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https://www.readbyqxmd.com/read/29346777/prrt2-regulates-synaptic-fusion-by-directly-modulating-snare-complex-assembly
#1
Jeff Coleman, Ouardane Jouannot, Sathish K Ramakrishnan, Maria N Zanetti, Jing Wang, Vincenzo Salpietro, Henry Houlden, James E Rothman, Shyam S Krishnakumar
Mutations in proline-rich transmembrane protein 2 (PRRT2) are associated with a range of paroxysmal neurological disorders. PRRT2 predominantly localizes to the pre-synaptic terminals and is believed to regulate neurotransmitter release. However, the mechanism of action is unclear. Here, we use reconstituted single vesicle and bulk fusion assays, combined with live cell imaging of single exocytotic events in PC12 cells and biophysical analysis, to delineate the physiological role of PRRT2. We report that PRRT2 selectively blocks the trans SNARE complex assembly and thus negatively regulates synaptic vesicle priming...
January 16, 2018: Cell Reports
https://www.readbyqxmd.com/read/29345350/activation-of-the-sympathetic-nervous-system-modulates-neutrophil-function
#2
Alyce J Nicholls, Shu Wen Wen, Pam Hall, Michael J Hickey, Connie H Y Wong
Emerging evidence has revealed that noradrenaline (NA), the main neurotransmitter of the sympathetic nervous system (SNS), regulates a variety of immune functions via binding to adrenergic receptors present on immune cells. In this study, we examined the role of NA in the regulation of neutrophil functions. Neutrophils were isolated from the bone marrow of naïve mice and treated with NA at various concentrations to assess the effect on various neutrophil functions. Additionally, we performed cremaster intravital microscopy to examine neutrophil-endothelial cell interactions following NA superfusion in vivo...
December 21, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29344832/mitogen-activated-protein-kinase-6-and-map-kinase-phosphatase-1-are-involved-in-the-response-of-arabidopsis-roots-to-l-glutamate
#3
Jesús Salvador López-Bucio, Javier Raya-González, Gustavo Ravelo-Ortega, León Francisco Ruiz-Herrera, Maricela Ramos-Vega, Patricia León, José López-Bucio, Ángel Arturo Guevara-García
The function and components of L-glutamate signaling pathways in plants have just begun to be elucidated. Here, using a combination of genetic and biochemical strategies, we demonstrated that a MAPK module is involved in the control of root developmental responses to this amino acid. Root system architecture plays an essential role in plant adaptation to biotic and abiotic factors via adjusting signal transduction and gene expression. L-Glutamate (L-Glu), an amino acid with neurotransmitter functions in animals, inhibits root growth, but the underlying genetic mechanisms are poorly understood...
January 17, 2018: Plant Molecular Biology
https://www.readbyqxmd.com/read/29344679/distribution-and-dynamic-expression-of-serotonin-and-dopamine-in-the-nervous-system-and-ovary-of-holothuria-scabra-during-ovarian-maturation
#4
Arada Chaiyamoon, Ruchanok Tinikul, Supakant Chaichotranunt, Tanes Poomthong, Worawit Suphamungmee, Prasert Sobhon, Yotsawan Tinikul
In the present study, the distribution and dynamic expression of serotonin and dopamine in the nervous system and ovary of the sea cucumber, Holothuria scabra, during different ovarian stages were investigated. We found that serotonin-immunoreactivity was more intense in the neurons and neuropils of the outer ectoneural part, the inner hyponeural part, and the wall of hyponeural canal of radial nerve cord during the mature stages of ovarian cycle, whereas dopamine-immunoreactivity was detected at a higher intensity in these tissues during the early stages...
January 18, 2018: Journal of Comparative Physiology. A, Neuroethology, Sensory, Neural, and Behavioral Physiology
https://www.readbyqxmd.com/read/29343526/mutations-in-cyb561-causing-a-novel-orthostatic-hypotension-syndrome
#5
Maarten P van den Berg, Rowida Almomani, Italo Biaggioni, Martijn van Faassen, Pim van der Harst, Herman H Silljé, Irene Mateo Leach, Marc Hemmelder, Gerjan Navis, Gert-Jan Luijckx, Arjan P de Brouwer, Hanka Venselaar, Marcel M Verbeek, Paul A van der Zwaag, Jan D Jongbloed, J P van Tintelen, Ron A Wevers, Ido P Kema
Rationale: Orthostatic hypotension is a common clinical problem, but the underlying mechanisms have not been fully delineated. Objective: We describe two families, with four patients in total, suffering from severe life-threatening orthostatic hypotension due to a novel cause. Methods and Results: As in dopamine β-hydroxylase deficiency (DβH), concentrations of norepinephrine and epinephrine in the patients were very low. Plasma DβH activity, however, was normal and the DBH gene had no mutations. Molecular genetic analysis was performed to determine the underlying genetic cause...
January 17, 2018: Circulation Research
https://www.readbyqxmd.com/read/29341829/climatic-modulation-of-neurotransmitter-release-in-amphibian-neuromuscular-junctions-role-of-dynorphin-a
#6
Dengyun Ge, Nickolas Anastasios Lavidis
Amphibian neuromuscular junctions become relatively more silent during the dry-winter season in Australia. Endogenous opioid peptides play an important role in the regulation of the physiological functions of active and dormant vertebrates. Previous findings suggest that dynorphin-A is more potent than other opiates in decreasing evoked neurotransmission in amphibian neuromuscular junctions. Dynorphin-A has been shown not to alter the amplitude or the frequency of spontaneous quantal neurotransmitter release...
January 17, 2018: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/29341331/the-relationship-between-thalamic-gaba-content-and-resting-cortical-rhythm-in-neuropathic-pain
#7
Flavia Di Pietro, Paul M Macey, Caroline D Rae, Zeynab Alshelh, Vaughan G Macefield, E Russell Vickers, Luke A Henderson
Recurrent thalamocortical connections are integral to the generation of brain rhythms and it is thought that the inhibitory action of the thalamic reticular nucleus is critical in setting these rhythms. Our work and others' has suggested that chronic pain that develops following nerve injury, that is, neuropathic pain, results from altered thalamocortical rhythm, although whether this dysrhythmia is associated with thalamic inhibitory function remains unknown. In this investigation, we used electroencephalography and magnetic resonance spectroscopy to investigate cortical power and thalamic GABAergic concentration in 20 patients with neuropathic pain and 20 pain-free controls...
January 17, 2018: Human Brain Mapping
https://www.readbyqxmd.com/read/29340966/cannabinomimetric-lipids-from-natural-extract-to-artificial-synthesis
#8
REVIEW
Ya-Ru Gao, Yong-Qiang Wang
Endocannabinoid system is related with various physiological and cognitive processes including fertility, pregnancy, during pre- and postnatal development, pain-sensation, mood, appetite, and memory. In the latest decades, an important milestone concerning the endocannabinoid system was the discovery of the existence of the cannabinoid receptors CB1 and CB2. Anandamide was the first reported endogenous metabolite, which adjusted the release of some neurotransmitters through binding to the CB1 or CB2 receptors...
January 16, 2018: Natural Products and Bioprospecting
https://www.readbyqxmd.com/read/29340775/global-versus-local-mechanisms-of-temperature-sensing-in-ion-channels
#9
REVIEW
Cristina Arrigoni, Daniel L Minor
Ion channels turn diverse types of inputs, ranging from neurotransmitters to physical forces, into electrical signals. Channel responses to ligands generally rely on binding to discrete sensor domains that are coupled to the portion of the channel responsible for ion permeation. By contrast, sensing physical cues such as voltage, pressure, and temperature arises from more varied mechanisms. Voltage is commonly sensed by a local, domain-based strategy, whereas the predominant paradigm for pressure sensing employs a global response in channel structure to membrane tension changes...
January 17, 2018: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/29339723/fasoracetam-in-adolescents-with-adhd-and-glutamatergic-gene-network-variants-disrupting-mglur-neurotransmitter-signaling
#10
Josephine Elia, Grace Ungal, Charlly Kao, Alexander Ambrosini, Nilsa De Jesus-Rosario, Lene Larsen, Rosetta Chiavacci, Tiancheng Wang, Christine Kurian, Kanani Titchen, Brian Sykes, Sharon Hwang, Bhumi Kumar, Jacqueline Potts, Joshua Davis, Jeffrey Malatack, Emma Slattery, Ganesh Moorthy, Athena Zuppa, Andrew Weller, Enda Byrne, Yun R Li, Walter K Kraft, Hakon Hakonarson
The glutamatergic neurotransmitter system may play an important role in attention-deficit hyperactivity disorder (ADHD). This 5-week, open-label, single-blind, placebo-controlled study reports the safety, pharmacokinetics and responsiveness of the metabotropic glutamate receptor (mGluR) activator fasoracetam (NFC-1), in 30 adolescents, age 12-17 years with ADHD, harboring mutations in mGluR network genes. Mutation status was double-blinded. A single-dose pharmacokinetic profiling from 50-800 mg was followed by a single-blind placebo at week 1 and subsequent symptom-driven dose advancement up to 400 mg BID for 4 weeks...
January 16, 2018: Nature Communications
https://www.readbyqxmd.com/read/29339289/characterization-of-two-extracellular-%C3%AE-glucosidases-produced-from-the-cellulolytic-fungus-aspergillus-sp-ydj216-and-their-potential-applications-for-the-hydrolysis-of-flavone-glycosides
#11
Jong Min Oh, Jae Pil Lee, Seung Cheol Baek, Seul Gi Kim, Yang Do Jo, Jungho Kim, Hoon Kim
A cellulolytic fungus YDJ216 was isolated from a compost and identified as an Aspergillus sp. strain. Two extracellular β-glucosidases, BGL1 and BGL2, were purified using ultrafiltration, ammonium sulfate fractionation, and High-Q chromatography. Molecular masses of BGL1 and BGL2 were estimated to be 97 and 45 kDa, respectively, by SDS-PAGE. The two enzymes eluted as one peak at 87 kDa by Sephacryl S-200 chromatography, and located at similar positions in a zymogram after intact gel electrophoresis, suggesting BGL1 and BGL2 might be monomeric and dimeric, respectively...
January 12, 2018: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29338302/neurotransmitter-pathway-genes-in-cognitive-decline-during-aging-evidence-for-gng4-and-kcnq2-genes
#12
Luke W Bonham, Daniel S Evans, Yongmei Liu, Steven R Cummings, Kristine Yaffe, Jennifer S Yokoyama
BACKGROUND/RATIONALE: Experimental studies support the role of neurotransmitter genes in dementia risk, but human studies utilizing single variants in candidate genes have had limited success. METHODS: We used the gene-based testing program Versatile Gene-based Association Study to assess whether aggregate variation across 6 neurotransmitter pathways influences risk of cognitive decline in 8159 cognitively normal elderly (≥65 years old) adults from 3 community-based cohorts...
January 1, 2018: American Journal of Alzheimer's Disease and Other Dementias
https://www.readbyqxmd.com/read/29338251/delivery-of-oxytocin-to-the-brain-for-the-treatment-of-autism-spectrum-disorder-by-nasal-application
#13
Akiko Tanaka, Tomoyuki Furubayashi, Mari Arai, Daisuke Inoue, Shunsuke Kimura, Akiko Kiriyama, Kosuke Kusamori, Hidemasa Katsumi, Reiko Yutani, Toshiyasu Sakane, Akira Yamamoto
Oxytocin (OXT) is a cyclic nonapeptide, two amino acids of which are cysteine, forming an intramolecular disulfide bond. OXT is produced in the hypothalamus and is secreted into the blood stream from the posterior pituitary. As recent studies have suggested that OXT is a neurotransmitter exhibiting central effects important for social deficits, it has drawn much attention as a drug candidate for the treatment of autism. Although human-stage clinical trials of the nasal spray of OXT for the treatment of autism have already begun, few studies have examined the pharmacokinetics and brain distribution of OXT after nasal application...
January 16, 2018: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29338042/a-pharmacological-screen-for-compounds-that-rescue-the-developmental-lethality-of-a-drosophila-atm-mutant
#14
Stacey A Rimkus, David A Wassarman
Ataxia-telangiectasia (A-T) is a neurodegenerative disease caused by mutation of the A-T mutated (ATM) gene. ATM encodes a protein kinase that is activated by DNA damage and phosphorylates many proteins, including those involved in DNA repair, cell cycle control, and apoptosis. Characteristic biological and molecular functions of ATM observed in mammals are conserved in Drosophila melanogaster. As an example, conditional loss-of-function ATM alleles in flies cause progressive neurodegeneration through activation of the innate immune response...
2018: PloS One
https://www.readbyqxmd.com/read/29335402/a-partially-open-inward-facing-intermediate-conformation-of-leut-is-associated-with-na-release-and-substrate-transport
#15
Daniel S Terry, Rachel A Kolster, Matthias Quick, Michael V LeVine, George Khelashvili, Zhou Zhou, Harel Weinstein, Jonathan A Javitch, Scott C Blanchard
Neurotransmitter:sodium symporters (NSS), targets of antidepressants and psychostimulants, clear neurotransmitters from the synaptic cleft through sodium (Na+)-coupled transport. Substrate and Na+ are thought to be transported from the extracellular to intracellular space through an alternating access mechanism by coordinated conformational rearrangements in the symporter that alternately expose the binding sites to each side of the membrane. However, the mechanism by which the binding of ligands coordinates conformational changes occurring on opposite sides of the membrane is not well understood...
January 15, 2018: Nature Communications
https://www.readbyqxmd.com/read/29332554/evaluating-the-dose-dependent-mechanism-of-action-of-trazodone-by-estimation-of-occupancies-for-different-brain-neurotransmitter-targets
#16
Luca Settimo, David Taylor
Trazodone is a drug that was introduced in the clinic almost 40 years ago. It is licensed to treat depression, but it is also commonly used off-label to treat insomnia. A recent study shows that it could be promising in preventing neurodegeneration in mice, and clinical trials to assess its possible beneficial effects on dementia and Alzheimer's disease are expected to start soon in humans. In this study, we describe the dose-dependent pharmacology of trazodone by carrying out pharmacokinetic simulations aiming to predict the brain concentrations of trazodone for different drug-dosing regimens and calculating occupancy for 28 different targets for which published trazodone-binding data are available...
January 2018: Journal of Psychopharmacology
https://www.readbyqxmd.com/read/29332272/comparative-study-of-selenium-and-selenium-nanoparticles-with-reference-to-acute-toxicity-biochemical-attributes-and-histopathological-response-in-fish
#17
Neeraj Kumar, Kishore Kumar Krishnani, Narendra Pratap Singh
Recent studies have demonstrated that selenium (Se) and selenium nanoparticles (Se-NPs) exhibited toxicity at a higher concentration. The lethal concentration of Se and Se-NPs was estimated as 5.29 and 3.97 mg/L at 96 h in Pangasius hypophthalmus. However, the effect of different definite concentration of Se (4.5, 5.0, 5.5, and 6.0 mg/L) and Se-NPs (2.5, 3.0, 3.5, and 4.0 mg/L) was decided for acute experiment. Selenium and Se-NPs alter the biochemical attributes such as anti-oxidative status [catalase (CAT), superoxide dismutase (SOD), and glutathione-S-transferase (GST) activities], neurotransmitter enzyme, cellular metabolic enzymes, stress marker, and histopathology of P...
January 13, 2018: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/29332256/dopamine-dependent-social-information-processing-in-non-human-primates
#18
Young-A Lee, Sarah Lionnet, Akemi Kato, Yukiori Goto
RATIONALE: Dopamine (DA) is a neurotransmitter whose roles have been suggested in various aspects of brain functions. Recent studies in rodents have reported its roles in social function. However, how DA is involved in social information processing in primates has largely remained unclear. OBJECTIVES: We investigated prefrontal cortical (PFC) activities associated with social vs. nonsocial visual stimulus processing. METHODS: Near-infrared spectroscopy (NIRS) was applied to Japanese macaques, along with pharmacological manipulations of DA transmission, while they were gazing at social and nonsocial visual stimuli...
January 14, 2018: Psychopharmacology
https://www.readbyqxmd.com/read/29331845/effect-of-levetiracetam-on-extracellular-amino-acid-levels-in-the-dorsal-hippocampus-of-rats-with-temporal-lobe-epilepsy
#19
Pichardo Macías Luz Adriana, Ramírez Mendiola Blanca Alcira, Contreras García Itzel Jatziri, Zamudio Hernández Sergio Roberto, Chávez Pacheco Juan Luis, Sánchez Huerta Karla Berenice, Mendoza Torreblanca Julieta Griselda
Levetiracetam (LEV) is an anticonvulsant drug with a unique mechanism of action that is not completely understood. However, its activity profile may involve effects on excitatory and/or inhibitory neurotransmission since the primary target of LEV, synaptic vesicle protein 2A, is ubiquitously expressed in all types of synaptic vesicles. Therefore, the objective of the present study was to explore the effect of LEV (300 mg/kg/day for one week, administered via osmotic mini-pumps) on neurotransmitter release and its probable selective effect on extracellular gamma-amino butyric acid (GABA), glutamate (Glu), aspartate (Asp), glutamine (Gln), taurine (Tau) and glycine (Gly) concentrations (using in vivo microdialysis under basal and high-K+ conditions) in the dorsal hippocampus (DH), a region that undergoes major synaptic changes during epilepsy...
January 5, 2018: Epilepsy Research
https://www.readbyqxmd.com/read/29331791/magnesium-sulfate-reduces-formalin-induced-orofacial-pain-in-rats-with-normal-magnesium-serum-levels
#20
Dragana P Srebro, Sonja M Vučković, Ivan S Dožić, Branko S Dožić, Katarina R Savić Vujović, Aleksandar P Milovanović, Branislav V Karadžić, Milica Š Prostran
BACKGROUND: In humans, orofacial pain has a high prevalence and is often difficult to treat. Magnesium is an essential element in biological a system which controls the activity of many ion channels, neurotransmitters and enzymes. Magnesium produces an antinociceptive effect in neuropathic pain, while in inflammatory pain results are not consistent. We examined the effects of magnesium sulfate using the rat orofacial formalin test, a model of trigeminal pain. METHODS: Male Wistar rats were injected with 1...
August 31, 2017: Pharmacological Reports: PR
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