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Stavros Stivaros, Shruti Garg, Maria Tziraki, Ying Cai, Owen Thomas, Joseph Mellor, Andrew A Morris, Carly Jim, Karolina Szumanska-Ryt, Laura M Parkes, Hamied A Haroon, Daniela Montaldi, Nicholas Webb, John Keane, Francisco X Castellanos, Alcino J Silva, Sue Huson, Stephen Williams, D Gareth Evans, Richard Emsley, Jonathan Green
Background: Neurofibromatosis 1 (NF1) is a monogenic model for syndromic autism. Statins rescue the social and cognitive phenotype in animal knockout models, but translational trials with subjects > 8 years using cognition/behaviour outcomes have shown mixed results. This trial breaks new ground by studying statin effects for the first time in younger children with NF1 and co-morbid autism and by using multiparametric imaging outcomes. Methods: A single-site triple-blind RCT of simvastatin vs...
2018: Molecular Autism
Kazushi Ichikawa, Megumi Tsuji, Yu Tsuyusaki, Moyoko Tomiyasu, Noriko Aida, Tomohide Goto
Gamma-aminobutyric acid transaminase (GABA-T) deficiency is a rare, autosomal recessive disorder characterized by severe psychomotor retardation, early-onset epileptic encephalopathy, intractable seizures, hypotonia, and hyperreflexia. The disease is caused by mutation in the 4-aminobutyrate aminotransferase (ABAT) gene, which encodes an enzyme involved in GABA catabolism. In this chapter, a 10-year follow-up of GABA-T deficiency in a rare case of a long-term survivor patient is discussed. The patient showed a progression of clinical phases with increasing age...
February 25, 2018: JIMD Reports
Jurairat Khongrum, Jintanaporn Wattanathorn
The novel therapeutic strategy against autism is essential due to the limited therapeutic efficacy. Based on the benefit of laser acupuncture at HT7 acupoint on the neurological disorders related with oxidative stress and inflammation, its benefit on oxidative stress, neuroinflammation, and GABAergic/glutamatergic imbalance in cerebellum of autism have been considered. To elucidate this issue, male rat pups were induced autistic-like conditions by valproic acid (VPA) and treated with laser acupuncture at HT7 acupoint once daily between postnatal Day 14 and Day 40...
August 2017: Journal of Acupuncture and Meridian Studies
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
Heath G Gasier, Ivan T Demchenko, Lynn G Tatro, Claude A Piantadosi
Breathing oxygen at partial pressures ≥2.5 atmospheres absolute, which can occur in diving and hyperbaric oxygen (HBO2) therapy, can rapidly become toxic to the central nervous system (CNS). This neurotoxicity culminates in generalized EEG epileptiform discharges, tonic-clonic convulsions and ultimately death. Increased production of neuronal nitric oxide (NO) has been implicated in eliciting hyperoxic seizures by altering the equilibrium between glutamatergic and GABAergic synaptic transmission. Inhibition of glutamic acid decarboxylase (GAD) activity in HBO2 promotes this imbalance; however, the mechanisms by which this occurs is unknown...
July 13, 2017: Neuroscience Letters
Zhifeng Xu, Yanchao Liu, Peng Wei, Kaiyang Feng, Jinzhi Niu, Guangmao Shen, Wencai Lu, Wei Xiao, Jinjun Wang, Guy J Smagghe, Qiang Xu, Lin He
Abamectin has been widely used as an insecticide/acaricide for more than 30 years because of its superior bioactivity. Recently, an interesting phenomenon was identified in the carmine spider mite, Tetranychus cinnabarinus, an important pest in agriculture. The gamma aminobutyric acid (GABA) contents in a laboratory abamectin resistant strain of T. cinnabarinus (AbR) were significantly increased. Decreases in activity and mRNA expression of GABA transaminase (GABA-T) were responsible for GABA accumulation in AbR mites...
2017: Frontiers in Physiology
Dora Ravasz, Gergely Kacso, Viktoria Fodor, Kata Horvath, Vera Adam-Vizi, Christos Chinopoulos
GABA is catabolized in the mitochondrial matrix through the GABA shunt, encompassing transamination to succinic semialdehyde followed by oxidation to succinate by the concerted actions of GABA transaminase (GABA-T) and succinic semialdehyde dehydrogenase (SSADH), respectively. Gamma-hydroxybutyrate (GHB) is a neurotransmitter and a psychoactive drug that could enter the citric acid cycle through transhydrogenation with α-ketoglutarate to succinic semialdehyde and d-hydroxyglutarate, a reaction catalyzed by hydroxyacid-oxoacid transhydrogenase (HOT)...
October 2017: Neurochemistry International
Arnab Dhar, Santosh Kumar Maurya, Ashish Mishra, Gireesh Kumar Singh, Manoj Kumar Singh, Ankit Seth
BACKGROUND: Epilepsy is a serious and complex central nervous system disorder associated with recurrent episodes of convulsive seizures due to the imbalance between excitatory (glutamatergic) and inhibitory (GABAergic) neurotransmitters level in the brain. The available treatments are neither competent to control the seizures nor prevent progress of disease. Since ages, Herbal medicines have remained important sources of medicines in many parts of world which is evidenced through their uses in traditional systems of medicine i...
July 2016: Ancient Science of Life
Morteza Soleimani Aghdam, Javad Rezapour Fard
Fresh strawberry fruits as perishable commodities have a short postharvest life and are prone to postharvest fungal decay. In this study, the impact of 0, 1, 10, 100 and 1000μmol/L melatonin on attenuating fungal decay and maintaining nutritional quality of strawberry fruits was investigated during storage at 4°C for 12days. Melatonin treatment at 100μmol/L triggered H2O2 accumulation, which result from higher superoxide dismutase (SOD) activity, associated with lower catalase (CAT) and ascorbate peroxidase (APX) activities, leading to fruits with lower decay...
April 15, 2017: Food Chemistry
Karen Sousa, Natalia Decker, Thienne Rocha Pires, Débora Kuck Mausolff Papke, Vanessa Rodrigues Coelho, Pricila Pflüger, Patrícia Pereira, Jaqueline Nascimento Picada
RATIONALE: Vigabatrin (VGB) is a drug indicated mostly for the treatment of spasms in childhood and West's syndrome patients. This drug inhibits irreversibly the enzyme GABA-transaminase (GABA-T), increasing GABA concentrations and enhancing GABAergic neurotransmission in the brain, which is known to induce behavioral changes. OBJECTIVES: The aims of this study were to evaluate the effects of VGB in the short-term memory (STM), long-term memory (LTM), motivation, locomotion, and exploratory behavior tests and to detect deleterious or protective effects on DNA in target tissues of the drug...
January 2017: Psychopharmacology
Lu Wang, Yan Wang, Shimeng Zhou, Liukun Yang, Qixin Shi, Yujiao Li, Kun Zhang, Le Yang, Minggao Zhao, Qi Yang
Fragile X syndrome (FXS) is a form of inherited mental retardation that results from the absence of the fragile X mental retardation protein (FMRP), the product of the Fmr1 gene. Numerous studies have shown that FMRP expression in astrocytes is important in the development of FXS. Although astrocytes affect neuronal dendrite development in Fmr1 knockout (KO) mice, the factors released by astrocytes are still unclear. We cultured wild type (WT) cortical neurons in astrocyte-conditioned medium (ACM) from WT or Fmr1 KO mice...
2016: Genes
Molin Zhou, Kessy H Ndeurumio, Lei Zhao, Zhuoyan Hu
Longan (Dimocarpus longan Lour.) fruit cultivars 'Chuliang' and 'Shixia' were analyzed for γ-aminobutyric acid (GABA) accumulation after precooling and in controlled-atmosphere storage. Fruit were exposed to 5% O2 plus 3%, 5%, or 10% CO2 at 4 °C, and GABA and associated enzymes, aril firmness, and pericarp color were measured. Aril softening and pericarp browning were delayed by 5% CO2 + 5% O2. GABA concentrations and glutamate decarboxylase (GAD; EC activities declined during storage at the higher-CO2 treatments...
August 24, 2016: Journal of Agricultural and Food Chemistry
Pedro Louro, Lina Ramos, Conceição Robalo, Cândida Cancelinha, Alexandra Dinis, Ricardo Veiga, Raquel Pina, Olinda Rebelo, Ana Pop, Luísa Diogo, Gajja S Salomons, Paula Garcia
Gamma-aminobutyric acid transaminase (GABA-T) deficiency is an autosomal recessive disorder reported in only three unrelated families. It is caused by mutations in the ABAT gene, which encodes 4-aminobutyrate transaminase, an enzyme of GABA catabolism and mitochondrial nucleoside salvage. We report the case of a boy, deceased at 12 months of age, with early-onset epileptic encephalopathy, severe psychomotor retardation, hypotonia, lower-limb hyporeflexia, central hypoventilation, and rapid increase in weight and, to a lesser rate, length and head circumference...
September 2016: Journal of Inherited Metabolic Disease
Morteza Soleimani Aghdam, Roohangiz Naderi, Abbasali Jannatizadeh, Mesbah Babalar, Mohammad Ali Askari Sarcheshmeh, Mojtaba Zamani Faradonbe
Anthurium flowers are susceptible to chilling injury, and the optimum storage temperature is 12.5-20 °C. The γ-aminobutyric acid (GABA) shunt pathway may alleviate chilling stress in horticultural commodities by providing energy (ATP), reducing molecules (NADH), and minimizing accumulation of reactive oxygen species (ROS). In this experiment, the impact of a preharvest spray treatment with 1 mM GABA and postharvest treatment of 5 mM GABA stem-end dipping on GABA shunt pathway activity of anthurium cut flowers (cv...
September 2016: Plant Physiology and Biochemistry: PPB
Laura Blancquaert, Shahid P Baba, Sebastian Kwiatkowski, Jan Stautemas, Sanne Stegen, Silvia Barbaresi, Weiliang Chung, Adjoa A Boakye, J David Hoetker, Aruni Bhatnagar, Joris Delanghe, Bert Vanheel, Maria Veiga-da-Cunha, Wim Derave, Inge Everaert
KEY POINTS: Using recombinant DNA technology, the present study provides the first strong and direct evidence indicating that β-alanine is an efficient substrate for the mammalian transaminating enzymes 4-aminobutyrate-2-oxoglutarate transaminase and alanine-glyoxylate transaminase. The concentration of carnosine and anserine in murine skeletal and heart muscle depends on circulating availability of β-alanine, which is in turn controlled by degradation of β-alanine in liver and kidney...
September 1, 2016: Journal of Physiology
Laura Gey, Manuela Gernert, Wolfgang Löscher
The subthalamic nucleus (STN) plays a crucial role as a regulator of basal ganglia outflow but also influences the activity of cortical and limbic structures, so that it is widely used as a therapeutic target in different brain diseases, including epilepsy. In addition to electrical stimulation of the STN, targeted delivery of anti-seizure drugs to the STN may constitute an alternative treatment approach in patients with pharmacoresistant epilepsy. In the present experimental study, we investigated the anti-seizure and adverse effects of chronic infusion of vigabatrin into the STN of rats...
July 2016: Neurobiology of Disease
Poorella Lingeshwar, Gurpreet Kaur, Neetu Singh, Seema Singh, Akanksha Mishra, Shubha Shukla, Rachumallu Ramakrishna, Tulsankar Sachin Laxman, Rabi Sankar Bhatta, Hefazat H Siddiqui, Kashif Hanif
Increased sympathetic nervous system (SNS) activity is associated with cardiovascular diseases but its role has not been completely explored in pulmonary hypertension (PH). Increased SNS activity is distinguished by elevated level of norepinephrine (NE) and activity of γ-Amino butyric acid Transminase (GABA-T) which degrades GABA, an inhibitory neurotransmitter within the central and peripheral nervous system. Therefore, we hypothesized that GABA-T may contribute in pathophysiology of PH by modulating level of GABA and NE...
February 2016: Pulmonary Pharmacology & Therapeutics
Hong Hu, Xi Bai, Assar Ali Shah, Sifa Dai, Like Wang, Jinling Hua, Chuanyan Che, Shaojun He, Aiyou Wen, Jinpeng Jiang
The present experiment was conducted to investigate the interactive effects between dietary glutamine (Gln, 0 and 5 g/kg) and gamma-aminobutyric acid (GABA, 0 and 100 mg/kg) on growth performance and amino acid (AA) metabolism of broilers under hot environment. A total of 360 22-day-old Arbor Acres male chickens were randomly assigned to five treatment groups under thermoneutral chamber (PC, 23 °C) and cyclic heat stress (HS, 30-34 °C cycling) conditions. Compared with the PC group, cyclic HS decreased (P < 0...
June 2016: International Journal of Biometeorology
Edward R Mariano, T Kyle Harrison, T Edward Kim, Jack Kan, Cynthia Shum, David M Gaba, Toni Ganaway, Alex Kou, Ankeet D Udani, Steven K Howard
OBJECTIVES: Practicing anesthesiologists have generally not received formal training in ultrasound-guided perineural catheter insertion. We designed this study to determine the efficacy of a standardized teaching program in this population. METHODS: Anesthesiologists in practice for 10 years or more were recruited and enrolled to participate in a 1-day program: lectures and live-model ultrasound scanning (morning) and faculty-led iterative practice and mannequin-based simulation (afternoon)...
October 2015: Journal of Ultrasound in Medicine: Official Journal of the American Institute of Ultrasound in Medicine
D Luger, G Poli, M Wieder, M Stadler, S Ke, M Ernst, A Hohaus, T Linder, T Seidel, T Langer, S Khom, S Hering
BACKGROUND AND PURPOSE: β2/3-subunit-selective modulation of GABAA receptors by valerenic acid (VA) is determined by the presence of transmembrane residue β2/3N265. Currently, it is not known whether β2/3N265 is part of VA's binding pocket or is involved in the transduction pathway of VA's action. The aim of this study was to clarify the localization of VA's binding pocket on GABAA receptors. EXPERIMENTAL APPROACH: Docking and a structure-based three-dimensional pharmacophore were employed to identify candidate amino acid residues that are likely to interact with VA...
November 2015: British Journal of Pharmacology
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