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Sample records for gamma aminobutyric acid

  1. Brain gamma-aminobutyric acid deficiency in dialysis encephalopathy.

    Science.gov (United States)

    Sweeney, V P; Perry, T L; Price, J D; Reeve, C E; Godolphin, W J; Kish, S J

    1985-02-01

    We measured levels of gamma-aminobutyric acid (GABA) in the CSF and in the autopsied brain of patients with dialysis encephalopathy. GABA concentrations were low in the CSF of three of five living patients. Mean GABA content was reduced by 30 to 50% in five brain regions (frontal, occipital, and cerebellar cortex, caudate nucleus, and medial dorsal thalamus) in five fatal cases. GABA content was normal in brain regions where GABA is characteristically reduced in Huntington's disease. Choline acetyltransferase activity was diminished (by 25 to 35%) in cerebral cortex of the dialysis encephalopathy patients.

  2. Increased brain uptake of gamma-aminobutyric acid in a rabbit model of hepatic encephalopathy

    International Nuclear Information System (INIS)

    Bassett, M.L.; Mullen, K.D.; Scholz, B.; Fenstermacher, J.D.; Jones, E.A.

    1990-01-01

    Transfer of the inhibitory neurotransmitter gamma-aminobutyric acid across the normal blood-brain barrier is minimal. One prerequisite for gamma-aminobutyric acid in plasma contributing to the neural inhibition of hepatic encephalopathy would be that increased transfer of gamma-aminobutyric acid across the blood-brain barrier occurs in liver failure. The aim of the present study was to determine if brain gamma-aminobutyric acid uptake is increased in rabbits with stage II-III (precoma) hepatic encephalopathy due to galactosamine-induced fulminant hepatic failure. A modification of the Oldendorf intracarotid artery-injection technique was applied. [3H] gamma-aminobutyric acid, [14C] butanol, and 113mIn-labeled serum protein (transferrin) were injected simultaneously 4 s before decapitation. The ipsilateral brain uptake index of gamma-aminobutyric acid was determined from measurements of the 3 isotopes in 5 brain regions. Uncorrected or simple brain uptake indices of [3H] gamma-aminobutyric acid and [113mIn] transferrin were calculated using [14C] butanol as the highly extracted reference compound. The [113mIn] transferrin data were also used to correct the brain uptake index of [3H] gamma-aminobutyric acid for intravascular retention of [3H] gamma-aminobutyric acid. The methodology adopted minimized problems attributable to rapid [3H] gamma-aminobutyric acid metabolism, and slow brain washout and recirculation of the radiolabeled tracers. Both the uncorrected and corrected brain uptake indices of gamma-aminobutyric acid as well as the simple brain uptake index of transferrin were significantly increased in both stage II and III hepatic encephalopathy in all brain regions studied. Moreover, these brain uptake indices were significantly greater in stage III hepatic encephalopathy than in stage II hepatic encephalopathy

  3. gamma-Aminobutyric acid stimulates ethylene biosynthesis in sunflower

    International Nuclear Information System (INIS)

    Kathiresan, A.; Tung, P.; Chinnappa, C.C.; Reid, D.M.

    1997-01-01

    gamma-Aminobutyric acid (GABA), a nonprotein amino acid, is often accumulated in plants following environmental stimuli that can also cause ethylene production. We have investigated the relationship between GABA and ethylene production in excised sunflower (Helianthus annuus L.) tissues. Exogenous GABA causes up to a 14-fold increase in the ethylene production rate after about 12 h. Cotyledons fed with [14C]GABA did not release substantial amounts of radioactive ethylene despite its chemical similarity to 1-aminocyclopropane-1-carboxylic acid (ACC), indicating that GABA is not likely to be an alternative precursor for ethylene. GABA causes increases in ACC synthase mRNA accumulation, ACC levels, ACC oxidase mRNA levels, and in vitro ACC oxidase activity. In the presence of aminoethoxyvinylglycine or alpha-aminoisobutyric acid, GABA did not stimulate ethylene production. We therefore conclude that GABA stimulates ethylene biosynthesis mainly by promoting ACC synthase transcript abundance. Possible roles of GABA as a signal transducer are suggested

  4. Biotechnological advances and perspectives of gamma-aminobutyric acid production.

    Science.gov (United States)

    Xu, Ning; Wei, Liang; Liu, Jun

    2017-03-01

    Gamma-aminobutyric acid (GABA) is a four-carbon non-protein amino acid that is widely distributed among various organisms. Since GABA has several well-known physiological functions, such as mediating neurotransmission and hypotensive activity, as well as having tranquilizer effects, it is commonly used as a bioactive compound in the food, pharmaceutical and feed industries. The major pathway of GABA biosynthesis is the irreversible decarboxylation of L-glutamate catalyzed by glutamate decarboxylase (GAD), which develops a safe, sustainable and environmentally friendly alternative in comparison with traditional chemical synthesis methods. To date, several microorganisms have been successfully engineered for high-level GABA biosynthesis by overexpressing exogenous GADs. However, the activity of almost all reported microbial GADs sharply decreases at physiological near-neutral pH, which in turn provokes negative effects on the application of these GADs in the recombinant strains for GABA production. Therefore, ongoing efforts in the molecular evolution of GADs, in combination with high-throughput screening and metabolic engineering of particular producer strains, offer fascinating new prospects for effective, environmentally friendly and economically viable GABA biosynthesis. In this review, we briefly introduce the applications in which GABA is used, and summarize the most important methods associated with GABA production. The major achievements and present challenges in the biotechnological synthesis of GABA, focusing on screening and enzyme engineering of GADs, as well as metabolic engineering strategy for one-step GABA biosynthesis, will be extensively discussed.

  5. Elevated gamma-aminobutyric acid levels in chronic schizophrenia.

    Science.gov (United States)

    Ongür, Dost; Prescot, Andrew P; McCarthy, Julie; Cohen, Bruce M; Renshaw, Perry F

    2010-10-01

    Despite widely replicated abnormalities of gamma-aminobutyric acid (GABA) neurons in schizophrenia postmortem, few studies have measured tissue GABA levels in vivo. We used proton magnetic resonance spectroscopy to measure tissue GABA levels in participants with schizophrenia and healthy control subjects in the anterior cingulate cortex and parieto-occipital cortex. Twenty-one schizophrenia participants effectively treated on a stable medication regimen (mean age 39.0, 14 male) and 19 healthy control subjects (mean age 36.3, 12 male) underwent a proton magnetic resonance spectroscopy scan using GABA-selective editing at 4 Tesla after providing informed consent. Data were collected from two 16.7-mL voxels and analyzed using LCModel. We found elevations in GABA/creatine in the schizophrenia group compared with control subjects [F(1,65) = 4.149, p = .046] in both brain areas (15.5% elevation in anterior cingulate cortex, 11.9% in parieto-occipital cortex). We also found a positive correlation between GABA/creatine and glutamate/creatine, which was not accounted for by % GM or brain region. We found elevated GABA/creatinine in participants with chronically treated schizophrenia. Postmortem studies report evidence for dysfunctional GABAergic neurotransmission in schizophrenia. Elevated GABA levels, whether primary to illness or compensatory to another process, may be associated with dysfunctional GABAergic neurotransmission in chronic schizophrenia. Copyright © 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  6. Detection of the in vivo conversion of 2-pyrrolidinone to gamma-aminobutyric acid in mouse brain.

    Science.gov (United States)

    Callery, P S; Stogniew, M; Geelhaar, L A

    1979-01-01

    Labeled gamma-aminobutyric acid was detected in mouse brain following intravenous injections of deuterium labeled 2-pyrrolidinone. [2H6]Pyrrolidinone was prepared by the reduction of [2H4]succinimide with lithium aluminum deuteride. Quantification was accomplished by a gas chromatography mass spectrometry assay method. gamma-Aminobutyric acid and internal standard, 5-aminovaleric acid, were converted to volatile derivatives by treatment with N,N-dimethylformamide dimethyl acetal. Quantitative estimates were derived from peak area measurements obtained from monitoring the parent ions of the gamma-aminobutyric acid and internal standard derivatives by repetitive scanning during the GC run. The conversion of pyrrolidinone to gamma-aminobutyric acid may provide a method for labeling central gamma-aminobutyric acid pools.

  7. Reduced gamma-aminobutyric acid concentration is associated with physical disability in progressive multiple sclerosis

    Science.gov (United States)

    Solanky, Bhavana S.; Muhlert, Nils; Tur, Carmen; Edden, Richard A. E.; Wheeler-Kingshott, Claudia A. M.; Miller, David H.; Thompson, Alan J.; Ciccarelli, Olga

    2015-01-01

    Neurodegeneration is thought to be the major cause of ongoing, irreversible disability in progressive stages of multiple sclerosis. Gamma-aminobutyric acid is the principle inhibitory neurotransmitter in the brain. The aims of this study were to investigate if gamma-aminobutyric acid levels (i) are abnormal in patients with secondary progressive multiple sclerosis compared with healthy controls; and (ii) correlate with physical and cognitive performance in this patient population. Thirty patients with secondary progressive multiple sclerosis and 17 healthy control subjects underwent single-voxel MEGA-PRESS (MEscher-GArwood Point RESolved Spectroscopy) magnetic resonance spectroscopy at 3 T, to quantify gamma-aminobutyric acid levels in the prefrontal cortex, right hippocampus and left sensorimotor cortex. All subjects were assessed clinically and underwent a cognitive assessment. Multiple linear regression models were used to compare differences in gamma-aminobutyric acid concentrations between patients and controls adjusting for age, gender and tissue fractions within each spectroscopic voxel. Regression was used to examine the relationships between the cognitive function and physical disability scores specific for these regions with gamma-aminobuytric acid levels, adjusting for age, gender, and total N-acetyl-aspartate and glutamine-glutamate complex levels. When compared with controls, patients performed significantly worse on all motor and sensory tests, and were cognitively impaired in processing speed and verbal memory. Patients had significantly lower gamma-aminobutyric acid levels in the hippocampus (adjusted difference = −0.403 mM, 95% confidence intervals −0.792, −0.014, P = 0.043) and sensorimotor cortex (adjusted difference = −0.385 mM, 95% confidence intervals −0.667, −0.104, P = 0.009) compared with controls. In patients, reduced motor function in the right upper and lower limb was associated with lower gamma-aminobutyric acid

  8. Complete Genome Sequence of the Gamma-Aminobutyric Acid-Producing Strain Streptococcus thermophilus APC151.

    Science.gov (United States)

    Linares, Daniel M; Arboleya, Silvia; Ross, R Paul; Stanton, Catherine

    2017-04-27

    Here is presented the whole-genome sequence of Streptococcus thermophilus APC151, isolated from a marine fish. This bacterium produces gamma-aminobutyric acid (GABA) in high yields and is biotechnologically suitable to produce naturally GABA-enriched biofunctional yogurt. Its complete genome comprises 2,097 genes and 1,839,134 nucleotides, with an average G+C content of 39.1%. Copyright © 2017 Linares et al.

  9. GABAA [gamma-aminobutyric acid] type binding sites on membranes of spermatozoa

    International Nuclear Information System (INIS)

    Erdoe, S.L.; Wekerle, L.

    1990-01-01

    The binding of [ 3 H] gamma-aminobutyric acid (GABA) to seminal membranes of swines and rams was examined. Specific, GABA binding was demonstrated in both species, which showed the features of GABA A type receptors. The affinity of binding was similar in both species, whereas the density of seminal GABA binding sites was 5 times higher in swine. Our findings suggest that GABA may have a direct effect on spermatozoa

  10. The anticonvulsant gabapentin (neurontin) does not act through gamma-aminobutyric acid-B receptors

    DEFF Research Database (Denmark)

    Jensen, Anders A.; Mosbacher, Johannes; Elg, Susanne

    2002-01-01

    The actions of the anticonvulsant gabapentin [1-(aminomethyl)cyclohexaneacetic acid, Neurontin] have been somewhat enigmatic until recently, when it was claimed to be a gamma-aminobutyric acid-B (GABA(B)) receptor agonist acting exclusively at a heterodimeric complex containing the GABA(B(1a...... in vitro assays. In light of these results, we find it highly questionable that gabapentin is a GABA(B) receptor agonist. Hence, the anticonvulsive effects of the compound have to arise from GABA(B) receptor-independent mechanisms. This also implies that the first GABA(B) receptor splice variant...

  11. Antisera to gamma-aminobutyric acid. I. Production and characterization using a new model system.

    Science.gov (United States)

    Hodgson, A J; Penke, B; Erdei, A; Chubb, I W; Somogyi, P

    1985-03-01

    Antisera to the amino acid gamma-aminobutyric acid (GABA) have been developed with the aim of immunohistochemical visualization of neurons that use it as a neurotransmitter. GABA bound to bovine serum albumin was the immunogen. The reactivities of the sera to GABA and a variety of structurally related compounds were tested by coupling these compounds to nitrocellulose paper activated with polylysine and glutaraldehyde and incubating the paper with the unlabeled antibody enzyme method, thus simulating immunohistochemistry of tissue sections. The antisera did not react with L-glutamate, L-aspartate, D-aspartate, glycine, taurine, L-glutamine, L-lysine, L-threonine, L-alanine, alpha-aminobutyrate, beta-aminobutyrate, putrescine, or delta-aminolevulinate. There was cross-reaction with gamma-amino-beta-hydroxybutyrate, 1-10%, and the homologues of GABA: beta-alanine, 1-10%, delta-aminovalerate, approximately 10%, and epsilon-amino-caproate, approximately 10%. The antisera reacted slightly with the dipeptide gamma-aminobutyrylleucine, but not carnosine or homocarnosine. Immunostaining of GABA was completely abolished by adsorption of the sera to GABA coupled to polyacrylamide beads by glutaraldehyde. The immunohistochemical model is simple, amino acids and peptides are bound in the same way as in aldehyde-fixed tissue and, in contrast to radioimmunoassay, it uses an immunohistochemical detection system. This method has enabled us to define the high specificity of anti-GABA sera and to use them in some novel ways. The model should prove useful in assessing the specificity of other antisera.

  12. Application of gamma-aminobutyric acid type A-benzodiazepine receptor imaging for study of neuropsychiatric disorders

    International Nuclear Information System (INIS)

    Bao Weiqi; Qiu Chun; Guan Yihui

    2012-01-01

    Gamma-aminobutyric acid type A-benzodiazepine receptors are heterogeneous polypeptide pentamers widely spread in the central nervous system on the neuron membrane. Different subunit combinations educe various neuro-inhibitory pharmacological effects such as sedative, hypnosis, anticonvulsion and anxiolysis. PET can be utilized to study the binding of the receptors in vivo. PET radioligands of gamma-aminobutyric acid type A-benzodiazepine receptors can be classified into 3 types: antagonists,agonists and reverse agonists, of which antagonist radiotracer 11 C-flumazenil is the most commonly applied in epilepsy, anxiety disorders, depression, vegetative state,addiction and other neuro-psychiatric disorders. (authors)

  13. Optimizing soaking and germination conditions to improve gamma-aminobutyric acid content in japonica and indica germinated brown rice

    NARCIS (Netherlands)

    Zhang, Q.; Xiang, J.; Zhang, L.; Zhu, X.; Evers, J.B.; Werf, van der W.; Duan, L.

    2014-01-01

    Germinated brown rice is a well-known functional food due to its high content of gamma-aminobutyric acid (GABA). This study was designed to test the difference of producing GABA in two domesticated rice genotypes (indica and japonica rice), and the effects of adding exogenous glutamic acid or

  14. [The interaction between gamma-aminobutyric acid and other related neurotransmitters in depression].

    Science.gov (United States)

    Li, Zhen; An, Shu-Cheng; Li, Jiang-Na

    2014-06-01

    Gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter of the central nervous system (CNS) in mammalian, which involved in several mood disorders such as anxiety, depression and schizophrenia. Nowadays, there are growing evidences showed that the depression is concerned with a deficiency in brain GABA. However, there are numerous studies based on the monoamine hypothesis and glutamatergic dysfunction, while the study on GABA is relatively less and scattered. Our aim is to discuss the relationship between depression and GABA by introducing the role of GABA receptors and the interaction between GABA and 5-hydroxytryptamine, dopamine and glutamic acid. It provides new ideas for further study on the pathogenesis and therapy of depression.

  15. Enrichment of Gamma-Aminobutyric Acid in Bean Sprouts: Exploring Biosynthesis of Plant Metabolite Using Common Household Reagents

    Science.gov (United States)

    Rojanarata, Theerasak; Plianwong, Samarwadee; Opanasopit, Praneet; Ngawhirunpat, Tanasait

    2018-01-01

    The enrichment of plant foods with gamma-aminobutyric acid (GABA) is currently an interesting issue in the field of nutraceuticals and can be used as an experiment for upper-division undergraduate students. Here, an interdisciplinary hands-on experiment to produce GABA-enriched mung bean sprouts using common household reagents is described. Based…

  16. Characterization of the gamma-aminobutyric acid receptor system in human brain gliomas

    International Nuclear Information System (INIS)

    Frattola, L.; Ferrarese, C.; Canal, N.; Gaini, S.M.; Galluso, R.; Piolti, R.; Trabucchi, M.

    1985-01-01

    The properties of [ 3 H]-gamma-aminobutyric acid [( 3 H]GABA) binding were studied in biopsied specimens from normal human brain and from 18 cases of human brain gliomas, made up of 6 astrocytomas, 6 glioblastomas, 3 oligodendrogliomas, and 3 medulloblastomas. In fresh membranes obtained from normal gray and white matter one population of Na+-dependent GABA receptors was observed, while in the frozen Triton X-100-treated membranes two distinct populations of Na+-independent binding sites were detected. Specific GABA binding sites in brain gliomas were shown only in frozen Triton X-100-treated membranes. As in normal tissue, these receptors are Na+-independent and bind [ 3 H]GABA with two distinct affinity components. The biochemical profiles of [ 3 H]GABA binding to membranes obtained from different tumors of glial origin are quite similar and cannot be related to the degree of malignancy of the neoplasia

  17. Effects of gamma-aminobutyric acid (GABA) on synaptogenesis and synaptic function

    DEFF Research Database (Denmark)

    Belhage, B; Hansen, G H; Elster, L

    1998-01-01

    The correct establishment and function of synapses depend on a variety of factors, such as guidance of pre- and postsynaptic neurons as well as receptor development and localization. gamma-Aminobutyric acid (GABA) has a pronounced effect on these events and elicits differentiation of neurons......; that is, GABA acts as a trophic signal. Accordingly, activating preexisting GABA receptors, a trophic GABA signal enhances the growth rate of neuronal processes, facilitates synapse formation, and promotes synthesis of specific proteins. Transcription and de novo synthesis are initiated by the GABA signal......, but the intracellular link between GABA receptor activation and DNA transcription is largely unknown. GABA also controls the induction and development of functionally and pharmacologically different GABAA receptor subtypes. The induced receptors are likely to be inserted only into the synaptic membrane domain. However...

  18. Effects of gamma-aminobutyric acid on the Hering-Breuer inspiration-inhibiting reflex.

    Science.gov (United States)

    Aleksandrova, N P; Aleksandrov, V G; Ivanova, T G

    2010-02-01

    Acute experiments on rats were performed to study the effects of intraventricular microinjections of gamma-aminobutyric acid (GABA) on the volume-time parameters of external respiration and the inspiration-inhibiting Hering-Breuer reflex. The state of this reflex before and after GABA administration was assessed in terms of the extent of changes in the duration and amplitude of inspiratory oscillations in intrathoracic pressure in response to end-expiratory occlusion of the trachea. Administration of 20 microM GABA into the lateral ventricles of the brain decreased the minute ventilation (due to reductions in the respiratory frequency and respiratory volume), weakened respiratory muscle contractions, and decreased the peak airflow rate on inspiration and expiration. The response to end-expiratory occlusion decreased significantly after administration of GABA, demonstrating the involvement of GABAergic mechanisms in mediating the inspiration-inhibiting Hering-Breuer reflex.

  19. Embryonic cerebellar neurons accumulate [3H-gamma-aminobutyric acid: visualization of developing gamma-aminobutyric acid-utilizing neurons in vitro and in vivo

    International Nuclear Information System (INIS)

    Hatten, M.E.; Francois, A.M.; Napolitano, E.; Roffler-Tarlov, S.

    1984-01-01

    gamma-Aminobutyric acid (GABA) is the proposed neurotransmitter for four types of cerebellar neurons-Purkinje, Golgi, basket, and stellate neurons. With this investigation we have begun studies to establish when these neurons acquire their neurotransmitter ''identification''. Autoradiographic studies of both cultured embryonic (embryonic day 13) cerebellar cells and of intact embryonic cerebellum (embryonic day 13) were conducted with tritiated GABA. Two to 5% of the embryonic cerebellar cells accumulated [ 3 H]GABA in vitro. By morphological and immunocytochemical criteria, labeled cells were large neurons with either a thick, apical process, a multipolar shape, or were bipolar with longer processes. The identification of cells which accumulated [ 3 H]GABA as neuronal precursors was supported by the differential sensitivity to drugs that preferentially inhibit accumulation of [ 3 H]GABA by neurons and glia. The results of the in vitro experiments were confirmed and extended with in vivo experiments. When intact cerebellar tissue was removed at embryonic day 13, stripped of meninges and choroid plexus, exposed to low concentrations of [ 3 H]GABA, and processed for light microscopic autoradiography, heavily labeled cells were seen in the middle of the cerebellar anlage. Labeled cells were not seen in the ventricular zone of proliferating neuroblasts lining the fourth ventricle or in the external granular layer emerging at the lateral aspect of the pial surface. The accumulation of [ 3 H]GABA by these cells also showed the pharmacological characteristics of uptake by neurons. This study shows that among migrating, immature forms of the larger neurons of the embryonic cerebellum, there is a select group which accumulates [ 3 H]GABA and other classes of cells which do not. These results indicate very early acquisition of transmitter expression by cerebellar neurons, far in advance of their final positioning and establishment of synapses

  20. EFFECT OF FOOD-MICROORGANISMS ON GAMMA-AMINOBUTYRIC ACID PRODUCTION BY FERMENTATION

    Directory of Open Access Journals (Sweden)

    Jozef Hudec

    2012-02-01

    Full Text Available Lactic acid bacteria (LAB are nice targets in order to study γ-aminobutyric acid (GABA production that has been reported to be effective in order to reduce blood pressure in experimental animals and human beings. In this study, we aimed to γ-aminobutyric acid (GABA production in aerobical and anaerobical conditions, using different sources of microorganisms. The highest selectivity of GABA from precursor L-monosodium glutamate (82.22% has been reported using of microorganisms from banana, and with addition of pyridoxal-5-phosphate (P-5-P. For augmentation of selectivity the application of the further stimulating factors of GABA biosynthesis is needed.

  1. Gamma-Aminobutyric Acid Concentration is Reduced in Visual Cortex in Schizophrenia and Correlates with Orientation-Specific Surround Suppression

    OpenAIRE

    Yoon, Jong H.; Maddock, Richard J.; Rokem, Ariel; Silver, Michael A.; Minzenberg, Michael J.; Ragland, J. Daniel; Carter, Cameron S.

    2010-01-01

    The neural mechanisms underlying cognitive deficits in schizophrenia remain largely unknown. The gamma-aminobutyric acid (GABA) hypothesis proposes that reduced neuronal GABA concentration and neurotransmission results in cognitive impairments in schizophrenia. However, few in vivo studies have directly examined this hypothesis. We employed magnetic resonance spectroscopy (MRS) at high field to measure visual cortical GABA levels in 13 subjects with schizophrenia and 13 demographically matche...

  2. Gamma aminobutyric acid radioreceptor assay: a confirmatory quantitative assay for toxaphene in environmental and biological samples

    International Nuclear Information System (INIS)

    Saleh, M.A.; Blancato, J.N.

    1993-01-01

    Toxaphene is a complex mixture of polychlorinated monoterpenes, and was found to be acutely and chronically toxic to aquatic and wild life and posed a carcinogenic risk to humans before its ban in 1982. However, it is still found in the environment due to its relative persistence with an estimated half life time of about 10 years in soils. Toxaphenes neurotoxicity is attributed to a few isomers with a mode of action through binding to the chloride channel of the gamma-aminobutyric acid (GABA) receptor ionophore complex. [ 35 S] tertiary butylbicyclophosphorothionate (TBPS) with specific activity higher than 60 Ci/mmole has a high binding affinity to the same sites and is now commercially available and can be used to label the GABA receptor for the development of radioreceptor assay technique. The GABA receptor was prepared by a sequence of ultra centrifugation and dialysis of mammalian (rats, cows, catfish and goats) brain homogenates. The receptor is then labeled with [ 35 S] TBPS and the assay was conducted by measuring the displacement of radioactivity following incubation with the sample containing the analytes. The assay is fast, sensitive and requires very little or no sample preparation prior to the analysis. (Author)

  3. Food deprivation modulates gamma-aminobutyric acid receptors and peripheral benzodiazepine binding sites in rats.

    Science.gov (United States)

    Weizman, A; Bidder, M; Fares, F; Gavish, M

    1990-12-03

    The effect of 5 days of food deprivation followed by 5 days of refeeding on gamma-aminobutyric acid (GABA) receptors, central benzodiazepine receptors (CBR), and peripheral benzodiazepine binding sites (PBzS) was studied in female Sprague-Dawley rats. Starvation induced a decrease in the density of PBzS in peripheral organs: adrenal (35%; P less than 0.001), kidney (33%; P less than 0.01), and heart (34%; P less than 0.001). Restoration of [3H]PK 11195 binding to normal values was observed in all three organs after 5 days of refeeding. The density of PBzS in the ovary, pituitary, and hypothalamus was not affected by starvation. Food deprivation resulted in a 35% decrease in cerebellar GABA receptors (P less than 0.01), while CBR in the hypothalamus and cerebral cortex remained unaltered. The changes in PBzS observed in the heart and kidney may be related to the long-term metabolic stress associated with starvation and to the functional changes occurring in these organs. The down-regulation of the adrenal PBzS is attributable to the suppressive effect of hypercortisolemia on pituitary ACTH release. The reduction in cerebellar GABA receptors may be an adaptive response to food deprivation stress and may be relevant to the proaggressive effect of hunger.

  4. Gamma-aminobutyric acid (GABA)-B receptor 1 in cerebellar cortex of essential tremor.

    Science.gov (United States)

    Luo, C; Rajput, A H; Robinson, C A; Rajput, A

    2012-06-01

    Some reports suggest cerebellar dysfunction as the basis of essential tremor (ET). Several drugs with the action of gamma-aminobutyric acid (GABA) are known to improve ET. Autopsy studies were performed on brains from nine former patients followed at the Movement Disorders Clinic Saskatchewan, Canada, and compared with five normal control brains. We aimed to measure the concentration of GABA B receptor 1 (GBR1) in the brains of patients who had had ET and to compare them to the GABA concentration in brains of controls. Western blot was used to determine the expression of GBR1 in cerebellar cortex tissue. We found that compared to the controls, the ET brains had three different patterns of GBR1 protein concentration--two with high, four comparable, and three with marginally low levels. There was no association between the age of onset, severity or duration of tremor, the response to alcohol or other drugs and GBR1 level. Thus, we conclude that our study does not support that GBR1 is involved in ET. Further studies are needed to verify these results. Copyright © 2011 Elsevier Ltd. All rights reserved.

  5. ANXIETY IN MAJOR DEPRESSION AND CEREBROSPINAL FLUID FREE GAMMA-AMINOBUTYRIC ACID

    Science.gov (United States)

    Mann, J. John; Oquendo, Maria A.; Watson, Kalycia Trishana; Boldrini, Maura; Malone, Kevin M.; Ellis, Steven P.; Sullivan, Gregory; Cooper, Thomas B.; Xie, Shan; Currier, Dianne

    2016-01-01

    Background Low gamma-aminobutyric acid (GABA) is implicated in both anxiety and depression pathophysiology. They are often comorbid, but most clinical studies have not examined these relationships separately. We investigated the relationship of cerebrospinal fluid (CSF) free GABA to the anxiety and depression components of a major depressive episode (MDE) and to monoamine systems. Methods and Materials Patients with a DSM-IV major depressive episode (N = 167: 130 major depressive disorder; 37 bipolar disorder) and healthy volunteers (N = 38) had CSF free GABA measured by gas chromatography mass spectroscopy. Monoamine metabolites were assayed by high performance liquid chromatography. Symptomatology was assessed by Hamilton depression rating scale. Results Psychic anxiety severity increased with age and correlated with lower CSF free GABA, controlling for age. CSF free GABA declined with age but was not related to depression severity. Other monoamine metabolites correlated positively with CSF GABA but not with psychic anxiety or depression severity. CSF free GABA was lower in MDD compared with bipolar disorder and healthy volunteers. GABA levels did not differ based on a suicide attempt history in mood disorders. Recent exposure to benzodiazepines, but not alcohol or past alcoholism, was associated with a statistical trend for more severe anxiety and lower CSF GABA. Conclusions Lower CSF GABA may explain increasing severity of psychic anxiety in major depression with increasing age. This relationship is not seen with monoamine metabolites, suggesting treatments targeting the GABAergic system should be evaluated in treatment-resistant anxious major depression and in older patients. PMID:24865448

  6. The association of plasma gamma-aminobutyric acid concentration with postoperative delirium in critically ill patients.

    Science.gov (United States)

    Yoshitaka, Shiho; Egi, Moritoki; Kanazawa, Tomoyuki; Toda, Yuichiro; Morita, Kiyoshi

    2014-12-01

    Delirium is a common complication in postoperative, critically ill patients. The mechanism of postoperative delirium is not well understood but many studies have shown significant associations between benzodiazepine use, alcohol withdrawal and cirrhosis, and an increased risk of delirium. We aimed to investigate a possible link with alterations of gamma-aminobutyric acid (GABA) activity. A prospective observational investigation of 40 patients > 20 years old who had undergone elective surgery with general anaesthesia and were expected to need postoperative intensive care for more than 48 hours. We assessed postoperative delirium using the confusion assessment method in the intensive care unit at 1 hour after the operation and on postoperative Day (POD) 1 and POD 2. We collected blood samples for measurement of plasma GABA concentrations before the operation and on POD 1 and 2. Postoperative delirium and perioperative plasma GABA concentrations in patients with and without delirium. Postoperative delirium occurred in 13 of the patients. Patients with delirium had significantly higher Acute Physiology and Chronic Health Evaluation II scores than patients without delirium. The mean plasma GABA concentration on POD 2 was significantly lower in patients with delirium than in those without delirium. After adjustment of relevant variables, plasma GABA concentration on POD 2 was independently associated with postoperative delirium. Plasma GABA level on POD 2 has a significant independent association with postoperative delirium.

  7. Gamma-aminobutyric acid aggravates nephrotoxicity induced by cisplatin in female rats.

    Science.gov (United States)

    Peysepar, Elham; Soltani, Nepton; Nematbakhsh, Mehdi; Eshraghi-Jazi, Fatemeh; Talebi, Ardeshir

    2016-01-01

    Cisplatin (CP) is a major antineoplastic drug for treatment of solid tumors. CP-induced nephrotoxicity may be gender-related. This is while gamma-aminobutyric acid (GABA) is an inhibitory neurotransmitter in the central nervous system that has renoprotective impacts on acute renal injury. This study was designed to investigate the protective role of GABA against CP-induced nephrotoxicity in male and female rats. Sixty Wistar male and female rats were used in eight experimental groups. Both genders received GABA (50 μg/kg/day; i. p.) for 14 days and CP (2.5 mg/kg/day; i. p.) was added from day 8 to the end of the study, and they were compared with the control groups. At the end of the study, all animals were sacrificed and the serum levels of blood urea nitrogen (BUN), creatinine (Cr), nitrite, malondialdehyde (MDA), and magnesium (Mg) were measured. The kidney tissue damage was also determined via staining. CP significantly increased the serum levels of Cr and BUN, kidney weight, and kidney tissue damage score in both genders (PGABA did not attenuate these markers in males; even these biomarkers were intensified in females. Serum level of Mg, and testis and uterus weights did not alter in the groups. However, the groups were significantly different in terms of nitrite and MDA levels. It seems that GABA did not improve nephrotoxicity induced by CP-treated rats, and it exacerbated renal damage in female rats.

  8. Anxiety in major depression and cerebrospinal fluid free gamma-aminobutyric acid.

    Science.gov (United States)

    Mann, J John; Oquendo, Maria A; Watson, Kalycia Trishana; Boldrini, Maura; Malone, Kevin M; Ellis, Steven P; Sullivan, Gregory; Cooper, Thomas B; Xie, Shan; Currier, Dianne

    2014-10-01

    Low gamma-aminobutyric acid (GABA) is implicated in both anxiety and depression pathophysiology. They are often comorbid, but most clinical studies have not examined these relationships separately. We investigated the relationship of cerebrospinal fluid (CSF) free GABA to the anxiety and depression components of a major depressive episode (MDE) and to monoamine systems. Patients with a DSM-IV major depressive episode (N = 167: 130 major depressive disorder; 37 bipolar disorder) and healthy volunteers (N = 38) had CSF free GABA measured by gas chromatography mass spectroscopy. Monoamine metabolites were assayed by high performance liquid chromatography. Symptomatology was assessed by Hamilton depression rating scale. Psychic anxiety severity increased with age and correlated with lower CSF free GABA, controlling for age. CSF free GABA declined with age but was not related to depression severity. Other monoamine metabolites correlated positively with CSF GABA but not with psychic anxiety or depression severity. CSF free GABA was lower in MDD compared with bipolar disorder and healthy volunteers. GABA levels did not differ based on a suicide attempt history in mood disorders. Recent exposure to benzodiazepines, but not alcohol or past alcoholism, was associated with a statistical trend for more severe anxiety and lower CSF GABA. Lower CSF GABA may explain increasing severity of psychic anxiety in major depression with increasing age. This relationship is not seen with monoamine metabolites, suggesting treatments targeting the GABAergic system should be evaluated in treatment-resistant anxious major depression and in older patients. © 2014 Wiley Periodicals, Inc.

  9. Gamma-aminobutyric acid (GABA) and neuropeptides in neural areas mediating motion-induced emesis

    Science.gov (United States)

    Damelio, F.; Daunton, Nancy G.; Fox, Robert A.

    1991-01-01

    Immunocytochemical methods were employed to localize the neurotransmitter amino acid gamma-aminobutyric acid and the neuropeptides substance P and Met-enkephalin in the area postrema (AP), area subpostrema (ASP), nucleus of the tractus solitarius (NTS), dorsal motor nucleus of the vagus nerve (DMNV), and lateral vestibular nucleus (LVN). Glutamic acid decarboxylase immunoreactive (GAD-IR) terminals and fibers were observed in the AP and particularly in the ASP. A gradual decrease in the density of terminals was seen towards the solitary complex. The DMNV revealed irregularly scattered GAD-IR terminals within the neuropil or closely surrounding neuronal cell bodies. The LVN, particularly the dorsal division, showed numerous axon terminals which were mostly localize around large neurons and their proximal dendrites. Substance P immunoreactive (SP-IR) terminals and fibers showed high density in the solitary complex, in particular within the lateral division. The ASP showed medium to low density of SP-IR fibers and terminals. The AP exhibited a small number of fibers and terminals irregularly distributed. The DMNV revealed a high density of SP-IR terminals and fibers that were mainly concentrated in the periphery. Very few terminals were detected in the LVN. Met-enkephalin immunoreactive (Met-Enk-IR) fibers and terminals showed high density and uniform distribution in the DMNV. Scattered terminals and fibers were observed in the AP, ASP, and NTS (particularly the lateral division). The very few fibers were observed in the LVN surrounded the neuronal cell bodies. The present report is part of a study designed to investigate the interaction between neuropeptides and conventional neurotransmitters under conditions producing motion sickness and in the process of sensory-motor adaptation.

  10. Gamma-aminobutyric acid fermentation with date residue by a lactic acid bacterium, Lactobacillus brevis.

    Science.gov (United States)

    Hasegawa, Momoko; Yamane, Daisuke; Funato, Kouichi; Yoshida, Atsushi; Sambongi, Yoshihiro

    2018-03-01

    Dates are commercially consumed as semi-dried fruit or processed into juice and puree for further food production. However, the date residue after juice and puree production is not used, although it appears to be nutrient enriched. Here, date residue was fermented by a lactic acid bacterium, Lactobacillus brevis, which has been generally recognized as safe. Through degradation of sodium glutamate added to the residue during the fermentation, γ-aminobutyric acid (GABA), which reduces neuronal excitability, was produced at the conversion rate of 80-90% from glutamate. In order to achieve this GABA production level, pretreatment of the date residue with carbohydrate-degrading enzymes, i.e., cellulase and pectinase, was necessary. All ingredients used for this GABA fermentation were known as being edible. These results provide us with a solution for the increasing commercial demand for GABA in food industry with the use of date residue that has been often discarded. Copyright © 2017 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  11. Vertical organization of gamma-aminobutyric acid-accumulating intrinsic neuronal systems in monkey cerebral cortex

    International Nuclear Information System (INIS)

    DeFelipe, J.; Jones, E.G.

    1985-01-01

    Light and electron microscopic methods were used to examine the neurons in the monkey cerebral cortex labeled autoradiographically following the uptake and transport of [ 3 H]-gamma-aminobutyric acid (GABA). Nonpyramidal cell somata in the sensory-motor areas and primary visual area (area 17) were labeled close to the injection site and at distances of 1 to 1.5 mm beyond the injection site, indicating labeling by retrograde axoplasmic transport. This labeling occurred preferentially in the vertical dimension of the cortex. Prior injections of colchicine, an inhibitor of axoplasmic transport, abolished all labeling of somata except those within the injection site. In each area, injections of superficial layers (I to III) produced labeling of clusters of cell somata in layer V, and injections of the deep layers (V and VI) produced labeling of clusters of cell somata in layers II and III. In area 17, injections of the superficial layers produced dense retrograde cell labeling in three bands: in layers IVC, VA, and VI. Vertically oriented chains of silver grains linked the injection sites with the resulting labeled cell clusters. In all areas, the labeling of cells in the horizontal dimension was insignificant. Electron microscopic examination of labeled neurons confirms that the neurons labeled at a distance from an injection site are nonpyramidal neurons, many with somata so small that they would be mistaken for neuroglial cells light microscopically. They receive few axosomatic synapses, most of which have symmetric membrane thickenings. The vertical chains of silver grains overlie neuronal processes identifiable as both dendrites and myelinated axons, but unmyelinated axons may also be included. The clusters of [ 3 H]GABA-labeled cells are joined to one another and to adjacent unlabeled cells by junctional complexes, including puncta adherentia and multi-lamellar cisternal complexes

  12. Postnatal changes in somatic gamma-aminobutyric acid signalling in the rat hippocampus.

    Science.gov (United States)

    Tyzio, Roman; Minlebaev, Marat; Rheims, Sylvain; Ivanov, Anton; Jorquera, Isabelle; Holmes, Gregory L; Zilberter, Yuri; Ben-Ari, Yehezkiel; Khazipov, Rustem

    2008-05-01

    During postnatal development of the rat hippocampus, gamma-aminobutyric acid (GABA) switches its action on CA3 pyramidal cells from excitatory to inhibitory. To characterize the underlying changes in the GABA reversal potential, we used somatic cell-attached recordings of GABA(A) and N-methyl-D-aspartate channels to monitor the GABA driving force and resting membrane potential, respectively. We found that the GABA driving force is strongly depolarizing during the first postnatal week. The strength of this depolarization rapidly declines with age, although GABA remains slightly depolarizing, by a few millivolts, even in adult neurons. Reduction in the depolarizing GABA driving force was due to a progressive negative shift of the reversal potential of GABA currents. Similar postnatal changes in GABA signalling were also observed using the superfused hippocampus preparation in vivo, and in the hippocampal interneurons in vitro. We also found that in adult pyramidal cells, somatic GABA reversal potential is maintained at a slightly depolarizing level by bicarbonate conductance, chloride-extrusion and chloride-loading systems. Thus, the postnatal excitatory-to-inhibitory switch in somatic GABA signalling is associated with a negative shift of the GABA reversal potential but without a hyperpolarizing switch in the polarity of GABA responses. These results also suggest that in adult CA3 pyramidal cells, somatic GABAergic inhibition takes place essentially through shunting rather than hyperpolarization. Apparent hyperpolarizing GABA responses previously reported in the soma of CA3 pyramidal cells are probably due to cell depolarization during intracellular or whole-cell recordings.

  13. Inhibitory actions of the gamma-aminobutyric acid in pediatric Sturge-Weber syndrome.

    Science.gov (United States)

    Tyzio, Roman; Khalilov, Ilgam; Represa, Alfonso; Crepel, Valerie; Zilberter, Yuri; Rheims, Sylvain; Aniksztejn, Laurent; Cossart, Rosa; Nardou, Romain; Mukhtarov, Marat; Minlebaev, Marat; Epsztein, Jérôme; Milh, Mathieu; Becq, Helene; Jorquera, Isabel; Bulteau, Christine; Fohlen, Martine; Oliver, Viviana; Dulac, Olivier; Dorfmüller, Georg; Delalande, Olivier; Ben-Ari, Yehezkel; Khazipov, Roustem

    2009-08-01

    The mechanisms of epileptogenesis in Sturge-Weber syndrome (SWS) are unknown. We explored the properties of neurons from human pediatric SWS cortex in vitro and tested in particular whether gamma-aminobutyric acid (GABA) excites neurons in SWS cortex, as has been suggested for various types of epilepsies. Patch-clamp and field potential recordings and dynamic biphoton imaging were used to analyze cortical tissue samples obtained from four 6- to 14-month-old pediatric SWS patients during surgery. Neurons in SWS cortex were characterized by a relatively depolarized resting membrane potential, as was estimated from cell-attached recordings of N-methyl-D-aspartate channels. Many cells spontaneously fired action potentials at a rate proportional to the level of neuronal depolarization. The reversal potential for GABA-activated currents, assessed by cell-attached single channel recordings, was close to the resting membrane potential. All spontaneously firing neurons recorded in cell-attached mode or imaged with biphoton microscopy were inhibited by GABA. Spontaneous epileptiform activity in the form of recurrent population bursts was suppressed by glutamate receptor antagonists, the GABA(A) receptor agonist isoguvacine, and the positive allosteric GABA(A) modulator diazepam. Blockade of GABA(A) receptors aggravated spontaneous epileptiform activity. The NKCC1 antagonist bumetanide had little effect on epileptiform activity. SWS cortical neurons have a relatively depolarized resting membrane potential and spontaneously fire action potentials that may contribute to increased network excitability. In contrast to previous data depicting excitatory and proconvulsive actions of GABA in certain pediatric and adult epilepsies, GABA plays mainly an inhibitory and anticonvulsive role in SWS pediatric cortex.

  14. Gamma-aminobutyric acid (GABA) stimulates pancreatic cancer growth through overexpressing GABAA receptor pi subunit.

    Science.gov (United States)

    Takehara, Akio; Hosokawa, Masayo; Eguchi, Hidetoshi; Ohigashi, Hiroaki; Ishikawa, Osamu; Nakamura, Yusuke; Nakagawa, Hidewaki

    2007-10-15

    Gamma-aminobutyric acid (GABA) functions primarily as an inhibitory neurotransmitter in the mature central nervous system, and GABA/GABA receptors are also present in nonneural tissues, including cancer, but their precise function in nonneuronal or cancerous cells has thus far been poorly defined. Through the genome-wide cDNA microarray analysis of pancreatic ductal adenocarcinoma (PDAC) cells as well as subsequent reverse transcription-PCR and Northern blot analyses, we identified the overexpression of GABA receptor pi subunit (GABRP) in PDAC cells. We also found the expression of this peripheral type GABAA receptor subunit in few adult human organs. Knockdown of endogenous GABRP expression in PDAC cells by small interfering RNA attenuated PDAC cell growth, suggesting its essential role in PDAC cell viability. Notably, the addition of GABA into the cell culture medium promoted the proliferation of GABRP-expressing PDAC cells, but not GABRP-negative cells, and GABAA receptor antagonists inhibited this growth-promoting effect by GABA. The HEK293 cells constitutively expressing exogenous GABRP revealed the growth-promoting effect of GABA treatment. Furthermore, GABA treatment in GABRP-positive cells increased intracellular Ca2+ levels and activated the mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/Erk) cascade. Clinical PDAC tissues contained a higher level of GABA than normal pancreas tissues due to the up-regulation of glutamate decarboxylase 1 expression, suggesting their autocrine/paracrine growth-promoting effect in PDACs. These findings imply that GABA and GABRP could play important roles in PDAC development and progression, and that this pathway can be a promising molecular target for the development of new therapeutic strategies for PDAC.

  15. Reducing prefrontal gamma-aminobutyric acid activity induces cognitive, behavioral, and dopaminergic abnormalities that resemble schizophrenia.

    Science.gov (United States)

    Enomoto, Takeshi; Tse, Maric T; Floresco, Stan B

    2011-03-01

    Perturbations in gamma-aminobutyric acid (GABA)-related markers have been reported in the prefrontal cortex of schizophrenic patients. However, a preclinical assessment of how suppression of prefrontal cortex GABA activity may reflect behavioral and cognitive pathologies observed in schizophrenia is forthcoming. We assessed the effects of pharmacologic blockade of prefrontal cortex GABA(A) receptors in rats on executive functions and other behaviors related to schizophrenia, as well as neural activity of midbrain dopamine neurons. Blockade of prefrontal cortex GABA(A) receptors with bicuculline (12.5-50 ng) did not affect working memory accuracy but did increase response latencies, resembling speed of processing deficits observed in schizophrenia. Prefrontal cortex GABA(A) blockade did not impede simple discrimination or reversal learning but did impair set-shifting in a manner dependent on when these treatments were given. Reducing GABA activity before the set-shift impaired the ability to acquire a novel strategy, whereas treatment before the initial discrimination increased perseveration during the shift. Latent inhibition was unaffected by bicuculline infusions before the preexposure/conditioning phases, suggesting that reduced prefrontal cortex GABA activity does not impair "learned irrelevance." GABA(A) blockade increased locomotor activity and showed synergic effects with a subthreshold dose of amphetamine. Furthermore, reducing medial prefrontal cortex GABA activity selectively increased phasic burst firing of ventral tegmental area dopamine neurons, without altering the their overall population activity. These results suggest that prefrontal cortex GABA hypofunction may be a key contributing factor to deficits in speed of processing, cognitive flexibility, and enhanced phasic dopamine activity observed in schizophrenia. Copyright © 2011 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  16. Cortical Gamma-Aminobutyric Acid and Glutamate in Posttraumatic Stress Disorder and Their Relationships to Self-Reported Sleep Quality

    Science.gov (United States)

    Meyerhoff, Dieter J.; Mon, Anderson; Metzler, Thomas; Neylan, Thomas C.

    2014-01-01

    Study Objectives: To test if posttraumatic stress disorder (PTSD) is associated with low brain gamma-aminobutyric acid (GABA) levels and if reduced GABA is mediated by poor sleep quality. Design: Laboratory study using in vivo proton magnetic resonance spectroscopy (1H MRS) and behavioral testing. Setting: VA Medical Center Research Service, Psychiatry and Radiology. Patients or Participants: Twenty-seven patients with PTSD (PTSD+) and 18 trauma-exposed controls without PTSD (PTSD−), recruited from United States Army reservists, Army National Guard, and mental health clinics. Interventions: None. Measurements and Results: 1H MRS at 4 Tesla yielded spectra from three cortical brain regions. In parieto-occipital and temporal cortices, PTSD+ had lower GABA concentrations than PTSD−. As expected, PTSD+ had higher depressive and anxiety symptom scores and a higher Insomnia Severity Index (ISI) score. Higher ISI correlated with lower GABA and higher glutamate levels in parieto-occipital cortex and tended to correlate with lower GABA in the anterior cingulate. The relationship between parieto-occipital GABA and PTSD diagnosis was fully mediated through insomnia severity. Lower N-acetylaspartate and glutamate concentrations in the anterior cingulate cortex correlated with higher arousal scores, whereas depressive and anxiety symptoms did generally not influence metabolite concentrations. Conclusions: Low brain gamma-aminobutyric acid (GABA) concentration in posttraumatic stress disorder (PTSD) is consistent with most findings in panic and social anxiety disorders. Low GABA associated with poor sleep quality is consistent with the hyperarousal theory of both primary insomnia and PTSD. Our data demonstrate that poor sleep quality mediates low parieto-occipital GABA in PTSD. The findings have implications for PTSD treatment approaches. Citation: Meyerhoff DJ, Mon A, Metzler T, Neylan TC. Cortical gamma-aminobutyric acid and glutamate in posttraumatic stress disorder and

  17. In Vivo Dentate Nucleus Gamma-aminobutyric Acid Concentration in Essential Tremor vs. Controls.

    Science.gov (United States)

    Louis, Elan D; Hernandez, Nora; Dyke, Jonathan P; Ma, Ruoyun E; Dydak, Ulrike

    2018-04-01

    Despite its high prevalence, essential tremor (ET) is among the most poorly understood neurological diseases. The presence and extent of Purkinje cell (PC) loss in ET is the subject of controversy. PCs are a major storehouse of central nervous system gamma-aminobutyric acid (GABA), releasing GABA at the level of the dentate nucleus. It is therefore conceivable that cerebellar dentate nucleus GABA concentration could be an in vivo marker of PC number. We used in vivo 1 H magnetic resonance spectroscopy (MRS) to quantify GABA concentrations in two cerebellar volumes of interest, left and right, which included the dentate nucleus, comparing 45 ET cases to 35 age-matched controls. 1 H MRS was performed using a 3.0-T Siemens Tim Trio scanner. The MEGA-PRESS J-editing sequence was used for GABA detection in two cerebellar volumes of interest (left and right) that included the dentate nucleus. The two groups did not differ with respect to our primary outcome of GABA concentration (given in institutional units). For the right dentate nucleus, [GABA] in ET cases = 2.01 ± 0.45 and [GABA] in controls = 1.86 ± 0.53, p = 0.17. For the left dentate nucleus, [GABA] in ET cases = 1.68 ± 0.49 and [GABA] controls = 1.80 ± 0.53, p = 0.33. The controls had similar dentate nucleus [GABA] in the right vs. left dentate nucleus (p = 0.52); however, in ET cases, the value on the right was considerably higher than that on the left (p = 0.001). We did not detect a reduction in dentate nucleus GABA concentration in ET cases vs. One interpretation of the finding is that it does not support the existence of PC loss in ET; however, an alternative interpretation is the observed pattern could be due to the effects of terminal sprouting in ET (i.e., collateral sprouting from surviving PCs making up for the loss of GABA-ergic terminals from PC degeneration). Further research is needed.

  18. Gamma-aminobutyric acid esters. 1. Synthesis, brain uptake, and pharmacological studies of aliphatic and steroid esters of gamma-aminobutyric acid

    International Nuclear Information System (INIS)

    Shashoua, V.E.; Jacob, J.N.; Ridge, R.; Campbell, A.; Baldessarini, R.J.

    1984-01-01

    Labeled and unlabeled aliphatic and steroid esters of gamma-amino[U- 14 C]butyric acid (GABA) were synthesized and tested for their capacity to penetrate the blood-brain barrier and for evidence of central neuropharmacological activity in rodents. The uptake of the labeled 9,12,15-octadecatrienyl (linolenyl), 3-cholesteryl, 1-butyl, and the 9-fluoro-11 beta,17-dihydroxy-16 alpha-methyl-3,20-dioxopregna -1,4-dien-21-yl (dexamethasone) esters of GABA into mouse brain increased 2-, 25-, 74-, and 81-fold over GABA, respectively. The cholesteryl ester of GABA depressed the general motor activity of mice and rats in a dose-dependent manner, whereas the 1-butyl, linolenyl, and dexamethasone esters were inactive by this test. Studies of the rates of hydrolysis, GABA receptor binding capacity, and octanol/water partition coefficients indicated that pharmacological activity of the esters after entry into the central nervous system (CNS) was dependent on their capacity to release GABA by enzymatic hydrolysis and their lipid solubility

  19. A GC-ECD method for estimation of free and bound amino acids, gamma-aminobutyric acid, salicylic acid, and acetyl salicylic acid from Solanum lycopersicum (L.).

    Science.gov (United States)

    Meher, Hari Charan; Gajbhiye, Vijay T; Singh, Ghanendra

    2011-01-01

    A gas chromatograph with electron capture detection method for estimation of selected metabolites--amino acids (free and bound), gamma-aminobutyric acid (GABA), salicylic acid (SA), and acetyl salicylic acid (ASA) from tomato--is reported. The method is based on nitrophenylation of the metabolites by 1-fluoro-2, 4-dinitrobenzene under aqueous alkaline conditions to form dinitophenyl derivatives. The derivatives were stable under the operating conditions of GC. Analysis of bound amino acids comprised perchloric acid precipitation of protein, alkylation (carboxymethylation) with iodoacetic acid, vapor-phase hydrolysis, and derivatization with 1-fluoro-2,4-dinitrobenzene in that order. The metabolites were resolved in 35 min, using a temperature-programmed run. The method is rapid, sensitive, and precise. It easily measured the typical amino acids (aspartate, asparagine, glutamate, glutamine, alanine, leucine, lysine, and phenylalanine) used for identification and quantification of a protein, resolved amino acids of the same mass (leucine and isoleucine), satisfactorily measured sulfur amino acid (methionine, cystine, and cysteine), and quantified GABA, SA, and ASA, as well. The developed method was validated for specificity, linearity, and precision. It has been applied and recommended for estimation of 25 metabolites from Solanum lycopersicum (L.).

  20. Prefrontal gamma-aminobutyric acid type A receptor insertion controls cue-induced relapse to nicotine seeking.

    Science.gov (United States)

    Lubbers, Bart R; van Mourik, Yvar; Schetters, Dustin; Smit, August B; De Vries, Taco J; Spijker, Sabine

    2014-11-01

    Current smoking cessation therapies offer limited success, as relapse rates remain high. Nicotine, which is the major component of tobacco smoke, is thought to be primarily responsible for the addictive properties of tobacco. However, little is known about the molecular mechanisms underlying nicotine relapse, hampering development of more effective therapies. The objective of this study was to elucidate the role of medial prefrontal cortex (mPFC) glutamatergic and gamma-aminobutyric acid (GABA)ergic receptors in controlling relapse to nicotine seeking. Using an intravenous self-administration model, we studied glutamate and gamma-aminobutyric acid receptor regulation in the synaptic membrane fraction of the rat mPFC following extinction and cue-induced relapse to nicotine seeking. Subsequently, we locally intervened at the level of GABAergic signaling by using a mimetic peptide of the GABA receptor associated protein-interacting domain of GABA type A (GABAA) receptor subunit γ2 (TAT-GABAγ2) and muscimol, a GABAA receptor agonist. Alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid and N-methyl-D-aspartate receptors were not regulated after the 30-min relapse test. However, GABAA receptor subunits α1 and γ2 were upregulated, and interference with GABAA receptor insertion in the cell membrane using the TAT-GABAγ2 peptide in the dorsal mPFC, but not the ventral mPFC, significantly increased responding during relapse. Increasing GABAA transmission with muscimol in the dorsal and ventral mPFC attenuated relapse. These data indicate that cue-induced relapse entails a GABAergic plasticity mechanism that limits nicotine seeking by restoring inhibitory control in the dorsal mPFC. GABAA receptor-mediated neurotransmission in the dorsal mPFC constitutes a possible future therapeutic target for maintaining smoking abstinence. Copyright © 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  1. Serotonin Transporter (5-HTT) and gamma-Aminobutyric Acid Receptor Subunit beta3 (GABRB3) Gene Polymorphisms are not Associated with Autism in the IMGSA Families

    DEFF Research Database (Denmark)

    Maestrini, E.; Lai, C.; Marlow, A.

    1999-01-01

    Previous studies have suggested that the serotonin transporter (5-HTT) gene and the gamma-aminobutyric acid receptor subunit beta3 (GABRB3) gene, or other genes in the 15q11-q13 region, are possibly involved in susceptibility to autism. To test this hypothesis we performed an association study on...

  2. CHANGES IN SELECTIVITY OF GAMMA-AMINOBUTYRIC ACID FORMATION EFFECTED BY FERMENTATION CONDITIONS AND MICROORGANISMS RESOURCES

    Directory of Open Access Journals (Sweden)

    Kamila Kovalovská

    2011-10-01

    Full Text Available In this study we observe the effect of fermentation conditions and resources of microorganisms for production of γ-aminobutyric acid (GABA. The content of produced GABA depends on various conditions such as the amount of precursor, an addition of salt, enzyme and the effect of pH. The highest selectivity of GABA (74.0 % from the precursor (L-monosodium glutamate has been determinate in the follow conditions: in the presence of pre-cultured microorganisms from Encián cheese in amount 1.66 % (w/v the source of microorganisms/volume of the fermentation mixture, after the addition of 0.028 % (w/v of CaCl2/volume of the fermentation mixture, 100 μM of pyridoxal-5-phosphate (P-5-P and the GABA precursor concentration in the fermentation mixture 2.6 mg ml-1 in an atmosphere of gas nitrogen. Pure cultures of lactic acid bacteria increased the selectivity of GABA by an average of 20 % compared with bacteria from the path of Encián.

  3. Measurement of gamma-aminobutyric acid in human cerebrospinal fluid: radioreceptor assay using [3H]muscimol

    International Nuclear Information System (INIS)

    Baraczka, K.; Sperk, G.

    1981-01-01

    A method is described for the determination of gamma-aminobutyric acid (GABA) levels in human cerebrospinal fluid by modification of the radioreceptor assay utilizing [ 3 H]muscimol as labelled ligand. This method is compared with the radioreceptor assay using [ 3 H]GABA as labelled ligand. Although the [ 3 H]muscimol assay is less sensitive than the [ 3 H]GABA method, it offers the advantage of being more rapid due to the use of a filtration step instead of the usual, more time-consuming centrifugation of the samples. Samples of CSF of patients with various neurological or psychiatric disturbances were analysed. There was a satisfactory correlation between the GABA values obtained by the two assays. (Auth.)

  4. Determination of gamma-aminobutyric acid in food matrices by isotope dilution hydrophilic interaction chromatography coupled to mass spectrometry.

    Science.gov (United States)

    Zazzeroni, Raniero; Homan, Andrew; Thain, Emma

    2009-08-01

    The estimation of the dietary intake of gamma-aminobutyric acid (GABA) is dependent upon the knowledge of its concentration values in food matrices. To this end, an isotope dilution liquid chromatography-mass spectrometry method has been developed employing the hydrophilic interaction chromatography technique for analyte separation. This approach enabled accurate quantification of GABA in apple, potato, soybeans, and orange juice without the need of a pre- or post-column derivatization reaction. A selective and precise analytical measurement has been obtained with a triple quadrupole mass spectrometer operating in multiple reaction monitoring using the method of standard additions and GABA-d(6) as an internal standard. The concentrations of GABA found in the matrices tested are 7 microg/g of apple, 342 microg/g of potatoes, 211 microg/g of soybeans, and 344 microg/mL of orange juice.

  5. A ketogenic diet modifies glutamate, gamma-aminobutyric acid and agmatine levels in the hippocampus of rats: A microdialysis study.

    Science.gov (United States)

    Calderón, Naima; Betancourt, Luis; Hernández, Luis; Rada, Pedro

    2017-03-06

    The ketogenic diet (KD) is acknowledged as an unconventional option in the treatment of epilepsy. Several lines of investigation point to a possible role of glutamate and gamma-aminobutyric acid (GABA) as main contributors in this protective effect. Other biomolecules could also be involved in the beneficial consequence of the KD, for example, the diamine agmatine has been suggested to block imidazole and glutamate NMDA receptor and serves as an endogenous anticonvulsant in different animal models of epilepsy. In the present report, we have used microdialysis coupled to capillary electrophoresis to monitor microdialysate levels of GABA, glutamate and agmatine in the hippocampus of rats submitted to a KD for 15days compared to rats on a normal rat chow diet. A significant increase in GABA and agmatine levels while no change in glutamate levels was observed. These results support the notion that the KD modifies different transmitters favoring inhibitory over excitatory neurotransmitters. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Gamma aminobutyric acid transporter subtype 1 gene knockout mice: a new model for attention deficit/hyperactivity disorder

    Institute of Scientific and Technical Information of China (English)

    Ping Yang; Guoqiang Cai; Youqing Cai; Jian Fei; Guoxiang Liu

    2013-01-01

    Attention deficit/hyperactivity disorder (ADHD) is characterized by hyperactivity,impaired sustained attention,impulsivity,and is usually accompanied by varying degrees of learning difficulties and lack of motor coordination.However,the pathophysiology and etiology of ADHD remain inconclusive so far.Our previous studies have demonstrated that the gamma aminobutyric acid transporter subtype 1 (GAT1) gene knockout (ko) mouse (gat1-/-)is hyperactive and exhibited impaired memory performance in the Morris water maze.In the current study,we found that the gat1-/-mice showed low levels of attentional focusing and increased impulsivity.In addition,the gat1-/-mice displayed ataxia characterized by defects in motor coordination and balance skills.The hyperactivity in the ko mice was reduced by both methylphenidate and amphetamine.Collectively,these results suggest that GAT1 ko mouse is a new animal model for ADHD studying and GAT1 may be a new target to treat ADHD.

  7. Conformational basis for the Li(+)-induced leak current in the rat gamma-aminobutyric acid (GABA) transporter-1

    DEFF Research Database (Denmark)

    MacAulay, Nanna; Zeuthen, Thomas; Gether, Ulrik

    2002-01-01

    The rat gamma-aminobutyric acid transporter-1 (GAT-1) was expressed in Xenopus laevis oocytes and the substrate-independent Li(+)-induced leak current was examined using two-electrode voltage clamp. The leak current was not affected by the addition of GABA and was not due to H(+) permeation. The Li......(+)-bound conformation of the protein displayed a lower passive water permeability than that of the Na(+)- and choline (Ch(+))-bound conformations and the leak current did not saturate with increasing amounts of Li(+) in the test solution. The mechanism that gives rise to the leak current did not support active water...... transport in contrast to the mechanism responsible for GABA translocation (approximately 330 water molecules per charge). Altogether, these data support the distinct nature of the leak conductance in relation to the substrate translocation process. It was observed that the leak current was inhibited by low...

  8. Cortical gamma-aminobutyric acid and glutamate in posttraumatic stress disorder and their relationships to self-reported sleep quality.

    Science.gov (United States)

    Meyerhoff, Dieter J; Mon, Anderson; Metzler, Thomas; Neylan, Thomas C

    2014-05-01

    To test if posttraumatic stress disorder (PTSD) is associated with low brain gamma-aminobutyric acid (GABA) levels and if reduced GABA is mediated by poor sleep quality. Laboratory study using in vivo proton magnetic resonance spectroscopy (1H MRS) and behavioral testing. VA Medical Center Research Service, Psychiatry and Radiology. Twenty-seven patients with PTSD (PTSD+) and 18 trauma-exposed controls without PTSD (PTSD-), recruited from United States Army reservists, Army National Guard, and mental health clinics. None. 1H MRS at 4 Tesla yielded spectra from three cortical brain regions. In parieto-occipital and temporal cortices, PTSD+ had lower GABA concentrations than PTSD-. As expected, PTSD+ had higher depressive and anxiety symptom scores and a higher Insomnia Severity Index (ISI) score. Higher ISI correlated with lower GABA and higher glutamate levels in parieto-occipital cortex and tended to correlate with lower GABA in the anterior cingulate. The relationship between parieto-occipital GABA and PTSD diagnosis was fully mediated through insomnia severity. Lower N-acetylaspartate and glutamate concentrations in the anterior cingulate cortex correlated with higher arousal scores, whereas depressive and anxiety symptoms did generally not influence metabolite concentrations. Low brain gamma-aminobutyric acid (GABA) concentration in posttraumatic stress disorder (PTSD) is consistent with most findings in panic and social anxiety disorders. Low GABA associated with poor sleep quality is consistent with the hyperarousal theory of both primary insomnia and PTSD. Our data demonstrate that poor sleep quality mediates low parieto-occipital GABA in PTSD. The findings have implications for PTSD treatment approaches.

  9. Somatostatin-Positive Gamma-Aminobutyric Acid Interneuron Deficits in Depression: Cortical Microcircuit and Therapeutic Perspectives.

    Science.gov (United States)

    Fee, Corey; Banasr, Mounira; Sibille, Etienne

    2017-10-15

    The functional integration of external and internal signals forms the basis of information processing and is essential for higher cognitive functions. This occurs in finely tuned cortical microcircuits whose functions are balanced at the cellular level by excitatory glutamatergic pyramidal neurons and inhibitory gamma-aminobutyric acidergic (GABAergic) interneurons. The balance of excitation and inhibition, from cellular processes to neural network activity, is characteristically disrupted in multiple neuropsychiatric disorders, including major depressive disorder (MDD), bipolar disorder, anxiety disorders, and schizophrenia. Specifically, nearly 3 decades of research demonstrate a role for reduced inhibitory GABA level and function across disorders. In MDD, recent evidence from human postmortem and animal studies suggests a selective vulnerability of GABAergic interneurons that coexpress the neuropeptide somatostatin (SST). Advances in cell type-specific molecular genetics have now helped to elucidate several important roles for SST interneurons in cortical processing (regulation of pyramidal cell excitatory input) and behavioral control (mood and cognition). Here, we review evidence for altered inhibitory function arising from GABAergic deficits across disorders and specifically in MDD. We then focus on properties of the cortical microcircuit, where SST-positive GABAergic interneuron deficits may disrupt functioning in several ways. Finally, we discuss the putative origins of SST cell deficits, as informed by recent research, and implications for therapeutic approaches. We conclude that deficits in SST interneurons represent a contributing cellular pathology and therefore a promising target for normalizing altered inhibitory function in MDD and other disorders with reduced SST cell and GABA functions. Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  10. Gamma-aminobutyric acid agonists for antipsychotic-induced tardive dyskinesia.

    Science.gov (United States)

    Alabed, Samer; Latifeh, Youssef; Mohammad, Husam Aldeen; Bergman, Hanna

    2018-04-17

    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. 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.2. Secondary objectivesThe secondary objectives were as follows.To examine whether any improvement occurred with short periods of intervention (less than six weeks) and, if this did occur, whether this effect was maintained at longer periods of follow-up.To examine whether there was a differential effect between the various compounds.To test the hypothesis that GABA agonist drugs are most effective for a younger age group (less than 40 years old). We searched the Cochrane Schizophrenia Group Trials Register (last searched April 2017), inspected references of all identified studies for further trials, and, when necessary, contacted authors of trials for additional information. We included randomised controlled trials of non-benzodiazepine GABA agonist drugs in people with antipsychotic-induced TD and schizophrenia or other chronic mental illness. Two review authors independently selected and critically appraised studies, extracted and analysed data on an intention-to-treat basis. Where possible and appropriate we calculated risk ratios (RRs) and their 95% confidence intervals (CIs). For continuous data we calculated mean differences (MD). We assumed that people who left early had no improvement. We contacted investigators to obtain missing information. We assessed risk of bias for included studies and created a 'Summary of findings' table using GRADE. We included 11 studies that randomised 343 people. Overall, the risk of bias

  11. Potentiation of gamma aminobutyric acid receptors (GABAAR by Ethanol: How are inhibitory receptors affected?

    Directory of Open Access Journals (Sweden)

    Benjamin eFörstera

    2016-05-01

    Full Text Available In recent years there has been an increase in the understanding of ethanol actions on the type A -aminobutyric acid chloride channel (GABAAR, a member of the pentameric ligand gated ion channels (pLGICs. However, the mechanism by which ethanol potentiates the complex is still not fully understood and a number of publications have shown contradictory results. Thus many questions still remain unresolved requiring further studies for a better comprehension of this effect. The present review concentrates on the involvement of GABAAR in the acute actions of ethanol and specifically focuses on the immediate, direct or indirect, synaptic and extra-synaptic modulatory effects. To elaborate on the immediate, direct modulation of GABAAR by acute ethanol exposure, electrophysiological studies investigating the importance of different subunits, and data from receptor mutants will be examined. We will also discuss the nature of the putative binding sites for ethanol based on structural data obtained from other members of the pLGICs family. Finally, we will briefly highlight the glycine gated chloride channel (GlyR, another member of the pLGIC family, as a suitable target for the development of new pharmacological tools.

  12. Gamma-aminobutyric acid depletion affects stomata closure and drought tolerance of Arabidopsis thaliana.

    Science.gov (United States)

    Mekonnen, Dereje Worku; Flügge, Ulf-Ingo; Ludewig, Frank

    2016-04-01

    A rapid accumulation of γ-aminobutyric acid (GABA) during biotic and abiotic stresses is well documented. However, the specificity of the response and the primary role of GABA under such stress conditions are hardly understood. To address these questions, we investigated the response of the GABA-depleted gad1/2 mutant to drought stress. GABA is primarily synthesized from the decarboxylation of glutamate by glutamate decarboxylase (GAD) which exists in five copies in the genome of Arabidopsis thaliana. However, only GAD1 and GAD2 are abundantly expressed, and knockout of these two copies dramatically reduced the GABA content. Phenotypic analysis revealed a reduced shoot growth of the gad1/2 mutant. Furthermore, the gad1/2 mutant was wilted earlier than the wild type following a prolonged drought stress treatment. The early-wilting phenotype was due to an increase in stomata aperture and a defect in stomata closure. The increase in stomata aperture contributed to higher stomatal conductance. The drought oversensitive phenotype of the gad1/2 mutant was reversed by functional complementation that increases GABA level in leaves. The functionally complemented gad1/2 x pop2 triple mutant contained more GABA than the wild type. Our findings suggest that GABA accumulation during drought is a stress-specific response and its accumulation induces the regulation of stomatal opening thereby prevents loss of water. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  13. Optimization of culture conditions for gamma-aminobutyric acid production in fermented adzuki bean milk

    Directory of Open Access Journals (Sweden)

    Hung Yi Song

    2018-01-01

    Full Text Available γ-Aminobutyric acid (GABA, a nonprotein amino acid, is widely distributed in nature and fulfills several physiological functions. In this study, various lactic acid strains commonly used to produce fermented milk products were inoculated into adzuki bean milk for producing GABA. The high GABA producing strain was selected in further experiment to improve the GABA production utilizing culture medium optimization. The results demonstrated that adzuki bean milk inoculated with Lactobacillus rhamnosus GG increased GABA content from 0.05 mg/mL to 0.44 mg/mL after 36 hours of fermentation, which showed the greatest elevation in this study. Furthermore, the optimal cultural condition to adzuki bean milk inoculated with L. rhamnosus GG to improve the GABA content was performed using response surface methodology. The results showed that GABA content was dependent on the addition of galactose, monosodium glutamate, and pyridoxine with which the increasing ratios of GABA were 23–38%, 24–68%, and 8–36%, respectively. The optimal culture condition for GABA production of adzuki bean milk was found at the content of 1.44% galactose, 2.27% monosodium glutamate, and 0.20% pyridoxine. Under the optimal cultural condition, the amount of GABA produced in the fermented adzuki bean milk was 1.12 mg/mL, which was 22.4-fold higher than that of the unfermented adzuki bean milk (0.05 mg/100 mL. The results suggested that the optimized cultural condition of adzuki bean milk inoculated with L. rhamnosus GG can increase GABA content for consumers as a daily supplement as suggested.

  14. Disruption of pknG enhances production of gamma-aminobutyric acid by Corynebacterium glutamicum expressing glutamate decarboxylase.

    Science.gov (United States)

    Okai, Naoko; Takahashi, Chihiro; Hatada, Kazuki; Ogino, Chiaki; Kondo, Akihiko

    2014-01-01

    Gamma-aminobutyric acid (GABA), a building block of the biodegradable plastic polyamide 4, is synthesized from glucose by Corynebacterium glutamicum that expresses Escherichia coli glutamate decarboxylase (GAD) B encoded by gadB. This strain was engineered to produce GABA more efficiently from biomass-derived sugars. To enhance GABA production further by increasing the intracellular concentration of its precursor glutamate, we focused on engineering pknG (encoding serine/threonine protein kinase G), which controls the activity of 2-oxoglutarate dehydrogenase (Odh) in the tricarboxylic acid cycle branch point leading to glutamate synthesis. We succeeded in expressing GadB in a C. glutamicum strain harboring a deletion of pknG. C. glutamicum strains GAD and GAD ∆pknG were cultured in GP2 medium containing 100 g L(-1) glucose and 0.1 mM pyridoxal 5'-phosphate. Strain GAD∆pknG produced 31.1 ± 0.41 g L(-1) (0.259 g L(-1) h(-1)) of GABA in 120 hours, representing a 2.29-fold higher level compared with GAD. The production yield of GABA from glucose by GAD∆pknG reached 0.893 mol mol(-1).

  15. Effects of exogenous gamma-aminobutyric acid on α-amylase activity in the aleurone of barley seeds.

    Science.gov (United States)

    Sheng, Yidi; Xiao, Huiyuan; Guo, Chunli; Wu, Hong; Wang, Xiaojing

    2018-03-03

    Gamma-aminobutyric acid (GABA), a nonprotein amino acid, often accumulates in plants exposed to certain environmental stimuli. Previous studies indicated that a closed relationship existed between endogenous GABA and seed germination. However, there are few studies on the effect of exogenous GABA on seed germination. The objective of this study was to explore whether exogenous GABA affected α-amylase activity which the activation is an important stage in seed germination. The level of endogenous GABA in barley seeds rose gradually during germination, suggesting that endogenous GABA was involved in germination. We measured starch degradation under application of various concentration GABA and found that GABA promoted seed starch degradation with a dose-responsive effect. The relationship between GABA and α-amylase activity was investigated by treating barley aleurone with exogenous GABA. The result showed that α-amylase activity began to rise after about 24 h and reached a peak at 48 h. Molecular evidence suggested that GABA increased α-amylase gene expression. We explore the possible roles played by GABA in signal transduction. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  16. Gamma-aminobutyric acid, a potential tumor suppressor for small airway-derived lung adenocarcinoma.

    Science.gov (United States)

    Schuller, Hildegard M; Al-Wadei, Hussein A N; Majidi, Mourad

    2008-10-01

    Pulmonary adenocarcinoma (PAC) is the leading type of lung cancer in smokers and non-smokers that arises in most cases from small airway epithelial cells. PAC has a high mortality due to its aggressive behavior and resistance to cancer therapeutics. We have shown previously that the proliferation of human PAC cells NCI-H322 and immortalized human small airway epithelial cells HPL1D is stimulated by cyclic adenosine monophosphate (cAMP)/protein kinase A-dependent phosphorylation of cyclic adenosine monophosphate response element-binding (CREB) protein and transactivation of the epidermal growth factor receptor and that this pathway is activated by beta-1-adrenoreceptors (beta(1)-ARs) and the non-genomic estrogen receptor beta. Our current in vitro studies with HPL1D and NCI-H322 cells showed that signaling via the gamma-amino butyric acid receptor (GABA(B)R) strongly inhibited base level and isoproterenol-induced cAMP, p-CREB, cyclic adenosine monophosphate response element-luciferase activity and p-extracellular regulated kinase-1 (ERK1)/2 and effectively blocked DNA synthesis and cell migration. The inhibitory effects of gamma-amino butyric acid (GABA) were disinhibited by the GABA(B)R antagonist CGP-35348 or GABA(B)R knockdown. Immunohistochemical investigation of hamster lungs showed significant underexpression of GABA in animals with small airway-derived PACs induced by the nicotine-derived carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). These findings suggest that GABA may have tumor suppressor function in small airway epithelia and the PACs derived from them and that downregulation of GABA by NNK may contribute to the development of this cancer in smokers. Our findings suggest that marker-guided treatment with GABA or a GABA(B)R agonist of individuals with downregulated pulmonary GABA may provide a novel targeted approach for the prevention of PAC in smokers.

  17. The gamma-aminobutyric acid uptake inhibitor, tiagabine, is anticonvulsant in two animal models of reflex epilepsy.

    Science.gov (United States)

    Smith, S E; Parvez, N S; Chapman, A G; Meldrum, B S

    1995-02-06

    The effects of i.p. administration of the gamma-aminobutyric acid (GABA) uptake inhibitors R(-)N-(4,4-di(3-methylthien-2-yl)-but-3-enyl) nipecotic acid hydrochloride (tiagabine; molecular weight 412.0), (1-(2-(((diphenylmethylene)-amino)oxy)ethyl)-1,2,5,6-tetrahydro-3- pyridinecarboxylic acid hydrochloride (NNC-711; molecular weight 386.9), and (+/-)-nipecotic acid (molecular weight 128.2) are compared with those of carbamazepine (molecular weight 236.3) on sound-induced seizures and locomotor performance in genetically epilepsy-prone (GEP) rats. The ED50 value against clonic seizures (in mumol kg-1 at the time of maximal anticonvulsant effect) for tiagabine was 23 (0.5 h), and for NNC-711 was 72 (1 h), and for carbamazepine was 98 (2 h). (+/-)-Nipecotic acid (0.4-15.6 mmol kg-1) was not anticonvulsant. High doses of NNC-711 (207-310 mumol kg-1) and of (+/-)-nipecotic acid (39-78 mmol kg-1) induced ataxia and myoclonic seizures 0.25-1 h. Tiagabine and carbamazepine did not induce myoclonic seizures and had similar therapeutic indices (locomotor deficit ED50/anticonvulsant ED50) ranging from 0.4 to 1.9. In Papio papio, we observed a reduction in photically induced myoclonic seizures with tiagabine (2.4 mumol kg-1 i.v.) accompanied with neurological impairment. Tiagabine has comparable anticonvulsant action to carbamazepine in rats and has anticonvulsant effects in non-human primates supporting the potential use of inhibitors of GABA uptake as therapy for epilepsy.

  18. [Influence of exogenous gamma-aminobutyric acid (GABA) on GABA metabolism and amino acid contents in roots of melon seedling under hypoxia stress].

    Science.gov (United States)

    Wang, Chun-Yan; Li, Jing-Rui; Xia, Qing-Ping; Wu, Xiao-Lei; Gao, Hong-Bo

    2014-07-01

    This paper investigated the influence of gamma-aminobutyric acid (GABA) on GABA metabolism and amino acid content under hypoxia stress by accurately controlling the level of dissolved oxygen in hydroponics, using the roots of melon 'Xiyu 1' seedlings as the test material. The results showed that compared with the control, the growth of roots was inhibited seriously under hypoxia stress. Meanwhile, the hypoxia-treated roots had significantly higher activities of glutamate decarboxylase (GAD), glutamate dehydrogenase (GDH), glutamate synthase (GOGAT), glutamine synthetase (GS), alanine aminotransferase (ALT), aspartate aminotransferase (AST) as well as the contents of GABA, pyruvic acid, alanine (Ala) and aspartic acid (Asp). But the contents of glutamic acid (Glu) and alpha-keto glutaric acid in roots under hypoxia stress was obviously lower than those of the control. Exogenous treatment with GABA alleviated the inhibition effect of hypoxia stress on root growth, which was accompanied by an increase in the contents of endogenous GABA, Glu, alpha-keto glutaric acid and Asp. Furthermore, under hypoxia stress, the activities of GAD, GDH, GOGAT, GS, ALT, AST as well as the contents of pyruvic acid and Ala significantly decreased in roots treated with GABA. However, adding GABA and viny-gamma-aminobutyric acid (VGB) reduced the alleviation effect of GABA on melon seedlings under hypoxia stress. The results suggested that absorption of GABA by roots could alleviate the injury of hypoxia stress to melon seedlings. This meant that GABA treatment allows the normal physiological metabolism under hypoxia by inhibiting the GAD activity through feedback and maintaining higher Glu content as well as the bal- ance of carbon and nitrogen.

  19. Analysis of subcomponents of the gamma-aminobutyric acid/benzodiazepine receptor macromolecular complex in mammalian central nervous system

    International Nuclear Information System (INIS)

    McCabe, R.T.

    1987-01-01

    Since the presence of endogenous gamma-aminobutyric acid (GABA) may affect benzodiazepine binding to tissue sections in autoradiographic studies, a protocol designed to check for this influence has been investigated. [ 3 H]Flunitrazepam (1 nM) was used to label benzodiazepine receptors for autoradiographic localization. Bicuculline was added to the incubation medium of an additional set of tissue sections to antagonize any potential effect of endogenous GABA. Binding in these sections was compared to that occurring in another set in which excess GABA was added to create further GABA enhancement. Binding was also compared to adjacent sections which were treated similarly but also preincubated in distilled-deionized water to burst the cells by osmotic shock and eliminate endogenous GABA, thereby preventing any effect on benzodiazepine binding. The results indicated that endogenous GABA is indeed present in the slide-mounted tissue sections and is affecting benzodiazepine receptor binding differentially in various regions of the brain depending on the density of GABAergic innervation. Scatchard analysis of saturation data demonstrated that the alteration in BZ binding due to GABA was a result of a change in the affinity rather than number of receptors present

  20. Probable gamma-aminobutyric acid involvement in bisphenol A effect at the hypothalamic level in adult male rats.

    Science.gov (United States)

    Cardoso, Nancy; Pandolfi, Matías; Lavalle, Justina; Carbone, Silvia; Ponzo, Osvaldo; Scacchi, Pablo; Reynoso, Roxana

    2011-12-01

    The aim of the present study was to investigate the effects of bisphenol A (BPA) on the neuroendocrine mechanism of control of the reproductive axis in adult male rats exposed to it during pre- and early postnatal periods. Wistar mated rats were treated with either 0.1% ethanol or BPA in their drinking water until their offspring were weaned at the age of 21 days. The estimated average dose of exposure to dams was approximately 2.5 mg/kg body weight per day of BPA. After 21 days, the pups were separated from the mother and sacrificed on 70 day of life. Gn-RH and gamma-aminobutyric acid (GABA) release from hypothalamic fragments was measured. LH, FSH, and testosterone concentrations were determined, and histological and morphometrical studies of testis were performed. Gn-RH release decreased significantly, while GABA serum levels were markedly increased by treatment. LH serum levels showed no changes, and FSH and testosterone levels decreased significantly. Histological studies showed abnormalities in the tubular organization of the germinal epithelium. The cytoarchitecture of germinal cells was apparently normal, and a reduction of the nuclear area of Leydig cells but not their number was observed. Taken all together, these results provide evidence of the effect caused by BPA on the adult male reproductive axis when exposed during pre- and postnatal period. Moreover, our findings suggest a probable GABA involvement in its effect at the hypothalamic level.

  1. Gamma-Aminobutyric Acid Concentration is Reduced in Visual Cortex in Schizophrenia and Correlates with Orientation-Specific Surround Suppression

    Science.gov (United States)

    Yoon, Jong H.; Maddock, Richard J.; Rokem, Ariel; Silver, Michael A.; Minzenberg, Michael J.; Ragland, J. Daniel; Carter, Cameron S.

    2010-01-01

    The neural mechanisms underlying cognitive deficits in schizophrenia remain largely unknown. The gamma-aminobutyric acid (GABA) hypothesis proposes that reduced neuronal GABA concentration and neurotransmission results in cognitive impairments in schizophrenia. However, few in vivo studies have directly examined this hypothesis. We employed magnetic resonance spectroscopy (MRS) at high field to measure visual cortical GABA levels in 13 subjects with schizophrenia and 13 demographically matched healthy control subjects. We found that the schizophrenia group had an approximately 10% reduction in GABA concentration. We further tested the GABA hypothesis by examining the relationship between visual cortical GABA levels and orientation-specific surround suppression (OSSS), a behavioral measure of visual inhibition thought to be dependent on GABAergic synaptic transmission. Previous work has shown that subjects with schizophrenia exhibit reduced OSSS of contrast discrimination (Yoon et al., 2009). For subjects with both MRS and OSSS data (n=16), we found a highly significant positive correlation (r=0.76) between these variables. GABA concentration was not correlated with overall contrast discrimination performance for stimuli without a surround (r=-0.10). These results suggest that a neocortical GABA deficit in subjects with schizophrenia leads to impaired cortical inhibition and that GABAergic synaptic transmission in visual cortex plays a critical role in OSSS. PMID:20220012

  2. Prefrontal cortical gamma-aminobutyric acid transmission and cognitive function: drawing links to schizophrenia from preclinical research.

    Science.gov (United States)

    Tse, Maric T; Piantadosi, Patrick T; Floresco, Stan B

    2015-06-01

    Cognitive dysfunction in schizophrenia is one of the most pervasive and debilitating aspects of the disorder. Among the numerous neural abnormalities that may contribute to schizophrenia symptoms, perturbations in markers for the inhibitory neurotransmitter gamma-aminobutyric acid (GABA), particularly within the frontal lobes, are some of the most reliable alterations observed at postmortem examination. However, how prefrontal GABA dysfunction contributes to cognitive impairment in schizophrenia remains unclear. We provide an overview of postmortem GABAergic perturbations in the brain affected by schizophrenia and describe circumstantial evidence linking these alterations to cognitive dysfunction. In addition, we conduct a survey of studies using neurodevelopmental, genetic, and pharmacologic rodent models that induce schizophrenia-like cognitive impairments, highlighting the convergence of these mechanistically distinct approaches to prefrontal GABAergic disruption. We review preclinical studies that have directly targeted prefrontal cortical GABAergic transmission using local application of GABAA receptor antagonists. These studies have provided an important link between GABA transmission and cognitive dysfunction in schizophrenia because they show that reducing prefrontal inhibitory transmission induces various cognitive, emotional, and dopaminergic abnormalities that resemble aspects of the disorder. These converging clinical and preclinical findings provide strong support for the idea that perturbations in GABA signaling drive certain forms of cognitive dysfunction in schizophrenia. Future studies using this approach will yield information to refine further a putative "GABA hypothesis" of schizophrenia. Copyright © 2015 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  3. Decreased Hepatocyte Growth Factor (HGF) and Gamma Aminobutyric Acid (GABA) in Individuals with Obsessive-Compulsive Disorder (OCD).

    Science.gov (United States)

    Russo, Anthony J; Pietsch, Stefanie C

    2013-01-01

    There is support for the role of gamma aminobutyric acid (GABA) in the etiology of mood disorders. Recent research has shown that hepatocyte growth factor (HGF) modulates GABAergic inhibition and seizure susceptibility. This study was designed to determine and correlate plasma levels of HGF and GABA as well as symptom severity in individuals with obsessive-compulsive disorder (OCD). Plasma from 15 individuals with OCD (9 males, 6 females;, mean age 38.7 years) and 17 neurotypical controls (10 males, 7 females; mean age 35.2 years) was assessed for HGF, GABA, urokinase plasminogen activator (uPA), and urokinase plasminogen activator receptor (uPAR) concentration using enzyme-linked immunosorbest assays ELISAs. Symptom severity was assessed in these OCD individuals and compared with HGF and GABA concentrations. In this preliminary study, individuals with OCD had significantly decreased HGF levels, decreased plasma levels of GABA and decreased uPA. We found that both uPA and uPAR levels correlate with HGF. Both low uPA and low uPAR levels correlate with high symptom severity in individuals with OCD. Low GABA levels in OCD individuals also correlate with high symptom severity. These results demonstrate a preliminary association between HGF, GABA, uPA levels, and OCD and suggest that plasma GABA and uPA levels are related to symptom severity in individuals with OCD.

  4. Higher gamma-aminobutyric acid neuron density in the white matter of orbital frontal cortex in schizophrenia.

    Science.gov (United States)

    Joshi, Dipesh; Fung, Samantha J; Rothwell, Alice; Weickert, Cynthia Shannon

    2012-11-01

    In the orbitofrontal cortex (OFC), reduced gray matter volume and reduced glutamic acid decarboxylase 67kDa isoform (GAD67) messenger (m)RNA are found in schizophrenia; however, how these alterations relate to developmental pathology of interneurons is unclear. The present study therefore aimed to determine if increased interstitial white matter neuron (IWMN) density exists in the OFC; whether gamma-aminobutyric acid (GABA)ergic neuron density in OFC white matter was altered; and how IWMN density may be related to an early-expressed inhibitory neuron marker, Dlx1, in OFC gray matter in schizophrenia. IWMN densities were determined (38 schizophrenia and 38 control subjects) for neuronal nuclear antigen (NeuN+) and 65/67 kDa isoform of glutamic acid decarboxylase immunopositive (GAD65/67+) neurons. In situ hybridization was performed to determine Dlx1 and GAD67 mRNA expression in the OFC gray matter. NeuN and GAD65/67 immunopositive cell density was significantly increased in the superficial white matter in schizophrenia. Gray matter Dlx1 and GAD67 mRNA expression were reduced in schizophrenia. Dlx1 mRNA levels were negatively correlated with GAD65/67 IWMN density. Our study provides evidence that pathology of IWMNs in schizophrenia includes GABAergic interneurons and that increased IWMN density may be related to GABAergic deficits in the overlying gray matter. These findings provide evidence at the cellular level that the OFC is a site of pathology in schizophrenia and support the hypothesis that inappropriate migration of cortical inhibitory interneurons occurs in schizophrenia. Copyright © 2012 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  5. gamma-Aminobutyric acid- and benzodiazepine-induced modulation of [35S]-t-butylbicyclophosphorothionate binding to cerebellar granule cells

    International Nuclear Information System (INIS)

    Gallo, V.; Wise, B.C.; Vaccarino, F.; Guidotti, A.

    1985-01-01

    t-Butylbicyclophosphorothionate (TBPS) is a bicyclophosphate derivative with potent picrotoxin-like convulsant activity that binds with high affinity and specificity to a Cl- channel-modulatory site of the gamma-aminobutyric acid (GABA)/benzodiazepine receptor complex. Using intact cerebellar granule cells maintained in primary culture, the authors have studied the modifications induced by GABA and diazepam on the ion channel-modulatory binding site labeled by [ 35 S]TBPS. At 25 degrees C, and in a modified Locke solution, the [ 35 S]TBPS specific binding, determined by displacing the radioligand with an excess (10(-4) M) of picrotoxin, was approximately 70% of the total radioactivity bound to the cells. [ 35 S]TBPS specific binding was saturable with a Kd of approximately 100 nM, a Bmax of approximately 440 fmol/mg of protein, and a Hill coefficient of 1.18. Neither cerebellar astrocytes maintained in culture for 2 weeks nor a neuroblastoma cell line (NB-2A) exhibited any specific [ 35 S]TBPS binding. Muscimol (0.3 to 5 microM) enhanced and bicuculline (0.1 to 5 microM) inhibited [ 35 S]TBPS specific binding to intact cerebellar granule cells. The effect of muscimol and bicuculline on [ 35 S]TBPS binding was noncompetitive. Muscimol (0.1 to 5 microM) reversed bicuculline inhibition in a dose-dependent fashion but failed to reverse picrotoxin-induced inhibition. [ 35 S]TBPS binding was also modulated by benzodiazepine receptor ligands. The binding was increased by diazepam and decreased by 6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylic acid methylester. Muscimol (0.05 microM) failed to reverse bicuculline inhibition in the absence of diazepam, but it became effective in the presence of 0.1 to 1 microM diazepam

  6. The Role of Ventral Tegmental Area Gamma-Aminobutyric Acid in Chronic Neuropathic Pain after Spinal Cord Injury in Rats.

    Science.gov (United States)

    Ko, Moon Yi; Jang, Eun Young; Lee, June Yeon; Kim, Soo Phil; Whang, Sung Hun; Lee, Bong Hyo; Kim, Hee Young; Yang, Chae Ha; Cho, Hee Jung; Gwak, Young S

    2018-04-20

    Spinal cord injury (SCI) frequently results in chronic neuropathic pain (CNP). However, the understanding of brain neural circuits in CNP modulation is unclear. The present study examined the changes of ventral tegmental area (VTA) putative GABAergic and dopaminergic neuronal activity with CNP attenuation in rats. SCI was established by T10 clip compression injury (35 g, 1 min) in rats, and neuropathic pain behaviors, in vivo extracellular single-cell recording of putative VTA gamma-aminobutyric acid (GABA)/dopamine neurons, extracellular GABA level, glutamic acid decarboxylase (GAD), and vesicular GABA transporters (VGATs) were measured in the VTA, respectively. The results revealed that extracellular GABA level was significantly increased in the CNP group (50.5 ± 18.9 nM) compared to the sham control group (10.2 ± 1.7 nM). In addition, expression of GAD 65/67 , c-Fos, and VGAT exhibited significant increases in the SCI groups compared to the sham control group. With regard to neuropathic pain behaviors, spontaneous pain measured by ultrasound vocalizations (USVs) and evoked pain measured by paw withdrawal thresholds showed significant alteration, which was reversed by intravenous (i.v.) administration of morphine (0.5-5.0 mg/kg). With regard to in vivo electrophysiology, VTA putative GABAergic neuronal activity (13.6 ± 1.7 spikes/sec) and putative dopaminergic neuronal activity (2.4 ± 0.8 spikes/sec) were increased and decreased, respectively, in the SCI group compared to the sham control group. These neuronal activities were reversed by i.v. administration of morphine. The present study suggests that chronic increase of GABAergic neuronal activity suppresses dopaminergic neuronal activity in the VTA and is responsible for negative emotion and motivation for attenuation of SCI-induced CNP.

  7. Affective and cognitive effects of global deletion of alpha3-containing gamma-aminobutyric acid-A receptors.

    Science.gov (United States)

    Fiorelli, Roberto; Rudolph, Uwe; Straub, Carolin J; Feldon, Joram; Yee, Benjamin K

    2008-09-01

    Gamma-aminobutyric acid (GABA)A receptors characterized by the presence of the alpha3 subunit are the major GABAA receptor subtype expressed in brain stem monoaminergic nuclei. These alpha3-GABAA receptors are therefore in a unique position to regulate monoaminergic functions. To characterize the functional properties of alpha3-GABAA receptors, we present a preliminary assessment of the expression of affective and cognitive behaviour in male mice with a targeted deletion of the Gabra3 gene encoding the alpha3 subunit [alpha3 knockout (KO) mice] on a C57BL/6Jx129X1/SvJ F1 hybrid genetic background. The alpha3 KO mice did not exhibit any gross change of anxiety-like behaviour or spontaneous locomotor behaviour. In the Porsolt forced swim test for potential antidepressant activity, alpha3 KO mice exhibited reduced floating and enhanced swimming behaviour relative to wild-type controls. Performance on a two-choice sucrose preference test, however, revealed no evidence for an increase in sucrose preference in the alpha3 KO mice that would have substantiated a potential phenotype for depression-related behaviour. In contrast, a suggestion of an enhanced negative contrast effect was revealed in a one-bottle sucrose consumption test across different sucrose concentrations. These affective phenotypes were accompanied by alterations in the balance between conditioned responding to the discrete conditioned stimulus and to the context, and a suggestion of faster extinction, in the Pavlovian conditioned freezing paradigm. Spatial learning in the water maze reference memory test, however, was largely unchanged in the alpha3 KO mice, except for a trend of preservation during reversal learning. The novel phenotypes following global deletion of the GABAA receptor alpha3 subunit identified here provided relevant insights, in addition to our earlier study, into the potential behavioural relevance of this specific receptor subtypes in the modulation of both affective and cognitive

  8. Channel opening of gamma-aminobutyric acid receptor from rat brain: molecular mechanisms of the receptor responses.

    Science.gov (United States)

    Cash, D J; Subbarao, K

    1987-12-01

    The function of gamma-aminobutyric acid (GABA) receptors, which mediate transmembrane chloride flux, can be studied by use of 36Cl- isotope tracer with membrane from mammalian brain by quench-flow technique, with reaction times that allow resolution of the receptor desensitization rates from the ion flux rates. The rates of chloride exchange into the vesicles in the absence and presence of GABA were characterized with membrane from rat cerebral cortex. Unspecific 36Cl- influx was completed in three phases of ca. 3% (t 1/2 = 0.6 s), 56% (t 1/2 = 82 s), and 41% (t 1/2 = 23 min). GABA-mediated, specific chloride exchange occurred with 6.5% of the total vesicular internal volume. The GABA-dependent 36Cl- influx proceeded in two phases, each progressively slowed by desensitization. The measurements supported the presence of two distinguishable active GABA receptors on the same membrane mediating chloride exchange into the vesicles with initial first-order rate constants of 9.5 s-1 and 2.3 s-1 and desensitizing with first-order rate constants of 21 s-1 and 1.4 s-1, respectively, at saturation. The half-response concentrations were similar for both receptors, 150 microM and 114 microM GABA for desensitization and 105 microM and 82 microM for chloride exchange, for the faster and slower desensitizing receptors, respectively. The two receptors were present in the activity ratio of ca. 4/1, similar to the ratio of "low-affinity" to "high-affinity" GABA sites found in ligand binding experiments. The desensitization rates have a different dependence on GABA concentration than the channel-opening equilibria.(ABSTRACT TRUNCATED AT 250 WORDS)

  9. Alterations of neurotransmitter norepinephrine and gamma-aminobutyric acid correlate with murine behavioral perturbations related to bisphenol A exposure.

    Science.gov (United States)

    Ogi, Hiroshi; Itoh, Kyoko; Ikegaya, Hiroshi; Fushiki, Shinji

    2015-09-01

    Humans are commonly exposed to endocrine-disrupting chemical bisphenol A (BPA), giving rise to concern over the psychobehavioral effects of BPA. The aim of this study was to investigate the effects of prenatal and lactational BPA exposure on neurotransmitters, including norepinephrine (NE), gamma-aminobutyric acid (GABA) and glutamate (Glu), and to assess the association with behavioral phenotypes. C57BL/6J mice were orally administered with BPA (500 μg/bwkg/day) or vehicle daily from embryonic day 0 to postnatal week 3 (P3W), through their dams. The IntelliCage behavioral experiments were conducted from P11W to P15W. At around P14-16W, NE, GABA and Glu levels in nine brain regions were measured by high performance liquid chromatography. Furthermore, the associations between the neurotransmitter levels and the behavioral indices were statistically analyzed. In females exposed to BPA, the GABA and Glu levels in almost all regions, and the NE levels in the cortex, hypothalamus and thalamus were higher than those in the controls. In males exposed to BPA, the GABA levels in the amygdala and hippocampus showed lower values, while Glu levels were higher in some regions, compared with the controls. In regard to the associations, the number of "diurnal corner visits without drinking" was correlated with the NE levels in the cortex and thalamus in females. The "nocturnal corner visit duration without drinking" was correlated with the GABA level in the hippocampus in males. These results suggest that prenatal and lactational exposure to low doses of BPA might modulate the NE, GABA and Glu systems, resulting in behavioral alterations. Copyright © 2014 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  10. Wheat bran with enriched gamma-aminobutyric acid attenuates glucose intolerance and hyperinsulinemia induced by a high-fat diet.

    Science.gov (United States)

    Shang, Wenting; Si, Xu; Zhou, Zhongkai; Strappe, Padraig; Blanchard, Chris

    2018-05-23

    In this study, the level of gamma-aminobutyric acid (GABA) in wheat bran was increased to be six times higher through the action of endogenous glutamate decarboxylase compared with untreated bran. The process of GABA formation in wheat bran also led to an increased level of phenolic compounds with enhanced antioxidant capacity 2 times higher than the untreated status. The interventional effect of a diet containing GABA-enriched bran on hyperinsulinemia induced by a high-fat diet (HFD) was investigated in a rat model. The results showed that, when compared with animals fed with HFD-containing untreated bran (NB group), the consumption of HFD-containing GABA-enriched bran (GB group) demonstrated a greater improvement of insulin resistance/sensitivity as revealed by the changes in the homeostatic model assessment for insulin resistance index (HOMA-IR) and the quantitative insulin sensitivity check index (QUICKI). The expression of hepatic genes, cytochrome P450 family 7 subfamily A member 1 (Cyp7a1) and ubiquitin C (Ubc), which are involved in the adipogenesis-associated PPAR signalling pathway, was found to be significantly down-regulated in the GB group compared with the HFD group (P = 0.0055). Meanwhile, changes in the expression of a number of genes associated with lipid metabolism and gluconeogenesis were also noted in the GB group versus the HFD group, but not in the NB group, indicating different regulatory patterns between the two brans in a high-fat diet. More importantly, the analysis of key genes related to glucose metabolism further revealed that the expression of insulin-induced gene 1/2 (Insig-1/2) was increased following GB intervention with a corresponding reduction in phosphoenolpyruvate carboxykinase 1 (Pepck) and glucose-6-phosphatase, catalytic subunit (G6pc) expression, suggesting that glucose homeostasis is greatly improved through the intervention of GABA-enriched bran in the context of a high-fat diet.

  11. The modern view of the idea of gamma-aminobutyric acid and its metabolite use to restore the motor function

    Directory of Open Access Journals (Sweden)

    А. G. Rodinskij

    2015-08-01

    Full Text Available Aim. The literature review is devoted to the idea of using gamma-aminobutyric acid and its metabolites as medicines in conditions of peripheral nervous system injury. We examined the modern problems of denervated muscles restoration and a wide range of GABA effects which could be useful in conditions of injury. GABA and its metabolites have elements of nootropic, antihypoxic, organoprotective and anabolic activity. It is obvious that traumas of peripheral nerves lead to degeneration of injured fibers and significant disorders of metabolism at a number of regulatory levels. Regeneration of the nerve and the rate of recovery of muscle activity depend significantly on the level of resistivity of the injured nerve tissue and on possibilities for supply of this tissue by additional energetic reserves. Under the above-mentioned conditions, disorders are determined, to a significant extent, by the development of hypoxia. This is why elucidation of the phenomenology and mechanisms of action of GABA and its metabolites (agent are having, as was mentioned above, protective and antihypoxic properties on the nerve/muscle apparatus and its links under conditions of traumatization of a large nerve is urgent. GABA and its metabolites have an antinociceptive activity which helps not only in inhibition of central and spinal neurons, but also helps to decrease pain sensitivity of patient after traumatic neuropathy to forming of motivation to recovery rehabilitation. Besides above mentioned, the ability of GABA to increase concentration of Ca2 + after injury was discussed. This ability may affect the expression of genes, the direction of the growth cone, and, perhaps, reduce cell death. Conclusion. This indicates that the GABA has a selectivity of action to the damaged structure and can be prospective agent for regenerative therapy.

  12. Effects of gamma-aminobutyric acid-modulating drugs on working memory and brain function in patients with schizophrenia.

    Science.gov (United States)

    Menzies, Lara; Ooi, Cinly; Kamath, Shri; Suckling, John; McKenna, Peter; Fletcher, Paul; Bullmore, Ed; Stephenson, Caroline

    2007-02-01

    Cognitive impairment causes morbidity in schizophrenia and could be due to abnormalities of cortical interneurons using the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). To test the predictions that cognitive and brain functional responses to GABA-modulating drugs are correlated and abnormal in schizophrenia. Pharmacological functional magnetic resonance imaging study of 2 groups, each undergoing scanning 3 times, using an N-back working memory task, after placebo, lorazepam, or flumazenil administration. Eleven patients with chronic schizophrenia were recruited from a rehabilitation service, and 11 healthy volunteers matched for age, sex, and premorbid IQ were recruited from the local community. Intervention Participants received 2 mg of oral lorazepam, a 0.9-mg intravenous flumazenil bolus followed by a flumazenil infusion of 0.0102 mg/min, or oral and intravenous placebo. Working memory performance was summarized by the target discrimination index at several levels of difficulty. Increasing (or decreasing) brain functional activation in response to increasing task difficulty was summarized by the positive (or negative) load response. Lorazepam impaired performance and flumazenil enhanced it; these cognitive effects were more salient in schizophrenic patients. Functional magnetic resonance imaging demonstrated positive load response in a frontoparietal system and negative load response in the temporal and posterior cingulate regions; activation of the frontoparietal cortex was positively correlated with deactivation of the temporocingulate cortex. After placebo administration, schizophrenic patients had abnormally attenuated activation of the frontoparietal cortex and deactivation of the temporocingulate cortex; this pattern was mimicked in healthy volunteers and exacerbated in schizophrenic patients by lorazepam. However, in schizophrenic patients, flumazenil enhanced deactivation of the temporocingulate and activation of the anterior cingulate

  13. An open-label tolerability study of BL-1020 antipsychotic: a novel gamma aminobutyric acid ester of perphenazine.

    Science.gov (United States)

    Anand, Ravi; Geffen, Yona; Vasile, Daniel; Dan, Irina

    2010-01-01

    BL-1020, a novel gamma aminobutyric acid (GABA) ester of perphenazine, is a new oral antipsychotic with a strong affinity for dopamine and serotonin receptors. Unlike first- and second-generation antipsychotics, it has agonist activity at GABA(A). This is the first study to examine tolerability and safety of BL-1020 in schizophrenia. This was a phase-II, open-label, multicenter, 6-week study treating patients (n = 36) with chronic schizophrenia. Dosing started at 20 mg/d and increased over 7 days to 40 mg/d. Weekly assessments were conducted. All but 1 patient was titrated to 30 mg/d at day 4; on day 7, 30 were titrated to 40 mg/d. Four patients discontinued the study prematurely. There was no clinically relevant increase in vital signs, sedation, dizziness, or other central nervous system effects or electrocardiogram or laboratory abnormalities and a small increase in weight. Ten patients experienced extrapyramidal symptoms (EPS) requiring treatment with an anticholinergic; 4 patients were unable to reach maximum dose because of EPS. Extrapyramidal Symptom Rating Scale did not indicate clinically significant changes in EPS. The most common adverse event was insomnia (6 patients); other frequent adverse effects (all n = 3) were extrapyramidal disorder, headache, parkinsonism, tremor, and hyperprolactinemia. There was improvement on Positive and Negative Syndrome Scale and Clinical Global Impression of Change with 22 patients showing at least 20% decrease by end point on Positive and Negative Syndrome Scale and 31 patients showing at least minimal improvement on Clinical Global Impression of Change. These data suggest that 20 to 40 mg/d of BL-1020 is associated with clinically relevant improvement of psychosis with no worsening of EPS and support further testing in randomized controlled trials.

  14. Localization of (/sup 3/H). gamma. -aminobutyric acid in the cochlea. Light and electron microscopic autoradiography

    Energy Technology Data Exchange (ETDEWEB)

    Richrath, W; Kraus, H; Fromme, H G [Muenster Univ. (F.R. Germany). Hals-, Nasen- und Ohrenklinik; Muenster Univ. (F.R. Germany). Inst. fuer Medizinische Physik)

    1974-01-01

    In guinea pigs, 1 h after intraarterial and local administration of /sup 3/H-GABA, autoradiographs of the cochlea and the brain were performed. As a parameter of distribution of this substance, silver grain density was examined by means of light and electron microscopy. Intraarterial injection was not followed by any activity neither in brain nor in the cochlea, an observation suggesting the existence of a blood-perilymph barrier additional to the blood-brain barrier. Perfusion of the cochlea produced a marked activity in the spiral ganglion. Different from other tritium labelled amino acids, /sup 3/H-GABA activity could be found only in glia cells but not in nerve cell bodies or axons. The significance of this finding is open to question. In the organ of Corti a selective labelling of efferent nerve fibres could be found by means of light microscopy, additionally, using electron microscopy, only efferent synapses proved to be labelled. Most of silver grains were attached to vesicles and mitochondria, some grains to the synaptie deft. Afferent synapses remained unlabelled. Comparing with publications concerning GABA localization and concentration in the brain, we conclude that the efferent system of the Organ of Corti contains a high concentration of GABA. As present electrophysiological results are contradictory the GABA distribution alone gives no convincing evidence that this substance may serve as a transmitter.

  15. [Construction of a recombinant Escherichia coli BL21/ pET-28a-lpgad and the optimization of transformation conditions for the efficient production of gamma-aminobutyric acid].

    Science.gov (United States)

    Tian, Lingzhi; Xu, Meijuan; Rao, Zhiming

    2012-01-01

    In order to enhance gamma-aminobutyric acid production from L-glutamate efficiently, we amplified the key enzyme glutamate decarboxylase (GAD) encoding gene lpgad from the strain Lactobacillus plantarum GB 01-21 which was obtained by way of multi-mutagenesis and overexpressed it in E. coli BL21. Then we purified GAD by Ni-NTA affinity chromatography and characterized the enzyme to optimize the conditions of the whole-cell transformation. The results showed that the recombinant E. coli BL21 (pET-28a-lpgad) produced 8.53 U/mg GAD, which was increased by 3.24 fold compared with the GAD activity in L. plantarum. The optimum pH and temperature of the enzyme were pH 4.8 and 37 degrees C, respectively. At the same time, we found that Ca2+ and Mg2+ could increase the activity significantly. Based on this, we investigated gamma-aminobutyric acid transformation in 5 L fermentor under the optimum transformation conditions. Accordingly, the yield of gamma-aminobutyric acid was 204.5 g/L at 24 h when the 600 g L-glutamate was added and the mole conversion rate had reached 97.92%. The production of gamma-aminobutyric acid was improved by 42.5% compared with that under the unoptimized transformation conditions. This paved a way for the gamma-aminobutyric acid construction of the industrial applications.

  16. Effects of inhibitors of protein synthesis and intracellular transport on the gamma-aminobutyric acid agonist-induced functional differentiation of cultured cerebellar granule cells

    DEFF Research Database (Denmark)

    Belhage, B; Hansen, Gert Helge; Meier, E

    1990-01-01

    The effect of inhibitors of protein synthesis (actinomycin D, cycloheximide), proteases (leupeptin), and intracellular transport (colchicine, monensin) on the gamma-aminobutyric acid (GABA) agonist [4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol (THIP)]-induced changes in morphological...... an intracellular and a plasma membrane localization of the receptors. In all experiments cultures treated with THIP alone served as controls. The inhibitors of protein synthesis totally abolished the ability of THIP to induce low-affinity GABA receptors. In contrast, the inhibitors of intracellular transport...

  17. gamma-Aminobutyric acid production in small and large intestine of normal and germ-free Wistar rats. Influence of food intake and intestinal flora.

    Science.gov (United States)

    van Berlo, C L; de Jonge, H R; van den Bogaard, A E; van Eijk, H M; Janssen, M A; Soeters, P B

    1987-09-01

    In recent hypotheses concerning the pathogenesis of hepatic encephalopathy, gamma-aminobutyric acid (GABA) is claimed to be produced by the colonic flora, although enzymes necessary to generate GABA have been reported to be present in intestinal mucosa. In this study, using normal and germ-free Wistar rats, we determined GABA levels and amino-grams of arterial blood and of venous effluent from small and large bowel. The data indicate that large and small intestinal mucosa significantly contribute to GABA production. In the fasted state GABA concentrations are greater in the venous effluent of the small bowel than in the venous effluent of the large bowel. Feeding increases the arterioportal differences, and uptake in the small bowel is still significantly higher than in the large bowel. This process is not, or can only be to a minor degree, bacterially mediated, because GABA production in the gut both in the fed and fasted state is of similar magnitude in germ-free and normal animals. gamma-Aminobutyric acid release correlates significantly with glutamine uptake in the small bowel of fasted rats. Only a small fraction of the glutamine taken up is needed to account for GABA release, so that conclusions concerning which amino acids may serve as precursors of GABA cannot be drawn. Further studies are needed to delineate the metabolic pathways leading to GABA synthesis.

  18. 7T Proton Magnetic Resonance Spectroscopy of Gamma-Aminobutyric Acid, Glutamate, and Glutamine Reveals Altered Concentrations in Patients With Schizophrenia and Healthy Siblings

    NARCIS (Netherlands)

    Thakkar, Katharine N; Rösler, Lara; Wijnen, Jannie P; Boer, Vincent O.; Klomp, Dennis W J; Cahn, Wiepke; Kahn, René S; Neggers, Sebastiaan F W

    BACKGROUND: The N-methyl-D-aspartate receptor hypofunction model of schizophrenia predicts dysfunction in both glutamatergic and gamma-aminobutyric acidergic (GABAergic) transmission. We addressed this hypothesis by measuring GABA, glutamate, glutamine, and the sum of glutamine plus glutamate

  19. Influence of cold stress on contents of soluble sugars, vitamin C and free amino acids including gamma-aminobutyric acid (GABA) in spinach (Spinacia oleracea).

    Science.gov (United States)

    Yoon, Young-Eun; Kuppusamy, Saranya; Cho, Kye Man; Kim, Pil Joo; Kwack, Yong-Bum; Lee, Yong Bok

    2017-01-15

    The contents of soluble sugars (sucrose, fructose, glucose, maltose and raffinose), vitamin C and free amino acids (34 compounds, essential and non-essential) were quantified in open-field and greenhouse-grown spinaches in response to cold stress using liquid chromatography. In general, greenhouse cultivation produced nutritionally high value spinach in a shorter growing period, where the soluble sugars, vitamin C and total amino acids concentrations, including essential were in larger amounts compared to those grown in open-field scenarios. Further, low temperature exposure of spinach during a shorter growth period resulted in the production of spinach with high sucrose, ascorbate, proline, gamma-aminobutyric acid, valine and leucine content, and these constitute the most important energy/nutrient sources. In conclusion, cultivation of spinach in greenhouse at a low temperature (4-7°C) and exposure for a shorter period (7-21days) before harvest is recommended. This strategy will produce a high quality product that people can eat. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Establishment of an efficient fermentation system of gamma-aminobutyric acid by a lactic acid bacterium, Enterococcus avium G-15, isolated from carrot leaves.

    Science.gov (United States)

    Tamura, Takayoshi; Noda, Masafumi; Ozaki, Moeko; Maruyama, Masafumi; Matoba, Yasuyuki; Kumagai, Takanori; Sugiyama, Masanori

    2010-01-01

    In the present study, we successfully isolated a carrot leaf-derived lactic acid bacterium that produces gamma-aminobutyric acid (GABA) from monosodium L-glutamate (L-MSG) at a hyper conversion rate. The GABA-producing bacterium, identified as Enterococcus (E.) avium G-15, produced 115.7±6.4 g/l GABA at a conversion rate of 86.0±5.0% from the added L-MSG under the optimum culture condition by a continuous L-MSG feeding method using a jar-fermentor, suggesting that the bacterium displays a great potential ability for the commercial-level fermentation production of GABA. Using the reverse transcription polymerase chain reaction (RT-PCR) method, we analyzed the expression of genes for the GABA transporter and glutamate decarboxylase, designated gadT and gadG, respectively, which were cloned from the E. avium G-15 chromosome. Both genes were expressed even without the added L-MSG, but their expression was enhanced by the addition of L-MSG.

  1. Successful combination immunotherapy of anti-gamma aminobutyric acid (GABA)A receptor antibody-positive encephalitis with extensive multifocal brain lesions.

    Science.gov (United States)

    Fukami, Yuki; Okada, Hiroaki; Yoshida, Mari; Yamaguchi, Keiji

    2017-08-31

    A 78-year old woman who presented with akinetic mutism was admitted to our hospital. Brain MRI showed multifocal increased T 2 /FLAIR signal with extensive cortical-subcortical involvement. We suspected autoimmune encephalitis and the patient received methylprednisolone pulse. Her conscious level gradually recovered, but later relapsed again and presented with refractory status epilepticus. We treated her with intravenous immunoglobulin, plasma exchange and pulsed cyclophosphamide, with satisfactory response. A brain biopsy showed perivascular lymphocytic infiltrates and reactive gliosis. Anti-gamma aminobutyric acid (GABA) A receptor antibodies test came back to be positive after her recovery, and the diagnosis of anti-GABA A receptor antibody-positive encephalitis was made. This is a very rare case where brain biopsies were performed in a patient with anti-GABA A receptor antibody-positive encephalitis.

  2. Feeding rumen-protected gamma-aminobutyric acid enhances the immune response and antioxidant status of heat-stressed lactating dairy cows.

    Science.gov (United States)

    Cheng, Jianbo; Zheng, Nan; Sun, Xianzhi; Li, Songli; Wang, Jiaqi; Zhang, Yangdong

    2016-08-01

    This experiment was conducted to investigate the effects of rumen-protected gamma-aminobutyric acid (GABA) on immune function and antioxidant status in heat-stressed dairy cows. Sixty Holstein dairy cows were randomly assigned to 1 of 4 treatments according to a completely randomized block design. The treatments consisted of 0 (control), 40, 80, or 120mg of GABA/kg DM from rumen-protected GABA. The trial lasted 10 weeks. The average temperature-humidity indices at 0700, 1400 and 2200h were 78.4, 80.2 and 78.7, respectively. Rectal temperatures decreased linearly at 0700, 1400, and 2200h with increasing GABA. As the GABA increased, the immunoglobulin (Ig) A and IgG contents and the proportions of CD4(+) and CD8(+) T lymphocytes increased linearly (Pheat-stressed dairy cows can improve their immune function and antioxidant activity. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Delta Subunit-Containing Gamma-Aminobutyric Acid A Receptor Disinhibits Lateral Amygdala and Facilitates Fear Expression in Mice.

    Science.gov (United States)

    Liu, Zhi-Peng; He, Qing-Hai; Pan, Han-Qing; Xu, Xiao-Bin; Chen, Wen-Bing; He, Ye; Zhou, Jin; Zhang, Wen-Hua; Zhang, Jun-Yu; Ying, Xiao-Ping; Han, Ren-Wen; Li, Bao-Ming; Gao, Tian-Ming; Pan, Bing-Xing

    2017-06-15

    Maintaining gamma-aminobutyric acidergic (GABAergic) inhibition in the amygdala within a physiological range is critical for the appropriate expression of emotions such as fear and anxiety. The synaptic GABA type A receptor (GABA A R) is generally known to mediate the primary component of amygdala inhibition and prevent inappropriate expression of fear. However, little is known about the contribution of the extrasynaptic GABA A R to amygdala inhibition and fear. By using mice expressing green fluorescent protein in interneurons (INs) and lacking the δ subunit-containing GABA A R (GABA A (δ)R), which is exclusively situated in the extrasynaptic membrane, we systematically investigated the role of GABA A (δ)R in regulating inhibition in the lateral amygdala (LA) and fear learning using the combined approaches of immunohistochemistry, electrophysiology, and behavior. In sharp contrast to the established role of synaptic GABA A R in mediating LA inhibition, we found that either pharmacological or physiological recruitment of GABA A (δ)R resulted in the weakening of GABAergic transmission onto projection neurons in LA while leaving the glutamatergic transmission unaltered, suggesting disinhibition by GABA A (δ)R. The disinhibition arose from IN-specific expression of GABA A (δ)R with its activation decreasing the input resistance of local INs and suppressing their activation. Genetic deletion of GABA A (δ)R attenuated its role in suppressing LA INs and disinhibiting LA. Importantly, the GABA A (δ)R facilitated long-term potentiation in sensory afferents to LA and permitted the expression of learned fear. Our findings suggest that GABA A (δ)R serves as a brake rather than a mediator of GABAergic inhibition in LA. The disinhibition by GABA A (δ)R may help to prevent excessive suppression of amygdala activity and thus ensure the expression of emotion. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  4. Altered Gradients of Glutamate and Gamma-Aminobutyric Acid Transcripts in the Cortical Visuospatial Working Memory Network in Schizophrenia.

    Science.gov (United States)

    Hoftman, Gil D; Dienel, Samuel J; Bazmi, Holly H; Zhang, Yun; Chen, Kehui; Lewis, David A

    2018-04-15

    Visuospatial working memory (vsWM), which is impaired in schizophrenia, requires information transfer across multiple nodes in the cerebral cortex, including visual, posterior parietal, and dorsolateral prefrontal regions. Information is conveyed across these regions via the excitatory projections of glutamatergic pyramidal neurons located in layer 3, whose activity is modulated by local inhibitory gamma-aminobutyric acidergic (GABAergic) neurons. Key properties of these neurons differ across these cortical regions. Consequently, in schizophrenia, alterations in the expression of gene products regulating these properties could disrupt vsWM function in different ways, depending on the region(s) affected. Here, we quantified the expression of markers of glutamate and GABA neurotransmission selectively in layer 3 of four cortical regions in the vsWM network from 20 matched pairs of schizophrenia and unaffected comparison subjects. In comparison subjects, levels of glutamate transcripts tended to increase, whereas GABA transcript levels tended to decrease, from caudal to rostral, across cortical regions of the vsWM network. Composite measures across all transcripts revealed a significant effect of region, with the glutamate measure lowest in the primary visual cortex and highest in the dorsolateral prefrontal cortex, whereas the GABA measure showed the opposite pattern. In schizophrenia subjects, the expression levels of many of these transcripts were altered. However, this disease effect differed across regions, such that the caudal-to-rostral increase in the glutamate measure was blunted and the caudal-to-rostral decline in the GABA measure was enhanced in the illness. Differential alterations in layer 3 glutamate and GABA neurotransmission across cortical regions may contribute to vsWM deficits in schizophrenia. Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  5. In Silico Prediction of Gamma-Aminobutyric Acid Type-A Receptors Using Novel Machine-Learning-Based SVM and GBDT Approaches

    Directory of Open Access Journals (Sweden)

    Zhijun Liao

    2016-01-01

    Full Text Available Gamma-aminobutyric acid type-A receptors (GABAARs belong to multisubunit membrane spanning ligand-gated ion channels (LGICs which act as the principal mediators of rapid inhibitory synaptic transmission in the human brain. Therefore, the category prediction of GABAARs just from the protein amino acid sequence would be very helpful for the recognition and research of novel receptors. Based on the proteins’ physicochemical properties, amino acids composition and position, a GABAAR classifier was first constructed using a 188-dimensional (188D algorithm at 90% cd-hit identity and compared with pseudo-amino acid composition (PseAAC and ProtrWeb web-based algorithms for human GABAAR proteins. Then, four classifiers including gradient boosting decision tree (GBDT, random forest (RF, a library for support vector machine (libSVM, and k-nearest neighbor (k-NN were compared on the dataset at cd-hit 40% low identity. This work obtained the highest correctly classified rate at 96.8% and the highest specificity at 99.29%. But the values of sensitivity, accuracy, and Matthew’s correlation coefficient were a little lower than those of PseAAC and ProtrWeb; GBDT and libSVM can make a little better performance than RF and k-NN at the second dataset. In conclusion, a GABAAR classifier was successfully constructed using only the protein sequence information.

  6. A fluorescence-coupled assay for gamma aminobutyric acid (GABA reveals metabolic stress-induced modulation of GABA content in neuroendocrine cancer.

    Directory of Open Access Journals (Sweden)

    Joseph E Ippolito

    Full Text Available Pathways involved in the synthesis of the neurotransmitter gamma-aminobutyric acid (GABA have been implicated in the pathogenesis of high grade neuroendocrine (NE neoplasms as well as neoplasms from a non-NE lineage. Using The Cancer Genome Atlas, overexpression of the GABA synthetic enzyme, glutamate decarboxylase 1 (GAD1, was found to be associated with decreased disease free-survival in prostate adenocarcinoma and decreased overall survival in clear cell renal cell carcinomas. Furthermore, GAD1 was found to be expressed in castrate-resistant prostate cancer cell lines, but not androgen-responsive cell lines. Using a novel fluorescence-coupled enzymatic microplate assay for GABA mediated through reduction of resazurin in a prostate neuroendocrine carcinoma (PNEC cell line, acid microenvironment-induced stress increased GABA levels while alkaline microenvironment-induced stress decreased GABA through modulation of GAD1 and glutamine synthetase (GLUL activities. Moreover, glutamine but not glucose deprivation decreased GABA through modulation of GLUL. Consistent with evidence in prokaryotic and eukaryotic organisms that GABA synthesis mediated through GAD1 may play a crucial role in surviving stress, GABA may be an important mediator of stress survival in neoplasms. These findings identify GABA synthesis and metabolism as a potentially important pathway for regulating cancer cell stress response as well as a potential target for therapeutic strategies.

  7. A functional assay to measure postsynaptic gamma-aminobutyric acidB responses in cultured spinal cord neurons: Heterologous regulation of the same K+ channel

    Energy Technology Data Exchange (ETDEWEB)

    Kamatchi, G.L.; Ticku, M.K. (Univ. of Texas Health Science Center, San Antonio (USA))

    1991-02-01

    The stimulation of postsynaptic gamma-aminobutyric acid (GABA)B receptors leads to slow inhibitory postsynaptic potentials due to the influx of K(+)-ions. This was studied biochemically, in vitro in mammalian cultured spinal cord neurons by using 86Rb as a substitute for K+. (-)-Baclofen, a GABAB receptor agonist, produced a concentration-dependent increase in the 86Rb-influx. This effect was stereospecific and blocked by GABAB receptor antagonists like CGP 35 348 (3-aminopropyl-diethoxymethyl-phosphonic acid) and phaclofen. Apart from the GABAB receptors, both adenosine via adenosine1 receptors and 5-hydroxytryptamine (5-HT) via 5-HT1 alpha agonists also increased the 86Rb-influx. These agonists failed to show any additivity between them when they were combined in their maximal concentration. In addition, their effect was antagonized specifically by their respective antagonists without influencing the others. These findings suggest the presence of GABAB, adenosine1 and 5-HT1 alpha receptors in the cultured spinal cord neurons, which exhibit a heterologous regulation of the same K(+)-channel. The effect of these agonists were antagonized by phorbol 12,13-didecanoate, an activator of protein kinase C, and pretreatment with pertussis toxin. This suggests that these agonists by acting on their own receptors converge on the same K(+)-channel through the Gi/Go proteins. In summary, we have developed a biochemical functional assay for studying and characterizing GABAB synaptic pharmacology in vitro, using spinal cord neurons.

  8. Comparison of the density of gamma-aminobutyric acid in the ventromedial prefrontal cortex of patients with first-episode psychosis and healthy controls.

    Science.gov (United States)

    Yang, Zhilei; Zhu, Yajing; Song, Zhenhua; Mei, Li; Zhang, Jianye; Chen, Tianyi; Wang, Yingchan; Xu, Yifeng; Jiang, Kaida; Li, Yao; Liu, Dengtang

    2015-12-25

    Abnormality in the concentration and functioning of gamma-aminobutyric acid (γ-aminobutyric acid, GABA) in the brain is not only an important hypothetical link to the cause of schizophrenia but it may also be correlated with the cognitive decline and negative symptoms of schizophrenia. Studies utilizing high field magnetic resonance spectroscopy (MRS) report abnormal density of GABA in the ventromedial prefrontal cortex (vmPFC) of patients with chronic schizophrenia, but these results may be confounded by study participants' prior use of antipsychotic medications. Compare the density of GABA in the vmPFC of patients with first-episode psychosis to that in healthy controls and assess the relationship of GABA density in the vmPFC to the severity of psychotic symptoms. Single-voxel (1)H-MRS was used to assess the concentration of GABA and other metabolites in the vmPFC of 22 patients with first-episode psychosis (10 with schizophrenia and 12 with schizophreniform disorder) and 23 healthy controls. Thirteen of the 22 patients were drug-naïve and 9 had used antipsychotic medication for less than 3 days. The Positive and Negative Syndrome Scale (PANSS) was used to evaluate the severity of psychotic symptoms in the patient group. The mean (sd) GABA density in the vmPFC was significantly higher in patients than in controls (2.28 [0.54] v. 1.93 [0.32] mM, t=2.62, p=0.012). The densities of other metabolites - including N-acetylaspartic acid (NAA), glutamic acid (GLU), and glutamine (GLN) - were not significantly different between patients and controls. Among the patients, GABA density in the vmPFC was not significantly correlated with PANSS total score or with any of the three PANSS subscale scores for positive symptoms, negative symptoms, and general psychopathology. GABA concentration was not associated with the duration of illness, but it was significantly correlated with patient age (r=0.47, p=0.026). Elevation of GABA density in the vmPFC of patients with first

  9. Effects of Traumatic Stress Induced in the Juvenile Period on the Expression of Gamma-Aminobutyric Acid Receptor Type A Subunits in Adult Rat Brain

    Directory of Open Access Journals (Sweden)

    Cui Yan Lu

    2017-01-01

    Full Text Available Studies have found that early traumatic experience significantly increases the risk of posttraumatic stress disorder (PTSD. Gamma-aminobutyric acid (GABA deficits were proposed to be implicated in development of PTSD, but the alterations of GABA receptor A (GABAAR subunits induced by early traumatic stress have not been fully elucidated. Furthermore, previous studies suggested that exercise could be more effective than medications in reducing severity of anxiety and depression but the mechanism is unclear. This study used inescapable foot-shock to induce PTSD in juvenile rats and examined their emotional changes using open-field test and elevated plus maze, memory changes using Morris water maze, and the expression of GABAAR subunits (γ2, α2, and α5 in subregions of the brain in the adulthood using western blotting and immunohistochemistry. We aimed to observe the role of GABAAR subunits changes induced by juvenile trauma in the pathogenesis of subsequent PTSD in adulthood. In addition, we investigated the protective effects of exercise for 6 weeks and benzodiazepine (clonazepam for 2 weeks. This study found that juvenile traumatic stress induced chronic anxiety and spatial memory loss and reduced expression of GABAAR subunits in the adult rat brains. Furthermore, exercise led to significant improvement as compared to short-term BZ treatment.

  10. Structure-activity relationships in a new series of insecticidally active dioxatricycloalkenes derived by structural comparison of the GABA (. gamma. -aminobutyric acid) antagonists bicycloorthocarboxylates and endosulfan

    Energy Technology Data Exchange (ETDEWEB)

    Ozoe, Yoshihisa; Sawada, Yoshihiro; Mochida, Kazuo; Nakamura, Toshiie (Shimane Univ. (Japan)); Matsumura, Fumio (Univ. of California, Davis (USA))

    1990-05-01

    To study structural requirements for picrotoxinin-type GABA ({gamma}-aminobutyric acid) antagonists to interact with the receptor site, 5-substituted 4,6-dioxatricyclo(7.2.1.0{sup 2,8})dodec-10-enes and related compounds were prepared and examined for their insecticidal activity and potency in displacing ({sup 35}S)tert-butylbicyclophosphorothionate (TBPS) binding. Compounds with high insecticidal activity possessed a phenyl group with an electron-withdrawing para substituent, a cycloalkyl group, or a C{sub 3}-C{sub 5} straight-chain alkyl group at the 5-position. The effect of the 5-substituents on insecticidal activity was very similar to that of the 1-substituents of the bicyloorthocarboxylate GABA antagonists. Representative dioxatricycloalkenes displaced the binding of the GABA antagonist ({sup 35}S)TBPS to housefly head membranes by 29-53% at 10 {mu}M. X-ray crystal structure analysis demonstrated that this class of compounds had structures superimposable on those of 4-tert-butylbicycloorthocarboxylates. These findings indicate that the dioxatricycloalkenes and some other analogues occupy the picrotoxinin binding site in such a way that the fourth interacting subsite of the receptor site accommodates the 5-substituent.

  11. Time-course study and effects of drying method on concentrations of gamma-aminobutyric acid, flavonoids, anthocyanin, and 2''-hydroxynicotianamine in leaves of buckwheats.

    Science.gov (United States)

    Suzuki, Tatsuro; Watanabe, Masami; Iki, Makiko; Aoyagi, Yasuo; Kim, Sun-Ju; Mukasa, Yuji; Yokota, Satoshi; Takigawa, Shigenobu; Hashimoto, Naoto; Noda, Takahiro; Yamauchi, Hiroaki; Matsuura-Endo, Chie

    2009-01-14

    Concentrations of gamma-aminobutyric acid (GABA), rutin, minor flavonoids (such as orientin), anthocyanin, and 2''-hydroxynicotianamine (2HN) were quantified in the leaves of common and tartary buckwheat (Fagopyrum esculentum Moench and Fagopyrum tataricum Gaertn., respectively), at 14, 28, and 42 days after sowing (DAS). GABA and rutin concentrations peaked at 42 DAS, whereas anthocyain, 2HN, and minor flavonoid concentrations declined with the age of the plants. However, at 42 DAS, anthocyanin concentrations in the leaves of tartary buckwheat Hokkai T10 leaves were at least 10-fold greater than in the other buckwheats tested. In addition, the effects on target compound concentrations and 1,1-diphenyl-2-picrylhydrazyl radical scavenging activity of three different drying methods (20 h at 40 degrees C, 7 h at 70 degrees C, or lyophilization) were investigated. In general, the drying method had no significant effect on the parameters tested. These results indicate that, in terms of GABA, rutin, and anthocyanin concentrations, leaf powder from 42 day old Hokkai T10 has the potential to be a useful food ingredient, such as Ao-jiru juice.

  12. Relationship of executive functioning deficits to N-acetyl aspartate (NAA) and gamma-aminobutyric acid (GABA) in youth with bipolar disorder.

    Science.gov (United States)

    Huber, Rebekah S; Kondo, Douglas G; Shi, Xian-Feng; Prescot, Andrew P; Clark, Elaine; Renshaw, Perry F; Yurgelun-Todd, Deborah A

    2018-01-01

    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. Thirty participants, twenty depressed BD participants and ten healthy comparison participants, ages 13-21, completed mood and executive function measures. 1 H-MRS data were also acquired from the anterior cingulate cortex (ACC) using two-dimensional (2D) J-resolved 1 H-MRS sequence. Proton metabolites including N-acetyl aspartate (NAA) and gamma-aminobutyric acid (GABA) were quantified for both groups. Participants with BD performed significantly lower on executive functioning measures than comparison participants. There were significant positive correlations between Wisconsin Card Sorting Test (WCST) performance and NAA (p NAA and GABA levels increased. Small sample size and lack of control for medications. These findings build on previous observations of biochemical alterations associated with BD and indicate that executive functioning deficits in bipolar youth are correlated with NAA and GABA. These results suggest that cognitive deficits occur early in the course of illness and may reflect risk factors associated with altered neurochemistry. Further investigation of the relationship between brain metabolites and cognition in BD may lead to important information for developing novel, targeted interventions. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Alternate cadmium exposure differentially affects the content of gamma-aminobutyric acid (GABA) and taurine within the hypothalamus, median eminence, striatum and prefrontal cortex of male rats

    Energy Technology Data Exchange (ETDEWEB)

    Esquifino, A.I. [Dept. de Bioquimica y Biologia Molecular III, Universidad Complutense, Madrid (Spain); Seara, R.; Fernandez-Rey, E.; Lafuente, A. [Lab. de Toxicologia, Universidad de Vigo, Orense (Spain)

    2001-05-01

    This work examines changes of gamma aminobutyric acid (GABA) and taurine contents in the hypothalamus, striatum and prefrontal cortex of the rat after an alternate schedule of cadmium administration. Age-associated changes were also evaluated, of those before puberty and after adult age. In control rats GABA content decreased with age in the median eminence and in anterior, mediobasal and posterior hypothalamus, prefrontal cortex and the striatum. Taurine content showed similar results with the exception of mediobasal hypothalamus and striatum, where no changes were detected. In pubertal rats treated with cadmium from 30 to 60 days of life, GABA content significantly decreased in all brain regions except in the striatum. When cadmium was administered from day 60 to 90 of life, GABA content was significantly changed in prefrontal cortex only compared with the age matched controls. Taurine content showed similar results in pubertal rats, with the exception of the median eminence and the mediobasal hypothalamus, neither of which showed a change. However, when cadmium was administered to rats from day 60 to 90 of life, taurine content only changed in prefrontal cortex compared with the age matched controls. These results suggest that cadmium differentially affects GABA and taurine contents within the hypothalamus, median eminence, striatum and prefrontal cortex as a function of age. (orig.)

  14. Glutamate decarboxylase and. gamma. -aminobutyric acid transaminase activity in brain structures during action of high concentrated sulfide gas on a background of hypo- and hypercalcemia

    Energy Technology Data Exchange (ETDEWEB)

    Kadyrov, G.K.; Aliyev, A.M.

    Activity of the following enzymes was studied on the background of hypo- and hypercalcemia and exposure to high concentration of sulfide gas: glutamate decarboxylase (GDC) and {gamma}-aminobutyric acid transaminase (GABA-T). These enzymes regulate metabolism of GABA. The results showed that a 3.5 hr exposure to sulfide gas at a concentration of 0.3 mg/1 led to significantly increased activity of GDC in cerebral hemispheres, cerebellum and in brain stem. Activity of GABA-T dropped correspondingly. On the background of hypercalcemia induced by im. injection of 10% calcium gluconate (0.6 m1/200 g body weight of experimental rats) the negative effect caused by the exposure to sulfide gas was diminished. Under conditions of hypocalcemia (im. injection of 10 mg/200 g body weight of sodium oxalate), exposure to sulfide gas led to a significantly decreased activity of GDC and GABA-T in the hemispheres and in the brain stem, but in the cerebellum the activity of GDC increased sharply while that of GABA-T decreased correspondingly. 8 refs.

  15. Effect of “Jian-Pi-Zhi-Dong Decoction” on Gamma-Aminobutyric Acid in a Mouse Model of Tourette Syndrome

    Directory of Open Access Journals (Sweden)

    Wen Zhang

    2014-01-01

    Full Text Available The purpose of this study was to explore the positive effects of Jian-Pi-Zhi-Dong Decoction (JPZDD on Tourette syndrome (TS by investigating the expression of gamma-aminobutyric acid (GABA and its type A receptor (GABAAR in the striatum of a TS mice model. The model was induced by 3,3′-iminodipropionitrile (IDPN treatment; then mice were divided into 4 groups (n=22, each; control and IDPN groups were gavaged with saline and the remaining 2 groups were gavaged with tiapride and JPZDD. We recorded the stereotypic behaviors of TS mice and measured the content of GABA in striatum by HPLC and GABAAR expression by immunohistochemistry and real-time PCR. Our results showed that JPZDD inhibited the abnormal behaviors of TS model mice and decreased GABA levels and GABAAR protein and mRNA expression in the striatum of TS model mice. In brief, the mechanism by which JPZDD alleviates TS symptoms may be associated with GABAAR expression downregulation in striatum which may regulate GABA metabolism.

  16. Failure of gamma-aminobutyrate acid-beta agonist baclofen to improve balance, gait, and postural control after vestibular schwannoma resection.

    Science.gov (United States)

    De Valck, Claudia F J; Vereeck, Luc; Wuyts, Floris L; Van de Heyning, Paul H

    2009-04-01

    Incomplete postural control often occurs after vestibular schwannoma (VS) surgery. Customized vestibular rehabilitation in man improves and speeds up this process. Animal experiments have shown an improved and faster vestibular compensation after administration of the gamma-aminobutyrate acid (GABA)-beta agonist baclofen. To examine whether medical treatment with baclofen provides an improvement of the compensation process after VS surgery. A time-series study with historical control. Tertiary referral center. Thirteen patients who underwent VS resection were included and compared with a matched group of patients. In addition to an individualized vestibular rehabilitation protocol, the study group received medical treatment with 30 mg baclofen (a GABA-beta agonist) daily during the first 6 weeks after surgery. Clinical gait and balance tests (Romberg maneuver, standing on foam, tandem Romberg, single-leg stance, Timed Up & Go test, tandem gait, Dynamic Gait Index) and Dizziness Handicap Inventory. Follow-up until 24 weeks after surgery. When examining the postoperative test results, the group treated with baclofen did not perform better when compared with the matched (historical control) group. Repeated-measures analysis of variance revealed no significant group effect, but a significant time effect for almost all balance tests during the acute recovery period was found. An interaction effect between time and intervention was seen concerning single-leg stance and Dizziness Handicap Inventory scores for the acute recovery period. Medical therapy with baclofen did not seem to be beneficial in the process of central vestibular compensation.

  17. Alternate cadmium exposure differentially affects the content of gamma-aminobutyric acid (GABA) and taurine within the hypothalamus, median eminence, striatum and prefrontal cortex of male rats

    International Nuclear Information System (INIS)

    Esquifino, A.I.; Seara, R.; Fernandez-Rey, E.; Lafuente, A.

    2001-01-01

    This work examines changes of gamma aminobutyric acid (GABA) and taurine contents in the hypothalamus, striatum and prefrontal cortex of the rat after an alternate schedule of cadmium administration. Age-associated changes were also evaluated, of those before puberty and after adult age. In control rats GABA content decreased with age in the median eminence and in anterior, mediobasal and posterior hypothalamus, prefrontal cortex and the striatum. Taurine content showed similar results with the exception of mediobasal hypothalamus and striatum, where no changes were detected. In pubertal rats treated with cadmium from 30 to 60 days of life, GABA content significantly decreased in all brain regions except in the striatum. When cadmium was administered from day 60 to 90 of life, GABA content was significantly changed in prefrontal cortex only compared with the age matched controls. Taurine content showed similar results in pubertal rats, with the exception of the median eminence and the mediobasal hypothalamus, neither of which showed a change. However, when cadmium was administered to rats from day 60 to 90 of life, taurine content only changed in prefrontal cortex compared with the age matched controls. These results suggest that cadmium differentially affects GABA and taurine contents within the hypothalamus, median eminence, striatum and prefrontal cortex as a function of age. (orig.)

  18. Effects of electroacupuncture on the levels of retinal gamma-aminobutyric acid and its receptors in a guinea pig model of lens-induced myopia.

    Science.gov (United States)

    Sha, F; Ye, X; Zhao, W; Xu, C-L; Wang, L; Ding, M-H; Bi, A-L; Wu, J-F; Jiang, W-J; Guo, D-D; Guo, J-G; Bi, H-S

    2015-02-26

    Gamma-aminobutyric acid (GABA) is a major inhibitory neurotransmitter of the retina and affects myopic development. Electroacupuncture (EA) is widely utilized to treat myopia in clinical settings. However, there are few reports on whether EA affects the level of retinal GABA during myopic development. To study this issue, in the present study, we explored the changes of retinal GABA content and the expression of its receptor subtypes, and the effects of EA stimulation on them in a guinea pig model with lens-induced myopia (LIM). Our results showed that the content of GABA and the expression of GABAA and GABAC receptors of retina were up-regulated during the development of myopia, and this up-regulation was inhibited by applying EA to Hegu (LI4) and Taiyang (EX-HN5) acupoints. Moreover, these effects of EA show a positional specificity. While applying EA at a sham acupoint, no apparent change of myopic retinal GABA and its receptor subtypes was observed. Taken together, our findings suggest that LIM is effective to up-regulate the level of retinal GABA, GABAA and GABAC receptors in guinea pigs and the effect may be inhibited by EA stimulation at LI4 and EX-HN5 acupoints. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

  19. Hypergravity exposure decreases gamma-aminobutyric acid immunoreactivity in axon terminals contacting pyramidal cells in the rat somatosensory cortex: a quantitative immunocytochemical image analysis

    Science.gov (United States)

    D'Amelio, F.; Wu, L. C.; Fox, R. A.; Daunton, N. G.; Corcoran, M. L.; Polyakov, I.

    1998-01-01

    Quantitative evaluation of gamma-aminobutyric acid immunoreactivity (GABA-IR) in the hindlimb representation of the rat somatosensory cortex after 14 days of exposure to hypergravity (hyper-G) was conducted by using computer-assisted image processing. The area of GABA-IR axosomatic terminals apposed to pyramidal cells of cortical layer V was reduced in rats exposed to hyper-G compared with control rats, which were exposed either to rotation alone or to vivarium conditions. Based on previous immunocytochemical and behavioral studies, we suggest that this reduction is due to changes in sensory feedback information from muscle receptors. Consequently, priorities for muscle recruitment are altered at the cortical level, and a new pattern of muscle activity is thus generated. It is proposed that the reduction observed in GABA-IR of the terminal area around pyramidal neurons is the immunocytochemical expression of changes in the activity of GABAergic cells that participate in reprogramming motor outputs to achieve effective movement control in response to alterations in the afferent information.

  20. Brain Targeted Intranasal Zaleplon Nano-emulsion: In-Vitro Characterization and Assessment of Gamma Aminobutyric Acid Levels in rabbits' Brain and Plasma at low and high Doses.

    Science.gov (United States)

    Abd-Elrasheed, Eman; El-Helaly, Sara Nageeb; El-Ashmoony, Manal M; Salah, Salwa

    2017-11-30

    Zaleplon is a pyrazolopyrimidin derivative hypnotic drug indicated for the short-term management of insomnia. Zaleplon belongs to Class II drugs, according to the biopharmaceutical classification system (BCS), showing poor solubility and high permeability. It undergoes extensive first-pass hepatic metabolism after oral absorption, with only 30% of Zaleplon being systemically available. It is available in tablet form which is unable to overcome the previous problems. The aim of this study is to enhance solubility and bioavailability via utilizing nanotechnology in the formulation of intranasal Zaleplon nano-emulsion (ZP-NE) to bypass the barriers and deliver an effective therapy to the brain. Screening studies were carried out wherein the solubility of zaleplon in various oils, surfactants(S) and co-surfactants(CoS) were estimated. Pseudo-ternary phase diagrams were constructed and various nano-emulsion formulations were prepared. These formulations were subjected to thermodynamic stability, in-vitro characterization, histopathological studies and assessment of the gamma aminobutyric acid (GABA) level in plasma and brain in rabbits compared to the market product (Sleep aid®). Stable NEs were successfully developed with a particle size range of 44.57±3.351 to 136.90±1.62 nm. A NE composed of 10% Miglyol® 812, 40%Cremophor® RH40 40%Transcutol® HP and 10% water successfully enhanced the bioavailability and brain targeting in the rabbits, showing a three to four folds increase than the marketed product. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  1. Effects of yoga on the autonomic nervous system, gamma-aminobutyric-acid, and allostasis in epilepsy, depression, and post-traumatic stress disorder.

    Science.gov (United States)

    Streeter, C C; Gerbarg, P L; Saper, R B; Ciraulo, D A; Brown, R P

    2012-05-01

    A theory is proposed to explain the benefits of yoga practices in diverse, frequently comorbid medical conditions based on the concept that yoga practices reduce allostatic load in stress response systems such that optimal homeostasis is restored. It is hypothesized that stress induces (1) imbalance of the autonomic nervous system (ANS) with decreased parasympathetic nervous system (PNS) and increased sympathetic nervous system (SNS) activity, (2) underactivity of the gamma amino-butyric acid (GABA) system, the primary inhibitory neurotransmitter system, and (3) increased allostatic load. It is further hypothesized that yoga-based practices (4) correct underactivity of the PNS and GABA systems in part through stimulation of the vagus nerves, the main peripheral pathway of the PNS, and (5) reduce allostatic load. Depression, epilepsy, post traumatic stress disorder (PTSD), and chronic pain exemplify medical conditions that are exacerbated by stress, have low heart rate variability (HRV) and low GABAergic activity, respond to pharmacologic agents that increase activity of the GABA system, and show symptom improvement in response to yoga-based interventions. The observation that treatment resistant cases of epilepsy and depression respond to vagal nerve stimulation corroborates the need to correct PNS underactivity as part of a successful treatment plan in some cases. According to the proposed theory, the decreased PNS and GABAergic activity that underlies stress-related disorders can be corrected by yoga practices resulting in amelioration of disease symptoms. This has far-reaching implications for the integration of yoga-based practices in the treatment of a broad array of disorders exacerbated by stress. Copyright © 2012 Elsevier Ltd. All rights reserved.

  2. Enhanced Production of Gamma-Aminobutyric Acid by Optimizing Culture Conditions of Lactobacillus brevis HYE1 Isolated from Kimchi, a Korean Fermented Food.

    Science.gov (United States)

    Lim, Hee Seon; Cha, In-Tae; Roh, Seong Woon; Shin, Hae-Hun; Seo, Myung-Ji

    2017-03-28

    This study evaluated the effects of culture conditions, including carbon and nitrogen sources, L-monosodium glutamate (MSG), and initial pH, on gamma-aminobutyric acid (GABA) production by Lactobacillus brevis HYE1 isolated from kimchi, a Korean traditional fermented food. L. brevis HYE1 was screened by the production analysis of GABA and genetic analysis of the glutamate decarboxylase gene, resulting in 14.64 mM GABA after 48 h of cultivation in MRS medium containing 1% (w/v) MSG. In order to increase GABA production by L. brevis HYE1, the effects of carbon and nitrogen sources on GABA production were preliminarily investigated via one-factor-at-a-time optimization strategy. As the results, 2% maltose and 3% tryptone were determined to produce 17.93 mM GABA in modified MRS medium with 1% (w/v) MSG. In addition, the optimal MSG concentration and initial pH were determined to be 1% and 5.0, respectively, resulting in production of 18.97 mM GABA. Thereafter, response surface methodology (RSM) was applied to determine the optimal conditions of the above four factors. The results indicate that pH was the most significant factor for GABA production. The optimal culture conditions for maximum GABA production were also determined to be 2.14% (w/v) maltose, 4.01% (w/v) tryptone, 2.38% (w/v) MSG, and an initial pH of 4.74. In these conditions, GABA production by L. brevis HYE1 was predicted to be 21.44 mM using the RSM model. The experiment was performed under these optimized conditions, resulting in GABA production of 18.76 mM. These results show that the predicted and experimental values of GABA production are in good agreement.

  3. Nicotine stimulates pancreatic cancer xenografts by systemic increase in stress neurotransmitters and suppression of the inhibitory neurotransmitter gamma-aminobutyric acid.

    Science.gov (United States)

    Al-Wadei, Hussein A N; Plummer, Howard K; Schuller, Hildegard M

    2009-03-01

    Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer mortality in Western countries. We have shown previously that four representative human PDAC cell lines were regulated by beta-adrenoreceptors via cyclic adenosine 3',5'-monophosphate (cAMP)-dependent signaling. In the current study, we have tested the hypothesis that nicotine stimulates the growth of PDAC xenografts in nude mice by increasing the systemic levels of the stress neurotransmitters adrenaline and noradrenaline, which are the physiological agonists for beta-adrenoreceptors and that inhibition by gamma-aminobutyric acid (GABA) of the adenylyl cyclase-dependent pathway downstream of adrenoreceptors blocks this effect. The size of xenografts from PDAC cell line Panc-1 was determined 30 days after inoculation of the cancer cells. Stress neurotransmitters in serum as well as cAMP in the cellular fraction of blood and in tumor tissue were assessed by immunoassays. Levels of GABA, its synthesizing enzymes GAD65 and GAD67 and beta-adrenergic signaling proteins in the tumor tissue were determined by western blotting. Nicotine significantly increased the systemic levels of adrenaline, noradrenaline and cAMP while increasing xenograft size and protein levels of cAMP, cyclic AMP response element-binding protein and p-extracellular signal-regulated kinase 1/2 in the tumor tissue. Nicotine additionally reduced the protein levels of both GAD isozymes and GABA in tumor tissue. Treatment with GABA abolished these responses to nicotine and blocked the development of xenografts in mice not exposed to nicotine. These findings suggest that the development and progression of PDAC is subject to significant modulation by stimulatory stress neurotransmitters and inhibitory GABA and that treatment with GABA may be useful for marker-guided cancer intervention of PDAC.

  4. Modulation of the release of norepinephrine by gamma-aminobutyric acid and morphine in the frontal cerebral cortex of the rat

    International Nuclear Information System (INIS)

    Peoples, R.W.

    1989-01-01

    Agents that enhance gamma-aminobutyric acid, or GABA, neurotransmission modulate certain effects of opioids, such as analgesia. Opioid analgesia is mediated in part by norepinephrine in the forebrain. In this study, the interactions between morphine and GABAergic agents on release of [ 3 H] norepinephrine from rat frontal cerebral cortical slices were examined. GABA, 5 x 10 -5 -10 -3 M, enhanced potassium stimulated [ 3 H] norepinephrine release and reversed the inhibitory effect of morphine in a noncompetitive manner. GABA did not enhance release of [ 3 H] norepinephrine stimulated by the calcium ionophore A23187. The effect of GABA was reduced by the GABA A receptor antagonists bicuculline methiodide or picrotoxin, and by the selective inhibitor of GABA uptake SKF 89976A, but was blocked completely only when bicuculline methiodide and SKF 89976A were used in combination. The GABA A agonist muscimol, 10 -4 M, mimicked the effect of GABA, but the GABA B agonist (±)baclofen, 10 -4 M, did not affect the release of [ 3 H] norepinephrine in the absence or the presence of morphine. Thus GABA appears to produce this effect by stimulating GABA uptake and GABA A , but not GABA B , receptors. In contrast to the results that would be predicted for an event involving GABA A receptors, however, the effect of GABA did not desensitize, and benzodiazepine agonists did not enhance the effect of GABA at any concentration tested between 10 -8 and 10 -4 M. Thus these receptors may constitute a subclass of GABA A receptors. These results support a role of GABA uptake and GABA A receptors in enhancing the release of norepinephrine and modulating its inhibition by opioids in the frontal cortex of the rat

  5. Prefrontal and Striatal Gamma-Aminobutyric Acid Levels and the Effect of Antipsychotic Treatment in First-Episode Psychosis Patients.

    Science.gov (United States)

    de la Fuente-Sandoval, Camilo; Reyes-Madrigal, Francisco; Mao, Xiangling; León-Ortiz, Pablo; Rodríguez-Mayoral, Oscar; Jung-Cook, Helgi; Solís-Vivanco, Rodolfo; Graff-Guerrero, Ariel; Shungu, Dikoma C

    2018-03-15

    Abnormally elevated levels of gamma-aminobutyric acid (GABA) in the medial prefrontal cortex (mPFC) have been reported in antipsychotic-free patients with schizophrenia. Whether such GABA elevations are also present in other brain regions and persist after antipsychotic treatment has not been previously investigated. Twenty-eight antipsychotic-naïve patients with first-episode psychosis (FEP) and 18 healthy control subjects completed the study. Following baseline proton magnetic resonance spectroscopy scans targeting the mPFC and a second region, the dorsal caudate, patients with FEP were treated with oral risperidone for 4 weeks at an initial dose of 1 mg/day that was titrated as necessary based on clinical judgment. After the 4-week treatment period, both groups were brought back to undergo outcome magnetic resonance spectroscopy scans, which were identical to the scans conducted at baseline. At baseline, higher GABA levels were found both in the mPFC and in the dorsal caudate of patients with FEP compared with healthy control subjects. Following 4 weeks of antipsychotic treatment, GABA levels in patients with FEP decreased relative to baseline in the mPFC, but decreased only at the trend level relative to baseline in the dorsal caudate. For either brain region, GABA levels at 4 weeks or posttreatment did not differ between patients with FEP and healthy control subjects. The results of the present study documented elevations of GABA levels both in the mPFC and, for the first time, in the dorsal caudate of antipsychotic-naïve patients with FEP, which normalized in both regions following 4 weeks of antipsychotic treatment. Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  6. The role of gamma-aminobutyric acid/glycinergic synaptic transmission in mediating bilirubin-induced hyperexcitation in developing auditory neurons.

    Science.gov (United States)

    Yin, Xin-Lu; Liang, Min; Shi, Hai-Bo; Wang, Lu-Yang; Li, Chun-Yan; Yin, Shan-Kai

    2016-01-05

    Hyperbilirubinemia is a common clinical phenomenon observed in human newborns. A high level of bilirubin can result in severe jaundice and bilirubin encephalopathy. However, the cellular mechanisms underlying bilirubin excitotoxicity are unclear. Our previous studies showed the action of gamma-aminobutyric acid (GABA)/glycine switches from excitatory to inhibitory during development in the ventral cochlear nucleus (VCN), one of the most sensitive auditory nuclei to bilirubin toxicity. In the present study, we investigated the roles of GABAA/glycine receptors in the induction of bilirubin hyperexcitation in early developing neurons. Using the patch clamp technique, GABAA/glycine receptor-mediated spontaneous inhibitory synaptic currents (sIPSCs) were recorded from bushy and stellate cells in acute brainstem slices from young mice (postnatal day 2-6). Bilirubin significantly increased the frequency of sIPSCs, and this effect was prevented by pretreatments of slices with either fast or slow Ca(2+) chelators BAPTA-AM and EGTA-AM suggesting that bilirubin can increase the release of GABA/glycine via Ca(2+)-dependent mechanisms. Using cell-attached recording configuration, we found that antagonists of GABAA and glycine receptors strongly attenuated spontaneous spiking firings in P2-6 neurons but produced opposite effect in P15-19 neurons. Furthermore, these antagonists reversed bilirubin-evoked hyperexcitability in P2-6 neurons, indicating that excitatory action of GABA/glycinergic transmission specifically contribute to bilirubin-induced hyperexcitability in the early stage of development. Our results suggest that bilirubin-induced enhancement of presynaptic release GABA/Glycine via Ca(2+)-dependent mechanisms may play a critical role in mediating neuronal hyperexcitation associated with jaundice, implicating potential new strategies for predicting, preventing, and treating bilirubin neurotoxicity. Copyright © 2015. Published by Elsevier Ireland Ltd.

  7. Increased Cortical Gamma-Aminobutyric Acid Precedes Incomplete Extinction of Conditioned Fear and Increased Hippocampal Excitatory Tone in a Mouse Model of Mild Traumatic Brain Injury.

    Science.gov (United States)

    Schneider, Brandy L; Ghoddoussi, Farhad; Charlton, Jennifer L; Kohler, Robert J; Galloway, Matthew P; Perrine, Shane A; Conti, Alana C

    2016-09-01

    Mild traumatic brain injury (mTBI) contributes to development of affective disorders, including post-traumatic stress disorder (PTSD). Psychiatric symptoms typically emerge in a tardive fashion post-TBI, with negative effects on recovery. Patients with PTSD, as well as rodent models of PTSD, demonstrate structural and functional changes in brain regions mediating fear learning, including prefrontal cortex (PFC), amygdala (AMYG), and hippocampus (HC). These changes may reflect loss of top-down control by which PFC normally exhibits inhibitory influence over AMYG reactivity to fearful stimuli, with HC contribution. Considering the susceptibility of these regions to injury, we examined fear conditioning (FC) in the delayed post-injury period, using a mouse model of mTBI. Mice with mTBI displayed enhanced acquisition and delayed extinction of FC. Using proton magnetic resonance spectroscopy ex vivo, we examined PFC, AMYG, and HC levels of gamma-aminobutyric acid (GABA) and glutamate as surrogate measures of inhibitory and excitatory neurotransmission, respectively. Eight days post-injury, GABA was increased in PFC, with no significant changes in AMYG. In animals receiving FC and mTBI, glutamate trended toward an increase and the GABA/glutamate ratio decreased in ventral HC at 25 days post-injury, whereas GABA decreased and GABA/glutamate decreased in dorsal HC. These neurochemical changes are consistent with early TBI-induced PFC hypoactivation facilitating the fear learning circuit and exacerbating behavioral fear responses. The latent emergence of overall increased excitatory tone in the HC, despite distinct plasticity in dorsal and ventral HC fields, may be associated with disordered memory function, manifested as incomplete extinction and enhanced FC recall.

  8. Modulation of the release of norepinephrine by gamma-aminobutyric acid and morphine in the frontal cerebral cortex of the rat

    Energy Technology Data Exchange (ETDEWEB)

    Peoples, R.W.

    1989-01-01

    Agents that enhance gamma-aminobutyric acid, or GABA, neurotransmission modulate certain effects of opioids, such as analgesia. Opioid analgesia is mediated in part by norepinephrine in the forebrain. In this study, the interactions between morphine and GABAergic agents on release of ({sup 3}H) norepinephrine from rat frontal cerebral cortical slices were examined. GABA, 5 {times} 10{sup {minus}5}-10{sup {minus}3} M, enhanced potassium stimulated ({sup 3}H) norepinephrine release and reversed the inhibitory effect of morphine in a noncompetitive manner. GABA did not enhance release of ({sup 3}H) norepinephrine stimulated by the calcium ionophore A23187. The effect of GABA was reduced by the GABA{sub A} receptor antagonists bicuculline methiodide or picrotoxin, and by the selective inhibitor of GABA uptake SKF 89976A, but was blocked completely only when bicuculline methiodide and SKF 89976A were used in combination. The GABA{sub A} agonist muscimol, 10{sup {minus}4} M, mimicked the effect of GABA, but the GABA{sub B} agonist ({plus minus})baclofen, 10{sup {minus}4} M, did not affect the release of ({sup 3}H) norepinephrine in the absence or the presence of morphine. Thus GABA appears to produce this effect by stimulating GABA uptake and GABA{sub A}, but not GABA{sub B}, receptors. In contrast to the results that would be predicted for an event involving GABA{sub A} receptors, however, the effect of GABA did not desensitize, and benzodiazepine agonists did not enhance the effect of GABA at any concentration tested between 10{sup {minus}8} and 10{sup {minus}4} M. Thus these receptors may constitute a subclass of GABA{sub A} receptors. These results support a role of GABA uptake and GABA{sub A} receptors in enhancing the release of norepinephrine and modulating its inhibition by opioids in the frontal cortex of the rat.

  9. In vivo gamma-aminobutyric acid and glutamate levels in people with first-episode schizophrenia: A proton magnetic resonance spectroscopy study.

    Science.gov (United States)

    Chiu, P W; Lui, Simon S Y; Hung, Karen S Y; Chan, Raymond C K; Chan, Queenie; Sham, P C; Cheung, Eric F C; Mak, Henry K F

    2018-03-01

    Gamma-aminobutyric acid (GABA) dysfunction and its consequent imbalance are implicated in the pathophysiology of schizophrenia. Reduced GABA production would lead to a disinhibition of glutamatergic neurons and subsequently cause a disruption of the modulation between GABAergic interneurons and glutamatergic neurons. In this study, levels of GABA, Glx (summation of glutamate and glutamine), and other metabolites in the anterior cingulate cortex were measured and compared between first-episode schizophrenia subjects and healthy controls (HC). Diagnostic potential of GABA and Glx as upstream biomarkers for schizophrenia was explored. Nineteen first-episode schizophrenia subjects and fourteen HC participated in this study. Severity of clinical symptoms of patients was measured with Positive and Negative Syndrome Scale (PANSS). Metabolites were measured using proton magnetic resonance spectroscopy, and quantified using internal water as reference. First-episode schizophrenia subjects revealed reduced GABA and myo-inositol (mI), and increased Glx and choline (Cho), compared to HC. No significant correlation was found between metabolite levels and PANSS scores. Receiver operator characteristics analyses showed Glx had higher sensitivity and specificity (84.2%, 92.9%) compared to GABA (73.7%, 64.3%) for differentiating schizophrenia patients from HC. Combined model of both GABA and Glx revealed the best sensitivity and specificity (89.5%, 100%). This study simultaneously showed reduction in GABA and elevation in Glx in first-episode schizophrenia subjects, and this might provide insights on explaining the disruption of modulation between GABAergic interneurons and glutamatergic neurons. Elevated Cho might indicate increased membrane turnover; whereas reduced mI might reflect dysfunction of the signal transduction pathway. In vivo Glx and GABA revealed their diagnostic potential for schizophrenia. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. In SilicoModel-driven Assessment of the Effects of Brain-derived Neurotrophic Factor Deficiency on Glutamate and Gamma-Aminobutyric Acid: Implications for Understanding Schizophrenia Pathophysiology.

    Science.gov (United States)

    Agrawal, Rimjhim; Kalmady, Sunil Vasu; Venkatasubramanian, Ganesan

    2017-05-31

    Deficient brain-derived neurotrophic factor (BDNF) is one of the important mechanisms underlying the neuroplasticity abnormalities in schizophrenia. Aberration in BDNF signaling pathways directly or circuitously influences neurotransmitters like glutamate and gamma-aminobutyric acid (GABA). For the first time, this study attempts to construct and simulate the BDNF-neurotransmitter network in order to assess the effects of BDNF deficiency on glutamate and GABA. Using CellDesigner, we modeled BDNF interactions with calcium influx via N-methyl-D-aspartate receptor (NMDAR)- Calmodulin activation; synthesis of GABA via cell cycle regulators protein kinase B, glycogen synthase kinase and β-catenin; transportation of glutamate and GABA. Steady state stability, perturbation time-course simulation and sensitivity analysis were performed in COPASI after assigning the kinetic functions, optimizing the unknown parameters using random search and genetic algorithm. Study observations suggest that increased glutamate in hippocampus, similar to that seen in schizophrenia, could potentially be contributed by indirect pathway originated from BDNF. Deficient BDNF could suppress Glutamate decarboxylase 67-mediated GABA synthesis. Further, deficient BDNF corresponded to impaired transport via vesicular glutamate transporter, thereby further increasing the intracellular glutamate in GABAergic and glutamatergic cells. BDNF also altered calcium dependent neuroplasticity via NMDAR modulation. Sensitivity analysis showed that Calmodulin, cAMP response element-binding protein (CREB) and CREB regulated transcription coactivator-1 played significant role in this network. The study presents in silico quantitative model of biochemical network constituting the key signaling molecules implicated in schizophrenia pathogenesis. It provides mechanistic insights into putative contribution of deficient BNDF towards alterations in neurotransmitters and neuroplasticity that are consistent with current

  11. Dual orexin receptor antagonists show distinct effects on locomotor performance, ethanol interaction and sleep architecture relative to gamma-aminobutyric acid-A receptor modulators

    Directory of Open Access Journals (Sweden)

    Andres D. Ramirez

    2013-12-01

    Full Text Available Dual orexin receptor antagonists (DORAs are a potential treatment for insomnia that function by blocking both the orexin 1 and orexin 2 receptors. The objective of the current study was to further confirm the impact of therapeutic mechanisms targeting insomnia on locomotor coordination and ethanol interaction using DORAs and gamma-aminobutyric acid (GABA-A receptor modulators of distinct chemical structure and pharmacologic properties in the context of sleep-promoting potential. The current study compared rat motor co-ordination after administration of DORAs, DORA-12 and almorexant, and GABA-A receptor modulators, zolpidem, eszopiclone and diazepam, alone or each in combination with ethanol. Motor performance was assessed by measuring time spent walking on a rotarod apparatus. Zolpidem, eszopiclone and diazepam (0.3–30 mg/kg administered orally [PO] impaired rotarod performance in a dose-dependent manner. Furthermore, all three GABA-A receptor modulators potentiated ethanol- (0.25–1.25 g/kg induced impairment on the rotarod. By contrast, neither DORA-12 (10–100 mg/kg, PO nor almorexant (30–300 mg/kg, PO impaired motor performance alone or in combination with ethanol. In addition, distinct differences in sleep architecture were observed between ethanol, GABA-A receptor modulators (zolpidem, eszopiclone and diazepam and DORA-12 in electroencephalogram studies in rats. These findings provide further evidence that orexin receptor antagonists have an improved motor side-effect profile compared with currently available sleep-promoting agents based on preclinical data and strengthen the rationale for further evaluation of these agents in clinical development.

  12. Substrate-Na{sup +} complex formation: Coupling mechanism for {gamma}-aminobutyrate symporters

    Energy Technology Data Exchange (ETDEWEB)

    Pallo, Anna; Simon, Agnes [Department of Neurochemistry, Institute of Biomolecular Chemistry, Chemical Research Center, Hungarian Academy of Sciences (Hungary); Bencsura, Akos [Department of Theoretical Chemistry, Institute of Structural Chemistry, Chemical Research Center, Hungarian Academy of Sciences, Budapest (Hungary); Heja, Laszlo [Department of Neurochemistry, Institute of Biomolecular Chemistry, Chemical Research Center, Hungarian Academy of Sciences (Hungary); Kardos, Julianna, E-mail: jkardos@chemres.hu [Department of Neurochemistry, Institute of Biomolecular Chemistry, Chemical Research Center, Hungarian Academy of Sciences (Hungary)

    2009-07-24

    Crystal structures of transmembrane transport proteins belonging to the important families of neurotransmitter-sodium symporters reveal how they transport neurotransmitters across membranes. Substrate-induced structural conformations of gated neurotransmitter-sodium symporters have been in the focus of research, however, a key question concerning the mechanism of Na{sup +} ion coupling remained unanswered. Homology models of human glial transporter subtypes of the major inhibitory neurotransmitter {gamma}-aminobutyric acid were built. In accordance with selectivity data for subtype 2 vs. 3, docking and molecular dynamics calculations suggest similar orthosteric substrate (inhibitor) conformations and binding crevices but distinguishable allosteric Zn{sup 2+} ion binding motifs. Considering the occluded conformational states of glial human {gamma}-aminobutyric acid transporter subtypes, we found major semi-extended and minor ring-like conformations of zwitterionic {gamma}-aminobutyric acid in complex with Na{sup +} ion. The existence of the minor ring-like conformation of {gamma}-aminobutyric acid in complex with Na{sup +} ion may be attributed to the strengthening of the intramolecular H-bond by the electrostatic effect of Na{sup +} ion. Coupling substrate uptake into cells with the thermodynamically favorable Na{sup +} ion movement through substrate-Na{sup +} ion complex formation may be a mechanistic principle featuring transmembrane neurotransmitter-sodium symporter proteins.

  13. Brain Gamma-Aminobutyric Acid (GABA) Concentration of the Prefrontal Lobe in Unmedicated Patients with Obsessive-Compulsive Disorder: A Research of Magnetic Resonance Spectroscopy.

    Science.gov (United States)

    Zhang, Zongfeng; Fan, Qing; Bai, Yanle; Wang, Zhen; Zhang, Haiyin; Xiao, Zeping

    2016-10-25

    In recent years, a large number of neuroimaging studies found that the Cortico-Striato- Thalamo-Cortical circuit (CSTC), including the prefrontal lobe, a significant part of CSTC, has disturbance metabolically in patients with Obsessive-Compulsive Disorder (OCD). Explore the correlation between the neuro-metabolic features and clinical characteristics of OCD patients using magnetic resonance spectroscopy technology. 88 patients with OCD who were not received medication and outpatient treatment for 8 weeks and 76 health controls were enrolled, there was no significant difference in gender, age or education level between the two groups. SIEMENS 3.0T MRI scanner was used to measure the spectral wave of Orbito Frontal Cortex (OFC) and Anterior Cingulate Cortex (ACC) of participants, setting mega-press sequences. Meanwhile, the concentrations of gamma-aminobutyric acid (GABA), glutamine/glutamate complex (Glx) and N-Acetyl Aspartate (NAA) were measured relative to concentration of water, on the ACC and OFC of participants, for statistical analysis via LC model version 6.3 software. The concentration of metabolic substances of the OCD group compared to the healthy control group was analyzed using two sample t-test. The correlation between substance concentration and scores on the scales, including Yale-Brown Obsessive Compulsive Scale (Y-BOCS), Hamilton Anxiety scale (HAMA) and Hamilton Depression scale (HAMD) was carried out using the Pearson correlation method. Compared with healthy controls, the GABA/W and NAA/W concentration in individuals with OCD are significantly decreased ( p =0.031, t =2.193, p =0.002, t =3.223). Also, the concentration of GABA/W had a trend of decrease in the ACC. The GABA/W of the OFC had a negative correlation with Y-BOCS-O, Y-BOCS-C and Y-BOCS-T scores ( p =0.037, r =0.221; p =0.007, r =0.283; p =0.014, r =0.259). These results support that GABA concentration in the OFC area of patients with OCD is significantly decreased and the

  14. Human α1β3γ2L gamma-aminobutyric acid type A receptors: High-level production and purification in a functional state.

    Science.gov (United States)

    Dostalova, Zuzana; Zhou, Xiaojuan; Liu, Aiping; Zhang, Xi; Zhang, Yinghui; Desai, Rooma; Forman, Stuart A; Miller, Keith W

    2014-02-01

    Gamma-aminobutyric acid type A receptors (GABA(A)Rs) are the most important inhibitory chloride ion channels in the central nervous system and are major targets for a wide variety of drugs. The subunit compositions of GABA(A)Rs determine their function and pharmacological profile. GABAA Rs are heteropentamers of subunits, and (α1)2 (β3)2 (γ2L)1 is a common subtype. Biochemical and biophysical studies of GABA(A)Rs require larger quantities of receptors of defined subunit composition than are currently available. We previously reported high-level production of active human α1β3 GABA(A)R using tetracycline-inducible stable HEK293 cells. Here we extend the strategy to receptors containing three different subunits. We constructed a stable tetracycline-inducible HEK293-TetR cell line expressing human (N)-FLAG-α1β3γ2L-(C)-(GGS)3 GK-1D4 GABA(A)R. These cells achieved expression levels of 70-90 pmol [(3)H]muscimol binding sites/15-cm plate at a specific activity of 15-30 pmol/mg of membrane protein. Incorporation of the γ2 subunit was confirmed by the ratio of [(3)H]flunitrazepam to [(3)H]muscimol binding sites and sensitivity of GABA-induced currents to benzodiazepines and zinc. The α1β3γ2L GABA(A)Rs were solubilized in dodecyl-D-maltoside, purified by anti-FLAG affinity chromatography and reconstituted in CHAPS/asolectin at an overall yield of ∼ 30%. Typical purifications yielded 1.0-1.5 nmoles of [(3)H]muscimol binding sites/60 plates. Receptors with similar properties could be purified by 1D4 affinity chromatography with lower overall yield. The composition of the purified, reconstituted receptors was confirmed by ligand binding, Western blot, and proteomics. Allosteric interactions between etomidate and [(3)H]muscimol binding were maintained in the purified state. © 2013 The Protein Society.

  15. 7T Proton Magnetic Resonance Spectroscopy of Gamma-Aminobutyric Acid, Glutamate, and Glutamine Reveals Altered Concentrations in Patients With Schizophrenia and Healthy Siblings

    DEFF Research Database (Denmark)

    Thakkar, Katharine N; Rösler, Lara; Wijnen, Jannie P

    2017-01-01

    BACKGROUND: The N-methyl-D-aspartate receptor hypofunction model of schizophrenia predicts dysfunction in both glutamatergic and gamma-aminobutyric acidergic (GABAergic) transmission. We addressed this hypothesis by measuring GABA, glutamate, glutamine, and the sum of glutamine plus glutamate...... concentrations in vivo in patients with schizophrenia using proton magnetic resonance spectroscopy at 7T, which allows separation of metabolites that would otherwise overlap at lower field strengths. In addition, we investigated whether altered levels of GABA, glutamate, glutamine, and the sum of glutamine plus...... glutamate reflect genetic vulnerability to schizophrenia by including healthy first-degree relatives. METHODS: Proton magnetic resonance spectroscopy at 7T was performed in 21 patients with chronic schizophrenia who were taking medication, 23 healthy first-degree relatives of patients with schizophrenia...

  16. Interactive effects of glutamine and gamma-aminobutyric acid on growth performance and skeletal muscle amino acid metabolism of 22-42-day-old broilers exposed to hot environment

    Science.gov (United States)

    Hu, Hong; Bai, Xi; Shah, Assar Ali; Dai, Sifa; Wang, Like; Hua, Jinling; Che, Chuanyan; He, Shaojun; Wen, Aiyou; Jiang, Jinpeng

    2016-06-01

    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 muscle at 28, 35, and 42 days, while it increased ( P muscle, the Gln supplementation increased ( P muscle Gln concentrations, glutaminase activities, GS activities at 28 and 35 days, and DWG, GABA concentrations, and GABA-T activities at 28, 35, and 42 days in broilers under cyclic HS. In conclusion, the present results indicated that the interactions of exogenous Gln and GABA could offer a potential nutritional strategy to prevent HS-related depression in skeletal muscle Gln and GABA metabolism of broilers.

  17. In vivo magnetic resonance spectroscopy measurement of gray-matter and white-matter gamma-aminobutyric acid concentration in sensorimotor cortex using a motion-controlled MEGA point-resolved spectroscopy sequence.

    Science.gov (United States)

    Bhattacharyya, Pallab K; Phillips, Micheal D; Stone, Lael A; Lowe, Mark J

    2011-04-01

    Gamma-aminobutyric acid (GABA) is a major inhibitory neurotransmitter in the brain. Understanding the GABA concentration, in vivo, is important to understand normal brain function. Using MEGA point-resolved spectroscopy sequence with interleaved water scans to detect subject motion, GABA level of sensorimotor cortex was measured using a voxel identified from a functional magnetic resonance imaging scan. The GABA level in a 20×20×20-mm(3) voxel consisting of 37%±7% gray matter, 52%±12% white matter and 11%±8% cerebrospinal fluid in the sensorimotor region was measured to be 1.43±0.48 mM. In addition, using linear regression analysis, GABA concentrations within gray and white matter were calculated to be 2.87±0.61 and 0.33±0.11 mM, respectively. Copyright © 2011 Elsevier Inc. All rights reserved.

  18. 7T Proton Magnetic Resonance Spectroscopy of Gamma-Aminobutyric Acid, Glutamate, and Glutamine Reveals Altered Concentrations in Patients With Schizophrenia and Healthy Siblings.

    Science.gov (United States)

    Thakkar, Katharine N; Rösler, Lara; Wijnen, Jannie P; Boer, Vincent O; Klomp, Dennis W J; Cahn, Wiepke; Kahn, René S; Neggers, Sebastiaan F W

    2017-03-15

    The N-methyl-D-aspartate receptor hypofunction model of schizophrenia predicts dysfunction in both glutamatergic and gamma-aminobutyric acidergic (GABAergic) transmission. We addressed this hypothesis by measuring GABA, glutamate, glutamine, and the sum of glutamine plus glutamate concentrations in vivo in patients with schizophrenia using proton magnetic resonance spectroscopy at 7T, which allows separation of metabolites that would otherwise overlap at lower field strengths. In addition, we investigated whether altered levels of GABA, glutamate, glutamine, and the sum of glutamine plus glutamate reflect genetic vulnerability to schizophrenia by including healthy first-degree relatives. Proton magnetic resonance spectroscopy at 7T was performed in 21 patients with chronic schizophrenia who were taking medication, 23 healthy first-degree relatives of patients with schizophrenia, and 24 healthy nonrelatives. Glutamate, glutamine, and GABA were measured cortically and subcortically in bilateral basal ganglia and occipital cortex. Patients with schizophrenia had reduced cortical GABA compared with healthy relatives and the combined sample of healthy relatives and healthy nonrelatives, suggesting that altered GABAergic systems in schizophrenia are associated with either disease state or medication effects. Reduced cortical glutamine relative to healthy control subjects was observed in patients with schizophrenia and the combined sample of healthy relatives and patients with schizophrenia, suggesting that altered glutamatergic metabolite levels are associated with illness liability. No group differences were found in the basal ganglia. Taken together, these findings are consistent with alterations in GABAergic and glutamatergic systems in patients with schizophrenia and provide novel insights into these systems in healthy relatives. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  19. Increased gamma-aminobutyric acid levels in mouse brain induce loss of righting reflex, but not immobility, in response to noxious stimulation.

    Science.gov (United States)

    Katayama, Sohtaro; Irifune, Masahiro; Kikuchi, Nobuhito; Takarada, Tohru; Shimizu, Yoshitaka; Endo, Chie; Takata, Takashi; Dohi, Toshihiro; Sato, Tomoaki; Kawahara, Michio

    2007-06-01

    The general anesthetic state comprises behavioral and perceptual components, including amnesia, unconsciousness, and immobility. gamma-Aminobutyric acidergic (GABAergic) inhibitory neurotransmission is an important target for anesthetic action at the in vitro cellular level. In vivo, however, the functional relevance of enhancing GABAergic neurotransmission in mediating essential components of the general anesthetic state is unknown. Gabaculine is a GABA-transaminase inhibitor that inhibits degradation of released GABA, and consequently increases endogenous GABA in the central nervous system. Here, we examined, behaviorally, the ability of increased GABA levels to produce components of the general anesthetic state. All drugs were administered systemically in adult male ddY mice. To assess the general anesthetic components, two end-points were used. One was loss of righting reflex (LORR; as a measure of unconsciousness); the other was loss of movement in response to tail-clamp stimulation (as a measure of immobility). Gabaculine induced LORR in a dose-dependent fashion with a 50% effective dose of 100 (75-134; 95% confidence limits) mg/kg. The behavioral and microdialysis studies revealed that the endogenous GABA-induced LORR occurred in a brain concentration-dependent manner. However, even larger doses of gabaculine (285-400 mg/kg) produced no loss of tail-clamp response. In contrast, all the tested volatile anesthetics concentration-dependently abolished both righting and tail-clamp response, supporting the evidence that volatile anesthetics act on a variety of molecular targets. These findings indicate that LORR is associated with enhanced GABAergic neurotransmission, but that immobility in response to noxious stimulation is not, suggesting that LORR and immobility are mediated through different neuronal pathways and/or regions in the central nervous system.

  20. Dual mechanisms regulating glutamate decarboxylases and accumulation of gamma-aminobutyric acid in tea (Camellia sinensis) leaves exposed to multiple stresses.

    Science.gov (United States)

    Mei, Xin; Chen, Yiyong; Zhang, Lingyun; Fu, Xiumin; Wei, Qing; Grierson, Don; Zhou, Ying; Huang, Yahui; Dong, Fang; Yang, Ziyin

    2016-03-29

    γ-Aminobutyric acid (GABA) is one of the major inhibitory neurotransmitters in the central nervous system. It has multiple positive effects on mammalian physiology and is an important bioactive component of tea (Camellia sinensis). GABA generally occurs at a very low level in plants but GABA content increases substantially after exposure to a range of stresses, especially oxygen-deficiency. During processing of tea leaves, a combination of anoxic stress and mechanical damage are essential for the high accumulation of GABA. This is believed to be initiated by a change in glutamate decarboxylase activity, but the underlying mechanisms are unclear. In the present study we characterized factors regulating the expression and activity of three tea glutamate decarboxylase genes (CsGAD1, 2, and 3), and their encoded enzymes. The results suggests that, unlike the model plant Arabidopsis thaliana, there are dual mechanisms regulating the accumulation of GABA in tea leaves exposed to multiple stresses, including activation of CsGAD1 enzymatic activity by calmodulin upon the onset of the stress and accumulation of high levels of CsGAD2 mRNA induced by a combination of anoxic stress and mechanical damage.

  1. Effect of feeding Rumen-protected capsule containing niacin, K2SO4, vitamin C, and gamma-aminobutyric acid on heat stress and performance of dairy cows.

    Science.gov (United States)

    Guo, W J; Zhen, L; Zhang, J X; Lian, S; Si, H F; Guo, J R; Yang, H M

    2017-10-01

    This study was conducted to evaluate the effects of supplemental rumen-protected capsule (RPC) on animal performance, serological indicators, and serum heat shock protein 70 (HSP70) of lactating Holstein cows under heat stress (HS). During summer months, 30 healthy multiparous lactating Holstein cows with a parity number of 3.1 ± 0.44, 70 ± 15 d in milk, an average body weight of 622 ± 62kg, and an average milk yield of 32.28 ± 0.96kg/d, were used. The cows were randomly allocated to two groups: a control group and an RPC-supplemented group (0.13373kg K 2 SO 4 , 0.02488kg vitamin C, 0.021148kg niacin, and 0.044784kggamma-aminobutyric acid per cow). During the 42-d experiment, ambient air temperature and relative humidity inside and outside the barn were recorded hourly every day for the determination of temperature-humidity index (THI). Milk and blood samples were collected every week, and body weight and body condition scoring were measured on day 0. Based on the THI values, the animals had moderate HS. On day 42, the RPC group had lower HSP70, adrenocorticotropic hormone (P = 0.0001), lactate dehydrogenase (P = 0.0338), and IL-6 (P = 0.0724) levels than the control group, with no significant differences in creatine kinase, glucocorticoid, or IL-2 levels. Milk yield, energy-corrected milk, and dry matter intake were higher in RPC than in the control group (P = 0.0196). There were no significant differences in milk fat or daily protein levels between the two groups; however, daily protein and milk fat levels were higher in the RPC group than in the control group (P = 0.0114 and P = 0.0665, respectively). Somatic cell counts were no different between the two groups. In conclusion, RPC may alleviate HS and improve dairy cow performance. Copyright © 2017. Published by Elsevier Ltd.

  2. Perinatal exposure to germinated brown rice and its gamma amino-butyric acid-rich extract prevents high fat diet-induced insulin resistance in first generation rat offspring

    Directory of Open Access Journals (Sweden)

    Hadiza Altine Adamu

    2016-02-01

    Full Text Available Background: Evidence suggests perinatal environments influence the risk of developing insulin resistance. Objective: The present study was aimed at determining the effects of intrauterine exposure to germinated brown rice (GBR and GBR-derived gammaaminobutyric acid (GABA extract on epigenetically mediated high fat diet–induced insulin resistance. Design: Pregnant Sprague Dawley rats were fed high-fat diet (HFD, HFD+GBR, or HFD+GABA throughout pregnancy until 4 weeks postdelivery. The pups were weighed weekly and maintained on normal pellet until 8 weeks postdelivery. After sacrifice, biochemical markers of obesity and insulin resistance including oral glucose tolerance test, adiponectin, leptin, and retinol binding protein-4 (RBP4 were measured. Hepatic gene expression changes and the global methylation and histone acetylation levels were also evaluated. Results: Detailed analyses revealed that mothers given GBR and GABA extract, and their offspring had increased adiponectin levels and reduced insulin, homeostasis model assessment of insulin resistance, leptin, oxidative stress, and RBP4 levels, while their hepatic mRNA levels of GLUT2 and IPF1 were increased. Furthermore, GBR and GABA extract lowered global DNA methylation levels and modulated H3 and H4 acetylation levels. Conclusions: These results showed that intrauterine exposure to GBR-influenced metabolic outcomes in offspring of rats with underlying epigenetic changes and transcriptional implications that led to improved glucose homeostasis.

  3. Antagonistic properties of a natural product-Bicuculline with the gamma-aminobutyric acid receptor: studied through electrostatic potential mapping, electronic and vibrational spectra using ab initio and density functional theory.

    Science.gov (United States)

    Srivastava, Anubha; Tandon, Poonam; Jain, Sudha; Asthana, B P

    2011-12-15

    (+)-Bicuculline (hereinafter referred to as bicuculline), a phthalide isoquinoline alkaloid is of current interest as an antagonist of gamma-aminobutyric acid (GABA). Its inhibitor properties have been studied through molecular electrostatic potential (MEP) mapping of this molecule and GABA receptor. The hot site on the potential surface of bicuculline, which is also isosteric with GABA receptor, has been used to interpret the inhibitor property. A systematic quantum chemical study of the possible conformations, their relative stabilities, FT-Raman, FT-IR and UV-vis spectroscopic analysis of bicuculline has been reported. The optimized geometries, wavenumber and intensity of the vibrational bands of all the conformers of bicuculline have been calculated using ab initio Hartree-Fock (HF) and density functional theory (DFT) employing B3LYP functional and 6-311G(d,p) basis set. Mulliken atomic charges, HOMO-LUMO gap ΔE, ionization potential, dipole moments and total energy have also been obtained for the optimized geometries of both the molecules. TD-DFT method is used to calculate the electronic absorption parameters in gas phase as well as in solvent environment using integral equation formalism-polarizable continuum model (IEF-PCM) employing 6-31G basis set and the results thus obtained are compared with the UV absorption spectra. The combination of experimental and calculated results provides an insight into the structural and vibrational spectroscopic properties of bicuculline. Copyright © 2011 Elsevier B.V. All rights reserved.

  4. Relationship of nocturnal concentrations of melatonin, gamma-aminobutyric acid and total antioxidants in peripheral blood with insomnia after stroke: study protocol for a prospective non-randomized controlled trial

    Institute of Scientific and Technical Information of China (English)

    Wei Zhang; Fang Li; Tong Zhang

    2017-01-01

    Melatonin and gamma-aminobutyric acid (GABA) have been shown to regulate sleep. The nocturnal concentrations of melatonin, GABA and total antioxidants may relate to insomnia in stroke patients. In this prospective single-center non-randomized controlled clinical trial performed in the China Rehabilitation Research Center, we analyzed the relationship of nocturnal concentrations of melatonin, GABA and total antioxidants with insomnia after stroke. Patients during rehabilitation of stroke were recruited and assigned to the insomnia group or non-insomnia group. Simultaneously, persons without stroke or insomnia served as normal controls. Each group contained 25 cases. The primary outcome was nocturnal concentrations of melatonin, GABA and total antioxidants in peripheral blood. The secondary outcomes were Pittsburgh Sleep Quality Index, Insomnia Severity Index, Epworth Sleepiness Scale, Fatigue Severity Scale, Morningness-Eveningness Questionnaire (Chinese version), and National Institute of Health Stroke Scale. The relationship of nocturnal concentrations of melatonin, GABA and total antioxidants with insomnia after stroke was analyzed and showed that they were lower in the insomnia group than in the non-insomnia group. The severity of stroke was higher in the insomnia group than in the non-insomnia group. Correlation analysis demonstrated that the nocturnal concentrations of melatonin and GABA were associated with insomnia after stroke. This trial was regis-tered at ClinicalTrials.gov, identifier: NCT03202121.

  5. Functional modulation of cerebral gamma-aminobutyric acidA receptor/benzodiazepine receptor/chloride ion channel complex with ethyl beta-carboline-3-carboxylate: Presence of independent binding site for ethyl beta-carboline-3-carboxylate

    Energy Technology Data Exchange (ETDEWEB)

    Taguchi, J.; Kuriyama, K. (Kyoto Prefectural Univ. of Medicine (Japan))

    1990-05-01

    Effect of ethyl beta-carboline-3-carboxylate (beta-CCE) on the function of gamma-aminobutyric acid (GABA)A receptor/benzodiazepine receptor/chloride ion channel complex was studied. Beta-CCE noncompetitively and competitively inhibited (3H)flunitrazepam binding to benzodiazepine receptor, but not (3H)muscimol binding to GABAA receptor as well as t-(3H)butylbicycloorthobenzoate (( 3H) TBOB) binding to chloride ion channel, in particulate fraction of the mouse brain. Ro15-1788 also inhibited competitively (3H) flunitrazepam binding. On the other hand, the binding of beta-(3H)CCE was inhibited noncompetitively and competitively by clonazepam and competitively by Ro15-1788. In agreement with these results, benzodiazepines-stimulated (3H)muscimol binding was antagonized by beta-CCE and Ro15-1788. Gel column chromatography for the solubilized fraction from cerebral particulate fraction by 0.2% sodium deoxycholate (DOC-Na) in the presence of 1 M KCl indicated that beta-(3H)CCE binding site was eluted in the same fraction (molecular weight, 250,000) as the binding sites for (3H)flunitrazepam, (3H)muscimol and (3H)TBOB. GABA-stimulated 36Cl- influx into membrane vesicles prepared from the bovine cerebral cortex was stimulated and attenuated by flunitrazepam and beta-CCE, respectively. These effects of flunitrazepam and beta-CCE on the GABA-stimulated 36Cl- influx were antagonized by Ro15-1788. The present results suggest that the binding site for beta-CCE, which resides on GABAA receptor/benzodiazepine receptor/chloride ion channel complex, may be different from that for benzodiazepine. Possible roles of beta-CCE binding site in the allosteric inhibitions on benzodiazepine binding site as well as on the functional coupling between chloride ion channel and GABAA receptor are also suggested.

  6. High gamma-aminobutyric acid level in cortical tubers in epileptic infants with tuberous sclerosis complex measured with the MEGA-editing J-difference method and a three-Tesla clinical MRI Instrument.

    Science.gov (United States)

    Taki, Masako Minato; Harada, Masafumi; Mori, Kenji; Kubo, Hitoshi; Nose, Ayumi; Matsuda, Tsuyoshi; Nishitani, Hiromu

    2009-10-01

    The purpose of this study was to estimate the gamma-aminobutyric acid (GABA) and glutamate plus glutamine (Glx) concentrations in the cortical tubers of patients with tuberous sclerosis complex (TSC) using the MEGA-editing J-difference method and a stimulated echo-acquisition mode with a short echo time, and to determine which abnormality was more dominant between GABA and Glx in patients with TSC with epilepsy. This study included six patients with TSC (mean age, 4.3 years) and seven control subjects (mean age, 4.8 years). Measurements were obtained with a three-Tesla apparatus and postprocessing was conducted with an LCModel. The GABA level in the cortical gray matter (cgGABA) was calculated as a result of segmentation in voxels and from the literature values for gray and white matter ratios for GABA. Increased GABA and myo-inositol (mI) concentrations and a decreased N-acetyl aspartate (NAA) concentration were observed in the cortical tubers. The cgGABA level, and cgGABA/NAA and cgGABA/Glx ratios were also higher in patients with TSC than in control subjects. No significant difference was found in Glx concentration between patients with TSC and control subjects. Although the number of patients with TSC in this study was small, the increase in GABA and no significant change in Glx were consistent with previous neurochemical studies and support the hypothesis that brain GABA plays a key role in the pathophysiology of epilepsy during the process of neuronal development.

  7. Invasive ability of human renal cell carcinoma cell line Caki-2 is accelerated by gamma-aminobutyric acid, via sustained activation of ERK1/2 inducible matrix metalloproteinases.

    Science.gov (United States)

    Inamoto, Teruo; Azuma, Haruhito; Sakamoto, Takeshi; Kiyama, Satoshi; Ubai, Takanobu; Kotake, Yatsugu; Watanabe, Masahito; Katsuoka, Yoji

    2007-10-01

    Gamma-aminobutyric acid (GABA) was first discovered as an inhibitory neurotransmitter in the central nervous system (CNS) and has been reported to have a variety of functions, including regulation of cell division, cell differentiation and maturation, and to be involved in the development of certain cancers outside the CNS. In the present study, using the human renal cell carcinoma cell line Caki-2, we demonstrated that GABA stimulation significantly increased the expression of MMP-2 and -9 and subsequently increased the invasive activity of the cancer cells. Because MAPK signaling is one of the key regulators of MMP expression, we further evaluated MAPK signaling after stimulation with GABA. It was found that GABA stimulation promoted the phosphorylation of MAPKs, including ERK1/2, JNK, and p38. ERK1/2 phosphorylation was sustained for up to 12 h, while phosphorylation of JNK and p38 returned to the endogenous level by 30 min. It was noteworthy that the ras/raf/MEK/ERK pathway inhibitor PD98059 attenuated GABA-induced MMP-9 expression and that both PD98059 and MMP inhibitors attenuated the GABA-induced invasive activity of Caki-2 cells. Moreover, data obtained by depletion of the MEK/ERK pathway using interfering RNA transfection of Caki-2 cells clearly corroborated the above results, as both MMP-9 expression and GABA-induced invasive ability were decreased significantly. We also demonstrated that the GABA-induced increase in invasive ability via ERK1/2 up-regulation was mediated mainly through the GABA-B receptor. These results indicate that GABA stimulation promotes cancer cell invasion and that the effect is partly due to ERK1/2-dependent up-regulation of MMPs.

  8. Exposure of mother rats to chronic unpredictable stress before pregnancy alters the metabolism of gamma-aminobutyric acid and glutamate in the right hippocampus of offspring in early adolescence in a sexually dimorphic manner.

    Science.gov (United States)

    Huang, Yuejun; Shen, Zhiwei; Hu, Liu; Xia, Fang; Li, Yuewa; Zhuang, Jingwen; Chen, Peishan; Huang, Qingjun

    2016-12-30

    There is increasing evidence that mothers' exposure to stress before or during pregnancy is linked to an incidence of psychiatric disorders in offspring. However, a few studies have estimated the role of sex in the detrimental effects of pre-gestational stress on the offspring rats at early adolescence. Sex differences regarding the metabolism of gamma-aminobutyric acid and glutamate in the right hippocampus were investigated by MRS when the offspring rats reached 30 days. Additionally, the impact of pre-gestational stress exposed on an additional short-term acute stressor, such as forced swim, was examined in the male and female offspring rats. Our findings showed female offspring rats were more vulnerable to stressful conditions for either pre-gestational stress or acute stress in early adolescence, and had decreased GABA/Cr+PCr and Glu/Cr+PCr in the right hippocampus. Interestingly, in response to forced swim, male offspring rats whose mothers were exposed to pre-gestational stress were more affected by the short-term acute stressor and this was manifested by change of Glu/GABA and Glu/Gln in the right hippocampus. These data indicated that although female offspring rats were more vulnerable to pre-gestational stress from their mothers than males, in response to an additional acute stressor they showed better response. Therefore, both sexually dimorphic manner and combination of stressful procedures should be carefully considered in the study of stress-related psychiatric disorders in early adolescence. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  9. The vapour pressures over saturated aqueous solutions of DL-2-aminobutyric acid, 4-aminobutyric acid, sodium-D-gluconate, sodium hippurate, and potassium magnesium-L-aspartate

    International Nuclear Information System (INIS)

    Apelblat, Alexander; Korin, Eli

    2008-01-01

    Vapour pressures of water over saturated solutions of DL-2-aminobutyric acid, 4-aminobutyric acid, sodium-D-gluconate, sodium hippurate, and potassium magnesium-L-aspartate were determined over the (278 to 322) K temperature range. The determined vapour pressures were used to obtain the water activities, the molar enthalpies of vaporization, and the osmotic coefficients of sodium-D-gluconate

  10. The vapour pressures over saturated aqueous solutions of DL-2-aminobutyric acid, 4-aminobutyric acid, sodium-D-gluconate, sodium hippurate, and potassium magnesium-L-aspartate

    Energy Technology Data Exchange (ETDEWEB)

    Apelblat, Alexander [Department of Chemical Engineering, Ben Gurion University of the Negev, Beer Sheva 84105 (Israel)], E-mail: apelblat@bgu.ac.il; Korin, Eli [Department of Chemical Engineering, Ben Gurion University of the Negev, Beer Sheva 84105 (Israel)

    2008-05-15

    Vapour pressures of water over saturated solutions of DL-2-aminobutyric acid, 4-aminobutyric acid, sodium-D-gluconate, sodium hippurate, and potassium magnesium-L-aspartate were determined over the (278 to 322) K temperature range. The determined vapour pressures were used to obtain the water activities, the molar enthalpies of vaporization, and the osmotic coefficients of sodium-D-gluconate.

  11. Effects of NaCl Replacement with Gamma-Aminobutyric acid (GABA) on the Quality Characteristics and Sensorial Properties of Model Meat Products

    Science.gov (United States)

    Chun, Ji-Yeon; Cho, Hyung-Yong; Min, Sang-Gi

    2014-01-01

    This study investigated the effects of γ-aminobutylic acid (GABA) on the quality and sensorial properties of both the GABA/NaCl complex and model meat products. GABA/NaCl complex was prepared by spray-drying, and the surface dimensions, morphology, rheology, and saltiness were characterized. For model meat products, pork patties were prepared by replacing NaCl with GABA. For characteristics of the complex, increasing GABA concentration increased the surface dimensions of the complex. However, GABA did not affect the rheological properties of solutions containing the complex. The addition of 2% GABA exhibited significantly higher saltiness than the control (no GABA treatment). In the case of pork patties, sensory testing indicated that the addition of GABA decreased the saltiness intensity. Both the intensity of juiciness and tenderness of patties containing GABA also scored lower than the control, based on the NaCl reduction. These results were consistent with the quality characteristics (cooking loss and texture profile analysis). Nevertheless, overall acceptability of the pork patties showed that up to 1.5%, patties containing GABA did not significantly differ from the control. Consequently, the results indicated that GABA has a potential application in meat products, but also manifested a deterioration of quality by the NaCl reduction, which warrants further exploration. PMID:26761294

  12. Phenibut (β-Phenyl-γ-aminobutyric Acid) Dependence and Management of Withdrawal: Emerging Nootropics of Abuse.

    Science.gov (United States)

    Ahuja, Tania; Mgbako, Ofole; Katzman, Caroline; Grossman, Allison

    2018-01-01

    This case report describes the development of withdrawal from phenibut, a gamma-aminobutyric acid-receptor type B agonist. Although phenibut is not an FDA-approved medication, it is available through online retailers as a nootropic supplement. There are reports of dependence in patients that misuse phenibut. We report a case in which a patient experienced withdrawal symptoms from phenibut and was successfully treated with a baclofen taper. This case report highlights the development of phenibut use disorder with coingestion of alcohol and potential management for phenibut withdrawal. We believe clinicians must be aware of how phenibut dependence may present and how to manage the withdrawal syndrome.

  13. Phenibut (β-Phenyl-γ-aminobutyric Acid Dependence and Management of Withdrawal: Emerging Nootropics of Abuse

    Directory of Open Access Journals (Sweden)

    Tania Ahuja

    2018-01-01

    Full Text Available This case report describes the development of withdrawal from phenibut, a gamma-aminobutyric acid-receptor type B agonist. Although phenibut is not an FDA-approved medication, it is available through online retailers as a nootropic supplement. There are reports of dependence in patients that misuse phenibut. We report a case in which a patient experienced withdrawal symptoms from phenibut and was successfully treated with a baclofen taper. This case report highlights the development of phenibut use disorder with coingestion of alcohol and potential management for phenibut withdrawal. We believe clinicians must be aware of how phenibut dependence may present and how to manage the withdrawal syndrome.

  14. Effect of Feeding High Gamma-Aminobutyric Acid-Containing Giant Embryo Black Sticky Rice (Oryza sativa L.) on Anxiety-Related Behavior of C57BL/6 Mice.

    Science.gov (United States)

    Jung, Woo-Young; Kim, Sung-Gon; Lee, Jin-Seong; Kim, Hyeon-Kyeong; Son, Beung-Gu; Kim, Jong-Woo; Suh, Jae-Won

    2017-08-01

    The aim of this study was to determine the effect of feeding high gamma-aminobutyric acid (GABA)-containing black sticky rice giant embryo (BSRGE, Oryza sativa L.) on anxiety-related behavior of C57BL/6 mice. Experimental feedstuff (BSRGE with high GABA+AIN-76A) and control (AIN-76A) were provided to C57BL/6 mouse for 10 days. Antianxiety effects of BSRGE with high GABA were measured using an elevated plus maze. On day 8, the number of open arm entries by GABA and control groups were 1.10 ± 1.60 (mean ± SD) and 0.00 ± 0.00 (P = .030). On day 10, the number of open arm entries by the GABA group was 2.00 ± 1.89, which was significantly (P = .025) higher than that in the control group (0.40 ± 0.84). On day 8, the time the mice spent in open arm in the GABA group and control group was 3.60 ± 7.06 and 0.00 ± 0.00 sec (P = .068), respectively. On day 10, the time the mice in the GABA and control groups spent in open arm was 6.20 ± 5.35 sec and 1.80 ± 3.82 sec (P = .042), respectively. In repeated analysis of variance for the number of entries into open arm and time spent in open arm, significant differences were found between the two groups. Therefore, BSRGE with high GABA content might have an antianxiety effect. This study can serve as a preliminary study so that further antianxiety effects of BSRGE can be determined in more extended animal or clinical research studies in the future.

  15. DNA Methylation at the Neonatal State and at the Time of Diagnosis: Preliminary Support for an Association with the Estrogen Receptor 1, Gamma-Aminobutyric Acid B Receptor 1, and Myelin Oligodendrocyte Glycoprotein in Female Adolescent Patients with OCD.

    Science.gov (United States)

    Nissen, Judith Becker; Hansen, Christine Søholm; Starnawska, Anna; Mattheisen, Manuel; Børglum, Anders Dupont; Buttenschøn, Henriette Nørmølle; Hollegaard, Mads

    2016-01-01

    Obsessive-compulsive disorder (OCD) is a neuropsychiatric disorder. Non-genetic factors and their interaction with genes have attracted increasing attention. Epigenetics is regarded an important interface between environmental signals and activation/repression of genomic responses. Epigenetic mechanisms have not previously been examined in OCD in children and adolescents. The aim of the present study was to examine the DNA methylation profile of selected genes in blood spots from neonates later diagnosed with OCD and in the same children/adolescents at the time of diagnosis compared with age- and sex-matched controls. Furthermore, we wanted to characterize the association of the differential methylation profiles with the severity of OCD and treatment outcome. Dried and new blood spot samples were obtained from 21 female children/adolescents with verified OCD and 12 female controls. The differential methylation was analyzed using a linear model and the correlation with the severity of OCD and treatment outcome was analyzed using the Pearson correlation. We evaluated selected Illumina Infinium HumanMethylation450 BeadChip probes within and up to 100,000 bp up- and downstream of 14 genes previously associated with OCD (SLC1A1, SLC25A12, GABBR1, GAD1, DLGAP1, MOG, BDNF, OLIG2, NTRK2 and 3, ESR1, SL6A4, TPH2, and COMT). The study found no significantly differential methylation. However, preliminary support for a difference was found for the gamma-aminobutyric acid (GABA) B receptor 1 (cg10234998, cg17099072) in blood samples at birth and for the estrogen receptor 1 (ESR1) (cg10939667), the myelin oligodendrocyte glycoprotein (MOG) (cg16650906), and the brain-derived neurotrophic factor (BDNF) (cg14080521) in blood samples at the time of diagnosis. Preliminary support for an association was observed between the methylation profiles of GABBR1 and MOG and baseline severity, treatment effect, and responder status; and between the methylation profile of ESR1 and baseline

  16. Aminobutyric acid and formation of higher alcohols by Saccharomyces carlsbergenesis

    Energy Technology Data Exchange (ETDEWEB)

    Babaeva, S A; Veselov, I Ya; Gracheva, I M

    1966-01-01

    Aminobutyric acid (1) added before the start of fermentation increased the formation of propyl-, isobutyl-, and isoamyl alcohols. With addition of I after 24, 28, or 72 hours of fermentation, the formation of the alcohols gradually decreased. Addition of I after 3 days of fermentation did not affect formation of the higher alcohols. I was not the source of formation of the higher alcohols, but affected the metabolism of carbohydrates and N in the cells. Formation of hexyl alcohols and high amounts of aldehydes was observed only during aerobic fermentation.

  17. Design and Mechanism of Tetrahydrothiophene-Based γ-Aminobutyric Acid Aminotransferase Inactivators

    Energy Technology Data Exchange (ETDEWEB)

    Le, Hoang V. [Departments; Hawker, Dustin D. [Departments; Wu, Rui [Department; Doud, Emma [Departments; Widom, Julia [Departments; Sanishvili, Ruslan [X-ray; Liu, Dali [Department; Kelleher, Neil L. [Departments; Silverman, Richard B. [Departments

    2015-03-25

    Low levels of gamma-aminobutyric acid (GABA), one of two major neurotransmitters that regulate brain neuronal activity, are associated with many neurological disorders, such as epilepsy, Parkinsons disease, Alzheimers disease, Huntingtons disease, and cocaine addiction. One of the main methods to raise the GABA level in human brain is to use small molecules that cross the bloodbrain barrier and inhibit the activity of gamma-aminobutyric acid aminotransferase (GABA-AT), the enzyme that degrades GABA. We have designed a series of conformationally restricted tetrahydrothiophene-based GABA analogues with a properly positioned leaving group that could facilitate a ring-opening mechanism, leading to inactivation of GABA-AT. One compound in the series is 8 times more efficient an inactivator of GABA-AT than vigabatrin, the only FDA-approved inactivator of GABA-AT. Our mechanistic studies show that the compound inactivates GABA-AT by a new mechanism. The metabolite resulting from inactivation does not covalently bind to amino acid residues of GABA-AT but stays in the active site via H-bonding interactions with Arg-192, a pi-pi interaction with Phe-189, and a weak nonbonded (SO)-O-...=C interaction with Glu-270, thereby inactivating the enzyme.

  18. Priming of plant innate immunity by rhizobacteria and β-aminobutyric acid: differences and similarities in regulation

    NARCIS (Netherlands)

    Ent, S. van der; Hulten, M.H.A. van; Pozo, Maria J.; Czechowski, Tomasz; Udvardi, Michael K.; Pieterse, C.M.J.; Ton, J.

    Pseudomonas fluorescens WCS417r bacteria and β-aminobutyric acid can induce disease resistance in Arabidopsis, which is based on priming of defence. In this study, we examined the differences and similarities of WCS417r- and β-aminobutyric acid-induced priming. Both WCS417r and β-aminobutyric acid

  19. Production of gaba (γ - aminobutyric acid by microorganisms: a review

    Directory of Open Access Journals (Sweden)

    Radhika Dhakal

    2012-12-01

    Full Text Available GABA (γ-aminobutyric acid is a four carbon non-protein amino acid that is widely distributed in plants, animals and microorganisms. As a metabolic product of plants and microorganisms produced by the decarboxylation of glutamic acid, GABA functions as an inhibitory neurotransmitter in the brain that directly affects the personality and the stress management. A wide range of traditional foods produced by microbial fermentation contain GABA, in which GABA is safe and eco-friendly, and also has the possibility of providing new health-benefited products enriched with GABA. Synthesis of GABA is catalyzed by glutamate decarboxylase, therefore, the optimal fermentation condition is mainly based on the biochemical properties of the enzyme. Major GABA producing microorganisms are lactic acid bacteria (LAB, which make food spoilage pathogens unable to grow and act as probiotics in the gastrointestinal tract. The major factors affecting the production of GABA by microbial fermentation are temperature, pH, fermentation time and different media additives, therefore, these factors are summarized to provide the most up-dated information for effective GABA synthesis. There has been a huge accumulation of knowledge on GABA application for human health accompanying with a demand on natural GABA supply. Only the GABA production by microorganisms can fulfill the demand with GABA-enriched health beneficial foods.

  20. Production of gaba (γ - Aminobutyric acid) by microorganisms: a review.

    Science.gov (United States)

    Dhakal, Radhika; Bajpai, Vivek K; Baek, Kwang-Hyun

    2012-10-01

    GABA (γ-aminobutyric acid) is a four carbon non-protein amino acid that is widely distributed in plants, animals and microorganisms. As a metabolic product of plants and microorganisms produced by the decarboxylation of glutamic acid, GABA functions as an inhibitory neurotransmitter in the brain that directly affects the personality and the stress management. A wide range of traditional foods produced by microbial fermentation contain GABA, in which GABA is safe and eco-friendly, and also has the possibility of providing new health-benefited products enriched with GABA. Synthesis of GABA is catalyzed by glutamate decarboxylase, therefore, the optimal fermentation condition is mainly based on the biochemical properties of the enzyme. Major GABA producing microorganisms are lactic acid bacteria (LAB), which make food spoilage pathogens unable to grow and act as probiotics in the gastrointestinal tract. The major factors affecting the production of GABA by microbial fermentation are temperature, pH, fermentation time and different media additives, therefore, these factors are summarized to provide the most up-dated information for effective GABA synthesis. There has been a huge accumulation of knowledge on GABA application for human health accompanying with a demand on natural GABA supply. Only the GABA production by microorganisms can fulfill the demand with GABA-enriched health beneficial foods.

  1. Cloning and characterization of a functional human ¿-aminobutyric acid (GABA) transporter, human GAT-2

    DEFF Research Database (Denmark)

    Christiansen, Bolette; Meinild, Anne-Kristine; Jensen, Anders A.

    2007-01-01

    Plasma membrane gamma-aminobutyric acid (GABA) transporters act to terminate GABA neurotransmission in the mammalian brain. Intriguingly four distinct GABA transporters have been cloned from rat and mouse, whereas only three functional homologs of these transporters have been cloned from human....... The aim of this study therefore was to search for this fourth missing human transporter. Using a bioinformatics approach, we successfully identified and cloned the full-length cDNA of a so far uncharacterized human GABA transporter (GAT). The predicted protein displays high sequence similarity to rat GAT......-2 and mouse GAT3, and in accordance with the nomenclature for rat GABA transporters, we therefore refer to the transporter as human GAT-2. We used electrophysiological and cell-based methods to demonstrate that this protein is a functional transporter of GABA. The transport was saturable...

  2. Submerged fermentation of Lactobacillus rhamnosus YS9 for γ-aminobutyric acid (GABA) production

    OpenAIRE

    Lin,Qian

    2013-01-01

    γ-Aminobutyric acid (GABA) is a major inhibitory neurotransmitter in central nervous system, and its application in drugs and functional foods has attracted great attention. To enhance production of y-aminobutyric acid, Lactobacillus rhamnosus YS9, a strain isolated from Chinese traditional fermented food pickled vegetable, was grown under submerged fermentation. Its cultivation conditions were investigated. When culture pH condition was adjusted to the optimal pH of glutamate decarboxyl...

  3. γ-Aminobutyric acid (GABA) signalling in plants.

    Science.gov (United States)

    Ramesh, Sunita A; Tyerman, Stephen D; Gilliham, Matthew; Xu, Bo

    2017-05-01

    The role of γ-aminobutyric acid (GABA) as a signal in animals has been documented for over 60 years. In contrast, evidence that GABA is a signal in plants has only emerged in the last 15 years, and it was not until last year that a mechanism by which this could occur was identified-a plant 'GABA receptor' that inhibits anion passage through the aluminium-activated malate transporter family of proteins (ALMTs). ALMTs are multigenic, expressed in different organs and present on different membranes. We propose GABA regulation of ALMT activity could function as a signal that modulates plant growth, development, and stress response. In this review, we compare and contrast the plant 'GABA receptor' with mammalian GABA A receptors in terms of their molecular identity, predicted topology, mode of action, and signalling roles. We also explore the implications of the discovery that GABA modulates anion flux in plants, its role in signal transduction for the regulation of plant physiology, and predict the possibility that there are other GABA interaction sites in the N termini of ALMT proteins through in silico evolutionary coupling analysis; we also explore the potential interactions between GABA and other signalling molecules.

  4. Anterior Cingulate Cortex γ-Aminobutyric Acid in Depressed Adolescents

    Science.gov (United States)

    Gabbay, Vilma; Mao, Xiangling; Klein, Rachel G.; Ely, Benjamin A.; Babb, James S.; Panzer, Aviva M.; Alonso, Carmen M.; Shungu, Dikoma C.

    2013-01-01

    Context Anhedonia, a core symptom of major depressive disorder (MDD) and highly variable among adolescents with MDD, may involve alterations in the major inhibitory amino acid neurotransmitter system of γ-aminobutyric acid (GABA). Objective To test whether anterior cingulate cortex (ACC) GABA levels, measured by proton magnetic resonance spectroscopy, are decreased in adolescents with MDD. The associations of GABA alterations with the presence and severity of anhedonia were explored. Design Case-control, cross-sectional study using single-voxel proton magnetic resonance spectroscopy at 3 T. Setting Two clinical research divisions at 2 teaching hospitals. Participants Twenty psychotropic medication-free adolescents with MDD (10 anhedonic, 12 female, aged 12–19 years) with episode duration of 8 weeks or more and 21 control subjects group matched for sex and age. Main Outcome Measures Anterior cingulate cortex GABA levels expressed as ratios relative to unsuppressed voxel tissue water (w) and anhedonia scores expressed as a continuous variable. Results Compared with control subjects, adolescents with MDD had significantly decreased ACC GABA/w (t= 3.2; PGABA/w levels compared with control subjects (t=4.08; PGABA/w levels were negatively correlated with anhedonia scores for the whole MDD group (r = −0.50; P = .02), as well as for the entire participant sample including the control subjects (r=−0.54; PGABA, the major inhibitory neurotransmitter in the brain, may be implicated in adolescent MDD and, more specifically, in those with anhedonia. In addition, use of a continuous rather than categorical scale of anhedonia, as in the present study, may permit greater specificity in evaluating this important clinical feature. PMID:21969419

  5. Association between Single Nucleotide Polymorphisms in Gamma-Aminobutyric Acid B Receptor, Insulin Receptor Substrate-1, and Hypocretin Neuropeptide Precursor Genes and Susceptibility to Obstructive Sleep Apnea Hypopnea Syndrome in a Chinese Han Population.

    Science.gov (United States)

    Li, Zhijun; Tang, Tingyu; Du, Jianzong; Wu, Wenjuan; Zhou, Xiaoxi; Qin, Guangyue

    2016-01-01

    To investigate genotype-phenotype changes between rs29230 in γ-aminobutyric acid B receptor (GABBR1), rs1801278 in insulin receptor substrate-1 (IRS-1), and rs9902709 in hypocretin neuropeptide precursor (HCRT) and obstructive sleep apnea hypopnea syndrome (OSAHS) in Chinese Han individuals. A total of 130 patients with OSAHS and 136 age- and gender-matched healthy controls were enrolled in this study. A brief description of DNA extraction and genotyping is given. Multivariate unconditional logistic regression analysis adjusted for gender and age was used to estimate the associations of single nucleotide polymorphisms (SNPs) rs29230 (GABBR1), rs1801278 (IRS-1), and rs9902709 (HCRT) with OSAHS risk. Subgroup analysis was performed to evaluate differences in these SNPs among subgroups according to gender, body mass index (BMI), and severity of disease. Genotype and allele frequencies of rs29230 were significantly different between cases and controls (p = 0.0205 and p = 0.0191, respectively; odds ratio = 0.493, 95% confidence interval = 0.271-0.896), especially for male patients (p = 0.0259 and p = 0.0202, respectively). Subgroup analysis according to BMI also revealed a significant allele difference for rs29230 between cases and controls in the overweight subgroup (p = 0.0333). Furthermore, allele and genotype frequencies of rs1801278 showed significant differences between cases and controls (p = 0.0488 and p = 0.0471, respectively). However, no association was observed between rs9902709 and OSAHS risk (p = 0.2762), and no differences were identified in other subgroups. In this study, there was an association between variants of rs29230 and rs1801278 and OSAHS risk in the Chinese Han population but not for rs9902709. © 2016 S. Karger AG, Basel.

  6. Study on Processing Technology and Quality of Moringa oleifera leaves with y - Aminobutyric Acid

    Directory of Open Access Journals (Sweden)

    Wei Zhou

    2017-01-01

    Full Text Available In order to obtain the high level of γ-aminobutyric acid Moringa oleifera leaves, Use 7% sodium glutamate solution to soak the fresh Moringa oleifera leaves, study effect of different treatment times and three different drying methods( hot air drying, vacuum freeze drying, shadow drying on the formation of y-aminobutyric acid and quality (total flavonoids, soluble sugar, amino acids, polyphenols, colorof dried Moringa oleifera leaves. The results indicated that shadow-dried Moringa oleifera leaves had the hightest retention of γ-aminobutyric acid, but its browning degree were not preferable, soluble sugar was damaged gravely, and its vulnerable to weather conditions. Vacuum freeze dried Moringa oleifera leaves had the hightest retention of flavonoids, polyphenols and amino acids. The y-aminobutyric acid content of Vacuum freeze dried and hot air dried Moringa oleifera leaves had no much difference. Hot air dried Moringa oleifera leaves browning degree were preferable, it’s had an moderate content of soluble sugar and amino acids, the short drying time is characteristics of this drying method.with the treatment time increased, the content of γ-aminobutyric acid and amino acids content first increased and then decreased. Flavonoids and polyphenols content first decreased and then increased. Soluble sugar content decreased. In summary, after soaking with 7% sodium glutamate solution for 10h, then dried by hot air drying(drying temperature of 60°C, was the most suitable way for industrial production of the high level of γ-aminobutyric acid Moringa oleifera leaves.

  7. Methylenetetrahydrofolate reductase deficiency alters levels of glutamate and γ-aminobutyric acid in brain tissue

    Directory of Open Access Journals (Sweden)

    N.M. Jadavji

    2015-06-01

    Full Text Available Methylenetetrahydrofolate reductase (MTHFR is an enzyme key regulator in folate metabolism. Deficiencies in MTHFR result in increased levels of homocysteine, which leads to reduced levels of S-adenosylmethionine (SAM. In the brain, SAM donates methyl groups to catechol-O-methyltransferase (COMT, which is involved in neurotransmitter analysis. Using the MTHFR-deficient mouse model the purpose of this study was to investigate levels of monoamine neurotransmitters and amino acid levels in brain tissue. MTHFR deficiency affected levels of both glutamate and γ-aminobutyric acid in within the cerebellum and hippocampus. Mthfr−/− mice had reduced levels of glutamate in the amygdala and γ-aminobutyric acid in the thalamus. The excitatory mechanisms of homocysteine through activation of the N-methyl-d-aspartate receptor in brain tissue might alter levels of glutamate and γ-aminobutyric acid.

  8. Study on Process Parameters of Extraction of γ-aminobutyric Acid Instant Moringa oleifera Powder

    Science.gov (United States)

    Tiaokun, Fu; Suhui, Zhang; Neng, Liu; Jihua, Li; Shaodan, Peng; Changqing, Guo; Wei, Zhou

    2017-12-01

    To preliminary optimize the extraction of γ-aminobutyric acid instant tea powder from Moringa oleifera leaves,taking γ-aminobutyric acid Moringa oleifera leaves as raw material and pure water as extraction solvent and GABA content as the main evaluation index,the effects of extraction temperature, ratio of liquid to material and extraction time on biochemical components and sensory qualities of Moringa oleifera leaves extractor was studied by using one-factor-at-a-time experiment.The results showed shat the optimal extraction conditions for γ-aminobutyric acid instant tea powder were extraction temperature of 60 °C, material-to-water ration of 1:10 and extraction time of 40 min.

  9. Submerged fermentation of Lactobacillus rhamnosus YS9 for γ-aminobutyric acid (GABA production

    Directory of Open Access Journals (Sweden)

    Qian Lin

    2013-01-01

    Full Text Available γ-Aminobutyric acid (GABA is a major inhibitory neurotransmitter in central nervous system, and its application in drugs and functional foods has attracted great attention. To enhance production of y-aminobutyric acid, Lactobacillus rhamnosus YS9, a strain isolated from Chinese traditional fermented food pickled vegetable, was grown under submerged fermentation. Its cultivation conditions were investigated. When culture pH condition was adjusted to the optimal pH of glutamate decarboxylase activity, culture of Lb. rhamnosus YS9 in medium supplemented with 200 mM of monosodium glutamate and 200 µM of pyridoxal phosphate (PLP, produced 187 mM of GABA.

  10. Submerged fermentation of Lactobacillus rhamnosus YS9 for γ-aminobutyric acid (GABA) production

    Science.gov (United States)

    Lin, Qian

    2013-01-01

    γ-Aminobutyric acid (GABA) is a major inhibitory neurotransmitter in central nervous system, and its application in drugs and functional foods has attracted great attention. To enhance production of γ-aminobutyric acid, Lactobacillus rhamnosus YS9, a strain isolated from Chinese traditional fermented food pickled vegetable, was grown under submerged fermentation. Its cultivation conditions were investigated. When culture pH condition was adjusted to the optimal pH of glutamate decarboxylase activity, culture of Lb. rhamnosus YS9 in medium supplemented with 200 mM of monosodium glutamate and 200 μM of pyridoxal phosphate (PLP), produced 187 mM of GABA. PMID:24159304

  11. A gene duplication led to specialized gamma-aminobutyrate and beta-alanine aminotransferase in yeast

    DEFF Research Database (Denmark)

    Andersen, Gorm; Andersen, Birgit; Dobritzsch, D.

    2007-01-01

    and related yeasts have two different genes/enzymes to apparently 'distinguish' between the two reactions in a single cell. It is likely that upon duplication similar to 200 million years ago, a specialized Uga1p evolved into a 'novel' transaminase enzyme with broader substrate specificity.......In humans, beta-alanine (BAL) and the neurotransmitter gamma-aminobutyrate (GABA) are transaminated by a single aminotransferase enzyme. Apparently, yeast originally also had a single enzyme, but the corresponding gene was duplicated in the Saccharomyces kluyveri lineage. SkUGA1 encodes a homologue...... to characterize the substrate specificity and kinetic parameters of the four enzymes. It was found that the cofactor pyridoxal 5'-phosphate is needed for enzymatic activity and alpha-ketoglutarate, and not pyruvate, as the amino group acceptor. SkPyd4p preferentially uses BAL as the amino group donor (V...

  12. GABA (γ-aminobutyric acid) production, antioxidant activity in some germinated dietary seeds and the effect of cooking on their GABA content

    OpenAIRE

    TIANSAWANG,Kasarin; LUANGPITUKSA,Pairoj; VARANYANOND,Warunee; HANSAWASDI,Chanida

    2016-01-01

    Abstract Germinated grains have been known as sources of Gamma-aminobutyric acid (GABA) that provide beneficial effects for human health. This study was aimed to investigate GABA production, dietary fiber, antioxidant activity, and the effect of cooking on GABA loss in germinated legumes and sesame. The highest GABA content was found in germinated mung bean, (0.8068 g kg-1, 24 h incubation) followed by germinated soybean, germinated black bean and soaked sesame. Beside GABA, dietary fiber con...

  13. Ca2+ and aminoguanidine on γ-aminobutyric acid accumulation in germinating soybean under hypoxia–NaCl stress

    Directory of Open Access Journals (Sweden)

    Runqiang Yang

    2015-06-01

    Full Text Available Gamma-aminobutyric acid (GABA, a nonproteinous amino acid with some benefits on human health, is synthesized by GABA-shunt and the polyamine degradation pathway in plants. The regulation of Ca2+ and aminoguanidine on GABA accumulation in germinating soybean (Glycine max L. under hypoxia-NaCl stress was investigated in this study. Exogenous Ca2+ increased GABA content significantly by enhancing glutamate decarboxylase gene expression and its activity. Addition of ethylene glycol tetra-acetic acid into the culture solution reduced GABA content greatly due to the inhibition of glutamate decarboxylase activity. Aminoguanidine reduced over 85% of diamine oxidase activity, and 33.28% and 36.35% of GABA content in cotyledon and embryo, respectively. Under hypoxia–NaCl stress, the polyamine degradation pathway contributed 31.61–39.43% of the GABA formation in germinating soybean.

  14. Plant perception of β-aminobutyric acid is mediated by an aspartyl-tRNA synthetase

    NARCIS (Netherlands)

    Luna, E.; Van Hulten, M.; Zhang, Y.; Berkowitz, O.; López, A.; Pétriacq, P.; Sellwood, M.A.; Chen, B.; Burrell, M.; Van de Meene, A.; Pieterse, C.M.J.; Flors, V.; Ton, J.

    2014-01-01

    Specific chemicals can prime the plant immune system for augmented defense. β-aminobutyric acid (BABA) is a priming agent that provides broad-spectrum disease protection. However, BABA also suppresses plant growth when applied in high doses, which has hampered its application as a crop defense

  15. Plant perception of β-aminobutyric acid is mediated by an aspartyl-tRNA synthetase

    NARCIS (Netherlands)

    Luna, Estrella; van Hulten, Marieke; Zhang, Yuhua; Berkowitz, Oliver; López, Ana; Pétriacq, Pierre; Sellwood, Matthew A; Chen, Beining; Burrell, Mike; van de Meene, Allison; Pieterse, Corné M J; Flors, Victor; Ton, Jurriaan

    Specific chemicals can prime the plant immune system for augmented defense. β-aminobutyric acid (BABA) is a priming agent that provides broad-spectrum disease protection. However, BABA also suppresses plant growth when applied in high doses, which has hampered its application as a crop defense

  16. Study on flavour volatiles of γ-aminobutyric acid (GABA) green tea ...

    African Journals Online (AJOL)

    The volatile components of γ-aminobutyric acid (GABA) tea produced by two different kinds of technological process separately namely: vacuum and water immersion were studied. It was shown by the sensory evaluation that the color of the soup and the extracted leaves of GABA tea were similar to that of the oolong tea, ...

  17. Syntheses of {gamma}-aminobutyric-1-{sup 14}C and of {alpha}-aminoadipic-6-{sup 14}C acid from methoxy-3 chloropropyl-magnesium and marked carbon dioxide; Syntheses de l'acide {gamma}-aminobutyrique{sup 14}C-1 et de l'acide {alpha}-aminoadipique {sup 14}C-6 a partir de methoxy-3 chloropropylmagnesium et d'anhydride carbonique marque

    Energy Technology Data Exchange (ETDEWEB)

    Liem, Phung Nhu [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires, Departement des radioelements, Service des molecules marquees

    1967-04-01

    Carbonation of {gamma}-methoxypropyl-magnesium chloride by CO{sub 2} gives {gamma}-methoxy-butyric carboxylic-{sup 14}C acid with a yield of about 95 per cent. When the latter is treated successively with anhydrous HBr and with diazomethane, methyl carboxylic {gamma}-bromobutyrate-{sup 14}C is formed. This in turn gives {gamma}-amino-butyric carboxylic-{sup 14}C acid with an overall yield of 66 per cent with respect to Ba{sup 14}CO{sub 3}, when it is condensed with potassium phthalimide and hydrolyzed by acid. By reacting methyl-{gamma}-bromobutyrate-{sup 14}C with the sodium derivative of ethyl cyanacetamido-acetate in ethanol, followed by an acid hydrolysis, {alpha}-aminoadipic-6-{sup 14}C acid is obtained with an overall yield of 46 per cent with respect to Ba{sup 14}CO{sub 3}. (author) [French] La carbonatation du chlorure de {gamma}-methoxypropylmagnesium par {sup 14}CO{sub 2} donne l'acide {gamma}-methoxybutyrique carboxyle {sup 14}C avec un rendement d'environ 95 pour cent. Ce dernier traite successivement par HBr anhydre et par le diazomethane conduit au {gamma}-bromobutyrate de methyle carboxyle {sup 14}C. Celui-ci condense avec le phtalimide de potassium suivi d'une hydrolyse acide fournit l'acide {gamma}-aminobutyrique carboxyle {sup 14}C avec un rendement global de 66 pour cent par rapport a Ba{sup 14}CO{sub 3}. L'action du {gamma}-bromobutyrate de methyle {sup 14}C sur le derive sode du cyanacetamidoacetate d'ethyle dans l'ethanol suivie d'hydrolyse acide donne l'acide {alpha}-aminoadipique {sup 14}C-6 avec un rendement global de 46 pour cent par rapport a Ba{sup 14}CO{sub 3}. (auteur)

  18. Absence of c-Aminobutyric Acid-A Receptor Potentiation in Central Hypersomnolence Disorders

    OpenAIRE

    Dauvilliers, Yves; Evangelista, Elisa; Lopez, Regis; Barateau, Lucie; Jaussent, Isabelle; Cens, Thierry; Rousset, Matthieu; Charnet, Pierre

    2016-01-01

    International audience; Objective: The pathophysiology of idiopathic hypersomnia (IH) remains unclear. Recently, cerebrospinal fluid (CSF)-induced enhancement of c-aminobutyric acid (GABA)-A receptor activity was found in patients with IH compared to controls. Methods: Fifteen unrelated patients (2 males and 13 females) affected with typical IH, 12 patients (9 males and 3 females) with narcolepsy type 1, and 15 controls (9 males and 6 females) with unspecified hypersomnolence (n 5 7) and misc...

  19. Gama-aminobutyric acid accumulation in Elsholtzia splendens in response to copper toxicity*

    OpenAIRE

    Yang, Xiao-e; Peng, Hong-yun; Tian, Sheng-ke

    2005-01-01

    A solution with different Cu supply levels was cultured to investigate gama-aminobutyric acid (GABA) accumulation in Elsholtzia splendens, a native Chinese Cu-tolerant and accumulating plant species. Increasing Cu from 0.25 to 500 μmol/L significantly enhanced levels of GABA and histidine (His), but considerably decreased levels of aspartate (Asp) and glutamate (Glu) in the leaves. The leaf Asp level negatively correlated with leaf Cu level, while leaf GABA level positively correlated with le...

  20. Highly Atom Economic Synthesis of d?2?Aminobutyric Acid through an In?Vitro Tri?enzymatic Catalytic System

    OpenAIRE

    Chen, Xi; Cui, Yunfeng; Cheng, Xinkuan; Feng, Jinhui; Wu, Qiaqing; Zhu, Dunming

    2017-01-01

    Abstract d?2?Aminobutyric acid is an unnatural amino acid serving as an important intermediate in pharmaceutical production. Developing a synthetic method that uses cheaper starting materials and produces less by?product is a pressing demand. A tri?enzymatic catalytic system, which is composed of l?threonine ammonia lyase (l?TAL), d?amino acid dehydrogenase (d?AADH), and formate dehydrogenase (FDH), has thus been developed for the synthesis of d?2?aminobutyric acid with high optical purity. I...

  1. Quantitative Autoradiography on [(35)S]TBPS Binding Sites of Gamma- Aminobutyric Acid(A) Receptors in Discrete Brain Regions of High- Alcohol-Drinking and Low-Alcohol- Drinking Rats Selectively Bred forHigh- and Low-Alcohol Preference.

    Science.gov (United States)

    Hwang, B.H.; Kunkler, P.E.; Lumeng, L.

    1997-01-01

    It has been documented that ethanol can potentiate brain gamma-aminobutyric acid (GABA)ergic function, and there is a close link between the GABA(A) receptor complex and effects of ethanol, including reinforcement of alcohol which is a fundamental element of alcohol preference. However, it is unknown in what discrete brain regions GABA(A) receptors might be associated with alcohol preference. In the present study, [(35)S]t-butylbicyclophosphorothionate ([(35)S]TBPS) was used to localize GABA(A) receptors in high-alcohol-drinking (HAD) rats and low-alcohol-drinking (LAD) rats which were selectively bred for high and low alcohol preference, respectively. Initial qualitative observations indicated that [(35)S]TBPS binding sites were abundant in many brain areas including the cerebral cortex, hypothalamus and amygdala of HAD and LAD rats. Furthermore, the quantitative autoradiographic analysis revealed fewer [(35)S]TBPS binding sites of GABA(A) receptors in the amygdaloid complex, central medial thalamic nucleus, lateral hypothalamic nucleus and anterior hypothalamic nucleus of HAD rats than LAD rats. Collectively, this study has indicated that HAD rats selectively bred for high alcohol preference possess lower [(35)S]TBPS binding in the brain. Since lower TBPS binding has been proposed to reflect enhanced GABAergic function, as evidenced in rats with seizure or under alcohol withdrawal, the results from the present study suggest that HAD rats might have an enhanced GABAergic function. It is thus likely that enhanced GABAergic function in the brain might be related to high alcohol preference which is characteristic in HAD rats. In addition, the present result showing no difference of [(35)S]TBPS binding in the nucleus accumbens is also in agreement with a notion that [(35)S]TBPS binding may represent only a small spectrum of the GABA(A) receptor complex which is constituted of a sophisticated subunit combination whose functional compositions are still unknown. In

  2. Design and mechanism of tetrahydrothiophene-based γ-aminobutyric acid aminotransferase inactivators.

    Science.gov (United States)

    Le, Hoang V; Hawker, Dustin D; Wu, Rui; Doud, Emma; Widom, Julia; Sanishvili, Ruslan; Liu, Dali; Kelleher, Neil L; Silverman, Richard B

    2015-04-08

    Low levels of γ-aminobutyric acid (GABA), one of two major neurotransmitters that regulate brain neuronal activity, are associated with many neurological disorders, such as epilepsy, Parkinson's disease, Alzheimer's disease, Huntington's disease, and cocaine addiction. One of the main methods to raise the GABA level in human brain is to use small molecules that cross the blood-brain barrier and inhibit the activity of γ-aminobutyric acid aminotransferase (GABA-AT), the enzyme that degrades GABA. We have designed a series of conformationally restricted tetrahydrothiophene-based GABA analogues with a properly positioned leaving group that could facilitate a ring-opening mechanism, leading to inactivation of GABA-AT. One compound in the series is 8 times more efficient an inactivator of GABA-AT than vigabatrin, the only FDA-approved inactivator of GABA-AT. Our mechanistic studies show that the compound inactivates GABA-AT by a new mechanism. The metabolite resulting from inactivation does not covalently bind to amino acid residues of GABA-AT but stays in the active site via H-bonding interactions with Arg-192, a π-π interaction with Phe-189, and a weak nonbonded S···O═C interaction with Glu-270, thereby inactivating the enzyme.

  3. Theoretical studies on the inactivation mechanism of γ-aminobutyric acid aminotransferase.

    Science.gov (United States)

    Durak, A T; Gökcan, H; Konuklar, F A S

    2011-07-21

    The inactivation mechanism of γ-aminobutyric acid aminotransferase (GABA-AT) in the presence of γ-vinyl-aminobutyric acid, an anti-epilepsy drug, has been studied by means of theoretical calculations. Density functional theory methods have been applied to compare the three experimentally proposed inactivation mechanisms (Silverman et al., J. Biol. Chem., 2004, 279, 363). All the calculations were performed at the B3LYP/6-31+G(d,p) level of theory. Single point solvent calculations were carried out in water, by means of an integral equation formalism-polarizable continuum model (IEFPCM) at the B3LYP/6-31+G(d,p) level of theory. The present calculations provide an insight into the mechanistic preferences of the inactivation reaction of GABA-AT. The results also allow us to elucidate the key factors behind the mechanistic preferences. The computations also confirm the importance of explicit water molecules around the reacting center in the proton transfer steps.

  4. The γ-aminobutyric acid type B (GABAB) receptor agonist baclofen inhibits morphine sensitization by decreasing the dopamine level in rat nucleus accumbens.

    Science.gov (United States)

    Fu, Zhenyu; Yang, Hongfa; Xiao, Yuqiang; Zhao, Gang; Huang, Haiyan

    2012-07-10

    Repeated morphine exposure can induce behavioral sensitization. There are evidences have shown that central gamma-aminobutyric acid (GABA) system is involved in morphine dependence. However, the effect of a GABAB receptor agonist baclofen on morphine-induced behavioral sensitization in rats is unclear. We used morphine-induced behavioral sensitization model in rat to investigate the effects of baclofen on behavioral sensitization. Moreover, dopamine release in the shell of the nucleus accumbens was evaluated using microdialysis assay in vivo. The present study demonstrated that morphine challenge (3 mg/kg, s.c.) obviously enhanced the locomotor activity following 4-day consecutive morphine administration and 3-day withdrawal period, which indicated the expression of morphine sensitization. In addition, chronic treatment with baclofen (2.5, 5 mg/kg) significantly inhibited the development of morphine sensitization. It was also found that morphine challenge 3 days after repeated morphine administration produced a significant increase of extracellular dopamine release in nucleus accumbens. Furthermore, chronic treatment with baclofen decreased the dopamine release induced by morphine challenge. Our results indicated that gamma-aminobutyric acid system plays an important role in the morphine sensitization in rat and suggested that behavioral sensitization is a promising model to study the mechanism underlying drug abuse.

  5. Detection of Glutamate and γ-aminobutyric Acid in Vitreous of Patients with Proliferative Diabetic Retinopathy

    Institute of Scientific and Technical Information of China (English)

    Juan Deng; De-Zheng Wu; Rulong Gao

    2000-01-01

    Purpose: To study the levels of glutamate and γ-aminobutyric acid (GABA) in vitreous of patients with proliferative diabetic retinopathy(PDR) and to investigate their roles in retinal ischemia.Method: Vitreous samples were collected from 25 patients (27 eyes) with PDR and 14patients ( 14 eyes) with idiopathic macular hole. Glutamate and GABA detection were performed by high-performance liquid chromatography (HPLC).Results: Patients with PDR had significantly higher concentrations of glutamate and GABA than the control group. The glutamate level has a significantly positive correlation with GABA level.Conclusion: Detection of glutamate and GABA in vitreous provides biochemical support for the mechanism and treatment of ischemic retinal damage in patients with PDR.

  6. Theoretical study of γ-aminobutyric acid conformers: Intramolecular interactions and ionization energies

    Science.gov (United States)

    Wang, Ke-Dong; Wang, Mei-Ting; Meng, Ju

    2014-10-01

    Allowing for all combinations of internal single-bond rotamers, 1,296 unique trial structures of γ-Aminobutyric acid (GABA) are obtained. All of these structures are optimized at the M06-2X level of theory and a total of 68 local minimal conformers are found. The nine low-lying conformers are used for further studies. According to the calculated relative Gibbs free energies at M06-2X level of theory, we find that the dispersion is important for the relative energy of GABA. The intramolecular hydrogen bonds and hyperconjugative interaction and their effects on the conformational stability are studied. The results show that both of them have great influence on the conformers. The vertical ionization energies (VIE) are calculated and match the experimental data well. The results show that the neutral GABA in the gas phase is a multi-conformer system and at least four conformations exist.

  7. Calming effect of orally administered γ-aminobutyric acid in Shih Tzu dogs.

    Science.gov (United States)

    Uetake, Katsuji; Okumoto, Ayano; Tani, Noriko; Goto, Akihiro; Tanaka, Toshio

    2012-12-01

    The calming effects of γ-aminobutyric acid (GABA) by oral administration were investigated in four adult Shih Tzu dogs. Three dosage levels (1, 2 and 4 mg/kg body weight) and non-administration were tested by an increase and decrease method. Changes in activity (for 1.5 h) and urinary cortisol levels (pre-administration, 3 and 7 h later) of dogs were monitored after administration. Without reference to dosage level, the mean times spent standing (P = 0.06), sitting (P level was observed at 7 h after administration (P GABA exerts calming effects on dogs as well as humans. © 2012 The Authors. Animal Science Journal © 2012 Japanese Society of Animal Science.

  8. Widespread abnormality of the γ-aminobutyric acid-ergic system in Tourette syndrome

    Science.gov (United States)

    Bagic, Anto; Simmons, Janine M.; Mari, Zoltan; Bonne, Omer; Xu, Ben; Kazuba, Diane; Herscovitch, Peter; Carson, Richard E.; Murphy, Dennis L.; Drevets, Wayne C.; Hallett, Mark

    2012-01-01

    Dysfunction of the γ-aminobutyric acid-ergic system in Tourette syndrome may conceivably underlie the symptoms of motor disinhibition presenting as tics and psychiatric manifestations, such as attention deficit hyperactivity disorder and obsessive–compulsive disorder. The purpose of this study was to identify a possible dysfunction of the γ-aminobutyric acid-ergic system in Tourette patients, especially involving the basal ganglia-thalamo-cortical circuits and the cerebellum. We studied 11 patients with Tourette syndrome and 11 healthy controls. Positron emission tomography procedure: after injection of 20 mCi of [11C]flumazenil, dynamic emission images of the brain were acquired. Structural magnetic resonance imaging scans were obtained to provide an anatomical framework for the positron emission tomography data analysis. Images of binding potential were created using the two-step version of the simplified reference tissue model. The binding potential images then were spatially normalized, smoothed and compared between groups using statistical parametric mapping. We found decreased binding of GABAA receptors in Tourette patients bilaterally in the ventral striatum, globus pallidus, thalamus, amygdala and right insula. In addition, the GABAA receptor binding was increased in the bilateral substantia nigra, left periaqueductal grey, right posterior cingulate cortex and bilateral cerebellum. These results are consistent with the longstanding hypothesis that circuits involving the basal ganglia and thalamus are disinhibited in Tourette syndrome patients. In addition, the abnormalities in GABAA receptor binding in the insula and cerebellum appear particularly noteworthy based upon recent evidence implicating these structures in the generation of tics. PMID:22577221

  9. Optimization of γ-aminobutyric acid production by Lactobacillus plantarum Taj-Apis362 from honeybees.

    Science.gov (United States)

    Tajabadi, Naser; Ebrahimpour, Afshin; Baradaran, Ali; Rahim, Raha Abdul; Mahyudin, Nor Ainy; Manap, Mohd Yazid Abdul; Bakar, Fatimah Abu; Saari, Nazamid

    2015-04-15

    Dominant strains of lactic acid bacteria (LAB) isolated from honey bees were evaluated for their γ-aminobutyric acid (GABA)-producing ability. Out of 24 strains, strain Taj-Apis362 showed the highest GABA-producing ability (1.76 mM) in MRS broth containing 50 mM initial glutamic acid cultured for 60 h. Effects of fermentation parameters, including initial glutamic acid level, culture temperature, initial pH and incubation time on GABA production were investigated via a single parameter optimization strategy. The optimal fermentation condition for GABA production was modeled using response surface methodology (RSM). The results showed that the culture temperature was the most significant factor for GABA production. The optimum conditions for maximum GABA production by Lactobacillus plantarum Taj-Apis362 were an initial glutamic acid concentration of 497.97 mM, culture temperature of 36 °C, initial pH of 5.31 and incubation time of 60 h, which produced 7.15 mM of GABA. The value is comparable with the predicted value of 7.21 mM.

  10. Optimization of γ-Aminobutyric Acid Production by Lactobacillus plantarum Taj-Apis362 from Honeybees

    Directory of Open Access Journals (Sweden)

    Naser Tajabadi

    2015-04-01

    Full Text Available Dominant strains of lactic acid bacteria (LAB isolated from honey bees were evaluated for their γ-aminobutyric acid (GABA-producing ability. Out of 24 strains, strain Taj-Apis362 showed the highest GABA-producing ability (1.76 mM in MRS broth containing 50 mM initial glutamic acid cultured for 60 h. Effects of fermentation parameters, including initial glutamic acid level, culture temperature, initial pH and incubation time on GABA production were investigated via a single parameter optimization strategy. The optimal fermentation condition for GABA production was modeled using response surface methodology (RSM. The results showed that the culture temperature was the most significant factor for GABA production. The optimum conditions for maximum GABA production by Lactobacillus plantarum Taj-Apis362 were an initial glutamic acid concentration of 497.97 mM, culture temperature of 36 °C, initial pH of 5.31 and incubation time of 60 h, which produced 7.15 mM of GABA. The value is comparable with the predicted value of 7.21 mM.

  11. Production of gaba (γ – Aminobutyric acid) by microorganisms: a review

    Science.gov (United States)

    Dhakal, Radhika; Bajpai, Vivek K.; Baek, Kwang-Hyun

    2012-01-01

    GABA (γ-aminobutyric acid) is a four carbon non-protein amino acid that is widely distributed in plants, animals and microorganisms. As a metabolic product of plants and microorganisms produced by the decarboxylation of glutamic acid, GABA functions as an inhibitory neurotransmitter in the brain that directly affects the personality and the stress management. A wide range of traditional foods produced by microbial fermentation contain GABA, in which GABA is safe and eco-friendly, and also has the possibility of providing new health-benefited products enriched with GABA. Synthesis of GABA is catalyzed by glutamate decarboxylase, therefore, the optimal fermentation condition is mainly based on the biochemical properties of the enzyme. Major GABA producing microorganisms are lactic acid bacteria (LAB), which make food spoilage pathogens unable to grow and act as probiotics in the gastrointestinal tract. The major factors affecting the production of GABA by microbial fermentation are temperature, pH, fermentation time and different media additives, therefore, these factors are summarized to provide the most up-dated information for effective GABA synthesis. There has been a huge accumulation of knowledge on GABA application for human health accompanying with a demand on natural GABA supply. Only the GABA production by microorganisms can fulfill the demand with GABA-enriched health beneficial foods. PMID:24031948

  12. Effects of γ-Aminobutyric acid transporter 1 inhibition by tiagabine on brain glutamate and γ-Aminobutyric acid metabolism in the anesthetized rat In vivo.

    Science.gov (United States)

    Patel, Anant B; de Graaf, Robin A; Rothman, Douglas L; Behar, Kevin L

    2015-07-01

    γ-Aminobutyric acid (GABA) clearance from the extracellular space after release from neurons involves reuptake into terminals and astrocytes through GABA transporters (GATs). The relative flows through these two pathways for GABA released from neurons remains unclear. This study determines the effect of tiagabine, a selective inhibitor of neuronal GAT-1, on the rates of glutamate (Glu) and GABA metabolism and GABA resynthesis via the GABA-glutamine (Gln) cycle. Halothane-anesthetized rats were administered tiagabine (30 mg/kg, i.p.) and 45 min later received an intravenous infusion of either [1,6-(13)C2]glucose (in vivo) or [2-(13)C]acetate (ex vivo). Nontreated rats served as controls. Metabolites and (13)C enrichments were measured with (1)H-[(13)C]-nuclear magnetic resonance spectroscopy and referenced to their corresponding endpoint values measured in extracts from in situ frozen brain. Metabolic flux estimates of GABAergic and glutamatergic neurons were determined by fitting a metabolic model to the (13)C turnover data measured in vivo during [1,6-(13)C2]glucose infusion. Tiagabine-treated rats were indistinguishable (P > 0.05) from controls in tissue amino acid levels and in (13)C enrichments from [2-(13)C]acetate. Tiagabine reduced average rates of glucose oxidation and neurotransmitter cycling in both glutamatergic neurons (↓18%, CMR(glc(ox)Glu): control, 0.27 ± 0.05 vs. tiagabine, 0.22 ± 0.04 µmol/g/min; ↓11%, V(cyc(Glu-Gln)): control 0.23 ± 0.05 vs. tiagabine 0.21 ± 0.04 µmol/g/min and GABAergic neurons (↓18-25%, CMR(glc(ox)GABA): control 0.09 ± 0.02 vs. tiagabine 0.07 ± 0.03 µmol/g/min; V(cyc(GABA-Gln)): control 0.08 ± 0.02 vs. tiagabine 0.07 ± 0.03 µmol/g/min), but the changes in glutamatergic and GABAergic fluxes were not significant (P > 0.10). The results suggest that any reduction in GABA metabolism by tiagabine might be an indirect response to reduced glutamatergic drive rather than direct compensatory effects. © 2015 Wiley

  13. Production of γ-aminobutyric acid by microorganisms from different food sources.

    Science.gov (United States)

    Hudec, Jozef; Kobida, Ľubomír; Čanigová, Margita; Lacko-Bartošová, Magdaléna; Ložek, Otto; Chlebo, Peter; Mrázová, Jana; Ducsay, Ladislav; Bystrická, Judita

    2015-04-01

    γ-Aminobutyric acid (GABA) is a potentially bioactive component of foods and pharmaceuticals. The aim of this study was screen lactic acid bacteria belonging to the Czech Collection of Microorganisms, and microorganisms (yeast and bacteria) from 10 different food sources for GABA production by fermentation in broth or plant and animal products. Under an aerobic atmosphere, very low selectivity of GABA production (from 0.8% to 1.3%) was obtained using yeast and filamentous fungi, while higher selectivity (from 6.5% to 21.0%) was obtained with bacteria. The use of anaerobic conditions, combined with the addition of coenzyme (pyridoxal-5-phosphate) and salts (CaCl2 , NaCl), led to the detection of a low concentration of GABA precursor. Simultaneously, using an optimal temperature of 33 °C, a pH of 6.5 and bacteria from banana (Pseudomonadaceae and Enterobacteriaceae families), surprisingly, a high selectivity of GABA was obtained. A positive impact of fenugreek sprouts on the proteolytic process and GABA production from plant material as a source of GABA precursor was identified. Lactic acid bacteria for the production of new plant and animal GABA-rich products from different natural sources containing GABA precursor can be used. © 2014 Society of Chemical Industry.

  14. Effect of ethanol on γ-aminobutyric acid in the brain

    International Nuclear Information System (INIS)

    Lassanova, M.; Tursky, T.; Homerova, D.

    1989-01-01

    The effect of acute and chronic ethanol administration on the level of γ-aminobutyric acid (GABA), glutamate, aspartate, and glutamine was investigated using 14 C-labelled compounds. The level of GABA rose after both acute and chronic ethanol administration. In chronic experiments also the levels of glutamate, aspartate and glutamine were increased. In acute experiments the incorporation from glucose into the studied amino acids (neuronal compartment) increased, while in chronic experiments a decreasing trend was observed. In the glial compartment the incorporation increased only into glutamate and glutamine in acute experiments, while in chronic experiments a decreased incorporation into glutamine was recorded. The activities of three enzymes were studied in seven parts of the brain after acute ethanol administration. The activity of glutamic acid decarboxylase increased in the hypothalamus and brain cortex and decreased in the medulla oblongata. The activity of GABA transaminase did not change and the activity of glutamine synthetase decreased only in the hippocampus. In accordance with several other studies, the presented results show that ethanol interferes with the GABA system in the brain. It is suggested that the primary effect of ethanol is exerted on the cell membranes with preference for the regions connected with the GABA system. (author). 3 figs., 6 tabs., 18 refs

  15. An autocrine γ-aminobutyric acid signaling system exists in pancreatic β-cell progenitors of fetal and postnatal mice.

    Science.gov (United States)

    Feng, Mary M; Xiang, Yun-Yan; Wang, Shuanglian; Lu, Wei-Yang

    2013-01-01

    Gamma-aminobutyric acid (GABA) is produced and secreted by adult pancreatic β-cells, which also express GABA receptors mediating autocrine signaling and regulating β-cell proliferation. However, whether the autocrine GABA signaling involves in β-cell progenitor development or maturation remains uncertain. By means of immunohistochemistry we analyzed the expression profiles of the GABA synthesizing enzyme glutamic acid decarboxylase (GAD) and the α1-subunit of type-A GABA receptor (GABAARα1) in the pancreas of mice at embryonic day 15.5 (E15.5), E18.5, postnatal day 1 (P1) and P7. Our data showed that at E15.5 the pancreatic and duodenum homeobox-1 (Pdx1) was expressed in the majority of cells in the developing pancreata. Notably, insulin immunoreactivity was identified in a subpopulation of pancreatic cells with a high level of Pdx1 expression. About 80% of the high-level Pdx-1 expressing cells in the pancreas expressed GAD and GABAARα1 at all pancreatic developmental stages. In contrast, only about 30% of the high-level Pdx-1 expressing cells in the E15.5 pancreas expressed insulin; i.e., a large number of GAD/GABAARα1-expressing cells did not express insulin at this early developmental stage. The expression level of GAD and GABAARα1 increased steadily, and progressively more GAD/GABAARα1-expressing cells expressed insulin in the course of pancreatic development. These results suggest that 1) GABA signaling proteins appear in β-cell progenitors prior to insulin expression; and 2) the increased expression of GABA signaling proteins may be involved in β-cell progenitor maturation.

  16. Evaluation of improved γ-aminobutyric acid production in yogurt using Lactobacillus plantarum NDC75017.

    Science.gov (United States)

    Shan, Y; Man, C X; Han, X; Li, L; Guo, Y; Deng, Y; Li, T; Zhang, L W; Jiang, Y J

    2015-04-01

    Most γ-aminobutyric acid (GABA)-producing microorganisms are lactic acid bacteria (LAB), but the yield of GABA is limited in most of these GABA-producing strains. In this study, the production of GABA was carried out by using Lactobacillus plantarum NDC75017, a strain screened from traditional fermented dairy products in China. Concentrations of substrate (l-monosodium glutamate, L-MSG) and coenzyme (pyridoxal-5-phosphate, PLP) of glutamate decarboxylase (GAD) and culture temperature were investigated to evaluate their effects on GABA yield of Lb. plantarum NDC75017. The results indicated that GABA production was related to GAD activity and biomass of Lb. plantarum NDC75017. Response surface methodology was used to optimize conditions of GABA production. The optimal factors for GABA production were L-MSG at 80 mM, PLP at 18 μM, and a culture temperature of 36 °C. Under these conditions, production of GABA was maximized at 314.56 mg/100 g. Addition of Lb. plantarum NDC75017 to a commercial starter culture led to higher GABA production in fermented yogurt. Flavor and texture of the prepared yogurt and the control yogurt did not differ significantly. Thus, Lb. plantarum NDC75017 has good potential for manufacture of GABA-enriched fermented milk products. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  17. γ-Aminobutyric acid (GABA) concentration inversely correlates with basal perfusion in human occipital lobe.

    Science.gov (United States)

    Donahue, Manus J; Rane, Swati; Hussey, Erin; Mason, Emily; Pradhan, Subechhya; Waddell, Kevin W; Ally, Brandon A

    2014-03-01

    Commonly used neuroimaging approaches in humans exploit hemodynamic or metabolic indicators of brain function. However, fundamental gaps remain in our ability to relate such hemo-metabolic reactivity to neurotransmission, with recent reports providing paradoxical information regarding the relationship among basal perfusion, functional imaging contrast, and neurotransmission in awake humans. Here, sequential magnetic resonance spectroscopy (MRS) measurements of the primary inhibitory neurotransmitter, γ-aminobutyric acid (GABA+macromolecules normalized by the complex N-acetyl aspartate-N-acetyl aspartyl glutamic acid: [GABA(+)]/[NAA-NAAG]), and magnetic resonance imaging (MRI) measurements of perfusion, fractional gray-matter volume, and arterial arrival time (AAT) are recorded in human visual cortex from a controlled cohort of young adult male volunteers with neurocognitive battery-confirmed comparable cognitive capacity (3 T; n=16; age=23±3 years). Regression analyses reveal an inverse correlation between [GABA(+)]/[NAA-NAAG] and perfusion (R=-0.46; P=0.037), yet no relationship between AAT and [GABA(+)]/[NAA-NAAG] (R=-0.12; P=0.33). Perfusion measurements that do not control for AAT variations reveal reduced correlations between [GABA(+)]/[NAA-NAAG] and perfusion (R=-0.13; P=0.32). These findings largely reconcile contradictory reports between perfusion and inhibitory tone, and underscore the physiologic origins of the growing literature relating functional imaging signals, hemodynamics, and neurotransmission.

  18. Subchronic toxicity evaluation of γ-aminobutyric acid (GABA) in rats.

    Science.gov (United States)

    Takeshima, Kazuhito; Yamatsu, Atsushi; Yamashita, Yusuke; Watabe, Kazuya; Horie, Noriko; Masuda, Kazuyuki; Kim, Mujo

    2014-06-01

    γ-Aminobutyric acid (GABA) is an amino acid compound contained in vegetables such as tomatoes and also widely distributed in mammals. GABA acts as an inhibitory neurotransmitter and promotes parasympathetic activity to provide several beneficial effects, for instance, relaxation, anti-stress, and insomnia. GABA, produced via a fermentation process, has been available as a functional food ingredient. As part of a program to assess its safety, GABA was administered by oral gavage at doses of 500, 1250, and 2500mg/kg body weight to groups of 10 male and 10 female Sprague-Dawley rats for 13weeks. Treatment was not associated with the test substance-related mortality and appeared to be well tolerated. There were no toxicologically and statistically significant changes in urinalysis, hematology, clinical chemistry parameters, and in necropsy findings. A few statistically significant changes in food consumption and body weights were noted in the male groups while any significant changes were not noted in female groups. There was no effect of treatment on organ weights or on the results of the histopathological examinations. The results of toxicity evaluation support the safety use of GABA and the potential use as a functional food ingredient. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. γ-Aminobutyric acid ameliorates fluoride-induced hypothyroidism in male Kunming mice.

    Science.gov (United States)

    Yang, Haoyue; Xing, Ronge; Liu, Song; Yu, Huahua; Li, Pengcheng

    2016-02-01

    This study evaluated the protective effects of γ-aminobutyric acid (GABA), a non-protein amino acid and anti-oxidant, against fluoride-induced hypothyroidism in mice. Light microscope sample preparation technique and TEM sample preparation technique were used to assay thyroid microstructure and ultrastructure; enzyme immunoassay method was used to assay hormone and protein levels; immunohistochemical staining method was used to assay apoptosis of thyroid follicular epithelium cells. Subacute injection of sodium fluoride (NaF) decreased blood T4, T3 and thyroid hormone-binding globulin (TBG) levels to 33.98 μg/l, 3 2.8 ng/ml and 11.67 ng/ml, respectively. In addition, fluoride intoxication induced structural abnormalities in thyroid follicles. Our results showed that treatment of fluoride-exposed mice with GABA appreciably decreased metabolic toxicity induced by fluoride and restored the microstructural and ultrastructural organisation of the thyroid gland towards normalcy. Compared with the negative control group, GABA treatment groups showed significantly upregulated T4, T3 and TBG levels (42.34 μg/l, 6.54 ng/ml and 18.78 ng/ml, respectively; Plevel and apoptosis inhibition in thyroid follicular epithelial cells. To the best of our knowledge, this is the first study to establish the therapeutic efficacy of GABA as a natural antioxidant in inducing thyroprotection against fluoride-induced toxicity. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. The effect of amino acid backbone length on molecular packing: crystalline tartrates of glycine, β-alanine, γ-aminobutyric acid (GABA) and DL-α-aminobutyric acid (AABA).

    Science.gov (United States)

    Losev, Evgeniy; Boldyreva, Elena

    2018-02-01

    We report a novel 1:1 cocrystal of β-alanine with DL-tartaric acid, C 3 H 7 NO 2 ·C 4 H 6 O 6 , (II), and three new molecular salts of DL-tartaric acid with β-alanine {3-azaniumylpropanoic acid-3-azaniumylpropanoate DL-tartaric acid-DL-tartrate, [H(C 3 H 7 NO 2 ) 2 ] + ·[H(C 4 H 5 O 6 ) 2 ] - , (III)}, γ-aminobutyric acid [3-carboxypropanaminium DL-tartrate, C 4 H 10 NO 2 + ·C 4 H 5 O 6 - , (IV)] and DL-α-aminobutyric acid {DL-2-azaniumylbutanoic acid-DL-2-azaniumylbutanoate DL-tartaric acid-DL-tartrate, [H(C 4 H 9 NO 2 ) 2 ] + ·[H(C 4 H 5 O 6 ) 2 ] - , (V)}. The crystal structures of binary crystals of DL-tartaric acid with glycine, (I), β-alanine, (II) and (III), GABA, (IV), and DL-AABA, (V), have similar molecular packing and crystallographic motifs. The shortest amino acid (i.e. glycine) forms a cocrystal, (I), with DL-tartaric acid, whereas the larger amino acids form molecular salts, viz. (IV) and (V). β-Alanine is the only amino acid capable of forming both a cocrystal [i.e. (II)] and a molecular salt [i.e. (III)] with DL-tartaric acid. The cocrystals of glycine and β-alanine with DL-tartaric acid, i.e. (I) and (II), respectively, contain chains of amino acid zwitterions, similar to the structure of pure glycine. In the structures of the molecular salts of amino acids, the amino acid cations form isolated dimers [of β-alanine in (III), GABA in (IV) and DL-AABA in (V)], which are linked by strong O-H...O hydrogen bonds. Moreover, the three crystal structures comprise different types of dimeric cations, i.e. (A...A) + in (III) and (V), and A + ...A + in (IV). Molecular salts (IV) and (V) are the first examples of molecular salts of GABA and DL-AABA that contain dimers of amino acid cations. The geometry of each investigated amino acid (except DL-AABA) correlates with the melting point of its mixed crystal.

  1. cAMP and forskolin decrease γ-aminobutyric acid-gated chloride flux in rat brain synaptoneurosomes

    International Nuclear Information System (INIS)

    Heuschneider, G.; Schwartz, R.D.

    1989-01-01

    The effects of the cyclic nucleotide cAMP on γ-aminobutyric acid-gated chloride channel function were investigated. The membrane-permeant cAMP analog N 6 , O 2' -dibutyryladenosine 3',5'-cyclic monophosphate inhibited muscimol-induced 36 Cl - uptake into rat cerebral cortical synaptoneurosomes in a concentration-dependent manner. The inhibition was due to a decrease in the maximal effect of muscimol, with no change in potency. Similar effects were observed with 8-(4-chlorophenylthio)adenosine 3',5'-cyclic monophosphate, 8-bromoadenosine 3',5'-cyclic monophosphate, and the phosphodiesterase inhibitor isobutylmethylxanthine. The effect of endogenous cAMP accumulation on the γ-aminobutyric acid-gated Cl - channel was studied with forskolin, an activator of adenylate cyclase. Under identical conditions, in the intact synaptoneurosomes, forskolin inhibited muscimol-induced 36 Cl - uptake and generated cAMP with similar potencies. Surprisingly, 1,9-dideoxyforskolin, which does not activate adenylate cyclase, also inhibited the muscimol response, suggesting that forskolin and its lipophilic derivatives may interact with the Cl - channel directly. The data suggest that γ-aminobutyric acid (GABA A ) receptor function in brain can be regulated by cAMP-dependent phosphorylation

  2. Inactivation of γ-aminobutyric acid aminotransferase by γ-ethynyl- and γ-vinyl GABA

    International Nuclear Information System (INIS)

    Silverman, R.B.; Burke, J.R.; Nanavati, S.M.

    1989-01-01

    γ-Ethynyl- and γ-vinyl GABA (vigabatrin) are anticonvulsant agents that have been shown to be mechanism-based inactivators of γ-aminobutyric acid aminotransferase (GABA-T). The inactivation mechanisms of these compounds have been investigated. Inactivation of GABA-T by [ 3 H]γ-ethynyl GABA led to the incorporation of 1.0 equiv of 3 H into the enzyme which is not released by enzyme denaturation. Inactivation by γ-ethynyl GABA of GABA-T reconstituted with [ 3 H]PLP followed by denaturation resulted in release of 3 H as PLP. Eight different possible adducts are consistent with that result. Experiments have been carried out to differentiate these possibilities. Similar studies have been carried out with γ-vinyl GABA. Inactivation by [ 14 C]γ-vinyl GABA resulted in the incorporation of 1.0 equiv of 14 C per active site. Unlike the case with γ-ethynyl GABA, γ-vinyl GABA inactivation of GABA-T reconstituted with [ 3 H]PLP followed by denaturation resulted in release of 3 H as PMP

  3. Identification of ɤ-Aminobutyric Acid (GABA in Loloh as A Potential Drink as Antihipertension

    Directory of Open Access Journals (Sweden)

    I Gusti Ayu Wita Kusumawati

    2018-04-01

    Full Text Available Loloh sembung (Blumea balsamifera is a functional drink that is widely consumed by Balinesse people and exhibit health-promoting effect. The purpose of this study was to identify GABA of loloh sembung which has physiological effect as antihypertensive. Proximate analysis was performed to determine nutritional value content of loloh sembung. Atomic Absorption Spectrophotometric (AAS method was employed to determine potassium and sodium content, and identificatio of ɤ-aminobutyric acid (GABA using Thin Layer Chromatography (TLC method. In this study, water content of loloh sembung was 99.2324%, ash 0.0117. Fresh sembung leaves have water content 83.8112%, ash content 2.0617%, protein 0.9659%, fat 2.850%, and carbohydrate 10.3109%. Loloh sembung contained sodium, 51.65 mg/L and potassium 1353.10 mg/L. Subsequently, fresh sembung leaves contained sodium 579.72 mg/L and pottasium 1353.19 mg/L respectively. In this study, GABA was detected in loloh sembung and has promising prospect as antihypertensive-functional drink.

  4. Effects of Aeration Treatment on γ-Aminobutyric Acid Accumulation in Germinated Tartary Buckwheat (Fagopyrum tataricum

    Directory of Open Access Journals (Sweden)

    Yuanxin Guo

    2016-01-01

    Full Text Available To explore the optimum condition of γ-aminobutyric acid (GABA accumulation in germinated tartary buckwheat, effects of some factors including aeration treatment, physiological indexes, air flow rate, culture temperature, and pH value of cultivating solution under hypoxia on GABA in germinated tartary buckwheat were investigated. The results showed that the dark cultures with distilled water at 30°C, 2 days, and aeration stress with 1.0 L/min air flow rate at 30°C were optimal for GABA accumulation. Under these conditions, the predicted content of GABA was up to 371.98 μg/g DW. The analysis of correlation indicated that there was a significant correlation (P<0.01 between GABA accumulation and physiological indexes. Box-Behnken experimental analysis revealed that optimal conditions with aeration treatment for GABA accumulation in germinated tartary buckwheat were air flow rate of 1.04 L/min, culture temperature of 31.25°C, and a pH value of 4.21. Under these conditions, the GABA content was predicted as high as 386.20 μg/g DW, which was close to the measured value (379.00±9.30 μg/g DW. The variance analysis and validation test suggested that this established regression model could predict GABA accumulation in tartary buckwheat during germination.

  5. Screening and mutagenesis of lactobacillus brevis for biosynthesis of γ-aminobutyric acid

    International Nuclear Information System (INIS)

    Xia Jiang; Mei Lehe; Huang Jun

    2006-01-01

    γ-aminobutyric acid (GABA) is a major inhibitory neurotransmitter in the central nervous system. In this study, a GABA-producing strain, hjxj-01, was isolated from the milk samples and identified as Lactobacillus brevis. In this GYP medium containing sodium glutamate, the highest GABA concentration accumulated by Lactobacillus brevis hjxj-01 is 7 g/L. The strain was treated with UV and 60 Co γ-rays. Based on high positive mutation rate, the final mutagenesis conditions were UV light 30 W, irradiation distance 45 cm, irradiation time 50 s, and 60 Co γ-rays irradiation of 500 Gy. The mutant strain, hjxj-08119, was bred by GABA resistance selection. Cultured for 12 generations continually, the GABA-producing capacity of hjxj-08119 maintained stably. The fermentation results indicate that compared with the origin strain hjxj-01, the average yield of GABA by hjij-08119 is 17 g/L, which is 142.9% of the origin strain. (authors)

  6. Utilization of barley or wheat bran to bioconvert glutamate to γ-aminobutyric acid (GABA).

    Science.gov (United States)

    Jin, Wen-Jie; Kim, Min-Ju; Kim, Keun-Sung

    2013-09-01

    This study deals with the utilization of agro-industrial wastes created by barley and wheat bran in the production of a value-added product, γ-aminobutyric acid (GABA). The simple and eco-friendly reaction requires no pretreatment or microbial fermentation steps but uses barley or wheat bran as an enzyme source, glutamate as a substrate, and pyridoxal 5'-phosphate (PLP) as a cofactor. The optimal reaction conditions were determined on the basis of the temperatures and times used for the decarboxylation reactions and the initial concentrations of barley or wheat bran, glutamate, and PLP. The optimal reactions produced 9.2 mM of GABA from 10 mM glutamate, yielding a 92% GABA conversion rate, when barley bran was used and 6.0 mM of GABA from 10 mM glutamate, yielding a 60% GABA conversion rate, when wheat bran was used. The results imply that barley bran is more efficient than wheat bran in the production of GABA. © 2013 Institute of Food Technologists®

  7. Separation and purification of γ-aminobutyric acid from fermentation broth by flocculation and chromatographic methodologies.

    Science.gov (United States)

    Gao, Qiang; Duan, Qiang; Wang, Depei; Zhang, Yunze; Zheng, Chunyang

    2013-02-27

    To date, the multifunctional γ-aminobutyric acid (GABA) is mainly produced by microbial fermentation in industry. The purpose of this study was to find an effective method for separation and purification of 31.2 g/L initial GABA from the fermentation broth of Enterococcus raffinosus TCCC11660. To remove the impurities from fermentation broth, flocculation pretreatment using chitosan and sodium alginate was first implemented to facilitate subsequent filtration. Ultrafiltration followed two discontinuous diafiltration steps to effectively remove proteins and macromolecular pigments, and the resulting permeate was further decolored by DA201-CII resin at a high decoloration ratio and GABA recovery. Subsequently, ion exchange chromatography (IEC) with Amberlite 200C resin and gradient elution were applied for GABA separation from glutamate and arginine. Finally, GABA crystals of 99.1% purity were prepared via warm ethanol precipitation twice. Overall, our results reveal that the successive process including flocculation, filtration, ultrafiltration, decoloration, IEC, and crystallization is promising for scale-up GABA extraction from fermentation broth.

  8. Induced resistance against the Asian citrus psyllid, Diaphorina citri, by β-aminobutyric acid in citrus.

    Science.gov (United States)

    Tiwari, Siddharth; Meyer, Wendy L; Stelinski, Lukasz L

    2013-10-01

    β-Aminobutyric acid (BABA) is known to induce resistance to microbial pathogens, nematodes and insects in several host plant/pest systems. The present study was undertaken to determine whether a similar effect of BABA occurred against the Asian citrus psyllid, Diaphorina citri Kuwayama, in citrus. A 25 mM drench application of BABA significantly reduced the number of eggs/plant as compared with a water control, whereas 200 and 100 mM applications of BABA reduced the numbers of nymphs/plant and adults/plants, respectively. A 5 mM foliar application of BABA significantly reduced the number of adults but not eggs or nymphs when compared with a water control treatment. In addition, leaf-dip bioassays using various concentrations (25–500 mM) of BABA indicated no direct toxic effect on 2nd and 5th instar nymphs or adult D. citri. BABA-treated plants were characterized by significantly lower levels of iron, magnesium, phosphorus, sodium, sulfur and zinc as compared with control plants. The expression level of the PR-2 gene (β-1,3-glucanase) in BABA-treated plants that were also damaged by D. citri adult feeding was significantly higher than in plants exposed to BABA, D. citri feeding alone or control plants. Our results indicate the potential for using BABA as a systemic acquired resistance management tool for D. citri.

  9. γ-Aminobutyric acid inhibits the proliferation and increases oxaliplatin sensitivity in human colon cancer cells.

    Science.gov (United States)

    Song, Lihua; Du, Aiying; Xiong, Ying; Jiang, Jing; Zhang, Yao; Tian, Zhaofeng; Yan, Hongli

    2016-11-01

    γ-Aminobutyric acid (GABA) is a natural non-protein amino acid, which broadly exists in many plant parts and is widely used as an ingredient in the food industry. In mammals, it is widely distributed in central nervous system and non-neural tissues. In addition to a primary inhibitory neurotransmitter in the central nervous system, endogenous GABA content has been found to be elevated in neoplastic tissues in colon cancer. However, the effect of extraneous GABA on colon cancer has rarely been reported. In this study, we found the inhibitory effects of GABA on the proliferation of colon cancer cells (CCCs). The amino acid also suppressed metastasis of SW480 and SW620 cells. To further study the correlated mechanism, we analyzed the changes in cell cycle distribution and found that GABA suppressed cell cycle progression through G2/M or G1/S phase. Furthermore, RNA sequencing analysis revealed GABA-induced changes in the mRNA expression of 30 genes, including EGR1, MAPK4, NR4A1, Fos, and FosB, in all the three types of CCC. Importantly, GABA enhanced the anti-tumor efficacy of oxaliplatin (OXA) in subcutaneous xenograft tumor model in nude mice. The data suggest that GABA inhibits colon cancer cell proliferation perhaps by attenuating EGR1-NR4A1 axis, EGR1-Fos axis, and by disrupting MEK-EGR1 signaling pathway. This work reveals the pharmacological value of GABA derived from food and suggests that exogenous GABA might play an auxiliary role in polychemotherapy of colon cancer.

  10. Evaluation of commercial soy sauce koji strains of Aspergillus oryzae for γ-aminobutyric acid (GABA) production.

    Science.gov (United States)

    Ab Kadir, Safuan; Wan-Mohtar, Wan Abd Al Qadr Imad; Mohammad, Rosfarizan; Abdul Halim Lim, Sarina; Sabo Mohammed, Abdulkarim; Saari, Nazamid

    2016-10-01

    In this study, four selected commercial strains of Aspergillus oryzae were collected from soy sauce koji. These A. oryzae strains designated as NSK, NSZ, NSJ and NST shared similar morphological characteristics with the reference strain (A. oryzae FRR 1675) which confirmed them as A. oryzae species. They were further evaluated for their ability to produce γ-aminobutyric acid (GABA) by cultivating the spore suspension in a broth medium containing 0.4 % (w/v) of glutamic acid as a substrate for GABA production. The results showed that these strains were capable of producing GABA; however, the concentrations differed significantly (P sauce production.

  11. High γ-aminobutyric acid production from lactic acid bacteria: Emphasis on Lactobacillus brevis as a functional dairy starter.

    Science.gov (United States)

    Wu, Qinglong; Shah, Nagendra P

    2017-11-22

    γ-Aminobutyric acid (GABA) and GABA-rich foods have shown anti-hypertensive and anti-depressant activities as the major functions in humans and animals. Hence, high GABA-producing lactic acid bacteria (LAB) could be used as functional starters for manufacturing novel fermented dairy foods. Glutamic acid decarboxylases (GADs) from LAB are highly conserved at the species level based on the phylogenetic tree of GADs from LAB. Moreover, two functionally distinct GADs and one intact gad operon were observed in all the completely sequenced Lactobacillus brevis strains suggesting its common capability to synthesize GABA. Difficulties and strategies for the manufacture of GABA-rich fermented dairy foods have been discussed and proposed, respectively. In addition, a genetic survey on the sequenced LAB strains demonstrated the absence of cell envelope proteinases in the majority of LAB including Lb. brevis, which diminishes their cell viabilities in milk environments due to their non-proteolytic nature. Thus, several strategies have been proposed to overcome the non-proteolytic nature of Lb. brevis in order to produce GABA-rich dairy foods.

  12. β-aminobutyric acid mediated drought stress alleviation in maize (Zea mays L.).

    Science.gov (United States)

    Shaw, Arun K; Bhardwaj, Pardeep K; Ghosh, Supriya; Roy, Sankhajit; Saha, Suman; Sherpa, Ang R; Saha, Samir K; Hossain, Zahed

    2016-02-01

    The present study highlights the role of β-aminobutyric acid (BABA) in alleviating drought stress effects in maize (Zea mays L.). Chemical priming was imposed by pretreating 1-week-old plants with 600 μM BABA prior to applying drought stress. Specific activities of key antioxidant enzymes and metabolites (ascorbate and glutathione) levels of ascorbate-glutathione cycle were studied to unravel the priming-induced modulation of plant defense system. Furthermore, changes in endogenous ABA and JA concentrations as well as mRNA expressions of key genes involved in their respective biosynthesis pathways were monitored in BABA-primed (BABA+) and non-primed (BABA-) leaves of drought-challenged plants to better understand the mechanistic insights into the BABA-induced hormonal regulation of plant response to water-deficit stress. Accelerated stomatal closure, high relative water content, and less membrane damage were observed in BABA-primed leaves under water-deficit condition. Elevated APX and SOD activity in non-primed leaves found to be insufficient to scavenge all H2O2 and O2 (·-) resulting in oxidative burst as evident after histochemical staining with NBT and DAB. A higher proline accumulation in non-primed leaves also does not give much protection against drought stress. Increased GR activity supported with the enhanced mRNA and protein expressions might help the BABA-primed plants to maintain a high GSH pool essential for sustaining balanced redox status to counter drought-induced oxidative stress damages. Hormonal analysis suggests that in maize, BABA-potentiated drought tolerance is primarily mediated through JA-dependent pathway by the activation of antioxidant defense systems while ABA biosynthesis pathway also plays an important role in fine-tuning of drought stress response.

  13. MS transport assays for γ-aminobutyric acid transporters--an efficient alternative for radiometric assays.

    Science.gov (United States)

    Schmitt, Sebastian; Höfner, Georg; Wanner, Klaus T

    2014-08-05

    Transport assays for neurotransmitters based on radiolabeled substrates are widely spread and often indispensable in basic research and the drug development process, although the use of radioisotopes is inherently coupled to issues concerning radioactive waste and safety precautions. To overcome these disadvantages, we developed mass spectrometry (MS)-based transport assays for γ-aminobutyric acid (GABA), which is the major inhibitory neurotransmitter in the central nervous system (CNS). These "MS Transport Assays" provide all capabilities of [(3)H]GABA transport assays and therefore represent the first substitute for the latter. The performance of our approach is demonstrated for GAT1, the most important GABA transporter (GAT) subtype. As GABA is endogenously present in COS-7 cells employed as hGAT1 expression system, ((2)H6)GABA was used as a substrate to differentiate transported from endogenous GABA. To record transported ((2)H6)GABA, a highly sensitive, short, robust, and reliable HILIC-ESI-MS/MS quantification method using ((2)H2)GABA as an internal standard was developed and validated according to the Center for Drug Evaluation and Research (CDER) guidelines. Based on this LC-MS quantification, a setup to characterize hGAT1 mediated ((2)H6)GABA transport in a 96-well format was established, that enables automated processing and avoids any sample preparation. The K(m) value for ((2)H6)GABA determined for hGAT1 is in excellent agreement with results obtained from [(3)H]GABA uptake assays. In addition, the established assay format enables efficient determination of the inhibitory potency of GAT1 inhibitors, is capable of identifying those inhibitors transported as substrates, and furthermore allows characterization of efflux. The approach described here combines the strengths of LC-MS/MS with the high efficiency of transport assays based on radiolabeled substrates and is applicable to all GABA transporter subtypes.

  14. γ-Aminobutyric Acid Type B (GABAB) Receptor Internalization Is Regulated by the R2 Subunit*

    Science.gov (United States)

    Hannan, Saad; Wilkins, Megan E.; Dehghani-Tafti, Ebrahim; Thomas, Philip; Baddeley, Stuart M.; Smart, Trevor G.

    2011-01-01

    γ-Aminobutyric acid type B (GABAB) receptors are important for slow synaptic inhibition in the CNS. The efficacy of inhibition is directly related to the stability of cell surface receptors. For GABAB receptors, heterodimerization between R1 and R2 subunits is critical for cell surface expression and signaling, but how this determines the rate and extent of receptor internalization is unknown. Here, we insert a high affinity α-bungarotoxin binding site into the N terminus of the R2 subunit and reveal its dominant role in regulating the internalization of GABAB receptors in live cells. To simultaneously study R1a and R2 trafficking, a new α-bungarotoxin binding site-labeling technique was used, allowing α-bungarotoxin conjugated to different fluorophores to selectively label R1a and R2 subunits. This approach demonstrated that R1a and R2 are internalized as dimers. In heterologous expression systems and neurons, the rates and extents of internalization for R1aR2 heteromers and R2 homomers are similar, suggesting a regulatory role for R2 in determining cell surface receptor stability. The fast internalization rate of R1a, which has been engineered to exit the endoplasmic reticulum, was slowed to that of R2 by truncating the R1a C-terminal tail or by removing a dileucine motif in its coiled-coil domain. Slowing the rate of internalization by co-assembly with R2 represents a novel role for GPCR heterodimerization whereby R2 subunits, via their C terminus coiled-coil domain, mask a dileucine motif on R1a subunits to determine the surface stability of the GABAB receptor. PMID:21724853

  15. Relationship among Glutamine, γ-Aminobutyric Acid, and Social Cognition in Autism Spectrum Disorders

    Science.gov (United States)

    Sikoglu, Elif M.; Hodge, Steven M.; Edden, Richard A.E.; Foley, Ann; Kennedy, David N.; Moore, Constance M.; Frazier, Jean A.

    2015-01-01

    Abstract Objective: An imbalance of excitatory and inhibitory neurotransmission in autism spectrum disorder (ASD) has been proposed. We compared glutamate (Glu), glutamine (Gln), and γ-aminobutyric acid (GABA) levels in the anterior cingulate cortex (ACC) of 13 males with ASD and 14 typically developing (TD) males (ages 13–17), and correlated these levels with intelligence quotient (IQ) and measures of social cognition. Methods: Social cognition was evaluated by administration of the Social Responsiveness Scale (SRS) and the Reading the Mind in the Eyes Test (RMET). We acquired proton magnetic resonance spectroscopy (1H-MRS) data from the bilateral ACC using the single voxel point resolved spectroscopy sequence (PRESS) to quantify Glu and Gln, and Mescher–Garwood point-resolved spectroscopy sequence (MEGA-PRESS) to quantify GABA levels referenced to creatine (Cr). Results: There were higher Gln levels (p=0.04), and lower GABA/Cre levels (p=0.09) in the ASD group than in the TD group. There was no difference in Glu levels between groups. Gln was negatively correlated with RMET score (rho=−0.62, p=0.001) and IQ (rho=−0.56, p=0.003), and positively correlated with SRS scores (rho=0.53, p=0.007). GABA/Cre levels were positively correlated with RMET score (rho=0.34, p=0.09) and IQ (rho=0.36, p=0.07), and negatively correlated with SRS score (rho=−0.34, p=0.09). Conclusions: These data suggest an imbalance between glutamatergic neurotransmission and GABA-ergic neurotransmission in ASD. Higher Gln levels and lower GABA/Cre levels were associated with lower IQ and greater impairments in social cognition across groups. PMID:25919578

  16. Conformational preferences of γ-aminobutyric acid in the gas phase and in water

    Science.gov (United States)

    Song, Il Keun; Kang, Young Kee

    2012-09-01

    The conformational study of γ-aminobutyric acid (GABA) has been carried out at the M06-2X/cc-pVTZ level of theory in the gas phase and the SMD M06-2X/cc-pVTZ level of theory in water. In the gas phase, the folded conformation gG1 with gauche- and gauche+ conformations for the Cβsbnd Cα and Cγsbnd Cβ bonds, respectively, is found to be lowest in energy and enthalpy, which can be ascribed to the favored hyperconjugative n → π* interaction between the lone electron pair of the amine nitrogen atom and the Cdbnd O bond of the carboxylic group and the favored antiparallel dipole-dipole interaction between the Nsbnd H bond and the Cdbnd O bond. In addition, the intramolecular hydrogen bonds between the carboxylic group and the amine Nsbnd H group have contributed to stabilize some low-energy conformers. However, the most preferred conformation is found to be tG1 and more stable by 0.4 kcal/mol in ΔG than the conformer gG1, in which the favored entropic term due to the conformational flexibility and the other favored n → σ*, σ → σ*, and π → σ* interactions seem to play a role. The conformational preferences of the neutral GABA calculated by ΔG's are reasonably consistent with the populations deduced from FT microwave spectroscopy in supersonic jets combined with laser ablation. In water, the two folded conformers Gg and gG of the zwitterionic GABA are dominantly populated, each of which has the population of 47%, and the hydrogen bond between the ammonium Nsbnd H group and the lone electron pair of the Csbnd O- group seems to be crucial in stabilizing these conformers. Our calculated result that the folded conformers preferentially exist in water is consistent with the 1H NMR experiments in D2O.

  17. Modelling zwitterions in solution: 3-fluoro-γ-aminobutyric acid (3F-GABA).

    Science.gov (United States)

    Cao, Jie; Bjornsson, Ragnar; Bühl, Michael; Thiel, Walter; van Mourik, Tanja

    2012-01-02

    The conformations and relative stabilities of folded and extended 3-fluoro-γ-aminobutyric acid (3F-GABA) conformers were studied using explicit solvation models. Geometry optimisations in the gas phase with one or two explicit water molecules favour folded and neutral structures containing intramolecular NH···O-C hydrogen bonds. With three or five explicit water molecules zwitterionic minima are obtained, with folded structures being preferred over extended conformers. The stability of folded versus extended zwitterionic conformers increases on going from a PCM continuum solvation model to the microsolvated complexes, though extended structures become less disfavoured with the inclusion of more water molecules. Full explicit solvation was studied with a hybrid quantum-mechanical/molecular-mechanical (QM/MM) scheme and molecular dynamics simulations, including more than 6000 TIP3P water molecules. According to free energies obtained from thermodynamic integration at the PM3/MM level and corrected for B3LYP/MM total energies, the fully extended conformer is more stable than folded ones by about -4.5 kJ mol(-1). B3LYP-computed (3)J(F,H) NMR spin-spin coupling constants, averaged over PM3/MM-MD trajectories, agree best with experiment for this fully extended form, in accordance with the original NMR analysis. The seeming discrepancy between static PCM calculations and experiment noted previously is now resolved. That the inexpensive semiempirical PM3 method performs so well for this archetypical zwitterion is encouraging for further QM/MM studies of biomolecular systems. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Efficient modulation of γ-aminobutyric acid type A receptors by piperine derivatives.

    Science.gov (United States)

    Schöffmann, Angela; Wimmer, Laurin; Goldmann, Daria; Khom, Sophia; Hintersteiner, Juliane; Baburin, Igor; Schwarz, Thomas; Hintersteininger, Michael; Pakfeifer, Peter; Oufir, Mouhssin; Hamburger, Matthias; Erker, Thomas; Ecker, Gerhard F; Mihovilovic, Marko D; Hering, Steffen

    2014-07-10

    Piperine activates TRPV1 (transient receptor potential vanilloid type 1 receptor) receptors and modulates γ-aminobutyric acid type A receptors (GABAAR). We have synthesized a library of 76 piperine analogues and analyzed their effects on GABAAR by means of a two-microelectrode voltage-clamp technique. GABAAR were expressed in Xenopus laevis oocytes. Structure-activity relationships (SARs) were established to identify structural elements essential for efficiency and potency. Efficiency of piperine derivatives was significantly increased by exchanging the piperidine moiety with either N,N-dipropyl, N,N-diisopropyl, N,N-dibutyl, p-methylpiperidine, or N,N-bis(trifluoroethyl) groups. Potency was enhanced by replacing the piperidine moiety by N,N-dibutyl, N,N-diisobutyl, or N,N-bistrifluoroethyl groups. Linker modifications did not substantially enhance the effect on GABAAR. Compound 23 [(2E,4E)-5-(1,3-benzodioxol-5-yl)-N,N-dipropyl-2,4-pentadienamide] induced the strongest modulation of GABAA (maximal GABA-induced chloride current modulation (IGABA-max = 1673% ± 146%, EC50 = 51.7 ± 9.5 μM), while 25 [(2E,4E)-5-(1,3-benzodioxol-5-yl)-N,N-dibutyl-2,4-pentadienamide] displayed the highest potency (EC50 = 13.8 ± 1.8 μM, IGABA-max = 760% ± 47%). Compound 23 induced significantly stronger anxiolysis in mice than piperine and thus may serve as a starting point for developing novel GABAAR modulators.

  19. Biodiversity and γ-aminobutyric acid production by lactic acid bacteria isolated from traditional alpine raw cow's milk cheeses.

    Science.gov (United States)

    Franciosi, Elena; Carafa, Ilaria; Nardin, Tiziana; Schiavon, Silvia; Poznanski, Elisa; Cavazza, Agostino; Larcher, Roberto; Tuohy, Kieran M

    2015-01-01

    "Nostrano-cheeses" are traditional alpine cheeses made from raw cow's milk in Trentino-Alto Adige, Italy. This study identified lactic acid bacteria (LAB) developing during maturation of "Nostrano-cheeses" and evaluated their potential to produce γ-aminobutyric acid (GABA), an immunologically active compound and neurotransmitter. Cheese samples were collected on six cheese-making days, in three dairy factories located in different areas of Trentino and at different stages of cheese ripening (24 h, 15 days, and 1, 2, 3, 6, and 8 months). A total of 1,059 LAB isolates were screened using Random Amplified Polymorphic DNA-PCR (RAPD-PCR) and differentiated into 583 clusters. LAB strains from dominant clusters (n = 97) were genetically identified to species level by partial 16S rRNA gene sequencing. LAB species most frequently isolated were Lactobacillus paracasei, Streptococcus thermophilus, and Leuconostoc mesenteroides. The 97 dominant clusters were also characterized for their ability in producing GABA by high-performance liquid chromatography (HPLC). About 71% of the dominant bacteria clusters evolving during cheeses ripening were able to produce GABA. Most GABA producers were Lactobacillus paracasei but other GABA producing species included Lactococcus lactis, Lactobacillus plantarum, Lactobacillus rhamnosus, Pediococcus pentosaceus, and Streptococcus thermophilus. No Enterococcus faecalis or Sc. macedonicus isolates produced GABA. The isolate producing the highest amount of GABA (80.0±2.7 mg/kg) was a Sc. thermophilus.

  20. Lactic Acid Bacterial Starter Culture with Antioxidant and γ-Aminobutyric Acid Biosynthetic Activities Isolated from Flatfish-Sikhae Fermentation.

    Science.gov (United States)

    Won, Yeong Geol; Yu, Hyun-Hee; Chang, Young-Hyo; Hwang, Han-Joon

    2015-12-01

    The aim of this study is to select a lactic acid bacterial strain as a starter culture for flatfish-Sikhae fermentation and to evaluate its suitability for application in a food system. Four strains of lactic acid bacteria isolated from commercial flatfish-Sikhae were identified and selected as starter culture candidates through investigation of growth rates, salt tolerance, food safety, and functional properties such as antioxidative and antimicrobial activities. The fermentation properties of the starter candidates were also examined in food systems prepared with these strains (candidate batch) in comparison with a spontaneous fermentation process without starter culture (control batch) at 15°C. The results showed that the candidate YG331 batch had better fermentation properties such as viable cell count, pH, and acidity than the other experimental batches, including the control batch. The results are expressed according to selection criteria based on a preliminary sensory evaluation and physiochemical investigation. Also, only a small amount of histamine was detected with the candidate YG331 batch. The radical scavenging activity of the candidate batches was better compared with the control batch, and especially candidate YG331 batch showed the best radical scavenging activity. Also, we isolated another starter candidate (identified as Lactobacillus brevis PM03) with γ-aminobutyric acid (GABA)-producing activity from commercial flatfish-Sikhae products. The sensory scores of the candidate YG331 batch were better than those of the other experimental batches in terms of flavor, color, and overall acceptance. In this study, we established selection criteria for the lactic acid bacterial starter for the flatfish-Sikhae production and finally selected candidate YG331 as the most suitable starter.

  1. The structure and diffusion behaviour of the neurotransmitter γ-aminobutyric acid (GABA) in neutral aqueous solutions

    International Nuclear Information System (INIS)

    Rodrigo, M.M.; Esteso, M.A.; Barros, M.F.; Verissimo, L.M.P.; Romero, C.M.; Suarez, A.F.; Ramos, M.L.; Valente, A.J.M.; Burrows, H.D.; Ribeiro, A.C.F.

    2017-01-01

    Highlights: • Diffusion coefficients and densities of binary aqueous solutions of γ-aminobutyric acid (GABA). • Dependence on both shape and size of GABA on its diffusion. • Interactions intramolecular and the solute-water interactions in these systems. - Abstract: GABA (γ-aminobutyric acid) is a non-protein amino acid with important physiological properties, and with considerable relevance to the food and pharmaceutical industries. Particular interest has focused on its role as an inhibitory neurotransmitter in the mammalian cerebral cortex. In this paper, we report density and mutual diffusion coefficients of GABA in non-buffered aqueous solutions (0.001–0.100) mol·dm −3 at 298.15 K. Under these conditions, 1 H and 13 C NMR spectroscopy and pH measurements show that it is present predominantly as a monomeric zwitterionic species. Diffusion coefficients have been computed assuming that this behaves as the binary system GABA/water. From density and intermolecular diffusion coefficients measurements, the molar volume, hydrodynamic radii, R h , diffusion coefficients at infinitesimal concentration, D 0 , activity coefficients and the thermodynamic factors, F T , have been estimated. Within experimental error, the hydrodynamic volume calculated from this is identical to the molar volume obtained from density measurements. From the NMR spectra and literature data, it is suggested that this amino acid diffuses in aqueous solution as a curved, coil-like hydrated zwitterionic entity.

  2. Transcriptional dysregulation of γ-aminobutyric acid transporter in parvalbumin-containing inhibitory neurons in the prefrontal cortex in schizophrenia.

    Science.gov (United States)

    Bitanihirwe, Byron K Y; Woo, Tsung-Ung W

    2014-12-30

    Parvalbumin (PV)-containing neurons are functionally compromised in schizophrenia. Using double in situ hybridization in postmortem human prefrontal cortex, we found that the messenger RNA (mRNA) for the γ-aminobutyric acid (GABA) transporter GAT-1 was undetectable in 22-41% of PV neurons in layers 3-4 in schizophrenia. In the remaining PV neurons with detectable GAT-1 mRNA, transcript expression was decreased by 26% in layer 3. Hence, the dysfunction of PV neurons involves the molecular dysregulation of presynaptic GABA reuptake. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  3. Metabolic pathways regulated by abscisic acid, salicylic acid and γ-aminobutyric acid in association with improved drought tolerance in creeping bentgrass (Agrostis stolonifera).

    Science.gov (United States)

    Li, Zhou; Yu, Jingjin; Peng, Yan; Huang, Bingru

    2017-01-01

    Abscisic acid (ABA), salicylic acid (SA) and γ-aminobutyric acid (GABA) are known to play roles in regulating plant stress responses. This study was conducted to determine metabolites and associated pathways regulated by ABA, SA and GABA that could contribute to drought tolerance in creeping bentgrass (Agrostis stolonifera). Plants were foliar sprayed with ABA (5 μM), GABA (0.5 mM) and SA (10 μM) or water (untreated control) prior to 25 days drought stress in controlled growth chambers. Application of ABA, GABA or SA had similar positive effects on alleviating drought damages, as manifested by the maintenance of lower electrolyte leakage and greater relative water content in leaves of treated plants relative to the untreated control. Metabolic profiling showed that ABA, GABA and SA induced differential metabolic changes under drought stress. ABA mainly promoted the accumulation of organic acids associated with tricarboxylic acid cycle (aconitic acid, succinic acid, lactic acid and malic acid). SA strongly stimulated the accumulation of amino acids (proline, serine, threonine and alanine) and carbohydrates (glucose, mannose, fructose and cellobiose). GABA enhanced the accumulation of amino acids (GABA, glycine, valine, proline, 5-oxoproline, serine, threonine, aspartic acid and glutamic acid) and organic acids (malic acid, lactic acid, gluconic acid, malonic acid and ribonic acid). The enhanced drought tolerance could be mainly due to the enhanced respiration metabolism by ABA, amino acids and carbohydrates involved in osmotic adjustment (OA) and energy metabolism by SA, and amino acid metabolism related to OA and stress-defense secondary metabolism by GABA. © 2016 Scandinavian Plant Physiology Society.

  4. Guanidinoacetic acid loading affects plasma γ-aminobutyric acid in healthy men.

    Science.gov (United States)

    Ostojic, Sergej M; Stojanovic, Marko

    2015-08-01

    Guanidinoacetic acid (GAA), a precursor of creatine and an innovative dietary agent, activates γ-amino butyric acid (GABA) receptors yet clinical effects of dietary GAA on GABA metabolism are currently unknown. The main aim of this pilot research was to investigate whether GAA loading affected peripheral GABA homeostasis in healthy humans. Eight healthy male volunteers aged 22-25 years were randomized in a double-blind design to receive either GAA (three grams daily) or placebo by oral administration for 3 weeks. At baseline and after 3 weeks participants provided fasting blood samples for free plasma levels of GABA, GAA, creatine and glutamine. Following 3 weeks of intervention, plasma GABA level dropped significantly in participants receiving 3 g of GAA per day as compared to the placebo (P = 0.03). GAA loading significantly decreased plasma GABA by 88.8 nmol/L (95% confidence interval; 5.4-172.1) after 3 weeks of intervention as compared to the baseline (P = 0.03). GAA intervention positively affected both plasma GAA and creatine (P GABA metabolism, and potentially down-regulates GABA synthesis in peripheral tissues. Possible GABAergic action of dietary GAA adds to the safety profile of this novel dietary supplement.

  5. Biochemical evidence for. gamma. -aminobutyrate containing fibres from the nucleus accumbens to the substantia nigra and ventral tegmental area in the rat

    Energy Technology Data Exchange (ETDEWEB)

    Walaas, I; Fonnum, F

    1980-01-01

    Glutamate decarboxylase activity, a specific marker for ..gamma..-aminobutyrate-containing neurons, has been analysed in microdissected samples from rat mesencephalon following unilateral electrocoagulations of the nucleus accumbens. This lesion resulted in a consistent decrease of 50% in the enzyme activity in the rostromedial substantia nigra, and a slight, but insignificant decrease (- 15%) in the medial parts of the caudal pars compacta of the substantia nigra. No change was found in the lateral pars compacta or the central pars reticulata. In the ventral tegmental area, the highest activity was found in the rostromedial part, adjacent to the mammillary body. At this level, a significant decrease of 20% was found in the ventral tegmental area on the lesioned side. In contrast, the activities in the medial accessory optic nucleus and the caudal ventral tegmental area adjacent to the interpenduncular nucleus were unchanged. The results indicate that the nucleus accumbens sends ..gamma..-aminobutyrate-containing fibres to the rostromedial substantia nigra and to the rostral ventral tegmental area. The caudal ventral tegmental area, the lateral pars compacta and the central pars reticulata do not receive measurable amounts of such fibres.

  6. Effect of glycine, DL-alanine and DL-2-aminobutyric acid on the temperature of maximum density of water

    International Nuclear Information System (INIS)

    Romero, Carmen M.; Torres, Andres Felipe

    2015-01-01

    Highlights: • Effect of α-amino acids on the temperature of maximum density of water is presented. • The addition of α-amino acids decreases the temperature of maximum density of water. • Despretz constants suggest that the amino acids behave as water structure breakers. • Despretz constants decrease as the number of CH 2 groups of the amino acid increase. • Solute disrupting effect becomes smaller as its hydrophobic character increases. - Abstract: The effect of glycine, DL-alanine and DL-2-aminobutyric acid on the temperature of maximum density of water was determined from density measurements using a magnetic float densimeter. Densities of aqueous solutions were measured within the temperature range from T = (275.65 to 278.65) K at intervals of T = 0.50 K over the concentration range between (0.0300 and 0.1000) mol · kg −1 . A linear relationship between density and concentration was obtained for all the systems in the temperature range considered. The temperature of maximum density was determined from the experimental results. The effect of the three amino acids is to decrease the temperature of maximum density of water and the decrease is proportional to molality according to Despretz equation. The effect of the amino acids on the temperature of maximum density decreases as the number of methylene groups of the alkyl chain becomes larger. The results are discussed in terms of (solute + water) interactions and the effect of amino acids on water structure

  7. The importance of glutamate, glycine, and γ-aminobutyric acid transport and regulation in manganese, mercury and lead neurotoxicity

    International Nuclear Information System (INIS)

    Fitsanakis, Vanessa A.; Aschner, Michael

    2005-01-01

    Historically, amino acids were studied in the context of their importance in protein synthesis. In the 1950s, the focus of research shifted as amino acids were recognized as putative neurotransmitters. Today, many amino acids are considered important neurochemicals. Although many amino acids play a role in neurotransmission, glutamate (Glu), glycine (Gly), and γ-aminobutyric acid (GABA) are among the more prevalent and better understood. Glu, the major excitatory neurotransmitter, and Gly and GABA, the major inhibitory neurotransmitters, in the central nervous system, are known to be tightly regulated. Prolonged exposure to environmental toxicants, such as manganese (Mn), mercury (Hg), or lead (Pb), however, can lead to dysregulation of these neurochemicals and subsequent neurotoxicity. While the ability of these metals to disrupt the regulation of Glu, Gly and GABA have been studied, few articles have examined the collective role of these amino acids in the respective metal's mechanism of toxicity. For each of the neurotransmitters above, we will provide a brief synopsis of their regulatory function, including the importance of transport and re-uptake in maintaining their optimal function. Additionally, the review will address the hypothesis that aberrant homeostasis of any of these amino acids, or a combination of the three, plays a role in the neurotoxicity of Mn, Hg, or Pb

  8. GABA (γ-aminobutyric acid production, antioxidant activity in some germinated dietary seeds and the effect of cooking on their GABA content

    Directory of Open Access Journals (Sweden)

    Kasarin TIANSAWANG

    2016-01-01

    Full Text Available Abstract Germinated grains have been known as sources of Gamma-aminobutyric acid (GABA that provide beneficial effects for human health. This study was aimed to investigate GABA production, dietary fiber, antioxidant activity, and the effect of cooking on GABA loss in germinated legumes and sesame. The highest GABA content was found in germinated mung bean, (0.8068 g kg-1, 24 h incubation followed by germinated soybean, germinated black bean and soaked sesame. Beside GABA, dietary fiber content also increased in all grains during germination where the insoluble dietary fiber fractions were always found in higher proportions to soluble dietary fiber fractions. Our results also confirmed that germinated mung bean is a rich source of GABA and dietary fibers. Microwave cooking resulted in the smallest loss of GABA in mung bean and sesame, while steaming led to the least GABA content loss in soybean and black bean. Therefore microwave cooking and steaming are the most recommended cooking processes to preserve GABA in germinated legumes and sesame.

  9. Induced resistance in tomato fruit by γ-aminobutyric acid for the control of alternaria rot caused by Alternaria alternata.

    Science.gov (United States)

    Yang, Jiali; Sun, Cui; Zhang, Yangyang; Fu, Da; Zheng, Xiaodong; Yu, Ting

    2017-04-15

    The study investigated the effect of γ-aminobutyric acid (GABA) on the control of alternaria rot in tomato fruit and the possible mechanism involved. Our results showed exogenous GABA could stimulate remarkable resistance to the alternaria rot, while it had no direct antifungal activity against Alternaria alternata. Moreover, the activities of antioxidant enzymes, including peroxidase, superoxide dismutase and catalase, along with the expression of these corresponding genes, were significantly induced in the GABA treatment. The obtained data suggested GABA induced resistance against the necrotrophic pathogen A. alternata, at least in part by activating antioxidant enzymes, restricting the levels of cell death caused by reactive oxygen species. Meanwhile, the key enzyme genes of GABA shunt, GABA transaminase and succinic-semialdehyde dehydrogenase, were found up-regulated in the GABA treatment. The activation of the GABA shunt might play a vital role in the resistance mechanism underpinning GABA-induced plant immunity. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Characterization of a Potential Probiotic Lactobacillus brevis RK03 and Efficient Production of γ-Aminobutyric Acid in Batch Fermentation

    Directory of Open Access Journals (Sweden)

    Chien-Hui Wu

    2018-01-01

    Full Text Available Lactic acid bacteria were isolated from fish and evaluated for their γ-aminobutyric acid (GABA-producing abilities. Out of thirty-two isolates, Lactobacillus brevis RK03 showed the highest GABA production ability. The effects of various fermentation parameters including initial glutamic acid level, culture temperature, initial pH, and incubation time on GABA production were investigated via a singleparameter optimization strategy. For industrial large-scale production, a low-cost GABA producing medium (GM broth was developed for fermentation with L. brevis RK03. We found that an optimized GM broth recipe of 1% glucose; 2.5% yeast extract; 2 ppm each of CaCO3, MnSO4, and Tween 80; and 10 μM pyridoxal phosphate (PLP resulted in a maximum GABA yield of 62,523 mg/L after 88 h following the addition of 650 mM monosodium glutamate (MSG, for a conversion rate of 93.28%. Our data provide a practical approach for the highly efficient and economic production of GABA. In addition, L. brevis RK03 is highly resistant to gastric acid and bovine bile salt. Thus, the discovery of Lactobacillus strains with the ability to synthesize GABA may offer new opportunities in the design of improved health-promoting functional foods.

  11. Characterization of a Potential Probiotic Lactobacillus brevis RK03 and Efficient Production of γ-Aminobutyric Acid in Batch Fermentation.

    Science.gov (United States)

    Wu, Chien-Hui; Hsueh, Yi-Huang; Kuo, Jen-Min; Liu, Si-Jia

    2018-01-04

    Lactic acid bacteria were isolated from fish and evaluated for their γ-aminobutyric acid (GABA)-producing abilities. Out of thirty-two isolates, Lactobacillus brevis RK03 showed the highest GABA production ability. The effects of various fermentation parameters including initial glutamic acid level, culture temperature, initial pH, and incubation time on GABA production were investigated via a singleparameter optimization strategy. For industrial large-scale production, a low-cost GABA producing medium (GM) broth was developed for fermentation with L. brevis RK03. We found that an optimized GM broth recipe of 1% glucose; 2.5% yeast extract; 2 ppm each of CaCO₃, MnSO₄, and Tween 80; and 10 μM pyridoxal phosphate (PLP) resulted in a maximum GABA yield of 62,523 mg/L after 88 h following the addition of 650 mM monosodium glutamate (MSG), for a conversion rate of 93.28%. Our data provide a practical approach for the highly efficient and economic production of GABA. In addition, L. brevis RK03 is highly resistant to gastric acid and bovine bile salt. Thus, the discovery of Lactobacillus strains with the ability to synthesize GABA may offer new opportunities in the design of improved health-promoting functional foods.

  12. Quantification of γ-Aminobutyric Acid in Cerebrospinal Fluid Using Liquid Chromatography-Electrospray Tandem Mass Spectrometry.

    Science.gov (United States)

    Arning, Erland; Bottiglieri, Teodoro

    2016-01-01

    We describe a simple stable isotope dilution method for accurate and precise measurement of γ-aminobutyric acid (GABA), a major inhibitory neurotransmitter in human cerebrospinal fluid (CSF) as a clinical diagnostic test. Determination of GABA in CSF (50 μL) was performed utilizing high performance liquid chromatography coupled with electrospray positive ionization tandem mass spectrometry (HPLC-ESI-MS/MS). Analysis of free and total GABA requires two individual sample preparations and mass spectrometry analyses. Free GABA in CSF is determined by a 1:2 dilution with internal standard (GABA-D2) and injected directly onto the HPLC-ESI-MS/MS system. Determination of total GABA in CSF requires additional sample preparation in order to hydrolyze all the bound GABA in the sample to the free form. This requires hydrolyzing the sample by boiling in acidic conditions (hydrochloric acid) for 4 h. The sample is then further diluted 1:10 with a 90 % acetonitrile/0.1 % formic acid solution and injected into the HPLC-ESI-MS/MS system. Each assay is quantified using a five-point standard curve and is linear from 6 nM to 1000 nM and 0.63 μM to 80 μM for free and total GABA, respectively.

  13. Carrier-mediated γ-aminobutyric acid transport across the basolateral membrane of human intestinal Caco-2 cell monolayers.

    Science.gov (United States)

    Nielsen, Carsten Uhd; Carstensen, Mette; Brodin, Birger

    2012-06-01

    The aim of the present study was to investigate the transport of γ-aminobutyric acid (GABA) across the basolateral membrane of intestinal cells. The proton-coupled amino acid transporter, hPAT1, mediates the influx of GABA and GABA mimetic drug substances such as vigabatrin and gaboxadol and the anticancer prodrug δ-aminolevulinic acid across the apical membrane of small intestinal enterocytes. Little is however known about the basolateral transport of these substances. We investigated basolateral transport of GABA in mature Caco-2 cell monolayers using isotope studies. Here we report that, at least two transporters seem to be involved in the basolateral transport of GABA. The basolateral uptake consisted of a high-affinity system with a K(m) of 290 μM and V(max) of 75 pmol cm(-2) min(-1) and a low affinity system with a K(m) of approximately 64 mM and V(max) of 1.6 nmol cm(-2) min(-1). The high-affinity transporter is Na(+) and Cl(-) dependent. The substrate specificity of the high-affinity transporter was further studied and Gly-Sar, Leucine, gaboxadol, sarcosine, lysine, betaine, 5-hydroxythryptophan, proline and glycine reduced the GABA uptake to approximately 44-70% of the GABA uptake in the absence of inhibitor. Other substances such as β-alanine, GABA, 5-aminovaleric acid, taurine and δ-aminolevulinic acid reduced the basolateral GABA uptake to 6-25% of the uptake in the absence of inhibitor. Our results indicate that the distance between the charged amino- and acid-groups is particular important for inhibition of basolateral GABA uptake. Thus, there seems to be a partial substrate overlap between the basolateral GABA transporter and hPAT1, which may prove important for understanding drug interactions at the level of intestinal transport. Copyright © 2012 Elsevier B.V. All rights reserved.

  14. Perinatal intermittent hypoxia alters γ-aminobutyric acid: a receptor levels in rat cerebellum.

    Science.gov (United States)

    Pae, Eung-Kwon; Yoon, Audrey J; Ahuja, Bhoomika; Lau, Gary W; Nguyen, Daniel D; Kim, Yong; Harper, Ronald M

    2011-12-01

    Perinatal hypoxia commonly causes brain injury in infants, but the time course and mechanisms underlying the preferential male injury are unclear. Intermittent hypoxia disturbs cerebellar γ-aminobutyric (GABA)-A receptor profiles during the perinatal period, possibly responding to transient excitatory processes associated with GABA(A) receptors. We examined whether hypoxic insults were particularly damaging to the male rodent cerebellum during a specific developmental time window. We evaluated cerebellar injury and GABA(A) receptor profiles following 5-h intermittent hypoxia (IH: 20.8% and 10.3% ambient oxygen, switched every 240s) or room-air control in groups of male and female rat pups on postnatal d 1-2, wk 1, or wk 3. The cerebella were harvested and compared between groups. The mRNA levels of GABA(A) receptors α6, normalized to a house-keeping gene GAPDH, and assessed using real-time reverse-transcriptase PCR assays were up-regulated by IH at wk 1, more extensively in male rats, with sex influencing the regulatory time-course. In contrast, GABA(A) α6 receptor protein expression levels, assessed using Western blot assays, reached a nadir at wk 1 in both male and female rats, possibly indicating involvement of a post-transcriptional mechanism. The extent of cerebellar damage and level of apoptosis, assessed by DNA fragmentation, were greatest in the wk 3 IH-exposed group. The findings suggest partial protection for female rats against early hypoxic insult in the cerebellum, and that down-regulation of GABA(A) receptors, rather than direct neural injury assessed by DNA fragmentation may modify cerebellar function, with potential later motor and other deficits. Copyright © 2011 ISDN. Published by Elsevier Ltd. All rights reserved.

  15. Influence of high-pressure processing on the generation of γ-aminobutyric acid and microbiological safety in coffee beans.

    Science.gov (United States)

    Chen, Bang-Yuan; Huang, Hsiao-Wen; Cheng, Ming-Ching; Wang, Chung-Yi

    2018-04-27

    The aim of this study was to investigate the influence of high-pressure processing (HPP) on γ-aminobutyric acid (GABA) content, glutamic acid (Glu) content, glutamate decarboxylase (GAD) activity, growth of Aspergillus fresenii, and accumulated ochratoxin A (OTA) content in coffee beans. The results indicated that coffee beans subjected to HPP at pressures ≥50 MPa for 5 min increased GAD activity and promoted the conversion of Glu to GABA, and showed a significantly doubling of GABA content compared with unprocessed coffee beans. Additionally, investigation of the influence of HPP on A. fresenii growth on coffee beans showed that application ≥400 MPa reduced A. fresenii concentrations to beans subjected to processing pressures of 600 MPa was 0.0066 μg g -1 , which was significantly lower than the OTA content of 0.1143 μg g -1 in the control group. This study shows that HPP treatment can simultaneously increase GABA content and inhibit the growth of A. fresenii, thereby effectively reducing the production and accumulation of OTA and maintaining the microbiological safety of coffee beans. © 2018 Society of Chemical Industry. © 2018 Society of Chemical Industry.

  16. Novel fermented chickpea milk with enhanced level of γ-aminobutyric acid and neuroprotective effect on PC12 cells

    Directory of Open Access Journals (Sweden)

    Wen Li

    2016-08-01

    Full Text Available In this study, novel fermented chickpea milk with high γ -aminobutyric acid (GABA content and potential neuroprotective activity was developed. Fermentation starter that can produce GABA was selected from 377 strains of lactic acid bacteria isolated from traditional Chinese fermented foods. Among the screened strains, strain M-6 showed the highest GABA-producing capacity in De Man–Rogosa and Sharp (MRS broth and chickpea milk. M-6 was identified as Lactobacillus plantarum based on Gram staining, API carbohydrate fermentation pattern testing, and 16s rDNA sequencing. The complete gene encoding glutamate decarboxylase was cloned to confirm the presence of the gene in L. plantarum M-6. The fermentation condition was optimized by response surface methodology. Results demonstrated that L. plantarum M-6 produced the highest GABA content of 537.23 mg/L. The optimal condition included an inoculum concentration of 7%, presence of 0.2% (m/v monosodium glutamate and 55 µ M pyridoxal-5-phosphate, incubation temperature of 39 °C and fermentation time of 48 h . GABA-enriched chickpea milk exerted protective effects on PC12 cells against MnCl2 -induced injury. GABA-enriched chickpea milk improved cell viability and markedly attenuated the release of lactate dehydrogenase compared with the impaired cells.

  17. Novel fermented chickpea milk with enhanced level of γ-aminobutyric acid and neuroprotective effect on PC12 cells.

    Science.gov (United States)

    Li, Wen; Wei, Mingming; Wu, Junjun; Rui, Xin; Dong, Mingsheng

    2016-01-01

    In this study, novel fermented chickpea milk with high γ -aminobutyric acid (GABA) content and potential neuroprotective activity was developed. Fermentation starter that can produce GABA was selected from 377 strains of lactic acid bacteria isolated from traditional Chinese fermented foods. Among the screened strains, strain M-6 showed the highest GABA-producing capacity in De Man-Rogosa and Sharp (MRS) broth and chickpea milk. M-6 was identified as Lactobacillus plantarum based on Gram staining, API carbohydrate fermentation pattern testing, and 16s rDNA sequencing. The complete gene encoding glutamate decarboxylase was cloned to confirm the presence of the gene in L. plantarum M-6. The fermentation condition was optimized by response surface methodology. Results demonstrated that L. plantarum M-6 produced the highest GABA content of 537.23 mg/L. The optimal condition included an inoculum concentration of 7%, presence of 0.2% (m/v) monosodium glutamate and 55 µ M pyridoxal-5-phosphate, incubation temperature of 39 °C and fermentation time of 48 h . GABA-enriched chickpea milk exerted protective effects on PC12 cells against MnCl2 -induced injury. GABA-enriched chickpea milk improved cell viability and markedly attenuated the release of lactate dehydrogenase compared with the impaired cells.

  18. Effect of temperature on the partial molar volume, isentropic compressibility and viscosity of DL-2-aminobutyric acid in water and in aqueous sodium chloride solutions

    International Nuclear Information System (INIS)

    Romero, Carmen M.; Rodríguez, Diana M.; Ribeiro, Ana C.F.; Esteso, Miguel A.

    2017-01-01

    Highlights: • Apparent volumes, apparent compressibilities, viscosities of DL-2-aminobutyric acid. • Effect of temperature on the values for these properties. • Hydrophobic and hydrophilic interactions and the effect of sodium chloride. - Abstract: Density, sound velocity and viscosity of DL-2-aminobutyric acid in water and in aqueous sodium chloride solutions have been measured at temperatures of (293.15, 298.15, 303.15, 308.15 and 313.15) K. The experimental results were used to determine the apparent molar volume and the apparent molar compressibility as a function of composition at these temperatures. The limiting values of both the partial molar volume and the partial molar adiabatic compressibility at infinite dilution of DL-2-aminobutyric acid in water and in aqueous sodium chloride solutions were determined at each temperature. The experimental viscosity values were adjusted by a least-squares method to a second order equation as proposed by Tsangaris-Martin to obtain the viscosity B coefficient which depends on the size, shape and charge of the solute molecule. The influence of the temperature on the behaviour of the selected properties is discussed in terms of both the solute hydration and the balance between hydrophobic and hydrophilic interactions between the acids and water, and the effect of the sodium chloride concentration.

  19. Pretreatment of liver grafts in vivo by γ-aminobutyric acid receptor regulation reduces cold ischemia/warm reperfusion injury in rat

    Science.gov (United States)

    Hori, Tomohide; Gardner, Lindsay B.; Hata, Toshiyuki; Chen, Feng; Baine, Ann-Marie T.; Uemoto, Shinji; Nguyen, Justin H.

    2014-01-01

    Summary Background: Gamma-aminobutyric acid (GABA) is found throughout the body. The regulation of GABA receptor (GABAR) reduces oxidative stress (OS). Ischemia/reperfusion injury after orthotopic liver transplantation (OLT) causes OS-induced graft damage. The effects of GABAR regulation in donors in vivo were investigated. Material/Methods: Donor rats received saline, a GABAR agonist or GABAR antagonist 4 h before surgery. Recipient rats were divided into four groups according to the donor treatments: laparotomy, OLT with saline, OLT with GABAR agonist and OLT with GABAR antagonist. Histopathological, biochemical and immunohistological examinations were performed at 6, 12 and 24 h after OLT. Protein assays were performed at 6 h after OLT. The 4-hydroxynonenal (4-HNE), ataxia-telangiectasia mutated kinase (ATM), phosphorylated histone H2AX (γH2AX), phosphatidylinositol-3 kinase (PI3K), Akt and superoxide dismutase (SOD) were assessed by western blot analysis. Results: In the univariate analysis, histopathological and biochemical profiles verified that the GABAR agonist reduced graft damage. Immunohistology revealed that the GABAR agonist prevented the induction of apoptosis. Measurement of 4-4-HNE levels confirmed OS-induced damage after OLT, and the GABAR agonist improved this damage. In the γH2AX, PI3K, Akt and antioxidant enzymes (SODs), ATM and H2AX were greatly increased after OLT, and were reduced by the GABAR agonist. In the multivariate analyses between multiple groups, histopathological assessment, aspartate aminotransferase level, immunohistological examinations for apoptotic induction and γH2AX showed statistical differences. Conclusions: A specific agonist demonstrated regulation of GABAR in vivo in the liver. This activation in vivo reduced OS after OLT via the ATM/H2AX pathway. PMID:23792534

  20. The novel isoxazoline ectoparasiticide lotilaner (Credelio™): a non-competitive antagonist specific to invertebrates γ-aminobutyric acid-gated chloride channels (GABACls)

    OpenAIRE

    Rufener, Lucien; Danelli, Vanessa; Bertrand, Daniel; Sager, Heinz

    2017-01-01

    Background The isoxazolines are a novel class of parasiticides that are potent inhibitors of γ-aminobutyric acid (GABA)-gated chloride channels (GABACls) and, to a lesser extent, of inhibitory glutamate-gated chloride channels (GluCls). Lotilaner (Credelio™), a novel representative of this chemical class, is currently evaluated for its excellent ectoparasiticide properties. Methods In this study, we investigated the molecular mode of action and pharmacology of lotilaner. We report the success...

  1. Genetic manipulation of the γ-aminobutyric acid (GABA) shunt in rice: overexpression of truncated glutamate decarboxylase (GAD2) and knockdown of γ-aminobutyric acid transaminase (GABA-T) lead to sustained and high levels of GABA accumulation in rice kernels.

    Science.gov (United States)

    Shimajiri, Yasuka; Oonishi, Takayuki; Ozaki, Kae; Kainou, Kumiko; Akama, Kazuhito

    2013-06-01

    Gamma-aminobutyric acid (GABA) is a non-protein amino acid commonly present in all organisms. Because cellular levels of GABA in plants are mainly regulated by synthesis (glutamate decarboxylase, GAD) and catabolism (GABA-transaminase, GABA-T), we attempted seed-specific manipulation of the GABA shunt to achieve stable GABA accumulation in rice. A truncated GAD2 sequence, one of five GAD genes, controlled by the glutelin (GluB-1) or rice embryo globulin promoters (REG) and GABA-T-based trigger sequences in RNA interference (RNAi) cassettes controlled by one of these promoters as well, was introduced into rice (cv. Koshihikari) to establish stable transgenic lines under herbicide selection using pyriminobac. T₁ and T₂ generations of rice lines displayed high GABA concentrations (2-100 mg/100 g grain). In analyses of two selected lines from the T₃ generation, there was a strong correlation between GABA level and the expression of truncated GAD2, whereas the inhibitory effect of GABA-T expression was relatively weak. In these two lines both with two T-DNA copies, their starch, amylose, and protein levels were slightly lower than non-transformed cv. Koshihikari. Free amino acid analysis of mature kernels of these lines demonstrated elevated levels of GABA (75-350 mg/100 g polished rice) and also high levels of several amino acids, such as Ala, Ser, and Val. Because these lines of seeds could sustain their GABA content after harvest (up to 6 months), the strategy in this study could lead to the accumulation GABA and for these to be sustained in the edible parts. © 2013 Society for Experimental Biology, Association of Applied Biologists and John Wiley & Sons Ltd.

  2. Pyridoxine Supplementation Improves the Activity of Recombinant Glutamate Decarboxylase and the Enzymatic Production of Gama-Aminobutyric Acid.

    Directory of Open Access Journals (Sweden)

    Yan Huang

    Full Text Available Glutamate decarboxylase (GAD catalyzes the irreversible decarboxylation of L-glutamate to the valuable food supplement γ-aminobutyric acid (GABA. In this study, GAD from Escherichia coli K12, a pyridoxal phosphate (PLP-dependent enzyme, was overexpressed in E. coli. The GAD produced in media supplemented with 0.05 mM soluble vitamin B6 analog pyridoxine hydrochloride (GAD-V activity was 154.8 U mL-1, 1.8-fold higher than that of GAD obtained without supplementation (GAD-C. Purified GAD-V exhibited increased activity (193.4 U mg-1, 1.5-fold higher than that of GAD-C, superior thermostability (2.8-fold greater than that of GAD-C, and higher kcat/Km (1.6-fold higher than that of GAD-C. Under optimal conditions in reactions mixtures lacking added PLP, crude GAD-V converted 500 g L-1 monosodium glutamate (MSG to GABA with a yield of 100%, and 750 g L-1 MSG with a yield of 88.7%. These results establish the utility of pyridoxine supplementation and lay the foundation for large-scale enzymatic production of GABA.

  3. J-difference-edited MRS measures of γ-aminobutyric acid before and after acute caffeine administration.

    Science.gov (United States)

    Oeltzschner, Georg; Zöllner, Helge J; Jonuscheit, Marc; Lanzman, Rotem S; Schnitzler, Alfons; Wittsack, Hans-Jörg

    2018-05-12

    The aim of this study was to investigate potential effects of acute caffeine intake on J-difference-edited MRS measures of the primary inhibitory neurotransmitter γ-aminobutyric acid (GABA). J-difference-edited Mescher-Garwood PRESS (MEGA-PRESS) and conventional PRESS data were acquired at 3T from voxels in the anterior cingulate and occipital area of the brain in 15 healthy subjects, before and after oral intake of a 200-mg caffeine dose. MEGA-PRESS data were analyzed with the MATLAB-based Gannet tool to estimate GABA+ macromolecule (GABA+) levels, while PRESS data were analyzed with LCModel to estimate levels of glutamate, glutamate+glutamine, N-acetylaspartate, and myo-inositol. All metabolites were quantified with respect to the internal reference compounds creatine and tissue water, and compared between the pre- and post-caffeine intake condition. For both MRS voxels, mean GABA+ estimates did not differ before and after caffeine intake. Slightly lower estimates of myo-inositol were observed after caffeine intake in both voxels. N-acetylaspartate, glutamate, and glutamate+glutamine did not show significant differences between conditions. Mean GABA+ estimates from J-difference-edited MRS in two different brain regions are not altered by acute oral administration of caffeine. These findings may increase subject recruitment efficiency for MRS studies. © 2018 International Society for Magnetic Resonance in Medicine.

  4. Effect of paraoxon on muscarinic, dopamine and γ-aminobutyric acid receptors of brain and sensitivity to muscarinic antagonists

    International Nuclear Information System (INIS)

    Fernando, J.C.R.; Hoskins, B.; Ho, I.K.

    1986-01-01

    Several acetylcholinesterase (AChE) inhibitors decrease muscarinic cholinergic (mACh) receptors in the brain, alteration of dopamine (DA) and γ-aminobutyric acid (GABA) receptors after AChE inhibition was also reported. In view of the important interactions among DA, GABA and ACh systems, whether this is a common effect of AChE inhibitors should be established. They report the effect of the AChE inhibitor, paraoxon, on DA, GABA and mACh receptors in the rat. The binding of 3 H-QNB (for mACh), 3 H-spiperone (for DA) and 3 H-muscimol (for GABA) to striatal and hippocampal membranes was analyzed. Also, behavioral sensitivity to atropine was studied. Twenty-four hr after a single dose (0.75 mg/kg, s.c.) of paraoxon, the density of mACh receptors in the striatum was decreased but, at 3 days, no change was seen. In the hippocampus, the mACh receptors were not affected. Repeated treatment with paraoxon (0.3 mg/kg, 48 hourly) for 2 weeks reduced the mACh receptor density in both regions. Neither single nor repeated paraoxon treatment had an effect on DA or GABA receptors. After single or repeated dosing with paraoxon, myoclonus induced by atropine (10 mg/kg, i.p.) was enhanced. The results show rapid downregulation of mACh receptors by paraoxon. DA or GABA, however, appear not to be affected under these treatment regimens

  5. Extraction, purification and anti-fatigue activity of γ-aminobutyric acid from mulberry (Morus alba L.) leaves

    Science.gov (United States)

    Chen, Hengwen; He, Xuanhui; Liu, Yan; Li, Jun; He, Qingyong; Zhang, Cuiying; Wei, Benjun; Zhang, Ye; Wang, Jie

    2016-01-01

    Mulberry (Morus alba L.) is a tree species of Moraceae widely distributed in Southern China. In the present study, the white crystal of γ-aminobutyric acid (GABA) was purified from mulberry leaves, and its bioactivity was also investigated. The main results were as follows: first, the crude GABA was extracted from mulberry leaves by using biochemical methods. Then, the crude was purified by chromatography over an S-8 macroporous resin, Sephadex G-10, and 732 cation exchange resin to yield a white crystal. Lavage administration and exposure of GABA to male NIH mice showed no adverse effects on their growth and development. In an endurance capacity test, the average loaded-swimming time of medium dose was 111.60% longer than the control (P levels of blood urea nitrogen (BUN) were 36.83% and 40.54% lower (P levels were 12.81% and 17.22% lower (P GABA has an advantage over taurine of anti-fatigue effect. These findings were indicative of the anti-fatigue activity of GABA.

  6. Brain infection with Staphylococcus aureus leads to high extracellular levels of glutamate, aspartate, γ-aminobutyric acid, and zinc.

    Science.gov (United States)

    Hassel, Bjørnar; Dahlberg, Daniel; Mariussen, Espen; Goverud, Ingeborg Løstegaard; Antal, Ellen-Ann; Tønjum, Tone; Maehlen, Jan

    2014-12-01

    Staphylococcal brain infections may cause mental deterioration and epileptic seizures, suggesting interference with normal neurotransmission in the brain. We injected Staphylococcus aureus into rat striatum and found an initial 76% reduction in the extracellular level of glutamate as detected by microdialysis at 2 hr after staphylococcal infection. At 8 hr after staphylococcal infection, however, the extracellular level of glutamate had increased 12-fold, and at 20 hr it had increased >30-fold. The extracellular level of aspartate and γ-aminobutyric acid (GABA) also increased greatly. Extracellular Zn(2+) , which was estimated at ∼2.6 µmol/liter in the control situation, was increased by 330% 1-2.5 hr after staphylococcal infection and by 100% at 8 and 20 hr. The increase in extracellular glutamate, aspartate, and GABA appeared to reflect the degree of tissue damage. The area of tissue damage greatly exceeded the area of staphylococcal infiltration, pointing to soluble factors being responsible for cell death. However, the N-methyl-D-aspartate receptor antagonist MK-801 ameliorated neither tissue damage nor the increase in extracellular neuroactive amino acids, suggesting the presence of neurotoxic factors other than glutamate and aspartate. In vitro staphylococci incubated with glutamine and glucose formed glutamate, so bacteria could be an additional source of infection-related glutamate. We conclude that the dramatic increase in the extracellular concentration of neuroactive amino acids and zinc could interfere with neurotransmission in the surrounding brain tissue, contributing to mental deterioration and a predisposition to epileptic seizures, which are often seen in brain abscess patients. © 2014 Wiley Periodicals, Inc.

  7. Determination and comparison of γ-aminobutyric acid (GABA) content in pu-erh and other types of Chinese tea.

    Science.gov (United States)

    Zhao, Ming; Ma, Yan; Wei, Zhen-zhen; Yuan, Wen-xia; Li, Ya-li; Zhang, Chun-hua; Xue, Xiao-ting; Zhou, Hong-jie

    2011-04-27

    Two previous studies have reported that pu-erh tea contains a high level of γ-aminobutyric acid (GABA), which is the major inhibitory neurotransmitter in the central nervous system and has several physiological functions. However, two other researchers have demonstrated that the GABA content of several pu-erh teas was low. Due to the high value and health benefits of GABA, analysis of mass-produced pu-erh tea is necessary to determine whether it is actually enriched with GABA. A high-performance liquid chromatography (HPLC) method was developed for the determination of GABA in tea, the results of which were verified by amino acid analysis using an Amino Acid Analyzer (AAA). A total of 114 samples of various types of Chinese tea, including 62 pu-erh teas, 13 green teas, 8 oolong teas, 8 black teas, 3 white teas, 4 GABA teas, and 16 process samples from two industrial fermentations of pu-erh tea (including the raw material and the first to seventh turnings), were analyzed using HPLC. Statistical analysis demonstrated that the GABA content in pu-erh tea was significantly lower than that in other types of tea (p GABA content decreased during industrial fermentation of pu-erh tea (p GABA was not a major bioactive constituent and resolved the disagreement GABA content in pu-erh tea. In addition, the GABA content in white tea was found to be significantly higher than that in the other types of tea (p GABA-enriched white tea.

  8. Specific gamma-hydroxybutyrate-binding sites but loss of pharmacological effects of gamma-hydroxybutyrate in GABA-B1-deficient mice

    DEFF Research Database (Denmark)

    Kaupmann, Klemens; Cryan, John F; Wellendorph, Petrine

    2003-01-01

    gamma-Hydroxybutyrate (GHB), a metabolite of gamma-aminobutyric acid (GABA), is proposed to function as a neurotransmitter or neuromodulator. gamma-Hydroxybutyrate and its prodrug, gamma-butyrolactone (GBL), recently received increased public attention as they emerged as popular drugs of abuse. T...

  9. Autoradiographic localization of binding sites for (/sup 3/H). gamma. -aminobutyrate, (/sup 3/H) muscimol, (+) (/sup 3/H) bicuculline methiodide and (/sup 3/H) flunitrazepam in cultures of rat cerebellum and spinal cord

    Energy Technology Data Exchange (ETDEWEB)

    Hoesli, E; Hoesli, L [Basel Univ. (Switzerland); Moehler, H; Richards, J G [Hoffmann-La Roche (F.) and Co., Basel (Switzerland)

    1980-01-01

    Cultures of rat cerebellum and spinal cord were used to visualize sites for (/sup 3/H)..gamma..-aminobutyrate, (/sup 3/H)muscimol, (/sup 3/H)bicuculline methiodide and (/sup 3/H) flunitrazepam by autoradiography. In cerebellar cultures, many large neurons (presumably Purkinje cells) and interneurons were labelled. In spinal cord cultures, these compounds were mainly bound to small and medium-sized neurons, whereas the majority of large neurons were unlabelled. No binding sites for these radioligands were found on glial cells. Binding of (/sup 3/H)..gamma..-aminobutyrate, (/sup 3/H)muscimol and (/sup 3/H)bicuculline methiodide was markedly reduced or inhibited by adding unlabelled ..gamma..-aminobutyrate, muscimol and bicuculline (10/sup -3/M) respectively to the incubation medium. Addition of a thienobenzazepine markedly reduced binding with (/sup 3/H)flunitrazepam. It is concluded that tissues cultures are an excellent tool to visualize the cellular localization of binding sites for neurotransmitters and drugs using autoradiography.

  10. On-line near-infrared spectroscopy optimizing and monitoring biotransformation process of γ-aminobutyric acid

    Directory of Open Access Journals (Sweden)

    Guoyu Ding

    2016-06-01

    Full Text Available Near-infrared spectroscopy (NIRS with its fast and nondestructive advantages can be qualified for the real-time quantitative analysis. This paper demonstrates that NIRS combined with partial least squares (PLS regression can be used as a rapid analytical method to simultaneously quantify l-glutamic acid (l-Glu and γ-aminobutyric acid (GABA in a biotransformation process and to guide the optimization of production conditions when the merits of NIRS are combined with response surface methodology. The high performance liquid chromatography (HPLC reference analysis was performed by the o-phthaldialdehyde pre-column derivatization. NIRS measurements of two batches of 141 samples were firstly analyzed by PLS with several spectral pre-processing methods. Compared with those of the HPLC reference analysis, the resulting determination coefficients (R2, root mean square error of prediction (RMSEP and residual predictive deviation (RPD of the external validation for the l-Glu concentration were 99.5%, 1.62 g/L, and 11.3, respectively. For the GABA concentration, R2, RMSEP, and RPD were 99.8%, 4.00 g/L, and 16.4, respectively. This NIRS model was then used to optimize the biotransformation process through a Box-Behnken experimental design. Under the optimal conditions without pH adjustment, 200 g/L l-Glu could be catalyzed by 7148 U/L glutamate decarboxylase (GAD to GABA, reaching 99% conversion at the fifth hour. NIRS analysis provided timely information on the conversion from l-Glu to GABA. The results suggest that the NIRS model can not only be used for the routine profiling of enzymatic conversion, providing a simple and effective method of monitoring the biotransformation process of GABA, but also be considered to be an optimal tool to guide the optimization of production conditions.

  11. Effects of rumen-protected γ-aminobutyric acid on performance and nutrient digestibility in heat-stressed dairy cows.

    Science.gov (United States)

    Cheng, J B; Bu, D P; Wang, J Q; Sun, X Z; Pan, L; Zhou, L Y; Liu, W

    2014-09-01

    This experiment was conducted to investigate the effects of rumen-protected γ-aminobutyric acid (GABA) on performance and nutrient digestibility in heat-stressed dairy cows. Sixty Holstein dairy cows (141±15 d in milk, 35.9±4.3kg of milk/d, and parity 2.0±1.1) were randomly assigned to 1 of 4 treatments according to a completely randomized block design. Treatments consisted of 0 (control), 40, 80, or 120mg of true GABA/kg of dry matter (DM). The trial lasted 10wk. The average temperature-humidity indices at 0700, 1400, and 2200h were 78.4, 80.2, and 78.7, respectively. Rectal temperatures decreased linearly at 0700, 1400, and 2200h with increasing GABA concentration. Supplementation of GABA had no effect on respiration rates at any time point. Dry matter intake, energy-corrected milk, 4% fat-corrected milk, and milk fat yield tended to increase linearly with increasing GABA concentration. Supplementation of GABA affected, in a quadratic manner, milk protein and lactose concentrations, and milk protein yield, and the peak values were reached at a dose of 40mg of GABA/kg. Milk urea nitrogen concentration responded quadratically. Total solids content increased linearly with increasing GABA concentration. Supplementation of GABA had no effect on milk yield, lactose production, total solids, milk fat concentration, somatic cell score, or feed efficiency. Apparent total-tract digestibilities of DM, organic matter, crude protein, neutral detergent fiber, and acid detergent fiber were similar among treatments. These results indicate that rumen-protected GABA supplementation to dairy cows can alleviate heat stress by reducing rectal temperature, increase DM intake and milk production, and improve milk composition. The appropriate supplemental GABA level for heat-stressed dairy cows is 40mg/kg of DM. Copyright © 2014 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  12. Modulation of cardiopulmonary depressor reflex in nucleus ambiguus by electroacupuncture: roles of opioids and γ-aminobutyric acid.

    Science.gov (United States)

    Tjen-A-Looi, Stephanie C; Li, Peng; Li, Min; Longhurst, John C

    2012-04-01

    Stimulation of cardiopulmonary receptors with phenylbiguanide (PBG) elicits depressor cardiovascular reflex responses, including decreases in blood pressure and heart rate mediated in part by the brain stem parasympathetic cardiac neurons in the nucleus ambiguus (NAmb). The present study examined NAmb neurotransmitter mechanisms underlying the influence of electroacupuncture (EA) on the PBG-induced hypotension and bradycardia. We hypothesized that somatic stimulation during EA modulates PBG responses through opioid and γ-aminobutyric acid (GABA) modulation in the NAmb. Anesthetized and ventilated cats were studied during repeated stimulation with PBG or cardiac vagal afferents while low-frequency EA (2 Hz) was applied at P5-6 acupoints overlying the median nerve for 30 min and NAmb neuronal activity, heart rate, and blood pressure were recorded. Microinjection of kainic acid into the NAmb attenuated the PBG-induced bradycardia from -60 ± 11 to -36 ± 11 beats/min. Likewise, EA reduced the PBG-induced depressor and bradycardia reflex by 52 and 61%, respectively. Cardiac vagal afferent evoked preganglionic cellular activity in the NAmb was reduced by EA for about 60 min. Blockade of opioid or GABA(A) receptors using naloxone and gabazine reversed the EA-related modulation of the evoked cardiac vagal activity by 73 and 53%, respectively. Similarly, naloxone and gabazine reversed EA modulation of the negative chronotropic responses from -11 ± 5 to -23 ± 6 and -13 ± 4 to -24 ± 3 beats/min, respectively. Thus EA at P5-6 decreases PBG evoked hypotension and bradycardia as well as the NAmb PBG-sensitive preganglionic cardiac vagal outflow through opioid and GABA neurotransmitter systems.

  13. Dairy Streptococcus thermophilus improves cell viability of Lactobacillus brevis NPS-QW-145 and its γ-aminobutyric acid biosynthesis ability in milk

    OpenAIRE

    Qinglong Wu; Yee-Song Law; Nagendra P. Shah

    2015-01-01

    Most high ?-aminobutyric acid (GABA) producers are Lactobacillus brevis of plant origin, which may be not able to ferment milk well due to its poor proteolytic nature as evidenced by the absence of genes encoding extracellular proteinases in its genome. In the present study, two glutamic acid decarboxylase (GAD) genes, gadA and gadB, were found in high GABA-producing L. brevis NPS-QW-145. Co-culturing of this organism with conventional dairy starters was carried out to manufacture GABA-rich f...

  14. The effect of fermented buckwheat on producing l-carnitine- and γ-aminobutyric acid (GABA)-enriched designer eggs.

    Science.gov (United States)

    Park, Namhyeon; Lee, Tae-Kyung; Nguyen, Thi Thanh Hanh; An, Eun-Bae; Kim, Nahyun M; You, Young-Hyun; Park, Tae-Sub; Kim, Doman

    2017-07-01

    The potential of fermented buckwheat as a feed additive was studied to increase l-carnitine and γ-aminobutyric acid (GABA) in designer eggs. Buckwheat contains high levels of lysine, methionine and glutamate, which are precursors for the synthesis of l-carnitine and GABA. Rhizopus oligosporus was used for the fermentation of buckwheat to produce l-carnitine and GABA that exert positive effects such as enhanced metabolism, antioxidant activities, immunity and blood pressure control. A novel analytical method for simultaneously detecting l-carnitine and GABA was developed using liquid chromatography/mass spectrometry (LC/MS) and LC/MS/MS. The fermented buckwheat extract contained 4 and 34 times more l-carnitine and GABA respectively compared with normal buckwheat. Compared with the control, the fermented buckwheat extract-fed group showed enriched l-carnitine (13.6%) and GABA (8.4%) in the yolk, though only l-carnitine was significantly different (P < 0.05). Egg production (9.4%), albumen weight (2.1%) and shell weight (5.8%) were significantly increased (P < 0.05). There was no significant difference in yolk weight, and total cholesterol (1.9%) and triglyceride (4.9%) in the yolk were lowered (P < 0.05). Fermented buckwheat as a feed additive has the potential to produce l-carnitine- and GABA-enriched designer eggs with enhanced nutrition and homeostasis. These designer eggs pose significant potential to be utilized in superfood production and supplement industries. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

  15. Channel opening of γ-aminobutyric acid receptor from rat brain: molecular mechanisms of the receptor responses

    International Nuclear Information System (INIS)

    Cash, D.J.; Subbarao, K.

    1987-01-01

    The function of γ-aminobutyric acid (GABA) receptors, which mediate transmembrane chloride flux, can be studied by use of 36 Cl - isotope tracer with membrane from mammalian brain by quench-flow technique, with reaction times that allow resolution of the receptor desensitization rates from the ion flux rates. The rates of chloride exchange into the vesicles in the absence and presence of GABA were characterized with membrane from rat cerebral cortex. Unspecific 36 Cl - influx was completed in three phases of ca. 3% (t/sub 1/2/ = 0.6 s), 56% (t/sub 1/2 = 82 s), and 41% (t/sub 1/2 = 23 min). GABA-mediated, specific chloride exchange occurred with 6.5% of the total vesicular internal volume. The GABA-dependent 36 Cl - influx proceeded in two phases, each progressively slowed by desensitization. The measurements supported the presence of two distinguishable active GABA receptors on the same membrane mediating chloride exchange into the vesicles. The half-response concentrations were similar for both receptors. The two receptors were present in the activity ratio of ca. 4/1, similar to the ratio of low affinity to high-affinity GABA sites found in ligand binding experiments. The desensitization rates have a different dependence on GABA concentration than the channel-opening equilibria. For both receptors, the measurements over a 2000-fold GABA concentration range required a minimal mechanism involving the occupation of both of the two GABA binding sites for significant channel opening; then the receptors were ca. 80% open. Similarly for both receptors, desensitization was mediated by a different pair of binding sites, although desensitization with only one ligand molecule bound could occur at a 20-fold slower rate

  16. Linking γ-aminobutyric acid A receptor to epidermal growth factor receptor pathways activation in human prostate cancer.

    Science.gov (United States)

    Wu, Weijuan; Yang, Qing; Fung, Kar-Ming; Humphreys, Mitchell R; Brame, Lacy S; Cao, Amy; Fang, Yu-Ting; Shih, Pin-Tsen; Kropp, Bradley P; Lin, Hsueh-Kung

    2014-03-05

    Neuroendocrine (NE) differentiation has been attributed to the progression of castration-resistant prostate cancer (CRPC). Growth factor pathways including the epidermal growth factor receptor (EGFR) signaling have been implicated in the development of NE features and progression to a castration-resistant phenotype. However, upstream molecules that regulate the growth factor pathway remain largely unknown. Using androgen-insensitive bone metastasis PC-3 cells and androgen-sensitive lymph node metastasis LNCaP cells derived from human prostate cancer (PCa) patients, we demonstrated that γ-aminobutyric acid A receptor (GABA(A)R) ligand (GABA) and agonist (isoguvacine) stimulate cell proliferation, enhance EGF family members expression, and activate EGFR and a downstream signaling molecule, Src, in both PC-3 and LNCaP cells. Inclusion of a GABA(A)R antagonist, picrotoxin, or an EGFR tyrosine kinase inhibitor, Gefitinib (ZD1839 or Iressa), blocked isoguvacine and GABA-stimulated cell growth, trans-phospohorylation of EGFR, and tyrosyl phosphorylation of Src in both PCa cell lines. Spatial distributions of GABAAR α₁ and phosphorylated Src (Tyr416) were studied in human prostate tissues by immunohistochemistry. In contrast to extremely low or absence of GABA(A)R α₁-positive immunoreactivity in normal prostate epithelium, elevated GABA(A)R α₁ immunoreactivity was detected in prostate carcinomatous glands. Similarly, immunoreactivity of phospho-Src (Tyr416) was specifically localized and limited to the nucleoli of all invasive prostate carcinoma cells, but negative in normal tissues. Strong GABAAR α₁ immunoreactivity was spatially adjacent to the neoplastic glands where strong phospho-Src (Tyr416)-positive immunoreactivity was demonstrated, but not in adjacent to normal glands. These results suggest that the GABA signaling is linked to the EGFR pathway and may work through autocrine or paracine mechanism to promote CRPC progression. Copyright © 2013 Elsevier

  17. Paclitaxel Causes Electrophysiological Changes in the Anterior Cingulate Cortex via Modulation of the γ-Aminobutyric Acid-ergic System.

    Science.gov (United States)

    Nashawi, Houda; Masocha, Willias; Edafiogho, Ivan O; Kombian, Samuel B

    The aim of this study was to elucidate any electrophysiological changes that may contribute to the development of neuropathic pain during treatment with the anticancer drug paclitaxel, particularly in the γ-aminobutyric acid (GABA) system. One hundred and eight Sprague-Dawley rats were used (untreated control: 43; vehicle-treated: 21, and paclitaxel-treated: 44). Paclitaxel (8 mg/kg) was administered intraperitoneally on 2 alternate days to induce mechanical allodynia. The rats were sacrificed 7 days after treatment to obtain slices of the anterior cingulate cortex (ACC), a brain region involved in the central processing of pain. Field excitatory postsynaptic potentials (fEPSPs) were recorded in layer II/III of ACC slices, and stimulus-response curves were constructed. The observed effects were pharmacologically characterized by bath application of GABA and appropriate drugs to the slices. The paclitaxel-treated rats developed mechanical allodynia (i.e. reduced withdrawal threshold to mechanical stimuli). Slices from paclitaxel-treated rats produced a significantly higher maximal response (Emax) than those from untreated rats (p GABA (0.4 µM) reversed this effect and returned the excitability to a level similar to control. Pretreatment of the slices with the GABAB receptor blocker CGP 55845 (50 µM) increased Emax in slices from untreated rats (p GABA deficit in paclitaxel-treated rats compared to untreated ones. Such a deficit could contribute to the pathophysiology of paclitaxel-induced neuropathic pain (PINP). Thus, the GABAergic system might be a potential therapeutic target for managing PINP. © 2016 S. Karger AG, Basel.

  18. Desensitization of γ-aminobutyric acid receptor from rat brain: two distinguishable receptors on the same membrane

    International Nuclear Information System (INIS)

    Cash, D.J.; Subbarao, K.

    1987-01-01

    Transmembrane chloride flux mediated by γ-aminobutyric acid (GABA) receptor can be measured with a mammalian brain homogenate preparation containing sealed membrane vesicles. The preparation can be mixed rapidly with solutions of defined composition. Influx of 36 Cl - tracer initiated by mixing with GABA was rapidly terminated by mixing with bicuculline methiodide. The decrease in the isotope influx measurement due to prior incubation of the vesicle preparation with GABA, which increased with preincubation time and GABA concentration, was attributed to desensitization of the GABA receptor. By varying the time of preincubation with GABA between 10 ms and 50 s with quench-flow technique, the desensitization rates could be measured over their whole time course independently of the chloride ion flux rate. Most of the receptor activity decreased in a fast phase of desensitization complete in 200 ms at saturation with GABA. Remaining activity was desensitized in a few seconds. These two phases of desensitization were each kinetically first order and were shown to correspond with two distinguishable GABA receptors on the same membrane. The receptor activities could be estimated, and the faster desensitizing receptor was the predominant one, giving on average ca. 80% of the total activity. The half-response concentrations were similar, 150 and 114 μM for the major and minor receptors, respectively. The dependence on GABA concentration indicated that desensitization is mediated by two GABA binding sites. The fast desensitization rate was approximately 20-fold faster than previously reported rates while the slower desensitization rate was slightly faster than previously reported rates

  19. Mechanism of Inactivation of γ-Aminobutyric Acid Aminotransferase by (1 S ,3 S )-3-Amino-4-difluoromethylene-1-cyclopentanoic Acid (CPP-115)

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Hyunbeom [Department; Doud, Emma H. [Department; Department; Wu, Rui [Department; Sanishvili, Ruslan [X-ray; Juncosa, Jose I. [Department; Liu, Dali [Department; Kelleher, Neil L. [Department; Department; Silverman, Richard B. [Department; Department

    2015-02-10

    gamma-Aminobutyric acid aminotransferase (GABA-AT) is a pyridoxal 5'-phosphate (PLP)-dependent enzyme that degrades GABA, the principal inhibitory neurotransmitter in mammalian cells. When the concentration of GABA falls below a threshold level, convulsions can occur. Inhibition of GABA-AT raises GABA levels in the brain, which can terminate seizures as well as have potential therapeutic applications in treating other neurological disorders, including drug addiction. Among the analogues that we previously developed, (1S,3S)-3-amino-4-difluoromethylene-1-cyclopentanoic acid (CPP-115) showed 187 times greater potency than that of vigabatrin, a known inactivator of GABA-AT and approved drug (Sabril) for the treatment of infantile spasms and refractory adult epilepsy. Recently, CPP-115 was shown to have no adverse effects in a Phase I clinical trial. Here we report a novel inactivation mechanism for CPP-115, a mechanism-based inactivator that undergoes GABA-AT-catalyzed hydrolysis of the difluoromethylene group to a carboxylic acid with concomitant loss of two fluoride ions and coenzyme conversion to pyridoxamine 5'-phosphate (PMP). The partition ratio for CPP-115 with GABA-AT is about 2000, releasing cyclopentanone-2,4-dicarboxylate (22) and two other precursors of this compound (20 and 21). Time-dependent inactivation occurs by a conformational change induced by the formation of the aldimine of 4-aminocyclopentane-1,3-dicarboxylic acid and PMP (20), which disrupts an electrostatic interaction between Glu270 and Arg445 to form an electrostatic interaction between Arg445 and the newly formed carboxylate produced by hydrolysis of the difluoromethylene group in CPP-115, resulting in a noncovalent, tightly bound complex. This represents a novel mechanism for inactivation of GABA-AT and a new approach for the design of mechanism-based inactivators in general.

  20. DL-β-aminobutyric acid-induced resistance in soybean against Aphis glycines Matsumura (Hemiptera: Aphididae.

    Directory of Open Access Journals (Sweden)

    Yunpeng Zhong

    Full Text Available Priming can improve plant innate capability to deal with the stresses caused by both biotic and abiotic factors. In this study, the effect of DL-β-amino-n-butyric acid (BABA against Aphis glycines Matsumura, the soybean aphid (SA was evaluated. We found that 25 mM BABA as a root drench had minimal adverse impact on plant growth and also efficiently protected soybean from SA infestation. In both choice and non-choice tests, SA number was significantly decreased to a low level in soybean seedlings drenched with 25 mM BABA compared to the control counterparts. BABA treatment resulted in a significant increase in the activities of several defense enzymes, such as phenylalanine ammonia-lyase (PAL, peroxidase (POX, polyphenol oxidase (PPO, chitinase (CHI, and β-1, 3-glucanase (GLU in soybean seedlings attacked by aphid. Meanwhile, the induction of 15 defense-related genes by aphid, such as AOS, CHS, MMP2, NPR1-1, NPR1-2, and PR genes, were significantly augmented in BABA-treated soybean seedlings. Our study suggest that BABA application is a promising way to enhance soybean resistance against SA.

  1. The Enantiomers of 4-Amino-3-fluorobutanoic Acid as Substrates for γ-Aminobutyric Acid Aminotransferase. Conformational Probes for GABA Binding†

    Science.gov (United States)

    Clift, Michael; Ji, Haitao; Deniau, Gildas P.; O’Hagan, David; Silverman, Richard B.

    2008-01-01

    γ-Aminobutyric acid aminotransferase (GABA-AT), a pyridoxal 5’-phosphate dependent enzyme, catalyzes the degradation of the inhibitory neurotransmitter γ-aminobutyric acid (GABA) to succinic semialdehyde with concomitant conversion of pyridoxal 5’-phosphate (PLP) to pyridoxamine 5’-phosphate (PMP). The enzyme then catalyzes the conversion of α-ketoglutarate to the excitatory neurotransmitter L-glutamate. Racemic 4-amino-3-fluorobutanoic acid (3-F-GABA) was shown previously to act as a substrate for GABA-AT, not for transamination, but for HF elimination. Here we report studies of the reaction catalyzed by GABA-AT on (R)- and (S)-3-F-GABA. Neither enantiomer is a substrate for transamination. Very little elimination from the (S)-enantiomer was detected using a coupled enzyme assay; The rate of elimination of HF from the (R)-enantiomer is at least 10 times greater than that for the (S)-enantiomer. The (R)-enantiomer is about 20 times more efficient as a substrate for GABA-AT catalyzed HF elimination than GABA is a substrate for transamination. The (R)-enantiomer also inhibits the transamination of GABA 10 times more effectively than the (S)-enantiomer. Using a combination of computer modeling and the knowledge that vicinal C-F and C-NH3+ bonds have a strong preference to align gauche rather than anti to each other, it is concluded that on binding of free 3-F-GABA to GABA-AT the optimal conformation places the C-NH3+ and C-F bonds gauche in the (R)-enantiomer but anti in the (S)-enantiomer. Furthermore, the dynamic binding process and the bioactive conformation of GABA bound to GABA-AT have been inferred based on the different biological behavior of the two enantiomers of 3-F-GABA when they bind to the enzyme. The present study suggests that the C-F bond can be utilized as a conformational probe to explore the dynamic binding process and provide insight into the bioactive conformation of substrates, which cannot be easily determined by other biophysical

  2. Regulation of Brain-Derived Neurotrophic Factor Exocytosis and Gamma-Aminobutyric Acidergic Interneuron Synapse by the Schizophrenia Susceptibility Gene Dysbindin-1.

    Science.gov (United States)

    Yuan, Qiang; Yang, Feng; Xiao, Yixin; Tan, Shawn; Husain, Nilofer; Ren, Ming; Hu, Zhonghua; Martinowich, Keri; Ng, Julia S; Kim, Paul J; Han, Weiping; Nagata, Koh-Ichi; Weinberger, Daniel R; Je, H Shawn

    2016-08-15

    Genetic variations in dystrobrevin binding protein 1 (DTNBP1 or dysbindin-1) have been implicated as risk factors in the pathogenesis of schizophrenia. The encoded protein dysbindin-1 functions in the regulation of synaptic activity and synapse development. Intriguingly, a loss of function mutation in Dtnbp1 in mice disrupted both glutamatergic and gamma-aminobutyric acidergic transmission in the cerebral cortex; pyramidal neurons displayed enhanced excitability due to reductions in inhibitory synaptic inputs. However, the mechanism by which reduced dysbindin-1 activity causes inhibitory synaptic deficits remains unknown. We investigated the role of dysbindin-1 in the exocytosis of brain-derived neurotrophic factor (BDNF) from cortical excitatory neurons, organotypic brain slices, and acute slices from dysbindin-1 mutant mice and determined how this change in BDNF exocytosis transsynaptically affected the number of inhibitory synapses formed on excitatory neurons via whole-cell recordings, immunohistochemistry, and live-cell imaging using total internal reflection fluorescence microscopy. A decrease in dysbindin-1 reduces the exocytosis of BDNF from cortical excitatory neurons, and this reduction in BDNF exocytosis transsynaptically resulted in reduced inhibitory synapse numbers formed on excitatory neurons. Furthermore, application of exogenous BDNF rescued the inhibitory synaptic deficits caused by the reduced dysbindin-1 level in both cultured cortical neurons and slice cultures. Taken together, our results demonstrate that these two genes linked to risk for schizophrenia (BDNF and dysbindin-1) function together to regulate interneuron development and cortical network activity. This evidence supports the investigation of the association between dysbindin-1 and BDNF in humans with schizophrenia. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  3. Biodiversity and γ-Aminobutyric Acid Production by Lactic Acid Bacteria Isolated from Traditional Alpine Raw Cow’s Milk Cheeses

    Directory of Open Access Journals (Sweden)

    Elena Franciosi

    2015-01-01

    Full Text Available “Nostrano-cheeses” are traditional alpine cheeses made from raw cow’s milk in Trentino-Alto Adige, Italy. This study identified lactic acid bacteria (LAB developing during maturation of “Nostrano-cheeses” and evaluated their potential to produce γ-aminobutyric acid (GABA, an immunologically active compound and neurotransmitter. Cheese samples were collected on six cheese-making days, in three dairy factories located in different areas of Trentino and at different stages of cheese ripening (24 h, 15 days, and 1, 2, 3, 6, and 8 months. A total of 1,059 LAB isolates were screened using Random Amplified Polymorphic DNA-PCR (RAPD-PCR and differentiated into 583 clusters. LAB strains from dominant clusters (n=97 were genetically identified to species level by partial 16S rRNA gene sequencing. LAB species most frequently isolated were Lactobacillus paracasei, Streptococcus thermophilus, and Leuconostoc mesenteroides. The 97 dominant clusters were also characterized for their ability in producing GABA by high-performance liquid chromatography (HPLC. About 71% of the dominant bacteria clusters evolving during cheeses ripening were able to produce GABA. Most GABA producers were Lactobacillus paracasei but other GABA producing species included Lactococcus lactis, Lactobacillus plantarum, Lactobacillus rhamnosus, Pediococcus pentosaceus, and Streptococcus thermophilus. No Enterococcus faecalis or Sc. macedonicus isolates produced GABA. The isolate producing the highest amount of GABA (80.0±2.7 mg/kg was a Sc. thermophilus.

  4. Gas release-based prescreening combined with reversed-phase HPLC quantitation for efficient selection of high-γ-aminobutyric acid (GABA)-producing lactic acid bacteria.

    Science.gov (United States)

    Wu, Qinglong; Shah, Nagendra P

    2015-02-01

    High γ-aminobutyric acid (GABA)-producing lactobacilli are promising for the manufacture of GABA-rich foods and to synthesize GRAS (generally recognized as safe)-grade GABA. However, common chromatography-based screening is time-consuming and inefficient. In the present study, Korean kimchi was used as a model of lactic acid-based fermented foods, and a gas release-based prescreening of potential GABA producers was developed. The ability to produce GABA by potential GABA producers in de Man, Rogosa, and Sharpe medium supplemented with or without monosodium glutamate was further determined by HPLC. Based on the results, 9 isolates were regarded as high GABA producers, and were further genetically identified as Lactobacillus brevis based on the sequences of 16S rRNA gene. Gas release-based prescreening combined with reversed-phase HPLC confirmation was an efficient and cost-effective method to identify high-GABA-producing LAB, which could be good candidates for probiotics. The GABA that is naturally produced by these high-GABA-producing LAB could be used as a food additive. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  5. Investigation of Gamma-aminobutyric acid (GABA A receptors genes and migraine susceptibility

    Directory of Open Access Journals (Sweden)

    Ciccodicola Alfredo

    2008-12-01

    Full Text Available Abstract Background Migraine is a neurological disorder characterized by recurrent attacks of severe headache, affecting around 12% of Caucasian populations. It is well known that migraine has a strong genetic component, although the number and type of genes involved is still unclear. Prior linkage studies have reported mapping of a migraine gene to chromosome Xq 24–28, a region containing a cluster of genes for GABA A receptors (GABRE, GABRA3, GABRQ, which are potential candidate genes for migraine. The GABA neurotransmitter has been implicated in migraine pathophysiology previously; however its exact role has not yet been established, although GABA receptors agonists have been the target of therapeutic developments. The aim of the present research is to investigate the role of the potential candidate genes reported on chromosome Xq 24–28 region in migraine susceptibility. In this study, we have focused on the subunit GABA A receptors type ε (GABRE and type θ (GABRQ genes and their involvement in migraine. Methods We have performed an association analysis in a large population of case-controls (275 unrelated Caucasian migraineurs versus 275 controls examining a set of 3 single nucleotide polymorphisms (SNPs in the coding region (exons 3, 5 and 9 of the GABRE gene and also the I478F coding variant of the GABRQ gene. Results Our study did not show any association between the examined SNPs in our test population (P > 0.05. Conclusion Although these particular GABA receptor genes did not show positive association, further studies are necessary to consider the role of other GABA receptor genes in migraine susceptibility.

  6. Gamma-aminobutyric acid-modulated benzodiazepine binding sites in bacteria

    International Nuclear Information System (INIS)

    Lummis, S.C.R.; Johnston, G.A.R.; Nicoletti, G.; Holan, G.

    1991-01-01

    Benzodiazepine binding sites, which were once considered to exist only in higher vertebrates, are here demonstrated in the bacteria E. coli. The bacterial [ 3 H]diazepam binding sites are modulated by GABA; the modulation is dose dependent and is reduced at high concentrations. The most potent competitors of E.Coli [ 3 H]diazepam binding are those that are active in displacing [ 3 H]benzodiazepines from vertebrate peripheral benzodiazepine binding sites. These vertebrate sites are not modulated by GABA, in contrast to vertebrate neuronal benzodiazepine binding sites. The E.coli benzodiazepine binding sites therefore differ from both classes of vertebrate benzodiazepine binding sites; however the ligand spectrum and GABA-modulatory properties of the E.coli sites are similar to those found in insects. This intermediate type of receptor in lower species suggests a precursor for at least one class of vertebrate benzodiazepine binding sites may have existed

  7. Comparison of Nootropic and Neuroprotective Features of Aryl-Substituted Analogs of Gamma-Aminobutyric Acid.

    Science.gov (United States)

    Tyurenkov, I N; Borodkina, L E; Bagmetova, V V; Berestovitskaya, V M; Vasil'eva, O S

    2016-02-01

    GABA analogs containing phenyl (phenibut) or para-chlorophenyl (baclofen) substituents demonstrated nootropic activity in a dose of 20 mg/kg: they improved passive avoidance conditioning, decelerated its natural extinction, and exerted antiamnestic effect on the models of amnesia provoked by scopolamine or electroshock. Tolyl-containing GABA analog (tolibut, 20 mg/kg) exhibited antiamnestic activity only on the model of electroshock-induced amnesia. Baclofen and, to a lesser extent, tolibut alleviated seizures provoked by electroshock, i.e. both agents exerted anticonvulsant effect. All examined GABA aryl derivatives demonstrated neuroprotective properties on the maximum electroshock model: they shortened the duration of coma and shortened the period of spontaneous motor activity recovery. In addition, these agents decreased the severity of passive avoidance amnesia and behavioral deficit in the open field test in rats exposed to electroshock. The greatest neuroprotective properties were exhibited by phenyl-containing GABA analog phenibut.

  8. Does gamma-aminobutyric acid (GABA influence the development of chronic inflammation in rheumatoid arthritis?

    Directory of Open Access Journals (Sweden)

    Bridges S Louis

    2008-01-01

    Full Text Available Abstract Background Recent studies have demonstrated a role for spinal p38 MAP kinase (MAPK in the development of chronic inflammation and peripheral arthritis and a role for GABA in the inhibition of p38 MAPK mediated effects. Integrating these data suggests that GABA may play a role in downregulating mechanisms that lead to the production of proinflammatory agents such as interleukin-1, interleukin-6, and matrix metalloproteinase 3 – agents implicated in the pathogenesis of rheumatoid arthritis (RA. Genetic studies have also associated RA with members of the p38 MAPK pathway. Hypothesis We propose a hypothesis for an inefficient GABA signaling system that results in unchecked proinflammatory cytokine production via the p38 MAPK pathway. This model also supports the need for increasing research in the integration of immunology and neuroscience.

  9. Nitrate uptake and utilization is modulated by exogenous gamma-aminobutyric acid in Arabidopsis thaliana seedlings.

    Science.gov (United States)

    Barbosa, Jose M; Singh, Narendra K; Cherry, Joe H; Locy, Robert D

    2010-06-01

    Exogenously applied GABA modulates root growth by inhibition of root elongation when seedlings were grown in vitro on full-strength Murashige and Skoog (MS) salts, but root elongation was stimulated when seedlings were grown on 1/8 strength MS salts. When the concentration of single ions in MS salts was individually varied, the control of growth between inhibition and stimulation was found to be related to the level of nitrate (NO(3)(-)) in the growth medium. At NO(3)(-) concentrations below 40 mM (full-strength MS salts level), root growth was stimulated by the addition of GABA to the growth medium; whereas at concentrations above 40 mM NO(3)(-), the addition of GABA to the growth medium inhibited root elongation. GABA promoted NO(3)(-) uptake at low NO(3)(-), while GABA inhibited NO(3)(-) uptake at high NO(3)(-). Activities of several enzymes involved in nitrogen and carbon metabolism including nitrate reductase (NR), glutamine synthetase (GS), glutamate synthase (NADH-GOGAT), NADP-dependent isocitrate dehydrogenase (NADP-ICDH), and phosphoenol pyruvate carboxylase (PEPCase) were regulated by GABA in the growth medium. Supplementing 1/8 strength MS medium with 50 mM GABA enhanced the activities of all of the above enzymes except ICDH activities in root tissues. However, at full-strength MS, GABA showed no inhibitory effect on the activities of these enzymes, except on GS in both root and shoot tissues, and PEPCase activity in shoot tissues. Exogenous GABA increased the amount of NR protein rather than its activation status in the tissues. This study shows that GABA affects the growth of Arabidopsis, possibly by acting as a signaling molecule, modulating the activity of enzymes involved in primary nitrogen metabolism and nitrate uptake.

  10. Effects of gamma-aminobutyric acid (GABA) on synaptogenesis and synaptic function

    DEFF Research Database (Denmark)

    Belhage, B; Hansen, Gert Helge; Elster, L

    1998-01-01

    , but the intracellular link between GABA receptor activation and DNA transcription is largely unknown. GABA also controls the induction and development of functionally and pharmacologically different GABAA receptor subtypes. The induced receptors are likely to be inserted only into the synaptic membrane domain. However...

  11. Influence of Gamma Aminobutyric Acid on Some Biochemical Alterations in Irradiated and Streptozotocin Treated Rats

    International Nuclear Information System (INIS)

    Mohamed, A.S.M.

    2015-01-01

    The objective of this study was to evaluate the role of GABA on some metabolic complications in STZ-treated, γ- irradiated and STZ-treated-γ-irradiated rats. Animals sacrificed 3 weeks after the different treatments showed that the intraperitoneal administration of STZ (60 mg/Kg) to male albino Sprague Dawley rats induced hyperglycemia and insulin deficiency (DM type 1). While whole body γ-irradiation with 6 Gy using Cs-137 source provoked hyperglycemia, hyperinsulinaemia and insulin resistance (DM type 2) and whole body γ-irradiation of STZ-treated rats induced hyperglycemia, insulin deficiency and insulin resistance. Dyslipidemia (elevated triglycerides, total cholesterol and LDL-C and decreased HDL-C) was recorded in STZ-treated, γ-irradiated and STZ-treated-γ-irradiated rats. Oxidative stress evidenced by significant decreases of SOD, catalase and GSH-Px activities and significant increases of MDA and AOPP was recorded in pancreas, liver and kidney tissues. Oxidative stress in pancreatic tissues was associated with damage of islets of Langerhans and significant decreases of GABA level and GAD activity. Oxidative stress in liver was accompanied by significant elevation of serum ALT and AST activities. Oxidative stress in kidney tissues was associated with significant increases of urea and creatinine levels. The administration of GABA daily via gavages (200 mg/Kg/day) during 3 weeks to STZ-treated, γ-irradiated and STZ-treated-γ-irradiated rats rectified insulin, glucose and lipid levels, reduced oxidative stress in pancreatic tissues accompanied by regenerating pancreatic islets of Langerhans and elevation of GABA level and GAD activity. GABA reduced also oxidative stress in liver and kidney tissues accompanied by lower serum ALT and AST activities and urea and creatinine levels

  12. Mechanism of inactivation of γ-aminobutyric acid aminotransferase by (1S,3S)-3-amino-4-difluoromethylene-1-cyclopentanoic acid (CPP-115).

    Science.gov (United States)

    Lee, Hyunbeom; Doud, Emma H; Wu, Rui; Sanishvili, Ruslan; Juncosa, Jose I; Liu, Dali; Kelleher, Neil L; Silverman, Richard B

    2015-02-25

    γ-Aminobutyric acid aminotransferase (GABA-AT) is a pyridoxal 5'-phosphate (PLP)-dependent enzyme that degrades GABA, the principal inhibitory neurotransmitter in mammalian cells. When the concentration of GABA falls below a threshold level, convulsions can occur. Inhibition of GABA-AT raises GABA levels in the brain, which can terminate seizures as well as have potential therapeutic applications in treating other neurological disorders, including drug addiction. Among the analogues that we previously developed, (1S,3S)-3-amino-4-difluoromethylene-1-cyclopentanoic acid (CPP-115) showed 187 times greater potency than that of vigabatrin, a known inactivator of GABA-AT and approved drug (Sabril) for the treatment of infantile spasms and refractory adult epilepsy. Recently, CPP-115 was shown to have no adverse effects in a Phase I clinical trial. Here we report a novel inactivation mechanism for CPP-115, a mechanism-based inactivator that undergoes GABA-AT-catalyzed hydrolysis of the difluoromethylene group to a carboxylic acid with concomitant loss of two fluoride ions and coenzyme conversion to pyridoxamine 5'-phosphate (PMP). The partition ratio for CPP-115 with GABA-AT is about 2000, releasing cyclopentanone-2,4-dicarboxylate (22) and two other precursors of this compound (20 and 21). Time-dependent inactivation occurs by a conformational change induced by the formation of the aldimine of 4-aminocyclopentane-1,3-dicarboxylic acid and PMP (20), which disrupts an electrostatic interaction between Glu270 and Arg445 to form an electrostatic interaction between Arg445 and the newly formed carboxylate produced by hydrolysis of the difluoromethylene group in CPP-115, resulting in a noncovalent, tightly bound complex. This represents a novel mechanism for inactivation of GABA-AT and a new approach for the design of mechanism-based inactivators in general.

  13. Discovery of α-Substituted Imidazole-4-acetic Acid Analogues as a Novel Class of ρ1 γ-Aminobutyric Acid Type A Receptor Antagonists with Effect on Retinal Vascular Tone

    DEFF Research Database (Denmark)

    Krall, Jacob; Brygger, Benjamin M.; Sigurðardóttir, Sara B.

    2016-01-01

    The ρ-containing γ-aminobutyric acid type A receptors (GABAA Rs) play an important role in controlling visual signaling. Therefore, ligands that selectively target these GABAA Rs are of interest. In this study, we demonstrate that the partial GABAA R agonist imidazole-4-acetic acid (IAA) is able...... to penetrate the blood-brain barrier in vivo; we prepared a series of α- and N-alkylated, as well as bicyclic analogues of IAA to explore the structure-activity relationship of this scaffold focusing on the acetic acid side chain of IAA. The compounds were prepared via IAA from l-histidine by an efficient...

  14. Alteration of Transcripts of Stress-Protective Genes and Transcriptional Factors by γ-Aminobutyric Acid (GABA Associated with Improved Heat and Drought Tolerance in Creeping Bentgrass (Agrostis stolonifera

    Directory of Open Access Journals (Sweden)

    Zhou Li

    2018-05-01

    Full Text Available Gamma-aminobutyric acid (GABA may play a positive role in regulating plant tolerance to drought or heat stress. The objectives of this study were to investigate the physiological effects of GABA on tolerance of creeping bentgrass (Agrostis stolonifera to heat and drought stress and to determine whether enhanced heat and drought tolerance due to GABA treatment was associated with the up-regulation of selected genes and transcriptional factors involved in stress protection. Creeping bentgrass (cultivar “Penncross” plants were treated with 0.5 mM GABA or water (untreated control as a foliar spray and were subsequently exposed to heat stress (35/30 °C, day/night, drought stress by withholding irrigation, or non-stress conditions in controlled-environment growth chambers. Exogenous application of GABA significantly improved plant tolerance to heat and drought stress, as reflected by increased leaf water content, cell membrane stability, and chlorophyll content. The analysis of gene transcript level revealed that exogenous GABA up-regulated the expression of ABF3, POD, APX, HSP90, DHN3, and MT1 during heat stress and the expression of CDPK26, MAPK1, ABF3, WRKY75, MYB13, HSP70, MT1, 14-3-3, and genes (SOD, CAT, POD, APX, MDHAR, DHAR, and GR encoding antioxidant enzymes during drought stress. The up-regulation of the aforementioned stress-protective genes and transcriptional factors could contribute to improved heat and drought tolerance in creeping bentgrass.

  15. Alteration of Transcripts of Stress-Protective Genes and Transcriptional Factors by γ-Aminobutyric Acid (GABA) Associated with Improved Heat and Drought Tolerance in Creeping Bentgrass (Agrostis stolonifera).

    Science.gov (United States)

    Li, Zhou; Peng, Yan; Huang, Bingru

    2018-05-31

    Gamma-aminobutyric acid (GABA) may play a positive role in regulating plant tolerance to drought or heat stress. The objectives of this study were to investigate the physiological effects of GABA on tolerance of creeping bentgrass ( Agrostis stolonifera ) to heat and drought stress and to determine whether enhanced heat and drought tolerance due to GABA treatment was associated with the up-regulation of selected genes and transcriptional factors involved in stress protection. Creeping bentgrass (cultivar "Penncross") plants were treated with 0.5 mM GABA or water (untreated control) as a foliar spray and were subsequently exposed to heat stress (35/30 °C, day/night), drought stress by withholding irrigation, or non-stress conditions in controlled-environment growth chambers. Exogenous application of GABA significantly improved plant tolerance to heat and drought stress, as reflected by increased leaf water content, cell membrane stability, and chlorophyll content. The analysis of gene transcript level revealed that exogenous GABA up-regulated the expression of ABF3 , POD , APX , HSP90 , DHN3 , and MT1 during heat stress and the expression of CDPK26 , MAPK1 , ABF3 , WRKY75 , MYB13 , HSP70 , MT1 , 14-3-3 , and genes ( SOD , CAT , POD , APX , MDHAR , DHAR , and GR ) encoding antioxidant enzymes during drought stress. The up-regulation of the aforementioned stress-protective genes and transcriptional factors could contribute to improved heat and drought tolerance in creeping bentgrass.

  16. Luminescence from {gamma}-irradiated humic acid

    Energy Technology Data Exchange (ETDEWEB)

    Goraczko, Wieslaw [Faculty of Chemical Technology, Radio- and Photochemistry Department, Poznan University of Technology, ul. Piotrowo 3, 60-965 Poznan (Poland); Slawinski, Janusz [Institute of Ecotechnology, State Higher Vocational School, ul. Ks. Kard. S.Wyszynskiego 38, 62-200 Gniezno (Poland)

    2008-07-15

    This study was conducted to investigate the ultraweak delayed radiochemiluminescence (RCL) spectra, kinetics and spectroscopic properties of humic acids (HAs) after {gamma}-radiation exposure (absorbed doses of 1-10 kGy, Co-60) in model systems. The kinetics and spectral distribution of RCL (340-650 nm) were measured using the single photon counting (SPC) method and cut-off filters. The intensity of fluorescence ({lambda}{sub ex}=390, 440, 490 and 540 nm) covering the spectral range 400-580 nm was heavily dependent on the {lambda}{sub ex} and slightly increased with the absorbed dose of {gamma}-radiation. Absorption spectra (the range 240-800 nm) and color coefficients E{sub 2.6/4} and E{sub 4/6} of irradiated solutions indicated that post-radiative degradation/polymerization processes take place in the HA, changing their macromolecule size or properties. Comparison of FTIR spectra and elemental analysis proved an increased O and decreased C atoms in irradiated samples. The data indicate on the radiolysis-induced degradation of native HA into fulvic-like acids with higher hydrophilicity and lower molecular size.

  17. Accumulation mechanism of γ-aminobutyric acid in tomatoes (Solanum lycopersicum L.) under low O2 with and without CO2.

    Science.gov (United States)

    Mae, Nobukazu; Makino, Yoshio; Oshita, Seiichi; Kawagoe, Yoshinori; Tanaka, Atsushi; Aoki, Koh; Kurabayashi, Atsushi; Akihiro, Takashi; Akama, Kazuhito; Koike, Satoshi; Takayama, Mariko; Matsukura, Chiaki; Ezura, Hiroshi

    2012-02-01

    The storage of ripe tomatoes in low-O(2) conditions with and without CO(2) promotes γ-aminobutyric acid (GABA) accumulation. The activities of glutamate decarboxylase (GAD) and α-ketoglutarate-dependent GABA transaminase (GABA-TK) were higher and lower, respectively, following storage under hypoxic (2.4 or 3.5% O(2)) or adjusted aerobic (11% O(2)) conditions compared to the activities in air for 7 days at 25 °C. GAD activity was consistent with the expression level of mRNA for GAD. The GABA concentration in tomatoes stored under hypoxic conditions and adjusted aerobic conditions was 60-90% higher than that when they are stored in air on the same day. These results demonstrate that upregulation of GAD activity and downregulation of GABA-TK activity cause GABA accumulation in tomatoes stored under low-O(2) conditions. Meanwhile, the effect of CO(2) on GABA accumulation is probably minimal.

  18. Exogenous γ-aminobutyric acid (GABA) affects pollen tube growth via modulating putative Ca2+-permeable membrane channels and is coupled to negative regulation on glutamate decarboxylase

    Science.gov (United States)

    Yu, Guang-Hui; Zou, Jie; Feng, Jing; Peng, Xiong-Bo; Wu, Ju-You; Wu, Ying-Liang; Palanivelu, Ravishankar; Sun, Meng-Xiang

    2014-01-01

    γ-Aminobutyric acid (GABA) is implicated in pollen tube growth, but the molecular and cellular mechanisms that it mediates are largely unknown. Here, it is shown that exogenous GABA modulates putative Ca2+-permeable channels on the plasma membranes of tobacco pollen grains and pollen tubes. Whole-cell voltage-clamp experiments and non-invasive micromeasurement technology (NMT) revealed that the influx of Ca2+ increases in pollen tubes in response to exogenous GABA. It is also demonstrated that glutamate decarboxylase (GAD), the rate-limiting enzyme of GABA biosynthesis, is involved in feedback controls of Ca2+-permeable channels to fluctuate intracellular GABA levels and thus modulate pollen tube growth. The findings suggest that GAD activity linked with Ca2+-permeable channels relays an extracellular GABA signal and integrates multiple signal pathways to modulate tobacco pollen tube growth. Thus, the data explain how GABA mediates the communication between the style and the growing pollen tubes. PMID:24799560

  19. The novel isoxazoline ectoparasiticide lotilaner (Credelio™: a non-competitive antagonist specific to invertebrates γ-aminobutyric acid-gated chloride channels (GABACls

    Directory of Open Access Journals (Sweden)

    Lucien Rufener

    2017-11-01

    Full Text Available Abstract Background The isoxazolines are a novel class of parasiticides that are potent inhibitors of γ-aminobutyric acid (GABA-gated chloride channels (GABACls and, to a lesser extent, of inhibitory glutamate-gated chloride channels (GluCls. Lotilaner (Credelio™, a novel representative of this chemical class, is currently evaluated for its excellent ectoparasiticide properties. Methods In this study, we investigated the molecular mode of action and pharmacology of lotilaner. We report the successful gene identification, cDNA cloning and functional expression in Xenopus oocytes of Drosohpila melanogaster (wild type and dieldrin/fipronil-resistant forms, Lepeophtheirus salmonis (an ectoparasite copepod crustacean of salmon, Rhipicephalus microplus and Canis lupus familiaris GABACls. Automated Xenopus oocyte two-electrode voltage clamp electrophysiology was used to assess GABACls functionality and to compare ion channel inhibition by lotilaner with that of established insecticides addressing GABACls as targets. Results In these assays, we demonstrated that lotilaner is a potent non-competitive antagonist of insects (fly GABACls. No cross-resistance with dieldrin or fipronil resistance mutations was detected, suggesting that lotilaner might bind to a site at least partly different from the one bound by known GABACl blockers. Using co-application experiments, we observed that lotilaner antagonism differs significantly from the classical open channel blocker fipronil. We finally confirmed for the first time that isoxazoline compounds are not only powerful antagonists of GABACls of acari (ticks but also of crustaceans (sea lice, while no activity on a dog GABAA receptor was observed up to a concentration of 10 μM. Conclusions Together, these results demonstrate that lotilaner is a non-competitive antagonist specific to invertebrate’s γ-aminobutyric acid-gated chloride channels (GABACls. They contribute to our understanding of the mode of

  20. The novel isoxazoline ectoparasiticide lotilaner (Credelio™): a non-competitive antagonist specific to invertebrates γ-aminobutyric acid-gated chloride channels (GABACls).

    Science.gov (United States)

    Rufener, Lucien; Danelli, Vanessa; Bertrand, Daniel; Sager, Heinz

    2017-11-01

    The isoxazolines are a novel class of parasiticides that are potent inhibitors of γ-aminobutyric acid (GABA)-gated chloride channels (GABACls) and, to a lesser extent, of inhibitory glutamate-gated chloride channels (GluCls). Lotilaner (Credelio™), a novel representative of this chemical class, is currently evaluated for its excellent ectoparasiticide properties. In this study, we investigated the molecular mode of action and pharmacology of lotilaner. We report the successful gene identification, cDNA cloning and functional expression in Xenopus oocytes of Drosohpila melanogaster (wild type and dieldrin/fipronil-resistant forms), Lepeophtheirus salmonis (an ectoparasite copepod crustacean of salmon), Rhipicephalus microplus and Canis lupus familiaris GABACls. Automated Xenopus oocyte two-electrode voltage clamp electrophysiology was used to assess GABACls functionality and to compare ion channel inhibition by lotilaner with that of established insecticides addressing GABACls as targets. In these assays, we demonstrated that lotilaner is a potent non-competitive antagonist of insects (fly) GABACls. No cross-resistance with dieldrin or fipronil resistance mutations was detected, suggesting that lotilaner might bind to a site at least partly different from the one bound by known GABACl blockers. Using co-application experiments, we observed that lotilaner antagonism differs significantly from the classical open channel blocker fipronil. We finally confirmed for the first time that isoxazoline compounds are not only powerful antagonists of GABACls of acari (ticks) but also of crustaceans (sea lice), while no activity on a dog GABA A receptor was observed up to a concentration of 10 μM. Together, these results demonstrate that lotilaner is a non-competitive antagonist specific to invertebrate's γ-aminobutyric acid-gated chloride channels (GABACls). They contribute to our understanding of the mode of action of this new ectoparasiticide compound.

  1. Cloning of the γ-aminobutyric acid (GABA) ρ1 cDNA: A GABA receptor subunit highly expressed in the retina

    International Nuclear Information System (INIS)

    Cutting, G.R.; Lu, Luo; Kasch, L.M.; Montrose-Rafizadeh, C.; Antonarakis, S.E.; Guggino, W.B.; Kazazian, H.H. Jr.; O'Hara, B.F.; Donovan, D.M.; Shimada, Shoichi; Uhl, G.R.

    1991-01-01

    Type A γ-aminobutyric acid (GABA A ) receptors are a family of ligand-gated chloride channels that are the major inhibitory neurotransmitter receptors in the nervous system. Molecular cloning has revealed diversity in the subunits that compose this heterooligomeric receptor, but each previously elucidated subunit displays amino acid similarity in conserved structural elements. The authors have used these highly conserved regions to identify additional members of this family by using the polymerase chain reaction (PCR). One PCR product was used to isolate a full-length cDNA from a human retina cDNA library. The mature protein predicted from this cDNA sequence is 458 amino acids long and displays between 30 and 38% amino acid similarity to the previously identified GABA A subunits. This gene is expressed primarily in the retina but transcripts are also detected in the brain, lung, and thymus. Injection of Xenopus oocytes with RNA transcribed in vitro produces a GABA-responsive chloride conductance and expression of the cDNA in COS cells yields GABA-displaceable muscimol binding. These features are consistent with our identification of a GABA subunit, GABA ρ 1 , with prominent retinal expression that increases the diversity and tissue specificity of this ligand-gated ion-channel receptor family

  2. Enhancement of gama-aminobutyric acid (GABA) and other health-related metabolites in germinated red rice (Oryza sativa L.) by ultrasonication.

    Science.gov (United States)

    Ding, Junzhou; Ulanov, Alexander V; Dong, Mengyi; Yang, Tewu; Nemzer, Boris V; Xiong, Shanbai; Zhao, Siming; Feng, Hao

    2018-01-01

    Red rice (Oryza sativa L.) that has a red (reddish brown) bran layer in de-hulled rice is known to contain rich biofunctional components. Germination is an effective technique to improve the nutritional quality, digestibility, and flavor of de-hulled rice. Ultrasonication, a form of physical stimulation, has been documented as a novel approach to improve the nutritional quality of plant-based food. This study was undertaken to test the use of ultrasound to enhance the nutritional value of red rice. Ultrasonication (5min, 16W/L) was applied to rice during soaking or after 66h germination. Changes of metabolites (amino acids, sugars, and organic acids) in red rice treated by ultrasonication were determined using a GC/MS plant primary metabolomics analysis platform. Differential expressed metabolites were identified through multivariate statistical analysis. Results showed that γ-aminobutyric acid (GABA) and riboflavin (vitamin B 2 ) in red rice significantly increased after germination for 72h, and then experienced a further increase after treatment by ultrasound at different stages during germination. The metabolomics analysis showed that some plant metabolites, i.e. GABA, O-phosphoethanolamine, and glucose-6-phosphate were significantly increased after the ultrasonic treatment (VIP>1.5) in comparison with the untreated germinated rice. The findings of this study showed that controlled germination with ultrasonic stress is an effective method to enhance GABA and other health-promoted components in de-hulled rice. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Enhancement of γ-aminobutyric acid (GABA) in Nham (Thai fermented pork sausage) using starter cultures of Lactobacillus namurensis NH2 and Pediococcus pentosaceus HN8.

    Science.gov (United States)

    Ratanaburee, Anussara; Kantachote, Duangporn; Charernjiratrakul, Wilawan; Sukhoom, Ampaitip

    2013-10-15

    The aim was to produce Nham that was enriched with γ-aminobutyric acid (GABA); therefore two GABA producing lactic acid bacteria (Pediococcus pentosaceus HN8 and Lactobacillus namurensis NH2) were used as starter cultures. By using the central composite design (CCD) we showed that addition of 0.5% monosodium glutamate (MSG) together with an inoculum size of roughly 6logCFU/g of each of the two strains produced a maximal amounts of GABA (4051 mg/kg) in the 'GABA Nham' product. This was higher than any current popular commercial Nham product by roughly 8 times. 'GABA Nham' with the additions of both starters and MSG (TSM) supported maximum populations of lactic acid bacteria (LAB) with a minimum of yeasts and no staphylococci or molds when compared to the controls that had no addition of any starters or MSG (TNN), or only the addition of MSG (TNM), or with only the starter (TSN). Based on proximate analysis among the Nham sets, 'GABA Nham' was low in fat, carbohydrate and energy although its texture and color were slightly different from the control (TNN). However, sensory evaluations of 'GABA Nham' were more acceptable than the controls and commercial Nham products for all tested parameters. Hence, a unique novel 'GABA Nham' fermented pork sausage was successfully developed. © 2013.

  4. Gamma radiolysis of aqueous solution of ascorbic acid

    International Nuclear Information System (INIS)

    Loyola V, V.M.; Azamer B, J.A.; Laviada C, A.; Luna V, P.

    1977-01-01

    A preliminary study of the gamma radiolysis of a 1.13 x 10 -4 Maqueous solution of ascorbic acid is presented. It was found that dehydroascorbic acid was the principal product at doses of about 75 Krad. An increase in the dehydroascorbic acid concentration rangins from 5 to 40% was obtained, these values depend mainly on the initial ascorbic acid concentration. (author)

  5. Comparison of γ-aminobutyric acid and biogenic amine content of different types of ewe’s milk cheese produced in Sardinia, Italy

    Directory of Open Access Journals (Sweden)

    Gavina Manca

    2015-06-01

    Full Text Available The bioactive compounds γ-aminobutyric acid (GABA and biogenic amines (BA, together with protein-free amino acids, were measured by high-performance liquid chromatography in ewe’s milk cheeses produced in Sardinia with different technological traits. The study included three types of cheese: Pecorino Sardo PDO, Pecorino and Casu Marzu. Farmhouse Casu Marzu and Pecorino showed GABA content (maximum levels: 1001.3 and 378.1 mg 100 g–1 respectively that had never been found so high in cheese before, suggesting that these types of cheese present ideal conditions to produce GABA. These two types of cheese also showed high levels of BA (their total maximum levels were 1035.7 and 288.0 mg 100 g–1 respectively. Pearson correlation analysis detected significant correlation between GABA and the main BA present in the cheeses (tyramine, cadaverine and putrescine, suggesting that the factors affecting the production of GABA are the same as those influencing BA formation.

  6. Dairy Streptococcus thermophilus improves cell viability of Lactobacillus brevis NPS-QW-145 and its γ-aminobutyric acid biosynthesis ability in milk

    Science.gov (United States)

    Wu, Qinglong; Law, Yee-Song; Shah, Nagendra P.

    2015-01-01

    Most high γ-aminobutyric acid (GABA) producers are Lactobacillus brevis of plant origin, which may be not able to ferment milk well due to its poor proteolytic nature as evidenced by the absence of genes encoding extracellular proteinases in its genome. In the present study, two glutamic acid decarboxylase (GAD) genes, gadA and gadB, were found in high GABA-producing L. brevis NPS-QW-145. Co-culturing of this organism with conventional dairy starters was carried out to manufacture GABA-rich fermented milk. It was observed that all the selected strains of Streptococcus thermophilus, but not Lactobacillus delbrueckii subsp. bulgaricus, improved the viability of L. brevis NPS-QW-145 in milk. Only certain strains of S. thermophilus improved the gadA mRNA level in L. brevis NPS-QW-145, thus enhanced GABA biosynthesis by the latter. These results suggest that certain S. thermophilus strains are highly recommended to co-culture with high GABA producer for manufacturing GABA-rich fermented milk. PMID:26245488

  7. Dairy Streptococcus thermophilus improves cell viability of Lactobacillus brevis NPS-QW-145 and its γ-aminobutyric acid biosynthesis ability in milk.

    Science.gov (United States)

    Wu, Qinglong; Law, Yee-Song; Shah, Nagendra P

    2015-08-06

    Most high γ-aminobutyric acid (GABA) producers are Lactobacillus brevis of plant origin, which may be not able to ferment milk well due to its poor proteolytic nature as evidenced by the absence of genes encoding extracellular proteinases in its genome. In the present study, two glutamic acid decarboxylase (GAD) genes, gadA and gadB, were found in high GABA-producing L. brevis NPS-QW-145. Co-culturing of this organism with conventional dairy starters was carried out to manufacture GABA-rich fermented milk. It was observed that all the selected strains of Streptococcus thermophilus, but not Lactobacillus delbrueckii subsp. bulgaricus, improved the viability of L. brevis NPS-QW-145 in milk. Only certain strains of S. thermophilus improved the gadA mRNA level in L. brevis NPS-QW-145, thus enhanced GABA biosynthesis by the latter. These results suggest that certain S. thermophilus strains are highly recommended to co-culture with high GABA producer for manufacturing GABA-rich fermented milk.

  8. Impact of Precooling and Controlled-Atmosphere Storage on γ-Aminobutyric Acid (GABA) Accumulation in Longan (Dimocarpus longan Lour.) Fruit.

    Science.gov (United States)

    Zhou, Molin; Ndeurumio, Kessy H; Zhao, Lei; Hu, Zhuoyan

    2016-08-24

    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 4.1.1.15) activities declined during storage at the higher-CO2 treatments. However, GABA aminotransferase (GABA-T; EC 2.6.1.19) activities in elevated CO2-treated fruit fluctuated during storage. GABA concentrations increased after precooling treatments. GAD activity and GABA-T activity were different between cultivars after precooling. GABA concentrations in fruit increased after 3 days of 10% CO2 + 5% O2 treatment and then declined as storage time increased. GABA accumulation was associated with stimulation of GAD activity rather than inhibition of GABA-T activity.

  9. Enhancing Contents of γ-Aminobutyric Acid (GABA) and Other Micronutrients in Dehulled Rice during Germination under Normoxic and Hypoxic Conditions.

    Science.gov (United States)

    Ding, Junzhou; Yang, Tewu; Feng, Hao; Dong, Mengyi; Slavin, Margaret; Xiong, Shanbai; Zhao, Siming

    2016-02-10

    Biofortification of staple grains with high contents of essential micronutrients is an important strategy to overcome micronutrient malnutrition. However, few attempts have targeted at γ-aminobutyric acid (GABA), a functional nutrient for aging populations. In this study, two rice cultivars, Heinuo and Xianhui 207, were used to investigate changes in GABA and other nutritional compounds of dehulled rice after germination under normoxic and hypoxic conditions. Forty-one metabolites were identified in both cultivars treated by normoxic germination, whereas the germinated dehulled rice of Heinuo and Xianhui 207 under hypoxic treatment had 43 and 41 metabolites identified, respectively. GABA increased in dehulled rice after germination, especially under hypoxia. Meanwhile, a number of other health-beneficial and/or flavor-related compounds such as lysine and d-mannose increased after the hypoxic treatment. The accumulation of GABA exhibited genotype-specific modes in both normoxic and hypoxic treatments. With regard to GABA production, Xianhui 207 was more responsive to the germination process than Heinuo, whereas Heinuo was more responsive to hypoxia than Xianhui 207. This study provides a promising approach to biofortify dehulled rice with increased GABA and other nutrients through metabolomic-based regulation.

  10. γ-Aminobutyric acid transaminase deficiency impairs central carbon metabolism and leads to cell wall defects during salt stress in Arabidopsis roots.

    Science.gov (United States)

    Renault, Hugues; El Amrani, Abdelhak; Berger, Adeline; Mouille, Grégory; Soubigou-Taconnat, Ludivine; Bouchereau, Alain; Deleu, Carole

    2013-05-01

    Environmental constraints challenge cell homeostasis and thus require a tight regulation of metabolic activity. We have previously reported that the γ-aminobutyric acid (GABA) metabolism is crucial for Arabidopsis salt tolerance as revealed by the NaCl hypersensitivity of the GABA transaminase (GABA-T, At3g22200) gaba-t/pop2-1 mutant. In this study, we demonstrate that GABA-T deficiency during salt stress causes root and hypocotyl developmental defects and alterations of cell wall composition. A comparative genome-wide transcriptional analysis revealed that expression levels of genes involved in carbon metabolism, particularly sucrose and starch catabolism, were found to increase upon the loss of GABA-T function under salt stress conditions. Consistent with the altered mutant cell wall composition, a number of cell wall-related genes were also found differentially expressed. A targeted quantitative analysis of primary metabolites revealed that glutamate (GABA precursor) accumulated while succinate (the final product of GABA metabolism) significantly decreased in mutant roots after 1 d of NaCl treatment. Furthermore, sugar concentration was twofold reduced in gaba-t/pop2-1 mutant roots compared with wild type. Together, our results provide strong evidence that GABA metabolism is a major route for succinate production in roots and identify GABA as a major player of central carbon adjustment during salt stress. © 2012 Blackwell Publishing Ltd.

  11. Effect of dietary γ-aminobutyric acid on the nerve growth factor and the choline acetyltransferase in the cerebral cortex and hippocampus of ovariectomized female rats.

    Science.gov (United States)

    Tujioka, Kazuyo; Thanapreedawat, Panicha; Yamada, Takashi; Yokogoshi, Hidehiko; Horie, Kenji; Kim, Mujo; Tsutsui, Kazumi; Hayase, Kazutoshi

    2014-01-01

    The brain protein synthesis and the plasma concentration of growth hormone (GH) is sensitive to the dietary γ-aminobutyric acid (GABA) in ovariectomized female rats; however, the role of dietary GABA on biomarkers including nerve growth factor (NGF) and choline acetyltransferase for the function of cholinergic neurons remains unknown in ovariectomized female rats. The purpose of this study was to determine whether the dietary GABA affects the concentration and mRNA level of NGF, and the activity of choline acetyltransferase in the brains of ovariectomized female rats. Experiments were done on two groups of 24-wk-old ovariectomized female rats given 0 or 0.5% GABA added to a 20% casein diet. The concentrations of NGF and activities of choline acetyltransferase in the cerebral cortex and hippocampus, and mRNA level of NGF in the hippocampus increased significantly with the 20% casein+0.5% GABA compared with the 20% casein diet alone. In the hippocampus, the mRNA level of NGF significantly correlated with the NGF concentration (r=0.714, pGABA to ovariectomized female rats is likely to control the mRNA level and concentration of NGF and cause an increase in the activity of choline acetyltransferase in the brains.

  12. Protective propensity of bacoside A and bromelain on renal cholinesterases, γ-Aminobutyric acid and serotonin level of Mus musculus intoxicated with dichlorvos.

    Science.gov (United States)

    Agarwal, Sonam; Chaudhary, Bharti; Bist, Renu

    2017-01-05

    Current study established a protective action of bacoside A and bromelain against the toxic effects of dichlorvos in kidneys of mice. Experimental design included five groups. The first group was control. Mice of groups II, III and IV were administered doses of dichlorvos, bromelain and bacoside A respectively. In group V, mice were treated with both the antioxidants (bacoside A and bromelain) and dichlorvos. After 21 days of exposure of different doses, levels of acetylcholinesterase (AChE), butyrylcholinesterase (BChE), γ-aminobutyric acid (GABA) and serotonin were measured in renal tissues. Dichlorvos significantly reduced the kidney AChE (p GABA level (p level (p GABA level. Meanwhile, a significant decline in serotonin level (p < 0.001) was revealed, compared to dichlorvos exposed mice. Bacoside A and bromelain occupy a tremendous antioxidant action in the mice kidneys and a combination of the same ameliorates the renal toxicity induced by dichlorvos. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  13. The Protective Effect of γ-aminobutyric Acid on Kidney Injury Induced by Renal Ischemia-reperfusion in Ovariectomized Estradiol-treated Rats.

    Science.gov (United States)

    Talebi, Nahid; Nematbakhsh, Mehdi; Monajemi, Ramesh; Mazaheri, Safoora; Talebi, Ardeshir; Vafapour, Marzieh

    2016-01-01

    Renal ischemia-reperfusion injury (IRI) is one of the most important causes of kidney injury, which is possibly gender-related. This study was designed to investigate the role of γ-aminobutyric acid (GABA) against IRI in ovariectomized estradiol-treated rats. Thirty-five ovariectomized Wistar rats were used in six experimental groups. The first three groups did not subject to estradiol treatment and assigned as sham-operated, control, and GABA-treated groups. GABA (50 μmol/kg) and saline were injected in the treated and control groups 30 min before the surgery, respectively. The second three groups received the same treatments but received estradiol valerate (500 μg/kg, intramuscularly) 3 days prior to the surgery. The IRI was induced in the control and treated groups by clamping the renal artery for 45 min and then 24 h of reperfusion. All animals were sacrificed for the measurements. The serum levels of creatinine and blood urea nitrogen, kidney weight, and kidney tissue damage score significantly increased in the IRI rats (P GABA significantly decreased the aforementioned parameters (P levels of nitrite (nitric oxide metabolite) did not alter significantly. Serum level of malondialdehyde increased significantly in the ovariectomized rats exposed to IRI (P GABA improved IRI in ovariectomized rats. Estradiol was also nephroprotective against IRI. However, co-administration of estradiol and GABA could not protect the kidney against IRI.

  14. Effect of Γ-aminobutyric acid on kidney injury induced by renal ischemia-reperfusion in male and female rats: Gender-related difference.

    Science.gov (United States)

    Vafapour, Marzieh; Nematbakhsh, Mehdi; Monajemi, Ramesh; Mazaheri, Safoora; Talebi, Ardeshir; Talebi, Nahid; Shirdavani, Soheyla

    2015-01-01

    The most important cause of kidney injury is renal ischemia/reperfusion injury (IRI), which is gender-related. This study was designed to investigate the protective role of Γ-aminobutyric acid (GABA (against IRI in male and female rats. Thirty-six female and male wistar rats were assigned to six experimental groups. The IRI was induced by clamping renal vessels for 45 min then was performed reperfusion for 24 h. The group sex posed to IRI were pretreated with GABA and were compared with the control groups. Serum levels of creatinine and blood urea nitrogen, kidney weight, and kidney tissue damage score increased in the IRI alone groups, (P GABA decreased these parameters in female significantly (P GABA. Testis weight did not alter in male rats. Serum level of nitrite and kidney level of malondialdehyde (MDA) had no significant change in both female and male rats. Kidney level of nitrite increased significantly in female rats experienced IRI and serum level of MDA increased significantly in males that were exposed to IRI (P GABA could ameliorate kidney injury induced by renal IRI in a gender dependent manner.

  15. Effect of dietary γ-aminobutyric acid on laying performance, egg quality, immune activity and endocrine hormone in heat-stressed Roman hens.

    Science.gov (United States)

    Zhang, Min; Zou, Xiao-Ting; Li, Hui; Dong, Xin-Yang; Zhao, Wenjing

    2012-02-01

    This study was conducted to evaluate the effect of γ-aminobutyric acid (GABA) on laying performance, egg quality, digestive enzyme activity, hormone level and immune activities in Roman hens under heat stress. Roman hens (320 days old) were fed with 0, 25, 50, 75 and 100 mg/kg GABA, respectively during a 60-day experiment. Compared with control, supplementation of 50 mg/kg GABA improved the laying performance and egg quality by significantly increasing egg production, average egg weight and shell strength (P level. Anti-oxidation activity was improved by significantly increasing the activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), but decreasing malondialdehyde level in serum (P level, follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E(2) ), insulin, triiodothyronine (T(3) ) and free triiodothyronine (FT(3) ) levels, and IgG, IgA and complement (C3)activity in serum (P GABA improved laying performance and physical condition mainly by modulating hormone secretion, enhancing anti-oxidation and immune activity, and maintaining electrolyte balance. Fifty mg/kg was the optimum level for laying hens under heat stress in the present study. © 2011 The Authors. Animal Science Journal © 2011 Japanese Society of Animal Science.

  16. Changes of tocopherols, tocotrienols, γ-oryzanol, and γ-aminobutyric acid levels in the germinated brown rice of pigmented and nonpigmented cultivars.

    Science.gov (United States)

    Ng, Lean-Teik; Huang, Shao-Hua; Chen, Yen-Ting; Su, Chun-Han

    2013-12-26

    This study examined the changes of tocopherols (Toc), tocotrienols (T3), γ-oryzanol (GO), and γ-aminobutyric acid (GABA) contents in germinated brown rice (GBR) of pigmented and nonpigmented cultivars under different germination conditions. Results showed that the Toc and T3 contents in GBR were significantly different between treatments in both rice cultivars. The pigmented GBR possessed higher total vitamin E, total Toc, total T3, and GO contents than the nonpigmented GBR; however, its level of GABA was lower. The order of the three highest vitamin E homologues in pigmented and nonpigmented GBR was γ-T3 > γ-Toc > α-Toc and α-Toc > γ-T3 > α-T3, respectively; β-Toc, β-T3, δ-Toc, and δ-T3 were present in only small amounts (≤1.0 mg/kg) in GBR of both cultivars. Although both cultivars showed an increase in GABA contents with increasing germination time, the GABA content in nonpigmented GBR was higher.

  17. Overexpression of Thioredoxin-1 Blocks Morphine-Induced Conditioned Place Preference Through Regulating the Interaction of γ-Aminobutyric Acid and Dopamine Systems.

    Science.gov (United States)

    Li, Xiang; Huang, Mengbing; Yang, Lihua; Guo, Ningning; Yang, Xiaoyan; Zhang, Zhimin; Bai, Ming; Ge, Lu; Zhou, Xiaoshuang; Li, Ye; Bai, Jie

    2018-01-01

    Morphine is one kind of opioid, which is currently the most effective widely utilized pain relieving pharmaceutical. Long-term administration of morphine leads to dependence and addiction. Thioredoxin-1 (Trx-1) is an important redox regulating protein and works as a neurotrophic cofactor. Our previous study showed that geranylgeranylaceton, an inducer of Trx-1 protected mice from rewarding effects induced by morphine. However, whether overexpression of Trx-1 can block morphine-induced conditioned place preference (CPP) in mice is still unknown. In this study, we first examined whether overexpression of Trx-1 affects the CPP after morphine training and further examined the dopamine (DA) and γ-aminobutyric acid (GABA) systems involved in rewarding effects. Our results showed that morphine-induced CPP was blocked in Trx-1 overexpression transgenic (TG) mice. Trx-1 expression was induced by morphine in the ventral tegmental area (VTA) and nucleus accumbens (NAc) in wild-type (WT) mice, which was not induced in Trx-1 TG mice. The DA level and expressions of tyrosine hydroxylase (TH) and D1 were induced by morphine in WT mice, which were not induced in Trx-1 TG mice. The GABA level and expression of GABA B R were decreased by morphine, which were restored in Trx-1 TG mice. Therefore, Trx-1 may play a role in blocking CPP induced by morphine through regulating the expressions of D1, TH, and GABA B R in the VTA and NAc.

  18. Structure-activity relationships in a new series of insecticidally active dioxatricycloalkenes derived by structural comparison of the GABA [γ-aminobutyric acid] antagonists bicycloorthocarboxylates and endosulfan

    International Nuclear Information System (INIS)

    Ozoe, Yoshihisa; Sawada, Yoshihiro; Mochida, Kazuo; Nakamura, Toshiie; Matsumura, Fumio

    1990-01-01

    To study structural requirements for picrotoxinin-type GABA (γ-aminobutyric acid) antagonists to interact with the receptor site, 5-substituted 4,6-dioxatricyclo[7.2.1.0 2,8 ]dodec-10-enes and related compounds were prepared and examined for their insecticidal activity and potency in displacing [ 35 S]tert-butylbicyclophosphorothionate (TBPS) binding. Compounds with high insecticidal activity possessed a phenyl group with an electron-withdrawing para substituent, a cycloalkyl group, or a C 3 -C 5 straight-chain alkyl group at the 5-position. The effect of the 5-substituents on insecticidal activity was very similar to that of the 1-substituents of the bicyloorthocarboxylate GABA antagonists. Representative dioxatricycloalkenes displaced the binding of the GABA antagonist [ 35 S]TBPS to housefly head membranes by 29-53% at 10 μM. X-ray crystal structure analysis demonstrated that this class of compounds had structures superimposable on those of 4-tert-butylbicycloorthocarboxylates. These findings indicate that the dioxatricycloalkenes and some other analogues occupy the picrotoxinin binding site in such a way that the fourth interacting subsite of the receptor site accommodates the 5-substituent

  19. The effect of D,L-β-aminobutyric acid on the growth and development of Fusarium oxysporum f. sp. tulipae (Apt.

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    Anna Jarecka

    2012-12-01

    Full Text Available The effect of D,L-β-aminobutyric acid (BABA on the growth and development of the root system and the development of fusariosis on tulip bulbs cv. Apeldoorn infected by Fusarium oxysporum f. sp. tulipae (F.ox.t. 218 was studied. The length and fresh weight of roots, the development of fusariosis on bulbs and the linear growth of mycelium of F.ox.t. 218 on PDA medium were measured. Preventively used BABA at a concentration of 100, 250 and 300 µg·cm-3 for soaking uncooled and cooled tulip bulbs greatly inhibited the development of fusariosis on the root system; the length and fresh weight of roots were similar to those of the bulbs not inoculated with F.ox.t. 218. At a concentration of 100 µg·cm-3;, BABA used for soaking bulbs limited the development of fusariosis on scales in about 50% and the concentration of 200 µg·cm-3 totally inhibited the disease symptoms induced by F.ox.t. 218. At a concentration of 100 - 1000 µg·cm-3, BABA did not inhibit the mycelium growth of F.ox.t. 17 and F.xo.t. 218 on PDA medium. This study suggests that BABA protects tulip roots and bulb scales against F. oxysporum f. sp. tulipae by inducing resistance in these organs and has no direct influence on the pathogen.

  20. Overexpression of Thioredoxin-1 Blocks Morphine-Induced Conditioned Place Preference Through Regulating the Interaction of γ-Aminobutyric Acid and Dopamine Systems

    Directory of Open Access Journals (Sweden)

    Xiang Li

    2018-05-01

    Full Text Available Morphine is one kind of opioid, which is currently the most effective widely utilized pain relieving pharmaceutical. Long-term administration of morphine leads to dependence and addiction. Thioredoxin-1 (Trx-1 is an important redox regulating protein and works as a neurotrophic cofactor. Our previous study showed that geranylgeranylaceton, an inducer of Trx-1 protected mice from rewarding effects induced by morphine. However, whether overexpression of Trx-1 can block morphine-induced conditioned place preference (CPP in mice is still unknown. In this study, we first examined whether overexpression of Trx-1 affects the CPP after morphine training and further examined the dopamine (DA and γ-aminobutyric acid (GABA systems involved in rewarding effects. Our results showed that morphine-induced CPP was blocked in Trx-1 overexpression transgenic (TG mice. Trx-1 expression was induced by morphine in the ventral tegmental area (VTA and nucleus accumbens (NAc in wild-type (WT mice, which was not induced in Trx-1 TG mice. The DA level and expressions of tyrosine hydroxylase (TH and D1 were induced by morphine in WT mice, which were not induced in Trx-1 TG mice. The GABA level and expression of GABABR were decreased by morphine, which were restored in Trx-1 TG mice. Therefore, Trx-1 may play a role in blocking CPP induced by morphine through regulating the expressions of D1, TH, and GABABR in the VTA and NAc.

  1. Analysis of persistent changes to γ-aminobutyric acid receptor gene expression in Plutella xylostella subjected to sublethal amounts of spinosad.

    Science.gov (United States)

    Yin, X-H; Wu, Q-J; Zhang, Y-J; Long, Y-H; Wu, X-M; Li, R-Y; Wang, M; Tian, X-L; Jiao, X-G

    2016-07-25

    A multi-generational approach was used to investigate the persistent effects of a sub-lethal dose of spinosad in Plutella xylostella. The susceptibility of various sub-populations of P. xylostella to spinosad and the effects of the insecticide on the gene expression of γ-aminobutyric acid receptor (GABAR) were determined. The results of a leaf dip bioassay showed that the sensitivity of P. xylostella to spinosad decreased across generations. The sub-strains had been previously selected based on a determined LC25 of spinosad. Considering that GABA-gated chloride channels are the primary targets of spinosad, the cDNA of P. xylostella was used to clone GABARα by using reverse transcription-polymerase chain reaction (RT-PCR). The mature peptide cDNA was 1477-bp long and contained a 1449-bp open reading frame encoding a protein of 483 amino acids. The resulting amino acid sequence was used to generate a neighbor-joining dendrogram, and homology search was conducted using NCBI BLAST. The protein had high similarity with the known GABAR sequence from P. xylostella. Subsequent semi-quantitative RT-PCR and real-time PCR analyses indicated that the GABAR transcript levels in the spinosad-resistant strain (RR, 145.82-fold) and in Sub1 strain (selected with LC25 spinosad for one generation) were the highest, followed by those in the spinosad-susceptible strain, the Sub10 strain (selected for ten generations), and the Sub5 strain (selected for five generations). This multi-generational study found significant correlations between spinosad susceptibility and GABAR gene expression, providing insights into the long-term effects of sub-lethal insecticide exposure and its potential to lead to the development of insecticide-resistant insect populations.

  2. Anticonvulsant action of gamma-irradiated diazepam with correlation to certain brain amino acids and electrocorticogram activity in experimental animals

    International Nuclear Information System (INIS)

    Saad, S.F.; Roushdy, H.M.; Hassan, S.H.M.; Elkashef, H.S.; Mahdy, A.M.; Elsayeh, B.M.

    1994-01-01

    The effect of sterilization by gamma irradiation (215 KGy) of diazepam on is anticonvulsant action, on norma and depleted cerebral gamma aminobutyric acid (GABA), on glutamic acid, as well as electrocorticogram activity (ECOG) was determined in the experimental animals. For the evaluation of the anticonvulsant action of either diazepam (D) or irradiated diazepam (ID), pentyl ene tetrazole seizure test, was used and the protective dose 50 (PD50) was determined in adult male mice. GABA, the main central inhibitory transmitter which is implicated in the mechanism of the anticonvulsant action of D and its precursor glutamic acid, were electrophoretically separated and spectrophotometrical evaluated. Moreover, brain electrical activity was recorded using an electroencephalograph apparatus. Although the PD50 of ID as well the effect on normal brain cerebral GABA and glutamic acids did not differ significantly from that of D, yet there was certain variabilities. Thus, the effect of D was about 4 times more potent than the ID on elevating depleted cerebral GABA. Also, electrocorticogram records demonstrated that D produced a slight inhibition while ID induced a decrease in B rhythm with remarkable in the amplitude of ECOG waves. The same pattern of effects were obtained when D or ID were used in combination with INH (250 mg kg-1). 1 tab. 1 fig

  3. An overview of gamma-hydroxybutyric acid: pharmacodynamics, pharmacokinetics, toxic effects, addiction, analytical methods, and interpretation of results.

    Science.gov (United States)

    Andresen, H; Aydin, B E; Mueller, A; Iwersen-Bergmann, S

    2011-09-01

    Abuse of gamma-hydroxybutyric acid (GHB) has been known since the early 1990's, but is not as widespread as the consumption of other illegal drugs. However, the number of severe intoxications with fatal outcomes is comparatively high; not the least of which is brought about by the consumption of the currently legal precursor substances gamma-butyrolactone (GBL) and 1,4-butanediol (1,4-BD). In regards to previous assumptions, addiction to GHB or its analogues can occur with severe symptoms of withdrawal. Moreover, GHB can be used for drug-facilitated sexual assaults. Its pharmacological effects are generated mainly by interaction with both GABA(B) and GHB receptors, as well as its influence on other transmitter systems in the human brain. Numerous analytical methods for determining GHB using chromatographic techniques were published in recent years, and an enzymatic screening method was established. However, the short window of GHB detection in blood or urine due to its rapid metabolism is a challenge. Furthermore, despite several studies addressing this problem, evaluation of analytical results can be difficult: GHB is a metabolite of GABA (gamma-aminobutyric acid); a differentiation between endogenous and exogenous concentrations has to be made. Apart from this, in samples with a longer storage interval and especially in postmortem specimens, higher levels can be measured due to GHB generation during this postmortem interval or storage time. Copyright © 2011 John Wiley & Sons, Ltd.

  4. Enhancement of γ-aminobutyric acid production in recombinant Corynebacterium glutamicum by co-expressing two glutamate decarboxylase genes from Lactobacillus brevis.

    Science.gov (United States)

    Shi, Feng; Jiang, Junjun; Li, Yongfu; Li, Youxin; Xie, Yilong

    2013-11-01

    γ-Aminobutyric acid (GABA), a non-protein amino acid, is a bioactive component in the food, feed and pharmaceutical fields. To establish an effective single-step production system for GABA, a recombinant Corynebacterium glutamicum strain co-expressing two glutamate decarboxylase (GAD) genes (gadB1 and gadB2) derived from Lactobacillus brevis Lb85 was constructed. Compared with the GABA production of the gadB1 or gadB2 single-expressing strains, GABA production by the gadB1-gadB2 co-expressing strain increased more than twofold. By optimising urea supplementation, the total production of L-glutamate and GABA increased from 22.57 ± 1.24 to 30.18 ± 1.33 g L⁻¹, and GABA production increased from 4.02 ± 0.95 to 18.66 ± 2.11 g L⁻¹ after 84-h cultivation. Under optimal urea supplementation, L-glutamate continued to be consumed, GABA continued to accumulate after 36 h of fermentation, and the pH level fluctuated. GABA production increased to a maximum level of 27.13 ± 0.54 g L⁻¹ after 120-h flask cultivation and 26.32 g L⁻¹ after 60-h fed-batch fermentation. The conversion ratio of L-glutamate to GABA reached 0.60-0.74 mol mol⁻¹. By co-expressing gadB1 and gadB2 and optimising the urea addition method, C. glutamicum was genetically improved for de novo biosynthesis of GABA from its own accumulated L-glutamate.

  5. Short-term memory impairment after isoflurane in mice is prevented by the α5 γ-aminobutyric acid type A receptor inverse agonist L-655,708.

    Science.gov (United States)

    Saab, Bechara J; Maclean, Ashley J B; Kanisek, Marijana; Zurek, Agnieszka A; Martin, Loren J; Roder, John C; Orser, Beverley A

    2010-11-01

    Memory blockade is an essential component of the anesthetic state. However, postanesthesia memory deficits represent an undesirable and poorly understood adverse effect. Inhibitory α5 subunit-containing γ-aminobutyric acid subtype A receptors (α5GABAA) are known to play a critical role in memory processes and are highly sensitive to positive modulation by anesthetics. We postulated that inhibiting the activity of α5GABAA receptors during isoflurane anesthesia would prevent memory deficits in the early postanesthesia period. Mice were pretreated with L-655,708, an α5GABAA receptor-selective inverse agonist, or vehicle. They were then exposed to isoflurane for 1 h (1.3%, or 1 minimum alveolar concentration, or air-oxygen control). Then, either 1 or 24 h later, mice were conditioned in fear-associated contextual and cued learning paradigms. In addition, the effect of L-655,708 on the immobilizing dose of isoflurane was studied. Motor coordination, sedation, anxiety, and the concentration of isoflurane in the brain at 5 min, 1 h, and 24 h after isoflurane were also examined. Motor and sensory function recovered within minutes after termination of isoflurane administration. In contrast, a robust deficit in contextual fear memory persisted for at least 24 h. The α5GABAA receptor inverse agonist, L-655,708, completely prevented memory deficits without changing the immobilizing dose of isoflurane. Trace concentrations of isoflurane were measured in the brain 24 h after treatment. Memory deficits occurred long after the sedative, analgesic, and anxiolytic effects of isoflurane subsided. L-655,708 prevented memory deficit, suggesting that an isoflurane interaction at α5GABAA receptors contributes to memory impairment during the early postanesthesia period.

  6. Oral treatment with γ-aminobutyric acid improves glucose tolerance and insulin sensitivity by inhibiting inflammation in high fat diet-fed mice.

    Directory of Open Access Journals (Sweden)

    Jide Tian

    Full Text Available Adipocyte and β-cell dysfunction and macrophage-related chronic inflammation are critical for the development of obesity-related insulin resistance and type 2 diabetes mellitus (T2DM, which can be negatively regulated by Tregs. Our previous studies and those of others have shown that activation of γ-aminobutyric acid (GABA receptors inhibits inflammation in mice. However, whether GABA could modulate high fat diet (HFD-induced obesity, glucose intolerance and insulin resistance has not been explored. Here, we show that although oral treatment with GABA does not affect water and food consumption it inhibits the HFD-induced gain in body weights in C57BL/6 mice. Furthermore, oral treatment with GABA significantly reduced the concentrations of fasting blood glucose, and improved glucose tolerance and insulin sensitivity in the HFD-fed mice. More importantly, after the onset of obesity and T2DM, oral treatment with GABA inhibited the continual HFD-induced gain in body weights, reduced the concentrations of fasting blood glucose and improved glucose tolerance and insulin sensitivity in mice. In addition, oral treatment with GABA reduced the epididymal fat mass, adipocyte size, and the frequency of macrophage infiltrates in the adipose tissues of HFD-fed mice. Notably, oral treatment with GABA significantly increased the frequency of CD4(+Foxp3(+ Tregs in mice. Collectively, our data indicated that activation of peripheral GABA receptors inhibited the HFD-induced glucose intolerance, insulin resistance, and obesity by inhibiting obesity-related inflammation and up-regulating Treg responses in vivo. Given that GABA is safe for human consumption, activators of GABA receptors may be valuable for the prevention of obesity and intervention of T2DM in the clinic.

  7. Investigation of Cortical Glutamate–Glutamine and γ-Aminobutyric Acid in Obsessive–Compulsive Disorder by Proton Magnetic Resonance Spectroscopy

    Science.gov (United States)

    Simpson, Helen B; Shungu, Dikoma C; Bender, James; Mao, Xiangling; Xu, Xiaoyan; Slifstein, Mark; Kegeles, Lawrence S

    2012-01-01

    Glutamatergic abnormalities in corticostriatal brain circuits are thought to underlie obsessive–compulsive disorder (OCD). Whether these abnormalities exist in adults with OCD is not clear. We used proton magnetic resonance spectroscopy (1H MRS) to test our hypothesis that unmedicated adults with OCD have reduced glutamate plus glutamine (Glx) levels in the medial prefrontal cortex (MPFC) compared with healthy controls. Levels of γ-aminobutyric acid (GABA) were also explored. Twenty-four unmedicated adults with OCD and 22 matched healthy control subjects underwent 1H MRS scans at 3.0 T. Resonances of both Glx and GABA were obtained using the standard J-editing technique and assessed as ratios relative to voxel tissue water (W) in the MPFC (the region of interest) and the dorsolateral prefrontal cortex (DLPFC) to explore the regional specificity of any finding. In the MPFC, Glx/W did not differ by diagnostic group (p=0.98) or sex (p=0.57). However, GABA/W was decreased in OCD (2.16±0.46 × 10−3) compared with healthy controls (2.43±0.45 × 10−3, p=0.045); moreover, age of OCD onset was inversely correlated with MPFC GABA/W (r=−0.50, p=0.015). MPFC GABA/W was higher in females than in males. In the DLPFC, there were no main effects of diagnosis or gender on Glx/W or GABA/W. These data indicate that unmedicated adults with OCD do not have Glx abnormalities in a MPFC voxel that includes the pregenual anterior cingulate cortex. However, they may have decreased MPFC GABA levels. How GABA abnormalities might contribute to corticostriatal dysfunction in OCD deserves further study. PMID:22850733

  8. A New Probiotic Cheddar Cheese with High ACE-Inhibitory Activity and γ-Aminobutyric Acid Content Produced with Koumiss-Derived Lactobacillus casei Zhang

    Directory of Open Access Journals (Sweden)

    Hai Kuan Wang

    2010-01-01

    Full Text Available Cheddar cheese has been manufactured with Lactobacillus casei Zhang as the dairy starter adjunct. L. casei Zhang had previously been isolated from koumiss collected from Xilin Guole in Inner Mongolia and characterized in detail with regard to their probiotic potential. The addition of L. casei Zhang to Cheddar cheese had no adverse effects on sensory criteria. The cheese made with 0.1, 1 and 2 % of the probiotic strain L. casei Zhang adjuncts contained high levels of the Lactobacillus after 6 months of ripening with final counts of 9.6·10^7, 7.7·10^7 and 1.02·10^8 CFU/g, respectively. In the ripe control cheese, without the addition of probiotic strain L. casei Zhang, the number of Lactobacillus reached 5.7·107 CFU/g. Enterobacterial repetitive intergenic consensus PCR (ERIC-PCR analysis was used to distinguish the added L. casei Zhang from the natural flora of the cheese and to determine whether L. casei Zhang grew in the cheese. ACE-inhibitory activity and γ-aminobutyric acid (GABA concentrations in the cheese were measured. Compared with control cheese, experimental cheese with 0.1, 1 and 2 % of probiotic strain L. casei Zhang revealed some increase in ACE-inhibitory activity and GABA mass fraction. In the present study, the production of both ACE-inhibitory activity and GABA in the probiotic cheese with the L. casei Zhang adjunct isolated from koumiss has been found for the first time. The results suggest that cheese with the probiotic strain L. casei Zhang showed good potential for application in the management of hypertension.

  9. The adjustment of γ-aminobutyric acidA tonic subunits in Huntington's disease: from transcription to translation to synaptic levels into the neostriatum

    Directory of Open Access Journals (Sweden)

    Abraham Rosas-Arellano

    2018-01-01

    Full Text Available γ-Aminobutyric acid (GABA, plays a key role in all stages of life, also is considered the main inhibitory neurotransmitter. GABA activates two kind of membrane receptors known as GABAA and GABAB, the first one is responsible to render tonic inhibition by pentameric receptors containing α4−6, β3, δ, or ρ1−3 subunits, they are located at perisynaptic and/or in extrasynaptic regions. The biophysical properties of GABAA tonic inhibition have been related with cellular protection against excitotoxic injury and cell death in presence of excessive excitation. On this basis, GABAA tonic inhibition has been proposed as a potential target for therapeutic intervention of Huntington's disease. Huntington's disease is a neurodegenerative disorder caused by a genetic mutation of the huntingtin protein. For experimental studies of Huntington's disease mouse models have been developed, such as R6/1, R6/2, HdhQ92, HdhQ150, as well as YAC128. In all of them, some key experimental reports are focused on neostriatum. The neostriatum is considered as the most important connection between cerebral cortex and basal ganglia structures, its cytology display two pathways called direct and indirect constituted by medium sized spiny neurons expressing dopamine D1 and D2 receptors respectively, they display strong expression of many types of GABAA receptors, including tonic subunits. The studies about of GABAA tonic subunits and Huntington's disease into the neostriatum are rising in recent years, suggesting interesting changes in their expression and localization which can be used as a strategy to delay the cellular damage caused by the imbalance between excitation and inhibition, a hallmark of Huntington's disease.

  10. Elevated prefrontal cortex γ-aminobutyric acid and glutamate-glutamine levels in schizophrenia measured in vivo with proton magnetic resonance spectroscopy.

    Science.gov (United States)

    Kegeles, Lawrence S; Mao, Xiangling; Stanford, Arielle D; Girgis, Ragy; Ojeil, Najate; Xu, Xiaoyan; Gil, Roberto; Slifstein, Mark; Abi-Dargham, Anissa; Lisanby, Sarah H; Shungu, Dikoma C

    2012-05-01

    Postmortem studies have found evidence of γ-aminobutyric acid (GABA) deficits in fast-spiking, parvalbumin-positive interneurons in the prefrontal cortex in schizophrenia. Magnetic resonance spectroscopy studies in unmedicated patients have reported glutamine or glutamate-glutamine (Glx) elevations in this region. Abnormalities in these transmitters are thought to play a role in cognitive impairments in the illness. To measure GABA and Glx levels in vivo in 2 prefrontal brain regions in unmedicated and medicated patients with schizophrenia and healthy controls. Case-control study. Inpatient psychiatric research unit and associated outpatient clinic. Sixteen unmedicated patients with schizophrenia, 16 medicated patients, and 22 healthy controls matched for age, sex, ethnicity, parental socioeconomic status, and cigarette smoking. Proton magnetic resonance spectroscopy with a 3-T system and the J-edited spin-echo difference method. The GABA and Glx levels were measured in the dorsolateral and medial prefrontal cortex and normalized to the simultaneously acquired water signal. Working memory performance was assessed in all subjects. The GABA and Glx concentrations determined by proton magnetic resonance spectroscopy. In the medial prefrontal cortex region, 30% elevations were found in GABA (P = .02) and Glx (P = .03) levels in unmedicated patients compared with controls. There were no alterations in the medicated patients or in either group in the dorsolateral prefrontal cortex. Both regions showed correlations between GABA and Glx levels in patients and controls. No correlations with working memory performance were found. To our knowledge, this study presents the first GABA concentration measurements in unmedicated patients with schizophrenia, who showed elevations in both GABA and Glx levels in the medial prefrontal cortex but not the dorsolateral prefrontal cortex. Medicated patients did not show these elevations, suggesting possible normalization of levels with

  11. Bl-1020, a new γ-aminobutyric acid-enhanced antipsychotic: results of 6-week, randomized, double-blind, controlled, efficacy and safety study.

    Science.gov (United States)

    Geffen, Yona; Keefe, Richard; Rabinowitz, Jonathan; Anand, Ravi; Davidson, Michael

    2012-09-01

    BL-1020 is a γ-aminobutyric acid (GABA)-enhanced antipsychotic that combines dopamine antagonism with GABA agonist activity. On the basis of animal models, we tested the hypotheses that BL-1020 would be effective in ameliorating both psychotic symptoms and cognitive impairments, with a favorable safety profile in acutely ill schizophrenia patients. 363 hospital-based psychiatric patients in India, Romania, and United States aged 18 to 65 years and meeting criteria for DSM-IV-TR diagnosis of chronic schizophrenia were randomized double-blind to receive BL-1020 10 mg/d, BL-1020 20-30 mg/d, placebo, or risperidone (2-8 mg/d) for 6 weeks. The main outcome measures were the positive and negative syndrome scale (PANSS), brief assessment of cognition in schizophrenia, readiness for discharge questionnaire, clinical global impressions scale (CGI) , and extrapyramidal symptom rating scale. The study ran from July 2008 to June 2009. BL-1020 20-30 mg was significantly better than placebo on PANSS (P = .02) and CGI (P schizophrenia composite score when compared to placebo (effect size = 0.50, P = .009), risperidone (effect size = 0.43, P = .019), and BL-1020 10 mg (effect size = 0.42, P = .013) after 6 weeks. BL-1020 appears to be an effective antipsychotic with possible procognitive effects that will need to be further tested for short- and long-term effects. A further randomized controlled trial using the U.S. Food and Drug Administration-recommended Measurement and Treatment Research to Improve Cognition in Schizophrenia cognitive battery is ongoing. ClinicalTrials.gov identifier: NCT00567710. © Copyright 2012 Physicians Postgraduate Press, Inc.

  12. Effect of γ-aminobutyric acid and nattokinase-enriched fermented beans on the blood pressure of spontaneously hypertensive and normotensive Wistar–Kyoto rats

    Directory of Open Access Journals (Sweden)

    Kanintra Suwanmanon

    2014-12-01

    Full Text Available In this study we have evaluated the changes in arterial blood pressure in spontaneously hypertensive rats (SHR caused by the short-term intake of Bacillus subtilis B060-fermented beans with significant γ-aminobutyric acid (GABA and nattokinase activity. After being weaned, 7-week-old male SHR and 7-week-old male Wistar–Kyoto (WKY rats were randomized into seven groups. Until the 8th week of life, the rats in each group were given one of the following: Group 1, high dose of GABA and nattokinase in the SHR (SHD; Group 2, medium dose of GABA and nattokinase in the SHR (SMD; Group 3, low dose of GABA and nattokinase in the SHR (SLD; Group 4, negative control in the SHR (SD; Group 5, positive control in the SHR (SM; Group 6, high dose of GABA and nattokinase in the WKY (WHD; and Group 7, negative control in the WKY (WD. Distilled water served as the negative control, and captopril (50 mg/kg, a known ACE inhibitor, served as the positive control. Systolic blood pressure and diastolic blood pressure values were measured weekly from the 8th week to the 16th week of life using the tail-cuff method. A definite decrease in systolic and diastolic blood pressure values could be observed in the rats treated with captopril and in the rats that received GABA and nattokinase. The greatest antihypertensive effect was observed when the pharmacological treatment was administered. The effect of the daily intake of fermented beans containing GABA and nattokinase may be helpful in controlling blood pressure levels in hypertensive model animals. The fermentation of beans with B. subtilis B060 may therefore constitute a successful strategy for producing a functional food with antihypertensive activity.

  13. Effect of γ-aminobutyric acid and nattokinase-enriched fermented beans on the blood pressure of spontaneously hypertensive and normotensive Wistar-Kyoto rats.

    Science.gov (United States)

    Suwanmanon, Kanintra; Hsieh, Pao-Chuan

    2014-12-01

    In this study we have evaluated the changes in arterial blood pressure in spontaneously hypertensive rats (SHR) caused by the short-term intake of Bacillus subtilis B060-fermented beans with significant γ-aminobutyric acid (GABA) and nattokinase activity. After being weaned, 7-week-old male SHR and 7-week-old male Wistar-Kyoto (WKY) rats were randomized into seven groups. Until the 8 th week of life, the rats in each group were given one of the following: Group 1, high dose of GABA and nattokinase in the SHR (SHD); Group 2, medium dose of GABA and nattokinase in the SHR (SMD); Group 3, low dose of GABA and nattokinase in the SHR (SLD); Group 4, negative control in the SHR (SD); Group 5, positive control in the SHR (SM); Group 6, high dose of GABA and nattokinase in the WKY (WHD); and Group 7, negative control in the WKY (WD). Distilled water served as the negative control, and captopril (50 mg/kg), a known ACE inhibitor, served as the positive control. Systolic blood pressure and diastolic blood pressure values were measured weekly from the 8 th week to the 16 th week of life using the tail-cuff method. A definite decrease in systolic and diastolic blood pressure values could be observed in the rats treated with captopril and in the rats that received GABA and nattokinase. The greatest antihypertensive effect was observed when the pharmacological treatment was administered. The effect of the daily intake of fermented beans containing GABA and nattokinase may be helpful in controlling blood pressure levels in hypertensive model animals. The fermentation of beans with B. subtilis B060 may therefore constitute a successful strategy for producing a functional food with antihypertensive activity. Copyright © 2014. Published by Elsevier B.V.

  14. Bipotential precursors of putative fibrous astrocytes and oligodendrocytes in rat cerebellar cultures express distinct surface features and neuron-like γ-aminobutyric acid transport

    International Nuclear Information System (INIS)

    Levi, G.; Gallo, V.; Ciotti, T.

    1986-01-01

    When postnatal rat cerebellar cells were cultured in a chemically defined, serum-free medium, the only type of astrocyte present was unable to accumulate γ-[ 3 H]aminobutyric acid (GABA), did not express surface antigens recognized by two monoclonal antibodies, A2B5 and LB1, and showed minimal proliferation. In these cultures, nonneuronal A2B5 + , LB1 + stellate cells exhibiting neuron-like [ 3 H]GABA uptake formed cell colonies of increasing size and were GFAP - . After about one week of culturing, the A2B5 + , LB1 + , GABA-uptake positive cell groups became galactocerebroside (GalCer) positive. Immunocytolysis of the A2B5 + cells at 3 and 4 days in vitro prevented the appearance of the A2B5 + , LB1 + , GABA-uptake positive cell colonies, and also of the GalCer + cell groups. If 10% (vol/vol) fetal calf serum was added to 6-day cultures, the A2B5 + , LB1 + , GABA-uptake positive cell groups expressed GFAP and not GalCer. If the serum was added to the cultures 2 days after lysing the A2B5 + cells, only A2B5 - , LB1 - , GABA-uptake negative astrocytes proliferated. It is concluded that the putative fibrous astrocytes previously described in serum-containing cultures derive from bipotential precursors that differentiate into oligodendrocytes (GalCer + ) in serum-free medium or into astrocytes (GFAP + ) in the presence of serum, while the epithelioid A2B5 - , LB1 - , GABA-uptake negative astrocytes originate from a different precursor not yet identified

  15. Carrier-mediated ¿-aminobutyric acid transport across the basolateral membrane of human intestinal Caco-2 cell monolayers

    DEFF Research Database (Denmark)

    Nielsen, Carsten Uhd; Carstensen, Mette; Brodin, Birger

    2012-01-01

    and the anticancer prodrug d-aminolevulinic acid across the apical membrane of small intestinal enterocytes. Little is however known about the basolateral transport of these substances. We investigated basolateral transport of GABA in mature Caco-2 cell monolayers using isotope studies. Here we report that, at least...... two transporters seem to be involved in the basolateral transport of GABA. The basolateral uptake consisted of a high-affinity system with a K(m) of 290µM and V(max) of 75pmolcm(-2)min(-1) and a low affinity system with a K(m) of approximately 64mM and V(max) of 1.6nmolcm(-2)min(-1). The high...

  16. Amino acids and hexosamines as indicators of organic matter degradation state in North Sea sediments

    NARCIS (Netherlands)

    Dauwe, B.; Middelburg, J.J.

    1998-01-01

    Sediment cores from six stations in the eastern North Sea were analyzed for protein amino acids, the nonprotein amino acids beta-alanine and gamma-aminobutyric acid and the hexosamines galactosamine and glucosamine, and bulk parameters (organic carbon, nitrogen, total hydrolyzable amino acids and

  17. Contribution of the activated catalase to oxidative stress resistance and γ-aminobutyric acid production in Lactobacillus brevis.

    Science.gov (United States)

    Lyu, Changjiang; Hu, Sheng; Huang, Jun; Luo, Maiqi; Lu, Tao; Mei, Lehe; Yao, Shanjing

    2016-12-05

    Lactic acid bacteria (LAB) are generally sensitive to H 2 O 2 , a compound which can paradoxically produce themselves and lead to the growth arrest and cell death. To counteract the potentially toxic effects of this compound, the gene katE encoding a heme-dependent catalase (CAT) belonging to the family of monofunctional CATs was cloned from Lactobacillus brevis CGMCC1306. The enhanced homologous CAT expression was achieved using the NICE system. L. brevis cells with overexpressed CAT showed 685-fold and 823-fold higher survival when exposed to 30mmol/L of H 2 O 2 and long-term aerated stress (after 72h), respectively, than that of the wild type cells. Furtherly, the effects of activated CAT on GABA production in L. brevis were investigated. A GABA production level of 66.4g/L was achieved using two-step biotransformation that successively employed the growing and resting cells derived from engineering L. brevis CAT. These results demonstrated clearly that overexpression of the KatE gene in L. brevis led to a marked increased survival in oxidizing environment, and shed light on a novel feasible approach to enhance the GABA production level by improving the antioxidative properties. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. Use of 3h-γ-aminobutyric acid for transport studies with isolated nerve-terminals from rat brain

    International Nuclear Information System (INIS)

    Halvarsson, G.B.; Karlsson, I.; Sellstroem, A.

    1985-01-01

    Isolated synaptosomes were used to study the problem of net accumulation of neurotransmitters. The time-course and the kinetics of exogenous and endogenous GABA transport were studied by liquid-scintillation counting and HPLC-amino acid analysis respectively. Different pools of GABA were suggested by a 6-fold difference in tissue-to-medium-ratio of endogenous vs. exogenous GABA. Net accumulation, exchange and net efflux of GABA was found to be a function of the GABA concentration in the incubation medium. The K/sub m/s for net accumulation and for 3 H-GABA accumulation were 2.68 +/- 1.16 and 6.19 +/- 1.26 μM respectively, whereas the V/sub max/s were 5.9 +/- 4.9 and 134 +/- 13 pmol/mg w.w min respectively. This means that the transport studies which use exogenous substances (e.g. 3 H-GABA) considerably overestimate the transport by overlooking the magnitude of the counter transport. 22 references, 5 figures, 2 tables

  19. Effect of Jian-Pi-Zhi-Dong Decoction on striatal glutamate and γ-aminobutyric acid levels detected using microdialysis in a rat model of Tourette syndrome

    Directory of Open Access Journals (Sweden)

    Zhang W

    2016-05-01

    Full Text Available Wen Zhang,1,* Li Wei,2,* Wenjing Yu,1 Xia Cui,1 Xiaofang Liu,2 Qian Wang,1 Sumei Wang2 1Department of Pediatrics, The Third Affiliated Hospital, 2Department of Pediatrics, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, People’s Republic of China *These authors contributed equally to this work Background: Jian-Pi-Zhi-Dong Decoction (JPZDD is a dedicated treatment of Tourette syndrome (TS. The balance of neurotransmitters in the cortico-striato-pallido-thalamo-cortical network is crucial to the occurrence of TS and related to its severity. This study evaluated the effect of JPZDD on glutamate (Glu and γ-aminobutyric acid (GABA and their receptors in a TS rat model.Materials and methods: Rats were divided into four groups (n=12 each. TS was induced in three of the groups by injecting them with 3,3'-iminodipropionitrile for 7 consecutive days. Two model groups were treated with tiapride (Tia or JPZDD, while the control and the remaining model group were gavaged with saline. Behavior was assessed by stereotypic score and autonomic activity. Striatal Glu and GABA contents were detected using microdialysis. Expressions of N-methyl-D-aspartate receptor 1 and GABAA receptor (GABAAR were observed using Western blot and real-time polymerase chain reaction.Results: Tia and JPZDD groups had decreased stereotypy compared with model rats; however, the JPZDD group showed a larger decrease in stereotypy than the Tia group at a 4-week time point. In a spontaneous activity test, the total distance of the JPZDD and Tia groups was significantly decreased compared with the model group. The Glu levels of the model group were higher than the control group and decreased with Tia or JPZDD treatment. The GABA level was higher in the model group than the control group. Expressions of GABAAR protein in the model group were higher than in the control group. Treatment with Tia or JPZDD reduced the expression of GABAAR protein. In the case of the m

  20. Effect of γ-Aminobutyric Acid-producing Strain on Laying Performance, Egg Quality and Serum Enzyme Activity in Hy-Line Brown Hens under Heat Stress

    Directory of Open Access Journals (Sweden)

    Y. Z. Zhu

    2015-07-01

    Full Text Available Heat-stress remains a costly issue for animal production, especially for poultry as they lack sweat glands, and alleviating heat-stress is necessary for ensuring animal production in hot environment. A high γ-aminobutyric acid (GABA-producer Lactobacillus strain was used to investigate the effect of dietary GABA-producer on laying performance and egg quality in heat-stressed Hy-line brown hens. Hy-Line brown hens (n = 1,164 at 280 days of age were randomly divided into 4 groups based on the amount of freeze-dried GABA-producer added to the basal diet as follows: i 0 mg/kg, ii 25 mg/kg, iii 50 mg/kg, and iv 100 mg/kg. All hens were subjected to heat-stress treatment through maintaining the temperature and the relative humidity at 28.83±3.85°C and 37% to 53.9%, respectively. During the experiment, laying rate, egg weight and feed intake of hens were recorded daily. At the 30th and 60th day after the start of the experiment, biochemical parameters, enzyme activity and immune activity in serum were measured. Egg production, average egg weight, average daily feed intake, feed conversion ratio and percentage of speckled egg, soft shell egg and misshaped egg were significantly improved (p<0.05 by the increasing supplementation of the dietary GABA-producer. Shape index, eggshell thickness, strength and weight were increased linearly with increasing GABA-producer supplementation. The level of calcium, phosphorus, glucose, total protein and albumin in serum of the hens fed GABA-producing strain supplemented diet was significantly higher (p<0.05 than that of the hens fed the basal diet, whereas cholesterol level was decreased. Compared with the basal diet, GABA-producer strain supplementation increased serum level of glutathione peroxidase (p = 0.009 and superoxide dismutase. In conclusion, GABA-producer played an important role in alleviating heat-stress, the isolated GABA-producer strain might be a potential natural and safe probiotic to use to

  1. Frontal Glutamate and γ-Aminobutyric Acid Levels and Their Associations With Mismatch Negativity and Digit Sequencing Task Performance in Schizophrenia.

    Science.gov (United States)

    Rowland, Laura M; Summerfelt, Ann; Wijtenburg, S Andrea; Du, Xiaoming; Chiappelli, Joshua J; Krishna, Nithin; West, Jeffrey; Muellerklein, Florian; Kochunov, Peter; Hong, L Elliot

    2016-02-01

    Auditory mismatch negativity (MMN) is a biomarker for schizophrenia thought to reflect glutamatergic N-methyl-d-aspartate receptor function and excitatory-inhibitory neurotransmission balance. However, the association of glutamate level with MMN has not been directly examined in patients with schizophrenia, to our knowledge. To investigate the contributions of glutamate and γ-aminobutyric acid (GABA) to MMN and digit sequencing task (DST) performance, an assessment of verbal working memory, in schizophrenia. Fifty-three control participants from the community and 45 persons with schizophrenia from outpatient clinics completed an electroencephalographic session for MMN, magnetic resonance spectroscopy for glutamate and GABA, and a DST. The study dates were July 2011 to May 2014, and the dates of our analysis were May 2014 to August 2015. Glutamate, GABA, the ratio of glutamine to glutamate, MMN amplitude, and DST. Structural equation modeling was used to test the effects of neurochemistry and MMN amplitude on DST performance. The 45 persons with schizophrenia were a mean (SD) of 37.7 (12.8) years and the control participants were 37.1 (13.1) years. The schizophrenia group had a mean (SD) of 14.7 (12.1) years of illness. Mismatch negativity amplitude (F = 4.39, P = .04) and glutamate (F = 9.69, P = .002) were reduced in the schizophrenia group. Smaller MMN amplitude was significantly associated with lower GABA level (P = .008), lower glutamate level (P = .05), and higher ratio of glutamine to glutamate (P = .003). Reduced MMN amplitude was linked to poor verbal working memory in schizophrenia (P = .002). Modeling revealed that a proxy of glutamatergic function, indexed by the ratio of glutamine to glutamate, influenced a path from the ratio of glutamine to glutamate to MMN to verbal working memory (P = .38 [root-mean-square error of approximation, P GABA in MMN and verbal working memory deficits in schizophrenia has been

  2. Effect of γ-Aminobutyric Acid-producing Lactobacillus Strain on Laying Performance, Egg Quality and Serum Enzyme Activity in Hy-Line Brown Hens under Heat Stress.

    Science.gov (United States)

    Zhu, Y Z; Cheng, J L; Ren, M; Yin, L; Piao, X S

    2015-07-01

    Heat-stress remains a costly issue for animal production, especially for poultry as they lack sweat glands, and alleviating heat-stress is necessary for ensuring animal production in hot environment. A high γ-aminobutyric acid (GABA)-producer Lactobacillus strain was used to investigate the effect of dietary GABA-producer on laying performance and egg quality in heat-stressed Hy-line brown hens. Hy-Line brown hens (n = 1,164) at 280 days of age were randomly divided into 4 groups based on the amount of freeze-dried GABA-producer added to the basal diet as follows: i) 0 mg/kg, ii) 25 mg/kg, iii) 50 mg/kg, and iv) 100 mg/kg. All hens were subjected to heat-stress treatment through maintaining the temperature and the relative humidity at 28.83±3.85°C and 37% to 53.9%, respectively. During the experiment, laying rate, egg weight and feed intake of hens were recorded daily. At the 30th and 60th day after the start of the experiment, biochemical parameters, enzyme activity and immune activity in serum were measured. Egg production, average egg weight, average daily feed intake, feed conversion ratio and percentage of speckled egg, soft shell egg and misshaped egg were significantly improved (pGABA-producer. Shape index, eggshell thickness, strength and weight were increased linearly with increasing GABA-producer supplementation. The level of calcium, phosphorus, glucose, total protein and albumin in serum of the hens fed GABA-producing strain supplemented diet was significantly higher (plevel was decreased. Compared with the basal diet, GABA-producer strain supplementation increased serum level of glutathione peroxidase (p = 0.009) and superoxide dismutase. In conclusion, GABA-producer played an important role in alleviating heat-stress, the isolated GABA-producer strain might be a potential natural and safe probiotic to use to improve laying performance and egg quality in heat-stressed hens.

  3. Effect of Functional Bread Rich in Potassium, γ-Aminobutyric Acid and Angiotensin-Converting Enzyme Inhibitors on Blood Pressure, Glucose Metabolism and Endothelial Function

    Science.gov (United States)

    Becerra-Tomás, Nerea; Guasch-Ferré, Marta; Quilez, Joan; Merino, Jordi; Ferré, Raimon; Díaz-López, Andrés; Bulló, Mònica; Hernández-Alonso, Pablo; Palau-Galindo, Antoni; Salas-Salvadó, Jordi

    2015-01-01

    Abstract Because it has been suggested that food rich in γ-aminobutyric acid (GABA) or angiotensin-converting enzyme inhibitor (ACEI) peptides have beneficial effects on blood pressure (BP) and other cardiovascular risk factors, we tested the effects of low-sodium bread, but rich in potassium, GABA, and ACEI peptides on 24-hour BP, glucose metabolism, and endothelial function. A randomized, double-blind, crossover trial was conducted in 30 patients with pre or mild-to-moderate hypertension, comparing three 4-week nutritional interventions separated by 2-week washout periods. Patients were randomly assigned to consume 120 g/day of 1 of the 3 types of bread for each nutritional intervention: conventional wheat bread (CB), low-sodium wheat bread enriched in potassium (LSB), and low-sodium wheat bread rich in potassium, GABA, and ACEI peptides (LSB + G). For each period, 24-hour BP measurements, in vivo endothelial function, and biochemical samples were obtained. After LSB + G consumption, 24-hour ambulatory BP underwent a nonsignificant greater reduction than after the consumption of CB and LSB (0.26 mm Hg in systolic BP and −0.63 mm Hg in diastolic BP for CB; −0.71 mm Hg in systolic BP and −1.08 mm Hg in diastolic BP for LSB; and −0.75 mm Hg in systolic BP and −2.12 mm Hg in diastolic BP for LSB + G, respectively). Diastolic BP at rest decreased significantly during the LSB + G intervention, although there were no significant differences in changes between interventions. There were no significant differences between interventions in terms of changes in in vivo endothelial function, glucose metabolism, and peripheral inflammatory parameters. Compared with the consumption of CB or LSB, no greater beneficial effects on 24-hour BP, endothelial function, or glucose metabolism were demonstrated after the consumption of LSB + G in a population with pre or mild-to-moderate hypertension. Further studies are warranted to clarify the

  4. Circuit- and Diagnosis-Specific DNA Methylation Changes at γ-Aminobutyric Acid-Related Genes in Postmortem Human Hippocampus in Schizophrenia and Bipolar Disorder.

    Science.gov (United States)

    Ruzicka, W Brad; Subburaju, Sivan; Benes, Francine M

    2015-06-01

    Dysfunction related to γ-aminobutyric acid (GABA)-ergic neurotransmission in the pathophysiology of major psychosis has been well established by the work of multiple groups across several decades, including the widely replicated downregulation of GAD1. Prior gene expression and network analyses within the human hippocampus implicate a broader network of genes, termed the GAD1 regulatory network, in regulation of GAD1 expression. Several genes within this GAD1 regulatory network show diagnosis- and sector-specific expression changes within the circuitry of the hippocampus, influencing abnormal GAD1 expression in schizophrenia and bipolar disorder. To investigate the hypothesis that aberrant DNA methylation contributes to circuit- and diagnosis-specific abnormal expression of GAD1 regulatory network genes in psychotic illness. This epigenetic association study targeting GAD1 regulatory network genes was conducted between July 1, 2012, and June 30, 2014. Postmortem human hippocampus tissue samples were obtained from 8 patients with schizophrenia, 8 patients with bipolar disorder, and 8 healthy control participants matched for age, sex, postmortem interval, and other potential confounds from the Harvard Brain Tissue Resource Center, McLean Hospital, Belmont, Massachusetts. We extracted DNA from laser-microdissected stratum oriens tissue of cornu ammonis 2/3 (CA2/3) and CA1 postmortem human hippocampus, bisulfite modified it, and assessed it with the Infinium HumanMethylation450 BeadChip (Illumina, Inc). The subset of CpG loci associated with GAD1 regulatory network genes was analyzed in R version 3.1.0 software (R Foundation) using the minfi package. Findings were validated using bisulfite pyrosequencing. Methylation levels at 1308 GAD1 regulatory network-associated CpG loci were assessed both as individual sites to identify differentially methylated positions and by sharing information among colocalized probes to identify differentially methylated regions. A total of

  5. Formation of biologically relevant carboxylic acids during the gamma irradiation of acetic acid

    Science.gov (United States)

    Negron-Mendoza, A.; Ponnamperuma, C.

    1976-01-01

    Irradiation of aqueous solutions of acetic acid with gamma rays produced several carboxylic acids in small yield. Their identification was based on the technique of gas chromatography combined with mass spectrometry. Some of these acids are Krebs Cycle intermediates. Their simultaneous formation in experiments simulating the primitive conditions on the earth suggests that metabolic pathways may have had their origin in prebiotic chemical processes.

  6. gamma-linolenic acid does not augment long-chain polyunsaturated fatty acid omega-3 status

    NARCIS (Netherlands)

    Brouwer, DAJ; Hettema, Y; van Doormaal, JJ; Muskiet, FAJ

    Augmentation of long chain polyunsaturated omega 3 fatty acid (LCPUFA omega 3) status can be reached by consumption of fish oil or by improvement of the conversion of a-linolenic acid (ALA) to LCPUFA omega 3. Since gamma-linolenic acid (GLA) might activate the rate-limiting Delta-6 desaturation, we

  7. The γ-aminobutyric acid-producing ability under low pH conditions of lactic acid bacteria isolated from traditional fermented foods of Ishikawa Prefecture, Japan, with a strong ability to produce ACE-inhibitory peptides.

    Science.gov (United States)

    Barla, Florin; Koyanagi, Takashi; Tokuda, Naoko; Matsui, Hiroshi; Katayama, Takane; Kumagai, Hidehiko; Michihata, Toshihide; Sasaki, Tetsuya; Tsuji, Atsushi; Enomoto, Toshiki

    2016-06-01

    Many traditional fermented products are onsumed in Ishikawa Prefecture, Japan, such as kaburazushi , narezushi , konkazuke , and ishiru. Various kinds of lactic acid bacteria (LAB) are associated with their fermentation, however, characterization of LAB has not yet been elucidated in detail. In this study, we evaluated 53 isolates of LAB from various traditional fermented foods by taxonomic classification at the species level by analyzing the 16S ribosomal RNA gene (rDNA) sequences and carbohydrate assimilation abilities. We screened isolates that exhibited high angiotensin-converting enzyme (ACE) inhibitory activities in skim milk or soy protein media and produced high γ-aminobutyric acid (GABA) concentrations in culture supernatants when grown in de Man Rogosa Sharpe broth in the presence of 1% (w/v) glutamic acid. The results revealed that 10 isolates, i.e., Lactobacillus buchneri (2 isolates), Lactobacillus brevis (6 isolates), and Weissella hellenica (2 isolates) had a high GABA-producing ability of >500 mg/100 ml after 72 h of incubation at 35 °C. The ACE inhibitory activity of the whey cultured with milk protein by using L. brevis (3 isolates), L. buchneri (2 isolates), and W. hellenica (2 isolates) was stronger than that of all whey cultured with soy protein media, and these IC 50 were GABA-producing activities at pH 3, suggesting that they could be powerful candidates for use in the fermentation of food materials having low pH.

  8. RP-HPLC method for simultaneous estimation of vigabatrin, gamma-aminobutyric acid and taurine in biological samples.

    Science.gov (United States)

    Police, Anitha; Shankar, Vijay Kumar; Narasimha Murthy, S

    2018-02-15

    Vigabatrin is used as first line drug in treatment of infantile spasms for its potential benefit overweighing risk of causing permanent peripheral visual field defects and retinal damage. Chronic administration of vigabatrin in rats has demonstrated these ocular events are result of GABA accumulation and depletion of taurine levels in retinal tissues. In vigabatrin clinical studies taurine plasma level is considered as biomarker for studying structure and function of retina. The analytical method is essential to monitor taurine levels along with vigabatrin and GABA. A RP-HPLC method has been developed and validated for simultaneous estimation of vigabatrin, GABA and taurine using surrogate matrix. Analytes were extracted from human plasma, rat plasma, retina and brain by simple protein precipitation method and derivatized by naphthalene 2, 3‑dicarboxaldehyde to produce stable fluorescent active isoindole derivatives. The chromatographic analysis was performed on Zorbax Eclipse AAA column using gradient elution profile and eluent was monitored using fluorescence detector. A linear plot of calibration curve was observed in concentration range of 64.6 to 6458, 51.5 to 5150 and 62.5 to 6258 ng/mL for vigabatrin, GABA and taurine, respectively with r 2  ≥ 0.997 for all analytes. The method was successfully applied for estimating levels of vigabatrin and its modulator effect on GABA and taurine levels in rat plasma, brain and retinal tissue. This RP-HPLC method can be applied in clinical and preclinical studies to explore the effect of taurine deficiency and to investigate novel approaches for alleviating vigabatrin induced ocular toxicity. Copyright © 2018. Published by Elsevier B.V.

  9. Effect of deltamethrin on transmission of gamma aminobutyric acid (GABA) and thyroid hormones in adult male albino rats

    International Nuclear Information System (INIS)

    Abdel-kader, S.M.; Abdel-Rahman, M.

    2005-01-01

    The oral administration of 1/5 LD 5 0 of deltamethrin for 15 days produced an increase in GABA content and a decrease in Cl - ions concentration in all tested brain areas (cerebellum, pons + medulla oblongata, striatum, cerebral cortex, hypothalamus, midbrain and hippocampus) of adult male albino rats, almost at most time intervals. Deltamethrin also resulted in a significant decrease in serum TSH and increase in T 3 and T 4 levels in the treated rats. From the present results, it was found that deltamethrin decreased the passage of Cl - ions in the cells which might be, in part, due to a decrease of the transmission of GABA and an increase of the circulating thyroid hormones (triiodothyronine and thyroxine). Accordingly, deltamethrin may act as GABA antagonist and may act on the hypothalamus pituitary thyroid axis. In conclusion the elevation of thyroid hormones as well as the decrease in both CL - ions and GABA transmission which could be all together responsible for the impairment of motor activity, hyper excitability and seizure that occurred in rats treated with the pyrethroid insecticide deltamethrin

  10. Development and Validation of a HPTLC Method for Simultaneous Estimation of L-Glutamic Acid and γ-Aminobutyric Acid in Mice Brain.

    Science.gov (United States)

    Sancheti, J S; Shaikh, M F; Khatwani, P F; Kulkarni, Savita R; Sathaye, Sadhana

    2013-11-01

    A new robust, simple and economic high performance thin layer chromatographic method was developed for simultaneous estimation of L-glutamic acid and γ-amino butyric acid in brain homogenate. The high performance thin layer chromatographic separation of these amino acid was achieved using n-butanol:glacial acetic acid:water (22:3:5 v/v/v) as mobile phase and ninhydrin as a derivatising agent. Quantitation of the method was achieved by densitometric method at 550 nm over the concentration range of 10-100 ng/spot. This method showed good separation of amino acids in the brain homogenate with Rf value of L-glutamic acid and γ-amino butyric acid as 21.67±0.58 and 33.67±0.58, respectively. The limit of detection and limit of quantification for L-glutamic acid was found to be 10 and 20 ng and for γ-amino butyric acid it was 4 and 10 ng, respectively. The method was also validated in terms of accuracy, precision and repeatability. The developed method was found to be precise and accurate with good reproducibility and shows promising applicability for studying pathological status of disease and therapeutic significance of drug treatment.

  11. Chronic effects of dichloromethane on amino acids, glutathione and phosphoethanolamine in gerbil brain

    Energy Technology Data Exchange (ETDEWEB)

    Briving, C.; Hamberger, A.; Kjellstrand, P.; Rosengren, L.; Karlsson, J.E.; Haglid, K.G.

    1986-06-01

    Mongolian gerbils were exposed to dichloromethane for three months by continuous inhalation at 210 ppm. Total free tissue amino acids, glutathione, and phosphoethanolamine were determined in the vermis posterior of the cerebellum and the frontal cerebral cortex. These two brain areas were chosen because humans occupationally exposed to dichloromethane have shown abnormalities in the electroencephalogram of the frontal part of the cerebral cortex. This study showed that long-term exposure of gerbils to dichloromethane (210 ppm) for three months leads to decreased levels of glutamate, gamma-aminobutyric acid, and phosphoethanolamine in the frontal cerebral cortex, while glutamine and gamma-aminobutyric acid are elevated in the posterior cerebellar vermis.

  12. Gas Phase Hydrogenation of Levulinic Acid to gamma-Valerolactone

    NARCIS (Netherlands)

    Bonrath, Werner; Castelijns, Anna Maria Cornelia Francisca; de Vries, Johannes Gerardus; Guit, Rudolf Philippus Maria; Schuetz, Jan; Sereinig, Natascha; Vaessen, Henricus Wilhelmus Leonardus Marie

    The gas phase hydrogenation of levulinic acid to gamma-valerolactone over copper and ruthenium based catalysts in a continuous fixed-bed reactor system was investigated. Among the catalysts a copper oxide based one [50-75 % CuO, 20-25 % SiO2, 1-5 % graphite, 0.1-1 % CuCO3/Cu(OH)(2)] gave

  13. Novel high-affinity and selective biaromatic 4-substituted ¿-hydroxybutyric acid (GHB) analogues as GHB ligands

    DEFF Research Database (Denmark)

    Høg, Signe; Wellendorph, Petrine; Nielsen, Birgitte

    2008-01-01

    Gamma-hydroxybutyrate (GHB) is a metabolite of gamma-aminobutyric acid (GABA) and has been proposed to function as a neurotransmitter or neuromodulator. GHB is used in the treatment of narcolepsy and is a drug of abuse. GHB binds to both GABA(B) receptors and specific high-affinity GHB sites...

  14. The γ-aminobutyric acid-producing ability under low pH conditions of lactic acid bacteria isolated from traditional fermented foods of Ishikawa Prefecture, Japan, with a strong ability to produce ACE-inhibitory peptides

    Directory of Open Access Journals (Sweden)

    Florin Barla

    2016-06-01

    Full Text Available Many traditional fermented products are onsumed in Ishikawa Prefecture, Japan, such as kaburazushi, narezushi, konkazuke, and ishiru. Various kinds of lactic acid bacteria (LAB are associated with their fermentation, however, characterization of LAB has not yet been elucidated in detail. In this study, we evaluated 53 isolates of LAB from various traditional fermented foods by taxonomic classification at the species level by analyzing the 16S ribosomal RNA gene (rDNA sequences and carbohydrate assimilation abilities. We screened isolates that exhibited high angiotensin-converting enzyme (ACE inhibitory activities in skim milk or soy protein media and produced high γ-aminobutyric acid (GABA concentrations in culture supernatants when grown in de Man Rogosa Sharpe broth in the presence of 1% (w/v glutamic acid. The results revealed that 10 isolates, i.e., Lactobacillus buchneri (2 isolates, Lactobacillus brevis (6 isolates, and Weissella hellenica (2 isolates had a high GABA-producing ability of >500 mg/100 ml after 72 h of incubation at 35 °C. The ACE inhibitory activity of the whey cultured with milk protein by using L. brevis (3 isolates, L. buchneri (2 isolates, and W. hellenica (2 isolates was stronger than that of all whey cultured with soy protein media, and these IC50 were < 1 mg protein/ml. Three of 10 isolates had high GABA-producing activities at pH 3, suggesting that they could be powerful candidates for use in the fermentation of food materials having low pH.

  15. Nicotinic and iso nicotinic acids: interactions with gamma radiation and acid-base equilibrium

    International Nuclear Information System (INIS)

    Ribeiro, Z.A.

    1984-01-01

    The values of pKa 1 and pKa 2 for nicotinic and iso nicotinic acids in aqueous medium were determined. The effects of gamma radiation about these acids by infrared and ultraviolet spectrophotometry and thermal gravimetric analysis were also studied. It was verified that the radiolysis of acids occurred by the two process of first order, determining the degradation constant and the degradation factors for each one of the solutions. (C.G.C.)

  16. gamma-Glutamyl amino acids. Transport and conversion to 5-oxoproline in the kidney

    International Nuclear Information System (INIS)

    Bridges, R.J.; Meister, A.

    1985-01-01

    Transport of gamma-glutamyl amino acids, a step in the proposed glutathione-gamma-glutamyl transpeptidase-mediated amino acid transport pathway, was examined in mouse kidney. The transport of gamma-glutamyl amino acids was demonstrated in vitro in studies on kidney slices. Transport was followed by measuring uptake of 35 S after incubation of the slices in media containing gamma-glutamyl methionine [ 35 S]sulfone. The experimental complication associated with extracellular conversion of the gamma-glutamyl amino acid to amino acid and uptake of the latter by slices was overcome by using 5-oxoproline formation (catalyzed by intracellular gamma-glutamyl-cyclotransferase) as an indicator of gamma-glutamyl amino acid transport. This method was also successfully applied to studies on transport of gamma-glutamyl amino acids in vivo. Transport of gamma-glutamyl amino acids in vitro and in vivo is inhibited by several inhibitors of gamma-glutamyl transpeptidase and also by high extracellular levels of glutathione. This seems to explain urinary excretion of gamma-glutamylcystine by humans with gamma-glutamyl transpeptidase deficiency and by mice treated with inhibitors of this enzyme. Mice depleted of glutathione by treatment with buthionine sulfoximine (which inhibits glutathione synthesis) or by treatment with 2,6-dimethyl-2,5-heptadiene-4-one (which effectively interacts with tissue glutathione) exhibited significantly less transport of gamma-glutamyl amino acids than did untreated controls. The findings suggest that intracellular glutathione functions in transport of gamma-glutamyl amino acids. Evidence was also obtained for transport of gamma-glutamyl gamma-glutamylphenylalanine into kidney slices

  17. Molecular determinants of desensitization and assembly of the chimeric GABA(A) receptor subunits (alpha1/gamma2) and (gamma2/alpha1) in combinations with beta2 and gamma2

    DEFF Research Database (Denmark)

    Elster, L; Kristiansen, U; Pickering, D S

    2001-01-01

    Two gamma-aminobutyric acid(A) (GABA(A)) receptor chimeras were designed in order to elucidate the structural requirements for GABA(A) receptor desensitization and assembly. The (alpha1/gamma2) and (gamma2/alpha1) chimeric subunits representing the extracellular N-terminal domain of alpha1 or gamma......, as opposed to the staining of the (gamma2/alpha1)-containing receptors, which was only slightly higher than background. To explain this, the (alpha1/gamma2) and (gamma2/alpha1) chimeras may act like alpha1 and gamma2 subunits, respectively, indicating that the extracellular N-terminal segment is important...... for assembly. However, the (alpha1/gamma2) chimeric subunit had characteristics different from the alpha1 subunit, since the (alpha1/gamma2) chimera gave rise to no desensitization after GABA stimulation in whole-cell patch-clamp recordings, which was independent of whether the chimera was expressed...

  18. Sodium p-Aminosalicylic Acid Reverses Sub-Chronic Manganese-Induced Impairments of Spatial Learning and Memory Abilities in Rats, but Fails to Restore γ-Aminobutyric Acid Levels

    Science.gov (United States)

    Li, Shao-Jun; Ou, Chao-Yan; He, Sheng-Nan; Huang, Xiao-Wei; Luo, Hai-Lan; Meng, Hao-Yang; Lu, Guo-Dong; Jiang, Yue-Ming; Vieira Peres, Tanara; Luo, Yi-Ni; Deng, Xiang-Fa

    2017-01-01

    Excessive manganese (Mn) exposure is not only a health risk for occupational workers, but also for the general population. Sodium para-aminosalicylic acid (PAS-Na) has been successfully used in the treatment of manganism, but the involved molecular mechanisms have yet to be determined. The present study aimed to investigate the effects of PAS-Na on sub-chronic Mn exposure-induced impairments of spatial learning and memory, and determine the possible involvements of γ-aminobutyric acid (GABA) metabolism in vivo. Sprague-Dawley male rats received daily intraperitoneal injections MnCl2 (as 6.55 mg/kg Mn body weight, five days per week for 12 weeks), followed by daily subcutaneous injections of 100, 200, or 300 mg/kg PAS-Na for an additional six weeks. Mn exposure significantly impaired spatial learning and memory ability, as noted in the Morris water maze test, and the following PAS-Na treatment successfully restored these adverse effects to levels indistinguishable from controls. Unexpectedly, PAS-Na failed to recover the Mn-induced decrease in the overall GABA levels, although PAS-Na treatment reversed Mn-induced alterations in the enzyme activities directly responsible for the synthesis and degradation of GABA (glutamate decarboxylase and GABA-transaminase, respectively). Moreover, Mn exposure caused an increase of GABA transporter 1 (GAT-1) and decrease of GABA A receptor (GABAA) in transcriptional levels, which could be reverted by the highest dose of 300 mg/kg PAS-Na treatment. In conclusion, the GABA metabolism was interrupted by sub-chronic Mn exposure. However, the PAS-Na treatment mediated protection from sub-chronic Mn exposure-induced neurotoxicity, which may not be dependent on the GABA metabolism. PMID:28394286

  19. Reduced γ-Aminobutyric Acid and Glutamate+Glutamine Levels in Drug-Naïve Patients with First-Episode Schizophrenia but Not in Those at Ultrahigh Risk

    Directory of Open Access Journals (Sweden)

    Junjie Wang

    2016-01-01

    Full Text Available Altered γ-aminobutyric acid (GABA, glutamate (Glu levels, and an imbalance between GABAergic and glutamatergic neurotransmissions have been involved in the pathophysiology of schizophrenia. However, it remains unclear how these abnormalities impact the onset and course of psychosis. In the present study, 21 drug-naïve subjects at ultrahigh risk for psychosis (UHR, 16 drug-naïve patients with first-episode schizophrenia (FES, and 23 healthy controls (HC were enrolled. In vivo GABA and glutamate+glutamine (Glx levels in the medial prefrontal cortex were measured using proton magnetic resonance spectroscopy. Medial prefrontal GABA and Glx levels in FES patients were significantly lower than those in HC and UHR, respectively. GABA and Glx levels in UHR were comparable with those in HC. In each group, there was a positive correlation between GABA and Glx levels. Reduced medial prefrontal GABA and Glx levels thus may play an important role in the early stages of schizophrenia.

  20. Reduced γ-Aminobutyric Acid and Glutamate+Glutamine Levels in Drug-Naïve Patients with First-Episode Schizophrenia but Not in Those at Ultrahigh Risk.

    Science.gov (United States)

    Wang, Junjie; Tang, Yingying; Zhang, Tianhong; Cui, Huiru; Xu, Lihua; Zeng, Botao; Li, Yu; Li, Gaiying; Li, Chunbo; Liu, Hui; Lu, Zheng; Zhang, Jianye; Wang, Jijun

    2016-01-01

    Altered γ -aminobutyric acid (GABA), glutamate (Glu) levels, and an imbalance between GABAergic and glutamatergic neurotransmissions have been involved in the pathophysiology of schizophrenia. However, it remains unclear how these abnormalities impact the onset and course of psychosis. In the present study, 21 drug-naïve subjects at ultrahigh risk for psychosis (UHR), 16 drug-naïve patients with first-episode schizophrenia (FES), and 23 healthy controls (HC) were enrolled. In vivo GABA and glutamate+glutamine (Glx) levels in the medial prefrontal cortex were measured using proton magnetic resonance spectroscopy. Medial prefrontal GABA and Glx levels in FES patients were significantly lower than those in HC and UHR, respectively. GABA and Glx levels in UHR were comparable with those in HC. In each group, there was a positive correlation between GABA and Glx levels. Reduced medial prefrontal GABA and Glx levels thus may play an important role in the early stages of schizophrenia.

  1. γ-Aminobutyric Acid (GABA) Production and Angiotensin-I Converting Enzyme (ACE) Inhibitory Activity of Fermented Soybean Containing Sea Tangle by the Co-Culture of Lactobacillus brevis with Aspergillus oryzae.

    Science.gov (United States)

    Jang, Eun Kyeong; Kim, Nam Yeun; Ahn, Hyung Jin; Ji, Geun Eog

    2015-08-01

    To enhance the γ-aminobutyric acid (GABA) content, the optimized fermentation of soybean with added sea tangle extract was evaluated at 30°C and pH 5.0. The medium was first inoculated with Aspergillus oryzae strain FMB S46471 and fermented for 3 days, followed by the subsequent inoculation with Lactobacillus brevis GABA 100. After fermentation for 7 days, the fermented soybean showed approximately 1.9 g/kg GABA and exhibited higher ACE inhibitory activity than the traditional soybean product. Furthermore, several peptides in the fraction containing the highest ACE inhibitory activity were identified. The novel fermented soybean enriched with GABA and ACE inhibitory components has great pharmaceutical and functional food values.

  2. Incorporation and distribution of dihomo-gamma-linolenic acid, arachidonic acid, and eicosapentaenoic acid in cultured human keratinocytes

    International Nuclear Information System (INIS)

    Punnonen, K.; Puustinen, T.; Jansen, C.T.

    1986-01-01

    Human keratinocytes in culture were labelled with 14 C-dihomo-gamma-linolenic acid, 14 C-arachidonic acid or 14 C-eicosapentaenoic acid. All three eicosanoid precursor fatty acids were effectively incorporated into the cells. In phospholipids most of the radioactivity was recovered, in neutral lipids a substantial amount, and as free unesterified fatty acids only a minor amount. Most of the radioactivity was found in phosphatidylethanolamine which was also the major phospholipid as measured by phosphorous assay. The incorporation of dihomo-gamma-linolenic acid and arachidonic acid into lipid subfractions was essentially similar. Eicosapentaenoic acid was, however, much less effectively incorporated into phosphatidylinositol + phosphatidylserine and, correspondingly, more effectively into triacylglycerols as compared to the two other precursor fatty acids. Once incorporated, the distribution of all three precursor fatty acids was relatively stable, and only minor amounts of fatty acids were released into the culture medium during short term culture (two days). Our study demonstrates that eicosanoid precursor fatty acids are avidly taken up by human keratinocytes and esterified into membrane lipids. The clinical implication of this finding is that dietary manipulations might be employed to cause changes in the fatty acid composition of keratinocytes

  3. Gamma amino butyric acid accumulation in medicinal plants without stress.

    Science.gov (United States)

    Anju, P; Moothedath, Ismail; Rema Shree, Azhimala Bhaskaranpillai

    2014-01-01

    Gamma amino butyric acid (GABA) is an important ubiquitous four carbon nonprotein amino acid with an amino group attached to gamma carbon instead of beta carbon. It exists in different organisms including bacteria, plants, and animals and plays a crucial role in humans by regulating neuronal excitability throughout the nervous system. It is directly responsible for the regulation of muscle tone and also effective in lowering stress, blood pressure, and hypertension. The aim of the study was to develop the fingerprint profile of selected medicinally and economically important plants having central nervous system (CNS) activity and to determine the quantity of GABA in the selected plants grown under natural conditions without any added stress. The high-performance thin layer chromatography analysis was performed on precoated silica gel plate 60F-254 plate (20 cm × 10 cm) in the form of bands with width 8 mm using Hamilton syringe (100 μl) using n-butanol, acetic acid, and water in the proportion 5:2:2 as mobile phase in a CAMAG chamber which was previously saturated for 30 min. CAMAG TLC scanner 3 was used for the densitometric scanning at 550 nm. Specific marker compounds were used for the quantification. Among the screened medicinal plants, Zingiber officinale and Solanum torvum were found to have GABA. The percentage of GABA present in Z. officinale and S. torvum were found to be 0.0114% and 0.0119%, respectively. The present work confirmed that among the selected CNS active medicinal plants, only two plants contain GABA. We found a negative correlation with plant having CNS activity and accumulation of GABA. The GABA shunt is a conserved pathway in eukaryotes and prokaryotes but, although the role of GABA as a neurotransmitter in mammals is clearly established, its role in plants is still vague.

  4. (1S, 3S)-3-amino-4-difluoromethylenyl-1-cyclopentanoic acid (CPP-115), a potent gamma-aminobutyric acid aminotransferase inactivator for the treatment of cocaine addiction

    DEFF Research Database (Denmark)

    Pan, Yue; Gerasimov, Madina R; Kvist, Trine

    2012-01-01

    Vigabatrin, a GABA aminotransferase (GABA-AT) inactivator, is used to treat infantile spasms and refractory complex partial seizures and is in clinical trials to treat addiction. We evaluated a novel GABA-AT inactivator (CPP-115) and observed that it does not exhibit other GABAergic or off-target...

  5. Fenton-enhanced {gamma}-radiolysis of cyanuric acid

    Energy Technology Data Exchange (ETDEWEB)

    Varghese, Rani [School of Chemical Sciences, Mahatma Gandhi University, Kottayam 686560, Kerala (India); Aravind, Usha K. [School of Chemical Sciences, Mahatma Gandhi University, Kottayam 686560, Kerala (India); Aravindakumar, Charuvila T. [School of Chemical Sciences, Mahatma Gandhi University, Kottayam 686560, Kerala (India)]. E-mail: CT-Aravindakumar@rocketmail.com

    2007-04-02

    Degradation of cyanuric acid (OOOT), a stable end product of oxidative decomposition of atrazine, is investigated in a combined field of gamma radiolysis and fenton reaction. The reaction of hydroxyl radical ({center_dot}OH) at pH 6 was carried out by irradiating N{sub 2}O saturated aqueous solutions containing OOOT (1 x 10{sup -3} mol dm{sup -3}), and this resulted only a marginal degradation (20%). However, when the same reaction was carried out in the presence of varying concentrations of ferrous sulfate ((5-10) x 10{sup -5} mol dm{sup -3}), the decay of OOOT has been enhanced to more than 80%. This decay followed a first order kinetics. Nearly similar effects were observed with another triazine derivative, 2,4-dioxohexahydro-1,3,5-triazine (DHT). Two major reaction mechanisms are proposed for the enhanced decay of OOOT. The formation of unstable hydroxyl radical adducts from the reaction of {center_dot}OH which is the result of gamma radiolysis and the Fenton reaction (resulting from the reaction of the added Fe(II) and of the H{sub 2}O{sub 2} from the radiolysis of water), is proposed as the first mechanism. The second mechanism, which is likely the major contributor to degradation, is proposed as the reaction of a nucleophilic adduct, Fe(II)OOH, which could directly react with the electron deficient triazine ring. It is highlighted that such degradation reactions must be explored for the complete degradation of the byproducts of the oxidative decomposition of atrazine.

  6. Poly-gamma-glutamic acid a substitute of salivary protein statherin

    International Nuclear Information System (INIS)

    Qamar, Z.; Rahim, Z.B.H.A.; Fatima, T.

    2016-01-01

    The modus operandi of salivary proteins in reducing the kinetics of enamel dissolution during simulated caries challenges is thought to be associated with interaction of glutamic acid residues with human teeth surfaces. Japanese traditional food stuff natto is rich with chain of repeating glutamic acid residues linked by gamma-peptide bond and hence, named poly-gamma-glutamic acid (PGGA). It is a naturally occurring polypeptide and may therefore perform similar caries inhibitory functions as statherin. (author)

  7. Determination of γ-Aminobutyric Acid (GABA) in Rambutan Fruit cv. Rongrian by HPLC-ELSD and Separation of GABA from Rambutan Fruit Using Dowex 50W-X8 Column.

    Science.gov (United States)

    Meeploy, Maneerat; Deewatthanawong, Rujira

    2016-03-01

    A high-performance liquid chromatography method coupled with an evaporative light scattering detector (ELSD) was validated for the determination of γ-aminobutyric acid (GABA) in rambutan fruit without any sample pretreatment or derivatization. In the concentration range of 0.05-1.0 mg/mL GABA, the ELSD response was linear with a correlation coefficient (r) >0.999. Limit of detection and limit of quantitation were found to be 0.7 and 2.0 µg/mL, respectively. The method enabled the complete separation of GABA in the aqueous extract of rambutan flesh from the impurity peaks at 45.7 min. The recoveries of sample added GABA were obtained in the range of 92.0-99.3%. Intraday and interday relative standard deviations were rambutan flesh, 0.71 ± 0.23 mg of GABA was found in 1 g fresh weight. The recovery of GABA after passing through the Dowex 50W-X8 column was 96.65%. The analytical methodology could be potentially applied to the detection and quantification of GABA in other fruits and complex matrices when a sufficient quantity is available. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  8. Production and Its Anti-hyperglycemic Effects of γ-Aminobutyric Acid from the Wild Yeast Strain Pichia silvicola UL6-1 and Sporobolomyces carnicolor 402-JB-1.

    Science.gov (United States)

    Han, Sang-Min; Lee, Jong-Soo

    2017-09-01

    This study was done to produce γ-aminobutyric acid (GABA) from wild yeast as well as investigate its anti-hyperglycemic effects. Among ten GABA-producing yeast strains, Pichia silvicola UL6-1 and Sporobolomyces carnicolor 402-JB-1 produced high GABA concentration of 134.4 µg/mL and 179.2 µg/mL, respectively. P. silvicola UL6-1 showed a maximum GABA yield of 136.5 µg/mL and 200.8 µg/mL from S. carnicolor 402-JB-1 when they were cultured for 30 hr at 30℃ in yeast extract-peptone-dextrose medium. The cell-free extract from P. silvicola UL6-1 and S. carnicolor 402-JB-1 showed very high anti-hyperglycemic α-glucosidase inhibitory activity of 72.3% and 69.9%, respectively. Additionally, their cell-free extract-containing GABA showed the anti-hyperglycemic effect in streptozotocin-induced diabetic Sprague-Dawley rats.

  9. Effect of gamma irradiation on the amino acid contents of seafood cooking drips

    International Nuclear Information System (INIS)

    Lee, Ju Woon; Kim, Yeon Joo; Choi, Jong Il; Kim, Yun Joo; Kim, Jae Hun; Kim, Jin Kyu; Byun, Myung Woo; Kwon, Joong Ho; Ahn, Dong Hyun; Chun, Byung Soo

    2008-01-01

    In this study, the effects of gamma irradiation on the change of structural and free amino acids contents of cooking drips from Hizikia fusiformis (HF) and Enteroctopus dofleini (ED) were investigated. The main structural amino acids were glutamic acid in HF cooking drip, and glutamic acid, glycine, arginine and aspartic acid in ED cooking drip, respectively. The concentrations of structural amino acids in both cooking drip extracts were decreased by the gamma irradiation at the dose of 10 kGy. Especially, the sulfur-containing amino acids were severely degraded by the irradiation. In free amino acid, ED cooking drip extract was contained the larger amount of free amino acid than that of HF cooking drip affecting its rich flavor. The free amino acid concentrations of cooking drips extracts from HF and ED were both increased by irradiation, and it explained the higher protein content by the irradiation

  10. Effect of γ-Aminobutyric Acid (GABA Producing Bacteria on Rumen Fermentation, Biogenic Amine Production and Anti-oxidation Using Corn Meal as Substrate

    Directory of Open Access Journals (Sweden)

    Bum Seung Ku

    2013-06-01

    Full Text Available The effects and significance of γ-amino butyric acid (GABA producing bacteria (GPB on in vitro rumen fermentation and reduction of biogenic amines (histamine, methylamine, ethylamine, and tyramine using corn meal as a substrate were determined. Ruminal samples collected from ruminally fistulated Holstein cows served as inoculum and corn was used as substrate at 2% dry matter (DM. Different inclusion rates of GPB and GABA were evaluated. After incubation, addition of GPB had no significant effect on in vitro fermentation pH and total gas production, but significantly increased the ammonia nitrogen (NH3-N concentration and reduced the total biogenic amines production (p<0.05. Furthermore, antioxidation activity was improved as indicated by the significantly higher concentration of superoxide dismutase (SOD and glutathione peroxidase (GSH-Px among treated samples when compared to the control (p<0.05. Additionally, 0.2% GPB was established as the optimum inclusion level. Taken together, these results suggest the potential of utilizing GPB as feed additives to improve growth performance in ruminants by reducing biogenic amines and increasing anti-oxidation.

  11. Effect of gamma radiation on the titrable acidity and vitamin c content of citrus fruits

    OpenAIRE

    Iftekhar Ahmad

    2012-01-01

    The study was carried out to assess effect of gamma radiation on the acidity and vitamin C content of the Citrus macroptera (Satkora) and Citrus assamensis (Ginger lime). Irradiation with doses 0.5, 1.0, 2.0, 3.0 kGy were applied to assess the effect on the titrable acidity and vitamin C contents every one week interval for total five weeks. Both titrable acidity and vitamin C content of C. macroptera, and C. assamensis are sensitive to both gamma radiation and storage time; have decreased wi...

  12. Effect of gamma radiation on the titrable acidity and vitamin c content of citrus fruits

    Directory of Open Access Journals (Sweden)

    Iftekhar Ahmad

    2012-06-01

    Full Text Available The study was carried out to assess effect of gamma radiation on the acidity and vitamin C content of the Citrus macroptera (Satkora and Citrus assamensis (Ginger lime. Irradiation with doses 0.5, 1.0, 2.0, 3.0 kGy were applied to assess the effect on the titrable acidity and vitamin C contents every one week interval for total five weeks. Both titrable acidity and vitamin C content of C. macroptera, and C. assamensis are sensitive to both gamma radiation and storage time; have decreased with increase of radiation does as well as storage time and this changes of vitamin C and titrable acidity content with gamma radiation and increasing storage period have found statistically significant.

  13. Effect of Yi-nao-jie-yu decoction on γ-aminobutyric acid type A receptor in the hippocampus and serum inflammatory factors in a rat model of poststroke anxiety

    Directory of Open Access Journals (Sweden)

    Zhang W

    2016-11-01

    Full Text Available Wen Zhang,1 Ruizhen Zhao,1 Xiaoli Li,1 Xia Cui,1 Zijun Zhao,1 Yingqiu Mao,2 Fengzhi Wu,3 Qisheng Tang1 1Department of Encephalopathy, The Third Affiliated Hospital, 2Center of Scientific Research, 3Center of Journals, Beijing University of Chinese Medicine, Chaoyang District, Beijing, People’s Republic of China Background: The Yi-nao-jie-yu decoction (YNJYD is a herbal preparation widely used in the clinics of traditional Chinese medicine and has been recently used as an important new therapeutic agent in poststroke anxiety (PSA. The neuroendocrine–immune system plays an important role in PSA mechanisms, although the modulating effects of YNJYD remain unknown. This study investigated the potential effects of YNJYD on the neuroendocrine–immune system in a rat model of PSA.Materials and methods: The PSA model was induced by injecting collagenase (type VII into the right globus pallidus, accompanied by empty water bottle stimulation for 2 weeks. The sham group and the PSA model group were gavaged with saline, while the treatment groups received buspirone (BuSpar or YNJYD. Behavior was evaluated with the open field test and elevated plus maze once a week. Pathological changes were observed by hematoxylin and eosin staining. Serum levels of tumor necrosis factor, interleukin (IL-6, adrenocorticotropic hormone, thyroid stimulating hormone, free triiodothyronine, free thyroxine, IL-1α, and cortisol were detected by radioimmunoassay. Expression of the γ-aminobutyric acid type A receptor (GABAAR α2 subunit was examined by Western blot and real-time polymerase chain reaction.Results: YNJYD-treated rats exhibited significantly better recovery than BuSpar-treated rats at 21 days and 28 days in the open field test and elevated plus maze. Hematoxylin and eosin staining revealed neural repair in the hippocampus in the treatment groups. Serum levels of IL-1α in the YNJYD group were significantly less than those in the model group and the Bu

  14. Effect of electroacupuncture on thermal pain threshold and expression of calcitonin-gene related peptide, substance P and γ-aminobutyric acid in the cervical dorsal root ganglion of rats with incisional neck pain.

    Science.gov (United States)

    Qiao, Li-Na; Liu, Jun-Ling; Tan, Lian-Hong; Yang, Hai-Long; Zhai, Xu; Yang, Yong-Sheng

    2017-08-01

    Acupuncture therapy effectively reduces post-surgical pain, but its mechanism of action remains unclear. The aim of this study was to investigate whether expression of γ-aminobutyric acid (GABA) and the neuropeptides substance P (SP) and calcitonin gene-related peptide (CGRP) in the primary sensory neurons of cervical dorsal root ganglia (DRG) are involved in electroacupuncture (EA)-induced analgesia in a rat model of incisional neck pain. The pain model was established by making a longitudinal midline neck incision in 60 rats. Another 15 rats underwent sham surgery (normal group). Post-incision, 15 rats remained untreated (model group) and 45 rats underwent EA (frequency 2/100 Hz, intensity 1 mA) at bilateral LI18, LI4-PC6 or ST36-GB34 (n=15 each) for 30 min at 4 hours, 24 hours, and 48 hours post-surgery, followed by thermal pain threshold (PT) measurement. 30 min later, the rats were euthanased and cervical (C3-6) DRGs removed for measurement of immunoreactivity and mRNA expression of SP/CGRP and the GABAergic neuronal marker glutamic acid decarboxylase 67 (GAD67). Thermal PT was significantly lower in the model group versus the normal group and increased in the LI18 and LI4-PC6 groups but not the ST36-GB34 group compared with the model group. Additionally, EA at LI18 and LI4-PC6 markedly suppressed neck incision-induced upregulation of mRNA/protein expression of SP/CGRP, and upregulated mRNA/protein expression of GAD67 in the DRGs of C3-6 segments. EA at LI18/LI4-PC6 increases PT in rats with incisional neck pain, which is likely related to downregulation of pronociceptive mediators SP/CGRP and upregulation of the inhibitory transmitter GABA in the primary sensory neurons of cervical DRGs. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  15. Physiological response of marigold (calendula officinalis L.) plants to gamma radiation, gibberellic acid and kinetin

    International Nuclear Information System (INIS)

    Noby, M.F.A.

    2010-01-01

    This study was carried out during the two successive seasons of 2005/2006 and 2006/2007 at the Experimental Field of Plant Research Department, Nuclear Research Center, Atomic Energy Authority at Inshas in a newly reclaimed sandy loam soil. The aim of this work was to study the effect of gamma radiation, gibberellic acid or kinetin and their interaction on the growth, flowering and the productivity of pot-marigold (Calendula officinalis L.) plants. The experimental trials included two factorial experiments; the first one was to study the effect of gamma radiation and gibberellic acid and the interaction between them on pot-marigold plants. Another experiment was conducted to study the effect of gamma radiation and kinetin and the interaction between them on pot-marigold plants. Pot-marigold seeds were irradiated before sowing with gamma rays at 0, 50, 100, 150 or 200 Gray (Gy) of gamma rays. After planting, plants were sprayed with either gibberellic acid (at the concentrations of 0, 50, 100, 150 or 200 ppm) or kinetin (at the concentrations of 0, 10, 20, 30 or 40 ppm). Generally, gamma rays treatments (50, 100 and 150 Gy) increased plant height, branch number/plant, leaf area, vegetative growth and roots fresh and dry weights of pot-marigold plants. Also, the same gamma doses accelerated flowering and decreased the period from sowing until flowering while increased flower head diameter, flower number/plant and flowers fresh and dry weights per plant and per feddan. In addition, gamma rays (50 - 150 Gy) increased volatile oil yield in flowers, leaf chlorophyll content, carotenoids and beta carotene in flowers, total soluble sugars and NPK %. The best values were obtained by 50 Gy dose of gamma rays, whereas the dose of 200 Gy gave the lowest values.

  16. Electrochemical behaviour of gamma hydroxybutyric acid at a platinum electrode in acidic medium

    International Nuclear Information System (INIS)

    Jiménez-Pérez, R.; Sevilla, J.M.; Pineda, T.; Blázquez, M.; González-Rodríguez, J.

    2013-01-01

    Highlights: • This is the first reported electrochemical study of the behaviour of GHB. • The first study of the interaction of GHB on solid electrodes. • The GHB oxidation process in platinum electrodes is a complex process. • Re-dissolution and reduction of Pt oxides and oxidation of the GHB OH group. • The oxidation process is also influenced by pH and GHB concentration. -- Abstract: The electrooxidation of gamma hydroxybutyric acid (GHB) on a polycrystalline platinum electrode is studied by cyclic voltammetry in acidic medium. Two oxidation peaks, A and B, are obtained in the positive scan within the potential range of the double layer region and of the platinum oxide region, respectively. In the negative going potential sweep an inverted oxidation peak with an onset partially overlapping with the tail of the cathodic peak for the reduction of the platinum oxide formed during the anodic scan is obtained (peak C). This inverted peak can be observed at a potential close to +0.2 V (vs Ag/AgCl at pH 2) and separated 0.4 and 0.8 V from the two other oxidation peaks obtained during the anodic scan and in such conditions that the surface is particularly activated to favour this electrochemical process. The response obtained in the electronic current for the different peaks when GHB concentration and scan rate were changed to allows inferring that these are the result of a potential dependent mechanism. The behaviour observed is according with the oxidation of the alcohol group to the corresponding aldehyde and carboxylic acid (succinic acid) as main products

  17. Gamma-irradiation of malic acid in aqueous solutions. [prebiotic significance

    Science.gov (United States)

    Negron-Mendoza, A.; Graff, R. L.; Ponnamperuma, C.

    1980-01-01

    The gamma-irradiation of malic acid in aqueous solutions was studied under initially oxygenated and oxygen-free conditions in an attempt to determine the possible interconversion of malic acid into other carboxylic acids, specifically those associated with Krebs cycle. The effect of dose on product formation of the system was investigated. Gas-liquid chromatography combined with mass spectrometry was used as the principal means of identification of the nonvolatile products. Thin layer chromatography and direct probe mass spectroscopy were also employed. The findings show that a variety of carboxylic acids are formed, with malonic and succinic acids in greatest abundance. These products have all been identified as being formed in the gamma-irradiation of acetic acid, suggesting a common intermediary. Since these molecules fit into a metabolic cycle, it is strongly suggestive that prebiotic pathways provided the basis for biological systems.

  18. Determination of fatty acid composition of {gamma}-irradiated hazelnuts, walnuts, almonds, and pistachios

    Energy Technology Data Exchange (ETDEWEB)

    Gecgel, Umit [Namik Kemal University, Agricultural Faculty, Department of Food Engineering, 59030 Tekirdag (Turkey); Gumus, Tuncay; Tasan, Murat; Daglioglu, Orhan; Arici, Muhammet [Namik Kemal University, Agricultural Faculty, Department of Food Engineering, 59030 Tekirdag (Turkey)

    2011-04-15

    Hazelnut, walnut, almonds, and pistachio nuts were treated with 1, 3, 5, and 7 kGy of gamma irradiation, respectively. Oil content, free fatty acid, peroxide value, and fatty acid composition of the nuts were investigated immediately after irradiation. The data obtained from the experiments indicated that gamma irradiation did not cause any significant change in the oil content of nuts. In contrast, free fatty acid and peroxide value of the nuts increased proportionally to the dose (p<0.05). Among the fatty acids determined, the concentration of total saturated fatty acids increased while total monounsaturated and total polyunsaturated fatty acids decreased with the irradiation dose (p<0.05 and <0.01).

  19. Effect of gamma-irradiation on the phenolic acids of some Indian spices

    International Nuclear Information System (INIS)

    Variyar, P.S.; Bandyopadhyay, C.; Thomas, P.

    1998-01-01

    Five commercially important spices, namely cinnamon, clove, cardamom, nutmeg and mace, were subjected to gamma-irradiation using a dose of 10 kGy, which is recommended for microbial decontamination. Various phenolic acids present in these spices were analysed by high-performance liquid chromatography (HPLC). In clove and nutmeg, quantitatively significant changes were noted in some of the phenolic acids upon irradiation. The content of gallic and syringic acids in irradiated clove increased by 2.2- and 4.4-fold respectively, whereas in irradiated nutmeg many of the phenolic acids showed wide increases and decreases in the range of two- to sixfold compared with the control samples. No qualitative and major quantitative changes were, however, observed in the phenolic acids of cinnamon, cardamom and mace upon irradiation. The possibility that gamma-radiation induced breakdown of tannins could be responsible for the changes in phenolic acids content of clove and nutmeg is discussed

  20. Effect of gamma irradiation on fatty acids of tomato seed oil

    International Nuclear Information System (INIS)

    El-Sayed, S.A.; Raouf, M.S.; Morad, M.M.; Rady, A.H.

    1979-01-01

    Since gamma irradiation of tomatoes is investigated as a tool for increasing tomato shelf-lefe, in this study the tomato seed oil produced from irradiated tomatoes was compared with that produced from industrial tomato seeds and with cotton seeds. Fatty acid contents of tomato seed oil, produced from industrial tomato seed waste and from tomato seeds (Variety Ace), were found nearly the same as in the edible cotton seed oil. Hence, both tomato seed oils may be considered as an additional source of essential fatty acids especially linoleic. Gamma irradiation doses ranged from 50-200 Krad had no significant effect on total saturated and total unsaturated fatty acids. 200 Krad led to significant increases in lenolic acid on the account of insignificant decrease in palmatic acid. Essentail and non essential amino acids of tomato seed meal seem to be equivalent to these of cotton seed meal. This suggests the possible use of tomato seed meal in animal feeding

  1. 檀香叶中的γ-氨基丁酸的HPLC测定研究%Determination of γ-Aminobutyric Acid in Leaves of Santalum album L.by HPLC

    Institute of Scientific and Technical Information of China (English)

    杨艳; 贺丽苹; 高向阳

    2013-01-01

    A method was established by reversed-phase high performance liquid chromatography for determining the content of y-aminobutyric acid ( GABA) in leaves of Santalum album L. The sample was pretreated by soxhlet extraction to eliminate the pigments with ether, and then by water extraction and alcohol precipitation to eliminate sugar and protein. GABA was derivatized with dansyl chloride (Dns-Cl) and isolated by reversed-phase HPLC. GABA was detected quantitatively by HPLC with fluorescence detection. Nice linear relationship between peak area and concentration was obtained with the linear regression equation as y=475 211x+69 037,R2 =0.999 8. The recovery of standard addition was in the range of 112% to 120%. The detection limit of GABA was 7 μg/g. The established HPLC method is simple, economic, stable and accurate with good reproducibility. It can be applied on determination of GABA in leaves of Santalum album L.%建立了檀香叶中γ-氨基丁酸(GABA)含量的高效液相色谱检测方法.以乙醚为溶剂,采用索氏提取除去色素,水提醇沉去除糖类和蛋白质的净化方法,以丹酰氯为衍生剂,高效液相色谱法分离,荧光检测器测定,外标法定量.峰面积与浓度之间线性关系良好,回归方程为y=475 211x+ 69 037,R2=0.999 8,加标回收率为112 %~120%,检测限为7μg/g.该方法操作步骤简单,灵敏度高,用于檀香叶中GABA的检测,方法简便、准确、高效.

  2. Transition from androgenic to neurosteroidal action of 5α-androstane-3α, 17β-diol through the type A γ-aminobutyric acid receptor in prostate cancer progression.

    Science.gov (United States)

    Xia, Ding; Lai, Doan V; Wu, Weijuan; Webb, Zachary D; Yang, Qing; Zhao, Lichao; Yu, Zhongxin; Thorpe, Jessica E; Disch, Bryan C; Ihnat, Michael A; Jayaraman, Muralidharan; Dhanasekaran, Danny N; Stratton, Kelly L; Cookson, Michael S; Fung, Kar-Ming; Lin, Hsueh-Kung

    2018-04-01

    Androgen ablation is the standard of care prescribed to patients with advanced or metastatic prostate cancer (PCa) to slow down disease progression. Unfortunately, a majority of PCa patients under androgen ablation progress to castration-resistant prostate cancer (CRPC). Several mechanisms including alternative intra-prostatic androgen production and androgen-independent androgen receptor (AR) activation have been proposed for CRPC progression. Aldo-keto reductase family 1 member C3 (AKR1C3), a multi-functional steroid metabolizing enzyme, is specifically expressed in the cytoplasm of PCa cells; and positive immunoreactivity of the type A γ-aminobutyric acid receptor (GABA A R), an ionotropic receptor and ligand-gated ion channel, is detected on the membrane of PCa cells. We studied a total of 72 radical prostatectomy cases by immunohistochemistry, and identified that 21 cases exhibited positive immunoreactivities for both AKR1C3 and GABA A R. In the dual positive cancer cases, AKR1C3 and GABA A R subunit α 1 were either expressed in the same cells or in neighboring cells. Among several possible substrates, AKR1C3 reduces 5α-dihydrotesterone (DHT) to form 5α-androstane-3α, 17β-diol (3α-diol). 3α-diol is a neurosteroid that acts as a positive allosteric modulator of the GABA A R in the central nervous system (CNS). We examined the hypothesis that 3α-diol-regulated pathological effects in the prostate are GABA A R-dependent, but are independent of the AR. In GABA A R-positive, AR-negative human PCa PC-3 cells, 3α-diol significantly stimulated cell growth in culture and the in ovo chorioallantoic membrane (CAM) xenograft model. 3α-diol also up-regulated expression of the epidermal growth factor (EGF) family of growth factors and activation of EGF receptor (EGFR) and Src as measured by quantitative polymerase chain reaction and immunoblotting, respectively. Inclusion of GABA A R antagonists reversed 3α-diol-stimulated tumor cell growth, expression of EGF

  3. Effect of Functional Bread Rich in Potassium, γ-Aminobutyric Acid and Angiotensin-Converting Enzyme Inhibitors on Blood Pressure, Glucose Metabolism and Endothelial Function: A Double-blind Randomized Crossover Clinical Trial.

    Science.gov (United States)

    Becerra-Tomás, Nerea; Guasch-Ferré, Marta; Quilez, Joan; Merino, Jordi; Ferré, Raimon; Díaz-López, Andrés; Bulló, Mònica; Hernández-Alonso, Pablo; Palau-Galindo, Antoni; Salas-Salvadó, Jordi

    2015-11-01

    Because it has been suggested that food rich in γ-aminobutyric acid (GABA) or angiotensin-converting enzyme inhibitor (ACEI) peptides have beneficial effects on blood pressure (BP) and other cardiovascular risk factors, we tested the effects of low-sodium bread, but rich in potassium, GABA, and ACEI peptides on 24-hour BP, glucose metabolism, and endothelial function.A randomized, double-blind, crossover trial was conducted in 30 patients with pre or mild-to-moderate hypertension, comparing three 4-week nutritional interventions separated by 2-week washout periods. Patients were randomly assigned to consume 120 g/day of 1 of the 3 types of bread for each nutritional intervention: conventional wheat bread (CB), low-sodium wheat bread enriched in potassium (LSB), and low-sodium wheat bread rich in potassium, GABA, and ACEI peptides (LSB + G). For each period, 24-hour BP measurements, in vivo endothelial function, and biochemical samples were obtained.After LSB + G consumption, 24-hour ambulatory BP underwent a nonsignificant greater reduction than after the consumption of CB and LSB (0.26 mm Hg in systolic BP and -0.63 mm Hg in diastolic BP for CB; -0.71 mm Hg in systolic BP and -1.08 mm Hg in diastolic BP for LSB; and -0.75 mm Hg in systolic BP and -2.12 mm Hg in diastolic BP for LSB + G, respectively). Diastolic BP at rest decreased significantly during the LSB + G intervention, although there were no significant differences in changes between interventions. There were no significant differences between interventions in terms of changes in in vivo endothelial function, glucose metabolism, and peripheral inflammatory parameters.Compared with the consumption of CB or LSB, no greater beneficial effects on 24-hour BP, endothelial function, or glucose metabolism were demonstrated after the consumption of LSB + G in a population with pre or mild-to-moderate hypertension. Further studies are warranted to clarify the effect of GABA on BP

  4. Effect of ouabain on the gamma-[3H]aminobutyric acid uptake and release in the absence of Ca(+)+ and K(+)-depolarization

    International Nuclear Information System (INIS)

    Santos, M.S.; Goncalves, P.P.; Carvalho, A.P.

    1990-01-01

    The effect of ouabain on the uptake of tritiated [ 3 H]GABA and on its release in the absence of Ca(+)+ was studied in brain cortex synaptosomes. Ouabain, in the absence of Ca(+)+ and K(+)-depolarization, induces the release of [ 3 H]GABA with half-maximal effect occurring at a concentration of about 7 X 10(-6) M. Parallel measurements of the effects of ouabain on the [ 3 H]GABA uptake and the Na+,K(+)-adenosine triphosphatase activity show that ouabain inhibits both mechanisms and that the half-maximal effect also occurs at about the same ouabain concentration. Although [ 3 H]GABA release is stimulated by ouabain, it appears that the inhibition of [ 3 H]GABA uptake is due to a direct effect on the uptake mechanism, inasmuch as the initial velocity of the process is inhibited by ouabain. Ouabain requires extracellular Na+ for [ 3 H]GABA release and for membrane depolarization and, in the absence of Na+, ouabain does not cause either [ 3 H]GABA release or membrane depolarization. No significant changes in the Na+ gradients occur under conditions which permit release of [ 3 H]GABA, but the Na+,K(+)-adenosine triphosphatase activity is inhibited, which may be responsible for membrane depolarization, which in turn may cause [ 3 H]GABA release or inhibit its uptake

  5. Residues in the extracellular loop 4 are critical for maintaining the conformational equilibrium of the gamma-aminobutyric acid transporter-1

    DEFF Research Database (Denmark)

    MacAulay, Nanna; Meinild, Anne-Kristine; Zeuthen, Thomas

    2003-01-01

    . Oocytes expressing M345H showed a decrease in apparent GABA affinity, an increase in apparent affinity for Na+, a shift in the charge/voltage (Q/Vm) relationship to more positive membrane potentials, and an increased Li+-induced leak current. Oocytes expressing T349H showed an increase in apparent GABA...... affinity, a decrease in apparent Na+ affinity, a profound shift in the Q/Vm relationship to more negative potentials, and a decreased Li+-induced leak current. The data are consistent with a shift in the conformational equilibrium of the mutant transporters, with M345H stabilized in an outward...

  6. Glutamate decarboxylase immunoreactivity and gamma-[3H] aminobutyric acid accumulation within the same neurons in dissociated cell cultures of cerebral cortex

    International Nuclear Information System (INIS)

    Neale, E.A.; Oertel, W.H.; Bowers, L.M.; Weise, V.K.

    1983-01-01

    In order to evaluate the reliability of high affinity [ 3 H]GABA accumulation as a marker for GABAergic neurons, murine cerebral cortical neurons were studied in dissociated cell culture. Cultures which had been incubated in [ 3 H]GABA were stained immunohistochemically for the GABA-synthesizing enzyme, glutamate decarboxylase, fixed with paraformaldehyde, and subsequently processed for radioautography. In mature cultures, there was an 84 to 94% correlation between the presence of the enzyme and [ 3 H]GABA uptake within the same cortical neurons. These data provide direct evidence that those neurons which synthesize GABA are the same neurons which are labeled by high affinity [ 3 H]GABA uptake

  7. Radioprotective effects of chlorogenic acid against mortality induced by gamma irradiation in mice

    International Nuclear Information System (INIS)

    Seyed Jalal Hosseinimehr; Amirhossein Ahmadi; Shahram Akhlaghpoor; Tehran University of Medical Sciences, Tehran

    2007-01-01

    Complete text of publication follows. The radioprotective effects of the naturally occurring compound chlorogenic acid has been investigated against mortality induced by gamma irradiation in mice. Chlorogenic acid administrated at single doses of 100, 200 and 400 mg/kg 1 and 24 h prior to lethal dose of gamma irradiation (8.5 Gy). At 30 days after treatment, the percentage of animal survival in each group was: control, 20%; 100 mg/kg, 20% and 15%; 200 mg/kg, 45% and 15%; 400 mg/kg, 25% and 35% for 1 h and 24 h treatment prior gamma irradiation, respectively. Percentage of survival increased in animal treated with this agent at 200 mg/kg at 1 h statistically compared with irradiated alone group. Other doses of chlorogenic acid have not showed any enhanced survival at 1 and 24 h before irradiation. Chlorogenic acid exhibited concentration-dependent activity on 1, 1-diphenyl 2-picrylhydrazyl free radical to show strong antioxidant activity. It appeared that chlorogenic acid with antioxidant activity reduced mortality induced by gamma irradiation.

  8. [Study on the encapsulation technique of high purity gamma-linolenic acid, part 1--saponification reaction and saponification value].

    Science.gov (United States)

    Liu, Feng-xia; Xue, Gang; Gao, Qiu-hua; Gao, Wei-xia; Zhang, Li-hua

    2005-03-01

    To measure the saponification value and fatty acid formation of evening primrose oil, to study the effects of pH value on production yield and fatty acid formation during the saponification reaction, and to provide rationales for the selection of raw material, the enhancement of production yield of saponification, and the encapsulation of gamma-linolenic acid with urea. To measure fatty acid's formation with gas chromatographic method and to measure the saponification value. The content of gamma-linolenic acid is 7%-10% in evening primrose oil. The content of gamma-linolenic acid is inversely correlated with that of unsaturated fatty acid. The saponification value, the amount of KOH for saponification of evening primrose oil, and the pH value for subsequent isolations of oils are determined. From the measurement of fatty acids of evening primrose oil in two different cultivation locations, the content of gamma-linolenic acid is determined to be 7%-10%, unsaturated oils account for 90%. The saponification value of evening primrose oil is between 180-200, pH value of isolated oil is 1.5-2.0 after saponification reaction. Fatty acids mainly include palmitic acid, stearic acid, oleic acid, linolic acid and gamma-linolenic acid.

  9. Effect of gamma sterilization on the fatty acid profile of lyophilized buffalo cheese

    International Nuclear Information System (INIS)

    Ivanova, S.; Nacheva, I.; Miteva, D.; Loginovska, K.; Tsvetkov, Ts.

    2009-01-01

    The changes in the fatty acid profile of buffalo cheese after lyophilization and gamma rays treatment at 2 kGy and 4 kGy doses have been studied with the objective of its shelf-live prolongation. The results of the experiments show a decrease of the content of the saturated fatty acids after irradiation at the aforesaid gamma rays doses. A favorable effect on human organism has the decrease of the quantity of the short-chain fatty acids – by 13.16 % on irradiation at 2 kGy and by 18.73% on irradiation at 4 kGy, compared to the control sample. A satisfactory correlation between the essential fatty acids omega-6/omega3 has been observed in the lyophilized buffalo cheese. In the process of irradiation this balanced correlation changes and increases up to 7.32 and 8.31 at 2 kGy and 4 kGy respectively

  10. Prevention Effect of Poly-Gamma-Glutamic Acid on Tissue Damage Induced by Gamma Irradiation as a Natural Cross-Linker

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jaehun; Sung, Nakyun; Kim, Jeongsoo; Jo, Euri; Choi, Jongil; Park, Jongheum; Lee, Juwoon [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of); Lee, Kwangwon [Eulji Univ. Hospital, Daejeon (Korea, Republic of); Kwon, Jungkee [Chonbuk National Univ., Jeonju (Korea, Republic of); Kim, Taewoon [Jeonbuk Technopark, Jeonju (Korea, Republic of)

    2012-03-15

    This study was to determine the prevention effect of poly-gamma-glutamic acid (PGA) on tissue damage induced by gamma irradiation for development of xenograft. PGA (MW 2000 kDa) extracted from permeated soy bean (natto) was used in this study as natural compound, and glutaraldehyde (GA) and 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) were used as a control, chemical based cross-linking agents. GA, EDC and PGA treated porcine tendons were gamma-irradiated at the dose of 30 kGy. Prevention effects against tissue damage were measured as the result of tensile strength, hydroxyproline contents and tissue morphological analysis. Tensile of porcine tendon was remarkably decreased by gamma irradiation, but increased in PGA treated group. Morphological analysis showed that collagen structure was broken by gamma irradiation, but attenuated by PGA treatment. Base on the results, it demonstrated that gamma irradiation can induce severe alteration of porcine tendon, but PGA can effectively improve the tissue damage.

  11. Prevention Effect of Poly-Gamma-Glutamic Acid on Tissue Damage Induced by Gamma Irradiation as a Natural Cross-Linker

    International Nuclear Information System (INIS)

    Kim, Jaehun; Sung, Nakyun; Kim, Jeongsoo; Jo, Euri; Choi, Jongil; Park, Jongheum; Lee, Juwoon; Lee, Kwangwon; Kwon, Jungkee; Kim, Taewoon

    2012-01-01

    This study was to determine the prevention effect of poly-gamma-glutamic acid (PGA) on tissue damage induced by gamma irradiation for development of xenograft. PGA (MW 2000 kDa) extracted from permeated soy bean (natto) was used in this study as natural compound, and glutaraldehyde (GA) and 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) were used as a control, chemical based cross-linking agents. GA, EDC and PGA treated porcine tendons were gamma-irradiated at the dose of 30 kGy. Prevention effects against tissue damage were measured as the result of tensile strength, hydroxyproline contents and tissue morphological analysis. Tensile of porcine tendon was remarkably decreased by gamma irradiation, but increased in PGA treated group. Morphological analysis showed that collagen structure was broken by gamma irradiation, but attenuated by PGA treatment. Base on the results, it demonstrated that gamma irradiation can induce severe alteration of porcine tendon, but PGA can effectively improve the tissue damage

  12. Inclusion polymerization of vinyl chloride monomer in deoxycholic acid host via {gamma}-ray irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Chirachanchai, S.; Kumkrong, A. [The Petroleum and Petrochemical College, Chulalongkorn University, Bangkok (Thailand); Ishida, Hatsuo [Department of Macromolecular Science, Case Western Reserve University, Cleveland, OH (United States)

    2000-03-01

    Inclusion polymerization of vinyl chloride monomer (VCM) was studied in the system of 3{alpha}, 12{alpha} -dihydroxy-5{beta}-cholan-24-oic acid (deoxycholic acid, DCA). DCA-VCM inclusion compound system was originally prepared by guest intercalation technique in DCA guest free crystal. The inclusion polymerization of DCA-VCM by {gamma}-irradiation at total dose 2 Mrad, gives a syndiotactic rich polyvinyl chloride (PVC) as can be confirmed by FT-IR and FT-NMR. (author)

  13. Solute-enhanced production of gamma-valerolactone (GVL) from aqueous solutions of levulinic acid

    Energy Technology Data Exchange (ETDEWEB)

    Dumesic, James A.; Wettstein, Stephanie G.; Alonso, David Martin; Gurbuz, Elif Ispir

    2016-06-28

    A method to produce levulinic acid (LA) and gamma-valerolactone (GVL) from biomass-derived cellulose or lignocellulose by selective extraction of LA using GVL and optionally converting the LA so isolated into GVL, with no purifications steps required to yield the GVL.

  14. Solute-enhanced production of gamma-valerolactone (GVL) from aqueous solutions of levulinic acid

    Energy Technology Data Exchange (ETDEWEB)

    Dumesic, James A; Wettstein, Stephanie G; Alonso, David Martin; Gurbuz, Elif Ispir

    2015-02-24

    A method to produce levulinic acid (LA) and gamma-valerolactone (GVL) from biomass-derived cellulose or lignocellulose by selective extraction of LA using GVL and optionally converting the LA so isolated into GVL, with no purifications steps required to yield the GVL.

  15. OH-radical induced degradation of hydroxybenzoic- and hydroxycinnamic acids and formation of aromatic products-A gamma radiolysis study

    Energy Technology Data Exchange (ETDEWEB)

    Krimmel, Birgit; Swoboda, Friederike [University of Vienna, Department of Nutritional Sciences, Section Radiation Biology (Austria); Solar, Sonja, E-mail: sonja.solar@univie.ac.a [University of Vienna, Department of Nutritional Sciences, Section Radiation Biology (Austria); Reznicek, Gottfried [Department of Pharmacognosy, Althanstrasse 14, A-1090 Vienna (Austria)

    2010-12-15

    The OH-radical induced degradation of hydroxybenzoic acids (HBA), hydroxycinnamic acids (HCiA) and methoxylated derivatives, as well as of chlorogenic acid and rosmarinic acid was studied by gamma radiolysis in aerated aqueous solutions. Primary aromatic products resulting from an OH-radical attachment to the ring (hydroxylation), to the position occupied by the methoxyl group (replacement -OCH{sub 3} by -OH) as well as to the propenoic acid side chain of the cinnamic acids (benzaldehyde formations) were analysed by HPLC-UV and LC-ESI-MS. A comparison of the extent of these processes is given for 3,4-dihydroxybenzoic acid, vanillic acid, isovanillic acid, syringic acid, cinnamic acid, 4-hydroxycinnamic acid, caffeic acid, ferulic acid, isoferulic acid, chlorogenic acid, and rosmarinic acid. For all cinnamic acids and derivatives benzaldehydes were significant oxidation products. With the release of caffeic acid from chlorogenic acid the cleavage of a phenolic glycoside could be demonstrated. Reaction mechanisms are discussed.

  16. Gamma Amino Butyric Acid Attenuates Liver and Kidney Damage Associated with Insulin Alteration in γ-Irradiated and Streptozotocin-Treated Rats

    International Nuclear Information System (INIS)

    Saada, H.N.; Eltahawy, N.A.; Hammad, A.S.; Morcos, N.Y.S.

    2016-01-01

    Gamma aminobutyric acid (GABA) is one of the inhibitory neurotransmitters that may have the ability to relive the intensity of stress. The aim of the current study was to evaluate the role of γ-amino butyric acid (GABA) in modulating insulin disturbance associated with liver and kidney damage in γ-irradiated and streptozotocin-treated rats. Irradiation was performed by whole body exposure to 6 Gy from a Cs-137 source. Streptozotocin (STZ) was administered in a single intraperitoneal dose (60 mg/kg body weight). GABA (200 mg/Kg body weight/day) was administered daily via gavages during 3 weeks to γ-irradiated and STZ-treated-rats. The results obtained showed that γ-irradiation induced hyperglycemia, hyperinsulinaemia and insulin resistance (similar to type 2 Diabetes), while STZ-treatment produced hyperglycemia, insulin deficiency with no insulin resistance detected (similar to type 1 Diabetes). In both cases, significant increases of alanine amino transferase (ALT) and aspartate amino transferase (AST) activities, urea and creatinine levels were recorded in the serum. These changes were associated with oxidative damage to the liver and kidney tissues notified by significant decreases of superoxide dismutase (SOD ), catalase and glutathione peroxidase ( GSH-Px) activities in parallel to significant increases of malondialdehyde (MDA) and advanced oxidation protein products ( AOPP) levels. The administration of GABA to irradiated as well as STZ-treated rats regulated insulin and glucose levels, minimized oxidative stress and reduced the severity of liver and kidney damage. It could be concluded that GABA could be a useful adjunct to reduce some metabolic complications associated with insulin deficiency and insulin resistance

  17. Effects of gamma irradiation and ozone treatment on microbial decontamination and fatty acid compositions of aloe and pollen powders

    International Nuclear Information System (INIS)

    Yook, H.S.; Chung, Y.J.; Kim, J.O.; Kwon, O.J.; Byun, M.W.

    1997-01-01

    The comparative effects of gamma irradiation and ozone treatment on the microbial inactivation and fatty acid composition were investigated for improving hygienic quality of aloe and pollen powders. Gamma irradiation at 10 kGy resulted in sterilizing total aerobic bacteria, molds and coliforms below detective levels, while ozone treatment for 8 hours up to 18 ppm did not sufficiently eliminate the microorganisms of aloe and pollen powders. The compositions of fatty acid were not significantly changed by gamma irradiation up to 10 kGy. However, ozone treatment markedly decreased unsaturated fatty acids by approximately 20-80% in contents, whereas it significantly increased saturated fatty acids (p<0.05)

  18. Ultraviolet B irradiation induces changes in the distribution and release of arachidonic acid, dihomo-gamma-linolenic acid, and eicosapentaenoic acid in human keratinocytes in culture

    International Nuclear Information System (INIS)

    Punnonen, K.; Puustinen, T.; Jansen, C.T.

    1987-01-01

    There is increasing evidence that derivatives of 20-carbon polyunsaturated fatty acids, the eicosanoids, play an important role in the inflammatory responses of the human skin. To better understand the metabolic fate of fatty acids in the skin, the effect of ultraviolet B (UVB) irradiation (280-320 nm) on the distribution and release of 14 C-labeled arachidonic acid, dihomo-gamma-linolenic acid, and eicosapentaenoic acid in human keratinocytes in culture was investigated. Ultraviolet B irradiation induced the release of all three 14 C-labeled fatty acids from the phospholipids, especially from phosphatidylethanolamine, and this was accompanied by increased labeling of the nonphosphorus lipids. This finding suggests that UVB induces a significant liberation of eicosanoid precursor fatty acids from cellular phospholipids, but the liberated fatty acids are largely reincorporated into the nonphosphorus lipids. In conclusion, the present study suggests that not only arachidonic acid but also dihomo-gamma-linolenic acid, and eicosapentaenoic acid might be involved in the UVB irradiation-induced inflammatory reactions of human skin

  19. Protective role of ascorbic acid in the decontamination of cow milk casein by gamma-irradiation.

    Science.gov (United States)

    Kouass Sahbani, Saloua; Klarskov, Klaus; Aloui, Amine; Kouass, Salah; Landoulsi, Ahmed

    2013-06-01

    The aim of this work was to investigate the protective role of ascorbic acid on irradiation-induced modification of casein. Casein stock solutions were irradiated with increasing doses 2-10 kGy using (60)Co Gamma rays at a dose rate D• = 136.73 Gy/min at room temperature. The total viable microorganism content of cow milk casein was evaluated by Plate Count Agar (PCA) incubation for 48 h at 37°C. Sodium dodecylsulfate gel electrophoresis (SDS-PAGE) and Matrix-Assisted Laser Desorption-Ionization Time-of-Flight mass spectrometry (MALDI-TOF-MS) analysis were used to evaluate the effect of gamma irradiation on casein integrity. Gamma irradiation reduced the bacterial contamination of casein solutions at a lower irradiation dose when performed in the presence of ascorbic acid. The irradiation treatment of casein in the absence of ascorbic acid with a dose of 4 kGy could reduce 99% of the original amount of bacterial colonies. However, in the presence of ascorbic acid the irradiation treatment of casein with a dose lower than 2 kGy could reduce 99% of the original amount of bacterial colonies which suggested that the irradiation dose lower than 2 kGy achieved almost the entire decontamination result. SDS-PAGE and MALDI-TOF-MS analysis showed that ascorbic acid protected cow milk casein from degradation and subsequent aggregation probably by scavenging oxygen and protein radicals produced by the irradiation. It is demonstrated that the combination of gamma irradiation and ascorbic acid produce additive effects, providing acceptable hygienic quality of cow milk casein and protects caseins against Reactive Oxygen Species (ROS) generated, during the irradiation process.

  20. Utilization of gamma rays in the selection of Aspergillus niger for acid production

    International Nuclear Information System (INIS)

    Silva, J.C. da; Azevedo, J.L.

    1978-01-01

    Selection of Aspergillus niger for acid production was studied by the method of Foster and Davis with the use of gamma rays. Three selection cycles were carried out, and the acid production character of each population was analyzed quantitatively by the unitage acid factor. Isolates with high unitage values in relation to the paternal strain were assayed in a liquid fermentation medium. No correlation was found that would indicate unlimited use of Foster and Davis' method in the selection of more productive strains. (Author) [pt

  1. Neocortical gamma oscillations in idiopathic generalized epilepsy

    DEFF Research Database (Denmark)

    Benedek, Krisztina; Berenyi, Antal; Gombkoto, Peter

    2016-01-01

    Objective: Absence seizures in patients with idiopathic generalized epilepsy (IGE) may in part be explained by a decrease in phasic GABAA (type-A c-aminobutyric acid) receptor function, but the mechanisms are only partly understood. Here we studied the relation between ictal and interictal spike......-wave discharges (SWDs) and electroencephalography (EEG) gamma oscillatory activity (30-60 Hz) in patients with IGE. Methods: EEG recordings were obtained of 14 children with IGE (mean age, 8.5 +/- 5 years) and 14 age-and sex-matched controls. Time-frequency analysis of each seizure and seizure-free control epochs...... was performed and cross-coherences of neocortical gamma oscillations were calculated to describe interictal and ictal characteristics of generalized seizures. Results: SWDs were characterized with an abrupt increase of oscillatory activity of 34 and 13-60 Hz, peaking at 3-4 and 30-60 Hz, and with a simultaneous...

  2. Remote sensing of acid sulfate soils using multispectral and gamma-ray data

    International Nuclear Information System (INIS)

    Bierwirth, P.N.; Graham, T.L.

    1998-01-01

    Acid sulfate soils are a significant environmental problem in coastal regions of Australia. Drainage and disturbance of coastal lands can result in acid soil degradation and the release of sulfuric acid and toxic metals into coastal waters. Remote sensing can provide a useful tool for detection of these soils and monitoring of their disturbance. As acid sulfate soils become oxidised with exposure to air, iron-minerals are produced and precipitate at the surface. This results from the breakdown of pyrite to form hydrated iron minerals and elemental sulfur, the oxidation of which produces acidity. The concentration of iron minerals at the surface can be an indicator of the level of acid sulfate soil activity in the near subsurface. These iron minerals include goethite, ferrihydrite and jarosite. Space-borne remote sensing scanners such as Landsat TM are capable of detecting iron minerals as a result of ferric ion absorption of solar radiation. Hyperspectral scanners are capable of further discrimination of individual minerals. This paper will discuss spectral characteristics of active acid sulfate soils and demonstrate the use of spectral unmixing algorithms on Landsat TM to detect problem areas at the surface. This method matches multispectral data to material reflectance-spectra known as end-members. These end-members or materials are then resolved mathematically as to their respective contributions to the overall reflectance (Bierwirth, 1990). In this way, abundances for particular materials can be derived.Digital elevation data was used to distinguish between the iron minerals due to weathering of bedrock in upland areas and acid sulfate soils on the plains. Also, the results of a high resolution (200m linespacing) airborne gamma-ray survey are presented. This data senses the concentration of radioelements down to about 40 cm depth and is largely unaffected by vegetation. Concentrations of gamma-emitting elements can indicate the type and depth of alluvium that

  3. The effect of gamma irradiation and endole butyric acid on Olive cutting

    Energy Technology Data Exchange (ETDEWEB)

    Albachir, M [Atomic Energy Commission, P.O. Box 6091, Damascus, (Syrian Arab Republic)

    1995-10-01

    This study was performed to investigate the effect of 2 - 4 - 6 Gy doses of gamma radiation, 2000 - 4000 ppm concentrations of indole butyric acid (IBA), and combined treatment of IBA, and combined treatment of IBA followed by irradiation,followed by IBA on root formation of olive cuttings (var. Khodairi). The results indicated that two Gy gamma radiation increased rooting percentage, and root length at the cuttings collected in january. Both concentrations of IBA increased rooting percentage, callus formation, number and length of the roots at all collection times. The best IBA concentration for rooting was 2000 ppm in october and march, and 4000 in january. However, the stimulatory effects of 2 Gy gamma radiation did not reach that obtained by either concentration of IBA used. 2 tabs.

  4. Palovarotene, a novel retinoic acid receptor gamma agonist for the treatment of emphysema.

    Science.gov (United States)

    Hind, Matthew; Stinchcombe, Sian

    2009-11-01

    Emphysema is characterized by the destruction of alveoli and alveolar ducts within the lungs. Retinoid signaling is believed to play a role in alveologenesis, with the retinoic acid receptor gamma thought to be required for alveolar formation. Based on this hypothesis, Roche Holding AG is developing palovarotene (R-667, RO-3300074), a selective retinoic acid receptor gamma agonist for the treatment of emphysema. In small animal studies, palovarotene was claimed to reverse the structural, functional and inflammatory features of cigarette smoke-induced emphysema. Phase I clinical trials of palovarotene in patients with emphysema demonstrated that the drug is well tolerated, with improvements observed in markers of emphysema progression. Unlike all-trans retinoic acid, the pharmacokinetic profile of palovarotene appears to be dose-proportional. At the time of publication, a phase II, placebo-controlled trial was ongoing, and was expected to report prospective measurements of exercise, gas transfer and lung densitometry endpoints. The development of a selective retinoic acid receptor gamma agonist for the treatment of emphysema represents the first of a new class of small-molecule regenerative therapies that may prove useful for the treatment of destructive or age-related lung disease.

  5. Responses of garlic bulbs to gamma irradiation. Changes in major amino acids

    International Nuclear Information System (INIS)

    Parolo, Maria E.; Orioli, Gustavo A.; Croci, Clara A.

    1997-01-01

    Studies were conducted to provide information about the amino acids composition of garlic bulbs cv Colorado and to determinate the effect of a dose of 60 Gy of gamma rays on the behavior of the major free amino acids in relation to sprout growth radioinhibition. TLC and HPLC were used for identification and quantification of free amino acids. Eighteen free amino acids were identified in both parts of garlic bulbs: alanine, glycine, proline, methionine, serine, phenylalanine, aspartic acid, glutamic acid, lysine, glutamine, arginine, tyrosine, threonine, cystine, cysteine, leucine + isoleucine and asparagine. In the inner sprout the major amino acids founded were: glutamine, glutamic acid, threonine, asparagine, cystine, cysteine and methionine; in the storage leaf also arginine was also predominant. In general concentration of amino acids appeared to less affected by irradiation in the storage leaf that in the inner sprout. An increase in the short time post-irradiation in glutamine, glutamic acid, asparagine, theorine and methionine was observed. Sprout grouth radioinhibition was evident about 70 days after treatment and was preceded by a decrease in the major amino acids except methionine. It appears that concentration of same major amino acidscan be used as monitors of radioinhibition process in inner sprout of garlic. (author). 15 refs., 8 figs

  6. Bioconversion of sugar cane molasses into glutamic acid by gamma irradiated corynebacterium glutamicum

    International Nuclear Information System (INIS)

    El-Batal, A.I.

    1996-01-01

    Corynebacterium glutamicum (ATCC 13058) was used for glutamic acid production from sugar cane molasses which contain sufficient. The addition of 5 units ml 4 of penicillin G was superior in glutamic acid production (11.5 g L 4 ). Tweens and their saturated fatty acids were effective on the accumulation of glutamic acid in the culture medium and the maximum yield (16.6 g L 4 ) was the addition of 5 mg ml 4 Tween 40. Gamma irradiation prior to Tween-40 treatment of bacterial cells resulted in an obvious increase in glutamic acid production and it was maximum (23.72 g L 4 ) at 0.1 k Gy exposure dose of inocula. 5 tabs

  7. Gamma radiolytic stability of CyMe4BTBP and effect of nitric acid

    Czech Academy of Sciences Publication Activity Database

    Schmidt, H.; Wilden, A.; Modolo, G.; Švehla, Jaroslav; Grüner, Bohumír; Ekberg, C.

    Roč. 60, č. 4 ( 2015 ), s. 879-884 ISSN 0029-5922 R&D Projects: GA MŠk(CZ) 7G13003 EU Projects: European Commission(XE) 323282 - SACSESS Institutional support: RVO:61388980 Keywords : CyMe4BTBP * Protective effect * Gamma radiolysis * Liquid-liquid extraction * Nitric acid Subject RIV: CA - Inorganic Chemistry Impact factor: 0.546, year: 2015

  8. Discovery of Azetidinone Acids as Conformationally-Constrained Dual PPARalpha/gamma Agonists

    Energy Technology Data Exchange (ETDEWEB)

    Wang, W.; Devasthale, P; Farrelly, D; Gu, L; Harrity, T; Cap, M; Chu, C; Kunselman, L; Morgan, N; et. al.

    2008-01-01

    A novel class of azetidinone acid-derived dual PPAR{alpha}/{gamma} agonists has been synthesized for the treatment of diabetes and dyslipidemia. The preferred stereochemistry in this series for binding and functional agonist activity against both PPARa and PPAR? receptors was shown to be 3S,4S. Synthesis, in vitro and in vivo activities of compounds in this series are described. A high-yielding method for N-arylation of azetidinone esters is also described.

  9. Hybrid ATDL-gamma distribution model for predicting area source acid gas concentrations

    Energy Technology Data Exchange (ETDEWEB)

    Jakeman, A J; Taylor, J A

    1985-01-01

    An air quality model is developed to predict the distribution of concentrations of acid gas in an urban airshed. The model is hybrid in character, combining reliable features of a deterministic ATDL-based model with statistical distributional approaches. The gamma distribution was identified from a range of distributional models as the best model. The paper shows that the assumptions of a previous hybrid model may be relaxed and presents a methodology for characterizing the uncertainty associated with model predictions. Results are demonstrated for the 98-percentile predictions of 24-h average data over annual periods at six monitoring sites. This percentile relates to the World Health Organization goal for acid gas concentrations.

  10. Amino Acid Content of the Gamma Irradiated Cotton Leaf-Worm, Spodoptera Littoralis (Boisd.)

    International Nuclear Information System (INIS)

    Sobeiha, A.K.; Sallam, H.A.; El-Shall, S.S.A.

    2000-01-01

    The effects of gamma irradiation on amino acid content of the cotton leaf worm Spodoptera Littoralis was studied.The identified amino acids in the total body tissue of male moths were Theronine, Serine, Glutamic, Glycine, Alanine, Valine, Cystine, Methionine, Isoleucine, Leucine, Tyrosine, Phenylalanine, Lysine, Histidine and Arginine. The irradiation of full grown male pupae with doses 100,200 and 300 Gy decreased the total quantity of amino acids and the amount of most individual amino acids in male moths of P 1 or F 1 generations with some exceptions for Threonine, Alanine, Glycine, Serine, Valine, Cystine and Methionine which were increased.The effect of irradiation on amino acid content of the reproductive system tissues for each male or female were also studied.The results indicated that irradiation decreased the total quantity of amino acid content of both sexes by increasing the dose and males were more radiosensitive than females. Also, irradiation decreased the amount of individual amino acids in both sexes with certain exceptions, e.g. Alanine, Methionine and Tyrosine which increased in the reproductive system of male, and Methionine which increased by more than four times as control.The amino acid content was determined as well in F 1 egg progeny, which was produced from irradiated males Irradiation doses (100, 200 and 300 Gy) decreased the total quantity of amino acids, and all individual ones except Cystine.The greatest reduction (54.9% was observed with Lysine at 300 Gy as compared to control

  11. Kinetics Studies on citric acid production by gamma ray induced mutant of Aspergillus niger

    International Nuclear Information System (INIS)

    Begum, A.A.; Choudhury, N.; Islam, M.S.

    1991-01-01

    Effect of cultural pH and incubation temperature on citric acid yield and kinetic patterns of citric acid fermentation by a natural isolate of aspergillus niger as CA16 and one of its gamma ray induced mutants were studied using cane molasses as growth and fermentation substrate. Mutant strain, 277/30 gave maximum citric acid yield of 85 g/l at pH 3.5 and 28 degree centigrade in molasses medium adjusted to 16% sugar and 25% prescott salt in the medium. Parent strain, CA16 gave a maximum yield of 34 g/l at pH 4.0 and 26 degree centigrade in molasses medium adjusted to 16% sugar and 100% prescott salt in the medium. In kinetic studies, strains showed combination kinetics of citric acid fermentation where product formation is directly related to growth and cell mass and indirectly related to carbohydrate uptake

  12. EPR study of gamma induced radicals in amino and iminodiacetic acid derivatives

    International Nuclear Information System (INIS)

    Aydin, Murat; Baskan, M. Halim; Osmanoglu, Y. Emre

    2009-01-01

    In this study, electron paramagnetic resonance spectroscopy was used to investigate free radicals formed in gamma irradiated L-glutamine hydrochloride, iminodiacetic acid hydrochloride and N-(2-hydroxyethyl) iminodiacetic acid powders. The free radicals produced in L-glutamine hydrochloride powders were attributed to the CH 2 CHCOOH radical; and those in iminodiacetic acid hydrochloride and N-(2-hydroxyethyl) iminodiacetic acid powders to the HNCHCH 2 (CO OH) 2 and HOCH 2 CH 2 NCHCH 2 (CO OH) 2 , respectively. The g-values of the radicals and the hyperfine structure constants of the free electron with the environmental protons and 14 N nucleus were determined. The samples were not displayed before they were not irradiated. The free radicals were found stable at room temperature for more than six months. Some spectroscopic properties and suggestions concerning possible structure of the radicals are discussed in this paper. (author)

  13. Induced mutants of Streptococcus lactis by gamma irradiation and its effect on milk acidity

    International Nuclear Information System (INIS)

    Daowd, A.H.; Sabbour, M.M.; Newigy, N.A.; Wahab, G.A.M.

    1988-01-01

    Streptococus lactis was exposed to different doses of gamma-irradiation (10, 50, 100 and 150 Kr). The results of acidity production in sterilized milk inoculated by isolates from radiation treatments and control could be summarized in the following: 1. The mean acidity produced by S. lactis isolates after irradiation at 10 Kr increased to be 0.66% than that of control isolates (0.62%). The acidity produced by the isolates of the 50 Kr treatment showed more increment to reach the peak (0.7%). Thereafter, acidity production decreased by isolates of the 100 Kr (0.53%) and 150 Kr (0.51%) treatments. Heme, the 50 Kr treatment could be considered activation dose to S. lactis starter for acid production. 2. Two mutants were selected. Acidity production by mutant I (from 10 Kr treatment) was 0.95%, and that of mutant II (from 50 Kr treatment) was 1.0%, while acid production by the parent S. lactis culture was 0.62%. Concerning the stability of the isolates, it was found that acid production by mutant I and mutant II slightly decreased by time. The mutants were re-irradiated after 37 and 60 days at doses 10, 25 and 50 Kr. Acid production in milk by isolates of the radiation treatments was determined. The following results were obtained: -The re-irradiation of the mutants decreased the ability of the isolates for acid production than that of parent mutants. -The re-irradiation of the mutants after 60 days yielded isolates which showed more reduction in acid produced than of isolates obtained from re-irridation of the mutants after 37-days. -The higher the dose of the re-irradiation of the mutants, the lower the mean of acid production by isolates of the treatment

  14. Alkaline and Acid Phosphatase Activity in Blood Plasma of Chickens Irradiated by Low dose Gamma Radiation

    International Nuclear Information System (INIS)

    Petar, K.; Marinko, V.; Saveta, M.; Miljenko, S.

    2004-01-01

    In our previous paper (Kraljevic et, al, 2000; Kraljevic et al 2002) we showed that the growth of the chickens hatched from eggs irradiated with 0.15 Gy gamma-rays before incubation was significantly higher than in controls during the fattening period (1-42 days). The concentration of total protein, glucose and cholesterol in the blood plasma of the same chickens was also significantly changed. In this paper an attempt was made to determine the effect of irradiation of eggs by low dose ionizing radiation before incubation upon activity of alkaline and acid phosphatase in the blood plasma of chickens hatched from irradiated eggs. The eggs of heavy breeding chickens were irradiated by dose of 0.15 Gy gamma radiation (60 Co) before incubation. Along with the chickens which were hatched from irradiated eggs, there was a control group of chickens hatched from nonirradiated eggs. All other conditions were the same for both groups. After hatching, blood samples were taken from the wing vein on days 1, 3, 5, 6, 10, 20, 30 and 42. The activity of both enzymes was determined spectrophotometrically by using Boehring Mannheim GmbH optimized kits. the activity of alkaline phosphatase in blood plasma was decreased on days 42, and the activity of acid phosphatase in the blood plasma of the same chickens was increased on day 42. Obtained results confirm our early obtained results that low dose of gamma radiation has effects upon metabolic processes in the chickens hatched from eggs irradiated before incubation. (Author)

  15. Effect of gamma Irradiation on the acidic hydrolysis of free-hemi cellulose thistle

    International Nuclear Information System (INIS)

    Suarez, C.; Paz, M. D.; Diaz, A.

    1983-01-01

    The effect of gamma-irradiation on the subsequent acidic hydrolysis of free-hemi cellulose Onopordum Nervosum Boiss thistle Ls determined. Its shown the influence of gamma-irradiation on the yield of sugar obtained flora the batch wise hydrol isis of the call ulose (1% H 2 SO 4 and 180 degree centigree at increasing doses. At all irradiation levels studied, the rate of hydrolysis of thistle samples was higher than the rate of hydrolysis of the cellulose from paper treated similarly. The maximum over-all yield of sugar in the irradiated lignocellulose material was about 66o at 100 MRad, less than two times the yield obtainable from the control. The corresponding yield from papel was 53%, 2'3 times that of the control. Irradiation under 1% H 2 SO 4 doesn't enhance the yield anyway. (Author) 21 refs

  16. Gamma radiation effects on fattly acid composition of lipids in cotton leaves

    International Nuclear Information System (INIS)

    Arslanova, S.V.; Stepanenko, G.A.; Umarov, A.K.; Nazirov, N.N.

    1976-01-01

    The mechanism of high irradiation dose (30 kR) effect on the lipid fatty acid composition of cotton leaves was studied in the ontogenesis. The experiment was carried out in vegetation vials (capacity 25 kg, humidity level - 65% of full water capacity). Before seeding, each vial was fertilized with 5g P 2 O 5 , 3g K 2 O and 5gN as an auxillary nutrition during vegetation. The test vials also contained 0.4 - 0.5 g CaO per kg of soil. A portion of irradiated seeds was soaked in 1.5% solution of CaO and Ca(NO 3 ) 2 before seeding. The cotton seeds were gamma-irradiated at 50 R/sec in the Institute of Nuclear Physics, Usbec SSR Academy of Sciences. The fatty acid composition of mature leaf lipids determined by gas-liquid chromatography proved to change in the blooming phase. Leaves of irradiated plants contained traces of myristic acid, higher levels of palmitic, palmitoleinic and strearinic acids and lower levels of oleinic and linoleic acids. Lower content of fatty acids with long carbon chains seemed to handicap the renewal of membranes and their components, especially in mitochondria. When irradiated seeds were soaked in calcium salt solution and CaO is added to the soil, the amount of unsaturated long chain fatty acids increased. The fact probably promotes the membrane renewal in irradiated plants

  17. Alterations in polyunsaturated fatty acid composition of Voandzeia subterranea seeds upon gamma irradiation

    International Nuclear Information System (INIS)

    Andrianarison, R.H.; Rakotoarisoa, Z.; Tixier, M.; Beneytout, J.L.

    1992-01-01

    Exposure of V. subterranea seeds, a herbaceous plant from Madagascar belonging to the family of legumes, to gamma irradiation resulted in a polyunsaturated fatty acids decrease associated with the formation of UV-absorbing substances. The finding that products containing conjugated diene structure are formed during lipid extract irradiation indicates that hydroperoxy fatty acids may arise not only by enzymatic reactions but also by nonenzymatic oxygenation of polyunsaturated fatty acids promoted by ionizing radiation. Dehulled green seeds, flour made from dehulled green seeds, and lipid extract were studied for irradiation dose dependent changes in fatty acids compositions and hydroperoxydiene synthesis. The irradiation dose is more efficient in lipid extract than in dehulled green seeds or in flour made from these seeds, suggesting that the formation of UV-absorbing products is not a reliable clue for enzyme activity owing to the absence of protein in lipid extract. A homolytic pathway for the biogenesis of hydroperoxy fatty acids from polyunsaturated fatty acids is proposed. This involves an initiating radical which promotes a chain mechanism in which the O2 adsorbed is converted to hydroperoxide. Conclusively, preservation of fatty acid oxygenation should be a primary goal in the ionizing radiation processes of V. subterranea seeds and generally in the preservation of food of plant origin by ionizing radiation

  18. Physicochemical properties of cross-linked poly-gamma-glutamic acid and its flocculating activity against kaolin suspension

    International Nuclear Information System (INIS)

    Taniguchi, M.; Kato, K.; Shimauchi, A.; Ping, X.; Fujita, K.; Tanaka, T.; Tarui, Y.; Hirasawa, E.

    2005-01-01

    Cross-linked poly-Gamma-glutamic acid (C-L Gamma-PGA) was prepared with Gamma-PGA irradiated with Gamma-PGA at various kGy values. The physicochemical properties including viscosity and water absorption capacity were compared between C-L Gamma-PGA and several typical flocculating agents. The viscosity of C-L Gamma-PGA increased with the dose of Gamma-lrradiatio, although the water absorption capacity of C-L Gamma-PGA did not, which showed a maximum of 1005.6 ml/g at 20 kGy. Flocculating activity against kaolin suspension was not observed for any of the test compounds when used singly. However, the activity of C-L Gamma-PGA markedly increased following the addition of polyaluminum chloride. The activity increased with temperature up to 80deg C and remained at 80 deg C of heat pretreatment for 1 h, but did not at more than 50 deg C of beat pretreatment for 24 h. The activity was also observed within a pH range of 4.5-10.0. Roth the water absorption capacity and flocculating activity of C-L Gamma-PGA decreased in parallel with increasing NaCl concentration, suggesting that the hocculating activity of C-L Gamma-PGA was associated with its water absorption capacity, rather than viscosity. An investigation of the effects of various cations on the flocculating activity of C-L Gamma-PGA showed that only trivalent catlons had a synergistic effect. The mechanism of C-L Gamma-PGA flocculating activity is discussed based on the results of preliminary experiments

  19. Effect of gamma irradiation on hyaluronic acid and dipalmitoylphosphatidylcholine (DPPC) interaction

    Energy Technology Data Exchange (ETDEWEB)

    Ahmad, Ainee Fatimah; Mohd, Hur Munawar Kabir; Taqiyuddin Mawardi bin Ayob, Muhammad; Rosli, Nur Ratasha Alia Md; Mohamed, Faizal; Radiman, Shahidan; Rahman, Irman Abdul [School of Applied Physics, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, 43600 Bangi, Selangor (Malaysia)

    2014-09-03

    DPPC lipids are the major component constituting the biological membrane, and their importances in various physiological functions are well documented. Hyaluronic acid (HA) in the synovial joint fluid functions as a lubricant, shock absorber and a nutrient carrier. Gamma irradiation has also been found to be effective in depolymerizing and cleaving molecular chains related to free radicals, thus extends with changes in chemical composition as well as its physiological functions. This research are conducted to investigate the hyaluronic acid (HA) and 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC) interaction in form of vesicles and its effect to gamma radiation. The size of DPPC vesicles formed via gentle hydration method is between 100 to 200 nm in diameter. HA (0.1, 0.5 and 1.0 mg/ml) was added into the vesicles and characterized by using TEM to determine vesicle size distributions, fusion and rupture of DPPC structure. The results demonstrated that the size of the vesicles approximately between 200 to 300 nm which caused by vesicles fusion with HA and formed even larger vesicles. After being irradiated by 0 to 200 Gy, the size of vesicles decreased as HA was degraded. To elucidate the mechanism of these effects, FTIR spectra were carried out and have shown that at absorption bands at 1700–1750 cm{sup −1} due to formation of carboxylic acid and leads to alteration of HA structure.

  20. Study of stability of humic acids from soil and peat irradiated by gamma rays

    International Nuclear Information System (INIS)

    Silva, Wilson Tadeu Lopes da

    1995-01-01

    Humic acids samples (one deriving from a sedimentary soil and other from a peat), in aqueous media, were irradiated with gamma rays, in doses of 10, 50 and 100 kGy, in order to understand their chemical behavior after the irradiation. The material, before and after irradiation, was analyzed by Elemental Analysis, Functional Groups (carboxylic acids and phenols), UV/Vis Spectroscopy (E 4 /E 6 ratio), IR spectroscopy, CO 2 content and Gel permeation Chromatography (GPC) ). The Elemental Analysis showed the humic acid derived from a peat had a most percentage quantity of Carbon and Hydrogen than the material from a sedimentary soil. From the UV/Vis Spectroscopy, it was observed a decrease of E 4 /E 6 ratio with an increase of the applied dose. The data from GPC are in agreement with this. The results showed that the molecular weight of the material increased by exposing it to a larger radiolitical dose. The peat material was less affected by the gamma radiation than the soil material. The carboxylic groups were responsible by radiochemical behavior of the material. (author)

  1. The radiolysis of CMPO: effects of acid, metal complexation and alpha vs. gamma radiation

    Energy Technology Data Exchange (ETDEWEB)

    Bruce J. Mincher; Stephen P. Mezyk; Gary S. Groenewold

    2016-05-01

    Abstract The group actinide/lanthanide complexing agent octylphenylcarbamoylmethyl phosphine oxide (CMPO) has been examined for its radiation stability by measuring the kinetics of its reactions with free radicals in both the aqueous and organic phases for the free and metal-complexed ligand, identifying its degradation products for both alpha and gamma irradiation, measuring the effects on solvent extraction performance, and measuring the G-values for its degradation under various conditions. This includes the G-values for CMPO in the absence of, and in contact with the acidic aqueous phase, where it is shown that the acidic aqueous phase provides radio-protection for this ligand. It was found that both solvent and metal complexation affect the kinetics of the reaction of the •NO3 radical, a product of HNO3 radiolysis, with CMPO. For example, CMPO complexed with lanthanides has a rate constant for this reaction an order of magnitude higher than for the free ligand, and the reaction for the free ligand in the organic phase is about three times faster than in the aqueous phase. In steady state radiolysis kinetics it was determined that HNO3, although not NO3- anion, provides radio-protection to CMPO, with the G-value for its degradation decreasing with increasing acidity, until it was almost completely suppressed by irradiation in contact with 5 M HNO3. The same degradation products were produced by irradiation with alpha and gamma-sources, except that the relative abundances of these products varied. For example, the product of C-C bond scission was produced only in low amounts for gamma-radiolysis, but it was an important product for samples irradiated with a He ion beam. These results are compared to the new data appearing in the literature on DGA radiolysis, since CMPO and the DGAs both contain the amide functional group.

  2. Furan formation from fatty acids as a result of storage, gamma irradiation, UV-C and heat treatments

    Science.gov (United States)

    Furan is a possible human carcinogen that has been found in many thermally processed foods. The effects of thermal processing, gamma and UV-C irradiation on formation of furan from different fatty acids was studied. In addition, formation of furan from fatty acid emulsions during storage at 25C and...

  3. Grafting of polyethylene films with acrylic acid and acrylonitril using gamma radiation

    International Nuclear Information System (INIS)

    Ajji, Z.; Al-Nesr, E.

    2003-12-01

    Acrylic acid (AAc) and acrylonitrile (AN) and their binary mixtures were graft copolymerized onto low density polyethylene (LDPE) films using gamma irradiation. The effects of different parameters on the graft yield were studies such as monomer concentration, inhibitor concentration, and irradiation dose. The obtained grafted films were characterized using FTIR spectroscopy, thermal gravimetry, and differential scanning calorimetry. Water uptake and the ion uptake were also evaluated, and the ability of grafted films to uptake heavy ions such as Ni 2+ and Cu 2+ was discussed. (author)

  4. Behavior of the nucleic acid ethidium complex sedimentation of human lymphocytes after gamma irradiation

    International Nuclear Information System (INIS)

    Langrock, K.

    1982-01-01

    Under standardized conditions the repair kinetic test by Fender and Hartwig demonstrates the dose dependence of the injury of the nucleic acid complex of human lymphocytes after gamma irradiation and their repair even in low dose regions. Seasonal changes with infect incubation, individual variability in the lymphocyte population and culture conditions are to be proved before clinical application of the test in radiotherapy to generalize the influence of the factors. 3.4 up to 6 μg/ml ethidium bromide should be chosen as an optimum ethidium concentration of the gradient. (author)

  5. Evaluate The Fluctuation Of Phytic Acid Content In Seed From Mutant Lines By Gamma Ray

    International Nuclear Information System (INIS)

    Nguyen Thi Lang; Pham Van Ut

    2011-01-01

    Phytic acid is a molecule composed of myo-inositol 1,2,3,4,5,6 hexakis dihydrogen phosphate (Ins P6), a major component in the source of phosphorus (P) reserves of about 50 plants - 80% of total seed phosphorus (Lott, 1984). At physiological pH in the form of phytic acid have negatively charged ions hold together the complex mineral nutrition creates indigestion. Moreover, phosphorus in the form of phytate or phytic humans and monogastric animals can not absorb, are all discharged polluted environment transitions. In rice OM819, OM4900, OM3536, D4 and D8 are irradiated with gamma rays at 5 doses: 100, 200, 300, 400 and 500 Gy to create mutant strains with low levels of phytic acid. Results in radiation levels may appear 100 Gy line grain phytic acid expression is low. At the level 200 Gy of radiation is three populations OM819, OM4900 and OM3536 with 8 lines for grain phytic acid expression is low. At 300 Gy extent, appeared seven lines with low nuclear expression of phytic acid 4 populations OM819, OM4900, OM3536 and D4. At the level 400 Gy of radiation there are 4 populations appear only 5 lines expressed low phytic acid, with 3-line expression levels 3 and 2 lines with level 4 expression. At the level of radiation 500 Gy only one line appears at level 3 of phytic acid this is OM819 populations. For genotype analysis using marker RM 261 with 66.67% of the rice low phytic acid content of the expression analysis of biochemical polymorphisms. (author)

  6. Chlorogenic acid was specifically induced among phenolic compounds in centipedegrass by gamma irradiation

    Energy Technology Data Exchange (ETDEWEB)

    An, Byung Chul; Barampuram, Shyamkumar; Lee, Seung Sik; Lee, Eun Mi; Chung, Byung Yeoup [Korea Atomic Energy Research Institute, Jeongeup (Korea, Republic of)

    2010-03-15

    Centipedegrass is a warm season turfgrass in the world. Chlorogenic acid (CA) is one of the important compounds present in the leaf of centipedegrass and already known as an antioxidant, CA has become a key resistance against insect pests and bacteria pathogens of agricultural and horticultural plants during seedlling stage. Furthermore, CA is accumulated by abiotic stress such as an UV irradiation. In present study, we investigated enhancement of the level of CA upon gamma irradiation in centipedegrass. The high performance liquid chromatography (HPLC) data analysis showed an approximately increasing of the CA levels from among the irradiated samples. However, plants irradiated at 50 Gy showed a constant increase in the CA level (0.0066 to 0.114 mg ml{sup -1} and 0.0258 to 0.2211 mg ml{sup -1}, respectively) from 3{sup rd} to 15{sup th} day among one and three month irradiated plants compared to control. The present study, indicates an increase in the CA level upon gamma irradiation, suggests strategy for conferment of strong resistance on seedling stage plants by gamma irradiation as simplicity and cheaply method.

  7. [Alterations of glial fibrillary acidic protein in rat brain after gamma knife irradiation].

    Science.gov (United States)

    Ma, Z M; Jiang, B; Ma, J R

    2001-08-28

    To study glial fibrillary acidic protein (GFAP) immunoreactivity in different time and water content of the rat brain treated with gamma knife radiotherapy and to understand the alteration course of the brain lesion after a single high dose radiosurgical treatment. In the brains of the normal rats were irradiated by gamma knife with 160 Gy-high dose. The irradiated rats were then killed on the 1st day, 7th day, 14th day, and 28th day after radiotherapy, respectively. The positive cells of GFAP in brain tissue were detected by immunostaining; the water content of the brain tissue was measured by microgravimetry. The histological study of the irradiated brain tissue was performed with H.E. and examined under light microscope. The numbers of GFAP-positive astrocytes began to increase on the 1st day after gamma knife irradiation. It was enlarged markedly in the number and size of GFAP-stained astrocytes over the irradiated areas. Up to the 28th day, circumscribed necrosis foci (4 mm in diameter) was seen in the central area of the target. In the brain tissue around the necrosis, GFAP-positive astrocytes significantly increased (P gravity in the irradiated brain tissue the 14th and 28th day after irradiation. The results suggest that GFAP can be used as a marker for the radiation-induced brain injury. The brain edema and disruption of brain-blood barrier can be occurred during the acute stage after irradiation.

  8. Yields of 2-deoxy-D-gluconic, D-gluconic and other sugar acids in gamma-irradiated aqueous solutions of D-glucose. [Gamma rays

    Energy Technology Data Exchange (ETDEWEB)

    Esterbauer, H; Schubert, J; Sanders, E B; Sweeley, C C [Pittsburgh Univ., Pa. (USA); Michigan State Univ., East Lansing (USA). Dept. of Biochemistry)

    1977-03-01

    The yields of 2-deoxy-D-gluconic, D-gluconic and other sugar acids from /sup 60/Co-gamma irradiated (dose-rate = 4 Krads/min) D-glucose solutions are reported. The acids produced upon radiolysis were separated from glucose and neutral products by anion exchange, assayed by gas chromatography of the trimethylsilyl derivatives, and definitive identification made by mass spectrometry. In He degassed, irradiated 0.055 M glucose G(2-deoxy-D-gluconic acid) = 0.62 and G(D-gluconic acid) = 0.20. The approximate G values for the other identified acids are: glyceric acid 0.03, 2-deoxy-tetronic acid 0.04, tetronic acid 0.03, 4-deoxypentonic acid 0.02, deoxyketogluconic acid 0.17. In N/sub 2/O saturated glucose solutions D-gluconic acid yields increased by a factor of approximately 1.9 while that of 2-deoxy-D-gluconic acid increased by a factor of only approximately 1.1.

  9. Evaluation and improvement of gamma-ray stability of chelating resins containing oxy-acid groups of phosphorus

    International Nuclear Information System (INIS)

    Jyo, Akinori; Yamabe, Kazunori; Shuto, Taketomi

    1998-01-01

    Chelating resins containing oxy-acid groups of phosphorus, such as phosphonic and phosphoric acid groups have been studied from the point of view of solvent extraction processes for the separation of nuclear fuel elements as well as of fission product ones. The present work was planned to evaluate the effect of gamma-ray on properties of the resins and to obtain directional information for design of the resins having high stability to gamma-ray. It was clarified that gamma-ray stability of the resins is not high; tolerance limit is ca. 2.3x10 3 C/kg. The present work also clarified that polymers crosslinked with divinylbenzene have much higher gamma-ray stability than ones crosslinked with dimetacrylate esters of oligo (ethylene glycol)s. (J.P.N.)

  10. [Enhanced electro-chemical oxidation of Acid Red 3R solution with phosphotungstic acid supported on gamma-Al2O3].

    Science.gov (United States)

    Yue, Lin; Wang, Kai-Hong; Guo, Jian-Bo; Yang, Jing-Liang; Liu, Bao-You; Lian, Jing; Wang, Tao

    2013-03-01

    Supported phosphotungstic acid catalysts on gamma-Al2O3 (HPW/gamma-Al2O3) were prepared by solution impregnation and characterized by FTIR, XRD, TG-DTA and SEM. The heteropolyanion shows a Keggin structure. Electro-chemical oxidation of Acid Red 3R was investigated in the presence of HPW supported on gamma-Al2O3 as packing materials in the reactor. The results show that HPW/gamma-Al2O3 has a good catalytic activity for decolorization of Acid Red 3R. When HPW loading was 4.6%, pH value of Acid Red 3R was 3, the voltage was 25.0 V, air-flow was 0.04 m3 x h(-1), and electrode span was 3.0 cm, the decolorization efficiency of Acid Red 3R can reach 97.6%. The removal rate of color had still about 80% in this electro-chemical oxidation system, after HPW/gamma-Al2O3 was used for 10 times, but active component loss existed. The interim product was analyzed by means of Vis-UV absorption spectrum. It shows that the conjugated structure of dye is destroyed primarily.

  11. Gamma rays induced mutation for low phytic acid and trypsin inhibitor content in soybean

    International Nuclear Information System (INIS)

    Gupta, S.K.; Manjaya, J.G.

    2017-01-01

    Soybean (Glycine max (L.) Merrill) is an important source of vegetable protein and is used as a food, feed and health supplement. However, consumption of soybean as food is limited because of the presence of many anti-nutritional factors. Trypsin inhibitors and phytic acid are two major anti-nutritional factors present in soybean that need to be removed for increasing the soybean consumption as food. Trypsin inhibitor is known to inhibit the trypsin/chymotrpsin activity and phytic acid reduces the bioavailability of essential micronutrients in digestive tract, resulting in adverse effect on health. Therefore, developing soybean cultivars having low trypsin inhibitors and phytic acid content is highly desirable. Soybean cultivar JS 93-05 was irradiated with 250 Gy gamma rays to induce mutation for various morphological and biochemical characters. A large number of mutants with altered morphological characters were identified. Ninety true breeding mutant lines in M6 generation were screened for trypsin inhibitor and phytic acid content. The phytic acid content was estimated using modified colorimetric method and trypsin inhibitor concentration was estimated using BAPNA as substrate in colorimetric method. The phytic acid content in the mutants varied from 7.59 to 24.14 mg g -1 . Two mutants lines TSG - 62 (7.59 mg g -1 ) and TSG - 66 (9.62 mg g -1 ) showed significant low phytic acid content as compared to the parent JS 93-05 (20.19 mg g -1 ). The trypsin inhibitor concentration in the mutants varied from 19.92 to 53.64 TIU mg -1 and one mutant line (TSG -14) was found with the lowest trypsin inhibitor concentration of 19.92 TIU mg -1 compared to parent JS 93-05 (50.90 TIU mg -1 ). The mutant lines identified in this study will serve as important genetic resources for developing low phytic acid and low trypsin inhibitor cultivars in soybean. (author)

  12. [The effect of gamma rays on glutathion and ascorbic acid content in rabbit lenses (author's transl)].

    Science.gov (United States)

    Zygulska-Mach, H; Mach, Z

    1975-01-01

    It is pointed out that the partner non radiated eye is also influenced after employment of high radiation on an eye. The authors radiated rabbit eyes with gamma rays employing Stallard-applicators and determined the glutathion and ascorbic acid content in the lenses. The lenses of the partner eye were also examined for comparison. In those eyes which were directly radiated there was a fall of concentration of the two substances indirectly proportional to the dose of rays employed. In the partner eyes which were not directly subjected to direct radiation there were changes of similar character which were however not so much pronounced. The role of glutathion and ascorbic acid in lens metabolism is pointed out.

  13. Histochemical alternations in the Nissl bodies and ribonucleic acid (RNA) in the spinal, gangalion neurones of gamma irradiated rats

    International Nuclear Information System (INIS)

    Mousa, Tohamy A.; Roushdy, Hamed M.; Raid, Nahed A.; Al-Zahaby, Al-Ahmady S.; Sanad, Samia M.

    1984-01-01

    Four groups of adult male albino rats were subjected to whole body gamma-irradiation at the exposure levels of 200, 400, 600 and 1000 rads and the spinal ganglia were dissected out after different intervals of 3 hr., 1, 3, 5, 7, 10, 15 and 30 days. Nissl bodies and ribonucleic acid were demonstrated histochemically. Gamma irradiation may cause a decrease in RNA synthesis which was reflected in a reduced amount of Nissl substance visible in toluidine blue stained you thick sections of spinal ganglion of gamma irradiated rats and in the total amount of cytoplasmic RNA in pyronin-methyl green stained sections compared with control animals

  14. Genetic manipulation of gamma-linolenic acid (GLA) synthesis in a commercial variety of evening primrose (Oenothera sp.).

    Science.gov (United States)

    de Gyves, Emilio Mendoza; Sparks, Caroline A; Sayanova, Olga; Lazzeri, Paul; Napier, Johnathan A; Jones, Huw D

    2004-07-01

    A robust Agrobacterium-mediated transformation procedure was developed for Rigel, a commercial cultivar of evening primrose, and used to deliver a cDNA encoding a Delta(6)-desaturase from borage under the control of a cauliflower mosaic virus (CaMV) 35S promoter. Analysis of the transformed plants demonstrated an altered profile of polyunsaturated fatty acids, with an increase in gamma-linolenic acid and octadecatetraenoic acid in leaf tissues when compared with control lines.

  15. Gamma-irradiation effect on a commercial composite anticorrosive pigment and acidity-to-alkalinity conversion

    Science.gov (United States)

    Song, Weiqiang; Niu, Kaihui; Wu, Longchao

    2016-05-01

    A commercial composite anticorrosive pigment based on aluminum dihydrogen tripolyphosphate was studied after exposure to gamma irradiation (Co60, 0, 20, 50, 100 and 150 kGy) using FTIR, XRD, TGA and acid-base titration technologies. Although the FTIR spectra showed that the effect of the irradiation on functional groups in the pigments was not obvious, the decrease in the crystal lattice parameters of the irradiated pigments was observed in the XRD spectra compared to the non-irradiated sample. But the extent of the lattice parameter decrease monotonically with the increase of absorbed dose from 20 to 150 kGy, which was attributed to the decomposition of water and the simultaneous occurrence of lattice damage when the pigments were exposed to gamma rays. Of particular significance was the displayed basicity of the aqueous solutions of the irradiated pigments compared to the acidity of the solution of the non-irradiated pigment, which was attributed to the decomposition of P-OH groups (combined water).

  16. 308.15 K、313.15 K和318.15K下4-氨基丁酸在硫酸沙丁胺醇水溶液中的体积和黏度研究%Volumetric and Viscometric Studies of 4-Aminobutyric Acid in Aqueous Solutions of Salbutamol Sulphate at 308.15,313.15 and 318.15 K

    Institute of Scientific and Technical Information of China (English)

    K. Rajagopal; S.S. Jayabalakrishnan

    2009-01-01

    Density (ρ) and viscosity (η) measurements were carried out for 4-aminobutyric acid in 0.0041, 0.0125 and 0.0207 mol·L~(-1) aqueous salbutamol sulphate at T= 308.15, 313.15 and 318.15 K.. The measured values of density and viscosity were used to estimate some important parameters such as apparent molar volume V_φ, limiting apparent molar volume V_φ~0, transfer volume ΔV_φ~0, hydration number nH , second derivative of infinite dilution of partial molar volume with temperature (e)~2V_φ~0 /(e)T~2 , viscosity B-coefficients, variation of B with temperature dB/dT, free energy of activation per mole of solvent Δμ_1~(0*) and solute Δμ_2~(0*), activation entropy ΔS_2~(0*) and activation enthalpy ΔH_2~(0*) of the amino acids. These parameters have been interpreted in terms of solute-solute and solute-solvent interactions and structure making/breaking ability of solutes in the given solution.

  17. Oxidation of ortho- and para-aminobenzoic acid. A pulse radiolysis- and gamma radiolysis study

    International Nuclear Information System (INIS)

    Solar, Sonja; Getoff, Nikola; Zona, Robert; Solar, Wolfgang

    2011-01-01

    The oxidation of anthranilic acid (ortho-aminobenzoic acid, ANA) and para-aminobenzoic acid (PABA) by · OH, N 3 · and O ·- in basic solution was studied by pulse radiolysis. The kinetic and spectroscopic characteristics of the intermediate transients were determined. For ANA the site attack of the OH radicals was established to be ∼50% on the -NH 2 moiety and ∼50% on the aromatic ring with an overall rate constant k( · OH+ANA)=(5.5x10 9 ) dm 3 mol -1 s -1 . The rate constant of PABA was k( · OH+PABA)=8x10 9 dm 3 mol -1 s -1 . The OH-adducts of both compounds showed a first order decay of 0.8x10 5 and 1.2x10 5 s -1 , respectively, whereby the corresponding anilino-radicals were formed. The rate constant of ANA with solvated electrons was k(e - aq +ANA)=2.9x10 9 dm 3 mol -1 s -1 . The radiation induced decomposition of both substrates was studied by gamma radiolysis as a function of the absorbed dose. They exhibited a distinct radiation resistance, the initial degradation yields were ∼0.16 μmol J -1 , i.e. only 28% of the · OH radicals contributed to their decomposition. The hydroxylation process was of minor importance, the yield of hydroxylated aminobenzoic acids was≤0.01 μmol J -1 .

  18. Use of X-ray and gamma-induced mutants of lactic acid bacteria in the manufacture of dairy products

    Energy Technology Data Exchange (ETDEWEB)

    Dilanian, Z; Makarian, K; Chuprina, D [Erevan Zootechnical and Veterinary Inst. (USSR). Chair of Dairying

    1976-04-01

    With the aid of X-ray and gamma irradiation were got mutants of lactic acid bacteria, which steadily retain acquired properties. Use of proteolytically active mutant strains in the production of armianski and sovetski cheeses shortened the time of their ripening and increased their quality. Gamma-mutant strain L. lactis 1621/I-M with high phenolstability was received and antibiotic activity with respect to some representatives of pathogenic microflora of the bowels. Use of this mutant in starters for sour milk products will raise their therapeutic effect against intestinal diseases. Deep morphological changes are taking place in lactic acid bacteria under the influence of ionizing radiation.

  19. Use of X-ray and gamma-induced mutants of lactic acid bacteria in the manufacture of dairy products

    International Nuclear Information System (INIS)

    Dilanian, Z.; Makarian, K.; Chuprina, D.

    1976-01-01

    With the aid of X-ray and gamma irradiation were got mutants of lactic acid bacteria, which steadily retain acquired properties. Use of proteolytically active mutant strains in the production of armianski and sovetski cheeses shortened the time of their ripening and increased their quality. Gamma-mutant strain L. lactis 1621/I-M with high phenolstability was received and antibiotic activity with respect to some representatives of pathogenic microflora of the bowels. Use of this mutant in starters for sour milk products will raise their therapeutic effect against intestinal diseases. Deep morphological changes are taking place in lactic acid bacteria under the influence of ionizing radiation. (orig.) [de

  20. FT-IR study of gamma-radiation induced degradation of polyvinyl alcohol (PVA) and PVA/humic acids blends

    International Nuclear Information System (INIS)

    Ilcin, M.; Hola, O.; Bakajova, B.; Kucerik, J.

    2010-01-01

    Samples of pure polyvinyl alcohol (PVA) and PVA doped with humic acids were exposed to gamma radiation. Gamma rays induced the degradation of the pure polymer. Degradation changes were observed using ATR FT-IR equipment. Dehydration, double bond creation, and their subsequent oxidation (surrounding atmosphere was air) were found out. Also, other degradation reactions (e.g. chain scission, cyclization) occur simultaneously. Formation of C=C and C=O bonds is apparent from FT-IR spectra. In contrast the presence of humic acids in the PVA sample showed stabilizing effect on PVA structure within the concentration range 0.5-10%. (author)

  1. Relation Between Acid and Catalytic Properties of Chlorinated Gamma-Alumina. a 31p Mas Nmr and Ftir Investigation

    Directory of Open Access Journals (Sweden)

    Guillaume D.

    1999-07-01

    Full Text Available In this paper, we have studied the effect of chlorine on the surface properties of gamma-alumina, especially on their acid properties. The use of FTIR spectroscopy and 31P MAS NMR of adsorbed trimethylphosphine allows to propose a chlorination mechanism. To correlate the surface properties of these chlorinated gamma-alumina with their catalytic properties, we have used a model reaction, the cracking of n-heptane under reforming conditions. The analysis of the correlation between acid properties determined by 31P MAS NMR and the catalytic results (in terms of activities and selectivities allows to identify which sites are involved in the cracking reaction.

  2. Evaluation of amino acids changes in liver and serum during the recovery from gamma-irradiation in rats

    International Nuclear Information System (INIS)

    Elkashef, H.S.; Saada, H.N.; Roushdy, H.M.; Abdelsamie, M.A.

    1989-01-01

    Recovery from radiation induced changes in glutamic and aspartic acids in both liver and serum was evaluated in rats treated with a mixture of testosterone and vitamin E and subjected to whole body gamma irradiation of 5.5 Gy. The intraperitoneal injection of the mixture 10 days before exposing the rat gamma radiation improved the recovery process from radiation induced changes in the level of aspartic and glutamic acid. The recovery occurred in liver two weeks after irradiation in injected irradiated rats, while in irradiated rats self recovery was noticed on the third week after irradiation for aspartic acid but this mixture has no protective effect on the radiation induced changes in the liver glutamic acid. With respect to changes in blood serum, recovery was recorded in the first week after irradiation in the case of aspartic acid while recovery in glutamic acid was attained latter, in the second week. The results suggested that blood serum is more sensitive to the radiation dose 5.5 Gy than the liver of whole body gamma-irradiated rats. Also, it could be suggested that glutamic acid and aspartic acid have different susceptibility to this radiation dose.2 tab

  3. Hepatic handling of a synthetic gamma-labeled bile acid (75SeHCAT)

    International Nuclear Information System (INIS)

    Galatola, G.; Jazrawi, R.P.; Bridges, C.; Joseph, A.E.; Northfield, T.C.

    1988-01-01

    75 Se-homocholic acid-taurine ( 75 SeHCAT) is the first available gamma-labeled bile acid, and should therefore be handled more efficiently and specifically by the liver than previous hepatoscintigraphic agents. We have measured serum and hepatic kinetics for 75 SeHCAT, and compared them with those for the conventional hepatobiliary scintigraphic agent 99mTc-hepatoiminodiacetic acid, and with serum kinetics for the corresponding natural bile acid, [ 14 C]cholic acid-taurine. We used a dynamic scintigraphic technique and serial blood sampling in 8 subjects. Initial hepatic uptake rate was identical to initial serum disappearance rate (14% dose/min) for 75 SeHCAT, but significantly lower for 99mTc-hepatoiminodiacetic acid (6% vs. 14% dose/min, p less than 0.001). Hepatic transit time was shorter for 75 SeHCAT (13 min vs. 22 min, p less than 0.02), net hepatic excretory rate was more rapid (1.4% vs. 0.8% dose/min, p less than 0.001), and urinary excretion was lower (1.0% vs. 9.0% dose, p less than 0.001). Initial and late-plasma disappearance rates were significantly lower for 75 SeHCAT (14.3% and 1.5% dose/min) than for [ 14 C]cholic acid-taurine (21.3% and 2.8% dose/min, respectively), and plasma clearance was also lower (2 75 vs. 670 ml/min). In vitro, 75 SeHCAT was bound to serum proteins more completely than [ 14 C]cholic acid-taurine (90.4% vs. 86.5%, p less than 0.005). We conclude that 75 SeHCAT provides a hepatoscintigraphic agent that is handled more efficiently and specifically by the liver than the conventionally used agent 99mTc-hepatoiminodiacetic acid. It is not cleared from the serum as rapidly as [ 14 C]cholic acid-taurine, probably due to its stronger protein binding. The clinical value of 75 SeHCAT in assessing liver disease should be investigated

  4. Influence of whole-body gamma irradiation upon arachidonic acid metabolism in rat platelets

    International Nuclear Information System (INIS)

    Lognonne, J.L.; Ducousso, R.; Rocquet, G.; Kergonou, J.F.

    1985-01-01

    The effects of whole-body gamma irradiation (8.4 Gy) were studied on arachidonic acid (AA) metabolism in rat's blood platelets, from day D + 1 to day D + 10 after irradiation. AA conversion into thromboxane B 2 (TxB 2 ) increased at D + 1 and then gradually decreased to very low values from D + 7 to D + 10. This decrease in the conversion of exogenous AA into TxB 2 was due to a lower AA incorporation into platelets and not to a decrease of cyclooxygenase and thromboxane-synthetase activities. AA incorporation into membrane phospholipids of blood platelets was much more decreased than AA incorporation into whole platelets; moreover, the lipid composition of the platelet membranes was markedly modified after irradiation, which must have resulted in structural and functional changes in these membranes; from these effects of whole-body gamma irradiation on platelets, the latter's membranes appeared as a major site of in vivo radiation damage in these cells

  5. Superabsorbent materials from grafting of acrylic acid onto Thai agricultural residues by gamma irradiation

    International Nuclear Information System (INIS)

    Wongsawaeng, Doonyapong; Jumpee, Chayanit

    2016-01-01

    Superabsorbent polymers based on ubiquitous agricultural residues: sugarcane, water hyacinth, rice straw, coconut shell and palm fruit bunch substrates, were successfully synthesized. Gamma radiation from Co-60 was employed to graft acrylic acid (AA) onto the substrates. Rice straw exhibited the highest equilibrium swelling ratio of 78.90 g/g at 6 kGy of absorbed gamma ray dose and 14%v/v AA concentration. The rate of water absorption was rapid at the beginning and became reduced with increasing immersion time. After about 3.5 hours, the absorption reached approximately 90% of the saturation value. Temperature plays a critical role on the rate of water evaporation from the superabsorbent. As for the one experiencing 35degC-40degC temperature, the weight of the saturated superabsorbent reduced to approximately 50% of the original value in 13 hours. However, for the one experiencing room temperature (24.2degC-27.7degC), approximately 58 hours were needed to reduce the weight by half. The superabsorbent polymer was able to absorb about 203% of the polymer's dry weight and did not release urea when eluded by water. Moreover, the polymer was able to hold water very well for at least 3 weeks and did not degrade until at least 6 weeks, ensuring biodegradability. (author)

  6. Synthesis and characterization of zinc chloride containing poly(acrylic acid) hydrogel by gamma irradiation

    International Nuclear Information System (INIS)

    Park, Jong-Seok; Kuang, Jia; Gwon, Hui-Jeong; Lim, Youn-Mook; Jeong, Sung-In; Shin, Young-Min; Seob Khil, Myung; Nho, Young-Chang

    2013-01-01

    In this study, the characterization of zinc chloride incorporated into a poly(acrylic acid) (PAAc) hydrogel prepared by gamma-ray irradiation was investigated. Zinc chloride powder with different concentrations was dissolved in the PAAc solution, and it was crosslinked with gamma-ray irradiation. The effects of various parameters such as zinc ion concentration and irradiation doses on characteristics of the hydrogel formed were investigated in detail for obtaining an antibacterial wound dressing. In addition, the gel content, pH-sensitive (pH 4 or 7) swelling ratio, and UV–vis absorption spectra of the zinc particles in the hydrogels were characterized. Moreover, antibacterial properties of these new materials against Staphylococcus aureus and Escherichia coli strains were observed on solid growth media. The antibacterial tests indicated that the zinc chloride containing PAAc hydrogels have good antibacterial activity. - Highlights: • The characterization of zinc chloride containing PAA hydrogel was investigated. • The gel content increased with an increase in absorbed dose up to 75 kGy. • Finally, the zinc chloride based hydrogels have an antibacterial activity

  7. Composition of the enzymatic and acid hydrolyzates of gamma-irradiated rice straw

    International Nuclear Information System (INIS)

    Abad, L.V.; Banzon, R.B.; Rosa, A. de la

    1989-01-01

    Gamma irradiation was utilized to induce structural changes in rice straw that would enhance the conversion of its cellulose and ligno-cellulosic components to glucose and other reducing sugars. With the appropriate fermentation conditions these sugars can eventually be converted into alcohol. Rice straw materials were irradiated at varying doses (0-500 kgy) and hydrolyzed by the use of a) cellulose enzyme and b) 1% sulfuric acid. The composition of the hydrolyzates of rice straw was studied by thin layer chromatography (TLC) coupled with the Nelson-Somogyi test for its quantification. Acid hydrolyzates of rice straw showed a maximum increase of 16.46% in its total reducing sugars at 300 Kgy. TLC of the acid hydrolyzates of rice straw revealed the presence of glucose, xylose, arabinose, and cellobiose. However, it was only with xylose that a significant increase in yield was observed with the non-irradiated straw 12.55% xylose yield was noted while with rice straw-irradiated at 400 Kgy a maximum yield of 15.90% xylose was obtained. Total reducing sugar of the enzymatic hydrolyzate of rice straw showed a maximum increase of 205% at 500 Kgy. TLC revealed that only glucose was present in the enzymatic hydrolyzate. Glucose yield increase from 2.49% (0 Kgy) to 7.31% (500 Kgy). The results showed that radiation pre-treatment of rice straw induces significant increases in reducing sugar for both enzymatic and hydrolyzate. (Auth.). 2 tabs.; 1 fig

  8. Spectral distribution of the radiochemiluminescence from gamma-irradiated humic acid

    International Nuclear Information System (INIS)

    Goraczko, W.; Slawinski, J.; Staninski, K.

    2008-01-01

    This study was conducted to investigate radiochemiluminescence (RCL) spectra (340-650 nm), kinetics and absorption spectra of humic acids (HA) after their exposure of gamma-radiation (absorbed doses of 1-10 kGy, 60 Co) in model systems. The kinetics and spectral distribution of RCL were measured using the single photon counting method (SPC) and cut-off filters. Absorption spectra (range 240-800 nm) of irradiated solutions indicated that post-radiative degradation/polymerization processes take place in the HA changing their macromolecule or properties. The intensity of the delayed RCL was nonlinearly and suggested that complex radical formation mechanisms were still involved in the post-radiative reactions. (author)

  9. Spectral distribution of the radiochemiluminescence from gamma-irradiated humic acid

    Energy Technology Data Exchange (ETDEWEB)

    Goraczko, W [Poznan University of Technology, Poznan (Poland). Faculty of Chemical Technology, Radio- and Photochemistry Department; Slawinski, J [Institute of Ecotechnology, Gniezno (Poland). State High Vocational School; Staninski, K [Adam Mickiewicz University, Poznan (Poland). Faculty of Chemistry, Department of Rare Earths

    2008-09-15

    This study was conducted to investigate radiochemiluminescence (RCL) spectra (340-650 nm), kinetics and absorption spectra of humic acids (HA) after their exposure of gamma-radiation (absorbed doses of 1-10 kGy, {sup 60}Co) in model systems. The kinetics and spectral distribution of RCL were measured using the single photon counting method (SPC) and cut-off filters. Absorption spectra (range 240-800 nm) of irradiated solutions indicated that post-radiative degradation/polymerization processes take place in the HA changing their macromolecule or properties. The intensity of the delayed RCL was nonlinearly and suggested that complex radical formation mechanisms were still involved in the post-radiative reactions. (author)

  10. Preparation of poly(acrylic acid)-chitosan hydrogels by gamma irradiation for metal ions sorption

    International Nuclear Information System (INIS)

    Tran Thu Hong; Le Hai; Nguyen Tan Man; Tran Thi Tam; Pham Thi Le Ha; Pham Thi Sam; Nguyen Duy Hang; Le Huu Tu; Le Van Toan

    2013-01-01

    Acid acrylic (AAc) was grafted onto crosslinked chitosan to make Chitosan-g-AAc copolymer with concentration of AAc from 0.5 to 15% by gamma irradiation. The optimal dose for grafting of 15% AAc onto chitosan was 5 kGy. Physical and chemical properties of irradiated samples such as SEM images, FTIR spectroscopy, TGA and swelling behavior at different pHs were evaluated. The grafting yield increased with the increase in dose, it reached 52% at 7 kGy irradiation dose. The application were grafted materials to adsorb metals ion from aqueous solutions was also investigated with both ungrafted and grafted chitosan beads under changing pH from 3 to 6. Grafted chitosan presented higher sorption capacity for most of metal ions than unmodified chitosan. (author)

  11. Tendon allograft sterilized by peracetic acid/ethanol combined with gamma irradiation.

    Science.gov (United States)

    Zhou, Mo; Zhang, Naili; Liu, Xiaoming; Li, Youchen; Zhang, Yumin; Wang, Xusheng; Li, Baoming; Li, Baoxing

    2014-07-01

    Research and clinical applications have demonstrated that the effects of tendon allografts are comparable to those of autografts when reconstructing injured tendons or ligaments, but allograft safety remains problematic. Sterilisation could eliminate or decrease the possibility of disease transmission, but current methods seldom achieve satisfactory sterilisation without affecting the mechanical properties of the tendon. Peracetic acid-ethanol in combination with low-dose gamma irradiation (PE-R) would inactivate potential deleterious microorganisms without affecting mechanical and biocompatible properties of tendon allograft. Controlled laboratory design. HIV, PPV, PRV and BVDV inactivation was evaluated. After verifying viral inactivation, the treated tendon allografts were characterised by optical microscopy, scanning electron microscopy and tensile testing, and the cytocompatibility was assessed with an MTT assay and by subcutaneous implantation. Effective and efficient inactivation of HIV, PPV, PRV and BVDV was observed. Histological structure and ultrastructure were unchanged in the treated tendon allograft, which also exhibited comparable biomechanical properties and good biocompatibility. The preliminary results confirmed our hypothesis and demonstrated that the PE-R tendon allograft has significant potential as an alternative to ligament/tendon reconstruction. Tendon allografts have been extensively used in ligament reconstruction and tendon repair. However, current sterilisation methods have various shortcomings, so PE-R has been proposed. This study suggests that PE-R tendon allograft has great potential as an alternative for ligament/tendon reconstruction. Sterilisation has been a great concern for tendon allografts. However, most sterilisation methods cannot inactivate viruses and bacteria without impairing the mechanical properties of the tendon allograft. Peracetic acid/ethanol with gamma irradiation can effectively inactivate viruses and bacteria

  12. Effects of dietary gamma-linolenic acid and docosahexaenoic acid with paclitaxel on the treatment of mice mammary carcinoma

    Directory of Open Access Journals (Sweden)

    Kamran Rakhshan

    2013-08-01

    Full Text Available Background: Breast cancer is one of the most important causes of death in women. One of the various gene expression involved in breast cancer is human epidermal growth factor receptor 2 (HER2/neu gene expression increases. Factors of dietary affect on regulation of hormone secretion and the rate of breast cancer. One of these factors is amount and type of fats in diet. Gamma-linolenic acid (GLA and Docosah-exaenoic acid (DHA are members of poly unsaturated fatty acids. In this study, effects of dietary GLA and DHA alone or together with paclitaxel on treatment of mice mammary carcinoma has been evaluated.Methods: Thirty female balb/c mice were divided in six groups randomly. Carcinoma-tous mass induced by tumor implantation method. Spontaneous breast adenocarcinoma of mice were used as tumor stock. The tumors of these mice were removed aseptically, dissected into 0.5 cm3 pieces. These pieces were transplanted subcutaneously into their right flank. GLA and DHA added to the mice diet two week prior to tumor implanta-tion. At the end of intervention, tumors were removed and HER2 gene expression was measured. The weight of animal and tumor volume measured weekly.Results: It was not significant change in the weight of animals that consumed DHA and DHA with taxol. Tumor volume in those groups that received corn oil with taxol (P<0.01, DHA (P<0.05 and DHA with taxol (P<0.001 showed significant decrease in comparison with control group. HER2 gene expression in DHA with taxol decreased significantly in comparison with control group (P<0.05.Conclusion: Consumption of DHA oil with taxol causes decrease the volume of carcin-oma mass. The future studies with large number of sample is needed to support this finding.

  13. Early continuous white noise exposure alters l-alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor subunit glutamate receptor 2 and gamma-aminobutyric acid type a receptor subunit beta3 protein expression in rat auditory cortex.

    Science.gov (United States)

    Xu, Jinghong; Yu, Liping; Zhang, Jiping; Cai, Rui; Sun, Xinde

    2010-02-15

    Auditory experience during the postnatal critical period is essential for the normal maturation of auditory function. Previous studies have shown that rearing infant rat pups under conditions of continuous moderate-level noise delayed the emergence of adult-like topographic representational order and the refinement of response selectivity in the primary auditory cortex (A1) beyond normal developmental benchmarks and indefinitely blocked the closure of a brief, critical-period window. To gain insight into the molecular mechanisms of these physiological changes after noise rearing, we studied expression of the AMPA receptor subunit GluR2 and GABA(A) receptor subunit beta3 in the auditory cortex after noise rearing. Our results show that continuous moderate-level noise rearing during the early stages of development decreases the expression levels of GluR2 and GABA(A)beta3. Furthermore, noise rearing also induced a significant decrease in the level of GABA(A) receptors relative to AMPA receptors. However, in adult rats, noise rearing did not have significant effects on GluR2 and GABA(A)beta3 expression or the ratio between the two units. These changes could have a role in the cellular mechanisms involved in the delayed maturation of auditory receptive field structure and topographic organization of A1 after noise rearing. Copyright 2009 Wiley-Liss, Inc.

  14. Kinetic modeling of levulinic acid hydrogenation to gamma-valerolactone in water using a carbon supported Ru catalyst

    NARCIS (Netherlands)

    Piskun, A.S.; van de Bovenkamp, H.H.; Rasrendra, C.B.; Winkelman, J.G.M.; Heeres, H.J.

    2016-01-01

    gamma-Valerolactone (GVL) is considered a very interesting green, bio-based platform chemical with highapplication potential for the production of both biofuels and biobased chemicals. In this contribution, wereport a kinetic study on the hydrogenation of levulinic acid (LA) to 4-hydroxypentanoic

  15. Effect of gamma Irradiation on the acidic hydrolysis of free-hemi cellulose thistle; Efecto de la irradiacion gamma en la hidrolisis acida de cardo exento de pentosas

    Energy Technology Data Exchange (ETDEWEB)

    Suarez, C.; Paz, M. D.; Diaz, A.

    1983-07-01

    The effect of gamma-irradiation on the subsequent acidic hydrolysis of free-hemi cellulose Onopordum Nervosum Boiss thistle Ls determined. Its shown the influence of gamma-irradiation on the yield of sugar obtained flora the batch wise hydrol isis of the call ulose (1% H{sub 2}SO{sub 4} and 180 degree centigree at increasing doses). At all irradiation levels studied, the rate of hydrolysis of thistle samples was higher than the rate of hydrolysis of the cellulose from paper treated similarly. The maximum over-all yield of sugar in the irradiated lignocellulose material was about 66o at 100 MRad, less than two times the yield obtainable from the control. The corresponding yield from papel was 53%, 2'3 times that of the control. Irradiation under 1% H{sub 2}SO{sub 4} doesn't enhance the yield anyway. (Author) 21 refs.

  16. Effect of gamma Irradiation on the acidic hydrolysis of free-hemi cellulose thistle; Efecto de la irradiacion gamma en la hidrolisis acida de cardo exento de pentosas

    Energy Technology Data Exchange (ETDEWEB)

    Suarez, C; Paz, M D; Diaz, A

    1983-07-01

    The effect of gamma-irradiation on the subsequent acidic hydrolysis of free-hemi cellulose Onopordum Nervosum Boiss thistle Ls determined. Its shown the influence of gamma-irradiation on the yield of sugar obtained flora the batch wise hydrol isis of the call ulose (1% H{sub 2}SO{sub 4} and 180 degree centigree at increasing doses). At all irradiation levels studied, the rate of hydrolysis of thistle samples was higher than the rate of hydrolysis of the cellulose from paper treated similarly. The maximum over-all yield of sugar in the irradiated lignocellulose material was about 66o at 100 MRad, less than two times the yield obtainable from the control. The corresponding yield from papel was 53%, 2'3 times that of the control. Irradiation under 1% H{sub 2}SO{sub 4} doesn't enhance the yield anyway. (Author) 21 refs.

  17. Glutamic acid decarboxylase isoform distribution in transgenic mouse septum: an anti-GFP immunofluorescence study.

    Science.gov (United States)

    Verimli, Ural; Sehirli, Umit S

    2016-09-01

    The septum is a basal forebrain region located between the lateral ventricles in rodents. It consists of lateral and medial divisions. Medial septal projections regulate hippocampal theta rhythm whereas lateral septal projections are involved in processes such as affective functions, memory formation, and behavioral responses. Gamma-aminobutyric acidergic neurons of the septal region possess the 65 and 67 isoforms of the enzyme glutamic acid decarboxylase. Although data on the glutamic acid decarboxylase isoform distribution in the septal region generally appears to indicate glutamic acid decarboxylase 67 dominance, different studies have given inconsistent results in this regard. The aim of this study was therefore to obtain information on the distributions of both of these glutamic acid decarboxylase isoforms in the septal region in transgenic mice. Two animal groups of glutamic acid decarboxylase-green fluorescent protein knock-in transgenic mice were utilized in the experiment. Brain sections from the region were taken for anti-green fluorescent protein immunohistochemistry in order to obtain estimated quantitative data on the number of gamma-aminobutyric acidergic neurons. Following the immunohistochemical procedures, the mean numbers of labeled cells in the lateral and medial septal nuclei were obtained for the two isoform groups. Statistical analysis yielded significant results which indicated that the 65 isoform of glutamic acid decarboxylase predominates in both lateral and medial septal nuclei (unpaired two-tailed t-test p glutamic acid decarboxylase isoform 65 in the septal region in glutamic acid decarboxylase-green fluorescent protein transgenic mice.

  18. Degradation Behaviour of Gamma Irradiated Poly(Acrylic Acid)-graft-Chitosan Superabsorbent Hydrogel

    Science.gov (United States)

    Ria Barleany, Dhena; Ilhami, Alpin; Yusuf Yudanto, Dea; Erizal

    2018-03-01

    A series of superabsorbent hydrogels were prepared from chitosan and partially neutralized acrylic acid at room temperature by gamma irradiation technique. The effect of irradiation and chitosan addition to the degradation behaviour of polymer were investigated. The gel content, swelling capacity, Equillibrium Degree of Swelling (EDS), Fourier Transform Infra Red (FTIR), and Scanning Electron Microscopy (SEM) study were also performed. Natural degradation in soil and thermal degradation by using of TGA analysis were observed. The variation of chitosan compositions were 0.5, 1, 1.5, and 2 g and the total irradiation doses were 5, 10, 15, and 20 kGy. The highest water capacity of 583.3 g water/g dry hydrogel was resulted from 5 kGy total irradiation dose and 0,5 g addition of chitosan. From the thermal degradation evaluation by using of TGA analysis showed that irradiation dose did not give a significant influence to the degradation rate. The rate of thermal degradation was ranged between 2.42 to 2.55 mg/min. In the natural test of degradation behaviour by using of soil medium, the hydrogel product with chitosan addition was found to have better degradability compared with the poly(acrylic acid) polymer without chitosan.

  19. EPR studies of the free radicals generated in gamma irradiated amino acid derivatives

    Science.gov (United States)

    Osmanoğlu, Y. Emre; Sütçü, Kerem

    2017-10-01

    Gamma irradiated powder forms of N-acetyl-DL-aspartic acid, N-carbamoyl-DL-aspartic acid and N-methyl-L-serine were investigated by electron paramagnetic resonance spectroscopy (EPR) at room temperature. In these compounds, the paramagnetic centers formed after irradiation were attributed to the HOOCCH2ĊHCOOH, COOHĊHCHNH and HOCH2ĊHCOOH radicals, respectively. The g values and the hyperfine coupling constants for the radical species are with values of g = 2.0038 ± 0.0005, aα = 2.15 mT, aβ(1) = 3.84 mT and aβ(2) = 2.15 for the first radical, g = 2.0039 ± 0.0005, aα = 1.7 mT, aß(1) = 0.62 mT, aß(2) = 0.54 mT, aγ = 0.53 mT for the second radical and g = 2.0039 ± 0.0005, aβ(1) = 2.40 mT, aβ(2) = 1.83 mT and aα = 1.83 mT for the third radical. The free radicals formed in three compounds were found to be stable for three months at room temperature. It was concluded that, spin density was concentrated predominantly in the 2pπ orbital of the carbon atom.

  20. Effect of Gamma Radiation on Amino Acid Based Vesicle Carrying Radiosensitizer

    International Nuclear Information System (INIS)

    Nur Ratasha Alia Mohd Rosli; Faizal Mohamed; Muhammad Amir Syafiq Mohd Sah; Irman Abdul Rahman

    2014-01-01

    Vesicles has been developed and studied to be used as a medium to transport radiosensitizer in treating cancer cells by increasing its sensitivity effectively towards the radiation given during radiotherapy. This study was conducted to investigate the effect of gamma radiation on amino acid-based vesicle carrying radiosensitizer. Amino acid based vesicles carrying radiosensitizer were synthesized using sonication method with sodium N-lauroylsarcosinate hydrate and decanol being the primary surfactant, while hydrogen peroxide and sodium hyaluronate as the encapsulated radiosensitizer. The synthesized vesicle was then irradiated at radiation doses equivalent to those given during radiotherapy. Irradiated vesicle carrying radiosensitizer were then characterized using Transmission Electron Microscopy (TEM), Fourier Transform Infrared Spectroscopy (FTIR) and Polarized Light Microscope. Results obtained shows that there were no significant changes in morphology and molecular conformation of the synthesized vesicle after irradiation. Even at higher radiation dose of 100 Gray and 200 Gray, the results remained unchanged. This indicates that the synthesized vesicle carrying radiosensitizer is morphologically and spectroscopically stable even at high radiation doses. (author)

  1. Effects of gamma-ray-induced free radicals on the metal content and amino acid composition of human metallothionein-1

    International Nuclear Information System (INIS)

    Goossens, Lieven

    2011-01-01

    Metallothioneins (MTs), a low-mass class of metalloproteins, are characterized by a high thiolate sulphur and metal content. MTs are involved in metal homeostasis and heavy metal detoxification, and are efficient scavengers of free radicals. This article describes zinc release from human MT-1 and modification of its amino acid composition when subjected to free radicals generated during gamma ray radiolysis. The effect of gamma ray radiolysis of untreated and metal-depleted human MT-1 was tested under multiple aerobic and anaerobic conditions at increasing irradiation doses. Under all conditions, a rapid increase of serine in the early stages of irradiation was observed. Irradiation for longer times led to cysteic acid formation, except under argon atmosphere. Several other amino acid concentrations gradually decreased. Formation of limited amounts of hydroxyproline, hydroxylysine and ornithine as well as some less common derivatives such as cystathionine occurred as side-effects. (author)

  2. The effect of gamma irradiation on the nucleic acids content of the mediterranean fruit fly ceratitis capitata (Wied)

    International Nuclear Information System (INIS)

    Fadel, A.M.; Amin, T.R.; Al-Elimi, M.H.

    1999-01-01

    This work was carried out study the effect of gamma irradiation on the deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) content in the whole body homogenate of the mediterranean fruit fly, ceratitis capitata (Wied.) pupae were gamma irradiated with different doses (o, 50, 70, 90 and 110 Gy) at two different pupal ages (2 and 4 days before adult emergence ) to estimate the nucleic acids in pupae and adult males, and females. Experimental results showed that gamma irradiation of pupae reduced RNA content, and this reduction was proportional with the applied dose and more pronounced in the younger pupae. However, DNA content was reduced only when the highest dose was applied to pupae irradiated 2 days before adult emergence (older pupae). Concerning adult insects which were gamma irradiated as pupae, the results revealed, generally, that males and females which were irradiated 2 days before adult emergence were more affected than those irradiated 4 days before adult emergence. The male DNA content and the female RNA content showed high degrees of reduction which, more or less, increased with increasing the dose used. On the other hand, female DNA and male RNA contents were slightly, changed. The significant importance of the results and some statistical interrelations were discussed

  3. Effect of "6"0Co-induced gamma radiation exposure and Jasmonic acid on antioxidant responses in Cowpea varieties

    International Nuclear Information System (INIS)

    Shukla, Pradeep Kumar; Bhagoji, Ravi; Ramteke, P.W.; Misra, Pragati; Maurice, Navodita

    2017-01-01

    Cowpea used to be the first crop harvested before the cereal crops are ready and therefore is referred to as 'hungry-season crop'. The gamma irradiation is known to increase nutritional values of food sources and also enhance and accelerate growth of certain vegetables Antioxidants are the metabolites, produced by the plant in response to different stress conditions e.g. radiation stress etc. Seeds of four cowpea varieties were treated with different doses of gamma radiation and effect of jasmonic acid (JA) on antioxidant response of cowpea was studied. The results showed that there was no linear correlation between application of JA and different antioxidant contents. (author)

  4. Effects of dietary supplementation with eicosapentaenoic acid or gamma-linolenic acid on neutrophil phospholipid fatty acid composition and activation responses.

    Science.gov (United States)

    Fletcher, M P; Ziboh, V A

    1990-10-01

    Previous data that alimentation with fish oil rich in eicosapentaenoic acid (EPA; 20:n-3) or vegetable oil rich in gamma-linolenic acid (GLA; 18:3n-6) can reduce symptoms of inflammatory skin disorders lead us to determine the effects of dietary supplements of oils rich in EPA or GLA on guinea pig (GP) neutrophil (PMN) membrane potential (delta gamma), secretion, and superoxide (O2-) responses. Weanling GPs were initially fed diets supplemented with olive oil (less than 0.1% EPA; less than 0.1% GLA) for 2 weeks, followed by a crossover by two sets of animals to diets supplemented with fish oil (19% EPA) or borage oil (25% GLA). At 4-week intervals, 12% sterile casein-elicited peritoneal neutrophils (PMN) were assessed for membrane polyunsaturated fatty acid (PUFA) profiles and FMLP-, LTB4-, and PMA-stimulated delta gamma changes, changes in flow cytometrically measured forward scatter (FWD-SC) (shape change), 90 degrees scatter (90 degrees -SC) in cytochalasin B-pretreated-PMN (secretion response), and superoxide responses, GP incorporated EPA and GLA (as the elongation product, dihomo-GLA or DGLA) into their PMN phospholipids by 4 weeks. The peritoneal PMN of all groups demonstrated broad resting FWD-SC and poor activation-related FWD-SC increases, suggesting in vivo activation. While secretion was comparable in the three groups in response to FMLP, there was a trend toward inhibition of LTB4-stimulated 90 degrees -SC loss in both fish and borage oil groups. This was significant only with borage oil (21.7 +/- 2.1 vs 15.3 +/- 1.2% loss of baseline 90 degrees -SC, olive vs borage: P = 0.03). PMN from borage- and fish oil-fed GPs showed a progressively lower O2- response to FMLP than the olive oil group (73.9 +/- 3.9 and 42.9 +/- 6.8% of olive oil response for borage and fish oils, respectively; P less than 0.005 and P less than 0.01, respectively, at 12 weeks), while PMA-stimulated O2- was inhibited only in the fish oil-fed group and only at 12 weeks (62.0 +/- 2

  5. Semi-pilot scale production of citric acid in cane molasses by gamma-ray induced mutants of Aspergillus niger

    Energy Technology Data Exchange (ETDEWEB)

    Islam, M.S.; Begum, R.; Choudhury, N.

    1986-08-01

    Utilizing cane molasses as substrate, semi-pilot scale production of citric acid was investigated in fermentation trays (40 x 35 cm) with several gamma-ray induced mutants of Aspergillus niger. Of the mutants tested, two were found to have high yield efficiency (14/20, 51.06%; 79/20, 50.35%) of sugar to citric acid. The yield of other mutants (HB3, 10/20, 164/20, 277/30 and 112/40) ranged between 30 to 42%. The prospect of utilizing the high yielding mutants for commercial production of citric acid has been discussed.

  6. Semi-pilot scale production of citric acid in cane molasses by gamma-ray induced mutants of Aspergillus niger

    International Nuclear Information System (INIS)

    Islam, M.s.; Begum, R.; Choudhury, N.

    1986-01-01

    Utilizing cane molasses as substrate, semi-pilot scale production of citric acid was investigated in fermentation trays (40 x 35 cm) with several gamma-ray induced mutants of Aspergillus niger. Of the mutants tested, two were found to have high yield efficiency (14/20, 51.06%; 79/20, 50.35%) of sugar to citric acid. The yield of other mutants (HB3, 10/20, 164/20, 277/30 and 112/40) ranged between 30 to 42%. The prospect of utilizing the high yielding mutants for commercial production of citric acid has been discussed. (author)

  7. Efect of Gamma 60Co Irradiation on The Growth, Lipid Content and Fatty Acid Composition of Botryococcus sp. Microalgae

    Directory of Open Access Journals (Sweden)

    Dini Ermavitalini

    2017-04-01

    Full Text Available Botryococcus sp. is one of microalgae species that has a high lipid content as much as 75% of their dry weight. But, lipid production by microalgae is regulated by their environmental condition (pH, light, temperature, nutrition, etc. Mutagenesis induced by Gamma 60Co irradiation can be utilized to alter the Botryococcus sp. genetic to get microalgae mutant strain that can produce a higher lipid content than the wild strain. Botryococcus sp. was irradiated with different doses of gamma ray of 60Co  (0, 2, 4, 6, and 10 Gy,  and the effect  on the growth, lipid content, and fatty acid composition of microalgae were observed. Research design used is random complete (RAL with 95 %  confident level for quantitive analysis based on the biomass and lipid contents. More over fatty acid composition was analyzed by Gas Cromatography-Mass Spectrometry (GC-MS. Results showed that Gamma irradiated gave an effect on growth and lipid content of Botryococcus sp. But between the control treatment (0 Gy with microalgae irradiated dose of 2 Gy, 4 Gy and 6 Gy were not significantly different. Whereas between the control with 10 Gy irradiated was significantly different. The highest biomassa and lipid content are found in 10 Gy irradiated microalgae with 0.833 gram biomass and 41% lipid content. Fatty acid profile of Botryococcus sp. control has 6 fatty acids while 10 Gy irradiated microalgae has 12 fatty acids, with the long-chain fatty acids increased, whereas short-chain fatty acids decreased.

  8. Bio-physicochemical effects of gamma irradiation treatment for naphthenic acids in oil sands fluid fine tailings

    Energy Technology Data Exchange (ETDEWEB)

    Boudens, Ryan; Reid, Thomas; VanMensel, Danielle; Sabari Prakasanm, M.R. [Great Lakes Institute for Environmental Research, University of Windsor, Windsor, ON (Canada); Ciborowski, Jan J.H. [Biological Sciences, University of Windsor, Windsor, ON (Canada); Weisener, Christopher G., E-mail: weisener@uwindsor.ca [Great Lakes Institute for Environmental Research, University of Windsor, Windsor, ON (Canada)

    2016-01-01

    Naphthenic acids (NAs) are persistent compounds that are components of most petroleum, including those found in the Athabasca oil sands. Their presence in freshly processed tailings is of significant environmental concern due to their toxicity to aquatic organisms. Gamma irradiation (GI) was used to reduce the toxicity and concentration of NAs in oil sands process water (OSPW) and fluid fine tailings (FFT). This investigation systematically studied the impact of GI on the biogeochemical development and progressive reduction of toxicity using laboratory incubations of fresh and aged tailings under anoxic and oxic conditions. GI reduced NA concentrations in OSPW by up to 97% in OSPW and in FFT by 85%. The GI-treated FFT exhibited increased rates of biogeochemical change, dependent on the age of the tailings source. Dissolved oxygen (DO) flux was enhanced in GI-treated FFT from fresh and aged source materials, whereas hydrogen sulfide (HS{sup −}) flux was stimulated only in the fresh FFT. Acute toxicity to Vibrio fischeri was immediately reduced following GI treatment of fresh OSPW. GI treatment followed by 4-week incubation reduced toxicity of aged OSPW to V. fischeri. - Highlights: • Gamma irradiation substantially reduced concentrations of ecotoxic naphthenic acids • Acute toxicity was reduced in gamma irradiated process water • Gamma irradiated tailings exhibited increased rates of microbial respiration.

  9. Effects of Gamma irradiation on uronic acid sugars as cell wall polysaccharide model systems

    International Nuclear Information System (INIS)

    Irawati, Zubaidah; Pilnik, W.

    2001-01-01

    Irradiation is an alternative preservation method with can be utilized to extend the self-life of agricultural products by eliminating number of insects, and decreasing microbial growth effectively. Cell wall polysaccharides which mainly consist of pectic substances, hemicelluloses and cellulose play a major role on the immediate fruits. their degradation mechanism can be elucidates by studying their degradation products resulting from the irradiated cell wall or cell wall components. Isolated apple pectin and alginates as different in solid state by gamma irradiation at 15-30 kGy under two different humidities. The parameters observed were viscosity, β-elimination in the ester groups of pectin, and distribution of molecular weight. Irradiation with the doses of 15-30 kGy could reduce the viscosity of pectin and alginates, while irradiation did not cause β-elimination in the ester groups of pectin as confirmed by titration and ion exchange chromatography methods. The formation of 4,5-unsaturated uronosyl residues as a product of cleavage of the pectin backbone via- β-elimination was not found in irradiated pectin as confirmed by thio barbiture acid (TBA) test. High Performance Size Exclusion Chromatography (HPSEC) analysis for the irradiated polysaccharide model systems revealed that the average number of molecular weight showed a decrease by increasing radiation dose. Storage condition in two different relative humidities affected significantly the degree of polymerization of pectin and alginates in solid state

  10. Low Dose Gamma Irradiation Does Not Affect the Quality or Total Ascorbic Acid Concentration of "Sweetheart" Passionfruit (Passiflora edulis).

    Science.gov (United States)

    Golding, John B; Blades, Barbara L; Satyan, Shashirekha; Spohr, Lorraine J; Harris, Anne; Jessup, Andrew J; Archer, John R; Davies, Justin B; Banos, Connie

    2015-08-26

    Passionfruit ( Passiflora edulis , Sims, cultivar "Sweetheart") were subject to gamma irradiation at levels suitable for phytosanitary purposes (0, 150, 400 and 1000 Gy) then stored at 8 °C and assessed for fruit quality and total ascorbic acid concentration after one and fourteen days. Irradiation at any dose (≤1000 Gy) did not affect passionfruit quality (overall fruit quality, colour, firmness, fruit shrivel, stem condition, weight loss, total soluble solids level (TSS), titratable acidity (TA) level, TSS/TA ratio, juice pH and rot development), nor the total ascorbic acid concentration. The length of time in storage affected some fruit quality parameters and total ascorbic acid concentration, with longer storage periods resulting in lower quality fruit and lower total ascorbic acid concentration, irrespective of irradiation. There was no interaction between irradiation treatment and storage time, indicating that irradiation did not influence the effect of storage on passionfruit quality. The results showed that the application of 150, 400 and 1000 Gy gamma irradiation to "Sweetheart" purple passionfruit did not produce any deleterious effects on fruit quality or total ascorbic acid concentration during cold storage, thus supporting the use of low dose irradiation as a phytosanitary treatment against quarantine pests in purple passionfruit.

  11. Potency of maternal folic acid supplementation on gamma irradiation- induced histological and embryological anomalies in albino rats

    International Nuclear Information System (INIS)

    Rezk, R.G.; Ibrahim, M.F.

    2006-01-01

    Folic acid, a member of the water-soluble vitamin B group, is emerged as an important nutritional factor especially during the course of pregnancy. It is rapidly absorbed from the proximal part of small intestine, distributed to the body tissues, stored in the liver and actively concentrated in the cerebrospinal fluid. The objective of this study was to evaluate the potency of maternal folic acid supplementation in ameliorating the maternal and fetal detrimental impacts of gamma irradiation. Folic acid, at a dose level of 4 mg/Kg body weight was daily administered via an oral stomach tube to pregnant adult albino rats from the 1st to the 20 th day of pregnancy, while mothers were subjected to gamma irradiation at the dose of 3 Gy on day 10 of gestation during the sensitive period of organogenesis. Experimental investigations carried out 1 day prior to parturition have demonstrated that folic acid intake throughout the whole gestational period had significantly diminished the deleterious histopathological disorders in large intestine, liver and uterus of irradiated mothers. Concomitantly, folic acid has been able to enfeeble the hazardous teratological effects of radiation including mainly the fetal intrauterine lethality, developmental delay and prominent morphological deformities. Conclusively, folic acid was found to offer protection during pregnancy against radiation injury, thus was capable of modulating the histopathological impacts of the studied maternal body organs and suppressing the embryonic mortality rates and serious fetal malformations induced by radiation

  12. Potency of maternal folic acid supplementation on gamma irradiation- induced histological and embryological anomalies in albino rats

    Energy Technology Data Exchange (ETDEWEB)

    Rezk, R G [Health Rad. Res., NCRRT, Cairo (Egypt); Ibrahim, M F [Rad. Biology Dept., NCRRT, Cairo (Egypt)

    2006-07-01

    Folic acid, a member of the water-soluble vitamin B group, is emerged as an important nutritional factor especially during the course of pregnancy. It is rapidly absorbed from the proximal part of small intestine, distributed to the body tissues, stored in the liver and actively concentrated in the cerebrospinal fluid. The objective of this study was to evaluate the potency of maternal folic acid supplementation in ameliorating the maternal and fetal detrimental impacts of gamma irradiation. Folic acid, at a dose level of 4 mg/Kg body weight was daily administered via an oral stomach tube to pregnant adult albino rats from the 1st to the 20 th day of pregnancy, while mothers were subjected to gamma irradiation at the dose of 3 Gy on day 10 of gestation during the sensitive period of organogenesis. Experimental investigations carried out 1 day prior to parturition have demonstrated that folic acid intake throughout the whole gestational period had significantly diminished the deleterious histopathological disorders in large intestine, liver and uterus of irradiated mothers. Concomitantly, folic acid has been able to enfeeble the hazardous teratological effects of radiation including mainly the fetal intrauterine lethality, developmental delay and prominent morphological deformities. Conclusively, folic acid was found to offer protection during pregnancy against radiation injury, thus was capable of modulating the histopathological impacts of the studied maternal body organs and suppressing the embryonic mortality rates and serious fetal malformations induced by radiation.

  13. Preparation of poly (styrene)-b-poly (acrylic acid)/{gamma}-Fe{sub 2}O{sub 3} composites

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, L.D. [School of Materials Science and Engineering, Shandong Polytechnic University, Key Laboratory of Processing and Testing Technology of Glass Functional Ceramics of Shandong Province, Daxue Road, Western University Science Park, Jinan 250353 (China); Liu, W.L., E-mail: wlliu@sdu.edu.cn [School of Materials Science and Engineering, Shandong Polytechnic University, Key Laboratory of Processing and Testing Technology of Glass Functional Ceramics of Shandong Province, Daxue Road, Western University Science Park, Jinan 250353 (China); Xiao, C.L.; Yao, J.S.; Fan, Z.P.; Sun, X.L.; Zhang, X.; Wang, L. [School of Materials Science and Engineering, Shandong Polytechnic University, Key Laboratory of Processing and Testing Technology of Glass Functional Ceramics of Shandong Province, Daxue Road, Western University Science Park, Jinan 250353 (China); Wang, X.Q. [State Key Laboratory of Crystal Materials, Shandong University, Jinan 250100 (China)

    2011-12-15

    The use of a block copolymer, poly (styrene)-b-poly (acrylic acid) (PS-b-PAA) to prepare a magnetic nanocomposite was investigated. Poly (styrene)-poly (t-butyl acrylate) block copolymer, being synthesized by atom transfer radical polymerization, was hydrolyzed with hydrochloric acid for obtaining PS-b-PAA. The obtained PS-b-PAA was then compounded with the modified {gamma}-Fe{sub 2}O{sub 3}, and subsequently the magnetic nanocomposite was achieved. The products were characterized by {sup 1}H NMR, FTIR, gel permeation chromatography, thermogravimetric analysis, transmission electron microscopy and vibrating sample magnetometer. The results showed that the nanocomposites exhibited soft magnetism, with the mean diameter of 100 nm approximately. - Highlights: > Magnetic composites were prepared using {gamma}-Fe{sub 2}O{sub 3} and PS-b-PAA. > PS-b-PAA was synthesized by atom transfer radical polymerization. > The obtained composite exhibited soft magnetism.

  14. Effect of gamma irradiation on the protein, amino acids and carbohydrate contents of soya-gari diet

    International Nuclear Information System (INIS)

    Ogbadu, G.H.

    1979-01-01

    Soya-gari diet, prepared by enrichment of gari (Manihot esculanta Cranz) with soya flour, methionine, lysine and salt mixture was irradiated with doses of 62.5, 125, 250 and 500 Krad from a Co 60 γ irradiator. Gamma irradiation of the soya-gari diet with doses as high as 500 Krad had no significant effect on the amino acids, total proteins, soluble carbohydrates, hemicelluloses, cellulose and lignin contents. (author)

  15. Controlled 5-fluorouracil release from hydrogels of Poly (acrylamide-co-metacrylic acid) crosslinked by means Of gamma irradiation techniques

    International Nuclear Information System (INIS)

    Rapado, M.; Sainz, D.; Altanes, S.; Prado, S.; Padron, S.; Salivar, D.; Chong, B.

    1999-01-01

    This report present the results on entrapped a cytostatic 5-Fluorouracil (5-F) in polymeric matrixes named hydrogels of polyacrylamide co -metacrylic acid crosslinked by means of gamma radiation with doses of 10,30, and 30 kGy at 25 o C. The drug delivery was followed by HPLC. The behavior of 5 -Fu migration from polymeric network was analyze by Iguchi equation for plain structure systems. The diffusion coefficients were obtained and drug release was in accordance with Fickian behavior

  16. The Effects of Cobalt-60 Gamma Radiation on Vitamin B{sub 6} and Folic Acid; Effets des rayons gamma (cobalt-60) sur la vitamine B{sub 6} et l’acide folique

    Energy Technology Data Exchange (ETDEWEB)

    Galatzeanu, I.; Antoni, F. [International Atomic Energy Agency, Vienna (Austria)

    1967-09-15

    A study has been made of the behaviour of pyridoxine and folic acid, including structural changes, after {sup 60}Co gamma irradiation. The irradiation of pyridoxine (vitamin B{sub 6}) and folic acid in aqueous solutions leads to their partial or total destruction, depending on the dose. The irradiation of pyridoxine and folic acid in the solid state mainly results in the elimination of hydrogen atoms (free radicals). After dissolving the irradiated samples in acid solutions it was observed that the irradiated molecule was renewed through replacement of the eliminated hydrogen atoms, which depend on the pH-value of the solution. This gives the possibility of sterilizing both pyridoxine and folic acid in the solid state by irradiation at 2 Mrad. Most of the radiolysis products of pyridoxine and folic acid irradiated in solution and in the solid state have been separated and identified by means of chromatography (paper and thin layer) and cellulose column electrophoresis. Electron spin resonance was used to determine the concentration and nature of the free radicals after irradiation of pyridoxine and folic acid in the solid state. (author) [French] On a Studie le comportement de la pyridoxine et de l'acide folique apres exposition aux rayons gamma ({sup 60}Co) et les changements dans leurs structures. L'irradiation de la pyridoxine (Vitamine B{sub 6}) et de l'acide folique en solutions aqueuses enttarne leur destruction partielle ou totale selon la dose. L'irradiation de la pyridoxine et de l'acide folique á l'etat solide enttarne principalement l'elimination d'atomes d'hydrogene (radicaux libres). Par dissolution des echanrilions irradies dans des solutions acides, on a observe un renouvellement de la molecule irradiee par remplacement des atomes d'hydrogene elimines qui est fonction du pH de la solution, ce qui permet de radiosteriliser a 2 Mrad á l'etat solide tant la pyridoxine que l'acide folique. On a separe et identifie la majorite des produits de radiolyse

  17. Acidity function p(a(H) gamma(Cl)) as a step to pH assessment.

    Science.gov (United States)

    Camões, Maria Filomena; Guiomar Lito, Maria

    2002-11-01

    The conventional assignment of pH reference buffer standards, pH(S), is achieved by means of a series of procedures that follow from measurement of Harned cell potentials for an electrolyte solution which is the buffer solution of interest. An intermediate step is assessment of the acidity function p( a(H) gamma(Cl))(0), the extrapolated value of a linear representation of the dependence of p( a(H) gamma(Cl)) on m(Cl) for at least three different molalities, m(Cl), of added alkali chloride (0.005; 0.010; 0.015 mol kg(-1) KCl). This experimental value can be compared with a theoretically expected value calculated from the dissociation constants of the buffer species. Whereas these calculations always give negative slopes for diprotic and triprotic acids and zero slope for monoprotic acids, experimental values with negative or positive slopes can be obtained for well fitting straight lines obtained for buffer solutions with ionic strengths from 0.0025 to 0.144 mol kg(-1). Such disagreement between theoretically and experimentally obtained values introduce an extra source of uncertainty in the establishment of pH(S) and on its traceability chain. In this work examples are presented and discussed for which the discrepancy between expected and experimental values leads to different intercept p( a(H) gamma(Cl))(0).

  18. Protective Role of Alpha Lipoic Acid Against Disorders Induced by Gamma Radiation

    International Nuclear Information System (INIS)

    Abd El Azeem, Kh.N.M.

    2011-01-01

    Ionizing radiation interacts with living cells, causing a variety of biochemical changes depending on exposed and absorbed doses, duration of exposure, interval after exposure and susceptibility of tissues to ionizing radiation. So, it may increase the oxidative stress and damage of body organs. Alpha-lipoic acid (ALA-also known as thioctic acid) appears to be readily absorbed from an oral dose and converts easily to its reduced form, dihydro lipoic acid (DHLA), in many tissues of the body. ALA can neutralize free radicals in both fatty and watery regions of cells. The present study has been designed to evaluate the possible efficiency of ALA as antioxidant and radio-protector against radiation induced oxidative stress in different organs (liver, kidney and heart) in rats through estimation of the activity of markers of serum liver, kidney and heart function, in addition to the histopathological differentiation of these organs by light and electron microscope. Five equal groups were conducted for the study: control, ALA (30 mg/kg body wt), irradiated (each rat was exposed to 6 Gy as a fractionated dose of gamma (γ) radiation), irradiated plus ALA (each rat received ALA for 9 days simultaneously during exposure) and ALA plus irradiation plus ALA groups (each rat received ALA for a week pre-exposure plus 9 days during exposure). Radiation doses were fractionated dose levels of 2 Gy each 3 days to reach accumulative dose of 6 Gy. After 3 days of each exposure rats were sacrificed, except, those left for recovery test one month after last exposure. The results revealed that whole body γ-irradiation of rats induces oxidative stress in liver, kidney and heart obviously manifested by significant elevation in alanine and aspartate transaminase ( ALT and AST), alkaline phosphatase (ALP), urea, creatinine and creatine kinase (CK-MB). ALA treated-irradiated rats showed lower significantly values indicating remarkable improvement in all measured parameters and

  19. Effects of gamma-radiation on some components of food and agricultural products (pyridoxine, folic acid, methionine)

    International Nuclear Information System (INIS)

    Gehlehtseanu, I.

    1974-01-01

    the effects of gamma radiation on individual components of food and agricultural products (Pyridoxine, folic acid, methionine) were investigated. Some of the studies have provided support for the hypothesis that the structural changes occurring in separately irradiated components of a foodstuff are greater than those taking place in the same components when present in the foodstuff. Results of irradiating pyridoxine and pyridoxal in an aqueous medium; of folic acid in aqueous solutions and in solid state; and of methionine in aqueous solutions and solid state, are given. (E.T.)

  20. Production of acetic acid from ethanol solution by acetobactor acetigenum and effect of gamma-ray irradiation on the bacteria

    International Nuclear Information System (INIS)

    Umar, J.M.; Matsuhashi, Shinpei; Hashimoto, Shoji.

    1996-03-01

    A preliminary study on fermentation of acetic acid by S. cerevisiae and A. acetigenum was carried out to obtain information to develop the effective utilization technology of agricultural liquid wastes. Aqueous solutions of glucose and/or ethanol were used as a model of agricultural liquid waste. The effect of gamma-ray irradiation on A. acetigenum for enhancement of the fermentation was also examined. In this study, irradiated A. acetigenum had activity to produce acetic acid even after loss the activity to grow. (author)

  1. Toxicological studies on the Use of acid applied or combined with gamma radiation for controlling the mediterranean fruit fly Ceratitis Capitata Wied

    International Nuclear Information System (INIS)

    Fadel, A.M.; Othman, K.S.A.

    1997-01-01

    Biological studies were conducted to determine the effect of boric acid applied alone to different stages of ceratitis capitata or combined with gamma radiation of the produced treated pupae (9 days old). At a concentration range of 200-2000 ppm of boric acid per gm larval diet, larval and pupal durations were insignificantly affected. Pupation significantly decreased with increasing concentration, and adult emergence significantly increased at higher concentrations. Lc50 value of boric acid applied to the larval diet was 250 ppm. Applying boric acid as a powder mixed with pupal medium, the Lc50 was 96 mg/gm sand. Male and emergence significantly decreased. Significant mortality was obtained in adults of C capitata after applying boric acid as a thin film on the inner surface of the experimental cages where the adults were kept or when mixed with their food or as powder on the cage bottom. Applying boric acid to larval diet and gamma radiation to the produced pupae (9 days old) insignificantly affected larval and durations, percent pupation, adult emergence or adult survival. In cross-mating experiments, egg hatch ability was significantly reduced in the combination treatments of boric acid (500, 1000 ppm) and gamma radiation (90 Gy). On the other hand gamma radiation combined with boric acid treatments significantly increased male mating competitiveness at the concentration of 1000 ppm of boric acid followed by gamma irradiation (90 Gy). 2 figs., 5 tabs

  2. Study of Gamma-Hydroxybutyric Acid (GHB Concentrations in Postmortem Blood and Urine

    Directory of Open Access Journals (Sweden)

    Huda M Hassan

    2015-12-01

    Full Text Available Gamma-hydroxybutyric acid (GHB is present in blood and urine of the general population as an endogenous compound. The published concentrations in postmortem blood ranged from 0-168 mg/L in cases with no previous history of GHB use. Interpretation of GHB results should be carefully considered due to the wide distribution of endogenous concentrations. The objectives of this study are to evaluate and verify the accuracy of a proposed published (50 mg/L cut-off in 120 blood and 64 urine samples in postmortem cases selected randomly, and to identify GHB-related fatalities. GHB was determined by gas chromatography– mass spectrometry (GC–MS after extraction of the blood and urine in the presence of the internal standard GHB-D6.  The GHB concentration in majority of the blood samples (95% was ≤ 50 mg/L, while in 81% it ranged from 10-50 mg/L. In 95% of the urine samples, the GHB concentration ranged from 10-20 mg/L while 82% of the samples had a concentration of 500 mg/L. The proposed published GHB concentration of 50 mg/L may be used as a cut-off to distinguish between natural endogenous concentrations and exogenous use, but this is not sufficient by itself. The detected GHB concentrations, both in vivo and in postmortem samples, require careful interpretation, not only due to its endogenous nature, but also due to the possibility of postmortem production and also due to its rapid metabolism and excretion.In order to distinguish the endogenous GHB concentration from those reflecting abusive GHB levels, defining a specific cut-off value in biological samples is very crucial. Other matrices, such as vitreous humour, femoral blood and hair must also be considered when interpreting postmortem GHB concentrations.

  3. Degradation of polylactic acid (Pla) at different doses of gamma radiation

    International Nuclear Information System (INIS)

    Castillo R, Y.

    2015-01-01

    The excessive use of polymers such as polyethylene (PET), polystyrene (Ps) and recently the polylactic acid (Pla) that take more than 20 years to degrade, have caused great pollution in the environment. In this study the effects of gamma radiation in the Pla to different doses were studied, in order to reduce the degradation time of this polymer. The changes in physico-chemical structure of Pla during radiation were studied by thermo-gravimetric/Mass analysis; differential scanning calorimetry; scanning electron microscopy; X-ray dispersive analysis; infrared spectroscopy; X-ray diffraction and mechanical tests of hardness, elasticity and deformation. With scanning electron microscopy, the morphology of the Pla surface unirradiated was observed, in which an apparently smooth surface was observed, after changes that had the Pla when irradiated also was observed, where the effects of radiation were observed in form of scratch, agglomeration and small fractures. By X-ray dispersive analysis was determined and verified the elemental chemical composition of the Pla; as expected the tests showed only carbon, oxygen and hydrogen. With thermo-gravimetric/Mass analysis the decomposition temperatures of Pla were determined, identifying that the degradation compounds are CO, CO 2 and CH 4 . With infrared spectrometry the major peaks of Pla were observed before and after being irradiated with increasing of radiation dose the intensity of the bands decreased. Also by X-ray diffraction was observed that the polymer is an amorphous material. The mechanical tests indicate that the values of each of the tests decrease significantly with increasing the radiation dose. (Author)

  4. Gamma-hydroxybutyric acid (GHB) and the mesoaccumbens reward circuit: evidence for GABA(B) receptor-mediated effects.

    Science.gov (United States)

    Pistis, M; Muntoni, A L; Pillolla, G; Perra, S; Cignarella, G; Melis, M; Gessa, G L

    2005-01-01

    Gamma-hydroxybutyric acid (GHB) is a short-chain fatty acid naturally occurring in the mammalian brain, which recently emerged as a major recreational drug of abuse. GHB has multiple neuronal mechanisms including activation of both the GABA(B) receptor, and a distinct GHB-specific receptor. This complex GHB-GABA(B) receptor interaction is probably responsible for the multifaceted pharmacological, behavioral and toxicological profile of GHB. Drugs of abuse exert remarkably similar effects upon reward-related circuits, in particular the mesolimbic dopaminergic system and the nucleus accumbens (NAc). We used single unit recordings in vivo from urethane-anesthetized rats to characterize the effects of GHB on evoked firing in NAc "shell" neurons and on spontaneous activity of antidromically identified dopamine (DA) cells located in the ventral tegmental area. GHB was studied in comparison with the GABA(B) receptor agonist baclofen and antagonist (2S)(+)-5,5-dimethyl-2-morpholineacetic acid (SCH50911). Additionally, we utilized a GHB analog, gamma-(p-methoxybenzil)-gamma-hydroxybutyric acid (NCS-435), devoid of GABA(B) binding properties, but with high affinity for specific GHB binding sites. In common with other drugs of abuse, GHB depressed firing in NAc neurons evoked by the stimulation of the basolateral amygdala. On DA neurons, GHB exerted heterogeneous effects, which were correlated to the baseline firing rate of the cells but led to a moderate stimulation of the DA system. All GHB actions were mediated by GABA(B) receptors, since they were blocked by SCH50911 and were not mimicked by NCS-435. Our study indicates that the electrophysiological profile of GHB is close to typical drugs of abuse: both inhibition of NAc neurons and moderate to strong stimulation of DA transmission are distinctive features of diverse classes of abused drugs. Moreover, it is concluded that addictive and rewarding properties of GHB do not necessarily involve a putative high affinity GHB

  5. Anisotropy in CNT composite fabricated by combining directional freezing and gamma irradiation of acrylic acid

    Czech Academy of Sciences Publication Activity Database

    Osička, J.; Ilčíková, M.; Mrlík, M.; Al-Maadeed, M. A. S. A.; Šlouf, Miroslav; Tkac, J.; Kasák, P.

    2016-01-01

    Roč. 97, 5 May (2016), s. 300-306 ISSN 0261-3069 Institutional support: RVO:61389013 Keywords : directional freezing * gamma irradiation * carbon nanotubes Subject RIV: CD - Macromolecular Chemistry Impact factor: 3.997, year: 2015

  6. Restoration of Respiratory Gases and Acid-base Balance of Blood of Gamma Irradiated Rats Through Bone Marrow Transplantation

    International Nuclear Information System (INIS)

    Eissa, S.M.; Roushdy, H.M.; Khamis, F. I.; Abu-Zeid, N.M.

    2000-01-01

    The present investigation aimed at elucidating the role played by bone marrow transplantation as a biological treatment against the deleterious effect of ionizing radiation. The parameters tested were PO2; PCO2; TCO2 and acid base balance encountering pH and (HCO3) in blood. Investigations were conducted 1,3,7,14 and 21 days post whole body gamma exposure at the dose levels 2 and 6 Gy. The data obtained showed highly significant changes in all tested parameters after whole body gamma irradiation. A higher depressant effect was more pronounced after exposure to higher radiation dose. Bone marrow transplantation to irradiated rats resulted in partial restoration or the radiation induced changes in both PO2 and PCO2 as recorded on the first week post treatment and succeeded to ameliorate the radiation induced changes in pH values and (HCO3) in blood

  7. Effect of gamma-irradiation on the fatty acid composition of salted, semi-dried Vietnamese scad and Bombay duck

    International Nuclear Information System (INIS)

    Vinh, P.Q.; Rao, V.S.; Adhikar, H.R.; Nair, P.M.

    1994-01-01

    Effect of gamma irradiation on the lipid and fatty acid composition of semi-dried Bombay duck (Harpodon nehcreus) and Vietnamese scad (Alepes mate) was studied. In both these dried fishes, c16:0 aand c18:1 were the predominant fatty acids and the fishes contained ignificant quantities of the n-3 polyunsaturated fatty acids (PUFAs), C20:5 and C22:6. Irradiation at a dose of 3 kGy, did not cause any alterations in the total lipid content and he overall lipid class profile in these fishes. However, in the Vietnamese scad, C18:3, C20:4 and C22:6 were significantly decreased in the irradiated samples. In spite of this decrease the irradiated semi-dried scad retained 82% of the initial amount of n-3 PUFAs

  8. Effects of gamma irradiation and storage temperature on carotenoids and ascorbic acid content of mangoes on ripening

    International Nuclear Information System (INIS)

    Thomas, P.; Janave, M.T.

    1975-01-01

    Synthesis and accumulation of carotenoids in the flesh of Alphonso mangoes on ripening was found to be maximal in fruits stored at tropical ambient temperatures (28 0 to 32 0 C). Gamma irradiation of preclimacteric fruits at 25 krad did not affect the formation of carotenoids. Storage of preclimacteric fruits either irradiated or unirradiated at 7 to 20 0 C for 16 to 43 days caused a substantial reduction in carotenoid formation even when these fruits were subsequently ripened under optimal conditions. Regardless of storage temperature, carotenes always exceeded xanthophylls in the ripe fruits and, in general, irradiated fruits showed higher levels of carotenes in comparison with unirradiated samples. Ascorbic acid loss during ripening was maximum at ambient temperatures while lengthy storage at low temperatures caused a net increase in ascorbic acid levels. Irradiation seemed to accentuate the loss in ascorbic acid during ripening. (author)

  9. IPN's of Acrylic Acid and N-Isopropylacrylamide by Gamma and Electron Beam Irradiation

    International Nuclear Information System (INIS)

    Burillo, G.

    2006-01-01

    In recent years, temperature and pH sensitive hydrogels have been investigated widely because of their unique properties and versatile applications in medicine and biotechnology, as well as drug delivery. However a serious limitation of hydrogels in many applications is the low mechanical strength of such gels when highly swollen. To overcome this problem, sensitive hydrogels were prepared with satisfactory mechanical properties as a semi-interpenetranting network, where one of them is a mechanically stable polymer. In this work temperature sensitive monomer N-isopropylacrylamide (NIPAAm) and a pH sensitive monomer, acrylic acid (AAc) were prepared as an interpenetranting network by a sequential method. Poly (AAc) hydrogels were prepared in glass tubes 3 mm inner diameter, at room temperature from an aqueous solutions 50%vol under argon atmosphere, and irradiated with a Co 6 0 gamma source, at doses from 5 to 30 kGy and dose rate of 3 kGy/h. Poly (AAc) hydrogels were also prepared by electron beam irradiation with a Van de Graaff at a dose rate of 19.4 kGy/min, and radiation doses from 10 to 30 kGy. After polymerization and crosslinking, the gels were washed in water during 48 h, and dried in vacuo to constant weight. Poly (NIPAAm) as secondary gel was synthetized directly within the primary gels in aqueous solution with the croslinker N, N' methylenebisacrylamide (BIS), the accelerator N,N,N , N tetramethyl ethylenediamidne TMEDA, and potasium persulfate as initiator. Equilibrium swelling properties of hydrogels were studied in pH 2.2-8 range and temperature 10-45degree; LCST and pH critic point of the IPN's were determined; the composition of the interpenetrating network was measured by elemental analysis, and the morphological structure characterized by SEM. The volume of the cells of PAAC hydrogels decreased with increase in radiation dose, their mechanic hardness increased and they lost elasticity. The interpenetrating networks of samples with PAAc irradiated

  10. The effect of heart-and kidney-Benefiting Chinese Herbal Medicine on the function of cholinergic M-and Gamma amino-butyric acid (GABA) receptor in brain tissues of analogue dementia rats

    International Nuclear Information System (INIS)

    Mo Qizhong; Gong Bin; Fang Jun

    1993-01-01

    3 H-QNB and 3 H-GABA were used as radioactive ligand for M-and GABA receptors respectively. M-and GABA receptors were assayed by radioligand binding assay (RBA) in cerebral cortex, hippocampus and cerebellum of analogue dementia rats. It was found that R t of M receptor was decreased in cerebral cortex and hippocampus and R t of GABA receptor was decreased in cerebellum of analogue dementia rats. The dissociation constant (K D ) of M-receptor was decreased significantly in cerebral cortex and K D value of (GABA) receptor was decreased in cerebellum of analogue dementia rats. The decreased R t of M-and GABA receptor in brain tissue of analogue dementia rats was raised by Heart- and Kidney-Benefiting Chinese Herbs as well as hydergin

  11. The effect of heart-and kidney-Benefiting Chinese Herbal Medicine on the function of cholinergic M-and Gamma amino-butyric acid (GABA) receptor in brain tissues of analogue dementia rats

    Energy Technology Data Exchange (ETDEWEB)

    Qizhong, Mo; Bin, Gong; Jun, Fang [Shanghai College of TCM, Shanghai (China); and others

    1993-05-01

    [sup 3]H-QNB and [sup 3]H-GABA were used as radioactive ligand for M-and GABA receptors respectively. M-and GABA receptors were assayed by radioligand binding assay (RBA) in cerebral cortex, hippocampus and cerebellum of analogue dementia rats. It was found that R[sub t] of M receptor was decreased in cerebral cortex and hippocampus and R[sub t] of GABA receptor was decreased in cerebellum of analogue dementia rats. The dissociation constant (K[sub D]) of M-receptor was decreased significantly in cerebral cortex and K[sub D] value of (GABA) receptor was decreased in cerebellum of analogue dementia rats. The decreased R[sub t] of M-and GABA receptor in brain tissue of analogue dementia rats was raised by Heart- and Kidney-Benefiting Chinese Herbs as well as hydergin.

  12. (QTLs) for γ- aminobutyric acid content in grain of barley

    African Journals Online (AJOL)

    Yomi

    2012-01-24

    Jan 24, 2012 ... protein content, while Schooner is a hull two-rowed cultivar malting barley with low ... being kept at 20°C for 4~8 min, the mixture was heated in a boiling water bath for ..... John Wiley & Sons, Inc. Hobokwen, New Jersey. Nie C ...

  13. The four human ¿-aminobutyric acid (GABA) transporters

    DEFF Research Database (Denmark)

    Kvist, Trine; Christiansen, Bolette; Jensen, Anders Asbjørn

    2009-01-01

    in high throughput screening. We find that the assay is categorized by high Z'-factors (Z' > 0.5) for all four GAT subtypes, demonstrating that the assay is excellent for a high throughput screen. This [3H]GABA uptake assay therefore enables future high through put screening of compound libraries...

  14. Ameliorative effect of salicylic acid and theophylline on photosynthetic pigment content in gamma irradiated french bean varieties, using "6"0Co as a source

    International Nuclear Information System (INIS)

    Shukla, Pradeep K.; Vishwakarma, Kapil Kumar; Shukla, Saumya; Sharma, Richa; Ramteke, P.W.; Misra, Pragati

    2017-01-01

    Irradiation of seeds may cause genetic variability that enable plant breeders to select new genotypes with improved qualitative and quantitative characteristics. An experiment was conducted to study the protective role of salicylic acid and theophylline on photosynthetic pigments of gamma exposed french bean. Seeds of four French bean were treated by different doses of gamma radiation using "6"0Co as source. The results showed that the application of salicylic acid and theophylline significantly increased chlorophyll a content, chlorophyll b content, total chlorophyll content and carotenoid content. Salicylic acid was more effective than theophylline in overcoming the radiation effects and therefore, showed more protection to the photosynthetic pigments. (author)

  15. Gamma radiation and temperature influence on the chemical effect produced by isomeric transition in the telluric acid

    International Nuclear Information System (INIS)

    Muriel G, M.

    1976-01-01

    When the gamma radiation due to the isomeric transition is internally converted an autoionization is produced. For atoms with a high atomic number this autoionization can be a large one and produce a fragmentation in a molecule. In the specific case of the solid state these fragments remain trapped in different places of the crystalline system. This can be considered as chemical change in the original molecule. These damages produced by the nuclear transformation can be measured by different methods: heating, gamma rays, pressure, etc. In this work the results of an experimental measurement of the behavior of the crystalline telluric acid molecule fragments under gamma radiation (0 to 20 Mrads) with controlled temperature of 2 0 C (-196 0 C to 50 0 C) it is presented. It was observed that the values of the mentioned behavior vary rapidly at first for relatively low doses and that for larger doses these values remained constant. Besides with a lower temperature these variation are progressively lower. (author)

  16. Effects of gamma-irradiation on elongation and indole-3-acetic acid level of maize (Zea mays) coleoptiles

    International Nuclear Information System (INIS)

    Momiyama, M.; Koshiba, T.; Furukawa, K.; Kamiya, Y.; Sato, M.

    1999-01-01

    The effects of gamma-irradiation on elongation and the level of indole-3-acetic acid (IAA) of maize (Zea mays) coleoptiles were investigated. When 3-day-old seedlings of maize were exposed to gamma-radiation lower than 1 kGy, a temporal retardation of coleoptile elongation was induced. This retardation was at least partly ascribed to a temporal decrease in the amount of free IAA in coleoptile tips on the basis of the following facts: (1) the reactivity to IAA of the elongating coleoptile cells was not altered by irradiation; (2) endogenous IAA level in the tip of irradiated coleoptiles was at first unchanged, but then declined before returning to nearly the same level as that of the non-irradiated control; and (3) the amount of IAA that diffused from coleoptile tip sections showed a similar pattern to that of endogenous IAA. The rate of conversion between free and conjugated IAA was not significantly affected by irradiation. These results suggest that a temporal inhibition of maize coleoptile elongation induced by gamma-irradiation can be ascribed to the reduction of endogenous IAA level in the coleoptile tip, and this may originate from the modulation in the rate of IAA biosynthesis or catabolism. (author)

  17. Effect of gamma irradiation on physicochemical properties of commercial poly(lactic acid) clamshell for food packaging

    International Nuclear Information System (INIS)

    Madera-Santana, Tomás J.; Meléndrez, R.; González-García, Gerardo; Quintana-Owen, Patricia; Pillai, Suresh D.

    2016-01-01

    Poly(lactic acid) (PLA) is a well-known biodegradable polymer with strong potential application in food packaging industry. In this paper, samples of PLA clamshell for tomatoes packaging were exposed with 60 CO γ-ray's source (1.33 MeV) at different dose levels (0, 10, 60, 150, 300, and 600 kGy), at room temperature and in presence of air. The physicochemical properties of neat PLA and sample exposed to gamma irradiation were investigated using Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), gel permeation chromatography (GPC), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), scanning electron microscopy (SEM) and tensile measurements. Results show as the dose increases, the molecular weight (M w ), melting temperature (T m ), tensile strength and elongation at break decreased. However, the tensile modulus increased with increasing doses. The surface of PLA clamshells was degraded (scratches and minor cracks) when samples were exposed to doses greater than 60 kGy. - Highlights: • The gamma irradiation effects on PLA clamshells were studied. • DSC, XRD, NMR and FTIR analysis were used for PLA clamshell characterization. • The M w , T m , strength and elongation of the irradiated PLA clamshells decreased. • The tensile modulus increased with increasing gamma doses. • The Surface of PLA clamshell showed scratches and minor cracks.

  18. The influence of feeding linoleic, gamma-linolenic and docosahexaenoic acid rich oils on rat brain tumor fatty acids composition and fatty acid binding protein 7 mRNA expression

    Directory of Open Access Journals (Sweden)

    Abdi Khosro

    2008-11-01

    Full Text Available Abstract Background Experimental studies indicate that gamma linolenic acid (GLA and docosahexaenoic acid (DHA may inhibit glioma cells growth but effects of oral consumption of these fatty acids on brain tumor fatty acid composition have not been determined in vivo. Methods GLA oil (GLAO; 72% GLA, DHA oil (DHAO; 73% DHA were fed to adult wistar rats (1 mL/rat/day starting one week prior to C6 glioma cells implantation and continued for two weeks after implantation. Control group were fed same amount of high linoleic acid safflower oil (74–77% linoleic acid. Fatty acid composition of tumor samples was determined in a set of 8–12 animals in each group and serum fatty acid in 6 animals per each group. Gene expression of tumor fatty acid binding protein 7 (FABP7, epidermal growth factor receptor (EGFR, peroxisome proliferator activated receptor γ (PPAR-γ and retinoid × receptor-α (RXR-α were determined in a set of 18 animals per group. Results DHAO feeding increased EPA of brain tumors and decreased ratio of n-6/n-3 fatty acids. Serum levels of EPA were also increased in DHAO group. A similar trend in serum and tumor levels of DHA were observed in DHAO group but it did not achieve statistical significance. GLAO increased serum concentration of GLA but had no significant effect on tumor GLA or dihomo-gamma linolenic acid (DGLA concentrations. Gene expression of FABP7 was up-regulated in tumors of DHAO group but no other significant effects were observed on EGFR, PPAR-γ or RXR-α expression, and expression of these genes in tumors of GLAO were not different from SFO group. Conclusion Dietary supplementation of DHA containing oil could be an effective way to increase levels of long chain n-3 fatty acids in brain tumors and this increase may be mediated partly by up-regulation of FABP7 expression.

  19. Beta-and gamma-turns in proteins revisited: a new set of amino acid turn-type dependent positional preferences and potentials.

    Science.gov (United States)

    Guruprasad, K; Rajkumar, S

    2000-06-01

    The number of beta-turns in a representative set of 426 protein three-dimensional crystal structures selected from the recent Protein Data Bank has nearly doubled and the number of gamma-turns in a representative set of 320 proteins has increased over seven times since the previous analysis. Beta-turns (7153) and gamma-turns (911) extracted from these proteins were used to derive a revised set of type-dependent amino acid positional preferences and potentials. Compared with previous results, the preference for proline, methionine and tryptophan has increased and the preference for glutamine, valine, glutamic acid and alanine has decreased for beta-turns. Certain new amino acid preferences were observed for both turn types and individual amino acids showed turn-type dependent positional preferences. The rationale for new amino acid preferences are discussed in the light of hydrogen bonds and other interactions involving the turns. Where main-chain hydrogen bonds of the type NH(i + 3) --> CO(i) were not observed for some beta-turns, other main-chain hydrogen bonds or solvent interactions were observed that possibly stabilize such beta-turns. A number of unexpected isolated beta-turns with proline at i + 2 position were also observed. The NH(i + 2) --> CO(i) hydrogen bond was observed for almost all gamma-turns. Nearly 20% classic gamma-turns and 43% inverse gamma-turns are isolated turns.

  20. Cation Exchange Efficiency Of Modified Bentonite Using In-Situ GAMMA Radiation Polymerization Of Acrylic Acid Or Acrylamide

    International Nuclear Information System (INIS)

    ISMAIL, S.A.; FALAZI, B.

    2009-01-01

    Modified bentonites as cation exchangers were prepared by treating raw bentonite with 3N NaOH at 95 0 C followed by in-situ polymerization using gamma irradiation as well as hydrogen peroxide initiation of acrylic acid or acrylamide in the matrix.Water swelling and acid capacity were determined and cation exchange capacity for Cu 2+ , Ni 2+ and Co 2+ was evaluated. It has been found that catiexchange capacity of treated bentonite was increased as result of formed polyacrylic acid and polyacrylamide in the matrix. In case of acrylic acid, the maximum cation exchange capacities of 3.5, 3.1 and 2.5 mg equivalent/g were determined for Cu 2+ , Ni 2+ and Co 2+ , respectively, and for acrylamide, the corresponding capacities were 2.9, 2.8 and 2.6 mg equivalent/g, respectively. Water swelling was found to be associated with holding large amounts of water, for instance, 49 g of water was sorbed per one gram of the sodium salt form of polyacrylic acid in bentonite matrix, in other words the degree of swelling in water achieved 4500%.

  1. Acid base balance in the rabbit following whole-body gamma irradiation

    International Nuclear Information System (INIS)

    Bassant, M.-H.; Touchard, Francoise; Court, Louis

    1981-01-01

    2 hrs. after whole-body gamma irradiation (doses of 1.5 and 4.5 Gy) a metabolic acidosis developed in curarised Rabbits placed under artificial respiration in order to eliminate radiation-induced respiratory effect. The metabolic acidosis was evaluated by measurement of the negative base excess. The results were compared to others obtained under different experimental procedures [fr

  2. Acid base balance in the rabbit following whole-body gamma irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Bassant, M.H.; Touchard, F.; Court, L. (CEA Centre d' Etudes Nucleaires de Fontenay-aux-Roses, 92 (France). Dept. de Recherches sur la Fusion Controlee)

    1981-07-06

    2 hrs. after whole-body gamma irradiation (doses of 1.5 and 4.5 Gy) a metabolic acidosis developed in curarised rabbits placed under artificial respiration in order to eliminate radiation-induced respiratory effect. The metabolic acidosis was evaluated by measurement of the negative base excess. The results were compared to others obtained under different experimental procedures.

  3. Sterilization by Gamma-Radiation of the Sodium Salt of p-Amino-Salicylic Acid

    International Nuclear Information System (INIS)

    Bellion, B.; Denti, E.; Massagli, A.

    1963-01-01

    Sodium p-amino-salicylate cannot be sterilized thermally. During manufacture or packing for medical purposes it must therefore be handled under sterilized conditions, with all the difficulties which this involves. The paper quotes experimental data to show that, using gamma irradiation, the product may be sterilized without damage and without the formation of substances harmful from the medical standpoint. (author) [fr

  4. EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA); Scientific Opinion on the substantiation of health claims related to docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA) and gamma-linolenic acid (GLA) and contribution to normal cognitive function (ID 532) and maintenance

    DEFF Research Database (Denmark)

    Tetens, Inge

    claims in relation to docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA) and gamma-linolenic acid (GLA) and contribution to normal cognitive function and maintenance of normal bone. The scientific substantiation is based on the information provided by the Member States in the consolidated list...... and fish oil”. From the references provided, the Panel assumes that the food constituents that are the subject of the claims are the n-6 fatty acid gamma-linolenic acid (GLA) in evening primrose oil and the n-3 long-chain polyunsaturated fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA...... of Article 13 health claims and references that EFSA has received from Member States or directly from stakeholders. The food constituents that are the subjects of the health claims are “omega-3 and omega-6 fatty acids (GLA)”, “gamma-linolenic acid + eicosapentaenoic acid (GLA+EPA)”, and “evening primrose oil...

  5. Nucleic acids in the mosquito, Culex Pipiens L. As affected by Gamma irradiation of the pupae. Vol. 4

    International Nuclear Information System (INIS)

    Kansouh, A.H.; Amin, A.H.; Shoman, A.A.; Wakid, A.M.; Aly, M.A.S.

    1996-01-01

    Pupae of the mosquito, Culex Pipiens L. Were gamma-irradiated with 3 doses (40, 60 and 80 Gy) and compared with nonirradiated group for nucleic acids in the newly emerged adults; 24, 48 and 72 hours post-emergence. Nucleic acids were estimated in starved adults or blood-fed females. The results showed that RNA content in the normal or irradiated unfed males or females decreased with time after emergence. Irradiation at different doses decreased RNA content in males after 48 and 72 hours. However, in females, irradiation at low doses had no effect after 24 hours but the effect was clear after 48 and hours. Gamma irradiation led to decreased RNA content in females after 72 hours post feeding on blood. This decrease was insignificant at 40 Gy but highly significant at 60 and 80 Gy. Normal males had a constant DNA content at all periods. However, irradiation reduced this content at 40 and 60 Gy, especially after 72 hours. At 80 Gy, DNA showed an increase at first then was reduced reaching the control value after 72 hours. Irradiation and time slightly reduced the DNA content, especially at 72 hours. Irradiation with 60 and 80 Gy showed a pronounced increase in DNA content in the blood-fed females 72 hours post feeding. The RNA/DNA ratio decreased by irradiation of non-fed males and females, while in the control blood-fed females, this ratio was higher after 72 hours post feeding than that unfed ones. The ratio decreased in irradiated females with increasing gamma dose after 72 hours post feeding. 8 figs

  6. Nucleic acids in the mosquito, Culex Pipiens L. As affected by Gamma irradiation of the pupae. Vol. 4

    Energy Technology Data Exchange (ETDEWEB)

    Kansouh, A H; Amin, A H; Shoman, A A [Plant protection Dept., Fac. of Agriculture, Ain Shams Univ. Cairo (Egypt); Wakid, A M [Applied Biology Dept., NRC, Atomic Energy Authority. Cairo (Egypt); Aly, M A.S. [Radio Isotope Dept., NBC, Atomic Energy Authority. Cairo (Egypt)

    1996-03-01

    Pupae of the mosquito, Culex Pipiens L. Were gamma-irradiated with 3 doses (40, 60 and 80 Gy) and compared with nonirradiated group for nucleic acids in the newly emerged adults; 24, 48 and 72 hours post-emergence. Nucleic acids were estimated in starved adults or blood-fed females. The results showed that RNA content in the normal or irradiated unfed males or females decreased with time after emergence. Irradiation at different doses decreased RNA content in males after 48 and 72 hours. However, in females, irradiation at low doses had no effect after 24 hours but the effect was clear after 48 and hours. Gamma irradiation led to decreased RNA content in females after 72 hours post feeding on blood. This decrease was insignificant at 40 Gy but highly significant at 60 and 80 Gy. Normal males had a constant DNA content at all periods. However, irradiation reduced this content at 40 and 60 Gy, especially after 72 hours. At 80 Gy, DNA showed an increase at first then was reduced reaching the control value after 72 hours. Irradiation and time slightly reduced the DNA content, especially at 72 hours. Irradiation with 60 and 80 Gy showed a pronounced increase in DNA content in the blood-fed females 72 hours post feeding. The RNA/DNA ratio decreased by irradiation of non-fed males and females, while in the control blood-fed females, this ratio was higher after 72 hours post feeding than that unfed ones. The ratio decreased in irradiated females with increasing gamma dose after 72 hours post feeding. 8 figs.

  7. Seasonal changes in amino acids, protein and total nitrogen in needles of fertilized Scots pine trees.

    Science.gov (United States)

    Näsholm, T; Ericsson, A

    1990-09-01

    Seasonal changes in amino acids, protein and total nitrogen in needles of 30-year-old, fertilized Scots pine (Pinus sylvestris L.) trees growing in Northern Sweden were investigated over two years in field experiments. The studied plots had been fertilized annually for 17 years with (i) a high level of N, (ii) a medium level of N, or (iii) a medium level of N, P and K. Trees growing on unfertilized plots served as controls. In control trees, glutamine, glutamic acid, gamma-aminobutyric acid, aspartic acid and proline represented 50-70% of the total free amino acids determined. Arginine was present only in low concentrations in control trees throughout the year, but it was usually the most abundant amino acid in fertilized trees. Glutamine concentrations were high during the spring and summer in both years of study, whereas proline concentrations were high in the spring but otherwise low throughout the year. In the first year of study, glutamic acid concentrations were high during the spring and summer, whereas gamma-aminobutyric acid was present in high concentrations during the winter months. This pattern was less pronounced in the second year of investigation. The concentrations of most amino acids, except glutamic acid, increased in response to fertilization. Nitrogen fertilization increased the foliar concentration of arginine from trees to a maximum of 110 micromol g(dw) (-1). Trees fertilized with nitrogen, phosphorus and potassium had significantly lower arginine concentrations than trees fertilized with the same amount of nitrogen only. Protein concentrations were similar in all fertilized trees but higher than those in control trees. For all treatments, protein concentrations were high in winter and at a minimum in early spring. In summer, the protein concentration remained almost constant except for a temporary decrease which coincided with the expansion of new shoots. Apart from arginine, the amino acid composition of proteins was similar in all

  8. Effect of Omega-3 Fatty Acids on Neurotransmitters Level in the Brain of Male Albino Rats Exposed to Gamma Irradiation

    International Nuclear Information System (INIS)

    Saada, H.N.; Said, U.Z.; Shedid, S.M.; Mahdy, E.M.E.; Elmezayen, H.E.

    2014-01-01

    The omega-3 fatty acids are essential dietary nutrients, and one of their important roles is providing docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) for growth and function of nervous tissue. Reduced level of DHA in the brain induce dramatic changes in brain function including changes in size of neurons as well as changes in learning and memory. The objective of this study was to evaluate the role of fish oil rich in omega-3 fatty acids on γ-radiation-induced physiological changes in the brain cerebral hemispheres. Omega-3 fatty acids was supplemented daily by gavages to rats at a dose of 400 mg/ kg body wt for 7 days pre- and 21 days post-exposure to whole body fractionated gamma rays at doses of 2 Gy/week up to a total dose of 8 Gy. The results demonstrated that whole body γ-irradiation induced oxidative stress, de - creased the main polyunsaturated fatty acids; DHA and EPA, and induced neurotransmitters alteration in brain tissues. Oxidative stress was manifested by a significant increase in lipid peroxidation product malondialdehyde (MDA) and decrease in the activity of antioxidant enzymes, superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px). Oxidative stress was accompanied by alterations in the level of the neurotransmitters manifested by a significant increase of glutamic and aspartic and a significant decrease of serotonin (5-HT) levels in brain cerebral hemispheres. Rats receiving fish oil 7 days before and 21 days after exposure to γ-radiation showed significant improvement in the levels of EPA and DHA associated with significant amelioration of oxidative stress and neurotransmitters alteration. It is concluded that fish oil protect the brain from radiation-induced physiological changes by protecting brain cellular membranes through counteracting the decrease of omega-3 fatty acids and minimizing oxidative stress

  9. Evaluation of gamma irradiation effects on carotenoids, ascorbic acid and sugar contents of buriti fruit (Mauritia flexuosa L.)

    International Nuclear Information System (INIS)

    Lima, Antonio Luis dos Santos; Lima, Keila dos Santos Cople; Silva, Jaqueline Michele; Coelho, Maysa Joppert; Godoy, Ronoel Luiz de Oliveira; Pacheco, Sidney

    2009-01-01

    Buriti (Mauritia flexuosa L.), a typical fruit from the Northeast and Center-West Amazon of Brazil, is used in many regional dishes. It is considered an excellent source of carotenoids that are A vitamin precursors, showing a majority of beta-carotene. It also presents ascorbic acid and sugar contents. Many studies have indicated that the lack of A vitamin is the main cause of night blindness and xerophthalmia. Also, ascorbic acid deficiency may cause scorbutic disease. The use of food irradiation is growing and represents an economic benefit to agriculture through the reduction of post-harvesting losses while maintaining food nutritional quality. In this study, buriti in natura was treated with gamma irradiation with doses of 0.5 kGy and 1.0 kGy. The objective was to evaluate the irradiation effects on total carotenoids, ascorbic acid and sugars concentrations of buriti. The fruit was evaluated through the total carotenoids analysis, by spectrophotometry, and the carotenoids (alpha and beta-carotene and lutein), ascorbic acid and sugars were determined by high performance liquid chromatography (HPLC). The results showed that buriti is an excellent source of total carotenoids (44600 μg/100 g). The irradiation of buriti with the dose of 0.5 kGy did not significantly change carotenoids and sugars contents. However, there was a reduction of ascorbic acid concentration with an increase of the dose, which may have been caused by irradiation or by intrinsic and extrinsic factors that alter ascorbic acid stability in food, converting ascorbic to dehydroascorbic acid, while keeping the C vitamin active form. (author)

  10. Effects of roasting temperatures and gamma irradiation on the content of chlorogenic acid, caffeic acid and soluble carbohydrates of coffee

    International Nuclear Information System (INIS)

    Deshpande, S.N.; Aguilar, A.A.

    1975-01-01

    Two varieties of Puerto Rican coffee, Coffea canephora L. var. Robusta, and Coffea arabica L. var. Borbon, were subjected to four different doses of radiation and roasted at two different temperatures. Aqueous extracts of the ground coffee beans were analyzed for chlorogenic acid and caffeic acid at 324 nm and 360 nm wavelength settings, respectively. Samples subjected to the roasting treatments in conjuction with irradiation treatments were treated with basic lead acetate prior to the colorimetric analyses in order to eliminate interfering substances. The total carbohydrate content was also determined by colorimetric techniques with anthrone reagent. The total nitrogen content of the pulverized samples were determined by the micro-Kjeldahl method. While roasting treatments caused a reduction in the concentrations of the chlorogenic acid, caffeic acid, and the carbohydrates, the radiation treatments increased the concentrations of soluble carbohydrates without affecting the concentrations of chlorogenic acid or caffeic acid. It therefore appears that radiation treatments seem to cause degradation of the acid-polysaccharide complexes liberating soluble sugars. There were no noticable changes in the total content of nitrogen caused by roasting or the radiation treatments as indicated by the statistical analysis employing the split plot design. (author)