milligram protein. Maximum citrate uptake of over 17 nanomoles per milligram protein occurs in the presence of inorganic phosphate, a dicarboxylic acid, and an external energy source (NADH), conditions where net anion accumulation proceeds, mediated by the interlinking of the inorganic phosphate, dicarboxylate, and tricarboxylate carriers. Maximum succinate uptake in the absence of respiratory inhibitors requires only added inorganic phosphate. Compounds which inhibit respiration (antimycin), the exchange carriers (mersalyl and benzylmalonate), or the establishment of the membrane proton motive force (uncouplers) reduce substrate accumulation. A potent inhibitor of the citrate carrier in animal mitochondria, 1,2,3-benzenetricarboxylic acid, does not inhibit citrate uptake in potato mitochondria. Citrate uptake is reduced by concurrent ADP phosphorylation and this reduction is sensitive to oligomycin. The initiation of state 3 after a 3-minute substrate state results in a reduction of the steady-state of citrate uptake by approximately 50%. Accumulation of succinate initially is inhibited by increasing sucrose concentration in the reaction medium from 50 to 400 millimolar. Limited substrate uptake is one of the factors responsible for the often observed depressed initial state 3 respiration rates in many mitochondrial preparations. Since nonlimiting levels of substrate in the matrix cannot be attained by energy-independent exchange, a dependence on respiration for adequate uptake results. Substrate limitation therefore occurs in the matrix for the period of time needed for energy-dependent accumulation of nonlimiting levels

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.

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

Science.gov (United States)

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.

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.

99mTc-labelled HYNIC-minigastrin with reduced kidney uptake for targeting of CCK-2 receptor-positive tumours

International Nuclear Information System (INIS)

Guggenberg, E. von; Gabriel, M.; Virgolini, I.J.; Decristoforo, C.; Dietrich, H.; Skvortsova, I.

2007-01-01

Different attempts have been made to develop a suitable radioligand for targeting CCK-2 receptors in vivo, for staging of medullary thyroid carcinoma (MTC) and other receptor-expressing tumours. After initial successful clinical studies with [DTPA 0 ,DGlu 1 ]minigastrin (DTPA-MG0) radiolabelled with 111 In and 90 Y, our group developed a 99m Tc-labelled radioligand, based on HYNIC-MG0. A major drawback observed with these derivatives is their high uptake by the kidneys. In this study we describe the preclinical evaluation of the optimised shortened peptide analogue, [HYNIC 0 ,DGlu 1 ,desGlu 2-6 ]minigastrin (HYNIC-MG11). 99m Tc labelling of HYNIC-MG11 was performed using tricine and EDDA as coligands. Stability experiments were carried out by reversed phase HPLC analysis in PBS, PBS/cysteine and plasma as well as rat liver and kidney homogenates. Receptor binding and cell uptake experiments were performed using AR4-2J rat pancreatic tumour cells. Animal biodistribution was studied in AR4-2J tumour-bearing nude mice. Radiolabelling was performed at high specific activities and radiochemical purity was >90%. 99m Tc-EDDA-HYNIC-MG11 showed high affinity for the CCK-2 receptor and cell internalisation comparable to that of 99m Tc-EDDA-HYNIC-MG0. Despite high stability in solution, a low metabolic stability in rat tissue homogenates was found. In a nude mouse tumour model, very low unspecific retention in most organs, rapid renal excretion with reduced renal retention and high tumour uptake were observed. 99m Tc-EDDA-HYNIC-MG11 shows advantages over 99m Tc-EDDA-HYNIC-MG0 in terms of lower kidney retention with unchanged uptake in tumours and CCK-2 receptor-positive tissue. However, the lower metabolic stability and impurities formed in the labelling process still leave room for further improvement. (orig.)

Use of Fe-Impregnated Biochar To Efficiently Sorb Chlorpyrifos, Reduce Uptake by Allium fistulosum L., and Enhance Microbial Community Diversity.

Science.gov (United States)

Tang, Xiao-Yan; Huang, Wen-Da; Guo, Jing-Jing; Yang, Yang; Tao, Ran; Feng, Xu

2017-07-05

Fe-impregnated biochar was assessed as a method to remove the pesticide pollutant chlorpyrifos, utilizing biochar/FeO x composite synthesized via chemical coprecipitation of Fe 3+ /Fe 2+ onto Cyperus alternifolius biochar. Fe-impregnated biochar exhibited a higher sorption capacity than pristine biochar, resulting in more efficient removal of chlorpyrifos from water. Soil was dosed with pristine or Fe-impregnated biochar at 0.1 or 1.0% w/w, to evaluate chlorpyrifos uptake in Allium fistulosum L. (Welsh onion). The results showed that the average concentration of chlorpyrifos and its degradation product, 3,5,6-trichloro-2-pyridinol (TCP), decreased in A. fistulosum L. with increased levels of pristine biochar and Fe-biochar. Fe-biochar was found to be more effective in reducing the uptake of chlorpyrifos by improving the sorption ability and increasing plant root iron plaque. Bioavailability of chlorpyrifos is reduced with both biochar and Fe-biochar soil dosing; however, the greatest persistence of chlorpyrifos residues was observed with 1.0% pristine biochar. Microbial community analysis showed Fe-biochar to have a positive impact on the efficiency of chlorpyrifos degradation in soils, possibly by altering microbial communities.

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...

Analysis of Neurotransmitter Tissue Content of Drosophila melanogaster in Different Life Stages

Science.gov (United States)

2015-01-01

Drosophila melanogaster is a widely used model organism for studying neurological diseases with similar neurotransmission to mammals. While both larva and adult Drosophila have central nervous systems, not much is known about how neurotransmitter tissue content changes through development. In this study, we quantified tyramine, serotonin, octopamine, and dopamine in larval, pupal, and adult fly brains using capillary electrophoresis coupled to fast-scan cyclic voltammetry. Tyramine and octopamine content varied between life stages, with almost no octopamine being present in the pupa, while tyramine levels in the pupa were very high. Adult females had significantly higher dopamine content than males, but no other neurotransmitters were dependent on sex in the adult. Understanding the tissue content of different life stages will be beneficial for future work comparing the effects of diseases on tissue content throughout development. PMID:25437353

Reduced 99mTc labelled NCA-95/CEA-antibody uptake in liver due to gentle antibody reconstitution

International Nuclear Information System (INIS)

Reske, S.N.; Buell, U.

1990-01-01

The influence of reconstituting a murine monoclonal IgG 1 antibody kit with pertechnetate Tc99m on antibody distribution in the liver, spleen and sternal bone marrow of patients was examined. The 99m Tc-labelled antibody used is directed against non-specific cross-reacting antigen (NCA-95) and carcinoembryonic antigen (CEA) and has been successfully applied for imaging tissue inflammation and bone marrow scanning. Radioactivity uptake was determined in the liver, spleen, bone marrow and a precordial background region in a consecutive series of 25 patients, examined with an antibody preparation, routinely radiolabelled according to the manufacturer's recommendations and in 14 patients, in whom the antibody was reconstituted with special care, avoiding bubble formation and dropping of buffer into the antibody-containing vial. Gentle compared with routine antibody reconstitution caused a highly significant reduction of the antibody uptake in the liver, as determined by count densities, normalized to injected dose and acquisition time (13.2±5.5 vs 20.1±6.0 cpm per pixel, anti x±SD, P=0.008). The liver to background ratio was reduced from 3.4±1.4 to 1.9±0.5 (P<0.001). Spleen, sternal bone marrow and precordial background count rates were not significantly affected. These results clearly demonstrate that gentle antibody reconstitution can decrease non-specific antibody uptake in the liver by 34%±6.4% (anti x±SEM). Thus, scan quality is improved, and the potential deleterious camouflage of underlying structures is avoided. (orig.)

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.

Combining in-school and community-based media efforts: reducing marijuana and alcohol uptake among younger adolescents.

Science.gov (United States)

Slater, Michael D; Kelly, Kathleen J; Edwards, Ruth W; Thurman, Pamela J; Plested, Barbara A; Keefe, Thomas J; Lawrence, Frank R; Henry, Kimberly L

2006-02-01

This study tests the impact of an in-school mediated communication campaign based on social marketing principles, in combination with a participatory, community-based media effort, on marijuana, alcohol and tobacco uptake among middle-school students. Eight media treatment and eight control communities throughout the US were randomly assigned to condition. Within both media treatment and media control communities, one school received a research-based prevention curriculum and one school did not, resulting in a crossed, split-plot design. Four waves of longitudinal data were collected over 2 years in each school and were analyzed using generalized linear mixed models to account for clustering effects. Youth in intervention communities (N = 4,216) showed fewer users at final post-test for marijuana [odds ratio (OR) = 0.50, P = 0.019], alcohol (OR = 0.40, P = 0.009) and cigarettes (OR = 0.49, P = 0.039), one-tailed. Growth trajectory results were significant for marijuana (P = 0.040), marginal for alcohol (P = 0.051) and non-significant for cigarettes (P = 0.114). Results suggest that an appropriately designed in-school and community-based media effort can reduce youth substance uptake. Effectiveness does not depend on the presence of an in-school prevention curriculum.

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

Psychosocial factors and uptake of risk-reducing salpingo-oophorectomy in women at high risk for ovarian cancer.

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Meiser, Bettina; Price, Melanie A; Butow, Phyllis N; Karatas, Janan; Wilson, Judy; Heiniger, Louise; Baylock, Brandi; Charles, Margaret; McLachlan, Sue-Anne; Phillips, Kelly-Anne

2013-03-01

Bilateral risk-reducing salpingo-oophorectomy (RRSO) has been shown to significantly reduce the risk of ovarian cancer. This study assessed factors predicting uptake of RRSO. Women participating in a large multiple-case breast cancer family cohort study who were at increased risk for ovarian and fallopian tube cancer (i.e. BRCA1 or BRCA2 mutation carrier or family history including at least one first- or second-degree relative with ovarian or fallopian tube cancer), with no personal history of cancer and with at least one ovary in situ at cohort enrolment, were eligible for this study. Women who knew they did not carry the BRCA1 or BRCA2 mutation segregating in their family (true negatives) were excluded. Sociodemographic, biological and psychosocial factors, including cancer-specific anxiety, perceived ovarian cancer risk, optimism and social support, were assessed using self-administered questionnaires and interviews at cohort enrolment. RRSO uptake was self-reported every three years during systematic follow-up. Of 2,859 women, 571 were eligible. Mean age was 43.3 years; 62 women (10.9 %) had RRSO a median of two years after cohort entry. Factors predicting RRSO were: being parous (OR 3.3, p = 0.015); knowing one's mutation positive status (OR 2.9, p cancer (OR 2.5, p = 0.013). Psychological variables measured at cohort entry were not associated with RRSO. These results suggest that women at high risk for ovarian cancer make decisions about RRSO based on risk and individual socio-demographic characteristics, rather than in response to psychological factors such as anxiety.

Chronic infusion of epigallocatechin-3-O-gallate into the hypothalamic paraventricular nucleus attenuates hypertension and sympathoexcitation by restoring neurotransmitters and cytokines.

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Yi, Qiu-Yue; Li, Hong-Bao; Qi, Jie; Yu, Xiao-Jing; Huo, Chan-Juan; Li, Xiang; Bai, Juan; Gao, Hong-Li; Kou, Bo; Liu, Kai-Li; Zhang, Dong-Dong; Chen, Wen-Sheng; Cui, Wei; Zhu, Guo-Qing; Shi, Xiao-Lian; Kang, Yu-Ming

2016-11-16

Reactive oxygen species (ROS) in the brain are involved in the pathogenesis of hypertension. Epigallocatechin-3-O-gallate (EGCG), one of the active compounds in green tea, has anti-oxidant, anti-inflammatory and vascular protective properties. This study was designed to determine whether chronic infusion of EGCG into the hypothalamic paraventricular nucleus (PVN) attenuates ROS and sympathetic activity and delays the progression of hypertension by up-regulating anti-inflammatory cytokines, reducing pro-inflammatory cytokines (PICs) and decreasing nuclear factor-kappa B (NF-κB) activity, as well as restoring the neurotransmitters balance in the PVN of spontaneously hypertensive rats (SHR). Adult normotensive Wistar-Kyoto (WKY) rats and SHR received bilateral PVN infusion of EGCG (20μg/h) or vehicle via osmotic minipumps for 4 weeks. SHR showed higher mean arterial pressure, plasma proinflammatory cytokines and circulating norepinephrine (NE) levels compared with WKY rats. SHR also had higher PVN levels of the subunit of NAD(P)H oxidase (gp91 phox ), ROS, tyrosine hydroxylase, and PICs; increased NF-κB activity; and lower PVN levels of interleukin-10 (IL-10) and 67kDa isoform of glutamate decarboxylase (GAD67) than WKY rats. PVN infusion of EGCG attenuated all these changes in SHR. These findings suggest that SHR have an imbalance between excitatory and inhibitory neurotransmitters, as well as an imbalance between pro- and anti-inflammatory cytokines in the PVN. Chronic inhibition of ROS in the PVN restores the balance of neurotransmitters and cytokines in the PVN, thereby attenuating hypertensive response and sympathetic activity. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

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.

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

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

Science.gov (United States)

Słoniecka, Marta; Le Roux, Sandrine; Boman, Peter; Byström, Berit; Zhou, Qingjun; Danielson, Patrik

2015-01-01

Keratocytes, the quiescent cells of the corneal stroma, play a crucial role in corneal wound healing. Neuropeptides and neurotransmitters are usually associated with neuronal signaling, but have recently been shown to be produced also by non-neuronal cells and to be involved in many cellular processes. The aim of this study was to assess the endogenous intracellular and secreted levels of the neuropeptides substance P (SP) and neurokinin A (NKA), and of the neurotransmitters acetylcholine (ACh), catecholamines (adrenaline, noradrenaline and dopamine), and glutamate, as well as the expression profiles of their receptors, in human primary keratocytes in vitro and in keratocytes of human corneal tissue sections in situ. Cultured keratocytes expressed genes encoding for SP and NKA, and for catecholamine and glutamate synthesizing enzymes, as well as genes for neuropeptide, adrenergic and ACh (muscarinic) receptors. Keratocytes in culture produced SP, NKA, catecholamines, ACh, and glutamate, and expressed neurokinin-1 and -2 receptors (NK-1R and NK-2R), dopamine receptor D2, muscarinic ACh receptors, and NDMAR1 glutamate receptor. Human corneal sections expressed SP, NKA, NK-1R, NK-2R, receptor D2, choline acetyl transferase (ChAT), M3, M4 and M5 muscarinic ACh receptors, glutamate, and NMDAR1, but not catecholamine synthesizing enzyme or the α1 and β2 adrenoreceptors, nor M1 receptor. In addition, expression profiles assumed significant differences between keratocytes from the peripheral cornea as compared to those from the central cornea, as well as differences between keratocytes cultured under various serum concentrations. In conclusion, human keratocytes express an array of neuropeptides and neurotransmitters. The cells furthermore express receptors for neuropeptides/neurotransmitters, which suggests that they are susceptible to stimulation by these substances in the cornea, whether of neuronal or non-neuronal origin. As it has been shown that neuropeptides/neurotransmitters

Attempt to define a repair threshold (or the prospects for kidneys of reduced uptake rate)

International Nuclear Information System (INIS)

Le Duc, A.; Camey, M.; Bourguignon, M.; CEA, 91 - Orsay

1976-01-01

The definition of a repair threshold hardly seems realistic whatever the etiology considered. It is impossible to set a lower uptake limit below which a kidney does not recover, nor an upper limit above which recuperation is inevitable. To be able to use an uptake rate result with discernment it is useful to know two facts: '0 degradation' prospects exist for very diseased kidneys; the prospects of recovery are very appreciable for kidneys subjected to an infected stasis, amply justifying conservation in uptake regions around 20%. All this obviously needs confirmation which can only be obtained by adding a functional study to certain files which already date back significantly [fr

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

Directory of Open Access Journals (Sweden)

Faramarz eFaghihi

2015-04-01

Full Text Available Synapses act as information filters by different molecular mechanisms including retrograde messenger that affect neuronal spiking activity. One of the well-known effects of retrograde messenger in presynaptic neurons is a change of the probability of neurotransmitter release. Hebbian learning describe a strengthening of a synapse between a presynaptic input onto a postsynaptic neuron when both pre- and postsynaptic neurons are coactive. In this work, a theory of homeostatic regulation of neurotransmitter release by retrograde messenger and Hebbian plasticity in neuronal encoding is presented. Encoding efficiency was measured for different synaptic conditions. In order to gain high encoding efficiency, the spiking pattern of a neuron should be dependent on the intensity of the input and show low levels of noise. In this work, we represent spiking trains as zeros and ones (corresponding to non-spike or spike in a time bin, respectively as words with length equal to three. Then the frequency of each word (here eight words is measured using spiking trains. These frequencies are used to measure neuronal efficiency in different conditions and for different parameter values. Results show that neurons that have synapses acting as band-pass filters show the highest efficiency to encode their input when both Hebbian mechanism and homeostatic regulation of neurotransmitter release exist in synapses. Specifically, the integration of homeostatic regulation of feedback inhibition with Hebbian mechanism and homeostatic regulation of neurotransmitter release in the synapses leads to even higher efficiency when high stimulus intensity is presented to the neurons. However, neurons with synapses acting as high-pass filters show no remarkable increase in encoding efficiency for all simulated synaptic plasticity mechanisms.

Metabolomics of Neurotransmitters and Related Metabolites in Post-Mortem Tissue from the Dorsal and Ventral Striatum of Alcoholic Human Brain.

Science.gov (United States)

Kashem, Mohammed Abul; Ahmed, Selina; Sultana, Nilufa; Ahmed, Eakhlas U; Pickford, Russell; Rae, Caroline; Šerý, Omar; McGregor, Iain S; Balcar, Vladimir J

2016-02-01

We report on changes in neurotransmitter metabolome and protein expression in the striatum of humans exposed to heavy long-term consumption of alcohol. Extracts from post mortem striatal tissue (dorsal striatum; DS comprising caudate nucleus; CN and putamen; P and ventral striatum; VS constituted by nucleus accumbens; NAc) were analysed by high performance liquid chromatography coupled with tandem mass spectrometry. Proteomics was studied in CN by two-dimensional gel electrophoresis followed by mass-spectrometry. Proteomics identified 25 unique molecules expressed differently by the alcohol-affected tissue. Two were dopamine-related proteins and one a GABA-synthesizing enzyme GAD65. Two proteins that are related to apoptosis and/or neuronal loss (BiD and amyloid-β A4 precursor protein-binding family B member 3) were increased. There were no differences in the levels of dopamine (DA), 3,4-dihydrophenylacetic acid (DOPAC), serotonin (5HT), homovanillic acid (HVA), 5-hydroxyindoleacetic acid (HIAA), histamine, L-glutamate (Glu), γ-aminobutyric acid (GABA), tyrosine (Tyr) and tryptophan (Tryp) between the DS (CN and P) and VS (NAc) in control brains. Choline (Ch) and acetylcholine (Ach) were higher and norepinephrine (NE) lower, in the VS. Alcoholic striata had lower levels of neurotransmitters except for Glu (30 % higher in the alcoholic ventral striatum). Ratios of DOPAC/DA and HIAA/5HT were higher in alcoholic striatum indicating an increase in the DA and 5HT turnover. Glutathione was significantly reduced in all three regions of alcohol-affected striatum. We conclude that neurotransmitter systems in both the DS (CN and P) and the VS (NAc) were significantly influenced by long-term heavy alcohol intake associated with alcoholism.

Lung damage and pulmonary uptake of serotonin in intact dogs

International Nuclear Information System (INIS)

Dawson, C.A.; Christensen, C.W.; Rickaby, D.A.; Linehan, J.H.; Johnston, M.R.

1985-01-01

The authors examined the influence of glass bead embolization and oleic acid, dextran, and imipramine infusion on the pulmonary uptake of trace doses of [ 3 H]serotonin and the extravascular volume accessible to [ 14 C]antipyrine in anesthetized dogs. Embolization and imipramine decreased serotonin uptake by 53 and 61%, respectively, but no change was observed with oleic acid or dextran infusion. The extravascular volume accessible to the antipyrine was reduced by 77% after embolization and increased by 177 and approximately 44% after oleic acid and dextran infusion, respectively. The results suggest that when the perfused endothelial surface is sufficiently reduced, as with embolization, the uptake of trace doses of serotonin will be depressed. In addition, decreases in serotonin uptake in response to imipramine in this study and in response to certain endothelial toxins in other studies suggest that serotonin uptake can reveal certain kinds of changes in endothelial function. However, the lack of a response to oleic acid-induced damage in the present study suggests that serotonin uptake is not sensitive to all forms of endothelial damage

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.

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.

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

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.

Selective uptake and biological consequences of environmentally relevant antidepressant pharmaceutical exposures on male fathead minnows

Science.gov (United States)

Schultz, Melissa M.; Painter, Meghan M.; Bartell, Stephen E.; Logue, Amanda; Furlong, Edward T.; Werner, Stephen L.; Schoenfuss, Heiko L.

2011-01-01

Antidepressant pharmaceuticals have been reported in wastewater effluent at the nanogram to low microgram-per-liter range, and include bupropion (BUP), fluoxetine (FLX), sertraline (SER), and venlafaxine (VEN). To assess the effects of antidepressants on reproductive anatomy, physiology, and behavior, adult male fathead minnows (Pimeplwles promelas) were exposed for 21 days either to a single concentration of the antidepressants FLX, SER, VEN, or BUP, or to an antidepressant mixture. The data demonstrated that exposure to VEN (305 ng/L and 1104 ng/L) and SER (5.2 ng/L) resulted in mortality. Anatomical alterations were noted within the testes of fish exposed to SER and FLX, both modulators of the neurotransmitter serotonin. Additionally, FLX at 28 ng/L induced vitellogenin in male fish—a common endpoint for estrogenic endocrine disruption. Significant alterations in male secondary sex characteristics were noted with single exposures. Effects of single compound exposures neither carried over, nor became additive in the antidepressant mixtures, and reproductive behavior was not affected. Analysis of brain tissues from the exposed fish suggested increased uptake of FLX, SER and BUP and minimal uptake of VEN when compared to exposure water concentrations. Furthermore, the only metabolite detected consistently in the brain tissues was norfluoxetine. Similar trends of uptake by brain tissue were observed when fish were exposed to antidepressant mixtures. The present study demonstrates that anatomy and physiology, but not reproductive behavior, can be disrupted by exposure to environmental concentrations of some antidepressants. The observation that antidepressant uptake into fish tissues is selective may have consequences on assessing the mode-of-action and effects of these compounds in future studies.

Uranium uptake of Vetiveria zizanioides (L.) Nash

International Nuclear Information System (INIS)

Luu Viet Hung; Maslov, O.D.; Trinh Thi Thu My; Phung Khac Nam Ho; Dang Duc Nhan

2010-01-01

Uranium uptake of vetiver grass (Vetiveria zizanioides (L.) Nash) from Eutric Fluvisols (AK), Albic Acrisols (BG), Dystric Fluvisols (HP) and Ferralic Acrisols (TC) in northern Vietnam is assessed. The soils were mixed with aqueous solution of uranyl nitrate to make soils contaminated with uranium at 0, 50, 100, 250 mg/kg before planting the grass. The efficiency of uranium uptake by the grass was assessed based on the soil-to-plant transfer factor (TF U , kg·kg -1 ). It was found that the TF U values are dependent upon the soils properties. CEC facilitates the uptake and the increased soil pH could reduce the uptake and translocation of uranium in the plant. Organic matter content, as well as iron and potassium, inhibits the uranium uptake of the grass. It was revealed that the lower fertile soil, the higher uranium uptake. The translocation of uranium in root for all the soil types studied is almost higher than that in its shoot. It seems that vetiver grass could potentially be used for the purpose of phytoremediation of soils contaminated with uranium

Monocyte transferrin-iron uptake in hereditary hemochromatosis

International Nuclear Information System (INIS)

Sizemore, D.J.; Bassett, M.L.

1984-01-01

Transferrin-iron uptake by peripheral blood monocytes was studied in vitro to test the hypothesis that the relative paucity of mononuclear phagocyte iron loading in hereditary hemochromatosis results from a defect in uptake of iron from transferrin. Monocytes from nine control subjects and 17 patients with hemochromatosis were cultured in the presence of 59Fe-labelled human transferrin. There was no difference in 59Fe uptake between monocytes from control subjects and monocytes from patients with hemochromatosis who had been treated by phlebotomy and who had normal body iron stores. However, 59Fe uptake by monocytes from iron-loaded patients with hemochromatosis was significantly reduced compared with either control subjects or treated hemochromatosis patients. It is likely that this was a secondary effect of iron loading since iron uptake by monocytes from treated hemochromatosis patients was normal. Assuming that monocytes in culture reflect mononuclear phagocyte iron metabolism in vivo, this study suggests that the relative paucity of mononuclear phagocyte iron loading in hemochromatosis is not related to an abnormality in transferrin-iron uptake by these cells

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...

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.

Flavonoid rutin increases thyroid iodide uptake in rats.

Directory of Open Access Journals (Sweden)

Carlos Frederico Lima Gonçalves

Full Text Available Thyroid iodide uptake through the sodium-iodide symporter (NIS is not only an essential step for thyroid hormones biosynthesis, but also fundamental for the diagnosis and treatment of different thyroid diseases. However, part of patients with thyroid cancer is refractory to radioiodine therapy, due to reduced ability to uptake iodide, which greatly reduces the chances of survival. Therefore, compounds able to increase thyroid iodide uptake are of great interest. It has been shown that some flavonoids are able to increase iodide uptake and NIS expression in vitro, however, data in vivo are lacking. Flavonoids are polyhydroxyphenolic compounds, found in vegetables present in human diet, and have been shown not only to modulate NIS, but also thyroperoxidase (TPO, the key enzyme in thyroid hormones biosynthesis, besides having antiproliferative effect in thyroid cancer cell lines. Therefore, we aimed to evaluate the effect of some flavonoids on thyroid iodide uptake in Wistar rats in vivo. Among the flavonoids tested, rutin was the only one able to increase thyroid iodide uptake, so we decided to evaluate the effect of this flavonoid on some aspects of thyroid hormones synthesis and metabolism. Rutin led to a slight reduction of serum T4 and T3 without changes in serum thyrotropin (TSH, and significantly increased hypothalamic, pituitary and brown adipose tissue type 2 deiodinase and decreased liver type 1 deiodinase activities. Moreover, rutin treatment increased thyroid iodide uptake probably due to the increment of NIS expression, which might be secondary to increased response to TSH, since TSH receptor expression was increased. Thus, rutin might be useful as an adjuvant in radioiodine therapy, since this flavonoid increased thyroid iodide uptake without greatly affecting thyroid function.

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

Lime and Phosphate Amendment Can Significantly Reduce Uptake of Cd and Pb by Field-Grown Rice

Directory of Open Access Journals (Sweden)

Rongbo Xiao

2017-03-01

Full Text Available Agricultural soils are suffering from increasing heavy metal pollution, among which, paddy soil polluted by heavy metals is frequently reported and has elicited great public concern. In this study, we carried out field experiments on paddy soil around a Pb-Zn mine to study amelioration effects of four soil amendments on uptake of Cd and Pb by rice, and to make recommendations for paddy soil heavy metal remediation, particularly for combined pollution of Cd and Pb. The results showed that all the four treatments can significantly reduce the Cd and Pb content in the late rice grain compared with the early rice, among which, the combination amendment of lime and phosphate had the best remediation effects where rice grain Cd content was reduced by 85% and 61%, respectively, for the late rice and the early rice, and by 30% in the late rice grain for Pb. The high reduction effects under the Ca + P treatment might be attributed to increase of soil pH from 5.5 to 6.7. We also found that influence of the Ca + P treatment on rice production was insignificant, while the available Cd and Pb content in soil was reduced by 16.5% and 11.7%, respectively.

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

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

Science.gov (United States)

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.

Excitant amino acid projections from rat amygdala and thalamus to nucleus accumbens

International Nuclear Information System (INIS)

Robinson, T.G.; Beart, P.M.

1988-01-01

High affinity uptake of D-[ 3 H]aspartate, [ 3 H]choline and [ 3 H]GABA was examined in synaptosomal-containing preparations of rat nucleus accumbens septi 7 to 10 days after unilateral or bilateral N-methyl-D-aspartate lesions confined to the parataenial nucleus of the thalamus or the basolateral nucleus of the amygdala. Uptake of both D-[ 3 H]aspartate and [ 3 H]choline was significantly reduced (11% and 14% less than control, respectively) by unilateral lesion of the thalamus, whereas [ 3 H]GABA uptake was unaffected. Bilateral thalamic lesions significantly reduced D-[ 3 H]aspartate uptake (11% less than control) into homogenates of the nucleus accumbens, whilst [ 3 H]GABA uptake was unaltered. D-[ 3 H]aspartate uptake was significantly reduced (26% less than control) following unilateral lesion of the amygdala, whereas both [ 3 H]GABA and [ 3 H]choline uptake were unaffected. Bilateral amygdaloid lesions significantly increased D-[ 3 H]aspartate uptake (39% greater than control), whilst uptake of [ 3 H]GABA was not affected. The results implicate glutamate and/or aspartate as putative neurotransmitters in afferent projections from the basolateral amygdala and the parataenial thalamus to the nucleus accumbens. Thalamic afferents to the nucleus accumbens may also utilize acetylcholine as their transmitter

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...

Biochar application to a contaminated soil reduces the availability and plant uptake of zinc, lead and cadmium.

Science.gov (United States)

Puga, A P; Abreu, C A; Melo, L C A; Beesley, L

2015-08-15

Heavy metals in soil are naturally occurring but may be enhanced by anthropogenic activities such as mining. Bio-accumulation of heavy metals in the food chain, following their uptake to plants can increase the ecotoxicological risks associated with remediation of contaminated soils using plants. In the current experiment sugar cane straw-derived biochar (BC), produced at 700 °C, was applied to a heavy metal contaminated mine soil at 1.5%, 3.0% and 5.0% (w/w). Jack bean (Canavalia ensiformis) and Mucuna aterrima were grown in pots containing soil and biochar mixtures, and control pots without biochar. Pore water was sampled from each pot to confirm the effects of biochar on metal solubility, whilst soils were analyzed by DTPA extraction to confirm available metal concentrations. Leaves were sampled for SEM analysis to detect possible morphological and anatomical changes. The application of BC decreased the available concentrations of Cd, Pb and Zn in 56, 50 and 54% respectively, in the mine contaminated soil leading to a consistent reduction in the concentration of Zn in the pore water (1st collect: 99 to 39 μg L(-1), 2nd: 97 to 57 μg L(-1) and 3rd: 71 to 12 μg L(-1)). The application of BC reduced the uptake of Cd, Pb and Zn by plants with the jack bean translocating high proportions of metals (especially Cd) to shoots. Metals were also taken up by Mucuna aterrima but translocation to shoot was more limited than for jack bean. There were no differences in the internal structures of leaves observed by scanning electron microscopy. This study indicates that biochar application during mine soil remediation reduce plant concentrations of potential toxic metals. Copyright © 2015 Elsevier Ltd. All rights reserved.

Nitrogen and phosphorous limitation reduces the effects of land use change on land carbon uptake or emission

International Nuclear Information System (INIS)

Wang, Ying-Ping; Zhang, Qian; Dai, Yongjiu; Pitman, Andrew J

2015-01-01

We used an Earth System Model that includes both nitrogen (N) and phosphorus (P) cycling to simulate the impacts of land-use and land-cover change (LULCC) for two representative concentration pathways (RCPs): a reforestation scenario (RCP4.5) and a deforestation scenario (RCP8.5). For each RCP, we performed simulations with and without LULCC using the carbon (C only) mode or including the full C, N and P cycles (CNP). We show, for the first time, that inclusion of N and P cycling reduces both the carbon uptake from reforestation in RCP4.5 and the carbon emission from deforestation in RCP8.5. Specifically, carbon-nutrient interaction reduces carbon uptake in RCP4.5 from 55 Pg C (C only) to 21 Pg C (CNP), or the emissions in RCP8.5 from 72 Pg C (C only) to 56 Pg C (CNP). Most of those reductions result from much weaker responses of net primary production to CO 2 fertilization and climate change when carbon-nutrient interaction is taken into account, as compared to C only simulations. Our results highlight the importance of including nutrient-carbon interaction in estimating the carbon benefit from reforestation and carbon loss from deforestation in a future world with higher CO 2 and a warmer climate. Because of the stronger nutrient limitation, carbon gain from reforestation in the temperate and boreal regions is much less than the carbon loss from deforestation in the subtropical and tropical regions from 2006 to 2100 for the two RCPs. Therefore protecting the existing subtropical and tropical forests is about twice as effective as planting new forests in the temperate and boreal regions for climate mitigation. (letter)

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.

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.

Reducing the barriers to the uptake of cataract surgical services in a ...

African Journals Online (AJOL)

A joint partnership between the Ophthalmology Department, the hospital management and a non-profit, non-governmental organization (NGO) was established to tackle the barriers of awareness, access and high cost of surgery to the uptake of cataract surgery from January 2005. The Ophthalmology Department and ...

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.

Application of fungistatics in soil reduces N uptake by an arctic ericoid shrub (Vaccinium vitis-idaea)

Energy Technology Data Exchange (ETDEWEB)

Walker, J.F.; Johnson, L.; Simpson, N.B.; Bill, M.; Jumpponen, A.

2009-11-01

In arctic tundra soil N is highly limiting, N mineralization is slow and organic N greatly exceeds inorganic N. We studied the effects of fungistatics (azoxystrobin [Quadris{reg_sign}] or propiconazole [Tilt{reg_sign}]) on the fungi isolated from ericaceous plant roots in vitro. In addition to testing the phytotoxicity of the two fungistatics we also tested their effects on growth and nitrogen uptake of an ericaceous plant (Vaccinium uliginosum) in a closed Petri plate system without root-associated fungi. Finally, to evaluate the fungistatic effects in an in vivo experiment we applied fungistatics and nitrogen isotopes to intact tundra soil cores from Toolik Lake, Alaska, and examined the ammonium-N and glycine-N use by Vaccinium vitis-idaea with and without fungistatics. The experiments on fungal pure cultures showed that Tilt{reg_sign} was more effective in reducing fungal colony growth in vitro than Quadris{reg_sign}, which was highly variable among the fungal strains. Laboratory experiments aiming to test the fungistatic effects on plant performance in vitro showed that neither Quadris{reg_sign} nor Tilt{reg_sign} affected V. uliginosum growth or N uptake. In this experiment V. uliginosum assimilated more than an order of magnitude more ammonium-N than glycine-N. The intact tundra core experiment provided contrasting results. After 10 wk of fungistatic application in the growth chamber V. vitis-idaea leaf %N was 10% lower and the amount of leaf {sup 15}N acquired was reduced from labeled ammonium (33%) and glycine (40%) during the 4 d isotope treatment. In contrast to the in vitro experiment leaf {sup 15}N assimilation from glycine was three times higher than from {sup 15}NH{sub 4} in the treatments that received no-fungistatics. We conclude that the function of the fungal communities is essential to the acquisition of N from organic sources and speculate that N acquisition from inorganic sources is mainly inhibited by competition with complex soil microbial

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

Science.gov (United States)

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).

Heavy metals and their radionuclides uptake by Bacillus Licheniformis

International Nuclear Information System (INIS)

Ramadan, A.A.; Ahmed, M.M.; Abo-state, M.A.M.; Sarhan, M.; Faroqe, M.

2007-01-01

Bacillus licheniformis is a gram positive spore forming bacterium. Different concentrations of cobalt affected the ability of Co uptake and growth of Bacillus licheniformis. As the concentration increased, both the uptake and growth were decreased. Maximum Co uptake was found at ph 7.0, while for growth was ph 8.0. The optimum temperature for uptake and growth was 40 degree C and 20% inoculum size represents the maximum cobalt uptake by Bacillus licheniformis. Also, maximum uptake was recorded after 72 hours, incubation period. As the concentration of cesium was increased till 400 mg/l, the uptake was also increased. The optimum cesium uptake and growth was at ph 8.0. The optimum growth was at 45 degree C while Cs uptake was found at 35 degree C and 15% inoculum size represented the maximum Cs uptake. After 72 hour incubation period, maximum Cs uptake was recorded. Generally, Bacillus licheniformis removed more than 80% of Co and 50% of Cs from the broth medium. Addition of clay to Bacillus licheniformis increased both Co or Cs uptake. Bacillus licheniformis was gamma resistant and 10 KGy reduced the viability by 5.3 log cycles. The irradiated and non-irradiated cultures can grow on 500 or 700 mg Co or Cs. Bacillus licheniformis removed 99.32% of the Co radionuclides and 99.28% of Cs radionuclides

Decreased cisplatin uptake by resistant L1210 leukemia cells

International Nuclear Information System (INIS)

Hromas, R.A.; North, J.A.; Burns, C.P.

1987-01-01

Cisplatin resistance remains poorly understood compared to other forms of anti-neoplastic drug resistance. In this report radiolabelled cisplatin and rapid separation techniques were used to compare drug uptake by L1210 leukemia cells that are sensitive (K25) or resistant (SCR9) to cisplatin. Uptake of cisplatin by both cell lines was linear without saturation kinetics up to 100 μM. The resistant ZCR9 cells had 36-60% reduced drug uptake as compared to its sensitive parent line, K25. In contrast, there was no difference in the rate of efflux. We conclude that a decreased rate of uptake is one possible mechanism of cellular cisplatin resistance. (Author)

Loss of nitric oxide-mediated inhibition of purine neurotransmitter release in the colon in the absence of interstitial cells of Cajal.

Science.gov (United States)

Durnin, Leonie; Lees, Andrea; Manzoor, Sheerien; Sasse, Kent C; Sanders, Kenton M; Mutafova-Yambolieva, Violeta N

2017-11-01

Regulation of colonic motility depends on the integrity of enteric inhibitory neurotransmission mediated by nitric oxide (NO), purine neurotransmitters, and neuropeptides. Intramuscular interstitial cells of Cajal (ICC-IM) and platelet-derived growth factor receptor-α-positive (PDGFRα + ) cells are involved in generating responses to NO and purine neurotransmitters, respectively. Previous studies have suggested a decreased nitrergic and increased purinergic neurotransmission in Kit W /Kit W-v ( W/W v ) mice that display lesions in ICC-IM along the gastrointestinal tract. However, contributions of NO to these phenotypes have not been evaluated. We used small-chamber superfusion assays and HPLC to measure the spontaneous and electrical field stimulation (EFS)-evoked release of nicotinamide adenine dinucleotide (NAD + )/ADP-ribose, uridine adenosine tetraphosphate (Up4A), adenosine 5'-triphosphate (ATP), and metabolites from the tunica muscularis of human, monkey, and murine colons and circular muscle of monkey colon, and we tested drugs that modulate NO levels or blocked NO receptors. NO inhibited EFS-evoked release of purines in the colon via presynaptic neuromodulation. Colons from W/W v , Nos1 -/- , and Prkg1 -/- mice displayed augmented neural release of purines that was likely due to altered nitrergic neuromodulation. Colons from W/W v mice demonstrated decreased nitrergic and increased purinergic relaxations in response to nerve stimulation. W/W v mouse colons demonstrated reduced Nos1 expression and reduced NO release. Our results suggest that enhanced purinergic neurotransmission may compensate for the loss of nitrergic neurotransmission in muscles with partial loss of ICC. The interactions between nitrergic and purinergic neurotransmission in the colon provide novel insight into the role of neurotransmitters and effector cells in the neural regulation of gastrointestinal motility. NEW & NOTEWORTHY This is the first study investigating the role of nitric

Neurotransmitter modulation of extracellular H+ fluxes from isolated retinal horizontal cells of the skate

Science.gov (United States)

Molina, Anthony J A; Verzi, Michael P; Birnbaum, Andrea D; Yamoah, Ebenezer N; Hammar, Katherine; Smith, Peter J S; Malchow, Robert Paul

2004-01-01

Self-referencing H+-selective microelectrodes were used to measure extracellular H+ fluxes from horizontal cells isolated from the skate retina. A standing H+ flux was detected from quiescent cells, indicating a higher concentration of free hydrogen ions near the extracellular surface of the cell as compared to the surrounding solution. The standing H+ flux was reduced by removal of extracellular sodium or application of 5-(N-ethyl-N-isopropyl) amiloride (EIPA), suggesting activity of a Na+–H+ exchanger. Glutamate decreased H+ flux, lowering the concentration of free hydrogen ions around the cell. AMPA/kainate receptor agonists mimicked the response, and the AMPA/kainate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) eliminated the effects of glutamate and kainate. Metabotropic glutamate agonists were without effect. Glutamate-induced alterations in H+ flux required extracellular calcium, and were abolished when cells were bathed in an alkaline Ringer solution. Increasing intracellular calcium by photolysis of the caged calcium compound NP-EGTA also altered extracellular H+ flux. Immunocytochemical localization of the plasmalemma Ca2+–H+-ATPase (PMCA pump) revealed intense labelling within the outer plexiform layer and on isolated horizontal cells. Our results suggest that glutamate modulation of H+ flux arises from calcium entry into cells with subsequent activation of the plasmalemma Ca2+–H+-ATPase. These neurotransmitter-induced changes in extracellular pH have the potential to play a modulatory role in synaptic processing in the outer retina. However, our findings argue against the hypothesis that hydrogen ions released by horizontal cells normally act as the inhibitory feedback neurotransmitter onto photoreceptor synaptic terminals to create the surround portion of the centre-surround receptive fields of retinal neurones. PMID:15272044

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

Science.gov (United States)

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.

Effect of Zuogui Pill () on monoamine neurotransmitters and sex hormones in climacteric rats with panic attack.

Science.gov (United States)

Li, Xiao-Yu; Wang, Xiao-Yun

2017-03-01

To explore the effects of Chinese medicine prescription Zuogui Pill (, ZGP) on monoamine neurotransmitters and sex hormones in climacteric rats with induced panic attacks. Forty-eight climacteric female rats were randomized into 6 groups with 8 rats in each group: the control group, the model group, the low-, medium- and high-dose ZGP groups and the alprazolam group. Rats in the low-, medium- and high-dose ZGP groups were administered 4.725, 9.45, or 18.9 g/kg ZGP by gastric perfusion, respectively. The alprazolam group was treated by gastric perfusion with 0.036 mg/kg alprazolam. The control and model groups were treated with distilled water. The animals were pretreated once daily for 8 consecutive weeks. The behaviors of rats in the open fifield test and the elevated T-maze (ETM) were observed after induced panic attack, and the levels of brain monoamine neurotransmitters and the plasma levels of sex hormones were measured. Compared with the control group, the mean ETM escape time and the levels of 5-hydroxytryptamine (5-HT) and noradrenalin (NE) of the model group were signifificantly reduced (P<0.05), Compared with the model group, the mean ETM escape time and the 5-HT and NE levels of all the ZGP groups increased signifificantly (P<0.05 or P<0.01). However, no signifificant difference was observed in the levels of sex hormones between the groups. Pretreatment with ZGP in climacteric rats may improve the behavior of panic attack, which may be related to increased 5-HT and NE in the brain.

Analysis of urinary neurotransmitters by capillary electrophoresis: Sensitivity enhancement using field-amplified sample injection and molecular imprinted polymer solid phase extraction

International Nuclear Information System (INIS)

Claude, Berengere; Nehme, Reine; Morin, Philippe

2011-01-01

Highlights: → Field-amplified sample injection (FASI) improves the sensitivity of capillary electrophoresis through the online pre-concentration samples. → The cationic analytes are stacked at the capillary inlet between a zone of low conductivity - sample and pre-injection plug - and a zone of high conductivity - running buffer. → The limits of quantification are 500 times lower than those obtained with hydrodynamic injection. → The presence of salts in the matrix greatly reduces the sensitivity of the FASI/CE-UV method. - Abstract: Capillary electrophoresis (CE) has been investigated for the analysis of some neurotransmitters, dopamine (DA), 3-methoxytyramine (3-MT) and serotonin (5-hydroxytryptamine, 5-HT) at nanomolar concentrations in urine. Field-amplified sample injection (FASI) has been used to improve the sensitivity through the online pre-concentration samples. The cationic analytes were stacked at the capillary inlet between a zone of low conductivity - sample and pre-injection plug - and a zone of high conductivity - running buffer. Several FASI parameters have been optimized (ionic strength of the running buffer, concentration of the sample protonation agent, composition of the sample solvent and nature of the pre-injection plug). Best results were obtained using H 3 PO 4 -LiOH (pH 4, ionic strength of 80 mmol L -1 ) as running buffer, 100 μmol L -1 of H 3 PO 4 in methanol-water 90/10 (v/v) as sample solvent and 100 μmol L -1 of H 3 PO 4 in water for the pre-injection plug. In these conditions, the linearity was verified in the 50-300 nmol L -1 concentration range for DA, 3-MT and 5-HT with a determination coefficient (r 2 ) higher than 0.99. The limits of quantification (10 nmol L -1 for DA and 3-MT, 5.9 nmol L -1 for 5-HT) were 500 times lower than those obtained with hydrodynamic injection. However, if this method is applied to the analysis of neurotransmitters in urine, the presence of salts in the matrix greatly reduces the sensitivity

Analysis of urinary neurotransmitters by capillary electrophoresis: Sensitivity enhancement using field-amplified sample injection and molecular imprinted polymer solid phase extraction

Energy Technology Data Exchange (ETDEWEB)

Claude, Berengere, E-mail: berengere.claude@univ-orleans.fr [Institut de Chimie Organique et Analytique, CNRS FR 2708 UMR 6005, Universite d' Orleans, 45067 Orleans (France); Nehme, Reine; Morin, Philippe [Institut de Chimie Organique et Analytique, CNRS FR 2708 UMR 6005, Universite d' Orleans, 45067 Orleans (France)

2011-08-12

Highlights: {yields} Field-amplified sample injection (FASI) improves the sensitivity of capillary electrophoresis through the online pre-concentration samples. {yields} The cationic analytes are stacked at the capillary inlet between a zone of low conductivity - sample and pre-injection plug - and a zone of high conductivity - running buffer. {yields} The limits of quantification are 500 times lower than those obtained with hydrodynamic injection. {yields} The presence of salts in the matrix greatly reduces the sensitivity of the FASI/CE-UV method. - Abstract: Capillary electrophoresis (CE) has been investigated for the analysis of some neurotransmitters, dopamine (DA), 3-methoxytyramine (3-MT) and serotonin (5-hydroxytryptamine, 5-HT) at nanomolar concentrations in urine. Field-amplified sample injection (FASI) has been used to improve the sensitivity through the online pre-concentration samples. The cationic analytes were stacked at the capillary inlet between a zone of low conductivity - sample and pre-injection plug - and a zone of high conductivity - running buffer. Several FASI parameters have been optimized (ionic strength of the running buffer, concentration of the sample protonation agent, composition of the sample solvent and nature of the pre-injection plug). Best results were obtained using H{sub 3}PO{sub 4}-LiOH (pH 4, ionic strength of 80 mmol L{sup -1}) as running buffer, 100 {mu}mol L{sup -1} of H{sub 3}PO{sub 4} in methanol-water 90/10 (v/v) as sample solvent and 100 {mu}mol L{sup -1} of H{sub 3}PO{sub 4} in water for the pre-injection plug. In these conditions, the linearity was verified in the 50-300 nmol L{sup -1} concentration range for DA, 3-MT and 5-HT with a determination coefficient (r{sup 2}) higher than 0.99. The limits of quantification (10 nmol L{sup -1} for DA and 3-MT, 5.9 nmol L{sup -1} for 5-HT) were 500 times lower than those obtained with hydrodynamic injection. However, if this method is applied to the analysis of

A protective effect of dietary calcium against acute waterborne cadmium uptake in rainbow trout

International Nuclear Information System (INIS)

Baldisserotto, B.; Kamunde, C.; Matsuo, A.; Wood, C.M.

2004-01-01

The present study examined the interactions between elevated dietary calcium (as ionic Ca 2+ in the form of CaCl 2 ·2H 2 O) and acute waterborne Cd exposure (50 μg/l as CdNO 3 for 3 h) on whole body uptake and internal distribution of newly accumulated Cd, Ca 2+ , and Na + in juvenile rainbow trout (Oncorhynchus mykiss). Fish were fed with three diets 20 (control), 30 and 60 mg Ca 2+ /g food: for 7 days before fluxes were measured with radiotracers over a 3 h period. The two elevated Ca 2+ diets reduced the whole body uptake of both Ca 2+ and Cd by >50% and similarly reduced the internalization of both newly accumulated metals in most tissues, effects which reflect the shared branchial uptake route for Ca 2+ and Cd. As the Ca 2+ concentrations of the fluid phases of the stomach and intestinal contents were greatly elevated by the experimental diets, increased gastrointestinal Ca 2+ uptake likely caused the down-regulation of the branchial Ca 2+ (and Cd) uptake pathway. Waterborne Na + uptake and internal distribution were not affected. While plasma Ca 2+ surged after the first two feedings of the 60 mg Ca 2+ /g diet, internal homeostasis was quickly restored. Total Ca 2+ , Na + , and Cl - levels in tissues were not affected by diets. While dietary Ca 2+ protected against waterborne Cd uptake, it did not protect against the relative inhibition of waterborne Ca 2+ uptake caused by waterborne Cd. Acute exposure to 50 μg/l Cd reduced the uptake and internalization of newly accumulated Ca 2+ (but not Na + ) by 70% or more, regardless of diet. Since elevated dietary Ca 2+ reduces waterborne Cd uptake, fish eating a Ca 2+ -rich invertebrate diet may be more protected against waterborne Cd toxicity in a field situation

A novel liquid chromatography/mass spectrometry method for determination of neurotransmitters in brain tissue: Application to human tauopathies.

Science.gov (United States)

Forgacsova, Andrea; Galba, Jaroslav; Garruto, Ralph M; Majerova, Petra; Katina, Stanislav; Kovac, Andrej

2018-01-15

Neurotransmitters, small molecules widely distributed in the central nervous system are essential in transmitting electrical signals across neurons via chemical communication. Dysregulation of these chemical signaling molecules is linked to numerous neurological diseases including tauopathies. In this study, a precise and reliable liquid chromatography method was established with tandem mass spectrometry detection for the simultaneous determination of aspartic acid, asparagine, glutamic acid, glutamine, γ-aminobutyric acid, N-acetyl-l-aspartic acid, pyroglutamic acid, acetylcholine and choline in human brain tissue. The method was successfully applied to the analysis of human brain tissues from three different tauopathies; corticobasal degeneration, progressive supranuclear palsy and parkinsonism-dementia complex of Guam. Neurotransmitters were analyzed on ultra-high performance chromatography (UHPLC) using an ethylene bridged hybrid amide column coupled with tandem mass spectrometry (MS/MS). Identification and quantification of neurotransmitters was carried out by ESI+ mass spectrometry detection. We optimized sample preparation to achieve simple and fast extraction of all nine analytes. Our method exhibited an excellent linearity for all analytes (all coefficients of determination >0.99), with inter-day and intra-day precision yielding relative standard deviations 3.2%-11.2% and an accuracy was in range of 92.6%-104.3%. The present study, using the above method, is the first to demonstrate significant alterations of brain neurotransmitters caused by pathological processes in the brain tissues of patient with three different tauopathies. Copyright © 2017 Elsevier B.V. All rights reserved.

Spexin is a Novel Human Peptide that Reduces Adipocyte Uptake of Long Chain Fatty Acids and Causes Weight Loss in Rodents with Diet-induced Obesity*

Science.gov (United States)

Walewski, José L.; Ge, Fengxia; Lobdell, Harrison; Levin, Nancy; Schwartz, Gary J.; Vasselli, Joseph; Pomp, Afons; Dakin, Gregory; Berk, Paul D.

2014-01-01

Objective Microarray studies identified Ch12:orf39 (Spexin) as the most dysregulated gene in obese human fat. Therefore we examined its role in obesity pathogenesis. Design and Methods Spexin effects on food intake, meal patterns, body weight, Respiratory Exchange Ratio (RER), and locomotor activity were monitored electronically in C57BL/6J mice or Wistar rats with dietary-induced obesity (DIO). Its effects on adipocyte [3H]-oleate uptake were determined. Results In humans, Spexin gene expression was down-regulated 14.9-fold in obese omental and subcutaneous fat. Circulating Spexin changed in parallel, correlating (r = −0.797) with Leptin. In rats, Spexin (35 μg/kg/day s.c) reduced caloric intake ~32% with corresponding weight loss. Meal patterns were unaffected. In mice, Spexin (25 μg/kg/day i.p.) significantly reduced the RER at night, and increased locomotion. Spexin incubation in vitro significantly inhibited facilitated fatty acid (FA) uptake into DIO mouse adipocytes. Conditioned taste aversion testing (70μg/kg/day i.p.) demonstrated no aversive Spexin effects. Conclusions Spexin gene expression is markedly down-regulated in obese human fat. The peptide produces weight loss in DIO rodents. Its effects on appetite and energy regulation are presumably central; those on adipocyte FA uptake appear direct and peripheral. Spexin is a novel hormone involved in weight regulation, with potential for obesity therapy. PMID:24550067

Spexin is a novel human peptide that reduces adipocyte uptake of long chain fatty acids and causes weight loss in rodents with diet-induced obesity.

Science.gov (United States)

Walewski, José L; Ge, Fengxia; Lobdell, Harrison; Levin, Nancy; Schwartz, Gary J; Vasselli, Joseph R; Pomp, Afons; Dakin, Gregory; Berk, Paul D

2014-07-01

Microarray studies identified Ch12:orf39 (Spexin) as the most down-regulated gene in obese human fat. Therefore, we examined its role in obesity pathogenesis. Spexin effects on food intake, meal patterns, body weight, respiratory exchange ratio (RER), and locomotor activity were monitored electronically in C57BL/6J mice or Wistar rats with diet-induced obesity (DIO). Its effects on adipocyte [(3)H]-oleate uptake were determined. In humans, Spexin gene expression was down-regulated 14.9-fold in obese omental and subcutaneous fat. Circulating Spexin changed in parallel, correlating (r = -0.797) with Leptin. In rats, Spexin (35 µg/kg/day SC) reduced caloric intake ∼32% with corresponding weight loss. Meal patterns were unaffected. In mice, Spexin (25 µg/kg/day IP) significantly reduced the RER at night, and increased locomotion. Spexin incubation in vitro significantly inhibited facilitated fatty acid (FA) uptake into DIO mouse adipocytes. Conditioned taste aversion testing (70 µg/kg/day IP) demonstrated no aversive Spexin effects. Spexin gene expression is markedly down-regulated in obese human fat. The peptide produces weight loss in DIO rodents. Its effects on appetite and energy regulation are presumably central; those on adipocyte FA uptake appear direct and peripheral. Spexin is a novel hormone involved in weight regulation, with potential for obesity therapy. Copyright © 2014 The Obesity Society.

Studies on neurotransmitter-stimulated phospholipid metabolism with cerebral tissue suspensions: a possible biochemical correlate of synaptogenesis in normal and undernourished rats

International Nuclear Information System (INIS)

Reddy, P.V.; Sastry, P.S.

1979-01-01

The phenomenon of neurotransmitter-stimulated incorporation of 32 Pi into phosphatidic acid and inositol phosphatides (neurotransmitter effect) in developing brain was studied in vitro as a possible measure of synaptogenesis. While the neurotransmitter effect was not observed with brain homogenates, highly consistent and significant effects were noted with brain tissue suspensions obtained by passing the tissue through nylon bolting cloth. The magnitude of the effect decreased with the increase in mesh number. Maximum stimulations obtained with the 33 mesh adult brain cortex preparations (mean +- S.E.M. of 6 experiments) were 203 +- 8%, 316 +- 17% and 150 +8% with 10 -3 M acetylcholine (ACh) + 10 -3 M eserine; 10 -2 M norepinephrine (NE) and 10 -2 M serotonin (5-HT), respectively. (Auth.)

A Glutamate Homeostat Controls the Presynaptic Inhibition of Neurotransmitter Release

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Xiling Li

2018-05-01

Full Text Available Summary: We have interrogated the synaptic dialog that enables the bi-directional, homeostatic control of presynaptic efficacy at the glutamatergic Drosophila neuromuscular junction (NMJ. We find that homeostatic depression and potentiation use disparate genetic, induction, and expression mechanisms. Specifically, homeostatic potentiation is achieved through reduced CaMKII activity postsynaptically and increased abundance of active zone material presynaptically at one of the two neuronal subtypes innervating the NMJ, while homeostatic depression occurs without alterations in CaMKII activity and is expressed at both neuronal subtypes. Furthermore, homeostatic depression is only induced through excess presynaptic glutamate release and operates with disregard to the postsynaptic response. We propose that two independent homeostats modulate presynaptic efficacy at the Drosophila NMJ: one is an intercellular signaling system that potentiates synaptic strength following diminished postsynaptic excitability, while the other adaptively modulates presynaptic glutamate release through an autocrine mechanism without feedback from the postsynaptic compartment. : Homeostatic mechanisms stabilize synaptic strength, but the signaling systems remain enigmatic. Li et al. suggest the existence of a homeostat operating at the Drosophila neuromuscular junction that responds to excess glutamate through an autocrine mechanism to adaptively inhibit presynaptic neurotransmitter release. This system parallels forms of plasticity at central synapses. Keywords: homeostatic synaptic plasticity, glutamate homeostasis, synaptic depression, Drosophila neuromuscular junction

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

Science.gov (United States)

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.

L-Menthone confers antidepressant-like effects in an unpredictable chronic mild stress mouse model via NLRP3 inflammasome-mediated inflammatory cytokines and central neurotransmitters.

Science.gov (United States)

Xue, Jinsong; Li, Hongyan; Deng, Xueyang; Ma, Zhanqiang; Fu, Qiang; Ma, Shiping

2015-07-01

L-Menthone (MTN) is a Chinese old remedy extracted from the genus Mentha. It has been widely used as a cooling agent and a counterirritant for pain relief, although its antidepressant-like effects have not yet been reported. The present study was designed to investigate whether MTN confers an antidepressant-like effect in mice exposed to unpredictable chronic mild stress (UCMS) and to explore its potential mechanisms. The effects of MTN on mouse behavioral changes were investigated in our study. We determined the levels of the nucleotide binding, oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome, inflammatory cytokines and neurotransmitters in the hippocampus of mice. Behavioral tests, including the sucrose preference test (SPT), open field test (OFT), forced swimming test (FST) and tail suspension test (TST) revealed that MTN (15 and 30mg/kg) treatments for 3weeks alleviated the depression symptoms of UCMS in mice. Mice receiving MTN treatments exhibited reduced levels of NLRP3 and caspase-1. Moreover, MTN treatments reversed the UCMS-induced alterations in the concentrations of neurotransmitter norepinephrine (NE) and serotonin (5-HT) and inhibited the expression of pro-inflammatory cytokines (PIC) interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α in the hippocampus of mice. Taken together, our findings suggested that MTN may play a potential antidepressant-like role in the UCMS mouse model by regulating the NLRP3 inflammasome and mediating inflammatory cytokines and central neurotransmitters, which together provide insight towards the development of novel therapeutic treatments for depression. Copyright © 2015 Elsevier Inc. All rights reserved.

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.

Short-term uptake of heavy metals by periphyton algae

Energy Technology Data Exchange (ETDEWEB)

Vymazal, J.

1984-12-31

The utilization of periphyton for the removal of heavy metals from enriched small streams has been examined. By means of short-term batch laboratory experiments the courses of metal uptake have been studied. For uptake study naturally growing periphyton community and periphytic filamentous algae Cladophora glomerata and Oedogonium rivulare have been used. Uptakes of nine heavy metals (Pb, Cd, Cu, Co, Cr, Ni, Zn, Fe and Mn) have been determined during four hours exposure. In addition the influence of humic substances on heavy metals uptake has been determined. Uptake of all metals increased during four hours exposure but not in the same way. Some metals were removed continuously (Ni, Cr, Fe and Mn), other metals were removed more rapidly during the first hour or first two hours of exposure and then only slight removal continued (Cu, Pb, Cd, Co). Uptake of Zn was rather unambiguous. Results of these experiments suggest that the course of uptake for individual metals could be similar for most periphyton algae. It was established that humic substances significantly reduce heavy metals uptake. The highest decrease of uptake was observed in Cu, Cr, Co and Cd. The results of model experiments are being tested in a pilot scale with respect to the demands of engineering practice. (J.R.)

[Mechanism Study of the Smectite-OR-SH Compound for Reducing Cadmium Uptake by Plants in Contaminated Soils].

Science.gov (United States)

Zeng, Yan-jun; Zhou, Zhi-jun; Zhao, Qiu-xiang

2015-06-01

Adsorption and desorption experiments, pot experiments and characterization test were performed to investigate the immobilization effect and mechanism of the smectite-OR-SH compound for reducing cadmium uptake by plants in contaminated soils. The results showed that the saturated adsorption capacity for the adsorption of Cd2+ on smectite raised distinctly after functionalized. The adsorption of Cd2+ on smectite-OR-SH compound was very stable and it was difficult for Cd2+ to be desorbed from it. Crop yields promoted differently in original soil, Cd 3 mg x kg(-1) soil and Cd 10 mg x kg(-1) soil after adding the smectite-OR-SH compound. And the cadmium content of the cabbage reduced 61.00%, 62.10% and 83.73% respectively compare with the control. Characterization test analysis showed that Cd was adsorbed by the compound successfully and ligand interaction occurred between Cd and the thiol group. Floc amount on the compound surface increased correspondingly. In addition to electrostatic adsorption, ion exchange and hydroxyl ligand adsorption, the reaction mechanism of smectite-OR-SH compound with Cd was mainly sulfhydryl ligand adsorption.

Ethanol intake and 3H-serotonin uptake I: A study in Fawn-Hooded rats

International Nuclear Information System (INIS)

Daoust, M.; Compagnon, P.; Legrand, E.; Boucly, P.

1991-01-01

Ethanol intake and synaptosomal 3 H-serotonin uptake were studied in male Fawn-Hooded and Sprague-Dawley rats. Fawn-Hooded rats consumed more alcohol and more water than Sprague-Dawley rats. Plasma alcohol levels of Sprague-Dawley rats were not detectable but were about 5 mg/dl in Fawn-Hooded rats. Ethanol intake increased the Vmax of serotonin uptake in Fawn-Hooded rats in hippocampus and cortex, but not in thalamus. In Fawn-Hooded rats, serotonin uptake (Vmax) was higher than in Sprague-Dawley rats cortex. Ethanol intake reduced the Vmax of serotonin uptake in Fawn-Hooded rats in hippocampus and cortex. In cortex, the carrier affinity for serotonin was increased in alcoholized Fawn-Hooded rats. These results indicate that synaptosomal 3 H-serotonin uptake is affected by ethanol intake. In Fawn-Hooded rats, high ethanol consumption is associated with high serotonin uptake. In rats presenting high serotonin uptake, alcoholization reduces 3 H-serotonin internalization in synaptosomes, indicating a specific sensitivity to alcohol intake of serotonin uptake system

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

Science.gov (United States)

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

Mechanisms of Hg(II) uptake and methylation in methylating bacteria

Energy Technology Data Exchange (ETDEWEB)

Morel, Francois M. M. [Princeton Univ., NJ (United States). Geosciences

2016-10-14

The goal of this project was to understand the critical factors which control the availability and transport of Hg(II) into cells, a first step in the production of the neurotoxin, methylmercury. Specifically, this research focused on understanding the mechanism of bacterial mercury uptake and how mercury speciation affects the specificity and kinetics of mercury transport. Our research has shown that Hg(II) uptake in three different iron and sulfate-reducing proteobacteria occurs by the following mechanism (1) : Hg(II) uptake is an active transport process requiring energy, (2) it is dependent upon the structure of the Hg binding ligand, and (3) it is mediated by a heavy metal transporter such as one which transports the essential metal, Zn(II). In order to determine whether this mechanism extends to more diverse phylogenetic groups, we have begun examining Hg(II) uptake and bioavailability in two representative Hg methylating strains within the Firmicutes. These organisms have remarkably different membrane structures distinct from the Proteobacteria. Our results show low uptake rates in these two species of Firmicutes relative to the previously characterized Proteobacteria. This may explain the low methylation rates and yields observed in these organisms. Most surprisingly, however, these organisms appear to take up Hg(II) passively, as the addition of a protonophore failed to reduce Hg(II) uptake in these organisms. This is quite different to what has been observed previously for the Proteobacteria and suggests a different mechanism for Hg(II) uptake in the Firmicutes. We are continuing to understand and describe Hg(II) uptake in these organisms. A manuscript is expected to be submitted on this research in June 2016.

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...

Variation for N Uptake System in Maize: Genotypic Response to N Supply

KAUST Repository

Garnett, Trevor; Plett, Darren; Conn, Vanessa; Conn, Simon; Rabie, Huwaida; Rafalski, J. Antoni; Dhugga, Kanwarpal; Tester, Mark A.; Kaiser, Brent N.

2015-01-01

An understanding of the adaptations made by plants in their nitrogen (N) uptake systems in response to reduced N supply is important to the development of cereals with enhanced N uptake efficiency (NUpE). Twenty seven diverse genotypes of maize (Zea mays, L.) were grown in hydroponics for 3 weeks with limiting or adequate N supply. Genotypic response to N was assessed on the basis of biomass characteristics and the activities of the nitrate (NO−3) and ammonium (NH+4) high-affinity transport systems. Genotypes differed greatly for the ability to maintain biomass with reduced N. Although, the N response in underlying biomass and N transport related characteristics was less than that for biomass, there were clear relationships, most importantly, lines that maintained biomass at reduced N maintained net N uptake with no change in size of the root relative to the shoot. The root uptake capacity for both NO−3 and NH+4 increased with reduced N. Transcript levels of putative NO−3 and NH+4 transporter genes in the root tissue of a subset of the genotypes revealed that predominately ZmNRT2 transcript levels responded to N treatments. The correlation between the ratio of transcripts of ZmNRT2.2 between the two N levels and a genotype's ability to maintain biomass with reduced N suggests a role for these transporters in enhancing NUpE. The observed variation in the ability to capture N at low N provides scope for both improving NUpE in maize and also to better understand the N uptake system in cereals.

Variation for N Uptake System in Maize: Genotypic Response to N Supply

KAUST Repository

Garnett, Trevor

2015-11-09

An understanding of the adaptations made by plants in their nitrogen (N) uptake systems in response to reduced N supply is important to the development of cereals with enhanced N uptake efficiency (NUpE). Twenty seven diverse genotypes of maize (Zea mays, L.) were grown in hydroponics for 3 weeks with limiting or adequate N supply. Genotypic response to N was assessed on the basis of biomass characteristics and the activities of the nitrate (NO−3) and ammonium (NH+4) high-affinity transport systems. Genotypes differed greatly for the ability to maintain biomass with reduced N. Although, the N response in underlying biomass and N transport related characteristics was less than that for biomass, there were clear relationships, most importantly, lines that maintained biomass at reduced N maintained net N uptake with no change in size of the root relative to the shoot. The root uptake capacity for both NO−3 and NH+4 increased with reduced N. Transcript levels of putative NO−3 and NH+4 transporter genes in the root tissue of a subset of the genotypes revealed that predominately ZmNRT2 transcript levels responded to N treatments. The correlation between the ratio of transcripts of ZmNRT2.2 between the two N levels and a genotype\\'s ability to maintain biomass with reduced N suggests a role for these transporters in enhancing NUpE. The observed variation in the ability to capture N at low N provides scope for both improving NUpE in maize and also to better understand the N uptake system in cereals.

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

Science.gov (United States)

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.

Comparison of chromium and nickel uptake of plants grown in different soils

Energy Technology Data Exchange (ETDEWEB)

Vago, I. [University of Agriculture, Faculty of Agronomy, H-4015 Debrecen, P.O. Box 36 (Hungary); Gyoeri, Z. [University of Agriculture, Faculty of Agronomy, H-4015 Debrecen, P.O. Box 36 (Hungary); Loch, J. [University of Agriculture, Faculty of Agronomy, H-4015 Debrecen, P.O. Box 36 (Hungary)

1996-03-01

The chromium and nickel uptake of ryegrass has been examined in pot experiments in extremely different soils, poor sandy and fertile black chernozem. The effect of calcium carbonate doses and nitrogen supply on heavy metal uptake of the plant has been studied for chromium and nickel loadings (0-100 mg/kg Cr{sup 3+} or Ni{sup 2+}) applied as inorganic salts. The ability to uptake Cr{sup 3+} and Ni{sup 2+} differs significantly and is highly affected by the characteristics of soils, and depends on the metal investigated. The heavy metal uptake of the plant differs significantly in acid, colloid deficient sandy soils; while artificial chromium contamination did not modify the dry-matter production in the pots in either soil, a large quantity of nickel reduced the yields significantly. Nitrogen application did not change significantly the uptake of heavy metals. Lime application reduced the Ni{sup 2+} uptake of plants considerably, especially in sandy soil. In case of a calcium carbonate addition the dry-matter production of the plant was not affected by nickel. In chernozem soil the effect of lime application - i.e., the reduction of nickel uptake - was of a lesser degree. The significantly lesser Cr{sup 3+} uptake was further limited by a calcium carbonate application for both soils studied. A graphic presentation of these effects is given. (orig.). With 3 figs., 3 tabs.

[Expressions of neurotransmitters in patients of insomnia differentiated as liver stagnation transforming into fire treated with acupuncture].

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Ji, Xiangdong; Wang, Qunsong; Zhu, Wenxian

2015-06-01

To compare the difference in the efficacy between acupuncture and oral administration of trazodone and the expressions of neurotransmitters in patients of insomnia differentiated as liver stagnation transforming into fire. Seventy patients of insomnia differentiated as liver stagnation transforming into fire were randomized into an observation group and a control group, 35 cases in each one. In the observation group, acupuncture therapy was adopted at Shenmen (HT 7), Baihui (GV 20), Yintang (GV 29), Hegu (LI 4), Taichong (LR 3), etc. The needles were retained for 20 min each time. The treatment was given once a day, the treatment of 2 weeks made one session. In the control group, trazodone, 100 mg, oral administration, once a day, the treatment of 2 weeks made one session. Two sessions were required in the two groups. The scores in Pittsburgh sleep quality index (PSQI) and Asberg rating scale for side effects (SERS), the levels of neurotransmitters such as 5-hydroxy tryptamine (5-HT) and norepinephrine (NE) and the expressions of protein kinase C (PKC) and brain-derived neurotrophic factor (BDNF) in peripheral blood were observed before and after treatment in the two groups. PSQI score and SERS score after treatment were all decreased compared with those in both groups before treatment (both Pinsomnia differentiated as liver stagnation transforming into fire, and reduces serum NE level and increases 5-HT content and BDNF expression, which achieves the better efficacy as compared with the oral administration of trazodone. It is one of the effective approaches to the treatment of insomnia differentiated as liver stagnation transforming into fire.

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.

A medicinal herb, Melissa officinalis L. ameliorates depressive-like behavior of rats in the forced swimming test via regulating the serotonergic neurotransmitter.

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Lin, Shih-Hang; Chou, Mei-Ling; Chen, Wei-Cheng; Lai, Yi-Syuan; Lu, Kuan-Hung; Hao, Cherng-Wei; Sheen, Lee-Yan

2015-12-04

Depression is a serious psychological disorder that causes extreme economic loss and social problems. However, the conventional medications typically cause side effects that result in patients opting to out of therapy. Lemon balm (Melissa officinalis L., MO) is an old and particularly reliable medicinal herb for relieving feelings of melancholy, depression and anxiety. The present study aims to investigate the antidepressant-like activity of water extract of MO (WMO) by evaluating its influence on the behaviors and the relevant neurotransmitters of rats performed to forced swimming test. Two phases of the experiment were conducted. In the acute model, rats were administered ultrapure water (control), fluoxetine, WMO, or the indicated active compound (rosmarinic acid, RA) three times in one day. In the sub-acute model, rats were respectively administered ultrapure water (control), fluoxetine, or three dosages of WMO once a day for 10 days. Locomotor activity and depression-like behavior were examined using the open field test and the forced swimming test, respectively. The levels of relevant neurotransmitters and their metabolites in the frontal cortex, amygdala, hippocampus, and striatum were analyzed by high performance liquid chromatography. In the acute model, WMO and RA significantly reduced depressive-like behavior but the type of related neurotransmitter could not be determined. The results indicated that the effect of WMO administration on the reduction of immobility time was associated with an increase in swimming time of the rats, indicative of serotonergic neurotransmission modulation. Chromatography data validated that the activity of WMO was associated with a reduction in the serotonin turnover rate. The present study shows the serotonergic antidepressant-like activity of WMO. Hence, WMO may offer a serotonergic antidepressant activity to prevent depression and to assist in conventional therapies. Copyright © 2015. Published by Elsevier Ireland Ltd.

A protective effect of dietary calcium against acute waterborne cadmium uptake in rainbow trout

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Baldisserotto, B.; Kamunde, C.; Matsuo, A.; Wood, C.M

2004-03-30

The present study examined the interactions between elevated dietary calcium (as ionic Ca{sup 2+} in the form of CaCl{sub 2}{center_dot}2H{sub 2}O) and acute waterborne Cd exposure (50 {mu}g/l as CdNO{sub 3} for 3 h) on whole body uptake and internal distribution of newly accumulated Cd, Ca{sup 2+}, and Na{sup +} in juvenile rainbow trout (Oncorhynchus mykiss). Fish were fed with three diets 20 (control), 30 and 60 mg Ca{sup 2+}/g food: for 7 days before fluxes were measured with radiotracers over a 3 h period. The two elevated Ca{sup 2+} diets reduced the whole body uptake of both Ca{sup 2+} and Cd by >50% and similarly reduced the internalization of both newly accumulated metals in most tissues, effects which reflect the shared branchial uptake route for Ca{sup 2+} and Cd. As the Ca{sup 2+} concentrations of the fluid phases of the stomach and intestinal contents were greatly elevated by the experimental diets, increased gastrointestinal Ca{sup 2+} uptake likely caused the down-regulation of the branchial Ca{sup 2+} (and Cd) uptake pathway. Waterborne Na{sup +} uptake and internal distribution were not affected. While plasma Ca{sup 2+} surged after the first two feedings of the 60 mg Ca{sup 2+}/g diet, internal homeostasis was quickly restored. Total Ca{sup 2+}, Na{sup +}, and Cl{sup -} levels in tissues were not affected by diets. While dietary Ca{sup 2+} protected against waterborne Cd uptake, it did not protect against the relative inhibition of waterborne Ca{sup 2+} uptake caused by waterborne Cd. Acute exposure to 50 {mu}g/l Cd reduced the uptake and internalization of newly accumulated Ca{sup 2+} (but not Na{sup +}) by 70% or more, regardless of diet. Since elevated dietary Ca{sup 2+} reduces waterborne Cd uptake, fish eating a Ca{sup 2+}-rich invertebrate diet may be more protected against waterborne Cd toxicity in a field situation.

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.

Social Cognitive Mediators of Sociodemographic Differences in Colorectal Cancer Screening Uptake

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Siu Hing Lo

2015-01-01

Full Text Available Background. This study examined if and how sociodemographic differences in colorectal cancer (CRC screening uptake can be explained by social cognitive factors. Methods. Face-to-face interviews were conducted with individuals aged 60–70 years (n=1309 living in England as part of a population-based omnibus survey. Results. There were differences in screening uptake by SES, marital status, ethnicity, and age but not by gender. Perceived barriers (stand. b=-0.40, p<0.001, social norms (stand. b=0.33, p<0.001, and screening knowledge (stand. b=0.17, p<0.001 had independent associations with uptake. SES differences in uptake were mediated through knowledge, social norms, and perceived barriers. Ethnic differences were mediated through knowledge. Differences in uptake by marital status were primarily mediated through social norms and to a lesser extent through knowledge. Age differences were largely unmediated, except for a small mediated effect via social norms. Conclusions. Sociodemographic differences in CRC screening uptake were largely mediated through social cognitive factors. Impact. Our findings suggest that multifaceted interventions might be needed to reduce socioeconomic inequalities. Ethnic differences might be reduced through improved screening knowledge. Normative interventions could emphasise screening as an activity endorsed by important others outside the immediate family to appeal to a wider audience.

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)

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.

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.

27-Hydroxycholesterol impairs neuronal glucose uptake through an IRAP/GLUT4 system dysregulation

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Mateos, Laura; Maioli, Silvia; Ali, Zeina; Gulyás, Balázs; Winblad, Bengt; Savitcheva, Irina

2017-01-01

Hypercholesterolemia is associated with cognitively deteriorated states. Here, we show that excess 27-hydroxycholesterol (27-OH), a cholesterol metabolite passing from the circulation into the brain, reduced in vivo brain glucose uptake, GLUT4 expression, and spatial memory. Furthermore, patients exhibiting higher 27-OH levels had reduced 18F-fluorodeoxyglucose uptake. This interplay between 27-OH and glucose uptake revealed the engagement of the insulin-regulated aminopeptidase (IRAP). 27-OH increased the levels and activity of IRAP, countered the IRAP antagonist angiotensin IV (AngIV)–mediated glucose uptake, and enhanced the levels of the AngIV-degrading enzyme aminopeptidase N (AP-N). These effects were mediated by liver X receptors. Our results reveal a molecular link between cholesterol, brain glucose, and the brain renin-angiotensin system, all of which are affected in some neurodegenerative diseases. Thus, reducing 27-OH levels or inhibiting AP-N maybe a useful strategy in the prevention of the altered glucose metabolism and memory decline in these disorders. PMID:28213512

Fasciola hepatica infection reduces Mycobacterium bovis burden and mycobacterial uptake and suppresses the pro-inflammatory response.

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Garza-Cuartero, L; O'Sullivan, J; Blanco, A; McNair, J; Welsh, M; Flynn, R J; Williams, D; Diggle, P; Cassidy, J; Mulcahy, G

2016-07-01

Bovine tuberculosis (BTB), caused by Mycobacterium bovis, has an annual incidence in cattle of 0.5% in the Republic of Ireland and 4.7% in the UK, despite long-standing eradication programmes being in place. Failure to achieve complete eradication is multifactorial, but the limitations of diagnostic tests are significant complicating factors. Previously, we have demonstrated that Fasciola hepatica infection, highly prevalent in these areas, induced reduced sensitivity of the standard diagnostic tests for BTB in animals co-infected with F. hepatica and M. bovis. This was accompanied by a reduced M. bovis-specific Th1 immune response. We hypothesized that these changes in co-infected animals would be accompanied by enhanced growth of M. bovis. However, we show here that mycobacterial burden in cattle is reduced in animals co-infected with F. hepatica. Furthermore, we demonstrate a lower mycobacterial recovery and uptake in blood monocyte-derived macrophages (MDM) from F. hepatica-infected cattle which is associated with suppression of pro-inflammatory cytokines and a switch to alternative activation of macrophages. However, the cell surface expression of TLR2 and CD14 in MDM from F. hepatica-infected cattle is increased. These findings reflecting the bystander effect of helminth-induced downregulation of pro-inflammatory responses provide insights to understand host-pathogen interactions in co-infection. © 2016 The Authors. Parasite Immunology Published by John Wiley & Sons Ltd.

[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.

Reduced intracellular drug accumulation in drug-resistant leukemia cells is not solely due to MDR-mediated efflux but also to decreased uptake

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Angela Oliveira Pisco

2014-10-01

Full Text Available Expression of ABC family transporter proteins that promote drug efflux from cancer cells is a widely observed mechanism of multi-drug resistance of cancer cells. Cell adaptation in long-term culture of HL60 leukemic cells in the presence of chemotherapy leads to induction and maintenance of the ABC transporters expression, preventing further accumulation of drugs. However, we found that decreased accumulation of drugs and fluorescent dyes was also contributed by a reduced uptake by the resistant cells. Confocal time-lapse microscopy and flow cytometry revealed that fluid-phase endocytosis was diminished in drug-resistant cells compared to drug-sensitive cells. Drug uptake was increased by insulin co-treatment when cells were grown in methylcellulose and monitored under the microscope, but not when cultured in suspension. We propose that multi-drug resistance is not solely achieved by enhanced efflux capacity but also by supressed intake of the drug offering an alternative target to overcome drug resistance or potentiate chemotherapy.

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

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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.

Immunization Uptake in Younger Siblings of Children with Autism Spectrum Disorder

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Kuwaik, Ghassan Abu; Roberts, Wendy; Zwaigenbaum, Lonnie; Bryson, Susan; Smith, Isabel M.; Szatmari, Peter; Modi, Bonnie M.; Tanel, Nadia; Brian, Jessica

2014-01-01

Background: Parental concerns persist that immunization increases the risk of autism spectrum disorder, resulting in the potential for reduced uptake by parents of younger siblings of children with autism spectrum disorder ("younger sibs"). Objective: To compare immunization uptake by parents for their younger child relative to their…

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.

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

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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.

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.

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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.

Relative uptake of technetium 99m stannous colloid by neutrophils and monocytes is altered by gram-negative infection

International Nuclear Information System (INIS)

Ramsay, Stuart C.; Maggs, Jacqueline A.; Ketheesan, Natkunam; Norton, Robert; LaBrooy, Justin

2005-01-01

Gram-negative infection alters phagocytic cell function; hence, it could affect phagocytic uptake of inorganic colloids by these cells. Neutrophil and monocyte uptake of technetium 99m stannous colloid ( 99m Tc SnC) in whole blood was measured in 10 patients with gram-negative infection (Burkholderia pseudomallei) and 7 controls. Mean uptake per individual neutrophil was reduced in infection. Uptake per monocyte was not significantly different. Blood from six normal individuals was incubated with lysed B. pseudomallei and colloid, which showed reduced neutrophil uptake, but increased monocyte uptake. These results indicate that uptake of 99m Tc SnC stannous colloid can be used to measure alteration in phagocytic cell function. They suggest that infection with B. pseudomallei is associated with reduced phagocytosis by individual neutrophils, possibly through toxic effects of bacterial products. This could have immunopathogenic consequences for this gram-negative infection and may explain why it responds to granulocyte colony-stimulating factor

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

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

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Meng-Li Chen

2012-01-01

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

Citric acid modifies surface properties of commercial CeO{sub 2} nanoparticles reducing their toxicity and cerium uptake in radish (Raphanus sativus) seedlings

Energy Technology Data Exchange (ETDEWEB)

Trujillo-Reyes, J. [Chemistry Department, The University of Texas at El Paso, 500 West University Av., El Paso, TX 79968 (United States); Vilchis-Nestor, A.R. [Centro Conjunto de Investigación en Química Sustentable UAEM—UNAM, Carretera Toluca—Atlacomulco km 14.5, San Cayetano, CP 50200 Toluca, Estado de México (Mexico); Majumdar, S. [Chemistry Department, The University of Texas at El Paso, 500 West University Av., El Paso, TX 79968 (United States); University of California Center for Environmental Implications of Nanotechnology (UC CEIN), The University of Texas at El Paso, 500 West University Av., El Paso, TX 79968 (United States); Peralta-Videa, J.R. [Chemistry Department, The University of Texas at El Paso, 500 West University Av., El Paso, TX 79968 (United States); Environmental Science and Engineering PhD program, The University of Texas at El Paso, 500 West University Ave., El Paso, TX 79968 (United States); University of California Center for Environmental Implications of Nanotechnology (UC CEIN), The University of Texas at El Paso, 500 West University Av., El Paso, TX 79968 (United States); Gardea-Torresdey, J.L., E-mail: jgardea@utep.edu [Chemistry Department, The University of Texas at El Paso, 500 West University Av., El Paso, TX 79968 (United States); Environmental Science and Engineering PhD program, The University of Texas at El Paso, 500 West University Ave., El Paso, TX 79968 (United States); University of California Center for Environmental Implications of Nanotechnology (UC CEIN), The University of Texas at El Paso, 500 West University Av., El Paso, TX 79968 (United States)

2013-12-15

Highlights: • The citric acid capping significantly reduced the ζ potential values. • As the amount of CA increased, thicker the layer surrounding the CeO{sub 2} NPs. • CeO{sub 2}/CA NPs had better distribution and small particle size than bare CeO{sub 2} NPs. • CeO{sub 2}/CA NPs decrease the Ce uptake by radish seedlings. -- Abstract: Little is known about the mobility, reactivity, and toxicity to plants of coated engineered nanoparticles (ENPs). Surface modification may change the interaction of ENPs with living organisms. This report describes surface changes in commercial CeO{sub 2} NPs coated with citric acid (CA) at molar ratios of 1:2, 1:3, 1:7, and 1:10 CeO{sub 2}:CA, and their effects on radish (Raphanus sativus) seed germination, cerium and nutrients uptake. All CeO{sub 2} NPs and their absorption by radish plants were characterized by TEM, DLS, and ICP-OES. Radish seeds were germinated in pristine and CA coated CeO{sub 2} NPs suspensions at 50 mg/L, 100 mg/L, and 200 mg/L. Deionized water and CA at 100 mg/L were used as controls. Results showed ζ potential values of 21.6 mV and −56 mV for the pristine and CA coated CeO{sub 2} NPs, respectively. TEM images showed denser layers surrounding the CeO{sub 2} NPs at higher CA concentrations, as well as better distribution and smaller particle sizes. None of the treatments affected seed germination. However, at 200 mg/L the CA coated NPs at 1:7 ratio produced significantly (p ≤ 0.05) more root biomass, increased water content and reduced by 94% the Ce uptake, compared to bare NPs. This suggests that CA coating decrease CeO{sub 2} NPs toxicity to plants.

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.

Excitatory amino acid transporters: recent insights into molecular mechanisms, novel modes of modulation and new therapeutic possibilities

DEFF Research Database (Denmark)

Jensen, Anders A.; Fahlke, Christoph; Bjørn-Yoshimoto, Walden Emil

2015-01-01

The five excitatory amino acid transporters (EAAT1–5) mediating the synaptic uptake of the major excitatory neurotransmitter glutamate are differently expressed throughout the CNS and at the synaptic level. Although EAATs are crucial for normal excitatory neurotransmission, explorations into the ......The five excitatory amino acid transporters (EAAT1–5) mediating the synaptic uptake of the major excitatory neurotransmitter glutamate are differently expressed throughout the CNS and at the synaptic level. Although EAATs are crucial for normal excitatory neurotransmission, explorations...

Arsenic Uptake and Translocation in Plants.

Science.gov (United States)

Li, Nannan; Wang, Jingchao; Song, Won-Yong

2016-01-01

Arsenic (As) is a highly toxic metalloid that is classified as a non-threshold class-1 carcinogen. Millions of people worldwide suffer from As toxicity due to the intake of As-contaminated drinking water and food. Reducing the As concentration in drinking water and food is thus of critical importance. Phytoremediation of soil contaminated with As and the reduction of As contamination in food depend on a detailed understanding of As uptake and transport in plants. As transporters play essential roles in As uptake, translocation and accumulation in plant cells. In this review, we summarize the current understanding of As transport in plants, with an emphasis on As uptake, mechanisms of As resistance and the long-distance translocation of As, especially the accumulation of As in grains through phloem-mediated transport. © The Author 2015. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Apolipoprotein E Mimetic Peptide Increases Cerebral Glucose Uptake by Reducing Blood-Brain Barrier Disruption after Controlled Cortical Impact in Mice: An 18F-Fluorodeoxyglucose PET/CT Study.

Science.gov (United States)

Qin, Xinghu; You, Hong; Cao, Fang; Wu, Yue; Peng, Jianhua; Pang, Jinwei; Xu, Hong; Chen, Yue; Chen, Ligang; Vitek, Michael P; Li, Fengqiao; Sun, Xiaochuan; Jiang, Yong

2017-02-15

Traumatic brain injury (TBI) disrupts the blood-brain barrier (BBB) and reduces cerebral glucose uptake. Vascular endothelial growth factor (VEGF) is believed to play a key role in TBI, and COG1410 has demonstrated neuroprotective activity in several models of TBI. However, the effects of COG1410 on VEGF and glucose metabolism following TBI are unknown. The current study aimed to investigate the expression of VEGF and glucose metabolism effects in C57BL/6J male mice subjected to experimental TBI. The results showed that controlled cortical impact (CCI)-induced vestibulomotor deficits were accompanied by increases in brain edema and the expression of VEGF, with a decrease in cerebral glucose uptake. COG1410 treatment significantly improved vestibulomotor deficits and glucose uptake and produced decreases in VEGF in the pericontusion and ipsilateral hemisphere of injury, as well as in brain edema and neuronal degeneration compared with the control group. These data support that COG1410 may have potential as an effective drug therapy for TBI.

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.

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.

Phosphorus deficiency enhances molybdenum uptake by tomato plants

International Nuclear Information System (INIS)

Heuwinkel, H.; Kirkby, E.A.; Le Bot, J.; Marschner, H.

1992-01-01

Water culture experiments are described which provide conclusive evidence that Mo uptake by tomato plants is markedly enhanced by P deficiency. In a longterm experiment, which ran for 11 days, in marked contrast to the uptake of other nutrients, a three fold higher Mo uptake rate was observed after only four days of withdrawal of P from the nutrient medium. In contrast to the gradual increase in pH of the nutrient medium of the plants supplied with P, the pH in the medium of the -P plants fell. Throughout the growth of these plants net H+ efflux could be accounted for by excess cation over anion uptake, indicating that organic acid extrusion plays no major role in the observed fall in pH. Further evidence that Mo uptake is enhanced in P deficient tomato plants is provided in short-term nutrient solution experiments (1h and 4h) using radioactive molybdenum (99Mo). Compared with P sufficient plants, the uptake rates of 99Mo by P deficient plants were three to five times higher after 1h and nine to twelve times higher after 4h. Resupplying P during the uptake periods to deficient plants reduced the uptake rate of 99Mo to values similar to those of P sufficient plants. It is concluded that the uptake of molybdate occurs via phosphate binding/ transporting sites at the plasma membrane of root cells. Further support for this conclusion comes from exchange experiments with non-labelled molybdenum, which show a much larger amount of 99Mo exchangeable from the roots of P deficient plants

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.

Desirable levels of exchangeable K and Ca and their concentration in the soil solution to reduce uptake of radioactive Cs by rice plants

International Nuclear Information System (INIS)

Sekimoto, Hitoshi; Yamada, Takashi; Hotsuki, Tomoe; Matsuzaki, Akio; Mimura, Tetsuro

2014-01-01

K in the soil solution can control the uptake of radioactive Cs by rice plants, but this control is not accomplished only by K; it is affected by other ionic species. It is therefore important to investigate uptake of radioactive Cs from the perspective of the concentration of major cations such as Ca in the soil solution and the levels of exchangeable cations in the soil. To clarify the effects of K and Ca in the soil solution and of the levels of soil exchangeable cations to prevent uptake of radioactive Cs, we conducted a pot experiment and field experiments in a paddy soil in 2011 and 2012. To reduce the uptake of radioactive Cs, it was necessary to achieve a K concentration in the soil solution of 0.5 mmol L"-"1, and a Ca concentration higher than 2 mmol L"-"1 based on the results of the pot experiment. In addition, we obtained the desirable levels of exchangeable cations and the cation exchange capacity (CEC) in the soil from previous reports and the results of our field experiments. On this basis, we propose the following threshold levels for exchangeable cations and CEC in the soil as a standard: 0.53 K cmol_c kg"-"1, 18.0 Ca cmol_c kg"-"1, 2.0 Mg cmol_c kg"-"1, i.e. 25 mg K_2O 100 g"-"1, 505 mg CaO 100 g"-"1, 40 Mg O mg 100 g"-"1, and a CEC of 30 cmol_c kg"-"1. Converting these values into the corresponding levels in the soil solution, we obtained concentrations of 0.71 mmol K L"-"1, 4.22 mmol Ca L"-"1, and 1.35 mmol Mg L"-"1. These levels are within the improving standard for fertility of paddy soils in Japan. Consequently, it will be necessary to improve the fertility of paddy soils to control the uptake of radioactive Cs by rice plants. (author)

Characteristics of sugar uptake by immature maize embryos

International Nuclear Information System (INIS)

Griffith, S.M.; Jones, R.J.; Brenner, M.L.

1986-01-01

Characteristics of sugar uptake by immature maize embryos were determined in vitro utilizing a 14 C-sugar solution incubation method. Hexose uptake rates were greater than those for sucrose, however, all showed biphasic kinetics. Glucose and fructose saturable components were evidence at <50 mM and sucrose at <5 mM. Chemical inhibitors (CCCP, DNP, NaCN, and PCMBS) and low temperature reduced sugar uptake. Sucrose influx was pH dependent while glucose was not. Embryos maintained a high sucrose to hexose ratio throughout development. At 25 days after pollination sucrose levels exceeded 200 mM while hexose levels remained below 5 mM. Glucose was rapidly converted to sucrose upon transport into the embryo. These circumstantial data indicate that sugar uptake by immature maize embryos is metabolically dependent and carrier mediated. Furthermore, sucrose transport appears to occur against its concentration gradient involving a H+/sucrose cotransport mechanism, while glucose influx is driven by its concentration gradient and subsequent metabolism

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.

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

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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)

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

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

Nitrogen deposition and prey nitrogen uptake control the nutrition of the carnivorous plant Drosera rotundifolia

Energy Technology Data Exchange (ETDEWEB)

Millett, J., E-mail: j.millett@lboro.ac.uk [Centre for Hydrological and Ecosystem Science, Department of Geography, Loughborough University, Loughborough LE11 3TU (United Kingdom); Foot, G.W. [Centre for Hydrological and Ecosystem Science, Department of Geography, Loughborough University, Loughborough LE11 3TU (United Kingdom); Svensson, B.M. [Department of Plant Ecology and Evolution, Uppsala University, Norbyvägen 18 D, SE-752 36 Uppsala (Sweden)

2015-04-15

Nitrogen (N) deposition has important negative impacts on natural and semi-natural ecosystems, impacting on biotic interactions across trophic levels. Low-nutrient systems are particularly sensitive to changes in N inputs and are therefore more vulnerable to N deposition. Carnivorous plants are often part of these ecosystems partly because of the additional nutrients obtained from prey. We studied the impact of N deposition on the nutrition of the carnivorous plant Drosera rotundifolia growing on 16 ombrotrophic bogs across Europe. We measured tissue N, phosphorus (P) and potassium (K) concentrations and prey and root N uptake using a natural abundance stable isotope approach. Our aim was to test the impact of N deposition on D. rotundifolia prey and root N uptake, and nutrient stoichiometry. D. rotundifolia root N uptake was strongly affected by N deposition, possibly resulting in reduced N limitation. The contribution of prey N to the N contained in D. rotundifolia ranged from 20 to 60%. N deposition reduced the maximum amount of N derived from prey, but this varied below this maximum. D. rotundifolia tissue N concentrations were a product of both root N availability and prey N uptake. Increased prey N uptake was correlated with increased tissue P concentrations indicating uptake of P from prey. N deposition therefore reduced the strength of a carnivorous plant–prey interaction, resulting in a reduction in nutrient transfer between trophic levels. We suggest that N deposition has a negative impact on D. rotundifolia and that responses to N deposition might be strongly site specific. - Highlights: • We measured nutrition of the carnivorous plant Drosera rotundifolia across Europe. • We measured tissue nutrient concentrations and prey and root N uptake at 16 sites. • Tissue N concentrations were a product of root N availability and prey N uptake. • N deposition reduced the maximum amount of N derived from prey. • N deposition reduced the strength of a

Nitrogen deposition and prey nitrogen uptake control the nutrition of the carnivorous plant Drosera rotundifolia

International Nuclear Information System (INIS)

Millett, J.; Foot, G.W.; Svensson, B.M.

2015-01-01

Nitrogen (N) deposition has important negative impacts on natural and semi-natural ecosystems, impacting on biotic interactions across trophic levels. Low-nutrient systems are particularly sensitive to changes in N inputs and are therefore more vulnerable to N deposition. Carnivorous plants are often part of these ecosystems partly because of the additional nutrients obtained from prey. We studied the impact of N deposition on the nutrition of the carnivorous plant Drosera rotundifolia growing on 16 ombrotrophic bogs across Europe. We measured tissue N, phosphorus (P) and potassium (K) concentrations and prey and root N uptake using a natural abundance stable isotope approach. Our aim was to test the impact of N deposition on D. rotundifolia prey and root N uptake, and nutrient stoichiometry. D. rotundifolia root N uptake was strongly affected by N deposition, possibly resulting in reduced N limitation. The contribution of prey N to the N contained in D. rotundifolia ranged from 20 to 60%. N deposition reduced the maximum amount of N derived from prey, but this varied below this maximum. D. rotundifolia tissue N concentrations were a product of both root N availability and prey N uptake. Increased prey N uptake was correlated with increased tissue P concentrations indicating uptake of P from prey. N deposition therefore reduced the strength of a carnivorous plant–prey interaction, resulting in a reduction in nutrient transfer between trophic levels. We suggest that N deposition has a negative impact on D. rotundifolia and that responses to N deposition might be strongly site specific. - Highlights: • We measured nutrition of the carnivorous plant Drosera rotundifolia across Europe. • We measured tissue nutrient concentrations and prey and root N uptake at 16 sites. • Tissue N concentrations were a product of root N availability and prey N uptake. • N deposition reduced the maximum amount of N derived from prey. • N deposition reduced the strength of a

Ocean carbon uptake and storage

International Nuclear Information System (INIS)

Tilbrook, Bronte

2007-01-01

Full text: The ocean contains about 95% of the carbon in the atmosphere, ocean and land biosphere system, and is of fundamental importance in regulating atmospheric carbon dioxide concentrations. In the 1990s an international research effort involving Australia was established to determine the uptake and storage of anthropogenic C02 for all major ocean basins. The research showed that about 118 of the 244 + 20 billion tons of the anthropogenic carbon emitted through fossil fuel burning and cement production has been stored in the ocean since preindustrial times, thus helping reduce the rate of increase in atmospheric C02. The research also showed the terrestrial biosphere has been a small net source of C02 (39 ± 28 billion tons carbon) to the atmosphere over the same period. About 60% of the total ocean inventory of the anthropogenic C02 was found in the Southern Hemisphere, with most in the 30 0 S to 50 0 S latitude band. This mid-latitude band is where surface waters are subducted as Mode and Intermediate waters, which is a major pathway controlling ocean C02 uptake. High storage (23% of the total) also occurs in the North Atlantic, associated with deep water formation in that basin. The ocean uptake and storage is expected to increase in the coming decades as atmospheric C02 concentrations rise. However, a number of feedback mechanisms associated with surface warming, changes in circulation, and biological effects are likely to impact on the uptake capacity. The accumulation or storage-of the C02 in the ocean is also the major driver of ocean acidification with potential to disrupt marine ecosystems. This talk will describe the current understanding of the ocean C02 uptake and storage and a new international research strategy to detect how the ocean uptake and storage will evolve on interannual through decadal scales. Understanding the ocean response to increasing atmospheric C02 will be a key element in managing future C02 increases and establishing

Effects of the Bee Venom Herbal Acupuncture on the Neurotransmitters of the Rat Brain Cortex

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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.

Uptake by Plants of Radiostrontium from Contaminated Soils

DEFF Research Database (Denmark)

Andersen, A. J.

1965-01-01

In a recent report from this department it was shown that the extractability of radiostrontium from contaminated soil samples was effectively reduced by heat treatment and by the addition of phosphate to the soil. It was pointed out that, under emergency conditions, heat-treatment of the contamin......In a recent report from this department it was shown that the extractability of radiostrontium from contaminated soil samples was effectively reduced by heat treatment and by the addition of phosphate to the soil. It was pointed out that, under emergency conditions, heat......-treatment of the contaminated soil surface and heavy phosphate application might thus reduce the uptake by plants of radiostrontium more efficiently than liming, which is only effective in soils of low calcium status. In the investigation reviewed here the influence of heat treatment and superphosphate application on the plant...... uptake of radiostrontium was examined in pot experiments. For comparison the effect of applying calcium carbonate to the contaminated soil surface was also determined....

Effect of exercise and obesity on skeletal muscle amino acid uptake

International Nuclear Information System (INIS)

Friedman, J.E.

1988-01-01

To determine if amino acid uptake by muscle of the obese Zucker rat is impaired, epitrochlearis (EPI) and soleus strip (SOL) muscles from 32 pairs of female lean (Fa/-) and obese (fa/fa) Zucker rats were incubated using [ 14 C]α-aminoisobutyric acid (AIB). Because contractile activity also influences amino acid uptake, the effect of acute endurance exercise on amino acid uptake by skeletal muscle from lean and obese rats was also studied. Muscle wet and dry weights were similar in lean and obese rats. However, both muscle protein content and concentration from obese rats were significantly reduced. In preliminary studies, pinning EPI at resting length during incubation significantly increased AIB uptake and reduced muscle water accumulation. AIB uptake was similar in stripped and intact SOL. Lean and obese rats were studied at rest or following a 1 hr treadmill run at 8% grade Muscles were pinned, and preincubated for 30 min at 37 degree C in Krebs Ringer bicarbonate buffer (KRB) containing 5mM glucose under 95:5 O 2 /CO 2 , followed by 30, 60, 120, or 180 min of incubation in KRB with 0.5 mM AIB, [ 14 C]-AIB to measure amino acid, and [ 3 H]-inulin to determine extracellular water

Diagnostic approach to neurotransmitter monoamine disorders: experience from clinical, biochemical, and genetic profiles.

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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.

Thallium and potassium uptake kinetics and competition differ between durum wheat and canola.

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Renkema, Heidi; Koopmans, Amy; Hale, Beverley; Berkelaar, Edward

2015-02-01

Thallium (Tl) is very toxic to mammals but little is known about its accumulation by plants, and it would be useful if prediction of Tl accumulation could be done using potassium (K) accumulation models. The objectives of this study were to compare the uptake kinetics of Tl(+) and K(+), and to determine how readily K(+) can inhibit Tl(+) uptake. Durum wheat (Triticum turgidum L.) and spring canola (Brassica napus L.) were grown hydroponically and exposed to 0-75 μM Tl or 0-250 μM K for up to 150 min (kinetics experiment), or to 0.1 or 10 μM Tl with Tl to K ratios of 1:1 to 1:10,000 for up to 300 min (competition experiment). The rate of uptake of Tl(+) by canola was about three to five times faster than by wheat, while the rate of Tl(+) uptake in wheat was the same as the rate of K(+) uptake by either species. Uptake of Tl(+) was more readily suppressed by K(+) in wheat than in canola. When exposed to 0.1 uM Tl for 300 min with 100 or 1,000 uM K(+), Tl(+) uptake by wheat was reduced by 20 % and 50 %, respectively, while Tl(+) uptake by canola was not reduced. Our results suggest that predicting Tl accumulation using a K accumulation model with a correction factor may be possible for canola, but would be much more difficult for wheat, since uptake of Tl(+) is very sensitive to levels of K(.)

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...

Identification of catecholamine neurotransmitters using fluorescence sensor array.

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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.

Effects of donepezil combined with folic acid and vitamin B12 on serum levels of inflammatory factors, HCY, NSE and neurotransmitters in elderly patients with Alzheimer' s disease complicated with hyperhomocysteinemia

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Fang-Fang Zheng

2017-08-01

Full Text Available Objective: To investigate the effects of donepezil combined with folic acid and vitamin B12 on the levels of serum inflammatory factors, Hcy, NSE and neurotransmitters in elderly patients with Alzheimer's disease (AD complicated with hyperhomocysteinemia. Methods: A total of 98 elderly patients with AD complicated with hyperhomocysteinemia were randomly divided into control group (n=48 and observation group (n=50 according to the random data table method. Patients in the control group were treated with donepezil. On this basis, the patients in the observation group were treated with folic acid and vitamin B12, all patients were treated for 3 months. Before and after treatment, the levels of serum inflammatory factors (TNF-α, IL-6 and hs-CRP, Hcy, NSE and brain neurotransmitter (5-HT, NE and DA were compared between the two groups. Results: Before treatment, the levels of TNF-α, IL-6, hs-CRP, Hcy, NSE, 5-HT, NE and DA of the control group and the observation group were not statistically significant. Compared with the group before treatment, the levels of TNF-α, IL-6, hs-CRP, Hcy and NSE in the two groups were significantly lower, and the level of the observation group was significantly lower than those of the control group, the difference was statistically significant; Compared with the group before treatment, the levels of 5-HT, NE and DA in the two groups were significantly increased, and the observation group was significantly higher than that of the control group, the difference was statistically significant. Conclusion: Donepezil combined folic acid and vitamin B12 in treatment of AD with hyperhomocysteinemia, which can effectively reduce the body's inflammatory response, reduced Hcy and NSE levels, elevated levels of brain neurotransmitters, has important clinical significance.

Phytate induced arsenic uptake and plant growth in arsenic-hyperaccumulator Pteris vittata.

Science.gov (United States)

Liu, Xue; Fu, Jing-Wei; Tang, Ni; da Silva, E B; Cao, Yue; Turner, Benjamin L; Chen, Yanshan; Ma, Lena Q

2017-07-01

Phytate is abundant in soils, which is stable and unavailable for plant uptake. However, it occurs in root exudates of As-hyperaccumulator Pteris vittata (PV). To elucidate its effect on As uptake and growth, P. vittata were grown on agar media (63 μM P) containing 50 μM As and/or 50 or 500 μM phytate with non As-hyperaccumulator Pteris ensiformis (PE) as a congeneric control for 60 d. Phytate induced efficient As and P uptake, and enhanced growth in PV, but had little effects on PE. The As concentrations in PV fronds and roots were 157 and 31 mg kg -1 in As 50 +phytate 50 , 2.2- and 3.1-fold that of As 50 treatment. Phosphorus uptake by PV was reduced by 27% in As treatment than the control (P vs. P+As) but increased by 73% comparing phytate 500 to phytate 500 +As, indicating that PV effectively took up P from phytate. Neither As nor phytate affected Fe accumulation in PV, but phytate reduced root Fe concentration in PE (46-56%). As such, the increased As and P and the unsuppressed Fe uptake in PV probably promoted PV growth. Thus, supplying phytate to As-contaminated soils may promote As uptake and growth in PV and its phytoremediation ability. Copyright © 2017 Elsevier Ltd. All rights reserved.

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.

Science.gov (United States)

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.

Depolarization by K+ and glutamate activates different neurotransmitter release mechanisms in GABAergic neurons: vesicular versus non-vesicular release of GABA

DEFF Research Database (Denmark)

Belhage, B; Hansen, Gert Helge; Schousboe, A

1993-01-01

differences in the mode of action of the two depolarizing stimuli were reflected in the properties of the increase in [Ca++]i elicited by 55 mM K+ and 100 microM glutamate, respectively. The K(+)-induced increase in [Ca++]i was reduced by both verapamil and Ca(++)-free media whereas the corresponding...... neurotransmitter glutamate (100 microM). Both depolarizing stimuli exerted prompt increases in the release of preloaded [3H]GABA as well as in [Ca++]i. However, the basic properties of transmitter release and the increase in [Ca++]i under a variety of conditions were different during stimulation with K...... was also reduced by organic (verapamil) and inorganic (Co++) Ca++ channel blockers but was insensitive to the GABA transport inhibitor SKF 89976A. In contrast, the second phase was less sensitive to nocodazole and Ca++ channel antagonists but could be inhibited by SKF 89976A. The glutamate-induced [3H...

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.

The mechanism of zinc uptake in excised roots and leaf discs of Phaseolus vulgaris L

International Nuclear Information System (INIS)

Van As, J.A.

1991-03-01

The mechanism and nature of zinc uptake was studied with the aid of 65 Zn. Uptake of zinc was also compared to that of potassium and phosphate, which are known to be ATP-dependent. Zinc uptake was characterized by a rapid initial uptake, followed by a slower linear phase. Decreasing the temperature from 25 to 2 deg C resulted in a decrease of only 30% in the rate of zinc uptake. Uptake of zinc was insensitive to DNP - possibly indicating the non-metabolic nature of the uptake process. A possible role for zinc in protein synthesis could not be demonstrated as CHI did not inhibit zinc uptake. Cyanide reduced zinc uptake to almost zero, possibly due to complexation of zinc by cyanide. Light had no effect on the accumulation of Zn, whereas dark incubation reduced potassium uptake substantially. The relative high rate of zinc uptake and the passive nature of the uptake process might be due to the high binding capacity of the free space for zinc ions. Transport of the zinc in the xylem and phloem of intact bean plants, as well as the metabolic dependence of the latter, was also investigated. The bulk of the zinc absorbed by bean plants remained in the roots and stems with only a very small fraction being translocated to shoots. Adsorption was the major uptake mechanism in roots and stems. In contrast to transport in the xylem, zinc was readily transported in the phloem. Loading and unloading of zinc in the phloem was not influenced by low temperature or DNP. Opposed to this, loading of potassium and phosphate was inhibited by DNP, while unloading was inhibited by low temperature. It can therefore be concluded that the uptake and transport of zinc is probably a passive process. 33 figs., 282 refs

Neurotransmitter-based strategies for the treatment of cognitive dysfunction in Down syndrome.

Science.gov (United States)

Das, Devsmita; Phillips, Cristy; Hsieh, Wayne; Sumanth, Krithika; Dang, Van; Salehi, Ahmad

2014-10-03

Down syndrome (DS) is a multisystem disorder affecting the cardiovascular, respiratory, gastrointestinal, neurological, hematopoietic, and musculoskeletal systems and is characterized by significant cognitive disability and a possible common pathogenic mechanism with Alzheimer's disease. During the last decade, numerous studies have supported the notion that the triplication of specific genes on human chromosome 21 plays a significant role in cognitive dysfunction in DS. Here we reviewed studies in trisomic mouse models and humans, including children and adults with DS. In order to identify groups of genes that contribute to cognitive disability in DS, multiple mouse models of DS with segmental trisomy have been generated. Over-expression of these particular genes in DS can lead to dysfunction of several neurotransmitter systems. Therapeutic strategies for DS have either focused on normalizing the expression of triplicated genes with important roles in DS or restoring the function of these systems. Indeed, our extensive review of studies on the pathogenesis of DS suggests that one plausible strategy for the treatment of cognitive dysfunction is to target the cholinergic, serotonergic, GABA-ergic, glutamatergic, and norepinephrinergic system. However, a fundamental strategy for treatment of cognitive dysfunction in DS would include reducing to normal levels the expression of specific triplicated genes in affected systems before the onset of neurodegeneration. Published by Elsevier Inc.

Effect of different iron levels on 65Zn uptake and transport in maize seedlings

International Nuclear Information System (INIS)

Rathore, V.S.; Sharma, D.; Kandala, J.C.

1974-01-01

Uptake and translocation of 65 Zn was studied in two week old maize seedlings at 0.01, 0.1, 1 and 5 ppm iron levels in half-strength Hoagland's solution. Four different zinc levels viz., 0.04, 0.4, 4 and 8 ppm were taken. Total 65 Zn uptake and translocation to shoots at 2, 4, 6 and 12 hours showed that increasing iron levels in the uptake medium reduced Zn-uptake in all combinations and at all uptake hours studied. This antagnnistic effect of iron on zinc uptake was more pronounced at the initial stages and could be partly inhibited by increasing zinc concentration in the uptake medium. Translocation of 65 Zn to shoots increased with increase in uptake time. Increasing iron levels in the medium decreased zinc dislocation to shoots at all zinc levels. (author)

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

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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.

Nutrient limitation reduces land carbon uptake in simulations with a model of combined carbon, nitrogen and phosphorus cycling

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D. S. Goll

2012-09-01

Full Text Available Terrestrial carbon (C cycle models applied for climate projections simulate a strong increase in net primary productivity (NPP due to elevated atmospheric CO₂ concentration during the 21st century. These models usually neglect the limited availability of nitrogen (N and phosphorus (P, nutrients that commonly limit plant growth and soil carbon turnover. To investigate how the projected C sequestration is altered when stoichiometric constraints on C cycling are considered, we incorporated a P cycle into the land surface model JSBACH (Jena Scheme for Biosphere–Atmosphere Coupling in Hamburg, which already includes representations of coupled C and N cycles.

The model reveals a distinct geographic pattern of P and N limitation. Under the SRES (Special Report on Emissions Scenarios A1B scenario, the accumulated land C uptake between 1860 and 2100 is 13% (particularly at high latitudes and 16% (particularly at low latitudes lower in simulations with N and P cycling, respectively, than in simulations without nutrient cycles. The combined effect of both nutrients reduces land C uptake by 25% compared to simulations without N or P cycling. Nutrient limitation in general may be biased by the model simplicity, but the ranking of limitations is robust against the parameterization and the inflexibility of stoichiometry. After 2100, increased temperature and high CO₂ concentration cause a shift from N to P limitation at high latitudes, while nutrient limitation in the tropics declines. The increase in P limitation at high-latitudes is induced by a strong increase in NPP and the low P sorption capacity of soils, while a decline in tropical NPP due to high autotrophic respiration rates alleviates N and P limitations. The quantification of P limitation remains challenging. The poorly constrained processes of soil P sorption and biochemical mineralization are identified as the main uncertainties in the strength of P limitation

Cardiomyocyte Triglyceride Accumulation and Reduced Ventricular Function in Mice with Obesity Reflect Increased Long Chain Fatty Acid Uptake and De Novo Fatty Acid Synthesis

Directory of Open Access Journals (Sweden)

Fengxia Ge

2012-01-01

Full Text Available A nonarteriosclerotic cardiomyopathy is increasingly seen in obese patients. Seeking a rodent model, we studied cardiac histology, function, cardiomyocyte fatty acid uptake, and transporter gene expression in male C57BL/6J control mice and three obesity groups: similar mice fed a high-fat diet (HFD and db/db and ob/ob mice. At sacrifice, all obesity groups had increased body and heart weights and fatty livers. By echocardiography, ejection fraction (EF and fractional shortening (FS of left ventricular diameter during systole were significantly reduced. The Vmax for saturable fatty acid uptake was increased and significantly correlated with cardiac triglycerides and insulin concentrations. Vmax also correlated with expression of genes for the cardiac fatty acid transporters Cd36 and Slc27a1. Genes for de novo fatty acid synthesis (Fasn, Scd1 were also upregulated. Ten oxidative phosphorylation pathway genes were downregulated, suggesting that a decrease in cardiomyocyte ATP synthesis might explain the decreased contractile function in obese hearts.

Plant uptake of dual-labeled organic N biased by inorganic C uptake

DEFF Research Database (Denmark)

Rasmussen, Jim; Sauheitl, Leopold; Eriksen, Jørgen

2010-01-01

glycine or CO2-3 , but found no differences in uptake rates between these C-sources. The uptake of inorganic C to the shoot tissue was higher for maize grown in full light compared to shading, which indicates a passive uptake of inorganic C with water. We conclude that uptake of inorganic C produced...

Downregulation of taurine uptake in multidrug resistant Ehrlich ascites tumor cells

DEFF Research Database (Denmark)

Poulsen, K A; Litman, Thomas; Eriksen, J

2002-01-01

In daunorubicin resistant Ehrlich ascites tumor cells (DNR), the initial taurine uptake was reduced by 56% as compared to the parental, drug sensitive Ehrlich cells. Kinetic experiments indicated that taurine uptake in Ehrlich cells occurs via both high- and low-affinity transporters. The maximal...... rate constant for the initial taurine uptake was reduced by 45% (high-affinity system) and 49% (low affinity system) in the resistant subline whereas the affinity of the transporters to taurine was unchanged. By immunoblotting we identified 3 TauT protein bands in the 50-70 kDa region. A visible...... reduction in the intensity of the band with the lowest molecular weight was observed in resistant cells. Quantitative RT-PCR indicated a significant reduction in the amount of taurine transporter mRNA in the resistant cells. Drug resistance in DNR Ehrlich cells is associated with overexpression of the mdr1...

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...

Lycium barbarum L. Polysaccharide (LBP Reduces Glucose Uptake via Down-Regulation of SGLT-1 in Caco2 Cell

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Huizhen Cai

2017-02-01

Full Text Available Lycium barbarum L. polysaccharide (LBP is prepared from Lycium barbarum L. (L. barbarum, which is a traditional Chinese medicine. LPB has been shown to have hypoglycemic effects. In order to gain some mechanistic insights on the hypoglycemic effects of LBP, we investigated the uptake of LBP and its effect on glucose absorption in the human intestinal epithelial cell line Caco2 cell. The uptake of LBP through Caco2 cell monolayer was time-dependent and was inhibited by phloridzin, a competitive inhibitor of SGLT-1. LPB decreased the absorption of glucose in Caco2 cell, and down-regulated the expression of SGLT-1. These results suggest that LBP might be transported across the human intestinal epithelium through SGLT-1 and it inhibits glucose uptake via down-regulating SGLT-1.

134cs uptake by plants from soil applying different absorbents

International Nuclear Information System (INIS)

Oncsik, M.

1998-01-01

A study of isotope uptake by plants using different zeolite clay minerals (montmorillonite, mordenite, clinoptilolite) was started with a view to reducing the rate of isotope uptake by plants by applying additives given to the soil. In pot experiments, the 134 Cs activity of green peas was reduced by 16% in average as compared to the control in the soils enriched with zeolite (mordenite type). Under field conditions, the radioactivity of millet and carrot yields were investigated in soils ameliorated with montmorillonite clay mineral. The radioactive contamination of the yield in soil treated with zeolite was in average 10% lower for millet and 24% for carrot roots as compared to the control

Multiple pathways for uptake of paraquat, methylglyoxal bis(guanylhydrazone), and polyamines

Energy Technology Data Exchange (ETDEWEB)

Byers, T.L.; Kameji, R.; Rannels, D.E.; Pegg, A.E.

1987-06-01

The uptake of polyamines, methylglyoxal bis(guanylhydrazone) (MGBG), and paraquat (N,N-dimethyl-4,4'-bipyridylium) into control Chinese hamster ovary (CHO) cells and a mutant CHO cell line selected for resistance to the toxicity of MGBG was examined. In contrast to control CHO cells, the mutant cells had no detectable uptake of (/sup 14/C)-MGBG or any of the polyamines. There was no difference between the two cell lines in the uptake of ..cap alpha..-aminoisobutyric (/sup 3/H-AIB), which indicates that there was no general change in membrane transport processes. The mutant cells were also found to be resistant to the toxicity of paraquat and to have a reduced capability to take up the herbicide. This finding confirms that the uptake of paraquat is necessary for the toxicity of this compound and that the paraquat is taken up by a transport system that also transports MGBG. Competition experiments showed that an excess of unlabeled paraquat inhibited uptake of MGBG and, to a lesser extent, uptake of putrescine and spermidine, but no inhibitory action on spermine uptake could be detected. Studies with type II cells isolated from rat lung also demonstrated uptake of paraquat and spermidine, but paraquat was only a weak inhibitor of spermidine uptake in this system. These results suggest that there may be multiple systems for the uptake of MGBG and polyamines and that paraquat is taken up by at least one but not by all of these systems.

Multiple pathways for uptake of paraquat, methylglyoxal bis(guanylhydrazone), and polyamines

International Nuclear Information System (INIS)

Byers, T.L.; Kameji, R.; Rannels, D.E.; Pegg, A.E.

1987-01-01

The uptake of polyamines, methylglyoxal bis(guanylhydrazone) (MGBG), and paraquat [N,N-dimethyl-4,4'-bipyridylium] into control Chinese hamster ovary (CHO) cells and a mutant CHO cell line selected for resistance to the toxicity of MGBG was examined. In contrast to control CHO cells, the mutant cells had no detectable uptake of [ 14 C]-MGBG or any of the polyamines. There was no difference between the two cell lines in the uptake of α-aminoisobutyric ( 3 H-AIB), which indicates that there was no general change in membrane transport processes. The mutant cells were also found to be resistant to the toxicity of paraquat and to have a reduced capability to take up the herbicide. This finding confirms that the uptake of paraquat is necessary for the toxicity of this compound and that the paraquat is taken up by a transport system that also transports MGBG. Competition experiments showed that an excess of unlabeled paraquat inhibited uptake of MGBG and, to a lesser extent, uptake of putrescine and spermidine, but no inhibitory action on spermine uptake could be detected. Studies with type II cells isolated from rat lung also demonstrated uptake of paraquat and spermidine, but paraquat was only a weak inhibitor of spermidine uptake in this system. These results suggest that there may be multiple systems for the uptake of MGBG and polyamines and that paraquat is taken up by at least one but not by all of these systems

Ammonium and nitrate uptake by the marine macrophytes Hypnea musciformis (Rhodophyta) and Macrocystis pyrifera (phaeophyta)

Energy Technology Data Exchange (ETDEWEB)

Haines, K.C. (Univ. of Texas Marine Science Inst., St. Croix, US Virgin Islands); Wheeler, P.A.

1978-01-01

NH/sub 4//sup +/ and NO/sub 3//sup -/ uptake were measured by continuous sampling with an autoanalyzer. For Hypnea musciformis (Wulfen) Lamouroux, NO/sub 3//sup -/ uptake followed saturable kinetics (K/sub s/ = 4.9 ..mu..g-at N.l/sup -1/, V/sub max/ = 2.85 ..mu..g-at N-g(wet)/sup -1/.h/sup -1/). The ammonium uptake data fit a truncated hyperbola, i.e., saturation was not reached at the concentrations used, NO/sub 3//sup -/ uptake was reduced one-half in the presence of NH/sub 4//sup +/, but presence of NO/sub 3//sup -/ had no effect on NH/sub 4//sup +/ uptake. Darkness reduced both NO/sub 3//sup -/ and NH/sub 4//sup +/ uptake by one-third to one-half. For Macrocystis pyrifera (L.) C. Agardh. NO/sub 3//sup -/ uptake followed saturable kinetics; K/sub s/ = 13.1 ..mu..g-at N.l/sup -1/, V/sub max/ = 3.05 ..mu..g-at N.g(wet)/sup -1/.h/sup -1/. NH/sub 4//sup +/ uptake showed saturable kinetics at concentrations below 22 ..mu..g-at N.l/sup -1/(K/sub s/ = 5.3 ..mu..g-at N.l/sup -1/, V/sub max/ = 2.38 ..mu..g-at N g(wet)/sup -1/.h/sup -1/); at higher concentrations uptake increased linearly with concentration. NO/sub 3//sup -/ and NH/sub 4//sup +/ were taken up simultaneously; presence of one form did not affect uptake of the other.

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.

Caffeine and Cannabis Effects on Vital Neurotransmitters and Enzymes in the Brain Tissue of Juvenile Experimental Rats.

Science.gov (United States)

Owolabi, J O; Olatunji, S Y; Olanrewaju, A J

2017-05-01

Caffeine and cannabis are globally consumed and abused psychoactive substances. While caffeine is legally used in various forms, including in tea and coffee as beverages, it is also consumed in soda and energy drinks as additives. Cannabis, on the other hand, is considered illegal in most countries; albeit, it is being consumed globally particularly by adolescents. The adolescent stage marks a critical stage of brain development and maturation. Influences of agents on the brain at this stage may affect neuronal structural and functional attributes. To this end, the current experiment considered the effects of cannabis and caffeine on selected key neurotransmitters and enzymes in the brain tissues after regimented caffeine and cannabis treatment for 21 days. A total of 72 juvenile Wistar rats that were approximately 40 days old were divided into 6 groups A-F. The group A served as the control. Other groups were administered various dosages of caffeine or cannabis in distilled water, using oral gavages as follows: group B animals received 100 mg/kg body weight of caffeine, group C animals received 50 mg/kg body weight of caffeine, group D animals received 500 mg/kg body weight of cannabis, group E animals received 200 mg/kg body weight of cannabis, and group F received a low dose of cannabis (200 mg/kg body weight) plus a low dose of caffeine (50 mg/kg body weight). The animals were killed by cervical dislocation 24 h after the last administration. The brain tissues were excised and homogenized. The enzymes cytochrome C oxidase and glucose-6-phosphate dehydrogenase were assayed to observe tissue energy metabolism while the neurotransmitters gamma-amino butyric acid (GABA), glutamate, and dopamine were assayed to observe the effects of the psychoactive substances on their activities relative to mental activities. GABA, glutamate, and dopamine were generally higher in the treated groups of animals. The levels of G-6-PDH were higher in all treated animals' brains

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.

Sugar uptake and starch biosynthesis by slices of developing maize endosperm

International Nuclear Information System (INIS)

Felker, F.C.; Liu, Kangchien; Shannon, J.C.

1990-01-01

14 C-Sugar uptake and incorporation into starch by slices of developing maize (Zea mays L.) endosperm were examined and compared with sugar uptake by maize endosperm-derived suspension cultures. Rates of sucrose, fructose, and D- and L-glucose uptake by slices were similar, whereas uptake rates for these sugars differed greatly in suspension cultures. Concentration dependence of sucrose, fructose, and D-glucose uptake was biphasic (consisting of linear plus saturable components) with suspension cultures but linear with slices. These and other differences suggest that endosperm slices are freely permeable to sugars. After diffusion into the slices, sugars were metabolized and incorporated into starch. Starch synthesis, but not sugar accumulation, was greatly reduced by 2.5 millimolar p-chloromercuribenzenesulfonic acid and 0.1 millimolar carbonyl cyanide m-chlorophenylhydrazone. Starch synthesis was dependent on kernel age and incubation temperature, but not on external pH (5 through 8). Competing sugars generally did not affect the distribution of 14 C among the soluble sugars extracted from endosperm slices incubated in 14 C-sugars. Competing hexoses reduced the incorporation of 14 C into starch, but competing sucrose did not, suggesting that sucrose is not a necessary intermediate in starch biosynthesis. The bidirectional permeability of endosperm slices to sugars makes the characterization of sugar transport into endosperm slices impossible, however the model system is useful for experiments dealing with starch biosynthesis which occurs in the metabolically active tissue

Nitrogen uptake efficiency of irrigated wheat in Egypt

International Nuclear Information System (INIS)

Abdel Monem, M.A.S.

2000-01-01

Egypt's current wheat production would be impossible without N fertilizers, the consumption of which has increased more than 75% in the last 20 years. The efficiency of uptake of applied N is low, and better management of both fertilizer and irrigation is needed to improve N recovery by crops and reduce losses from the plant/soil system. Field trials were conducted over a 3-year period, on Egypt's three main soil types: old irrigated land of the Nile valley, newly reclaimed sandy and calcareous soils, and salt-affected soil of the north delta. The responses of wheat cultivars to N, and patterns of N uptake and N loss, as affected by irrigation regime, were examined using 15 N. Cultivar Sakha 69 was more responsive to applied N and assimilated N more efficiently than other varieties under different soil types. Nitrogen loss from the sandy soil was as high as 57% whereas average loss in the clay soil was 17%. A higher water table in the salt-affected soil negatively affected N uptake. Irrigation with 75% of the required water for wheat had no effect on yield or N-uptake. (author)

Determination of maximum physiologic thyroid uptake and correlation with 24-hour RAI uptake value

International Nuclear Information System (INIS)

Duldulao, M.; Obaldo, J.

2007-01-01

Full text: In hyperthyroid patients, thyroid uptake values are overestimated, sometimes approaching or exceeding 100%. This is physiologically and mathematically impossible. This study was undertaken to determine the maximum physiologic thyroid uptake value through a proposed simple method using a gamma camera. Methodology: Twenty-two patients (17 females and 5 males), with ages ranging from 19-61 y/o (mean age ± SD; 41 ± 12), with 24-hour uptake value of >50%, clinically hyperthyroid and referred for subsequent radioactive iodine therapy were studied. The computed maximum physiologic thyroid uptake was compared with the 24-hour uptake using the paired Student t-test and evaluated using linear regression analysis. Results: The computed physiologic uptake correlated poorly with the 24-hour uptake value. However, in the male subgroup, there was no statistically significant difference between the two (p=0.77). Linear regression analysis gives the following relationship: physiologic uptake (%) = 77.76 - 0.284 (24-hour RAI uptake value). Conclusion: Provided that proper regions of interest are applied with correct attenuation and background subtraction, determination of physiologic thyroid uptake may be obtained using the proposed method. This simple method may be useful prior to I-131 therapy for hyperthyroidism especially when a single uptake determination is performed. (author)

Bioanalysis of a panel of neurotransmitters and their metabolites in plasma samples obtained from pediatric patients with neuroblastoma and Wilms' tumor.

Science.gov (United States)

Konieczna, Lucyna; Roszkowska, Anna; Stachowicz-Stencel, Teresa; Synakiewicz, Anna; Bączek, Tomasz

2018-02-01

This paper details the quantitative analysis of neurotransmitters, including dopamine (DA), norepinephrine (NE), epinephrine (E), and serotonin (5-HT), along with their respective precursors and metabolites in children with solid tumors: Wilms' tumor (WT) and neuroblastoma (NB). A panel of neurotransmitters was determined with the use of dispersive liquid-liquid microextraction (DLLME) technique combined with liquid-chromatography mass spectrometry (LC-MS/MS) in plasma samples obtained from a group of pediatric subjects with solid tumors and a control group of healthy children. Next, statistical univariate analysis (t-test) and multivariate analysis (Principal Component Analysis) were performed using chromatographic data. The levels of tyrosine (Tyr) and tryptophan (Trp) (the precursors of analyzed neurotransmitters) as well as 3,4-dihydroxyphenylacetic acid (DOPAC) (a product of metabolism of DA) were significantly higher in the plasma samples obtained from pediatric patients with WT than in the samples taken from the control group. Moreover, statistically significant differences were observed between the levels of 5-HT and homovanillic acid (HVA) in the plasma samples from pediatric patients with solid tumors and the control group. However, elevated levels of these analytes did not facilitate a clear distinction between pediatric patients with WT and those with NB. Nonetheless, the application of advanced statistical tools allowed the healthy controls to be differentiated from the pediatric oncological patients. The identification and quantification of a panel of neurotransmitters as potential prognostic factors in selected childhood malignancies may provide clinically relevant information about ongoing metabolic alterations, and it could potentially serve as an adjunctive strategy in the effective diagnosis and treatment of solid tumors in children. Copyright © 2017 Elsevier B.V. All rights reserved.

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

Science.gov (United States)

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.

Do Proxies for the Neurotransmitter Cortisol Predict Adaptation to Life with Chronic Pain?

Science.gov (United States)

Deamond, Wade

Among the numerous difficulties encountered by chronic pain patients, impulsive and dysfunctional decision-making complicate their already difficult life situations yet remains relatively understudied. This study examined a recently published neurobiological decision making model that identifies eight specific neurotransmitters and hormones (Dopamine, Testosterone, Endogenous Opioids Glutamate, Serotonin, Norepinephrine, Cortisol, and GABA) linked to unsound decision making related to cognitive, motivational and emotional dysregulation (Nussbaum et al., 2011) (see Appendix 2). The Perceived Stress Scale (PSS), a proxy for the cortisol element in the pharmacological decision making model was analyzed for the neurotransmitter's relationship to functionality and quality of life in a group of 37 chronic pain patients. Participants were comprised of males and females ranging from 23 to 52 years of age and were classified with respect to levels of adjustment to living with chronic pain based on the Quality of Life Scale (QLS), the Dartmouth WONCA COOP Charts and the Global Assessment of Functioning (GAF). The Iowa Gambling Task (IGT) and Frontal System Behavioral Scale (FSBS) measured decision making related to immediate gratification and daily living respectively. Results suggest that emotional dysregulation, as measured by the PSS is a significant predictor for adaptation to life with chronic pain and the PSS is superior to predicting adaptation to life with chronic pain than reported levels of pain as measured by the McGill Pain Questionnaire.

Influence of water relations and growth rate on plant element uptake and distribution

International Nuclear Information System (INIS)

Greger, Maria

2006-02-01

Plant uptake of Ni, Sr, Mo, Cs, La, Th, Se, Cl and I was examined to determine how plant water relations and growth rate influence the uptake and distribution of these elements in the studied plants. The specific questions were how water uptake and growth rate influenced the uptake of various nuclides and how transpiration influenced translocation to the shoot. The knowledge gained will be used in future modelling of radionuclide leakage from nuclear waste deposits entering the ecosystem via plants. The plant studied was willow, Salix viminalis, a common plant in the areas suggested for waste disposal; since there can be clone variation, two different clones having different uptake properties for several other heavy metals were used. The plants were grown in nutrient solution and the experiments on 3-month-old plants were run for 3 days. Polyethylene glycol was added to the medium to decrease the water uptake rate, a fan was used to increase the transpiration rate, and different light intensities were used to produce different growth rates. Element concentration was analysed in roots and shoots. The results show that both the uptake and distribution of various elements are influenced in different ways and to various extents by water flow and plant growth rate, and that it is not possible from the chemical properties of these elements to know how they will react. However, in most cases increased growth rate diluted the concentration of the element in the tissue, reduced water uptake reduced the element uptake, while transpiration had no effect on the translocation of elements to the shoot. The clones did not differ in terms of either the uptake or translocation of the elements, except that I was not taken up and translocated to the shoot in one of the clones when the plant water flow or growth rate was too low. Not all of the elements were found in the plant in the same proportions as they had been added to the nutrient solution

Influence of water relations and growth rate on plant element uptake and distribution

Energy Technology Data Exchange (ETDEWEB)

Greger, Maria [Stockholm Univ. (Sweden). Dept. of Botany

2006-02-15

Plant uptake of Ni, Sr, Mo, Cs, La, Th, Se, Cl and I was examined to determine how plant water relations and growth rate influence the uptake and distribution of these elements in the studied plants. The specific questions were how water uptake and growth rate influenced the uptake of various nuclides and how transpiration influenced translocation to the shoot. The knowledge gained will be used in future modelling of radionuclide leakage from nuclear waste deposits entering the ecosystem via plants. The plant studied was willow, Salix viminalis, a common plant in the areas suggested for waste disposal; since there can be clone variation, two different clones having different uptake properties for several other heavy metals were used. The plants were grown in nutrient solution and the experiments on 3-month-old plants were run for 3 days. Polyethylene glycol was added to the medium to decrease the water uptake rate, a fan was used to increase the transpiration rate, and different light intensities were used to produce different growth rates. Element concentration was analysed in roots and shoots. The results show that both the uptake and distribution of various elements are influenced in different ways and to various extents by water flow and plant growth rate, and that it is not possible from the chemical properties of these elements to know how they will react. However, in most cases increased growth rate diluted the concentration of the element in the tissue, reduced water uptake reduced the element uptake, while transpiration had no effect on the translocation of elements to the shoot. The clones did not differ in terms of either the uptake or translocation of the elements, except that I was not taken up and translocated to the shoot in one of the clones when the plant water flow or growth rate was too low. Not all of the elements were found in the plant in the same proportions as they had been added to the nutrient solution.

Maintenance of water uptake and reduced water loss contribute to water stress tolerance of Spiraea alba Du Roi and Spiraea tomentosa L.

Science.gov (United States)

Stanton, Kelly M; Mickelbart, Michael V

2014-01-01

Two primarily eastern US native shrubs, Spiraea alba Du Roi and Spiraea tomentosa L., are typically found growing in wet areas, often with standing water. Both species have potential for use in the landscape, but little is known of their environmental requirements, including their adaptation to water stress. Two geographic accessions of each species were evaluated for their response to water stress under greenhouse conditions. Above-ground biomass, water relations and gas exchange were measured in well-watered and water stress treatments. In both species, water stress resulted in reduced growth, transpiration and pre-dawn water potential. However, both species also exhibited the ability to osmotically adjust to lower soil water content, resulting in maintained midday leaf turgor potential in all accessions. Net CO2 assimilation was reduced only in one accession of S. alba, primarily due to large reductions in stomatal conductance. S. tomentosa lost a larger proportion of leaves than S. alba in response to water stress. The primary water stress tolerance strategies of S. alba and S. tomentosa appear to be the maintenance of water uptake and reduced water loss.

Stretched graphene tented by polycaprolactone and polypyrrole net–bracket for neurotransmitter detection

International Nuclear Information System (INIS)

Wang, Zhenzhen; Ying, Ye; Li, Li; Xu, Ting; Wu, Yiping; Guo, Xiaoyu; Wang, Feng; Shen, Haojie; Wen, Ying; Yang, Haifeng

2017-01-01

Highlights: • A new DA sensor is constructed with RGO and electrospun polymer fiber film. • RGO sheets can be mechanically stretched by the as-fabricated net-brackets. • The DA sensor shows highly catalytic activity toward the oxidation of dopamine. • The as-prepared sensor is used to detect DA in injection or urine. • The protocol to make sensors in large scale way has good reproducibility. - Abstract: A net-bracket built out from the core@shell structure of chemically oxidized polypyrrole (PPy) coated electrospun polycaprolactone (PCL) nanofibers, and the following surface modification of a thin layer of positively charged poly(dimethyl diallyl ammonium chloride) (PDDA) has been applied for stretching the reduced graphene oxide (RGO) sheets to some extent with the electrochemical deposition method. The as-formed RGO/PDDA/PCL@PPy nanocomposites were investigated by using scanning electron microscopy, transmission electron microscope, X-ray diffraction and Raman spectroscopy. The graphene tented by the net-bracket showed remarkable electrocatalytic properties in detecting the neurotransmitter dopamine (DA). Low detection limit of 0.34 μM (S/N = 3) with the wide linear detection range from 4 μM to 690 μM was obtained. The successful determination of DA in real urine samples and DA injection were achieved. Such attractive fabrication strategy can be extended to make other graphene sheet-based sensors.

Stretched graphene tented by polycaprolactone and polypyrrole net–bracket for neurotransmitter detection

Energy Technology Data Exchange (ETDEWEB)

Wang, Zhenzhen; Ying, Ye; Li, Li; Xu, Ting; Wu, Yiping; Guo, Xiaoyu; Wang, Feng; Shen, Haojie; Wen, Ying, E-mail: ying.wen@shnu.edu.cn; Yang, Haifeng, E-mail: Hfyang@shnu.edu.cn

2017-02-28

Highlights: • A new DA sensor is constructed with RGO and electrospun polymer fiber film. • RGO sheets can be mechanically stretched by the as-fabricated net-brackets. • The DA sensor shows highly catalytic activity toward the oxidation of dopamine. • The as-prepared sensor is used to detect DA in injection or urine. • The protocol to make sensors in large scale way has good reproducibility. - Abstract: A net-bracket built out from the core@shell structure of chemically oxidized polypyrrole (PPy) coated electrospun polycaprolactone (PCL) nanofibers, and the following surface modification of a thin layer of positively charged poly(dimethyl diallyl ammonium chloride) (PDDA) has been applied for stretching the reduced graphene oxide (RGO) sheets to some extent with the electrochemical deposition method. The as-formed RGO/PDDA/PCL@PPy nanocomposites were investigated by using scanning electron microscopy, transmission electron microscope, X-ray diffraction and Raman spectroscopy. The graphene tented by the net-bracket showed remarkable electrocatalytic properties in detecting the neurotransmitter dopamine (DA). Low detection limit of 0.34 μM (S/N = 3) with the wide linear detection range from 4 μM to 690 μM was obtained. The successful determination of DA in real urine samples and DA injection were achieved. Such attractive fabrication strategy can be extended to make other graphene sheet-based sensors.

Reevaluation of the 131I thyroid uptake in Rio de Janeiro

International Nuclear Information System (INIS)

Rosenthal, D.; Frankenfeld, T.G.P.; Assis Paiva, H.J. de; Fridman, J.

1982-01-01

The values of the 3 and 24 hour thyroid radioiodine uptake were analysed in 919 of the patients examined during 1977-1980. Reference values determined for 95% of the normal population are 2.5 - 17.5% for the 3 hour thyroid uptake values, and 10.5 - 41.2% for the 24 hour values. The non-toxic diffuse goiter group has significantly higher mean values than normals or patients with non-toxic nodular goiters and cold nodules, their upper values reaching 24.7% and 52.9% for 3 and 24 hour uptake. The discriminatory power of the test for non-toxic diffuse goiters may be increased if higher limits than those determined for normals are used in day to day routine. Values of 20% for 3 hour uptake and 45% for the 24 hour uptake improve diagnosis in these patients without seriously reducing the capacity for identification of thyrotoxicosis. A value greater than 0.6 for the ratio between the 3 hour and 24 hour uptake can serve as a coadjuvant factor in the diagnosis of diffuse toxic goiters; values higher than 0.8 were found in less than 0.5% of the non-toxic patients. (Author) [pt

Immunohistochemical profile of various neurotransmitters, neurotrophins and MIB-1 in cholesteatomas of the petrous bone.

Science.gov (United States)

Artico, Marco; Bronzetti, Elena; Lo Vasco, Vincenza Rita; Ionta, Brunella; Alicino, Valentina; D'Ambrosio, Anna; Magliulo, Giuseppe

2008-01-01

Compared to the normal epidermal epithelium, cholesteatomas have altered growth properties characterized by the excessive growth of keratinocytes leading to mucosal destruction. Either congenital or acquired, these lesions, which grow in the middle ear space, the petrous apex or the mastoid of temporal bones, are mostly considered benign skin tumoral lesions. However, many questions remain concerning their pathophysiology. Numerous studies have been proposed to identify those cholesteatoma lesions at risk of recurrence, a possible event that may cause hearing loss. We examined patients with petrous apex or mastoid cholesteatoma in order to analyze the expression of various neurotransmitters, neurotrophins and their receptors and the Ki-67 antigen for identification of a possible relationship between clinical outcome and histopathological behaviour in terms of the proliferative activity of cholesteatomas. Expression of the analyzed molecules was studied using immunohistochemical methods in seven adult patients with petrous apex cholesteatoma who underwent surgical removal of the lesion. Our results, in accordance with published data, confirm that Molecular Immunology Borstel-1 (MIB-1) and certain neurotransmitters could be useful in the prognostic evaluation of the risk of recurrence of aggressive forms of cholesteatoma.

The influence of aripiprazole and olanzapine on neurotransmitters level in frontal cortex of prenatally stressed rats.

Science.gov (United States)

Ratajczak, P; Kus, K; Gołembiowska, K; Noworyta-Sokołowska, K; Woźniak, A; Zaprutko, T; Nowakowska, E

2016-09-01

The study aims to verify whether alterations in the level of neurotransmitters have occurred in prenatally stressed rats (animal model of schizophrenia), and whether aripiprazole (ARI) and olanzapine (OLA) modify this level. The effects of ARI (1.5mg/kg) and OLA (0.5mg/kg) were studied by means of microdialysis in freely moving rats (observation time 120min). The level of neurotransmitters (DA, 5-HT, NA) and their metabolites (DOPAC, HVA, 5-HIAA) was analyzed by HPLC with coulochemical detection. Obtained results indicate that after a single administration of ARI and OLA in the prenatally stressed rats the increase of DA, DOPAC, and 5-HT was observed. In turn ARI administration increase the level of HVA and 5-HIAA and also decrease the level of NA. After OLA administration the level of NA and HVA increased and no significant change in 5-HIAA was observed. Alterations observed as a result of ARI and OLA administration may be pivotal in identifying animal models of mental disorders and in the analysis of neuroleptics effectiveness. Copyright © 2016 Elsevier B.V. All rights reserved.

Expression of neurotransmitters and neurotrophins in neurogenic inflammation of the rat retina

Directory of Open Access Journals (Sweden)

E Bronzetti

2009-08-01

Full Text Available Antidromic stimulation of the rat trigeminal ganglion triggers the release of substance P (SP and calcitonin gene-related peptide (CGRP from sensory nerve terminals of the capsaicin sensitive C-fibers. These pro-inflammatory neuropeptides produce a marked hyperemia in the anterior segment of the eye, accompanied by increased intraocular pressure, breakdown of the blood-aqueous barrier and myosis. To assess the effects of neurogenic inflammation on the retina, specifically on the immunostaining of neurotransmitters and neurotrophins, as well as on the expression of neurotrophin receptors in the retina. RT-PCR was also accomplished in control and stimulated animals to confirm the immunohistochemical results. In the electrically stimulated eyes, immunostaining for SP, CGRP, VIP and nNOS demonstrated a marked increase in the RPE/POS (Retinal Pigment Epithelium/Photoreceptor Outer Segments, in the inner and outer granular layers and in the ganglion cells in comparison to the control eyes. CGRP and SP were found increased in stimulated animals and this result has been confirmed by RT- PCR. Changes in neurotrophin immunostaining and in receptor expression were also observed after electric stimulation of trigeminal ganglia. Decrease of BDNF and NT4 in the outer and inner layers and in ganglion cells was particularly marked. In stimulated rat retinas immunostaining and RT-PCR showed a NGF expression increase. Neurotrophin receptors remained substantially unchanged. These studies demonstrated, for the first time, that antidromic stimulation of the trigeminal ganglion and subsequent neurogenic inflammation affect immunostaining of retinal cell neurotransmitter/ neuropeptides and neurotrophins as well as the expression of neurotrophin receptors.

ASTROCYTIC CONTROL OF BIOSYNTHESIS AND TURNOVER OF THE NEUROTRANSMITTERS GLUTAMATE AND GABA

Directory of Open Access Journals (Sweden)

Arne eSchousboe

2013-08-01

Full Text Available 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 (PC, 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 involves the enzymes glutamine synthetase (GS and glutaminase (PAG together with the plasma membrane transporters for glutamate, GABA and glutamine. The distribution of these proteins between neurons and astrocytes determines the efficacy of the cycle and it is of particular importance that GS is exclusively expressed in astrocytes. It should be kept in mind that the operation of the cycle is associated with movement of ammonia nitrogen between the two cell types and different mechanisms which can mediate this have been proposed.This review is intended to delineate the above mentioned processes and to discuss quantitatively their relative importance in the homeostatic mechanisms responsible for the maintenance of optimal conditions for the respective neurotransmission processes to operate.

Nutrient uptake by intact mycorrhizal Pinus sylvestris seedlings: a diagnostic tool to detect copper toxicity.

Science.gov (United States)

Van Tichelen, Katia K.; Vanstraelen, Tom; Colpaert, Jan V.

1999-03-01

We developed a nondestructive method for detecting early toxic effects of inflethal copper (Cu) concentrations on ectomycorrhizal and non-mycorrhizal (NM) Scots pine (Pinus sylvestris L.) seedlings. The fungal symbionts examined were Paxillus involutus (Fr.) Fr., Suillus luteus (Fr.) S.F. Gray and Thelephora terrestris (Ehrh.) Fr. The accumulation of Cu in needles and fungal development (ergosterol) in roots and infstrate were assessed. Inorganic phosphate (P(i)) and ammonium (NH(4) (+)) uptake capacities were determined in a semi-hydroponic cultivation system on intact P-limited plants that were exposed for 3 weeks to 0.32 (control), 8 or 16 &mgr;moles Cu(2+). Short-term effects of a 1-hour exposure to 32 &mgr;moles Cu(2+) on nutrient uptake rates were also determined. None of the Cu(2+) treatments affected plant growth or root ergosterol concentrations. The active fungal biomass in infstrate invaded by S. luteus was reduced by 50% in the 16 &mgr;M Cu(2+) treatment compared with the control treatment; however, colonization by S. luteus prevented an increased accumulation of Cu in the needles. In contrast, the 16 &mgr;M Cu(2+) treatment caused a 2.2-fold increase in needle Cu concentration in NM plants. Ergosterol concentrations in the infstrate colonized by P. involutus and T. terrestris were not affected by 16 &mgr;molar Cu(2+). Although P. involutus and T. terrestris were less sensitive to Cu(2+) than S. luteus, T. terrestris did not prevent the accumulation of Cu in needles of its host plant in the 16 &mgr;molar Cu(2+) treatment. Mycorrhizal plants consistently had higher P(i) and NH(4) (+) uptake capacities than NM plants. In the control treatment, specific P(i) uptake rates were almost 10, 4 and 3 times higher in plants associated with P. involutus, S. luteus and T. terrestris, respectively, than in NM plants, and specific NH(4) (+) uptake rates were about 2, 2 and 5 times higher, respectively, than those of NM seedlings. Compared with the corresponding

Metal uptake and acute toxicity in zebrafish: Common mechanisms across multiple metals

Energy Technology Data Exchange (ETDEWEB)

Alsop, Derek, E-mail: alsopde@mcmaster.ca [Department of Biology, McMaster University, 1280 Main St. W., Hamilton, ON L8S 4K1 (Canada); Wood, Chris M. [Department of Biology, McMaster University, 1280 Main St. W., Hamilton, ON L8S 4K1 (Canada)

2011-10-15

All metals tested reduced calcium uptake in zebrafish larvae. However, it was whole body sodium loss that was functionally related to toxicity. The zebrafish larvae acute toxicity assay save time, space and resources. - Abstract: Zebrafish larvae (Danio rerio) were used to examine the mechanisms of action and acute toxicities of metals. Larvae had similar physiological responses and sensitivities to waterborne metals as adults. While cadmium and zinc have previously been shown to reduce Ca{sup 2+} uptake, copper and nickel also decreased Ca{sup 2+} uptake, suggesting that the epithelial transport of all these metals is through Ca{sup 2+} pathways. However, exposure to cadmium, copper or nickel for up to 48 h had little or no effect on total whole body Ca{sup 2+} levels, indicating that the reduction of Ca{sup 2+} uptake is not the acute toxic mechanism of these metals. Instead, mortalities were effectively related to whole body Na{sup +}, which decreased up to 39% after 48 h exposures to different metals around their respective 96 h LC50s. Decreases in whole body K{sup +} were also observed, although they were not as pronounced or frequent as Na{sup +} losses. None of the metals tested inhibited Na{sup +} uptake in zebrafish (Na{sup +} uptake was in fact increased with exposure) and the observed losses of Na{sup +}, K{sup +}, Ca{sup 2+} and Mg{sup 2+} were proportional to the ionic gradients between the plasma and water, indicating diffusive ion loss with metal exposure. This study has shown that there is a common pathway for metal uptake and a common mechanism of acute toxicity across groups of metals in zebrafish. The disruption of ion uptake accompanying metal exposure does not appear to be responsible for the acute toxicity of metals, as has been previously suggested, but rather the toxicity is instead due to total ion loss (predominantly Na{sup +}).

Uptake of [18F]fluorodeoxyglucose in human monocyte-macrophages in vitro

International Nuclear Information System (INIS)

Deichen, Jan Thiess; Prante, Olaf; Gack, Michaela; Schmiedehausen, Kristin; Kuwert, Torsten

2003-01-01

The fact that fluorine-18 fluorodeoxyglucose ([ 18 F]FDG) accumulates in inflammatory lesions as well as in tumours reduces the diagnostic specificity of positron emission tomography (PET) in oncology. The aim of this study was to characterise the uptake of [ 18 F]FDG in isolated human monocyte-macrophages (HMMs) in vitro in comparison with that in human glioblastoma (GLI) and pancreatic carcinoma cells (PAN). The purity of HMM preparations was determined by immunohistochemical staining and their functional integrity was assessed by long-term incubation with iodine-131 acetylated bovine serum albumin. [ 18 F]FDG uptake in HMMs was quantified as percent of whole [ 18 F]FDG activity per well (% ID) or as % ID in relation to total protein mass. [ 18 F]FDG uptake in HMMs significantly increased with culture duration, yielding 7.5%±0.9% (% ID/100 μg) at day 14. Stimulation by lipopolysaccharide further enhanced [ 18 F]FDG uptake in HMMs by a factor of 2. [ 18 F]FDG uptake significantly decreased with increasing glucose concentration in the medium. Radio-thin layer chromatography of intracellular metabolites revealed that [ 18 F]FDG was trapped by HMMs mainly as [ 18 F]FDG-6-phosphate and [ 18 F]FDG-1,6-diphosphate. [ 18 F]FDG uptake was in the range of uptake values measured in GLI and PAN. By accumulating [ 18 F]FDG in a manner analogous to uptake by tumour cells, activated HMMs may contribute to the [ 18 F]FDG uptake values measured by PET in neoplasms. (orig.)

Plant traits related to nitrogen uptake influence plant-microbe competition.

Science.gov (United States)

Moreau, Delphine; Pivato, Barbara; Bru, David; Busset, Hugues; Deau, Florence; Faivre, Céline; Matejicek, Annick; Strbik, Florence; Philippot, Laurent; Mougel, Christophe

2015-08-01

Plant species are important drivers of soil microbial communities. However, how plant functional traits are shaping these communities has received less attention though linking plant and microbial traits is crucial for better understanding plant-microbe interactions. Our objective was to determine how plant-microbe interactions were affected by plant traits. Specifically we analyzed how interactions between plant species and microbes involved in nitrogen cycling were affected by plant traits related to 'nitrogen nutrition in interaction with soil nitrogen availability. Eleven plant species, selected along an oligotrophic-nitrophilic gradient, were grown individually in a nitrogen-poor soil with two levels of nitrate availability. Plant traits for both carbon and nitrogen nutrition were measured and the genetic structure and abundance of rhizosphere. microbial communities, in particular the ammonia oxidizer and nitrate reducer guilds, were analyzed. The structure of the bacterial community in the rhizosphere differed significantly between plant species and these differences depended on nitrogen availability. The results suggest that the rate of nitrogen uptake per unit of root biomass and per day is a key plant trait, explaining why the effect of nitrogen availability on the structure of the bacterial community depends on the plant species. We also showed that the abundance of nitrate reducing bacteria always decreased with increasing nitrogen uptake per unit of root biomass per day, indicating that there was competition for nitrate between plants and nitrate reducing bacteria. This study demonstrates that nitrate-reducing microorganisms may be adversely affected by plants with a high nitrogen uptake rate. Our work puts forward the role of traits related to nitrogen in plant-microbe interactions, whereas carbon is commonly considered as the main driver. It also suggests that plant traits related to ecophysiological processes, such as nitrogen uptake rates, are more

Uptake of antibiotics by human polymorphonuclear leukocyte cytoplasts

International Nuclear Information System (INIS)

Hand, W.L.; King-Thompson, N.L.

1990-01-01

Enucleated human polymorphonuclear leukocytes (PMN cytoplasts), which have no nuclei and only a few granules, retain many of the functions of intact neutrophils. To better define the mechanisms and intracellular sites of antimicrobial agent accumulation in human neutrophils, we studied the antibiotic uptake process in PMN cytoplasts. Entry of eight radiolabeled antibiotics into PMN cytoplasts was determined by means of a velocity gradient centrifugation technique. Uptakes of these antibiotics by cytoplasts were compared with our findings in intact PMN. Penicillin entered both intact PMN and cytoplasts poorly. Metronidazole achieved a concentration in cytoplasts (and PMN) equal to or somewhat less than the extracellular concentration. Chloramphenicol, a lipid-soluble drug, and trimethoprim were concentrated three- to fourfold by cytoplasts. An unusual finding was that trimethroprim, unlike other tested antibiotics, was accumulated by cytoplasts more readily at 25 degrees C than at 37 degrees C. After an initial rapid association with cytoplasts, cell-associated imipenem declined progressively with time. Clindamycin and two macrolide antibiotics (roxithromycin, erythromycin) were concentrated 7- to 14-fold by cytoplasts. This indicates that cytoplasmic granules are not essential for accumulation of these drugs. Adenosine inhibited cytoplast uptake of clindamycin, which enters intact phagocytic cells by the membrane nucleoside transport system. Roxithromycin uptake by cytoplasts was inhibited by phagocytosis, which may reduce the number of cell membrane sites available for the transport of macrolides. These studies have added to our understanding of uptake mechanisms for antibiotics which are highly concentrated in phagocytes

Electrochemical Label-Free Aptasensor for Specific Analysis of Dopamine in Serum in the Presence of Structurally Related Neurotransmitters

DEFF Research Database (Denmark)

Álvarez-Martos, Isabel; Ferapontova, Elena

2016-01-01

Cellular and brain metabolism of dopamine can be correlated with a number of neurodegenerative disorders, and as such, in vivo analysis of dopamine in the presence of structurally related neurotransmitters (NT) represents a holy grail of neuroscience. Interference from those NTs generally does...

[14C]-Sucrose uptake by guard cell protoplasts of pisum sativum, argenteum mutant

International Nuclear Information System (INIS)

Rohrig, K.; Raschke, K.

1991-01-01

Guard cells rely on import for their supply with reduced carbon. The authors tested by silicone oil centrifugation the ability of guard cell protoplasts to accumulated [ 14 C]-sucrose. Uptake rates were corrected after measurement of 14 C-sorbitol and 3 H 2 O spaces. Sucrose uptake followed biphasic kinetics, with a high-affinity component below 1 mM external sucrose (apparent K m 0.8 mM at 25C) and a low-affinity nonsaturable component above. Uptake depended on pH (optimum at pH 5.0). Variations in the concentrations of external KCl, CCCP, and valinomycin indicated that about one-half of the sucrose uptake rate could be related to an electrochemical gradient across the plasmalemma. Total uptake rates measured at 5 mM external sucrose seem to be sufficient to replenish emptied plastids with starch within a few hours

Rac1- a novel regulator of contraction-stimulated glucose uptake in skeletal muscle

DEFF Research Database (Denmark)

Sylow, Lykke; Møller, Lisbeth L V; Kleinert, Maximilian

2014-01-01

-stimulated glucose uptake in skeletal muscle, since muscle-specific Rac1 knockout mice display reduced ex vivo contraction- and in vivo exercise-stimulated glucose uptake in skeletal muscle. The molecular mechanisms by which Rac1 regulate glucose uptake is presently unknown. However, recent studies link Rac1......Muscle contraction stimulates muscle glucose uptake by facilitating translocation of the glucose transporter 4 from intracellular locations to the cell surface, which allows for diffusion of glucose into the myofibers. However, the intracellular mechanisms regulating this process are not well...... understood. The GTPase, Rac1 has, until recently, only been investigated with regards to its involvement in insulin-stimulated glucose uptake. However, we recently found that Rac1 is activated during muscle contraction and exercise in mice and humans. Remarkably, Rac1 seems to be necessary for exercise/contraction...

NEUROTRANSMITTERS AND IMMUNITY: 1. DOPAMINE

Directory of Open Access Journals (Sweden)

Lucian Hritcu

2007-08-01

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

Cadmium uptake by tobacco as affected by liming, N form, and year of cultivation

International Nuclear Information System (INIS)

Tsadilas, C.D.; Karaivazoglou, N.A.; Tsotsolis, N.C.; Stamatiadis, S.; Samaras, V.

2005-01-01

Tobacco is able to accumulate cadmium and reduction of cadmium content can reduce health hazards to smokers. Soil pH and form of N fertilizers are among the factors affecting Cd uptake by tobacco. This hypothesis was tested in an acid soil in northern Greece by a four year field experiment. The variability of Cd uptake by tobacco was attributed to the variation of soil Cd availability as affected by soil pH. Liming with 3000 kg Ca(OH) 2 ha -1 increased soil pH by 0.8 units and decreased extractable with DTPA soil and leaf Cd by 40% and 35%, respectively. The ammonium fertilizer caused the opposite, but weaker, effects. Liming reduced soil Cd more in the ammonium treatment than in nitrate or combined N treatments. The year of cultivation strongly affected soil and leaf Cd. Four years after tobacco cultivation, soil pH was reduced by 0.5 units, whereas soil and leaf Cd reduction was more than 60% in the limed treatments. Liming affected Cd uptake only in the first three years of cultivation. - Liming and N form affect Cd uptake by Virginia tobacco which contributes significantly to the great reduction of extractable soil Cd after three years of continuous cultivation

Downstream mechanisms of nitric oxide-mediated skeletal muscle glucose uptake during contraction.

Science.gov (United States)

Merry, Troy L; Lynch, Gordon S; McConell, Glenn K

2010-12-01

There is evidence that nitric oxide (NO) is required for the normal increases in skeletal muscle glucose uptake during contraction, but the mechanisms involved have not been elucidated. We examined whether NO regulates glucose uptake during skeletal muscle contractions via cGMP-dependent or cGMP-independent pathways. Isolated extensor digitorum longus (EDL) muscles from mice were stimulated to contract ex vivo, and potential NO signaling pathways were blocked by the addition of inhibitors to the incubation medium. Contraction increased (P contraction by ∼50% (P contraction; however, DTT attenuated (P contraction-stimulated glucose uptake (by 70%). NOS inhibition and antioxidant treatment reduced contraction-stimulated increases in protein S-glutathionylation and tyrosine nitration (P skeletal muscle glucose uptake during ex vivo contractions via a cGMP/PKG-, AMPK-, and p38 MAPK-independent pathway. In addition, it appears that NO and ROS may regulate skeletal muscle glucose uptake during contraction through a similar pathway.

Effect of amine uptake inhibitors on the uptake of 14C-bretylium in intact and degenerating sympathetic nerves of the rat

International Nuclear Information System (INIS)

Almgren, O.

1981-01-01

The effect of different amine uptake inhibitors on the accumulation of 14 C-bretylium in sympathetically denervated or decentralized salivary glands were studied in vivo in rats 11-14 hours after the surgical intervention. The time period chosen is known to be critical for the delaying effect of bretylium on the degeneration transmitter release in sympathetically innervated organs. Cocaine, desmethylimipramine (DMI), protriptyline or reserpine all depressed the uptake of 14 C-bretylium in both denervated and decentralized salivary glands, cocaine being the most efficient one. DMI and protriptyline, but not cocaine inhibit the degeneration delaying effect of bretylium, while all three agents inhibit amine uptake at level of the nerve cell membrane. Apparently, bretylium reaches the critical sites of its degeneration delaying action by the axonal amine pump but only a small fraction of the drug entering the degenerating adrenergic nerve terminal is needed at the critical sites to interact with the degeneration processes. The difference between the tricyclic antidepressants on one hand and cocaine on the other with respect to the effect on the degeneration delaying action of bretylium, must depend on some action different from the axonal membrane uptake inhibition. Reserpine which is known not to interfere with the delaying effect of bretylium on the denervation degeneration did reduce the uptake of 14 C-bretylium. This fact seems to indicate that the site of action of bretylium is located outside the adrenergic nerve granules. (author)

A Preliminary Study of Gene Polymorphisms Involved in the Neurotransmitters Metabolism of a Homogeneous Spanish Autistic Group

Science.gov (United States)

Calahorro, Fernando; Alejandre, Encarna; Anaya, Nuria; Guijarro, Teresa; Sanz, Yolanza; Romero, Auxiliadora; Tienda, Pilar; Burgos, Rafael; Gay, Eudoxia; Sanchez, Vicente; Ruiz-Rubio, Manuel

2009-01-01

Twin studies have shown a strong genetic component for autism. Neurotransmitters, such as serotonin and catecholamines, have been suggested to play a role in the disease since they have an essential function in synaptogenesis and brain development. In this preliminary study, polymorphism of genes implicated in the serotonergic and dopaminergic…

Warmer temperatures reduce net carbon uptake, but not water use, in a mature southern Appalachian forest

Science.gov (United States)

Increasing air temperature is expected to extend growing season length in temperate, broadleaf forests, leading to potential increases in evapotranspiration and net carbon uptake. However, other key processes affecting water and carbon cycles are also highly temperature-dependent...

An Investigation into the Effects of Peptide Neurotransmitters and Intracellular Second Messengers in Rat Central Neurons in Culture.

Science.gov (United States)

1988-02-04

Purkinje neurons. 3. Neuromodulation of synaptic efficacy in an invertebrate preparation that may be a useful model system for the actions of histamine in...neurotransmitters, neuromodulators , affect brain function. Nerve cells are the functional units of the brain, and changes in neuronal activity are ultimately

Thyroid Scan and Uptake

Medline Plus

Full Text Available ... for a thyroid scan is 30 minutes or less. Thyroid Uptake You will be given radioactive iodine (I-123 or I-131) in liquid or capsule form to swallow. The thyroid uptake will begin several hours to 24 hours later. Often, two separate uptake ...

Amphetamine, 3,4-methylenedioxymethamphetamine, lysergic acid diethylamide, and metabolites of the catecholamine neurotransmitters are agonists of a rat trace amine receptor.

Science.gov (United States)

Bunzow, J R; Sonders, M S; Arttamangkul, S; Harrison, L M; Zhang, G; Quigley, D I; Darland, T; Suchland, K L; Pasumamula, S; Kennedy, J L; Olson, S B; Magenis, R E; Amara, S G; Grandy, D K

2001-12-01

The trace amine para-tyramine is structurally and functionally related to the amphetamines and the biogenic amine neurotransmitters. It is currently thought that the biological activities elicited by trace amines such as p-tyramine and the psychostimulant amphetamines are manifestations of their ability to inhibit the clearance of extracellular transmitter and/or stimulate the efflux of transmitter from intracellular stores. Here we report the discovery and pharmacological characterization of a rat G protein-coupled receptor that stimulates the production of cAMP when exposed to the trace amines p-tyramine, beta-phenethylamine, tryptamine, and octopamine. An extensive pharmacological survey revealed that psychostimulant and hallucinogenic amphetamines, numerous ergoline derivatives, adrenergic ligands, and 3-methylated metabolites of the catecholamine neurotransmitters are also good agonists at the rat trace amine receptor 1 (rTAR1). These results suggest that the trace amines and catecholamine metabolites may serve as the endogenous ligands of a novel intercellular signaling system found widely throughout the vertebrate brain and periphery. Furthermore, the discovery that amphetamines, including 3,4-methylenedioxymethamphetamine (MDMA; "ecstasy"), are potent rTAR1 agonists suggests that the effects of these widely used drugs may be mediated in part by this receptor as well as their previously characterized targets, the neurotransmitter transporter proteins.

Identification of a single sinusoidal bile salt uptake system in skate liver

International Nuclear Information System (INIS)

Fricker, G.; Hugentobler, G.; Meier, P.J.; Kurz, G.; Boyer, J.L.

1987-01-01

To identify the sinusoidal bile acid uptake system(s) of skate liver, photoaffinity labeling and kinetic transport studies were performed in isolated plasma membranes as well as intact hepatocytes. In both preparations photoaffinity labeling with the photolabile bile salt derivative revealed the presence of a predominant bile salt binding polypeptide with an apparent molecular weight of 54,000. The [ 3 H]-labeling of this polypeptide was inhibited by taurocholate and cholate in a concentration-dependent manner and was virtually abolished by 1 mM of the anion transport inhibitor 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid. Kinetic studies of hepatic uptake with taurocholate, cholate, and the photoreactive bile salt derivative indicated the involvement of a single transport system, and all three substrates mutually competed with the uptake of each other. Finally, irreversible inhibition of the bile salt uptake system of photoaffinity labeling of hepatocytes with high concentrations of photolabile derivative reduced the V max but the K m of taurocholate uptake. These findings strongly indicate that a single polypeptide with an apparent molecular weight of 54,000 is involved in sinusoidal bile salt uptake into skate hepatocytes. These findings contrast with similar studies in rat liver that implicate both a 54,000- and 48,000-K polypeptide in bile salt uptake and are consistent with a single Na + -independent transport mechanism for hepatic bile salt uptake in this primitive vertebrate

Impact of Silver and Iron Nanoparticle Exposure on Cholesterol Uptake by Macrophages

Directory of Open Access Journals (Sweden)

Jonathan H. Shannahan

2015-01-01

Full Text Available Macrophages are central to the development of atherosclerosis by absorbing lipids, promoting inflammation, and increasing plaque deposition. Nanoparticles (NPs are becoming increasingly common in biomedical applications thereby increasing exposure to the immune and vascular systems. This project investigated the influence of NPs on macrophage function and specifically cholesterol uptake. Macrophages were exposed to 20 nm silver NPs (AgNPs, 110 nm AgNPs, or 20 nm Fe3O4 NPs for 2 h and NP uptake, cytotoxicity, and subsequent uptake of fluorescently labeled cholesterol were assessed. Macrophage uptake of NPs did not induce cytotoxicity at concentrations utilized (25 μg/mL; however, macrophage exposure to 20 nm AgNPs reduced subsequent uptake of cholesterol. Further, we assessed the impact of a cholesterol-rich environment on macrophage function following NP exposure. In these sets of experiments, macrophages internalized NPs, exhibited no cytotoxicity, and altered cholesterol uptake. Alterations in the expression of scavenger receptor-B1 following NP exposure, which likely influences cholesterol uptake, were observed. Overall, NPs alter cholesterol uptake, which may have implications in the progression of vascular or immune mediated diseases. Therefore, for the safe development of NPs for biomedical applications, it is necessary to understand their impact on cellular function and biological interactions in underlying disease environments.

A preliminary assessment on the use of biochar as a soil additive for reducing soil-to-plant uptake of cesium isotopes in radioactively contaminated environments

International Nuclear Information System (INIS)

Hamilton, T.F.; Martinelli, R.E.; Kehl, S.R.; Peters, S.K.G.; Tamblin, M.W.; Schmitt, C.L.; Hawk, Daniel

2016-01-01

A series of K d tracer batch experiments were conducted to assess the absorptive-desorption properties of Biochar as a potential agent to selectively sequester labile soil Cs or otherwise help reduce the uptake of Cs isotopes into plants. A parallel experiment was conducted for strontium. Fine-grained fractionated Woodlands tree Biochar was found to have a relatively high affinity for Cs ions (K d > 100) relative to coral soil (K d < 10) collected from the Marshall Islands. The Biochar material also contains an abundance of K (and Mg). These findings support a hypothesis that the addition of Biochar as a soil amendment may provide a simple yet effective method for reducing soil-to-plant transfer of Cs isotopes in contaminated environments. (author)

Channel-mediated and carrier-mediated uptake of K+ into cultured ovine oligodendrocytes

Energy Technology Data Exchange (ETDEWEB)

Hertz, L.; Soliven, B.; Hertz, E.; Szuchet, S.; Nelson, D.J. (Univ. of Saskatchewan, Saskatoon (Canada))

1990-01-01

Uptake of radioactive K+ by mature ovine oligodendrocytes (OLGs) maintained in primary culture was measured under steady-state conditions, i.e., in cells maintained in a normal tissue culture medium (5.4 mM K+), and in cells after depletion of intracellular K+ to less than 15% of its normal value by pre-incubation in K(+)-free medium. The latter value is dominated by an active, carrier-mediated uptake (although it may include some diffusional uptake), whereas the former, in addition to active uptake, also reflects passive K+ diffusion through ion selective channels and possible self-exchange between extracellular and intracellular K+, which may be carrier-mediated. The total uptake rate was 144 +/- 10 nmol/min/mg protein, and the uptake after K+ depletion was 60 +/- 2 nmol/min/mg protein, much lower rates than previously observed in astrocytes. The uptake into K(+)-depleted cells was inhibited by about 80% in the presence of ouabain (1 mM) and about 30% in the presence of furosemide (2 mM). Activators of protein kinase C (phorbol esters) and cAMP-dependent protein kinase (forskolin) have been shown to alter the myelinogenic metabolism as well as outward K+ current in cultured OLGs. The present study demonstrates that K+ homeostasis in OLGs is modulated through similar second messenger pathways. Active uptake was inhibited by about 60% in the presence of active phorbol esters (100 nM) but was not affected by forskolin (100 nM). Forskolin likewise had no effect on total uptake, whereas phorbol esters caused a much larger inhibition than expected from their effect on carrier-mediated uptake alone, suggesting that channel-mediated uptake was also reduced.

Neurotransmitter regulation of adult neurogenesis: putative therapeutic targets.

Science.gov (United States)

Vaidya, V A; Vadodaria, K C; Jha, S

2007-10-01

The evidence that new neuron addition takes place in the mammalian brain throughout adult life has dramatically altered our perspective of the potential for plasticity in the adult CNS. Although several recent reports suggest a latent neurogenic capacity in multiple brain regions, the two major neurogenic niches that retain the ability to generate substantial numbers of new neurons in adult life are the subventricular zone (SVZ) lining the lateral ventricles and the subgranular zone (SGZ) in the hippocampal formation. The discovery of adult neurogenesis has also unveiled a novel therapeutic target for the repair of damaged neuronal circuits. In this regard, understanding the endogenous mechanisms that regulate adult neurogenesis holds promise both for a deeper understanding of this form of structural plasticity, as well as the identification of pathways that can serve as therapeutic targets to manipulate adult neurogenesis. The purpose of the present review is to discuss the regulation of adult neurogenesis by neurotransmitters and to highlight the relevance of these endogenous regulators as targets to modulate adult neurogenesis in a clinical context.

Effects of urban stream burial on nitrogen uptake and ...

Science.gov (United States)

Urbanization has resulted in extensive burial and channelization of headwater streams, yet little is known about impacts on stream ecosystem functions critical for reducing downstream nitrogen pollution. To characterize the biogeochemical impact of stream burial, we measured NO3- uptake, using 15N-NO3- isotope tracer releases, and whole stream metabolism, during four seasons in three paired buried and open streams reaches within the Baltimore Ecosystem Study Long-term Ecological Research Network. Stream burial increased NO3- uptake lengths, by a factor of 7.5 (p < 0.01) and decreased nitrate uptake velocity and areal nitrate uptake rate by factors of 8.2 (p = 0.01) and 9.6 (p < 0.001), respectively. Stream burial decreased gross primary productivity by a factor of 9.2 (p < 0.05) and decreased ecosystem respiration by a factor of 4.2 (p = 0.06). From statistical analysis of Excitation Emissions Matrices (EEMs), buried streams were also found to have significantly less labile dissolved organic matter. Furthermore, buried streams had significantly lower transient storage and water temperatures. Overall, differences in NO3- uptake and metabolism were primarily explained by decreased transient storage and light availability in buried streams. We estimate that stream burial increases daily watershed nitrate export by as much as 500% due to decreased in-stream retention and may considerably decrease carbon export via decreased primary production. These results

Plant uptake and availability of antimony, lead, copper and zinc in oxic and reduced shooting range soil.

Science.gov (United States)

Hockmann, Kerstin; Tandy, Susan; Studer, Björn; Evangelou, Michael W H; Schulin, Rainer

2018-03-19

Shooting ranges polluted by antimony (Sb), lead (Pb), copper (Cu) and zinc (Zn) are used for animal grazing, thus pose a risk of contaminants entering the food chain. Many of these sites are subject to waterlogging of poorly drained soils. Using field lysimeter experiments, we compared Sb, Pb, Cu and Zn uptake by four common pasture plant species (Lolium perenne, Trifolium repens, Plantago lanceolata and Rumex obtusifolius) growing on a calcareous shooting range soil under waterlogged and drained conditions. To monitor seasonal trends, the same plants were collected at three times over the growing season. Additionally, variations in soil solution concentrations were monitored at three depths over the experiment. Under reducing conditions, soluble Sb concentrations dropped from ∼50 μg L -1 to ∼10 μg L -1 , which was attributed to the reduction of Sb(V) to Sb(III) and the higher retention of the trivalent species by the soil matrix. Shoot Sb concentrations differed by a factor of 60 between plant species, but remained at levels <0.3 μg g -1 . Despite the difference in soil solution concentrations between treatments, total Sb accumulation in shoots for plants collected on the waterlogged soil did not change, suggesting that Sb(III) was much more available for plant uptake than Sb(V), as only 10% of the total Sb was present as Sb(III). In contrast to Sb, Pb, Cu and Zn soil solution concentrations remained unaffected by waterlogging, and shoot concentrations were significantly higher in the drained treatment for many plant species. Although showing an increasing trend over the season, shoot metal concentrations generally remained below regulatory values for fodder plants (40 μg g -1  Pb, 150 μg g -1 Zn, 15-35 μg g -1 Cu), indicating a low risk of contaminant transfer into the food chain under both oxic and anoxic conditions for the type of shooting range soil investigated in this study. Copyright © 2018 Elsevier Ltd. All rights

Sphagnum mosses--masters of efficient N-uptake while avoiding intoxication.

Science.gov (United States)

Fritz, Christian; Lamers, Leon P M; Riaz, Muhammad; van den Berg, Leon J L; Elzenga, Theo J T M

2014-01-01

Peat forming Sphagnum mosses are able to prevent the dominance of vascular plants under ombrotrophic conditions by efficiently scavenging atmospherically deposited nitrogen (N). N-uptake kinetics of these mosses are therefore expected to play a key role in differential N availability, plant competition, and carbon sequestration in Sphagnum peatlands. The interacting effects of rain N concentration and exposure time on moss N-uptake rates are, however, poorly understood. We investigated the effects of N-concentration (1, 5, 10, 50, 100, 500 µM), N-form ((15)N-ammonium or nitrate) and exposure time (0.5, 2, 72 h) on uptake kinetics for Sphagnum magellanicum from a pristine bog in Patagonia (Argentina) and from a Dutch bog exposed to decades of N-pollution. Uptake rates for ammonium were higher than for nitrate, and N-binding at adsorption sites was negligible. During the first 0.5 h, N-uptake followed saturation kinetics revealing a high affinity (Km 3.5-6.5 µM). Ammonium was taken up 8 times faster than nitrate, whereas over 72 hours this was only 2 times. Uptake rates decreased drastically with increasing exposure times, which implies that many short-term N-uptake experiments in literature may well have overestimated long-term uptake rates and ecosystem retention. Sphagnum from the polluted site (i.e. long-term N exposure) showed lower uptake rates than mosses from the pristine site, indicating an adaptive response. Sphagnum therefore appears to be highly efficient in using short N pulses (e.g. rainfall in pristine areas). This strategy has important ecological and evolutionary implications: at high N input rates, the risk of N-toxicity seems to be reduced by lower uptake rates of Sphagnum, at the expense of its long-term filter capacity and related competitive advantage over vascular plants. As shown by our conceptual model, interacting effects of N-deposition and climate change (changes in rainfall) will seriously alter the functioning of Sphagnum peatlands.

Sphagnum Mosses - Masters of Efficient N-Uptake while Avoiding Intoxication

Science.gov (United States)

Fritz, Christian; Lamers, Leon P. M.; Riaz, Muhammad; van den Berg, Leon J. L.; Elzenga, Theo J. T. M.

2014-01-01

Peat forming Sphagnum mosses are able to prevent the dominance of vascular plants under ombrotrophic conditions by efficiently scavenging atmospherically deposited nitrogen (N). N-uptake kinetics of these mosses are therefore expected to play a key role in differential N availability, plant competition, and carbon sequestration in Sphagnum peatlands. The interacting effects of rain N concentration and exposure time on moss N-uptake rates are, however, poorly understood. We investigated the effects of N-concentration (1, 5, 10, 50, 100, 500 µM), N-form (15N - ammonium or nitrate) and exposure time (0.5, 2, 72 h) on uptake kinetics for Sphagnum magellanicum from a pristine bog in Patagonia (Argentina) and from a Dutch bog exposed to decades of N-pollution. Uptake rates for ammonium were higher than for nitrate, and N-binding at adsorption sites was negligible. During the first 0.5 h, N-uptake followed saturation kinetics revealing a high affinity (Km 3.5–6.5 µM). Ammonium was taken up 8 times faster than nitrate, whereas over 72 hours this was only 2 times. Uptake rates decreased drastically with increasing exposure times, which implies that many short-term N-uptake experiments in literature may well have overestimated long-term uptake rates and ecosystem retention. Sphagnum from the polluted site (i.e. long-term N exposure) showed lower uptake rates than mosses from the pristine site, indicating an adaptive response. Sphagnum therefore appears to be highly efficient in using short N pulses (e.g. rainfall in pristine areas). This strategy has important ecological and evolutionary implications: at high N input rates, the risk of N-toxicity seems to be reduced by lower uptake rates of Sphagnum, at the expense of its long-term filter capacity and related competitive advantage over vascular plants. As shown by our conceptual model, interacting effects of N-deposition and climate change (changes in rainfall) will seriously alter the functioning of Sphagnum peatlands

Gbu Glycine Betaine Porter and Carnitine Uptake in Osmotically Stressed Listeria monocytogenes Cells

Science.gov (United States)

Mendum, Mary Lou; Smith, Linda Tombras

2002-01-01

The food-borne pathogen Listeria monocytogenes grows actively under high-salt conditions by accumulating compatible solutes such as glycine betaine and carnitine from the medium. We report here that the dominant transport system for glycine betaine uptake, the Gbu porter, may act as a secondary uptake system for carnitine, with a Km of 4 mM for carnitine uptake and measurable uptake at carnitine concentrations as low as 10 μM. This porter has a Km for glycine betaine uptake of about 6 μM. The dedicated carnitine porter, OpuC, has a Km for carnitine uptake of 1 to 3 μM and a Vmax of approximately 15 nmol/min/mg of protein. Mutants lacking either opuC or gbu were used to study the effects of four carnitine analogs on growth and uptake of osmolytes. In strain DP-L1044, which had OpuC and the two glycine betaine porters Gbu and BetL, triethylglycine was most effective in inhibiting growth in the presence of glycine betaine, but trigonelline was best at inhibiting growth in the presence of carnitine. Carnitine uptake through OpuC was inhibited by γ-butyrobetaine. Dimethylglycine inhibited both glycine betaine and carnitine uptake through the Gbu porter. Carnitine uptake through the Gbu porter was inhibited by triethylglycine. Glycine betaine uptake through the BetL porter was strongly inhibited by trigonelline and triethylglycine. These results suggest that it is possible to reduce the growth of L. monocytogenes under osmotically stressful conditions by inhibiting glycine betaine and carnitine uptake but that to do so, multiple uptake systems must be affected. PMID:12406761

Barriers and facilitators to the uptake of voluntary medical male ...

African Journals Online (AJOL)

VMMC) among adolescent boys in KwaZulu–Natal, South Africa. ... Individual cognitive factors facilitating uptake included the belief that VMMC reduced the risk of HIV infection, led to better hygiene and improvement in sexual desirability and ...

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.

Uptake and localization of sup(99m)technetium-methylene-diphosphonate in bone

International Nuclear Information System (INIS)

Savelkoul, T.J.F.

1984-01-01

The author investigated the uptake and localization of 99m-technetium-methylene-diphosphonate (99m-Tc-MDP) in bone, to develop a sensitive mean for the detection of early osseous disease. In an electrolysis procedure without the presence of contaminating reductants a 99m-Tc-MDP complex is formed with clear bone-seeking properties. The scans performed in experimental animals are comparable in quality with 99m-Tc(Sn)-MDP scans. The uptake of 99m-Tc-MDP is faster and higher than the uptake of reduced hydrolyzed 99m-Tc. Uptake of 99m-Tc(Sn)-MDP in bone can only take place after decomposition of the complex. As 99m-Tc-MDP is taken up as a unit, this may be a better agent to evaluate the osteoblastic activity in the skeleton. (Auth./R.B.)

Role of diacylglycerol in adrenergic-stimulated sup 86 Rb uptake by proximal tubules

Energy Technology Data Exchange (ETDEWEB)

Baines, A.D.; Drangova, R.; Ho, P. (Univ. of Toronto, Ontario (Canada))

1990-05-01

We used rat proximal tubule fragments purified by Percoll centrifugation to examine the role of diacylglycerol (DAG) in noradrenergic-stimulated Na+ reabsorption. Tubular DAG concentration and ouabain-inhibitable 86Rb uptake increased within 30 s after adding norepinephrine (NE) and remained elevated for at least 5 min. NE (1 microM) increased DAG content 17% and ouabain-inhibitable 86Rb uptake 23%. Cirazoline-stimulated 86Rb uptake was not inhibited by BaCl, quinidine, or bumetanide (1-10 microM) or by the omission of HCO3- or Cl- from the medium, but it was completely inhibited by ouabain and furosemide. Oleoyl-acetyl glycerol, L-alpha-1,2-dioctanoylglycerol, and L-alpha-1,2-dioleoylglycerol (DOG) increased total 86Rb uptake 8-11%. 12-O-tetradecanoylphorbol-13-acetate (TPA) (5 nM) increased uptake by only 4%. Staurosporine at 5 nM inhibited DOG stimulation completely, whereas 50 nM staurosporine was required to inhibit NE stimulation completely. Sphingosine inhibited DOG stimulation by 66% but did not inhibit NE stimulation. Amiloride (1 mM) completely blocked DOG stimulation. Monensin increased 86Rb uptake 31% and completely blocked the DOG effect but reduced the NE effect by only 26% (P = 0.08). In tubules from salt-loaded rats, NE did not increase DAG concentration, but NE-stimulated 86Rb uptake was reduced by only 23% (P = 0.15). Thus DAG released by NE may stimulate Na+ entry through Na(+)-H+ exchange. NE predominantly stimulates Na(+)-K(+)-adenosinetriphosphatase (ATPase) by activating a protein kinase that is insensitive to DAG and TPA and is inhibited by staurosporine but not by sphingosine. NE may also stimulate K+ efflux through a BaCl-insensitive K+ channel that is inhibited by millimolar furosemide.

The levels of monoamine neurotransmitters and measures of mental and emotional health in HCV patients treated with ledipasvir (LDV) and sofosbuvir (SOF) with or without ribavirin (RBV).

Science.gov (United States)

Golabi, Pegah; Elsheikh, Elzafir; Karrar, Azza; Estep, James M; Younossi, Issah; Stepanova, Maria; Gerber, Lynn; Younossi, Zobair M

2016-11-01

Mental and emotional health (MEH) impairment is commonly encountered in hepatitis C patients. Although the exact mechanism remains unknown, alterations in neurotransmitter and cytokine levels maybe associated with hepatitis C virus (HCV)-related MEH issues.The aim of the study was to assess association of serum biomarkers with self-reports of MEH in HCV patients before treatment and after achieving sustained virologic response (SVR).The HCV genotype-1-infected patients who achieved SVR at 12 weeks after treatment with ledipasvir (LDV)/sofosbuvir (SOF) ± ribavirin (RBV) were selected. Frozen serum samples from baseline, end of treatment (EOT), and posttreatment week 4 (PTW4) were used to assay 16 cytokines and monoamine neurotransmitters. Validated self-reports were used to assess MEH.Hundred patients were evaluated. Mean age was 53 years (57% male, 86% white). Compared with baseline, emotional well-being and emotional health significantly increased by EOT, and role emotional, emotional well-being, and emotional health significantly increased at PTW4 in the RBV-containing arm (P neurotransmitters and cytokines were found to be independent predictors of MEH scores in multiple regression analysis.Cytokine and neurotransmitter changes are associated with mental and emotional health. Patient-reported outcome scores change during and after treatment.

New caged neurotransmitter analogs selective for glutamate receptor sub-types based on methoxynitroindoline and nitrophenylethoxycarbonyl caging groups

Czech Academy of Sciences Publication Activity Database

Palma-Cerda, F.; Auger, C.; Crawford, D.J.; Hodgson, A.C.C.; Reynolds, S.J.; Cowell, J.K.; Swift, K.A.D.; Cais, Ondřej; Vyklický ml., Ladislav; Corrie, J.E.T.; Ogden, D.

2012-01-01

Roč. 63, č. 4 (2012), s. 624-634 ISSN 0028-3908 R&D Projects: GA ČR(CZ) GA309/07/0271 Grant - others:EC(XE) LSHM-CT-2007-037765 Institutional research plan: CEZ:AV0Z50110509 Keywords : photolysis * glutamate receptors * caged neurotransmitters Subject RIV: ED - Physiology Impact factor: 4.114, year: 2012

Uptake of nuclides by plants

International Nuclear Information System (INIS)

Greger, Maria

2004-04-01

This review on plant uptake of elements has been prepared to demonstrate how plants take up different elements. The work discusses the nutrient elements, as well as the general uptake and translocation in plants, both via roots and by foliar absorption. Knowledge of the uptake by the various elements within the periodic system is then reviewed. The work also discusses transfer factors (TF) as well as difficulties using TF to understand the uptake by plants. The review also focuses on species differences. Knowledge necessary to understand and calculate plant influence on radionuclide recirculation in the environment is discussed, in which the plant uptake of a specific nuclide and the fate of that nuclide in the plant must be understood. Plants themselves determine the uptake, the soil/sediment determines the availability of the nuclides and the nuclides themselves can interact with each other, which also influences the uptake. Consequently, it is not possible to predict the nuclide uptake in plants by only analysing the nuclide concentration of the soil/substrate

Uptake of nuclides by plants

Energy Technology Data Exchange (ETDEWEB)

Greger, Maria [Stockholm Univ. (Sweden). Dept. of Botany

2004-04-01

This review on plant uptake of elements has been prepared to demonstrate how plants take up different elements. The work discusses the nutrient elements, as well as the general uptake and translocation in plants, both via roots and by foliar absorption. Knowledge of the uptake by the various elements within the periodic system is then reviewed. The work also discusses transfer factors (TF) as well as difficulties using TF to understand the uptake by plants. The review also focuses on species differences. Knowledge necessary to understand and calculate plant influence on radionuclide recirculation in the environment is discussed, in which the plant uptake of a specific nuclide and the fate of that nuclide in the plant must be understood. Plants themselves determine the uptake, the soil/sediment determines the availability of the nuclides and the nuclides themselves can interact with each other, which also influences the uptake. Consequently, it is not possible to predict the nuclide uptake in plants by only analysing the nuclide concentration of the soil/substrate.

Uptake and distribution of soil-applied labelled heavy metals in cereal plants and products

International Nuclear Information System (INIS)

Oberlaender, H.E.; Roth, K.

1983-01-01

In the present paper investigations are described on the uptake, distribution and translocation of mercury, cadmium, chromium and zinc by spring and winter varieties of wheat, rye and barley. Pot experiments were carried out at low concentrations of the heavy metals in order to avoid growth interference during the uptake. Using radioisotopes the pathway of the metals was traced through different organs into the milling products. An ion-exchanger was added to the soils and its efficiency of reducing the uptake of the metals by the plants was tested

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

Science.gov (United States)

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.

Uptake of post‑abortion contraception among women who had ...

African Journals Online (AJOL)

Background: Unexpected or unplanned pregnancy poses a major public health challenge in women of reproductive age, especially in low resource countries. Post‑abortion contraception is one of the key methods of reducing maternal mortality globally. Objectives: This study was conducted to determine the uptake of ...

Quantitative understanding of nanoparticle uptake in watermelon plants

Directory of Open Access Journals (Sweden)

Ramesh Raliya

2016-08-01

Full Text Available The use of agrochemical-nutrient fertilizers has come under scrutiny in recent years due to concerns that they damage the ecosystem and endanger public health. Nanotechnology offers many possible interventions to mitigate these risks by use of nanofertilizers, nanopesticides, and nanosensors; and concurrently increases profitability, yields, and sustainability within the agricultural industry. Aerosol based foliar delivery of nanoparticles may help to enhance nanoparticle uptake and reduce environmental impacts of chemical fertilizers conventionally applied through a soil route. The purpose of this work was to study uptake, translocation, and accumulation of various gold nanostructures, 30 to 80 nm, delivered by aerosol application to a watermelon plant. Cellular uptake and accumulation of gold nanoparticles were quantified by Inductively Coupled Plasma-Mass Spectroscopy (ICP-MS. Observations suggested that nanoparticles could be taken up by the plant through direct penetration and transport through the stomatal opening. Observed translocation of nanoparticles from leaf to root shows evidence that nanoparticles travel by the phloem transport mechanism. Accumulation and transport of nanoparticles depend on nanoparticle shape, application method, and nature of plant tissues.

Tau Antibody Targeting Pathological Species Blocks Neuronal Uptake and Interneuron Propagation of Tau in Vitro.

Science.gov (United States)

Nobuhara, Chloe K; DeVos, Sarah L; Commins, Caitlin; Wegmann, Susanne; Moore, Benjamin D; Roe, Allyson D; Costantino, Isabel; Frosch, Matthew P; Pitstick, Rose; Carlson, George A; Hock, Christoph; Nitsch, Roger M; Montrasio, Fabio; Grimm, Jan; Cheung, Anne E; Dunah, Anthone W; Wittmann, Marion; Bussiere, Thierry; Weinreb, Paul H; Hyman, Bradley T; Takeda, Shuko

2017-06-01

The clinical progression of Alzheimer disease (AD) is associated with the accumulation of tau neurofibrillary tangles, which may spread throughout the cortex by interneuronal tau transfer. If so, targeting extracellular tau species may slow the spreading of tau pathology and possibly cognitive decline. To identify suitable target epitopes, we tested the effects of a panel of tau antibodies on neuronal uptake and aggregation in vitro. Immunodepletion was performed on brain extract from tau-transgenic mice and postmortem AD brain and added to a sensitive fluorescence resonance energy transfer-based tau uptake assay to assess blocking efficacy. The antibodies reduced tau uptake in an epitope-dependent manner: N-terminal (Tau13) and middomain (6C5 and HT7) antibodies successfully prevented uptake of tau species, whereas the distal C-terminal-specific antibody (Tau46) had little effect. Phosphorylation-dependent (40E8 and p396) and C-terminal half (4E4) tau antibodies also reduced tau uptake despite removing less total tau by immunodepletion, suggesting specific interactions with species involved in uptake. Among the seven antibodies evaluated, 6C5 most efficiently blocked uptake and subsequent aggregation. More important, 6C5 also blocked neuron-to-neuron spreading of tau in a unique three-chamber microfluidic device. Furthermore, 6C5 slowed down the progression of tau aggregation even after uptake had begun. Our results imply that not all antibodies/epitopes are equally robust in terms of blocking tau uptake of human AD-derived tau species. Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Optimization of ultra-performance liquid chromatography (UPLC) with fluorescence detector (FLD) method for the quantitative determination of selected neurotransmitters in rat brain.

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Stragierowicz, Joanna; Daragó, Adam; Brzeźnicki, Sławomir; Kilanowicz, Anna

2017-07-26

Glutamate (Glu) and γ-aminobutyric acid (GABA) are the main neurotransmitters in the central nervous system for excitatory and inhibitory processes, respectively. Monitoring these neurotransmitters is an essential tool in establishing pathological functions, among others in terms of occupational exposure to toxic substances. We present modification of the HPLC (high-performance liquid chromatography) to the UPLC (ultra-performance liquid chromatography) method for the simultaneous determination of glutamate and γ-aminobutyric acid in a single injection. The isocratic separation of these neurotransmitter derivatives was performed on Waters Acquity BEH (ethylene bridged hybrid) C18 column with particle size of 1.7 μm at 35°C using a mobile phase consisting of 0.1 M acetate buffer (pH 6.0) and methanol (60:40, v/v) at a flow rate of 0.3 ml/min. The analytes were detected with the fluorescence detector (FLD) using derivatization with o-phthaldialdehyde (OPA), resulting in excitation at 340 nm and emission at 455 nm. Several validation parameters including linearity (0.999), accuracy (101.1%), intra-day precision (1.52-1.84%), inter-day precision (2.47-3.12%), limit of detection (5-30 ng/ml) and quantification (100 ng/ml) were examined. The developed method was also used for the determination of these neurotransmitters in homogenates of selected rat brain structures. The presented UPLC-FLD is characterized by shorter separation time (3.5 min), which is an adaptation of the similar HPLC methods and is an alternative for more expensive references techniques such as liquid chromatography coupled with tandem mass-spectrometry (LC-MS/MS) methods. Med Pr 2017;68(5):583-591. This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.

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.

Science.gov (United States)

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.

Pyrethroid insecticides evoke neurotransmitter release from rabbit striatal slices

International Nuclear Information System (INIS)

Eells, J.T.; Dubocovich, M.L.

1988-01-01

The effects of the synthetic pyrethroid insecticide fenvalerate ([R,S]-alpha-cyano-3-phenoxybenzyl[R,S]-2-(4-chlorophenyl)-3- methylbutyrate) on neurotransmitter release in rabbit brain slices were investigated. Fenvalerate evoked a calcium-dependent release of [ 3 H]dopamine and [ 3 H]acetylcholine from rabbit striatal slices that was concentration-dependent and specific for the toxic stereoisomer of the insecticide. The release of [ 3 H]dopamine and [ 3 H]acetylcholine by fenvalerate was modulated by D2 dopamine receptor activation and antagonized completely by the sodium channel blocker, tetrodotoxin. These findings are consistent with an action of fenvalerate on the voltage-dependent sodium channels of the presynaptic membrane resulting in membrane depolarization, and the release of dopamine and acetylcholine by a calcium-dependent exocytotic process. In contrast to results obtained in striatal slices, fenvalerate did not elicit the release of [ 3 H]norepinephrine or [ 3 H]acetylcholine from rabbit hippocampal slices indicative of regional differences in sensitivity to type II pyrethroid actions

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

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

2016-07-01

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

The market dynamics of selective serotonin re-uptake inhibitors: a ...

African Journals Online (AJOL)

re-uptake inhibitors: a private sector study in South Africa. Afri Health ... the public and private sectors to reduce medicine costs, and increase ... Fig 1: Comparison between the market volume of generics vs. originators for the period June 2009 ...

Uptake of acidic and basic sugar derivatives in Lemna gibba G1

International Nuclear Information System (INIS)

Sanz, A.; Ullrich, C.I.

1989-01-01

The uptake of acidic and basic sugar derivatives in Lemna gibba L. was studied. Uronic acids applied to the experimental solution induced a small decrease of the membrane potential. After incubation of the plants in a 0.1 millimolar solution of these substrates, no decrease in the concentration of reducing groups in the external solution was detected. Respiration increased by 31% with 50 millimolar galacturonic acid, whereas no effect was found with the same concentration of glucuronic acid. Glucosamine caused a considerable concentration-dependent membrane depolarization. ( 14 C)glucosamine uptake followed Michaelis-Menten kinetics together with a linear component. Influx of this substrate was inhibited by glucose but the type of competition could not be clearly distinguished. Glucosamine, 50 millimolar, inhibited the respiration rate by 30%. The glucosamine uptake was pH-dependent, with maximum uptake at around pH 7. Lack of enhancement of uptake by low pH as well as the permanent membrane depolarization suggest a uniport mechanism for the charged species of the substrate and an electroneutral diffusion of the uncharged species

Chromate and phosphate inhibited each other's uptake and translocation in arsenic hyperaccumulator Pteris vittata L

International Nuclear Information System (INIS)

Oliveira, Letúzia M. de; Lessl, Jason T.; Gress, Julia; Tisarum, Rujira; Guilherme, Luiz R.G.; Ma, Lena Q.

2015-01-01

We investigated the effects of chromate (CrVI) and phosphate (P) on their uptake and translocation in As-hyperaccumulator Pteris vittata (PV). Plants were exposed to 1) 0.10 mM CrVI and 0, 0.25, 1.25, or 2.50 mM P or 2) 0.25 mM P and 0, 0.50, 2.5 or 5.0 mM CrVI for 24 h in hydroponics. PV accumulated 2919 mg/kg Cr in the roots at CrVI 0.10 , and 5100 and 3500 mg/kg P in the fronds and roots at P 0.25 . When co-present, CrVI and P inhibited each other's uptake in PV. Increasing P concentrations reduced Cr root concentrations by 62–82% whereas increasing CrVI concentrations reduced frond P concentrations by 52–59% but increased root P concentrations by 11–15%. Chromate reduced P transport, with more P being accumulated in PV roots. Though CrVI was supplied, 64−78% and 92−93% CrIII were in PV fronds and roots. Based on X-ray diffraction, Cr 2 O 3 was detected in the roots confirming CrVI reduction to CrIII by PV. In short, CrVI and P inhibited each other in uptake and translocation by PV, and CrVI reduction to CrIII in PV roots served as its detoxification mechanism. The finding helps to understand the interactions of P and Cr during their uptake in PV. - Highlights: • Phosphate and CrVI inhibited each other in uptake and translocation by Pteris vittata. • P. vittata was more efficient in CrVI uptake than CrIII, but little Cr being translocated to the fronds. • CrVI was provided in the media, but 64–78% and 92–93% CrIII were in the fronds and roots of P. vittata. • CrVI was taken up by P. vittata and reduced to CrIII in the roots possibly as Cr 2 O 3 . - Pteris vittata was efficient in CrVI uptake, concentrating in the roots after reducing to CrIII

Simultaneous determination of amino acids and neurotransmitters in plasma samples from schizophrenic patients by hydrophilic interaction liquid chromatography with tandem mass spectrometry.

Science.gov (United States)

Domingues, Diego Soares; Crevelin, Eduardo José; de Moraes, Luiz Alberto Beraldo; Cecilio Hallak, Jaime Eduardo; de Souza Crippa, José Alexandre; Costa Queiroz, Maria Eugênia