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GABA receptors

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https://www.readbyqxmd.com/read/28339662/hiv-1-proteins-influence-novelty-seeking-behavior-and-alter-region-specific-transcriptional-responses-to-chronic-nicotine-treatment-in-hiv-1tg-rats
#1
Zhongli Yang, Tanseli Nesil, Taylor Wingo, Sulie L Chang, Ming D Li
Introduction: Clinical studies suggest that HIV-1-infected patients are more likely to use or abuse addictive drugs than is the general population. We hypothesized that HIV-1 proteins impact novelty-seeking behavior and enhance the transcriptional response to nicotine in genes implicated in both novelty-seeking behavior and drug addiction. Methods: We assessed the effects of HIV-1 proteins on novelty-seeking behavior by comparing baseline activity differences of HIV-1Tg and F344 control rats in the open-field test...
February 17, 2017: Nicotine & Tobacco Research: Official Journal of the Society for Research on Nicotine and Tobacco
https://www.readbyqxmd.com/read/28324056/gabaergic-neurons-and-their-modulatory-effects-on-gnrh3-in-zebrafish
#2
Yanlong Song, Binbin Tao, Ji Chen, Shaoting Jia, Zuoyan Zhu, Vance L Trudeau, Wei Hu
Gamma-aminobutyric acid (GABA) is a major amino acid neurotransmitter in the vertebrate brain. To provide detailed information on the distribution of the GABA in zebrafish (Danio rerio), neurons were labeled with mCherry driven by the glutamic acid decarboxylase 67 (gad67) promoter. In the transgenic line Tg(gad67:mCherry), mCherry-positive gad67 cell bodies were predominantly localized to the olfactory bulb, pallial zones, subpallium zones, parvocellular preoptic nucleus, periventricular gray zone of optic tectum, torus semicircularis, posterior tuberculum, medial longitudinal fascicle, caudal zone of periventricular hypothalamus, and oculomotor nucleus...
January 23, 2017: Endocrinology
https://www.readbyqxmd.com/read/28323850/ligand-guided-homology-modelling-of-the-gabab2-subunit-of-the-gabab-receptor
#3
Thibaud Freyd, Dawid Warszycki, Stefan Mordalski, Andrzej J Bojarski, Ingebrigt Sylte, Mari Gabrielsen
γ-aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the central nervous system, and disturbances in the GABAergic system have been implicated in numerous neurological and neuropsychiatric diseases. The GABAB receptor is a heterodimeric class C G protein-coupled receptor (GPCR) consisting of GABAB1a/b and GABAB2 subunits. Two GABAB receptor ligand binding sites have been described, namely the orthosteric GABA binding site located in the extracellular GABAB1 Venus fly trap domain and the allosteric binding site found in the GABAB2 transmembrane domain...
2017: PloS One
https://www.readbyqxmd.com/read/28322281/identification-of-a-novel-fast-acting-gabaergic-antidepressant
#4
K M J McMurray, M J Ramaker, A M Barkley-Levenson, P S Sidhu, P K Elkin, M K Reddy, M L Guthrie, J M Cook, V H Rawal, L A Arnold, S C Dulawa, A A Palmer
Current pharmacotherapies for depression exhibit slow onset, side effects and limited efficacy. Therefore, identification of novel fast-onset antidepressants is desirable. GLO1 is a ubiquitous cellular enzyme responsible for the detoxification of the glycolytic byproduct methylglyoxal (MG). We have previously shown that MG is a competitive partial agonist at GABA-A receptors. We examined the effects of genetic and pharmacological inhibition of GLO1 in two antidepressant assay models: the tail suspension test (TST) and the forced swim test (FST)...
March 21, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28318542/monoamine-transporters-as-ionotropic-receptors
#5
Louis J De Felice
It is well established that glutamate and GABA signal through both ionotropic and metabotropic receptors. Conversely, it is thought that, with one exception, monoamines (dopamine, serotonin, and norepinephrine) signal via metabotropic receptors. Given their capacity to generate fast-acting currents, I suggest that the monoamine transporters should be considered as ionotropic receptors.
March 16, 2017: Trends in Neurosciences
https://www.readbyqxmd.com/read/28316115/gabaa-and-gabab-receptor-dysregulation-in-superior-frontal-cortex-of-subjects-with-schizophrenia-and-bipolar-disorder
#6
S Hossein Fatemi, Timothy D Folsom, Paul D Thuras
Schizophrenia and bipolar disorder are complex psychiatric disorders that affect millions of people worldwide. Evidence from gene association and postmortem studies has identified abnormalities of the gamma-aminobutyric acid (GABA) signaling system in both disorders. Abnormal GABAergic signaling and transmission could contribute to the symptomatology of these disorders, potentially through impaired gamma oscillations which normally occur during cognitive processing. In the current study, we examined the protein expression of 14 GABAA and two GABAB receptor subunits in the superior frontal cortex of subjects with schizophrenia, bipolar disorder, and healthy controls...
March 18, 2017: Synapse
https://www.readbyqxmd.com/read/28306133/injection-of-toll-like-receptor-4-sirna-into-the-ventrolateral-periaqueductal-gray-attenuates-withdrawal-syndrome-in-morphine-dependent-rats
#7
Q F Liu, L Li, Y Q Guo, X Li, Z D Mou, X Wang, G Z Du
We assessed the role of the Toll-like receptor 4 (TLR4) gene in the ventrolateral periaqueductal gray (vlPAG) region of morphine-dependent rats on attenuating withdrawal syndrome, and regulating glutamic acid decarboxylase (GAD67), glutamic acid (Glu), and gamma-aminobutyric acid (GABA). After siRNA-mediated downregulation of TLR4, changes were observed in withdrawal behavior and downstream signaling molecules. Rats were injected into the vlPAG with TLR4 siRNA, followed by intraperitoneal injection of morphine for 5 consecutive days, and then naloxone, and the behavioral indices of morphine withdrawal were observed...
December 1, 2016: Archives Italiennes de Biologie
https://www.readbyqxmd.com/read/28301408/k-cl-cotransporter-2-mediated-cl-extrusion-determines-developmental-stage-dependent-impact-of-propofol-anesthesia-on-dendritic-spines
#8
Martin Puskarjov, Hubert Fiumelli, Adrian Briner, Timea Bodogan, Kornel Demeter, Claudia-Marvine Lacoh, Martina Mavrovic, Peter Blaesse, Kai Kaila, Laszlo Vutskits
BACKGROUND: General anesthetics potentiating γ-aminobutyric acid (GABA)-mediated signaling are known to induce a persistent decrement in excitatory synapse number in the cerebral cortex when applied during early postnatal development, while an opposite action is produced at later stages. Here, the authors test the hypothesis that the effect of general anesthetics on synaptogenesis depends upon the efficacy of GABA receptor type A (GABAA)-mediated inhibition controlled by the developmental up-regulation of the potassium-chloride (K-Cl) cotransporter 2 (KCC2)...
March 16, 2017: Anesthesiology
https://www.readbyqxmd.com/read/28300633/the-medullary-dorsal-reticular-nucleus-as-a-relay-for-descending-pronociception-induced-by-the-mglur5-in-the-rat-infralimbic-cortex
#9
Ana David-Pereira, Boriss Sagalajev, Hong Wei, Armando Almeida, Antti Pertovaara, Filipa Pinto-Ribeiro
Metabotropic glutamate receptor 5 (mGluR5) activation in the infralimbic cortex (IL) induces pronociceptive behavior in healthy and monoarthritic rats. Here we studied whether the medullary dorsal reticular nucleus (DRt) and the spinal TRPV1 are mediating the IL/mGluR5-induced spinal pronociception and whether the facilitation of pain behavior is correlated with changes in spinal dorsal horn neuron activity. For drug administrations, all animals had a cannula in the IL as well as a cannula in the DRt or an intrathecal catheter...
March 11, 2017: Neuroscience
https://www.readbyqxmd.com/read/28300552/monoaminergic-modulation-of-gabaergic-transmission-onto-cerebellar-globular-cells
#10
Moritoshi Hirono, Soichi Nagao, Yuchio Yanagawa, Shiro Konishi
Cerebellar Purkinje cells (PCs) project their axon collaterals to underneath of the PC layer and make GABAergic synaptic contacts with globular cells, a subgroup of Lugaro cells. GABAergic transmission derived from the PC axon collaterals is so powerful that it could inhibit globular cells and regulate their firing patterns. However, the physiological properties and implications of the GABAergic synapses on globular cells remain unknown. Using whole-cell patch-clamp recordings from globular cells in the mouse cerebellum, we examined the monoaminergic modulation of GABAergic inputs to these cells...
March 11, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28299900/development-of-a-robust-mammalian-cell-based-assay-for-studying-recombinant-%C3%AE-4-%C3%AE-1-3-%C3%AE-gabaa-receptor-subtypes
#11
Christina B Falk-Petersen, Rikke Søgaard, Kenneth L Madsen, Anders B Klein, Bente Frølund, Petrine Wellendorph
δ-Containing GABAA receptors are located extrasynaptically and mediate tonic inhibition. Their involvement in brain physiology positions them as interesting drug targets. There is thus a continued interest in establishing reliable recombinant expression systems for δ-containing GABAA receptors. Inconveniently, the recombinant expression of especially α4 β1/3 δ receptors has been found to be notoriously difficult, due to mixed receptor populations and/or stoichiometries and differential pharmacology depending on the expression system used...
March 16, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28299422/homeostatic-regulation-through-gaba-and-acetylcholine-muscarinic-receptors-of-motor-trigeminal-neurons-following-sleep-deprivation
#12
Hanieh Toossi, Esther Del Cid-Pellitero, Barbara E Jones
Muscle tone is regulated across sleep-wake states, being maximal in waking, reduced in slow wave sleep (SWS) and absent in paradoxical or REM sleep (PS or REMS). Such changes in tone have been recorded in the masseter muscles and shown to correspond to changes in activity and polarization of the trigeminal motor 5 (Mo5) neurons. The muscle hypotonia and atonia during sleep depend in part on GABA acting upon both GABAA and GABAB receptors (Rs) and acetylcholine (ACh) acting upon muscarinic 2 (AChM2) Rs. Here, we examined whether Mo5 neurons undergo homeostatic regulation through changes in these inhibitory receptors following prolonged activity with enforced waking...
March 15, 2017: Brain Structure & Function
https://www.readbyqxmd.com/read/28295330/in-vitro-characterisation-of-cell-level-neurophysiological-diversity-in-the-rostral-nucleus-reuniens-of-adult-mice
#13
D A Walsh, J T Brown, A D Randall
The nucleus reuniens (Re) is the largest of the midline thalamic nuclei. We have performed a detailed neurophysiological characterization of neurons in the rostral Re of brain slices prepared from adult male mice. At resting potential (-63.7 ± 0.6 mV), circa 90% of Re neurons fired action potentials, typically continuously at ∼8 Hz. Although Re neurons experience a significant spontaneous barrage of fast, amino-acid-mediate synaptic transmission, this was not predominantly responsible for spontaneous spiking as firing persisted in the presence of glutamate and GABA receptor antagonists...
March 11, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28294280/cyclic-peptide-unguisin-a-is-an-anion-receptor-with-high-affinity-for-phosphate-and-pyrophosphate
#14
A Daryl Ariawan, James E A Webb, Ethan N W Howe, Philip A Gale, Pall Thordarson, Luke Hunter
Unguisin A (1) is a marine-derived, GABA-containing cyclic heptapeptide. The biological function of this flexible macrocycle is obscure. Here we show that compound 1 lacks any detectable activity in antimicrobial growth inhibition assays, a result that runs contrary to a previous report. However, we find that 1 functions as a promiscuous host molecule in a variety of anion-binding interactions, with high affinity particularly for phosphate and pyrophosphate. We also show that a series of rigidified, backbone-fluorinated analogues of 1 displays altered affinity for chloride ions...
March 15, 2017: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/28293190/gaba-selank-and-olanzapine-affect-the-expression-of-genes-involved-in-gabaergic-neurotransmission-in-imr-32-cells
#15
Elena Filatova, Anastasiya Kasian, Timur Kolomin, Ekaterina Rybalkina, Anelya Alieva, Lyudmila Andreeva, Svetlana Limborska, Nikolay Myasoedov, Galina Pavlova, Petr Slominsky, Maria Shadrina
Clinical studies have shown that Selank had an anxiolytic effect comparable to that of classical benzodiazepine drugs, which can enhance the inhibitory effect of GABA by allosteric modulation of GABAA receptors. These data suggest that the molecular mechanism of the effect of Selank may also be related to its ability to affect the performance of the GABAergic system. To test this hypothesis, we studied the changes in expression of 84 genes involved in the functioning of the GABAergic system and in the processes of neurotransmission in the culture of neuroblastoma IMR-32 cells using qPCR method...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28292021/antinociceptive-pharmacological-profile-of-dysphania-graveolens-in-mouse
#16
Myrna Déciga-Campos, Rachel Mata, Isabel Rivero-Cruz
This work evaluates the potential antinociceptive activity of Dysphania graveolens, traditional medicinal plant used in Mexico to treat stomach pain. A CH2Cl2-MeOH extract, infusion and essential oil from aerial parts of Dysphania graveolens were evaluated in hot plate and writhing tests in mice. The metabolites pinostrobin, pinocembrin and chrysin were isolated from the Dysphania graveolens infusion; next, they were evaluated in both nociceptive tests. To confirm the antinociceptive activity and explore the possible participation of opioid, GABA and serotonin receptors in the pharmacological mechanism, a formalin test was used...
March 7, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28290133/the-effects-of-acute-gaba-treatment-on-the-functional-connectivity-and-network-topology-of-cortical-cultures
#17
Yao Han, Hong Li, Yiran Lang, Yuwei Zhao, Hongji Sun, Peng Zhang, Xuan Ma, Jiuqi Han, Qiyu Wang, Jin Zhou, Changyong Wang
γ-Aminobutyric acid (GABA) is an inhibitory transmitter, acting on receptor channels to reduce neuronal excitability in matured neural systems. However, electrophysiological responses of whole neuronal ensembles to the exposure to GABA are still unclear. We used micro-electrode arrays (MEAs) to study the effects of the increasing amount of GABA on functional network of cortical neural cultures. Then the recorded data were analyzed by the cross-covariance analysis and graph theory. Results showed that after the GABA treatment, the activity parameters of firing rate, bursting rate, bursting duration and network burst frequency in neural cultures decreased as expected...
March 13, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28286225/immunological-alteration-toxic-molecular-inductions-leading-to-cognitive-impairment-neurotoxicity-in-transgenic-mouse-model-of-alzheimer-s-disease
#18
Manuj Ahuja, Manal Buabeid, Engy Abdel-Rehman, Mohammed Majrashi, Kodeeswaran Parameshwaran, Rajesh Amin, Sindhu Ramesh, Kariharan Thiruchelvan, Satyanarayana Pondugula, Vishnu Suppiramaniam, Muralikrishnan Dhanasekaran
AIMS: Inflammation is considered to be one of the crucial pathological factors associated with the development of Alzheimer's disease, although supportive experimental evidence remains undiscovered. Therefore, the current study was carried out to better understand and establish the pathophysiological involvement of chronic inflammation in a double transgenic mouse model of Alzheimer's disease. MAIN METHODS: We analyzed amyloid-beta deposition, oxidative stress, biochemical, neurochemical and immunological markers in a 10month old (APΔE9) mouse model...
March 9, 2017: Life Sciences
https://www.readbyqxmd.com/read/28286129/fret-based-sensors-unravel-activation-and-allosteric-modulation-of-the-gabab-receptor
#19
Nathalie Lecat-Guillet, Carine Monnier, Xavier Rovira, Julie Kniazeff, Laurent Lamarque, Jurriaan M Zwier, Eric Trinquet, Jean-Philippe Pin, Philippe Rondard
The main inhibitory neurotransmitter, γ-aminobutyric acid (GABA), modulates many synapses by activating the G protein-coupled receptor GABAB, which is a target for various therapeutic applications. It is an obligatory heterodimer made of GB1 and GB2 that can be regulated by positive allosteric modulators (PAMs). The molecular mechanism of activation of the GABAB receptor remains poorly understood. Here, we have developed FRET-based conformational GABAB sensors compatible with high-throughput screening. We identified conformational changes occurring within the extracellular and transmembrane domains upon receptor activation, which are smaller than those observed in the related metabotropic glutamate receptors...
March 16, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28285877/neurotransmitter-regulated-regeneration-in-the-zebrafish-retina
#20
Mahesh B Rao, Dominic Didiano, James G Patton
Current efforts to repair damaged or diseased mammalian retinas are inefficient and largely incapable of fully restoring vision. Conversely, the zebrafish retina is capable of spontaneous regeneration upon damage using Müller glia (MG)-derived progenitors. Understanding how zebrafish MG initiate regeneration may help develop new treatments that prompt mammalian retinas to regenerate. We show that inhibition of γ-aminobutyric acid (GABA) signaling facilitates initiation of MG proliferation. GABA levels decrease following damage, and MG are positioned to detect decreased ambient levels and undergo dedifferentiation...
March 6, 2017: Stem Cell Reports
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