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https://www.readbyqxmd.com/read/28811646/pafah1b1-haploinsufficiency-disrupts-gaba-neurons-and-synaptic-e-i-balance-in-the-dentate-gyrus
#1
Matthew T Dinday, Kelly M Girskis, Sunyoung Lee, Scott C Baraban, Robert F Hunt
Hemizygous mutations in the human gene encoding platelet-activating factor acetylhydrolase IB subunit alpha (Pafah1b1), also called Lissencephaly-1, can cause classical lissencephaly, a severe malformation of cortical development. Children with this disorder suffer from deficits in neuronal migration, severe intellectual disability, intractable epilepsy and early death. While many of these features can be reproduced in Pafah1b1(+/-) mice, the impact of Pafah1b1(+/-) on the function of individual subpopulations of neurons and ultimately brain circuits is largely unknown...
August 15, 2017: Scientific Reports
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
#2
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/28809922/increased-signaling-by-the-autism-related-engrailed-2-protein-enhances-dendritic-branching-and-spine-density-alters-synaptic-structural-matching-and-exaggerates-protein-synthesis
#3
Asma Soltani, Solène Lebrun, Gilles Carpentier, Giulia Zunino, Sandrine Chantepie, Auriane Maïza, Yuri Bozzi, Claire Desnos, François Darchen, Olivier Stettler
Engrailed 1 (En1) and 2 (En2) code for closely related homeoproteins acting as transcription factors and as signaling molecules that contribute to midbrain and hindbrain patterning, to development and maintenance of monoaminergic pathways, and to retinotectal wiring. En2 has been suggested to be an autism susceptibility gene and individuals with autism display an overexpression of this homeogene but the mechanisms remain unclear. We addressed in the present study the effect of exogenously added En2 on the morphology of hippocampal cells that normally express only low levels of Engrailed proteins...
2017: PloS One
https://www.readbyqxmd.com/read/28808187/g-aminobutyric-acid-promotes-methionine-choline-deficient-diet-induced-nonalcoholic-steatohepatitis
#4
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/28807873/neurophysiologically-informed-markers-of-individual-variability-and-pharmacological-manipulation-of-human-cortical-gamma
#5
A D Shaw, R J Moran, S D Muthukumaraswamy, J Brealy, D E Linden, K J Friston, K D Singh
The ability to quantify synaptic function at the level of cortical microcircuits from non-invasive data would be enormously useful in the study of neuronal processing in humans and the pathophysiology that attends many neuropsychiatric disorders. Here, we provide proof of principle that one can estimate inter-and intra-laminar interactions among specific neuronal populations using induced gamma responses in the visual cortex of human subjects - using dynamic causal modelling based upon the canonical microcircuit (CMC; a simplistic model of a cortical column)...
August 11, 2017: NeuroImage
https://www.readbyqxmd.com/read/28807784/gabapentin-prevents-cortical-spreading-depolarization-induced-disinhibition
#6
Masoud Mesgari, Johanna Krüger, Christopher Theo Riemer, Maryam Khaleghi Ghadiri, Stjepana Kovac, Ali Goji
Cortical spreading depolarization (CSD) has an important role in brain diseases such as stroke, subarachnoid haemorrhage, migraine with aura, and epilepsy. Several anti-epileptic drugs (AEDs) are used to treat paroxysmal brain diseases and are thus known to suppress CSD. One of these AEDs is gabapentin (GBP) which has been traditionally used for treatment of some CSD-related neurological diseases. We applied intra- and extracellular recordings to investigate the effect of CSD on inhibitory post synaptic potentials (IPSPs) and synaptic properties of rodent neocortex after application of GBP...
August 11, 2017: Neuroscience
https://www.readbyqxmd.com/read/28807671/selective-inhibition-of-extra-synaptic-%C3%AE-5-gabaa-receptors-by-s44819-a-new-therapeutic-agent
#7
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/28807279/acaricidal-activity-of-fluralaner-against-ornithodoros-moubata-and-ornithodoros-erraticus-argasid-ticks-evaluated-through-in-vitro-feeding
#8
R Pérez-Sánchez, A Oleaga
Ornithodoros erraticus and Ornithodoros moubata are argasid tick vectors that transmit severe diseases such as African swine fever and human relapsing fever. Elimination of the synanthropic populations of these vectors would facilitate the control of these diseases. Fluralaner is a novel isoxazoline that selectively blocks the GABA- and glutamate-gated channels, providing potent insecticidal and acaricidal activity. The aim of the current study was to provide quantitative data on the susceptibility of males, females and third nymphal instar of O...
August 30, 2017: Veterinary Parasitology
https://www.readbyqxmd.com/read/28807167/treatment-of-insomnia-with-traditional-chinese-herbal-medicine
#9
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/28806600/design-synthesis-and-evaluation-of-newer-5-6-dihydropyrimidine-2-1h-thiones-as-gaba-at-inhibitors-for-anticonvulsant-potential
#10
Meeta Sahu, Nadeem Siddiqui, Ramsha Iqbal, Vidushi Sharma, Sharad Wakode
Several new 5,6-dihydropyrimidine-2(1H)-thione derivatives have been prepared and investigated for their potencies for anticonvulsant activity against maximal electroshock (MES) and subcutaneous pentylenetetrazole (scPTZ) test in mice. The acute neurotoxicity was measured by rotarod test. Compounds 3c and 3l were found active in both of the animal models. Further, in vitro GABA-AT enzyme activity assay was carried out to investigate the possible mechanism of action through GABA-AT inhibition. The most potent compounds 3c and 3l showed inhibitory potency (IC50) of 18...
July 28, 2017: Bioorganic Chemistry
https://www.readbyqxmd.com/read/28804557/motor-neuron-degeneration-following-glycine-mediated-excitotoxicity-induces-spastic-paralysis-after-spinal-cord-ischemia-reperfusion-injury-in-rabbit
#11
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/28803850/association-of-exposure-to-manganese-and-iron-with-striatal-and-thalamic-gaba-and-other-neurometabolites-neuroimaging-results-from-the-weldox-ii-study
#12
Swaantje Casjens, Urike Dydak, Shalmali Dharmadhikari, Anne Lotz, Martin Lehnert, Clara Quetscher, Christoph Stewig, Benjamin Glaubitz, Tobias Schmidt-Wilcke, David Edmondson, Chien-Lin Yeh, Tobias Weiss, Christoph van Thriel, Lennard Herrmann, Siegfried Muhlack, Dirk Woitalla, Michael Aschner, Thomas Brüning, Beate Pesch
OBJECTIVE: Magnetic resonance spectroscopy (MRS) is a non-invasive method to quantify neurometabolite concentrations in the brain. Within the framework of the WELDOX II study, we investigated the association of exposure to manganese (Mn) and iron (Fe) with γ-aminobutyric acid (GABA) and other neurometabolites in the striatum and thalamus of 154 men. MATERIAL AND METHODS: GABA-edited and short echo-time MRS at 3T was used to assess brain levels of GABA, glutamate, total creatine (tCr) and other neurometabolites...
August 10, 2017: Neurotoxicology
https://www.readbyqxmd.com/read/28803659/seizing-control-of-kcc2-a-new-therapeutic-target-for-epilepsy
#13
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/28802192/soft-diet-feeding-impairs-neural-transmission-between-mitral-cells-and-interneurons-in-the-mouse-olfactory-bulb
#14
Tomohiro Noguchi, Chizuru Utsugi, Makoto Kashiwayanagi
(Objective) The subventricular zone in mice generates a lot of neuroblasts even during adulthood. These neuroblasts migrate to the olfactory bulb and differentiate into inhibitory interneurons such as granule cells and periglomerular cells. Olfactory sensory neurons receive information from various odorants and transmit it to the olfactory bulb. Our previous study showed that soft-diet feeding impairs neurogenesis in the subventricular zone, in turn leading to the reduction of odor-induced behaviors and Fos-immunoreactivities, the latter of which are markers of neural activity, at the olfactory bulb after exposure to odors...
July 29, 2017: Archives of Oral Biology
https://www.readbyqxmd.com/read/28800966/reconstruction-of-a-metabolic-regulatory-network-in-escherichia-coli-for-purposeful-switching-from-cell-growth-mode-to-production-mode-in-direct-gaba-fermentation-from-glucose
#15
Yuki Soma, Yuri Fujiwara, Takuya Nakagawa, Keigo Tsuruno, Taizo Hanai
γ-aminobutyric acid (GABA) is a drug and functional food additive and is used as a monomer for producing the biodegradable plastic, polyamide 4. Recently, direct GABA fermentation from glucose has been developed as an alternative to glutamate-based whole cell bioconversion. Although total productivity in fermentation is determined by the specific productivity and cell amount responsible for GABA production, the optimal metabolic state for GABA production conflicts with that for bacterial cell growth. Herein, we demonstrated metabolic state switching from the cell growth mode based on the metabolic pathways of the wild type strain to a GABA production mode based on a synthetic metabolic pathway in Escherichia coli through rewriting of the metabolic regulatory network and pathway engineering...
August 8, 2017: Metabolic Engineering
https://www.readbyqxmd.com/read/28800937/vortioxetine-a-new-alternative-for-the-treatment-of-major-depressive-disorder
#16
Estela Salagre, Iria Grande, Brisa Solé, Jose Sanchez-Moreno, Eduard Vieta
Major Depressive Disorder (MDD) is a serious psychiatric condition. Its treatment remains a challenge nowadays. Vortioxetine is a novel antidepressant with a unique profile, as it acts as a multimodal serotoninergic agent. Its efficacy in MDD has been established in many short- and long-term studies, with 7 positive, 4 negative and 1 failed randomized controlled trials. Moreover, its ability to modulate a wide range of neurotransmitters (serotonin, dopamine, norepinephrine, histamine, glutamate or GABA) confers vortioxetine pro-cognitive effects...
August 8, 2017: Revista de Psiquiatrí́a y Salud Mental
https://www.readbyqxmd.com/read/28800423/relationship-of-executive-functioning-deficits-to-n-acetyl-aspartate-naa-and-gamma-aminobutyric-acid-gaba-in-youth-with-bipolar-disorder
#17
Rebekah S Huber, Douglas G Kondo, Xian-Feng Shi, Andrew P Prescot, Elaine Clark, Perry F Renshaw, Deborah A Yurgelun-Todd
BACKGROUND: Although cognitive deficits in bipolar disorder (BD) have been repeatedly observed, our understanding of these impairments at a mechanistic level remains limited. Few studies that investigated cognitive impairments in bipolar illness have examined the association with brain biochemistry. This pilot study utilized proton magnetic resonance spectroscopy ((1)H-MRS) to evaluate the relationship between neurocognitive performance and brain metabolites in youth with BD. METHODS: Thirty participants, twenty depressed BD participants and ten healthy comparison participants, ages 13-21, completed mood and executive function measures...
August 1, 2017: Journal of Affective Disorders
https://www.readbyqxmd.com/read/28799512/modulation-of-gabaa-receptors-in-the-treatment-of-epilepsy
#18
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
#19
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
#20
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
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