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https://www.readbyqxmd.com/read/28430869/inhibition-of-the-p2x7-panx1-complex-suppresses-spreading-depolarization-and-neuroinflammation
#1
Shih-Pin Chen, Tao Qin, Jessica L Seidel, Yi Zheng, Matthias Eikermann, Michel D Ferrari, Arn M J M van den Maagdenberg, Michael A Moskowitz, Cenk Ayata, Katharina Eikermann-Haerter
Spreading depolarization is a wave of neuronal and glial depolarization. Within minutes after spreading depolarization, the neuronal hemichannel pannexin 1 (PANX1) opens and forms a pore complex with the ligand-gated cation channel P2X7, allowing the release of excitatory neurotransmitters to sustain spreading depolarization and activate neuroinflammation. Here, we explore the hypothesis that the P2X7-PANX1 pore complex is a critical determinant of spreading depolarization susceptibility with important consequences for neuroinflammation and trigeminovascular activation...
April 20, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28430154/circadian-rhythm-neuropeptides-in-drosophila-signals-for-normal-circadian-function-and-circadian-neurodegenerative-disease
#2
REVIEW
Qiankun He, Binbin Wu, Jeffrey L Price, Zhangwu Zhao
Circadian rhythm is a ubiquitous phenomenon in many organisms ranging from prokaryotes to eukaryotes. During more than four decades, the intrinsic and exogenous regulations of circadian rhythm have been studied. This review summarizes the core endogenous oscillation in Drosophila and then focuses on the neuropeptides, neurotransmitters and hormones that mediate its outputs and integration in Drosophila and the links between several of these (pigment dispersing factor (PDF) and insulin-like peptides) and neurodegenerative disease...
April 21, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28430139/the-metalloproteinase-adam28-promotes-metabolic-dysfunction-in-mice
#3
Lakshini Herat, Caroline Rudnicka, Yasunori Okada, Satsuki Mochizuki, Markus Schlaich, Vance Matthews
Obesity and diabetes are major causes of morbidity and mortality globally. The current study builds upon our previous association studies highlighting that A Disintegrin And Metalloproteinase 28 (ADAM28) appears to be implicated in the pathogenesis of obesity and type 2 diabetes in humans. Our novel study characterised the expression of ADAM28 in mice with the metabolic syndrome and used molecular inhibition approaches to investigate the functional role of ADAM28 in the pathogenesis of high fat diet-induced obesity...
April 21, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28430025/synthesis-of-dopamine-in-e-coli-using-plasmid-based-expression-system-and-its-marked-effect-on-host-growth-profiles
#4
Arunangshu Das, Anita Verma, Krishna J Mukherjee
L-Dopa and dopamine are important pathway intermediates towards the synthesis of catecholamine like epinephrine and norepinephrine from amino acid L-tyrosine. Dopamine, secreted from dopaminergic nerve cells, serves as an important neurotransmitter. We report the synthesis of dopamine by extending the aromatic amino acid pathway of E.coli DH5α by expression of 4-hydroxyphenylacetate-3-hydrolase (HpaBC) from E.coli and an engineered dopa decarboxylase (DDC) from pig kidney cell. The activity of HpaBC and DDC require 200 µM iron supplementation and 50 µM vitamin B6 respectively as additives to the growth media...
April 21, 2017: Preparative Biochemistry & Biotechnology
https://www.readbyqxmd.com/read/28429899/neurotransmitter-systems-neuroanatomical-pathology-and-cell-death-in-schizophrenia-update-and-perspectives
#5
Hazael Avila-Rojas, Hugo Sandoval-Zamora, Iván Pérez-Neri
Schizophrenia is a thought disorder characterized by delusional thinking which may be accompanied by hallucinations involving any sensory modality. Schizophrenia may be associated with several neurologic and psychiatric disorders. Also, it may be induced by drugs. In spite of the similarity in psychoses symptomatology, it is unknown if it involves the same underlying neurobiologic mechanisms in those cases. Schizophrenic patients exhibit not only neuroanatomical alterations, but also, distortion of several neurotransmitter systems...
June 2016: Investigación Clínica
https://www.readbyqxmd.com/read/28429217/adrenoceptors-in-dopaminergic-regulation-of-rat-myocardial-contractility-in-rats-during-ontogeny
#6
G A Bilalova, F G Sitdikov, N B Dikopol'skaya, M V Shaikhelislamova, T L Zefirov
The effects of different dopamine concentrations on contractility of myocardium with blocked α- or β-adrenoceptors were examined in vitro in 21- and 100-day old rats. In myocardial strips with blocked α-adrenoceptors, dopamine (10(-5) M) increased the right atrial contractile force. By contrast, this neurotransmitter (10(-9)-10(-5) M) reduced the contractile force of atrial and ventricular strips with blocked β-adrenoceptors.
April 20, 2017: Bulletin of Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28429067/neuronal-oscillations-and-synchronicity-associated-with-gamma-hydroxybutyrate-during-resting-state-in-healthy-male-volunteers
#7
Robin von Rotz, Michael Kometer, Dario Dornbierer, Jürg Gertsch, M Salomé Gachet, Franz X Vollenweider, Erich Seifritz, Oliver G Bosch, Boris B Quednow
RATIONALE: Gamma-hydroxybutyrate (GHB) is a putative neurotransmitter, a drug of abuse, an anesthetic agent, and a treatment for neuropsychiatric disorders. In previous electroencephalography (EEG) studies, GHB was shown to induce an electrophysiological pattern of "paradoxical EEG-behavioral dissociation" characterized by increased delta and theta oscillations usually associated with sleep during awake states. However, no detailed source localization of these alterations and no connectivity analyses have been performed yet...
April 20, 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28428755/pharmacological-analysis-of-the-anti-epileptic-mechanisms-of-fenfluramine-in-scn1a-mutant-zebrafish
#8
Jo Sourbron, Ilse Smolders, Peter de Witte, Lieven Lagae
Dravet syndrome (DS) is a genetic encephalopathy that is characterized by severe seizures and prominent co-morbidities (e.g., physical, intellectual disabilities). More than 85% of the DS patients carry an SCN1A mutation (sodium channel, voltage gated, type I alpha subunit). Although numerous anti-epileptic drugs have entered the market since 1990, these drugs often fail to adequately control seizures in DS patients. Nonetheless, current clinical data shows significant seizure reduction in DS patients treated with the serotonergic (5-hydroxytryptamine, 5-HT) drug fenfluramine (FA)...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28428744/mutational-analysis-at-intersubunit-interfaces-of-an-anionic-glutamate-receptor-reveals-a-key-interaction-important-for-channel-gating-by-ivermectin
#9
Nurit Degani-Katzav, Revital Gortler, Marina Weissman, Yoav Paas
The broad-spectrum anthelmintic drug ivermectin (IVM) activates and stabilizes an open-channel conformation of invertebrate chloride-selective glutamate receptors (GluClRs), thereby causing a continuous inflow of chloride ions and sustained membrane hyperpolarization. These effects suppress nervous impulses and vital physiological processes in parasitic nematodes. The GluClRs are pentamers. Homopentameric receptors assembled from the Caenorhabditis elegans (C. elegans) GluClα (GLC-1) subunit can inherently respond to IVM but not to glutamate (the neurotransmitter)...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28427932/reciprocal-changes-in-noradrenaline-and-gaba-levels-in-discrete-brain-regions-upon-rapid-eye-movement-sleep-deprivation-in-rats
#10
Rachna Mehta, Sudhuman Singh, Mudasir Ahmad Khanday, Birendra Nath Mallick
Rapid eye movement sleep (REMS) plays important role in maintenance of normal brain functions. Neurons containing various neurotransmitters in different brain regions interact to regulate this complex phenomenon in health and diseases. The number of neuronal projections, their firing rates and neurotransmitter levels vary in different brain regions under various conditions leading to normal or altered patho-physio-behavioral states. In this study using high performance liquid chromatography (HPLC) we quantified noradrenaline (NA) and gamma-amino butyric acid (GABA) levels in locus coeruleus (LC), dorsal raphe (DR), pedunculo-pontine tegmentum (PPT), frontal lobe (FL), cortex and hippocampus (Hippo) in control and after 96h REMS deprivation (REMSD) rats...
April 17, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28426993/a-new-combined-method-of-stable-isotope-labeling-derivatization-ultrasound-assisted-dispersive-liquid-liquid-microextraction-for-the-determination-of-neurotransmitters-in-rat-brain-microdialysates-by-ultra-high-performance-liquid-chromatography-tandem-mass
#11
Longfang Zheng, Xian-En Zhao, Shuyun Zhu, Yanduo Tao, Wenhua Ji, Yanling Geng, Xiao Wang, Guang Chen, Jinmao You
In this work, for the first time, a new hyphenated technique of stable isotope-labeling derivatization-ultrasound-assisted dispersive liquid-liquid microextraction has been developed for the simultaneous determination of monoamine neurotransmitters (MANTs) and their biosynthesis precursors and metabolites. The developed method was based on ultra high performance liquid chromatography tandem mass spectrometry detection using multiple-reaction monitoring mode. A pair of mass spectrometry sensitizing reagents, d0-10-methyl-acridone-2-sulfonyl chloride and d3-10-methyl-acridone-2-sulfonyl chloride, as stable isotope probes was utilized to facilely label neurotransmitters, respectively...
April 10, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/28426956/amines-astrocytes-and-arousal
#12
Narges Bazargani, David Attwell
Amine neurotransmitters, such as noradrenaline, mediate arousal, attention, and reward in the CNS. New data suggest that, from flies to mammals, a major mechanism for amine transmitter action is to raise astrocyte [Ca(2+)]i and release gliotransmitters that modulate neuronal activity and behavior.
April 19, 2017: Neuron
https://www.readbyqxmd.com/read/28425871/the-journey-of-the-non-vascular-relief-for-migraine-from-triptans-to-ditans
#13
Alphienes Stanley Xavier, Mageshwaran Lakshmanan, Vikneswaran Gunaseelan
Migraine is a recurrent, disabling, complex and highly prevalent neurological disorder. The mystery behind the cause of migraine is continuously evolving, according to the scientific understanding of the disease. This growing understanding helps to identify novel therapeutic targets for the management of migraine to treat the ailing migraineurs. The role of serotonin (5HT) in migraine is recognized to be the cornerstone for the currently available therapeutic options namely ergot alkaloids and triptans. The role of mediators such as Calcitonin Gene-Related Peptide (CGRP), nitric oxide and excitatory neurotransmitter glutamate, has been realized and ignited the development of drugs targeting these factors...
April 19, 2017: Current Clinical Pharmacology
https://www.readbyqxmd.com/read/28425701/the-effects-of-glutamate-receptor-activation-on-local-oxygen-changes
#14
Lindsay Walton, Nick G Boustead, Susan Carroll, R Mark Wightman
Glutamate is ubiquitous throughout the brain and serves as the primary excitatory neurotransmitter. Neurons require energy to fire, and energetic substrates (i.e., O2, glucose) are renewed via cerebral blood flow (CBF) to maintain metabolic homeostasis. Magnetic resonance brain functionality studies rely on the assumption that CBF and neuronal activity are coupled consistently throughout the brain; however, the origin of neuronal activity does not always coincide with signals indicative of energy consumption (e...
April 20, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28425095/psychomotor-tremor-and-proprioceptive-control-problems-in-current-and-former-stimulant-drug-users-an-accelerometer-study-of-heavy-users-of-amphetamine-mdma-and-other-recreational-stimulants
#15
Luke A Downey, Brenda Tysse, Talitha C Ford, Angela C Samuels, Rory P Wilson, Andrew C Parrott
The recreational use of various stimulant drugs has been implicated in the development of movement disorders through dysregulation of the dopaminergic and serotoninergic neurotransmitter systems. The present study investigated psychomotor differences in current and former recreational stimulant drug users compared with nonusing controls. Sixty participants comprised 3 groups: 20 current stimulant drug users (CSUs; 11 men, aged 31.4 ± 9.1 years), 20 former stimulant drug users (FSUs; 5 men, aged 39.1 ± 8.5 years), and 20 nonuser controls (NUCs; 5 men, aged 35...
April 19, 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28424589/the-calcium-channel-c-terminal-and-synaptic-vesicle-tethering-analysis-by-immuno-nanogold-localization
#16
Robert H C Chen, Qi Li, Christine A Snidal, Sabiha R Gardezi, Elise F Stanley
At chemical synapses the incoming action potential triggers the influx of Ca(2+) through voltage-sensitive calcium channels (CaVs, typically CaV2.1 and 2.2) and the ions binds to sensors associated with docked, transmitter filled synaptic vesicles (SVs), triggering their fusion and discharge. The CaVs and docked SVs are located within the active zone (AZ) region of the synapse which faces a corresponding neurotransmitter receptor-rich region on the post-synaptic cell. Evidence that the fusion of a SV can be gated by Ca(2+) influx through a single CaV suggests that the channel and docked vesicle are linked by one or more molecular tethers (Stanley, 1993)...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28424515/structure-and-allosteric-inhibition-of-excitatory-amino-acid-transporter-1
#17
Juan C Canul-Tec, Reda Assal, Erica Cirri, Pierre Legrand, Sébastien Brier, Julia Chamot-Rooke, Nicolas Reyes
Human members of the solute carrier 1 (SLC1) family of transporters take up excitatory neurotransmitters in the brain and amino acids in peripheral organs. Dysregulation of the function of SLC1 transporters is associated with neurodegenerative disorders and cancer. Here we present crystal structures of a thermostabilized human SLC1 transporter, the excitatory amino acid transporter 1 (EAAT1), with and without allosteric and competitive inhibitors bound. The structures reveal architectural features of the human transporters, such as intra- and extracellular domains that have potential roles in transport function, regulation by lipids and post-translational modifications...
April 19, 2017: Nature
https://www.readbyqxmd.com/read/28424220/gababr-induced-egfr-transactivation-promotes-migration-of-human-prostate-cancer-cells
#18
Shuai Xia, Cong He, Yini Zhu, Suyun Wang, Huiping Li, Zhongling Zhang, Xinnong Jiang, Jianfeng Liu
G protein-coupled receptors (GPCRs) and receptor tyrosine kinases (RTKs) act in concert to regulate cell growth, proliferation, survival, and migration. Metabotropic GABAB receptor (GABABR) is the GPCR for the main inhibitory neurotransmitter GABA in the central nervous system. Increased expression of GABABR has been detected in human cancer tissues and cancer cell lines, but the role of GABABR in these cells is controversial and the underlying mechanism remains poorly understood. Here, we investigated whether GABABR hijacks RTK signaling to modulate the fates of human prostate cancer cells...
April 19, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28423914/current-views-on-neuropeptide-y-and-diabetes-related-atherosclerosis
#19
Wei-Wei Sun, Ping Zhu, Yan-Chuan Shi, Chen-Liang Zhang, Xu-Feng Huang, Shi-Yu Liang, Zhi-Yuan Song, Shu Lin
Diabetes-induced atherosclerotic cardiovascular disease is the leading cause of death of diabetic patients. Neuronal regulation plays a critical role in glucose metabolism and cardiovascular function under physiological and pathological conditions, among which, neurotransmitter neuropeptide Y has been shown to be closely involved in these two processes. Elevated central neuropeptide Y level promotes food intake and reduces energy expenditure, thereby increasing adiposity. Neuropeptide Y is co-localized with noradrenaline in central and sympathetic nervous systems...
April 1, 2017: Diabetes & Vascular Disease Research
https://www.readbyqxmd.com/read/28423892/o2-plasma-etching-and-anti-static-gun-surface-modifications-for-cnt-yarn-microelectrode-improve-sensitivity-and-anti-fouling-properties
#20
Cheng Yang, Ying Wang, Christopher B Jacobs, Ilia Ivanov, B Jill Venton
Carbon nanotube (CNT) based microelectrodes exhibit rapid and selective detection of neurotransmitters. While different fabrication strategies and geometries of CNT microelectrodes have been characterized, relatively little research has investigated ways to selectively enhance their electrochemical properties. In this work, we introduce two simple, reproducible, low-cost, and efficient surface modification methods for carbon nanotube yarn microelectrodes (CNTYMEs): O2 plasma etching and anti-static gun treatment...
April 20, 2017: Analytical Chemistry
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