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gamma-aminobutyric acid

Igor Alexander Harsch, Peter Christopher Konturek
The investigation of the human microbiome is the most rapidly expanding field in biomedicine. Early studies were undertaken to better understand the role of microbiota in carbohydrate digestion and utilization. These processes include polysaccharide degradation, glycan transport, glycolysis, and short-chain fatty acid production. Recent research has demonstrated that the intricate axis between gut microbiota and the host metabolism is much more complex. Gut microbiota—depending on their composition—have disease-promoting effects but can also possess protective properties...
April 17, 2018: Medical Sciences: Open Access Journal
Marta Skelin, Danijel Bursać, Viviana Kozina, Tristan Winters, Marija Macan, Marija Ćurlin
Cervical mucus modulates fertility by cyclical changes of its biophysical and functional properties. Based on an analogy with bronchial goblet cells we set out to investigate the possible role of the gamma-aminobutyric acid (GABA) signalling pathway in the mediation of oestrogen-induced mucus secretion from endocervical secretory cells. The aim of the study was to examine the existence of GABAA receptor (GABAAR), glutamic acid decarboxylase 65/67 (GAD65/67) and vesicular GABA transporter (VGAT) in human and mouse cervical tissue...
April 18, 2018: Reproduction, Fertility, and Development
Mehdi Farokhnia, Mikela B Sheskier, Mary R Lee, April N Le, Erick Singley, Sofia Bouhlal, Timmy Ton, Zhen Zhao, Lorenzo Leggio
Gamma-aminobutyric acid (GABA), the main inhibitory neurotransmitter in the nervous system, plays an important role in biobehavioral processes that regulate alcohol seeking, food intake, and stress response. The metabotropic GABA-B receptor has been investigated as a potential therapeutic target for alcohol use disorder, by using orthosteric agonists (e.g., baclofen) and positive allosteric modulators. Whether and how pharmacological manipulation of the GABA-B receptor, in combination with alcohol intake, may affect feeding- and stress-related neuroendocrine pathways remains unknown...
April 14, 2018: Neuropharmacology
Samer Alabed, Youssef Latifeh, Husam Aldeen Mohammad, Hanna Bergman
BACKGROUND: Chronic antipsychotic drug treatment may cause tardive dyskinesia (TD), a long-term movement disorder. Gamma-aminobutyric acid (GABA) agonist drugs, which have intense sedative properties and may exacerbate psychotic symptoms, have been used to treat TD. OBJECTIVES: 1. Primary objectiveThe primary objective was to determine whether using non-benzodiazepine GABA agonist drugs for at least six weeks was clinically effective for the treatment of antipsychotic-induced TD in people with schizophrenia, schizoaffective disorder or other chronic mental illnesses...
April 17, 2018: Cochrane Database of Systematic Reviews
B Calvo-Flores Guzmán, C Vinnakota, K Govindpani, H Waldvogel, R L Faull, A Kwakowsky
Glutamatergic and cholinergic dysfunction are well-attested features of Alzheimer's disease (AD), progressing with other pathological indices of the disorder and exacerbating neuronal and network dysfunction. However, relatively little attention has been paid to the inhibitory component of the excitatory/inhibitory (E/I) network, particularly dysfunction in the gamma-aminobutyric acid (GABA) signaling system. There is growing evidence in support of GABAergic remodeling in the AD brain, potentially beginning in early stages of disease pathogenesis, and this could thus be a valid molecular target for drug development and pharmacological therapies...
April 12, 2018: Journal of Neurochemistry
Zhibing Tan, Heath L Robinson, Dong-Min Yin, Yu Liu, Fang Liu, Hongsheng Wang, Thiri W Lin, Guanglin Xing, Lin Gan, Wen-Cheng Xiong, Lin Mei
Top-down attention is crucial for meaningful behaviors and impaired in various mental disorders. However, its underpinning regulatory mechanisms are poorly understood. We demonstrate that the hippocampal-prefrontal synchrony associates with levels of top-down attention. Both attention and synchrony are reduced in mutant mice of ErbB4, a receptor of neuregulin-1. We used chemical genetic and optogenetic approaches to inactivate ErbB4 kinase and ErbB4+ interneurons, respectively, both of which reduce gamma-aminobutyric acid (GABA) activity...
April 3, 2018: Neuron
Bo Zhang, Lei Zhang, Lujue He, Xiaodong Yang, Yali Shi, Shaowei Liao, Shan Yang, Jiagao Cheng, Tianrui Ren
Fipronil is an efficient phenylpyrazole insecticide that acts on insect gamma-aminobutyric acid (GABA) receptors (GABARs) and has low toxicity to mammals but high toxicity to non-target organisms such as fish. To develop novel efficient low-toxicity insecticides, it is necessary to determine the detailed toxic mechanism at the molecular target level. In this work, methods including affinity chromatography, fluorescent-labeled binding assays and molecular modeling were integrated to explore the binding of fipronil to GABARs in fish (A...
April 7, 2018: Journal of Agricultural and Food Chemistry
Satoru Ikemoto, Shin-Ichiro Hamano, Yuko Hirata, Ryuki Matsuura, Kenjiro Kikuchi
BACKGROUND: Iodine 123 (I-123) iomazenil is a specific ligand of the central benzodiazepine receptor, which is a part of the postsynaptic gamma-aminobutyric acid A receptor complex. We performed statistical image processing of I-123 iomazenil single-photon emission computed tomography to elucidate maturational changes in the GABAergic system. METHODS: Thirty patients (18 boys and 12 girls, aged 17 days to 14 years) with cryptogenic focal epilepsy were enrolled and underwent I-123 iomazenil single-photon emission computed tomography...
April 3, 2018: Pediatric Neurology
Nethrajeith Srinivasalu, Sally A McFadden, Callan Medcalf, Lena Fuchs, Jessica Chung, Gayle Philip, Andrea Richardson, Moeen Riaz, Paul N Baird
Purpose: Posterior scleral remodeling accompanies myopia. In guinea pigs developing myopia, the region around the optic nerve (peripapillary zone, PPZ) rapidly expands followed by inhibition in eye size in the periphery. We studied the differential gene expression in the sclera that accompanies these changes. Methods: Guinea pigs were form-deprived (FD) for 2 weeks to induce myopia, while the fellow eye served as a control. After 2 weeks, the PPZ and the peripheral temporal sclera were isolated in representative animals to extract the RNA...
March 1, 2018: Investigative Ophthalmology & Visual Science
Sara Guzzetti, Luciano Calzari, Lucia Buccarello, Valentina Cesari, Ivan Toschi, Stefania Cattaldo, Alessandro Mauro, Francesca Pregnolato, Silvia Michela Mazzola, Silvia Russo
Angelman syndrome (AS, MIM 105830) is a rare neurodevelopmental disorder affecting 1:10-20,000 children. Patients show moderate to severe intellectual disability, ataxia and absence of speech. Studies on both post-mortem AS human brains and mouse models revealed dysfunctions in the extra synaptic gamma-aminobutyric acid (GABA) receptors implicated in the pathogenesis. Taurine is a free intracellular sulfur-containing amino acid, abundant in brain, considered an inhibiting neurotransmitter with neuroprotective properties...
April 5, 2018: International Journal of Molecular Sciences
Daniel Friedman, Kasthuri Kannan, Arline Faustin, Seema Shroff, Cheddhi Thomas, Adriana Heguy, Jonathan Serrano, Matija Snuderl, Orrin Devinsky
Sudden unexpected death in epilepsy (SUDEP) is the leading cause of epilepsy-related mortality in young adults. The exact mechanisms are unknown but death often follows a generalized tonic-clonic seizure. Proposed mechanisms include seizure-related respiratory, cardiac, autonomic, and arousal dysfunction. Genetic drivers underlying SUDEP risk are largely unknown. To identify potential SUDEP risk genes, we compared whole-exome sequences (WES) derived from formalin-fixed paraffin embedded surgical brain specimens of eight epilepsy patients who died from SUDEP with seven living controls matched for age at surgery, sex, year of surgery and lobe of resection...
2018: NPJ Genomic Medicine
Sunita A Ramesh, Muhammad Kamran, Wendy Sullivan, Larissa Chirkova, Mamoru Okamoto, Fien Degryse, Michael McLauchlin, Matthew Gilliham, Stephen D Tyerman
Plant aluminium-activated malate transporters (ALMTs) are currently classified as anion channels; they are also known to be regulated by diverse signals, leading to a range of physiological responses. Gamma-aminobutyric acid (GABA) regulation of anion flux through ALMT proteins requires a specific amino acid motif in ALMTs that shares similarity with a GABA-binding site in mammalian GABAA receptors. Here, we explore why TaALMT1-activation leads to a negative correlation between malate efflux and endogenous GABA concentrations ([GABA]i) in both wheat (Titicum aestivum L) root tips and in heterologous expression systems...
April 4, 2018: Plant Cell
José J Miguel-Hidalgo
Postmortem studies reveal structural and molecular alterations of astrocytes and oligodendrocytes in both the gray and white matter (GM and WM) of the prefrontal cortex (PFC) in human subjects with chronic alcohol abuse or dependence. These glial cellular changes appear to parallel and may largely explain structural and functional alterations detected using neuroimaging techniques in subjects with alcohol use disorders (AUDs). Moreover, due to the crucial roles of astrocytes and oligodendrocytes in neurotransmission and signal conduction, these cells are very likely major players in the molecular mechanisms underpinning alcoholism-related connectivity disturbances between the PFC and relevant interconnecting brain regions...
2018: Frontiers in Molecular Neuroscience
Ronan A Mooney, John Cirillo, Winston D Byblow
Primary motor cortex excitability can be modulated by anodal and cathodal transcranial direct current stimulation (tDCS). These neuromodulatory effects may, in part, be dependent on modulation within gamma-aminobutyric acid (GABA)-mediated inhibitory networks. GABAergic function can be quantified non-invasively using adaptive threshold hunting paired-pulse transcranial magnetic stimulation (TMS). The previous studies have used TMS with posterior-anterior (PA) induced current to assess tDCS effects on inhibition...
April 2, 2018: Experimental Brain Research. Experimentelle Hirnforschung. Expérimentation Cérébrale
Pengfei Sui, Darin L Wiesner, Jinhao Xu, Yan Zhang, Jinwoo Lee, Steven Van Dyken, Amber Lashua, Chuyue Yu, Bruce S Klein, Richard M Locksley, Gail Deutsch, Xin Sun
Pulmonary neuroendocrine cells (PNECs) are rare airway epithelial cells whose function is poorly understood. Here we show that Ascl1 -mutant mice which have no PNECs exhibit severely blunted mucosal type 2 response in models of allergic asthma. PNECs reside in close proximity to group 2 innate lymphoid cells (ILC2s) near airway branch points. PNECs act through calcitonin gene-related peptide (CGRP) to stimulate ILC2s and elicit downstream immune responses. In addition, PNECs act through neurotransmitter gamma-aminobutyric acid (GABA) to induce goblet-cell hyperplasia...
March 29, 2018: Science
Mi Jung Kim, Hye Jin Yang, Younghoon Kim, Insug Kang, Sung Soo Kim, Young-Wuk Cho
Serotonergic neurons in the dorsal raphe nucleus (DRN) act as wake-inducing neurons in the sleep-wake cycle and are controlled by gamma-aminobutyric acid (GABA) synaptic inputs. We investigated daily changes in GABAergic inhibition of the rat DRN neurons and the role of nitric oxide (NO) and cation-chloride co-transporters in the GABAergic action. Neuronal NO synthase (nNOS) was co-expressed in 74% of serotonergic DRN neurons and nNOS expression was higher during daytime (the sleep cycle) than that during nighttime (the wake cycle)...
March 27, 2018: Neuropharmacology
Doodipala Samba Reddy, Ryan F Yoshimura, Gunasekaran Ramanathan, Chase Carver, Timothy B Johnstone, Derk J Hogenkamp, Kelvin W Gee
OBJECTIVE: Subunit-specific positive allosteric modulators (PAMs) of gamma-aminobutyric acid-A (GABA-A) receptors are commonly used to uncover the role of GABA-A receptor isoforms in brain function. Recently, we have designed novel PAMs selective for β2/3 -subunit containing GABA-A receptors (β2/3 -selective PAMs) that are nonbenzodiazepine site-mediated and do not show an α-subunit isoform selectivity, yet exhibit anxiolytic efficacy with reduced potential for sedation, cognitive impairment, and tolerance...
March 24, 2018: Epilepsy & Behavior: E&B
Justyna Pyrzanowska, Adriana Wawer, Ilona Joniec-Maciejak, Agnieszka Piechal, Kamilla Blecharz-Klin, Konstantia Graikou, Ioanna Chinou, Ewa Widy-Tyszkiewicz
Royal Jelly (RJ) is a unique substance obtained from bees that has been used widely in European and Asian traditional medicine for its potential to prevent signs of aging through its antioxidative, anti-inflammatory, anti-hyperglycemic and anti-hypercholesterolemic properties. We recently reported an enhancement in spatial memory along with changes in monoaminergic transmission in aged rats after chronic RJ administration. Here, we aim to further explore the action of RJ on central nervous system activity by examining levels of amino acids in selected brain structures of aged male Wistar rats following 2-months of Greek RJ administration...
March 22, 2018: Neuroscience Letters
Aryo Zare, Ali Jahanshahi, Celine Meriaux, Harry Wm Steinbusch, Gommert A van Koeveringe
OBJECTIVES: To determine the phenotype of the ventrolateral part of the periaqueductal gray matter neurons after bladder stimulation. METHODS: In the experimental group, electrical stimulation of the bladder was carried out under freely moving condition by a bipolar stimulation electrode implanted in the bladder wall. Thereafter, the brain sections were processed for immunohistochemical analysis using antibodies against c-Fos (neuronal activation marker) together with one of the following: tyrosine hydroxylase (dopaminergic cell marker), vesicular glutamate transporter (glutamatergic cell marker), serotonin, glutamate decarboxylase (glutamate decarboxylase 67, gamma-aminobutyric acid cell marker) and neuronal nitric oxide synthase...
March 25, 2018: International Journal of Urology: Official Journal of the Japanese Urological Association
Elisenda Cortès-Saladelafont, Marta Molero-Luis, Daniel Cuadras, Mercedes Casado, Judith Armstrong-Morón, Dèlia Yubero, Julio Montoya, Rafael Artuch, Àngels García-Cazorla
AIM: Gamma-aminobutyric acid (GABA) is a major modulator in brain maturation and its role in many different neurodevelopmental disorders has been widely reported. Although the involvement of GABA in different disorders has been related to its regulatory function as an inhibitory neurotransmitter in the mature brain, co-transmitter, and signalling molecule, little is known about its role as a clinical biomarker in neuropaediatric disorders. The aim of this study is to report the cerebrospinal fluid (CSF) free-GABA concentrations in a large cohort of patients (n=85) with different neurological disorders...
March 25, 2018: Developmental Medicine and Child Neurology
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