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GABA receptor

Shehla Akbar, Fazal Subhan, Nasiara Karim, Muhammad Shahid, Nisar Ahmad, Gowhar Ali, Wajahat Mahmood, Khwaja Fawad
BACKGROUND: Diabetic neuropathy is the most prevalent, persistent and debilitating complication of diabetes mellitus often coupled with vulvodynia that may present as an isolated symptom or as a part of constellation of other neuropathic abnormalities. OBJECTIVE: Flavonoids have selective affinity for GABA receptors and 6-methoxyflavanone (6-MeOF) is a positive allosteric modulator of GABA responses at human recombinant GABAA receptors. GABAergic and opioidergic system inhibition have been shown to facilitate neuropathic pain...
October 17, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Thomas J Younts, Hannah R Monday, Barna Dudok, Matthew E Klein, Bryen A Jordan, István Katona, Pablo E Castillo
Long-term changes of neurotransmitter release are critical for proper brain function. However, the molecular mechanisms underlying these changes are poorly understood. While protein synthesis is crucial for the consolidation of postsynaptic plasticity, whether and how protein synthesis regulates presynaptic plasticity in the mature mammalian brain remain unclear. Here, using paired whole-cell recordings in rodent hippocampal slices, we report that presynaptic protein synthesis is required for long-term, but not short-term, plasticity of GABA release from type 1 cannabinoid receptor (CB1)-expressing axons...
October 19, 2016: Neuron
Sergio Valbuena, Juan Lerma
Neurotransmitter receptors are responsible for the transfer of information across the synapse. While ionotropic receptors form ion channels and mediate rapid membrane depolarization, so-called metabotropic receptors exert their action though slower, less direct intracellular signaling pathways. Glutamate, GABA, and acetylcholine can activate both ionotropic and metabotropic receptors, yet the distinction between these "canonical" signaling systems has become less clear since ionotropic receptors were proposed to also activate second messenger systems, defining a "non-canonical" signaling pathway...
October 19, 2016: Neuron
Juexin Wang, Dingding Shen, Geqing Xia, Wangzhen Shen, Robert L Macdonald, Dong Xu, Jing-Qiong Kang
Mutations in GABAA receptor subunit genes are frequently associated with epilepsy, and nonsense mutations in GABRG2 are associated with several epilepsy syndromes including childhood absence epilepsy, generalized tonic clonic seizures and the epileptic encephalopathy, Dravet syndrome. The molecular basis for the phenotypic heterogeneity of mutations is unclear. Here we focused on three nonsense mutations in GABRG2 (GABRG2(R136*), GABRG2(Q390*) and GABRG2(W429*)) associated with epilepsies of different severities...
October 20, 2016: Scientific Reports
Seok Roh Yoon, Cho Ara, Zhou Zixiong, Jeong Hyuneui, Park Jeong-Eun, Cha Youn-Soo, Oh Suk-Heung, Lim Chae-Woong, Kim Bumseok
<p>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
Mark J Millan, Jean-Michel Rivet, Alain Gobert
The highly-interconnected and neurochemically-rich frontal cortex plays a crucial role in the regulation of mood and cognition, domains disrupted in depression and other central nervous system disorders, and it is an important site of action for their therapeutic control. For improving our understanding of the function and dysfunction of the frontal cortex, and for identifying improved treatments, quantification of extracellular pools of neuromodulators by microdialysis in freely-moving rodents has proven indispensable...
October 17, 2016: Journal of Psychopharmacology
Mi-Na Kim, Young-Beom Kim, Seong-Mi Park, Yang In Kim, Wan-Joo Shim
OBJECTIVE: Estrogen has cardio-protective effect via several peripheral mechanism. But its action on central nervous system has not been fully investigated. Estrogen receptors are expressed in the hypothalamic magnocellular neurons, secreting vasopressin. In the male-rat models of DOCA-salt, GABA functions as an excitatory, rather than inhibitory neurotransmitter in vasopressin neurons. It might contribute to the development and maintenance of hypertension. In the current study, the effect of estrogen on central GABA action was investigated in the female rat models...
September 2016: Journal of Hypertension
Michael Saul, Petra Majdak, Samuel Perez, Matthew Reilly, Theodore Garland, Justin S Rhodes
Though exercise is critical for health, many lack the motivation to exercise, and it is unclear how motivation might be increased. To uncover the molecular underpinnings of increased motivation for exercise, we analyzed the transcriptome of the striatum in four mouse lines selectively bred for high voluntary wheel running and four non-selected control lines. The striatum was dissected and RNA was extracted and sequenced from four individuals of each line. We found multiple genes and gene systems with strong relationships to both selection and running history over the previous 6 days...
October 17, 2016: Genes, Brain, and Behavior
Vincenzo De Iuliis, Raimondo Gelormini, Mariarosaria Flacco, Giuseppe Moriello, Marika Caruso, Eugenia Barone, Maria Golato, Elena Toniato, Pio Conti, Stefano Martinotti
BACKGROUND: Valproate is a broad-spectrum anticonvulsant that is effective in the treatment of tonic-clonic, myoclonic and absence seizures as well as in partial seizures as a second-line drug. It has been widely demonstrated in the literature that the effect of valproate on type-A γ-aminobutyric acid (GABA-A) receptors may reduce relapse to ethanol abuse. This retrospective study evaluated a 3-year period in which 42 patients from the Department of Alcoholism and Substance Abuse (DASA) were treated with valproate...
March 2016: Drugs—Real World Outcomes
Ryota Tokunaga, Rie Shimoju, Hideshi Shibata, Mieko Kurosawa
Noxious cutaneous stimulation increases, whereas innocuous cutaneous stimulation decreases serotonin (5-HT) release in the central nucleus of the amygdala (CeA) in anesthetized rats. In the present study, we investigated the contribution of corticotropin releasing factor (CRF) receptors and gamma-aminobutyric acid (GABA) receptors in the dorsal raphe nucleus (DRN) to those responses. Release of 5-HT in the CeA was monitored by microdialysis before and after 10-min stimulation by pinching or stroking. Increased 5-HT release in the CeA in response to pinching was abolished by CRF2 receptor antagonism in the DRN...
October 15, 2016: Journal of Physiological Sciences: JPS
Meg Waraczynski, Samantha Abbott, Alex V Schultz
Previous work in our laboratory has shown that stimulating D2 dopamine receptors in the central sublenticular extended amygdala (SLEAc) can render medial forebrain bundle (MFB) stimulation less rewarding. One of the many ways in which D2 stimulation could affect the activity status of SLEAc neurons is by indirectly blocking calcium ion (Ca(2+)) influx through CaV1.3 channels. He we directly investigate the effects of blocking CaV1.3 channels on the rewarding effect of MFB stimulation. In experiment one, CaV1...
October 12, 2016: Behavioural Brain Research
Ignat Printsev, Daniel Curiel, Kermit L Carraway
The canonical function of the endoplasmic reticulum-associated degradation (ERAD) system is to enforce quality control among membrane-associated proteins by targeting misfolded secreted, intra-organellar, and intramembrane proteins for degradation. However, increasing evidence suggests that ERAD additionally functions in maintaining appropriate levels of a subset of membrane-associated proteins. In this 'quantity control' capacity, ERAD responds to environmental cues to regulate the proteasomal degradation of specific ERAD substrates according to cellular need...
October 14, 2016: Journal of Membrane Biology
Marie Gendrel, Emily G Atlas, Oliver Hobert
Neurotransmitter maps are important complements to anatomical maps and represent an invaluable resource to understand nervous system function and development. We report here a comprehensive map of neurons in the C. elegans nervous system that contain the neurotransmitter GABA, revealing twice as many GABA-positive neuron classes as previously reported. We define previously unknown glia-like cells that take up GABA, as well as 'GABA uptake neurons' which do not synthesize GABA but take it up from the extracellular environment, and we map the expression of previously uncharacterized ionotropic GABA receptors...
October 14, 2016: ELife
Mona A Alqazzaz, Kerry L Price, Sarah C R Lummis
Cys-loop receptors play important roles in signal transduction in multicellular organisms, but similar proteins exist in prokaryotes, the best studied of which is the Gloeobacter ligand-gated ion channel (GLIC). GLIC is activated by protons with 50% activation (pH50) at pH 5.5, and while a histidine residue in its pore-forming α-helix (M2) is known to be involved in gating, there is also evidence of a proton-sensitive region in the extracellular domain. However, this proton-sensitive region does not appear to be located in the region of GLIC equivalent to the agonist binding site in related proteins...
October 14, 2016: Biochemistry
Inge Mick, Anna C Ramos, Jim Myers, Paul R Stokes, Samantha Chandrasekera, David Erritzoe, Maria A Mendez, Roger N Gunn, Eugenii A Rabiner, Graham E Searle, José C F Galduróz, Adam D Waldman, Henrietta Bowden-Jones, Luke Clark, David J Nutt, Anne R Lingford-Hughes
As a behavioural addiction, gambling disorder (GD) provides an opportunity to characterize addictive processes without the potentially confounding effects of chronic excessive drug and alcohol exposure. Impulsivity is an established precursor to such addictive behaviours, and GD is associated with greater impulsivity. There is also evidence of GABAergic dysregulation in substance addiction and in impulsivity. This study therefore investigated GABAA receptor availability in 15 individuals with GD and 19 healthy volunteers (HV) using [(11) C]Ro15-4513, a relatively selective α5 benzodiazepine receptor PET tracer and its relationship with impulsivity...
October 13, 2016: Addiction Biology
Rocio Saravia, África Flores, Ainhoa Plaza-Zabala, Arnau Busquets-Garcia, Antoni Pastor, Rafael de la Torre, Vincenzo Di Marzo, Giovanni Marsicano, Andrés Ozaita, Rafael Maldonado, Fernando Berrendero
BACKGROUND: Tobacco withdrawal is associated with deficits in cognitive function, including attention, working memory, and episodic memory. Understanding the neurobiological mechanisms involved in these effects is crucial because cognitive deficits during nicotine withdrawal may predict relapse in humans. METHODS: We investigated in mice the role of CB1 cannabinoid receptors (CB1Rs) in memory impairment and spine density changes induced by nicotine withdrawal precipitated by the nicotinic antagonist mecamylamine...
July 16, 2016: Biological Psychiatry
S Hossein Fatemi, Timothy D Folsom, Stephanie B Liesch, Rachel E Kneeland, Mahtab Karkhane Yousefi, Paul D Thuras
Prenatal viral infection has been identified as a potential risk factor for the development of neurodevelopmental disorders such as schizophrenia and autism. Additionally, dysfunction in gamma-aminobutyric acid, Reelin, and fragile X mental retardation protein (FMRP)-metabotropic glutamate receptor 5 signaling systems has also been demonstrated in these two disorders. In the current report, we have characterized the developmental profiles of selected markers for these systems in cerebella of mice born to pregnant mice infected with human influenza (H1N1) virus on embryonic day 16 or sham-infected controls using SDS-PAGE and Western blotting techniques and evaluated the presence of abnormalities in the above-mentioned markers during brain development...
October 13, 2016: Journal of Neuroscience Research
Nicola Forte, Lucian Medrihan, Beatrice Cappetti, Pietro Baldelli, Fabio Benfenati
OBJECTIVE: The inhibition of glycolysis exerts potent antiseizure effects, as demonstrated by the efficacy of ketogenic and low-glucose/nonketogenic diets in the treatment of drug-resistant epilepsy. ATP-sensitive potassium (KATP ) channels have been initially identified as the main determinant of the reduction of neuronal hyperexcitability. However, a plethora of other mechanisms have been proposed. Herein, we report the ability of 2-deoxy-d-glucose (2-DG), a glucose analog that inhibits glycolytic enzymes, of potentiating γ-aminobutyric acid (GABA)ergic tonic inhibition via neurosteroid-mediated activation of extrasynaptic GABAA receptors...
October 13, 2016: Epilepsia
Edyta K Bichler, Courtney C Elder, Paul S García
Antibiotics are used in the treatment and prevention of bacterial infections, but effects on neuron excitability have been documented. A recent study demonstrated that clarithromycin alleviates daytime sleepiness in hypersomnia patients (Trotti et al. 2014). To explore the potential application of clarithromycin as a stimulant, we performed whole cell patch clamp recordings in rat pyramidal cells from the CA3 region of hippocampus. In the presence of the antibiotic, rheobase current was reduced by 50%, F-I relationship (number of action potentials as a function of injected current) was shifted to the left, and the resting membrane potential was more depolarized...
October 12, 2016: Journal of Neurophysiology
Sivan Subburaju, Andrew J Coleman, Miles G Cunningham, W Brad Ruzicka, Francine M Benes
GABAergic dysfunction in hippocampus, a key feature of schizophrenia (SZ), may contribute to cognitive impairment in this disorder. In stratum oriens (SO) of sector CA3/2 of the human hippocampus, a network of genes involved in the regulation of glutamic acid decarboxylase GAD67 has been identified. Several of the genes in this network including epigenetic factors histone deacetylase 1 (HDAC1) and death-associated protein 6 (DAXX), the GABAergic enzyme GAD65 as well as the kainate receptor (KAR) subunits GluR6 and 7 show significant changes in expression in this area in SZ...
October 12, 2016: Cerebral Cortex
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