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https://www.readbyqxmd.com/read/28810599/effects-of-niflumic-acid-on-%C3%AE-aminobutyric-acid-induced-currents-in-isolated-dorsal-root-ganglion-neurons-of-neuropathic-pain-rats
#1
Li-Jie Wang, Yang Wang, Meng-Jie Chen, Zhen-Pu Tian, Bi-Han Lu, Ke-Tao Mao, Liang Zhang, Lei Zhao, Li-Ya Shan, Li Li, Jun-Qiang Si
Niflumic acid (NFA) is a type of non-steroidal anti-inflammatory drug. Neuropathic pain is caused by a decrease in presynaptic inhibition mediated by γ-aminobutyric acid (GABA). In the present study, a whole-cell patch-clamp technique and intracellular recording were used to assess the effect of NFA on GABA-induced inward current in dorsal root ganglion (DRG) neurons of a chronic constriction injury (CCI) model. It was observed that 1-1,000 µmol/l GABA induced a concentration-dependent inward current in DRG neurons...
August 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28808187/g-aminobutyric-acid-promotes-methionine-choline-deficient-diet-induced-nonalcoholic-steatohepatitis
#2
Yoon Seok Roh, Ara Cho, Zixiong Zhou, Hyuneui Jeong, Jeong-Eun Park, Youn-Soo Cha, Suk-Heung Oh, Chae-Woong Lim, Bumseok Kim
Nonalcoholic steatohepatitis (NASH) is one of the most common liver diseases and a major cause of liver fibrosis worldwide. G-Aminobutyric acid (GABA) is one of the most abundant inhibitory neurotransmitters in the central nervous system. Recently, it has been reported that GABAergic signaling pathways are found in various non-neuronal tissues including the immune system and play a functional role. In the present study, we investigated whether administration of GABA has effects on NASH through its immunomodulatory effects...
October 17, 2016: Journal of Biomedical Research
https://www.readbyqxmd.com/read/28807671/selective-inhibition-of-extra-synaptic-%C3%AE-5-gabaa-receptors-by-s44819-a-new-therapeutic-agent
#3
Lori-An Etherington, Balázs Mihalik, Adrienn Pálvölgyi, István Ling, Katalin Pallagi, Szabolcs Kertész, Péter Varga, Ben G Gunn, Adam R Brown, Matthew R Livesey, Olivia Monteiro, Delia Belelli, József Barkóczy, Michael Spedding, István Gacsályi, Ferenc A Antoni, Jeremy J Lambert
In the mammalian central nervous system (CNS) GABAA receptors (GABAARs) mediate neuronal inhibition and are important therapeutic targets. GABAARs are composed of 5 subunits, drawn from 19 proteins, underpinning expression of 20-30 GABAAR subtypes. In the CNS these isoforms are heterogeneously expressed and exhibit distinct physiological and pharmacological properties. We report the discovery of S44819, a novel tricyclic oxazolo-2,3-benzodiazepine-derivative, that selectively inhibits α5-subunit-containing GABAARs (α5-GABAARs)...
August 11, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28807167/treatment-of-insomnia-with-traditional-chinese-herbal-medicine
#4
Amrinder Singh, Kaicun Zhao
Insomnia is a condition with sleep problems and many people suffered from it. Chronic insomnia can last for long time and it will severely affect people's health and the quality of life. In conventional medicine, the most commonly used the medicine is benzodiazepine. It is effective but also has significant side effects. Patients try to use some kinds of alternative medicines. Chinese medicinal herbs and formulas have been used in the treatment of insomnia for more than 2000 years in China. In recent decades, Chinese herbal medicine has been widely used in the Western countries...
2017: International Review of Neurobiology
https://www.readbyqxmd.com/read/28804557/motor-neuron-degeneration-following-glycine-mediated-excitotoxicity-induces-spastic-paralysis-after-spinal-cord-ischemia-reperfusion-injury-in-rabbit
#5
Li Wang, Sen Li, Yuan Liu, Dong-Liang Feng, Long Jiang, Zai-Yun Long, Ya-Min Wu
Spinal cord ischemia and reperfusion (SCIR) injury is the major cause of a wide range of complications, including neural degeneration and devastating paraplegia. Decrease of inhibitory neurotransmitters and increase of excitory neurotransmitters are the major cause for the excitotoxicity of neurons. However, no study has reported the temporal loss of motor neuron in the ventral horn of spinal cord area following SCIR-induced spastic paralysis, not even the mechanism under it. In the present study, we found that the rabbits were mainly spastic paralyzed after spinal cord ischemia-reperfusion injury...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28803659/seizing-control-of-kcc2-a-new-therapeutic-target-for-epilepsy
#6
REVIEW
Yvonne E Moore, Matt R Kelley, Nicholas J Brandon, Tarek Z Deeb, Stephen J Moss
Deficits in GABAergic inhibition result in the abnormal neuronal activation and synchronization that underlies seizures. However, the molecular mechanisms responsible for transforming a normal brain into an epileptic one remain largely unknown. Hyperpolarizing inhibition mediated by type A GABA (GABAA) receptors is dependent on chloride extrusion by the neuron-specific type 2K(+)-Cl(-) cotransporter (KCC2). Loss-of-function mutations in KCC2 are a known cause of infantile epilepsy in humans and KCC2 dysfunction is present in patients with both idiopathic and acquired epilepsy...
August 10, 2017: Trends in Neurosciences
https://www.readbyqxmd.com/read/28799512/modulation-of-gabaa-receptors-in-the-treatment-of-epilepsy
#7
Eleonora Palma, Gabriele Ruffolo, Pierangelo Cifelli, Cristina Roseti, Erwin A van Vliet, Eleonora Aronica
BACKGROUND: A variety of evidence suggested that an imbalance in excitatory and inhibitory neurotransmission could be one of the pathophysiological mechanisms underlying the occurrence and progression of seizures. Understanding the causes of this imbalance may provide essential insight into the basic mechanisms of epilepsy and may uncover novel targets for future drug therapies. Accordingly, GABA is the most important inhibitory neurotransmitter in the CNS and its receptors (e.g., GABAARs) can still be relevant targets of new antiepileptic drugs (AEDs)...
August 9, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28798678/striatal-neuropeptides-enhance-selection-and-rejection-of-sequential-actions
#8
David Buxton, Enrico Bracci, Paul G Overton, Kevin Gurney
The striatum is the primary input nucleus for the basal ganglia, and receives glutamatergic afferents from the cortex. Under the hypothesis that basal ganglia perform action selection, these cortical afferents encode potential "action requests." Previous studies have suggested the striatum may utilize a mutually inhibitory network of medium spiny neurons (MSNs) to filter these requests so that only those of high salience are selected. However, the mechanisms enabling the striatum to perform clean, rapid switching between distinct actions that form part of a learned action sequence are still poorly understood...
2017: Frontiers in Computational Neuroscience
https://www.readbyqxmd.com/read/28798394/orthosteric-versus-allosteric-dependent-activation-of-the-gabaa-receptor-requires-numerically-distinct-subunit-level-rearrangements
#9
Jahanshah Amin, Meena S Subbarayan
Anaesthetic molecules act on synaptic transmission via the allosteric modulation of ligand-gated chloride channels, such as hetero-oligomeric α1β2γ2 GABAA receptors. To elucidate the overall activation paradigm via allosteric versus orthosteric sites, we used highly homologous, but homo-oligomeric, ρ1 receptors that are contrastingly insensitive to anaesthetics and respond partially to several full GABA α1β2γ2 receptor agonists. Here, we coexpressed varying ratios of RNAs encoding the wild-type and the mutated ρ1 subunits, which are anaesthetic-sensitive and respond with full efficacy to partial GABA agonists, to generate distinct ensembles of receptors containing five, four, three, two, one, or zero mutated subunits...
August 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28794459/multiple-excitatory-actions-of-orexins-upon-thalamo-cortical-neurons-in-dorsal-lateral-geniculate-nucleus-implications-for-vision-modulation-by-arousal
#10
Lukasz Chrobok, Katarzyna Palus-Chramiec, Anna Chrzanowska, Mariusz Kepczynski, Marian Henryk Lewandowski
The orexinergic system of the lateral hypothalamus plays a crucial role in maintaining wakefulness and mediating arousal in a circadian time-dependent manner. Due to the extensive connections of orexinergic neurons, both orexins (OXA and OXB) exert mainly excitatory effects upon remote brain areas, including the thalamus. The dorsal lateral geniculate nucleus (DLG) is a relay thalamic centre for the visual system. Its thalamo-cortical (TC) neurons convey photic information from the retina to the primary visual cortex...
August 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28793908/transcriptomic-analysis-comparing-mouse-strains-with-extreme-total-lung-capacities-identifies-novel-candidate-genes-for-pulmonary-function
#11
Leema George, Ankita Mitra, Tania A Thimraj, Martin Irmler, Sangeetha Vishweswaraiah, Lars Lunding, Dorothea Hühn, Alicia Madurga, Johannes Beckers, Heinz Fehrenbach, Swapna Upadhyay, Holger Schulz, George D Leikauf, Koustav Ganguly
BACKGROUND: Failure to attain peak lung function by early adulthood is a risk factor for chronic lung diseases. Previously, we reported that C3H/HeJ mice have about twice total lung capacity (TLC) compared to JF1/MsJ mice. We identified seven lung function quantitative trait loci (QTL: Lfnq1-Lfnq7) in backcross/intercross mice derived from these inbred strains. We further demonstrated, superoxide dismutase 3, extracellular (Sod3), Kit oncogene (Kit) and secreted phosphoprotein 1 (Spp1) located on these Lfnqs as lung function determinants...
August 9, 2017: Respiratory Research
https://www.readbyqxmd.com/read/28790148/the-actions-of-drug-combinations-on-the-gabaa-receptor-manifest-as-curvilinear-isoboles-of-additivity
#12
Daniel J Shin, Allison L Germann, Joseph H Steinbach, Gustav Akk
Drug interactions are often analyzed in terms of isobolograms. In the isobologram, the line connecting the axial points corresponding to the concentrations of two different drugs that produce an effect of the same magnitude is termed an isobole of additivity. Although the isobole of additivity can be a straight line in some special cases, previous work has found that it is curvilinear when the two drugs differ in their maximal effects or Hill slopes. Modulators of transmitter-gated ion channels have a wide range of maximal effects as well as Hill slopes, suggesting that the isoboles for drug actions on ion channel function are not linear...
August 8, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28782830/altered-behavioral-responses-to-gamma-aminobutyric-acid-pharmacological-agents-in-a-mouse-model-of-huntington-s-disease
#13
Yi-Ting Hsu, Ya-Gin Chang, Ching-Pang Chang, Jian-Jing Siew, Hui-Mei Chen, Chon-Haw Tsai, Yijuang Chern
BACKGROUND: Disruptions in gamma-aminobutyric (GABA) acid signaling are believed to be involved in Huntington's disease pathogenesis, but the regulation of GABAergic signaling remains elusive. Here we evaluated GABAergic signaling by examining the function of GABAergic drugs in Huntington's disease and the expression of GABAergic molecules using mouse models and human brain tissues from Huntington's disease. METHODS: We treated wild-type and R6/2 mice (a transgenic Huntington's disease mouse model) acutely with vehicle, diazepam, or gaboxadol (drugs that selectively target synaptic or extrasynaptic GABAA receptors) and monitored their locomotor activity...
August 7, 2017: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/28782641/nitric-oxide-cgmp-signaling-via-guanylyl-cyclase-isoform-1-modulates-glutamate-and-gaba-release-in-somatosensory-cortex-of-mice
#14
Qi Wang, Evanthia Mergia, Doris Koesling, Thomas Mittmann
In hippocampus, two guanylyl cyclases (NO-GC1 and NO-GC2) are involved in the transduction of the effects of nitric oxide (NO) on synaptic transmission. However, the respective roles of the NO-GC isoforms on synaptic transmission are less clear in other regions of the brain. In the present study, we used knock-out mice deficient for the NO-GC1 isoform (NO-GC1 KO) to analyze its role in the glutamatergic and GABAergic neurotransmission at pyramidal neurons in layers II/III of somatosensory cortex. NO-GC1 KO slices revealed reduced frequencies of miniature excitatory- and inhibitory-postsynaptic currents, increased paired-pulse ratios and decreased input-output curves of evoked signals, which indicated the reduction of glutamate and GABA release in NO-GC1 KO mice...
August 4, 2017: Neuroscience
https://www.readbyqxmd.com/read/28777735/evidence-for-the-involvement-of-the-gaba-ergic-pathway-in-the-anticonvulsant-activity-of-the-roots-bark-aqueous-extract-of-anthocleista-djalonensis-a-chev-loganiaceae
#15
Germain Sotoing Taiwe, Arielle Larissa Ndieudieu Kouamou, Armelle Rosalie Mbang Ambassa, Joseph Renaud Menanga, Thierry Bang Tchoya, Paul Desire Djomeni Dzeufiet
BACKGROUND: The root bark of Anthocleista djalonensis A. Chev. (Loganiaceae) is widely used in traditional medicine in Northern Cameroon to treat epilepsy and related conditions, such as migraine, insomnia, dementia, anxiety, and mood disorders. METHODS: To investigate the anticonvulsant effects and the possible mechanisms of this plant, an aqueous extract of Anthocleista djalonensis (AEAD) was evaluated by using animal models of bicuculline-, picrotoxin-, pilocarpine-, and pentylenetetrazole-induced convulsions...
August 4, 2017: Journal of Basic and Clinical Physiology and Pharmacology
https://www.readbyqxmd.com/read/28777177/chronic-insomnia-disorder
#16
Alon Y Avidan, David N Neubauer
PURPOSE OF REVIEW: Neurologists, along with all health care providers, commonly encounter patients with insomnia, which is a condition that impacts patients' underlying neurologic conditions in a bidirectional manner. While chronic insomnia is one of the most common sleep disturbances, only a small proportion of individuals with this condition discuss their sleep problems with their providers. When insomnia is described, it is more often in relationship to another medical problem, as opposed to an independent condition...
August 2017: Continuum: Lifelong Learning in Neurology
https://www.readbyqxmd.com/read/28768196/a-cooperative-mechanism-involving-ca-2-permeable-ampa-receptors-and-retrograde-activation-of-gabab-receptors-in-interpeduncular-nucleus-plasticity
#17
Peter Koppensteiner, Riccardo Melani, Ipe Ninan
The medial habenula-interpeduncular nucleus (MHb-IPN) pathway, which connects the limbic forebrain to the midbrain, has recently been implicated in aversive behaviors. The MHb-IPN circuit is characterized by a unique topographical organization, an excitatory role of GABA, and a prominent co-release of neurotransmitters and neuropeptides. However, little is known about synaptic plasticity in this pathway. An application of a high-frequency stimulation resulted in a long-lasting potentiation of glutamate release in IPN neurons...
August 1, 2017: Cell Reports
https://www.readbyqxmd.com/read/28764646/a-randomized-double-blind-placebo-controlled-trial-of-ganaxolone-in-children-and-adolescents-with-fragile-x-syndrome
#18
Andrew Ligsay, Anke Van Dijck, Danh V Nguyen, Reymundo Lozano, Yanjun Chen, Erika S Bickel, David Hessl, Andrea Schneider, Kathleen Angkustsiri, Flora Tassone, Berten Ceulemans, R Frank Kooy, Randi J Hagerman
BACKGROUND: Gamma-aminobutyric acid (GABA) system deficits are integral to the pathophysiologic development of fragile X syndrome (FXS). Ganaxolone, a GABAA receptor positive allosteric modulator, is hypothesized to improve symptoms such as anxiety, hyperactivity, and attention deficits in children with FXS. METHODS: This study was a randomized, double-blind, placebo-controlled, crossover trial of ganaxolone in children with FXS, aged 6-17 years. RESULTS: Sixty-one participants were assessed for eligibility, and 59 were randomized to the study...
August 2, 2017: Journal of Neurodevelopmental Disorders
https://www.readbyqxmd.com/read/28762595/perinatal-high-fat-diet-increases-inhibition-of-dorsal-motor-nucleus-of-the-vagus-neurons-regulating-gastric-functions
#19
C A McMenamin, R A Travagli, K N Browning
BACKGROUND: Previous studies suggest an increased inhibition of dorsal motor nucleus of the vagus (DMV) neurons following exposure to a perinatal high fat diet (PNHFD); the underlying neural mechanisms, however, remain unknown. This study assessed the effects of PNHFD on inhibitory synaptic inputs to DMV neurons and the vagally dependent control of gastric tone and motility. METHODS: Whole-cell patch clamp recordings were made from DMV neurons in thin brainstem slices from Sprague-Dawley rats fed either a control diet or HFD (14 or 60% kcal from fat, respectively) from embryonic day 13 onwards; gastric tone and motility were recorded in in vivo anesthetized rats...
August 1, 2017: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
https://www.readbyqxmd.com/read/28762314/insights-into-nicotinic-receptor-signaling-in-nicotine-addiction-implications-for-prevention-and-treatment
#20
Wuyi Liu, Ming D Li
Nicotinic acetylcholine receptors (nAChRs) belong to the Cys-loop ligand-gated ion-channel (LGIC) superfamily, which also includes the GABA, glycine, and serotonin receptors. Many nAChR subunits have been identified and shown to be involved in signal transduction on binding to them of either the neurotransmitter acetylcholine or exogenous ligands such as nicotine. The nAChRs are pentameric assemblies of homologous subunits surrounding a central pore that gates cation flux, and they are expressed at neuromuscular junctions throughout the nervous system...
August 1, 2017: Current Neuropharmacology
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