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Neurotransmitter Precursor

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https://www.readbyqxmd.com/read/27907050/when-is-the-brain-dead-living-like-electrophysiological-responses-and-photon-emissions-from-applications-of-neurotransmitters-in-fixed-post-mortem-human-brains
#1
Michael A Persinger, Nicolas Rouleau, Nirosha J Murugan, Lucas W E Tessaro, Justin N Costa
The structure of the post-mortem human brain can be preserved by immersing the organ within a fixative solution. Once the brain is perfused, cellular and histological features are maintained over extended periods of time. However, functions of the human brain are not assumed to be preserved beyond death and subsequent chemical fixation. Here we present a series of experiments which, together, refute this assumption. Instead, we suggest that chemical preservation of brain structure results in some retained functional capacity...
2016: PloS One
https://www.readbyqxmd.com/read/27891231/a-pharmacokinetic-evaluation-and-metabolite-identification-of-the-ghb-receptor-antagonist-ncs-382-in-mouse-informs-novel-therapeutic-strategies-for-the-treatment-of-ghb-intoxication
#2
Garrett R Ainslie, K Michael Gibson, Kara R Vogel
Gamma-aminobutyric acid (GABA) is an endogenous inhibitory neurotransmitter and precursor of gamma-hydroxybutyric acid (GHB). NCS-382 (6,7,8,9-tetrahydro-5-hydroxy-5H-benzo-cyclohept-6-ylideneacetic acid), a known GHB receptor antagonist, has shown significant efficacy in a murine model of succinic semialdehyde dehydrogenase deficiency (SSADHD), a heritable neurological disorder featuring chronic elevation of GHB that blocks the final step of GABA degradation. NCS-382 exposures and elimination pathways remain unknown; therefore, the goal of the present work was to obtain in vivo pharmacokinetic data in a murine model and to identify the NCS-382 metabolites formed by mouse and human...
December 2016: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/27873132/mechanisms-of-excessive-extracellular-glutamate-accumulation-in-temporal-lobe-epilepsy
#3
Jan Albrecht, Magdalena Zielińska
There is compelling evidence that initiation and maintenance of epileptic seizures in temporal lobe epilepsy (TLE) is facilitated by excessive accumulation in the extracellular (perisynaptic) space of the excitatory neurotransmitter glutamate (Glu). This review discusses the mechanisms underlying this phenomenon. Glu released from neurons is taken up by astrocytes and activated there by glutamine synthetase (GS) to form glutamine (Gln) which upon entry to neurons is degraded back to Glu by phosphate-activated glutaminase (PAG): this chain of reactions has been defined as the glutamine/glutamate/cycle (GGC)...
November 21, 2016: Neurochemical Research
https://www.readbyqxmd.com/read/27814772/-manganese-induced-neurotoxicity-a-review-of-its-behavioral-consequences-and-neuroprotective-strategies
#4
REVIEW
Tanara V Peres, Maria Rosa C Schettinger, Pan Chen, Fabiano Carvalho, Daiana S Avila, Aaron B Bowman, Michael Aschner
Manganese (Mn) is an essential heavy metal. However, Mn's nutritional aspects are paralleled by its role as a neurotoxicant upon excessive exposure. In this review, we covered recent advances in identifying mechanisms of Mn uptake and its molecular actions in the brain as well as promising neuroprotective strategies. The authors focused on reporting findings regarding Mn transport mechanisms, Mn effects on cholinergic system, behavioral alterations induced by Mn exposure and studies of neuroprotective strategies against Mn intoxication...
November 4, 2016: BMC Pharmacology & Toxicology
https://www.readbyqxmd.com/read/27814246/serum-metabolomic-profiles-in-neonatal-mice-following-oral-brominated-flame-retardant-exposures-to-hexabromocyclododecane-hbcd-alpha-gamma-and-commercial-mixture
#5
David T Szabo, Wimal Pathmasiri, Susan Sumner, Linda S Birnbaum
BACKGROUND: Hexabromocyclododecane (HBCD) is a high production volume brominated flame retardant added to building insulation foams, electronics, and textiles. HBCD is a commercial-mixture (CM-HBCD) composed of 3 main stereoisomers: α-HBCD (10%); β-HBCD (10%); γ-HBCD (80%). A shift from the dominant stereoisomer γ-HBCD to α-HBCD is detected in humans and wildlife. OBJECTIVES: Considering CM-HBCD has been implicated in neurodevelopment and endocrine disruption, with expected metabolism perturbations, metabolomics was performed on mice serum obtained during a window-of-developmental neurotoxicity to draw correlations between early-life exposures, developmental outcomes, and predict health risks...
November 4, 2016: Environmental Health Perspectives
https://www.readbyqxmd.com/read/27798097/genetic-and-pharmacological-correction-of-aberrant-dopamine-synthesis-using-patient-ipscs-with-bh4-metabolism-disorders
#6
Taizo Ishikawa, Keiko Imamura, Takayuki Kondo, Yasushi Koshiba, Satoshi Hara, Hiroshi Ichinose, Mahoko Furujo, Masako Kinoshita, Tomoko Oeda, Jun Takahashi, Ryosuke Takahashi, Haruhisa Inoue
Dopamine (DA) is a neurotransmitter in the brain, playing a central role in several disease conditions, including tetrahydrobiopterin (BH4) metabolism disorders and Parkinson's disease (PD). BH4 metabolism disorders present a variety of clinical manifestations including motor disturbance via altered DA metabolism, since BH4 is a cofactor for tyrosine hydroxylase (TH), a rate-limiting enzyme for DA synthesis. Genetically, BH4 metabolism disorders are, in an autosomal recessive pattern, caused by a variant in genes encoding enzymes for BH4 synthesis or recycling, including 6-pyruvoyltetrahydropterin synthase (PTPS) or quinonoid-dihydropteridine reductase (DHPR), respectively...
October 18, 2016: Human Molecular Genetics
https://www.readbyqxmd.com/read/27787475/enzyme-activities-involved-in-the-glutamate-glutamine-cycle-are-altered-to-reduce-glutamate-after-spinal-cord-injury-in-rats
#7
Araceli Diaz-Ruiz, Sergio Montes, Hermelinda Salgado-Ceballos, Valente Maldonado, Liliana Rivera-Espinosa, Camilo Ríos
Glutamate (Glu) neurotransmitter is involved in the excitotoxic damage after spinal cord injury (SCI). Glu is transformed into glutamine (Gln) by glutamine synthetase (GS) enzyme in glial cells. Once into the neurons, Gln is transformed back into Glu by phosphate-activated glutaminase (PAG). Glu is also a precursor for the synthesis of γ-aminobutyric acid through the action of the glutamic acid decarboxylase (GAD) enzyme. The contribution of all these Glu biotransformations after SCI has not been determined...
October 26, 2016: Neuroreport
https://www.readbyqxmd.com/read/27769404/determination-of-dopamine-serotonin-biosynthesis-precursors-and-metabolites-in-rat-brain-microdialysates-by-ultrasonic-assisted-in-situ-derivatization-dispersive-liquid-liquid-microextraction-coupled-with-uhplc-ms-ms
#8
Na Wei, Xian-En Zhao, Shuyun Zhu, Yongrui He, Longfang Zheng, Guang Chen, Jinmao You, Shu Liu, Zhiqiang Liu
This paper, for the first time, reported a simple, rapid, sensitive and environmental friendly ultrasonic-assisted in situ derivatization-dispersive liquid-liquid microextraction (in situ UAD-DLLME) method followed by ultra high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) for the simultaneous determination of dopamine (DA), serotonin (5-HT) and their biosynthesis precursors and metabolites in rat brain microdialysates. In this work, a commercial reagent, Lissamine rhodamine B sulfonylchloride (LRSC), was proposed as a derivatization reagent...
December 1, 2016: Talanta
https://www.readbyqxmd.com/read/27737572/molecularly-imprinted-cyclodextrin-nanosponges-for-the-controlled-delivery-of-l-dopa-perspectives-for-the-treatment-of-parkinson-s-disease
#9
Francesco Trotta, Fabrizio Caldera, Roberta Cavalli, Marco Soster, Chiara Riedo, Miriam Biasizzo, Gloria Uccello Barretta, Federica Balzano, Valentina Brunella
BACKGROUND: L-DOPA is an amino acid precursor to the neurotransmitter dopamine that is extensively used as a prodrug for the treatment of Parkinson's disease. However, L-DOPA is an unstable compound: when exposed to light or added to aqueous solutions, it may degrade, compromising its therapeutic properties. RESEARCH DESIGN AND METHODS: In this work, a new type of drug-loaded cyclodextrin-based nanosponge, obtained using molecular imprinting, is described for the prolonged and controlled release of L-DOPA...
October 13, 2016: Expert Opinion on Drug Delivery
https://www.readbyqxmd.com/read/27671966/phosphatidic-acid-and-neurotransmission
#10
Daniel M Raben, Casey N Barber
Lipids play a vital role in the health and functioning of neurons and interest in the physiological role of neuronal lipids is certainly increasing. One neuronal function in which neuronal lipids appears to play key roles in neurotransmission. Our understanding of the role of lipids in the synaptic vesicle cycle and neurotransmitter release is becoming increasingly more important. Much of the initial research in this area has highlighted the major roles played by the phosphoinositides (PtdIns), diacylglycerol (DAG), and phosphatidic acid (PtdOH)...
September 20, 2016: Advances in Biological Regulation
https://www.readbyqxmd.com/read/27649042/combined-glutamate-and-glutamine-levels-in-pain-processing-brain-regions-are-associated-with-individual-pain-sensitivity
#11
Matthias Zunhammer, Lauren M Schweizer, Vanessa Witte, Richard E Harris, Ulrike Bingel, Tobias Schmidt-Wilcke
The relationship between glutamate and γ-aminobutyric acid (GABA) levels in the living human brain and pain sensitivity is unknown. Combined glutamine/glutamate (Glx), as well as GABA levels can be measured in vivo with single-voxel proton magnetic resonance spectroscopy. In this cross-sectional study, we aimed at determining whether Glx and/or GABA levels in pain-related brain regions are associated with individual differences in pain sensitivity. Experimental heat, cold, and mechanical pain thresholds were obtained from 39 healthy, drug-free individuals (25 men) according to the quantitative sensory testing protocol and summarized into 1 composite measure of pain sensitivity...
October 2016: Pain
https://www.readbyqxmd.com/read/27647959/the-antidepressant-effect-of-l-tyrosine-loaded-nanoparticles-behavioral-aspects
#12
Abdelrahman Alabsi, Adel Charbel Khoudary, Wassim Abdelwahed
BACKGROUND: Depression has been linked to disruption in the cerebral levels of specific neurotransmitters. L-tyrosine is a precursor of more than one of the neurotransmitters affected by depression. Even though setbacks of monoamines precursors include high doses and low efficiency, many studies have suggested using L-tyrosine as antidepressant. PURPOSE: The purpose of this study was to explore the possible antidepressant effect of L-tyrosine loaded in a nanoparticle-designed formula, using behavioral tests in acute and chronic mild stress (CMS) models of depression in rats...
July 2016: Annals of Neurosciences
https://www.readbyqxmd.com/read/27644104/ng2-glial-cells-integrate-synaptic-input-in-global-and-dendritic-calcium-signals
#13
Wenjing Sun, Elizabeth A Matthews, Vicky Nicolas, Susanne Schoch, Dirk Dietrich
Synaptic signaling to NG2-expressing oligodendrocyte precursor cells (NG2 cells) could be key to rendering myelination of axons dependent on neuronal activity, but it has remained unclear whether NG2 glial cells integrate and respond to synaptic input. Here we show that NG2 cells perform linear integration of glutamatergic synaptic inputs and respond with increasing dendritic calcium elevations. Synaptic activity induces rapid Ca(2+) signals mediated by low-voltage activated Ca(2+) channels under strict inhibitory control of voltage-gated A-type K(+) channels...
September 19, 2016: ELife
https://www.readbyqxmd.com/read/27623126/-autism-spectrum-disorders-and-bisphenol-a-is-serotonin-the-lacking-link-in-the-chain
#14
D Sarrouilhe, C Dejean
The etiology of autism spectrum disorders (ASD) is believed to be multifactorial and to involve genetic and environmental components. Environmental chemical exposures are increasingly understood to be important in causing neurotoxicity in fetuses and newborns. Recent data from the Centers for Disease Control and Prevention in the United States suggest a substantial increase in ASD prevalence, only partly explicable by factors such as diagnostic substitution. Bisphenol A (BPA) is an ubiquitous xenoestrogen widely employed in a variety of consumer products including plastic and metal food and beverage containers, dental sealants and fillings, medical equipment and thermal receipts...
September 9, 2016: L'Encéphale
https://www.readbyqxmd.com/read/27615793/effect-of-bilateral-prefrontal-rtms-on-left-prefrontal-naa-and-glx-levels-in-schizophrenia-patients-with-predominant-negative-symptoms-an-exploratory-study
#15
Jozarni J Dlabac-de Lange, Edith J Liemburg, Leonie Bais, Aida T van de Poel-Mustafayeva, Elly S M de Lange-de Klerk, Henderikus Knegtering, André Aleman
BACKGROUND: Prefrontal repetitive Transcranial Magnetic Stimulation (rTMS) may improve negative symptoms in patients with schizophrenia, but few studies have investigated the underlying neural mechanism. OBJECTIVE: This study aims to investigate changes in the levels of glutamate and glutamine (Glx, neurotransmitter and precursor) and N-Acetyl Aspartate (NAA) in the left dorsolateral prefrontal cortex of patients with schizophrenia treated with active bilateral prefrontal rTMS as compared to sham-rTMS, as measured with (1)H-Magnetic Resonance Spectroscopy ((1)H-MRS)...
August 5, 2016: Brain Stimulation
https://www.readbyqxmd.com/read/27562098/long-term-safety-and-effectiveness-of-pramipexole-in-tetrahydrobiopterin-deficiency
#16
Francesco Porta, Alberto Ponzone, Marco Spada
Tetrahydrobiopterin (BH4) deficiencies are inherited neuro-metabolic disorders leading to monoamine neurotransmitters deficiency. An individualized replacement therapy with neurotransmitters precursors is necessary to restore dopaminergic and serotoninergic homeostasis. The correction of dopaminergic tone is complicated, like in Parkinson disease, by l-dopa short half-life and adverse effects. To improve this picture, since 2009 we introduced the non-ergot dopamine agonist pramipexole as an adjunct to l-dopa therapy in the treatment of the most common causes of BH4 deficiency, 6-pyruvoyl tetrahydropterin synthase (PTPS) deficiency and dihydropteridine reductase (DHPR) deficiency...
December 0: European Journal of Paediatric Neurology: EJPN
https://www.readbyqxmd.com/read/27560194/adult-neurogenesis-lessons-from-crayfish-and-the-elephant-in-the-room
#17
Barbara S Beltz, Georg Brenneis, Jeanne L Benton
The 1st-generation neural precursors in the crustacean brain are functionally analogous to neural stem cells in mammals. Their slow cycling, migration of their progeny, and differentiation of their descendants into neurons over several weeks are features of the neural precursor lineage in crayfish that also characterize adult neurogenesis in mammals. However, the 1st-generation precursors in crayfish do not self-renew, contrasting with conventional wisdom that proposes the long-term self-renewal of adult neural stem cells...
August 24, 2016: Brain, Behavior and Evolution
https://www.readbyqxmd.com/read/27539857/a-novel-developmental-role-for-dopaminergic-signaling-to-specify-hypothalamic-neurotransmitter-identity
#18
Yu-Chia Chen, Svetlana Semenova, Stanislav Rozov, Maria Sundvik, Joshua L Bonkowsky, Pertti Panula
Hypothalamic neurons expressing histamine and orexin/hypocretin (hcrt) are necessary for normal regulation of wakefulness. In Parkinson's disease, the loss of dopaminergic neurons is associated with elevated histamine levels and disrupted sleep/wake cycles, but the mechanism is not understood. To characterize the role of dopamine in the development of histamine neurons, we inhibited the translation of the two non-allelic forms of tyrosine hydroxylase (th1 and th2) in zebrafish larvae. We found that dopamine levels were reduced in both th1 and th2 knockdown, but the serotonin level and number of serotonin neurons remained unchanged...
October 14, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27513937/evaluation-of-tetrahydrobiopterin-therapy-with-large-neutral-amino-acid-supplementation-in-phenylketonuria-effects-on-potential-peripheral-biomarkers-melatonin-and-dopamine-for-brain-monoamine-neurotransmitters
#19
Shoji Yano, Kathryn Moseley, Xiaowei Fu, Colleen Azen
BACKGROUND: Phenylketonuria (PKU) is due to a defective hepatic enzyme, phenylalanine (Phe) hydroxylase. Transport of the precursor amino acids from blood into the brain for serotonin and dopamine synthesis is reported to be inhibited by high blood Phe concentrations. Deficiencies of serotonin and dopamine are involved in neurocognitive dysfunction in PKU. OBJECTIVE: (1) To evaluate the effects of sapropterin (BH4) and concurrent use of large neutral amino acids (LNAA) on the peripheral biomarkers, melatonin and dopamine with the hypothesis they reflect brain serotonin and dopamine metabolism...
2016: PloS One
https://www.readbyqxmd.com/read/27503090/solute-carriers-in-the-blood-brain-barier-safety-in-abundance
#20
Katarzyna A Nałęcz
Blood-brain barrier formed by brain capillary endothelial cells, being in contact with astrocytes endfeet and pericytes, separates extracellular fluid from plasma. Supply of necessary nutrients and removal of certain metabolites takes place due to the activity of transporting proteins from ABC (ATP binding cassette) and SLC (solute carrier) superfamilies. This review is focused on the SLC families involved in transport though the blood-brain barrier of energetic substrates (glucose, monocarboxylates, creatine), amino acids, neurotransmitters and their precursors, as well as organic ions...
August 9, 2016: Neurochemical Research
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