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Sample records for systemic monosodium glutamate

  1. Systemic administration of monosodium glutamate elevates intramuscular glutamate levels and sensitizes rat masseter muscle afferent fibers.

    Science.gov (United States)

    Cairns, Brian E; Dong, Xudong; Mann, Mandeep K; Svensson, Peter; Sessle, Barry J; Arendt-Nielsen, Lars; McErlane, Keith M

    2007-11-01

    There is evidence that elevated tissue concentrations of glutamate may contribute to pain and sensitivity in certain musculoskeletal pain conditions. In the present study, the food additive monosodium glutamate (MSG) was injected intravenously into rats to determine whether it could significantly elevate interstitial concentrations of glutamate in the masseter muscle and whether MSG administration could excite and/or sensitize slowly conducting masseter afferent fibers through N-methyl-D-aspartate (NMDA) receptor activation. The interstitial concentration of glutamate after systemic injection of isotonic phosphate-buffered saline (control) or MSG (10 and 50mg/kg) was measured with a glutamate-selective biosensor. The pre-injection baseline interstitial concentration of glutamate in the rat masseter muscle was 24+/-11 microM. Peak interstitial concentration after injection of 50mg/kg MSG was 63+/-18 microM and remained elevated above baseline for approximately 18 min. In vivo single unit recording experiments were undertaken to assess the effect of MSG (50mg/kg) on masseter afferent fibers. Injection of MSG evoked a brief discharge in one afferent fiber, and significantly decreased ( approximately 25%) the average afferent mechanical threshold (n=10) during the first 5 min after injection of MSG. Intravenous injection of ketamine (1mg/kg), 5 min prior to MSG, prevented the MSG-induced decreases in the mechanical threshold of masseter afferent fibers. The present results indicate that a 2- to 3-fold elevation in interstitial glutamate levels in the masseter muscle is sufficient to excite and induce afferent mechanical sensitization through NMDA receptor activation. These findings suggest that modest elevations of interstitial glutamate concentration could alter musculoskeletal pain sensitivity in humans.

  2. Genotoxicity of monosodium glutamate.

    Science.gov (United States)

    Ataseven, Nazmiye; Yüzbaşıoğlu, Deniz; Keskin, Ayten Çelebi; Ünal, Fatma

    2016-05-01

    Monosodium glutamate (MSG) is one of the most widely used flavor enhancers throughout the world. The aim of this study is to investigate the genotoxic potential of MSG by using chromosome aberrations (CAs), sister-chromatid exchanges (SCEs), cytokinesis-blocked micronucleus (CBMN), and random amplified polymorphic DNA-polimerase chain reaction (RAPD-PCR) in cultured human lymphocytes and alkaline comet assays in isolated human lymphocytes, which were incubated with six concentrations (250, 500, 1000, 2000, 4000 and 8000 μg/mL) of MSG. The result of this study indicated that MSG significantly and dose dependently increased the frequencies of CAs, SCE and MN in all treatments and times, compared with control. However, the replication (RI) and nuclear division indices (NDI) were not affected. In this paper, in vitro genotoxic effects of the MSG was also investigated on human peripheral lymphocytes by analysing the RAPD-PCR with arbitrary 10-mer primers. The changes occurring in RAPD profiles after MSG treatment include increase or decrease in band intensity and gain or loss of bands. In the comet assay, this additive caused DNA damage at all concentrations in isolated human lymphocytes after 1-h in vitro exposure. Our results demonstrate that MSG is genotoxic to the human peripheral blood lymphocytes in vitro. Copyright © 2016. Published by Elsevier Ltd.

  3. Muscle pain sensitivity after glutamate injection is not modified by systemic administration of monosodium glutamate.

    Science.gov (United States)

    Shimada, Akiko; Castrillon, Eduardo; Baad-Hansen, Lene; Ghafouri, Bijar; Gerdle, Björn; Ernberg, Malin; Cairns, Brian; Svensson, Peter

    2015-01-01

    Monosodium glutamate (MSG) is often thought to be associated with headache and craniofacial pains like temporomandibular disorders. This randomized, double-blinded, placebo-controlled study was performed to investigate how ingestion of MSG affects muscle pain sensitivity before and after experimentally induced muscle pain. Sixteen healthy adult subjects participated in 2 sessions with at least 1-week interval between sessions. In each session, two injections of glutamate (Glu, 0.5 M, 0.2 ml) and two injections of saline (0.9%, 0.2 ml) into the masseter and temporalis muscles, respectively, were undertaken, with a 15 min interval between each injection. Injections of saline were made contralateral to Glu injections and done in a randomized order. Participants drank 400 mL of soda mixed with either MSG (150 mg/kg) or NaCl (24 mg/kg, placebo) 30 min before the intramuscular injections. Pressure pain thresholds (PPT), autonomic parameters and pain intensity were assessed prior to (baseline) and 30 min after ingestion of soda, as well as 5 min and 10 min after the intramuscular injections and at the end of the session. Whole saliva samples were collected prior to and 30, 45, 60, and 75 min after the ingestion of soda. MSG administration resulted in a significantly higher Glu level in saliva than administration of NaCl and was associated with a significant increase in systolic blood pressure. Injections of Glu were significantly more painful than injections of NaCl. However, ingestion of MSG did not change the intensity of Glu-evoked pain. Glu injections also significantly increased systolic and diastolic blood pressure, but without an additional effect of MSG ingestion. Glu injections into the masseter muscle significantly reduced the PPT. However, pre-injection MSG ingestion did not significantly alter this effect. Interestingly, PPT was significantly increased in the trapezius after MSG ingestion and intramuscular injection of Glu in the jaw muscles. The main finding

  4. the effect of monosodium glutamate (msg)

    African Journals Online (AJOL)

    Uwaifoh

    2012-03-30

    Mar 30, 2012 ... Neuronal vulnerability in mouse models of Huntington's disease: Membrane channel protein changes. J Neurosci Res; 80: 634 - 645. Ashaolu, J.O., Ukwenya, V.O., Okonoboh, A.B., Ghazal, O.K. and Jimoh A.A.G. (2011). Effect of monosodium glutamate on hematological parameters in Wistar rats.

  5. Monosodium glutamate: Potentials at inducing prostate pathologies ...

    African Journals Online (AJOL)

    The health implication of the alteration could be compounded by the opposing response elicited by increasing the concentration of either MSG or DW. Key words: Monosodium glutamate, total acid phosphatase, prostatic acid phosphatase, prostate cancer, prostatitis, benign prostate hyperplasia, infertility. African Journal of ...

  6. Monosodium glutamate for simple photometric iron analysis

    Science.gov (United States)

    Prasetyo, E.

    2018-01-01

    Simple photometric method for iron analysis using monosodium glutamate (MSG) was proposed. The method could be used as an alternative method, which was technically simple, economic, quantitative, readily available, scientifically sound and environmental friendly. Rapid reaction of iron (III) with glutamate in sodium chloride-hydrochloric acid buffer (pH 2) to form red-brown complex was served as a basis in the photometric determination, which obeyed the range of iron (III) concentration 1.6 – 80 µg/ml. This method could be applied to determine iron concentration in soil with satisfactory results (accuracy and precision) compared to other photometric and atomic absorption spectrometry results.

  7. Histochemical Studies of the Effects of Monosodium Glutamate on ...

    African Journals Online (AJOL)

    Background: Monosodium glutamate (MSG) is a commonly used food additive and there is growing concern that excitotoxins such as MSG play a critical role in the development of several hepatic disorders. Objectives: The histochemical effect of monosodium glutamate was investigated on the liver of adult Wistar rats.

  8. Histological Studies of the Effects of Monosodium Glutamate on the ...

    African Journals Online (AJOL)

    Background: Monosodium glutamate (MSG) is a commonly used food additive and there is growing concern that this may play a critical role in the aethiopathogenesis of anovulatory infertility. Objectives: The effect of monosodium glutamate (MSG) used as food additive on the ovaries of adult Wistar rat was investigated.

  9. Enrichment of anammox bacteria from three sludge sources for the startup of monosodium glutamate industrial wastewater treatment system.

    Science.gov (United States)

    Li-dong, Shen; An-hui, Hu; Ren-cun, Jin; Dong-qing, Cheng; Ping, Zheng; Xiang-yang, Xu; Bao-lan, Hu

    2012-01-15

    Three activated sludges from a landfill leachate treatment plant (S1), a municipal sewage treatment plant (S2) and a monosodium glutamate (MSG) wastewater treatment plant (S3) were used as inocula to enrich anaerobic ammonium oxidation (anammox) bacteria for the startup of MSG industrial wastewater treatment system. After 360 days of cultivation using MSG wastewater, obvious anammox activity was observed in all three cultures. The maximum specific anammox activities of cultures S1, S2 and S3 were 0.11 kg N kg(-1) VSS day(-1), 0.09 kg N kg(-1) VSS day(-1) and 0.16 kg N kg(-1) VSS day(-1), respectively. Brownish-red anammox granules having diameters in the range of 0.2-1.0mm were visible in cultures S1 and S2, and large red granules having diameters in the range of 0.5-2.5mm were formed in culture S3 after 420 days of cultivation. Phylogenetic analysis of 16S rRNA genes showed that Kuenenia organisms were the dominant anammox species in all three cultures. The copy numbers of 16S rRNA genes of anammox bacteria in cultures S1, S2 and S3 were 6.8 × 10(7) copies mL(-1), 9.4 × 10(7) copies mL(-1) and 7.5 × 10(8) copies mL(-1), respectively. The results of this study demonstrated that anammox cultivation from conventional activated sludges was highly possible using MSG wastewater. Thus the anammox process has possibility of applying to the nitrogen removal from MSG wastewater. Copyright © 2011 Elsevier B.V. All rights reserved.

  10. 78 FR 65269 - Monosodium Glutamate From the People's Republic of China and the Republic of Indonesia...

    Science.gov (United States)

    2013-10-31

    ...) petitions concerning imports of monosodium glutamate (MSG) from Indonesia and the PRC filed in proper form... September 26, 2013.\\3\\ \\1\\ See Countervailing Duty Petitions on Monosodium Glutamate from the PRC and... Duties and Countervailing Duties on Imports of Monosodium Glutamate from the People's Republic of China...

  11. Monosodium glutamate is not likely to be genotoxic.

    Science.gov (United States)

    Rogers, Michael D

    2016-08-01

    The International Glutamate Technical Committee (IGTC) wishes to comment on a recent publication in the Journal entitled "Genotoxicity of monosodium glutamate" (authored by Ataseven N, Yüzbaşıoğlu D, Keskin AÇ and Ünal F) (Ataseven et al. 2016). In particular, we wish to highlight that, in our considered view, the results of this study were inappropriately discussed and that references were selectively used. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Histological studies of the effects of monosodium glutamate on the ...

    African Journals Online (AJOL)

    Background: The effect of monosodium glutamate used as food additive on the fallopian tubes of adult Wistar rat was investigated. Material and Methods: Adult female Wistar rats (n=24) of average weight of 230g were randomly assigned into three groups A, B and C of (n=8) in each group. The treatment groups (A and B) ...

  13. Effect of monosodium glutamate and aspartame on behavioral and ...

    African Journals Online (AJOL)

    The present study aimed to investigate the individual and combined effect of mono-sodium glutamate (MSG) and aspartame (ASM) on biochemical, blood parameters and neuro-behavioral aspects of mice. The results indicated that exposure induced many changes in fear and anxiety behavior. The non-social and social ...

  14. Effects Of Monosodium Glutamate (MSG) On The Histological ...

    African Journals Online (AJOL)

    An investigation was carried out on the effects of monosodium glutamate (MSG), a commonly ues food additive, on the spinal cord of adult Wistar rats. Twenty-four adult Wistar rats weighing between 180-250g were divided into four groups of six rats per group. Graduated doses of 6mg, 12mg and 18mg per kilogram body ...

  15. The effects of Groundnut, Spices, Monosodium Glutamate and Salt ...

    African Journals Online (AJOL)

    This study was intended to determine the effect of salt, groundnut, monosodium glutamate and spices, especially in combinations as used in Yaji, on the histology of the brain. The rats were divided into nine (9) groups (A – I) of eight rats (8) each. Groups A, B, C, D, E, F, G, H, constituted the test groups whereas group I ...

  16. 78 FR 76321 - Monosodium Glutamate From China and Indonesia

    Science.gov (United States)

    2013-12-17

    ... United States at less than fair value (LTFV) and subsidized by the Governments of China and Indonesia. \\1... INTERNATIONAL TRADE COMMISSION [Investigation Nos. 701-TA-503-504 and 731-TA-1229-1230 (Preliminary)] Monosodium Glutamate From China and Indonesia Determinations On the basis of the record \\1...

  17. Monosodium glutamate toxicity: Sida acuta leaf extract ameliorated ...

    African Journals Online (AJOL)

    The brain is reportedly sensitive to monosodium glutamate (MSG) toxicity via oxidative stress. Sida acuta leaf ethanolic extract (SALEE) possesses antioxidant activity which can mitigate this neurotoxicity. The present study investigated the possible protective effect of SALEE on MSG-induced toxicity in rats. Twenty-six ...

  18. Reduction of sodium content in spicy soups using monosodium glutamate

    DEFF Research Database (Denmark)

    Jinap, Selamat; Hajeb, Parvaneh; Karim, Roslina

    2016-01-01

    Background: Excessive dietary sodium intake causes several diseases, such as hypertension, cardiovascular and renal disease, etc. Hence, reducing sodium intake has been highly recommended. In this study the effect of monosodium glutamate (MSG), as an umami substance, on saltiness and sodium...

  19. 78 FR 74115 - Monosodium Glutamate From the People's Republic of China and the Republic of Indonesia...

    Science.gov (United States)

    2013-12-10

    ... (the Department) initiated the countervailing duty investigations of monosodium glutamate from.... \\1\\ See Monosodium Glutamate from the People's Republic of China and the Republic of Indonesia... DEPARTMENT OF COMMERCE International Trade Administration [C-570-993, C-560-827] Monosodium...

  20. Glibenclamide treatment blocks metabolic dysfunctions and improves vagal activity in monosodium glutamate-obese male rats.

    Science.gov (United States)

    Franco, Claudinéia C S; Prates, Kelly V; Previate, Carina; Moraes, Ana M P; Matiusso, Camila C I; Miranda, Rosiane A; de Oliveira, Júlio C; Tófolo, Laize P; Martins, Isabela P; Barella, Luiz F; Ribeiro, Tatiane A; Malta, Ananda; Pavanello, Audrei; Francisco, Flávio A; Gomes, Rodrigo M; Alves, Vander S; Moreira, Veridiana M; Rigo, Késia P; Almeida, Douglas L; de Sant Anna, Juliane R; Prado, Marialba A A C; Mathias, Paulo C F

    2017-05-01

    Autonomic nervous system imbalance is associated with metabolic diseases, including diabetes. Glibenclamide is an antidiabetic drug that acts by stimulating insulin secretion from pancreatic beta cells and is widely used in the treatment of type 2 diabetes. Since there is scarce data concerning autonomic nervous system activity and diabetes, the aim of this work was to test whether glibenclamide can improve autonomic nervous system activity and muscarinic acetylcholine receptor function in pre-diabetic obese male rats. Pre-diabetes was induced by treatment with monosodium L-glutamate in neonatal rats. The monosodium L-glutamate group was treated with glibenclamide (2 mg/kg body weight /day) from weaning to 100 days of age, and the control group was treated with water. Body weight, food intake, Lee index, fasting glucose, insulin levels, homeostasis model assessment of insulin resistance, omeostasis model assessment of β-cell function, and fat tissue accumulation were measured. The vagus and sympathetic nerve electrical activity were recorded. Insulin secretion was measured in isolated islets challenged with glucose, acetylcholine, and the selective muscarinic acetylcholine receptor antagonists by radioimmunoassay technique. Glibenclamide treatment prevented the onset of obesity and diminished the retroperitoneal (18%) and epididymal (25%) fat pad tissues. In addition, the glibenclamide treatment also reduced the parasympathetic activity by 28% and glycemia by 20% in monosodium L-glutamate-treated rats. The insulinotropic effect and unaltered cholinergic actions in islets from monosodium L-glutamate groups were increased. Early glibenclamide treatment prevents monosodium L-glutamate-induced obesity onset by balancing autonomic nervous system activity.

  1. Antioxidant effect of phycocyanin on oxidative stress induced with monosodium glutamate in rats

    OpenAIRE

    Bertolin, Telma Elita; Farias, Daniele; Guarienti, Cíntia; Petry, Fernanda Tais Souza; Colla, Luciane Maria; Costa, Jorge Alberto Vieira

    2011-01-01

    The objective of this work was to study the antioxidant effect of phycocyanin on the oxidative stress induced by monosodium glutamate in the rats. The tests were performed with 32 rats of Wistar breed, divided into four groups, which were administered saline solution of phycocyanin, monosodium glutamate and monosodium glutamate plus phycocyanin. Sulfhydryl groups and the secondary substances derived from lipid oxidation were determined through the level of TBA. The evaluation of these values ...

  2. Antioxidant effect of phycocyanin on oxidative stress induced with monosodium glutamate in rats

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    Telma Elita Bertolin

    2011-08-01

    Full Text Available The objective of this work was to study the antioxidant effect of phycocyanin on the oxidative stress induced by monosodium glutamate in the rats. The tests were performed with 32 rats of Wistar breed, divided into four groups, which were administered saline solution of phycocyanin, monosodium glutamate and monosodium glutamate plus phycocyanin. Sulfhydryl groups and the secondary substances derived from lipid oxidation were determined through the level of TBA. The evaluation of these values and the level of sulfhydryl showed that the administration of phycocyanin presented significant antioxidant effect (p < 0.05 reducing the oxidative stress induced by the monosodium glutamate in vivo.

  3. Foreign body granuloma caused by monosodium glutamate after BCG vaccination.

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    Chiu, Yao-Kun; Huang, Chao-Cheng; Jeng, Jingyueh; Shiea, Jentaie; Chen, Wei-Jen

    2006-08-01

    We describe a 7-month-old male infant with a foreign body granuloma caused by monosodium glutamate (MSG) after a Bacille Calmette-Guérin (BCG) immunization. A ridged, erythematous, indurated plaque developed over a BCG injection site on his left upper arm 1 month after the first BCG immunization. Biopsy showed multiple noncaseating foreign body granulomas without detectable mycobacteria by both Ziehl-Neelsen stain and polymerase chain reaction assay. Birefringent crystals were identified in the foreign body giant cells with polarized light microscopy. The crystals were further determined to be glutamic acid by the method of fast atom bombardment. Hence, MSG, the only composite of BCG vaccine except the bacillus, was believed to be responsible for the granulomatous foreign body reaction. On review of the literature, we could find no previous report of an adverse reaction of BCG immunization attributable to MSG (glutamic acid).

  4. Molecularly Imprinted Polymers Chitosan-Glutaraldehyde for Monosodium Glutamate

    Science.gov (United States)

    Mulyasuryani, Ani; Haryanto, Edi; Sulistyarti, Hermin; Rumhayati, Barlah

    2018-01-01

    Chitosan has been used as a functional monomer in the synthesis of molecularly imprinted polymers (MIP) for monosodium glutamate (MSG). MIP is made from a mixture of 5 g chitosan, 50 mg glutaraldehyde and 2 g MSG, MIP is formed as flakes and beads. MIPs are identified by the FTIR spectrum, SEM image and their adsorption capabilities. MIP flakes and beads have no structural differences if they are based on FTIR or SEM spectra, but MIP adsorption capacity of beads higher than flakes. Adsorption capacity of MIP flakes is 548 mg/g and MIP beads 627 mg/g.

  5. Update on food safety of monosodium l-glutamate (MSG).

    Science.gov (United States)

    Henry-Unaeze, Helen Nonye

    2017-12-01

    This evidence-based safety review of the flavor enhancer monosodium l-glutamate (MSG) was triggered by its global use and recent studies expressing some safety concerns. This article obtained information through search of evidence-based scientific databases, especially the US National Library of Medicine NIH. (A) MSG is a water-soluble salt of glutamate, a non-essential amino acid, normally synthesized in the body and prevalent in protein foods. (B) MSG is utilized world-wide for its "umami" taste and flavor enhancement qualities, (C) the human body does not discriminate between glutamate present in food and that added as seasoning, (D) glutamate metabolism is compartmentalized in the human body without reported ethnic differences, (E) glutamate does not passively cross biological membranes, (F) food glutamate is completely metabolized by gut cells as energy source and serves as key substrate for other important metabolites in the liver, (G) normal food use of MSG is dose-dependent and self-limiting without elevation in plasma glutamate, (H) the recent EFSA acceptable daily intake (30mg/kg body weight/day) is not attainable when MSG is consumed at normal dietary level, (I) scientists have not been able to consistently elicit reactions in double-blind studies with 'sensitive' individuals using MSG or placebo in food. Based on the above observations (A-I), high quality MSG is safe for all life-cycle stages without respect to ethnic origin or culinary background. MSG researchers are advised to employ appropriate scientific methodologies, consider glutamate metabolism and its normal food use before extrapolating pharmacological rodent studies to humans. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Monosodium glutamate neonatal treatment induces cardiovascular autonomic function changes in rodents

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    Signorá Peres Konrad

    2012-10-01

    Full Text Available OBJECTIVES: The aim of this study was to evaluate cardiovascular autonomic function in a rodent obesity model induced by monosodium glutamate injections during the first seven days of life. METHOD: The animals were assigned to control (control, n = 10 and monosodium glutamate (monosodium glutamate, n = 13 groups. Thirty-three weeks after birth, arterial and venous catheters were implanted for arterial pressure measurements, drug administration, and blood sampling. Baroreflex sensitivity was evaluated according to the tachycardic and bradycardic responses induced by sodium nitroprusside and phenylephrine infusion, respectively. Sympathetic and vagal effects were determined by administering methylatropine and propranolol. RESULTS: Body weight, Lee index, and epididymal white adipose tissue values were higher in the monosodium glutamate group in comparison to the control group. The monosodium glutamate-treated rats displayed insulin resistance, as shown by a reduced glucose/insulin index (-62.5%, an increased area under the curve of total insulin secretion during glucose overload (39.3%, and basal hyperinsulinemia. The mean arterial pressure values were higher in the monosodium glutamate rats, whereas heart rate variability (>7 times, bradycardic responses (>4 times, and vagal (~38% and sympathetic effects (~36% were reduced as compared to the control group. CONCLUSION: Our results suggest that obesity induced by neonatal monosodium glutamate treatment impairs cardiac autonomic function and most likely contributes to increased arterial pressure and insulin resistance.

  7. Monosodium glutamate neonatal treatment induces cardiovascular autonomic function changes in rodents.

    Science.gov (United States)

    Konrad, Signorá Peres; Farah, Vera; Rodrigues, Bruno; Wichi, Rogério Brandão; Machado, Ubiratan Fabres; Lopes, Heno Ferreira; D'Agord Schaan, Beatriz; De Angelis, Kátia; Irigoyen, Maria Cláudia

    2012-10-01

    The aim of this study was to evaluate cardiovascular autonomic function in a rodent obesity model induced by monosodium glutamate injections during the first seven days of life. The animals were assigned to control (control, n = 10) and monosodium glutamate (monosodium glutamate, n = 13) groups. Thirty-three weeks after birth, arterial and venous catheters were implanted for arterial pressure measurements, drug administration, and blood sampling. Baroreflex sensitivity was evaluated according to the tachycardic and bradycardic responses induced by sodium nitroprusside and phenylephrine infusion, respectively. Sympathetic and vagal effects were determined by administering methylatropine and propranolol. Body weight, Lee index, and epididymal white adipose tissue values were higher in the monosodium glutamate group in comparison to the control group. The monosodium glutamate-treated rats displayed insulin resistance, as shown by a reduced glucose/insulin index (-62.5%), an increased area under the curve of total insulin secretion during glucose overload (39.3%), and basal hyperinsulinemia. The mean arterial pressure values were higher in the monosodium glutamate rats, whereas heart rate variability (>7 times), bradycardic responses (>4 times), and vagal (~38%) and sympathetic effects (~36%) were reduced as compared to the control group. Our results suggest that obesity induced by neonatal monosodium glutamate treatment impairs cardiac autonomic function and most likely contributes to increased arterial pressure and insulin resistance.

  8. Histochemical studies of the effects of monosodium glutamate on the liver of adult wistar rats.

    Science.gov (United States)

    Eweka, Ao; Igbigbi, Ps; Ucheya, Re

    2011-01-01

    Monosodium glutamate (MSG) is a commonly used food additive and there is growing concern that excitotoxins such as MSG play a critical role in the development of several hepatic disorders. The histochemical effect of monosodium glutamate was investigated on the liver of adult Wistar rats. Adult male Wistar rats (n = 24), with an average weight of 230 g were randomly assigned into two treatment groups, (A & B) (n=16) and Control (C) (n=8). The rats in the treatment groups (A & B) received 0.04mg/kg and 0.08mg/kg of monosodium glutamate thoroughly mixed with the grower's mash, respectively on a daily basis for forty-two days. The 0.04mg/kg and 0.08mg/kg monosodium glutamate doses were chosen and extrapolated in this experiment based on the previous work done with the additive. The control group (C) received equal amount of feed (Growers' mash) without monosodium glutamate added for the same period. The rats were given water ad libitum. Both the treatment and control rats were sacrificed by cervical dislocation on day forty-three of the experiment. The Liver was carefully dissected out and quickly fixed in Bouin's fluid for histochemical studies, while blood was collected for estimation of total protein, albumin, transaminasese (aspartate aminotransferase (AST) and alanine aminotransferase (ALT). The histological findings showed changes like dilatation of the central vein, which contained lysed red blood cells, cyto-architectural distortions of the hepatocytes, atrophic and degenerative changes on the liver of the animals that received feed incoporated with monosodium glutamate. Furthermore, the biochemical parameters were significantly higher in the test than control groups (P monosodium glutamate mixed in their feed. These findings showed that monosodium glutamate consumption may have some deleterious effects on the liver of adult Wistar rats at higher doses and by extension may affect the functions of the liver.

  9. The immunoreactivity of satellite glia of the spinal ganglia of rats treated with monosodium glutamate

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    Aleksandra Ewa Krawczyk

    2016-01-01

    Full Text Available Satellite glia of the peripheral nervous system ganglia provide metabolic protection to the neurons. The aim of this study was to determine the effects of monosodium glutamate administered parenterally to rats on the expression of glial fibrillary acidic protein, S-100β protein and Ki-67 antigen in the satellite glial cells. Adult, 60-day-old male rats received monosodium glutamate at two doses of 2 g/kg b.w. (group 1 and 4 g/kg b.w. (group 2 subcutaneously for 3 consecutive days. Animals in the control group (group C were treated with corresponding doses of 0.9% sodium chloride. Immediately after euthanasia, spinal ganglia of the lumbar region were dissected. Immunohistochemical peroxidase anti-peroxidase reactions were performed on the sections containing the examined material using antibodies against glial fibrillary acidic protein, S-100β and Ki-67. Next, morphological and morphometric analyses of immunopositive and immunonegative glia were conducted. The data were presented as the mean number of cells with standard deviation. Significant differences were analysed using ANOVA (P < 0.05. In all 63-day-old rats, immunopositivity for the examined proteins glia was observed. Increased number of cells expressing glial fibrillary acidic protein was demonstrated in group 2, whereas the number of S-100β-positive glia grew in the groups with the increasing doses of monosodium glutamate. The results indicate the early stage reactivity of glia in response to increased levels of glutamate in the extracellular space. These changes may be of a neuroprotective nature under the conditions of excitotoxicity induced by the action of this excitatory neurotransmitter.

  10. Chronic Monosodium Glutamate Administration Induced Hyperalgesia in Mice

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    Anca Zanfirescu

    2017-12-01

    Full Text Available Monosodium glutamate (MSG is a widely used food additive. Although it is generally considered safe, some questions regarding the impact of its use on general health have arisen. Several reports correlate MSG consumption with a series of unwanted reactions, including headaches and mechanical sensitivity in pericranial muscles. Endogenous glutamate plays a significant role in nociceptive processing, this neurotransmitter being associated with hyperalgesia and central sensitization. One of the mechanisms underlying these phenomena is the stimulation of Ca2+/calmodulin sensitive nitric oxide synthase, and a subsequent increase in nitric oxide production. This molecule is a key player in nociceptive processing, with implications in acute and chronic pain states. Our purpose was to investigate the effect of this food additive on the nociceptive threshold when given orally to mice. Hot-plate and formalin tests were used to assess nociceptive behaviour. We also tried to determine if a correlation between chronic administration of MSG and variations in central nitric oxide (NO concentration could be established. We found that a dose of 300 mg/kg MSG given for 21 days reduces the pain threshold and is associated with a significant increase in brain NO level. The implications of these findings on food additive-drug interaction, and on pain perception in healthy humans, as well as in those suffering from affections involving chronic pain, are still to be investigated.

  11. [Effects of dietary monosodium-glutamate on gene expression].

    Science.gov (United States)

    Jurasek, Júlia Vanda; Raposa, László Bence; Gubicskóné Kisbenedek, Andrea; Varga, Veronika; Szabó, Zoltán; Varjas, Tímea

    2017-03-01

    Nowadays, the food industry more often uses different type of additives during the food production. Our aim was to examine the monosodium-glutamate's effect (in animal experiment) on DNA-methyltransferases in gene expression patterns of mRNA levels. In the investigation we used 24 (n=24) CD1 type female mice. The animals were fed with different equivalent human doses of the tested substance. After autopsy, mRNA was isolated from different tissues (lung, liver, kidney, spleen). DNMT1, DNMT3A and DNMT3B levels were determined by Quantitative Real-Time PCR. DNMT1 significantly suppressed the gene expression in all the three treated groups (pmonosodium glutamate, suppressed the DNMT1 and DNMT3A gene expression - on mRNA levels of several organs - in mice. It can be a similar chemopreventive effect to epigallo-catechin-gallate's, curcumin's, genistein's, likopine's and rezveratrol's effects. In this case it can be possible that the MSG has anticarcinogenic effects. Orv. Hetil., 2017, 158(10), 380-385.

  12. Neonatal exposure to monosodium glutamate results in dysmorphology of orofacial lower motor neurons.

    Science.gov (United States)

    Foran, Lindsey; Kupelian, Chloe; Laroia, Swati; Esper, Jeffrey; Kulesza, Randy Joseph

    2017-06-14

    Glutamate is the most abundant excitatory neurotransmitter in the central nervous system, and is stored and released by both neurons and astrocytes. Despite the important role of glutamate as a neurotransmitter, high levels of extracellular glutamate can result in excitotoxicity and apoptosis. Monosodium glutamate (MSG) is a naturally occurring sodium salt of glutamic acid that is used as a flavor enhancer in many processed foods. Neonatal exposure to MSG has been shown to result in neurodegeneration in several forebrain regions, characterized by neuronal loss and neuroendocrine abnormalities. However, the brainstem effects of neonatal monosodium glutamate exposure have not been investigated. It is therefore hypothesized that MSG exposure during the early postnatal period would impact brainstem lower motor neurons involved in feeding behavior. The effect of neonatal MSG exposure on brainstem lower motor neurons was investigated by exposing rat pups to either 4mg/g MSG or saline from postnatal day (P) 4 through 10. On P28, brains were preserved by vascular perfusion with fixative, frozen sectioned and stained for Nïssl substance. The number, size and shape of brainstem motor neurons were compared between MSG and saline-exposed animals. MSG exposure had no impact on the total number of neurons in the nuclei examined. However, MSG exposure was associated with a significant increase in the number of round somata in both the trigeminal and facial nuclei. Furthermore, MSG exposure resulted in significantly smaller neurons in all motor nuclei examined. These results suggest that neonatal exposure to MSG impacts the development of brainstem lower motor neurons which may impact feeding and swallowing behaviors in young animals.

  13. Auditory hindbrain atrophy and anomalous calcium binding protein expression after neonatal exposure to monosodium glutamate.

    Science.gov (United States)

    Foran, Lindsey; Blackburn, Kaitlyn; Kulesza, Randy J

    2017-03-06

    Glutamate is the most abundant excitatory neurotransmitter in the central nervous system, and is stored and released by both neurons and astrocytes. Despite the important role of glutamate as a neurotransmitter, elevated extracellular glutamate can result in excitotoxicity and apoptosis. Monosodium glutamate (MSG) is a naturally occurring sodium salt of glutamic acid that is used as a flavor enhancer in many processed foods. Previous studies have shown that MSG administration during the early postnatal period results in neurodegenerative changes in several forebrain regions, characterized by neuronal loss and neuroendocrine abnormalities. Systemic delivery of MSG during the neonatal period and induction of glutamate neurotoxicity in the cochlea have both been shown to result in fewer neurons in the spiral ganglion. We hypothesized that an MSG-induced loss of neurons in the spiral ganglion would have a significant impact on the number of neurons in the cochlear nuclei and superior olivary complex (SOC). Indeed, we found that exposure to MSG from postnatal days 4 through 10 resulted in significantly fewer neurons in the cochlear nuclei and SOC and significant dysmorphology in surviving neurons. Moreover, we found that neonatal MSG exposure resulted in a significant decrease in the expression of both calretinin and calbindin. These results suggest that neonatal exposure to MSG interferes with early development of the auditory brainstem and impacts expression of calcium binding proteins, both of which may lead to diminished auditory function. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  14. Supplementing monosodium glutamate to partial enteral nutrition slows gastric emptying in preterm pigs

    Science.gov (United States)

    Emerging evidence suggests that free glutamate may play a functional role in modulating gastroduodenal motor function. We hypothesized that supplementing monosodium glutamate (MSG) to partial enteral nutrition stimulates gastric emptying in preterm pigs. Ten-day-old preterm, parenterally fed pigs re...

  15. Monosodium glutamate neonatal treatment as a seizure and excitotoxic model.

    Science.gov (United States)

    López-Pérez, Silvia Josefina; Ureña-Guerrero, Mónica Elisa; Morales-Villagrán, Alberto

    2010-03-04

    Monosodium glutamate (MSG) subcutaneously administrated to neonatal rats induces several neurochemical alterations in the brain, which have been associated with an excitotoxic process triggered by an over activation of glutamate receptors; however there are few systematic studies about initial changes in intracerebroventricular (i.c.v.) Glu levels produced by MSG in the brain. Thus, to characterize these changes, rat pups were injected with a MSG solution at 1, 3, 5 and 7 postnatal days (PD), and i.c.v. Glu levels and hippocampal total content of related amino acids (Asp, Glu, Gln, Gly, Tau, Ala and GABA) were estimated before, immediately and after each injection. Behavioral and EEG responses were also monitored after MSG administrations. Significant rise in i.c.v. Glu levels were found, mainly in response to the first and second injection. Moreover, the total content of all amino acids evaluated also increased during the first hour after the first MSG administration but only Glu and GABA remained elevated after 24 h. These biochemical modifications were accompanied with behavioral alterations characterized by: screeching, tail stiffness, head nodding, emprosthotonic flexion episodes and generalized tonic-clonic convulsions, which were associated with electroencephalographic pattern alterations. Altered behavior found in animals treated with MSG suggests an initial seizure situation. Although four MSG administrations were used, the most relevant findings were observed after the first and second administrations at PD1 and PD3, suggesting that only two MSG injections could be sufficient to resemble a seizure and/or excitotoxic model. 2009 Elsevier B.V. All rights reserved.

  16. Monosodium glutamate intake, dietary patterns and asthma in Chinese adults.

    Directory of Open Access Journals (Sweden)

    Zumin Shi

    Full Text Available OBJECTIVES: Emerging evidence shows that diet is related to asthma. The aim of this analysis was to investigate the association between monosodium glutamate (MSG intake, overall dietary patterns and asthma. METHODS: Data from 1486 Chinese men and women who participated in the Jiangsu Nutrition Study (JIN were analyzed. In this study, MSG intake and dietary patterns were quantitatively assessed in 2002. Information on asthma history was collected during followed-up in 2007. RESULTS: Of the sample, 1.4% reported ever having asthma. MSG intake was not positively associated with asthma. There was a significant positive association between 'traditional' (high loadings on rice, wheat flour, and vegetable food pattern and asthma. No association between 'macho' (rich in meat and alcohol, 'sweet tooth' (high loadings on cake, milk, and yoghurt 'vegetable rich' (high loadings on whole grain, fruit, and vegetable food patterns and asthma was found. Smoking and overweight were not associated with asthma in the sample. CONCLUSION: While a 'Traditional' food pattern was positively associated with asthma among Chinese adults, there was no significant association between MSG intake and asthma.

  17. Reduction of sodium content in spicy soups using monosodium glutamate

    Directory of Open Access Journals (Sweden)

    Selamat Jinap

    2016-06-01

    Full Text Available Background: Excessive dietary sodium intake causes several diseases, such as hypertension, cardiovascular and renal disease, etc. Hence, reducing sodium intake has been highly recommended. In this study the effect of monosodium glutamate (MSG, as an umami substance, on saltiness and sodium reduction was investigated. Methods and Results: The trained panellists were presented with basic spicy soups (curry chicken and chili chicken containing different amounts of sodium chloride (NaCl (0–1.2% and MSG (0–1.2%. They tasted the optimum concentrations of NaCl and MSG for the two spicy soups and the overall acceptability were 0.8% and 0.7%, respectively. There was no significant effect of spiciness level on the saltiness and umami taste of both soups. The optimum levels of combined NaCl and MSG for overall acceptance in the chili and curry soups were 0.3% and 0.7%, respectively. The results showed that with the addition of MSG, it is possible to reduce sodium intake without changing the overall acceptability of the spicy soup. A 32.5% reduction in sodium level is made feasible by adding 0.7% MSG to the spicy soups. Conclusions: This study suggests that low-sodium soups can be developed by the addition of appropriate amounts of MSG, while maintaining the acceptability of the spicy soups. It was also proven that it is feasible to reduce sodium intake by replacing NaCl with MSG.

  18. Neuroprotective Activity of Pongamia pinnata in Monosodium Glutamate-induced Neurotoxicity in Rats.

    Science.gov (United States)

    Swamy, A H M Viswanatha; Patel, N L; Gadad, P C; Koti, B C; Patel, U M; Thippeswamy, A H M; Manjula, D V

    2013-11-01

    This study was designed to evaluate the neuroprotective activity of ethanol extract of Pongamia pinnata stem bark in monosodium glutamate-induced neurotoxicity in rats. Neurotoxicity was induced by intraperitoneal injection of monosodium glutamate 2 g per kg body weight daily for 7 days. Ethanol extract of Pongamia pinnata stem bark (200 and 400 mg/kg) was administered orally after 1 h of monosodium glutamate treatment. Dextromethorphan (30 mg/kg, p.o.) was used as standard drug for the comparison. The degree of protection was determined by various behavioural, locomotor, muscle grip activity, lipid peroxidation and measurement of antioxidant status of glutathione, catalase and superoxide dismutase. Estimation of calcium, sodium and potassium ions in brain tissue and gamma aminobutyric acid level in serum was carried out. The histopathological study of brain tissue was also carried out. Treatment with Pongamia pinnata significantly improved monosodium glutamate-induced alteration in behavioural and locomotor activity and muscle strength. Significant decrease in lipid peroxidation and increase in glutathione, superoxide dismutase and catalase was observed in Pongamia pinnata treated group. Further, Pongamia pinnata also significantly reduced the monosodium glutamate-induced excitotoxicity by decreasing the level of Ca(+2) and Na(+) with concomitant increase in the level of K(+). Serum gamma aminobutyric acid level was also increased in Pongamia pinnata treated animals. Further, the histopathological evidence supports the neuroprotective activity of Pongamia pinnata. In conclusion, the present study suggests that the ethanol extract of stem bark of Pongamia pinnata possesses significant neuroprotective activity in albino rats.

  19. Monosodium glutamate-induced oxidative kidney damage and possible mechanisms: a mini-review.

    Science.gov (United States)

    Sharma, Amod

    2015-10-22

    Animal studies suggest that chronic monosodium glutamate (MSG) intake induces kidney damage by oxidative stress. However, the underlying mechanisms are still unclear, despite the growing evidence and consensus that α-ketoglutarate dehydrogenase, glutamate receptors and cystine-glutamate antiporter play an important role in up-regulation of oxidative stress in MSG-induced renal toxicity. This review summaries evidence from studies into MSG-induced renal oxidative damage, possible mechanisms and their importance from a toxicological viewpoint.

  20. Flavor preferences conditioned by oral monosodium glutamate in mice.

    Science.gov (United States)

    Ackroff, Karen; Sclafani, Anthony

    2013-11-01

    The prototypic umami substance monosodium glutamate (MSG) reinforces preferences for its own flavor, as well as preferences for flavors associated with it, by conditioning processes. Mice of 3 inbred strains (C57BL/6J (B6), 129P3/J, and FVB/NJ) and 2 taste-knockout (KO) groups derived from the B6 lineage were initially indifferent to 200mM MSG, but this evaluation was altered by forced exposure to MSG. B6 and KO mice acquired an MSG preference, 129 mice remained indifferent, and FVB mice avoided MSG. The shifts in preference imply a postoral basis for MSG effects, suggesting that it could produce preferences for associated flavors. New mice were trained with a conditioned stimulus (CS+) flavor mixed in 200mM MSG and a CS- flavor in water. Similar to the parent B6 strain, mice missing the T1r3 element of an umami receptor or the downstream signaling component Trpm5 learned to prefer the CS+ flavor and subsequently showed similar preferences for MSG in an ascending concentration series. Consistent with their responses to forced exposure, the 129 strain did not acquire a significant CS+ preference, and the FVB strain avoided the CS+ flavor. The 129 and FVB strains showed little attraction in the ascending MSG concentration series. Together, these data indicate that the postoral effects of MSG can modulate responses to its own and MSG-paired flavors. The basis for strain differences in the responses to MSG is not certain, but the taste-signaling elements T1r3 and Trpm5, which are also present in the gut, are not required for mediation of this flavor learning.

  1. The sensitivity of male rat reproductive organs to monosodium glutamate

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    Sitthichai Iamsaard

    2014-05-01

    Full Text Available Objective. This study aimed to investigate the sensitivity of the testis, epididymis, seminal vesicle, and sperm acrosome reaction (AR to monosodium L- glutamate (MSG in rats. Materials and methods. Rats were divided into four groups and fed with non-acidic MSG at 0.25, 3 or 6 g/kg body weight for 30 days or without MSG. The morphological changes in the reproductive organs were studied. The plasma testosterone level, epididymal sperm concentration, and sperm AR status were assayed. Results. Compared to the control, no significant changes were discerned in the morphology and weight of the testes, or the histological structures of epididymis, vas deferens and seminal vesicle. In contrast, significant decreases were detected in the weight of the epididymis, testosterone levels, and sperm concentration of rats treated with 6 g/kg body weight of MSG. The weight loss was evident in the seminal vesicle in MSG-administered rats. Moreover, rats treated with MSG 3 and 6 g/kg exhibited partial testicular damage, characterized by sloughing of spermatogenic cells into the seminiferous tubular lumen, and their plasma testosterone levels were significantly decreased. In the 6 g/kg MSG group, the sperm concentration was significantly decreased compared with the control or two lower dose MSG groups. In AR assays, there was no statistically significant difference between MSG-rats and normal rats. Conclusion. Testicular morphological changes, testosterone level, and sperm concentration were sensitive to high doses of MSG while the rate of AR was not affected. Therefore, the consumption of high dose MSG must be avoided because it may cause partial infertility in male.

  2. Monosodium glutamate avoidance for chronic asthma in adults and children.

    Science.gov (United States)

    Zhou, Yan; Yang, Ming; Dong, Bi Rong

    2012-06-13

    Monosodium glutamate (MSG) is the sodium salt of the non-essential amino acid, glutamic acid, and is used as a flavour enhancer. It has been implicated in causing adverse reactions, which have been referred to as "Chinese restaurant syndrome". Over the last two decades there have been a number of studies investigating whether MSG ingestion induces an asthmatic response, and several reviews have been published (ILSI 1991; Stevenson 2000; Woods 2001), but no meta-analysis or Cochrane systematic review has been performed. The objectives of this review are to: 1) identify randomised controlled trials (RCTs) of MSG ingestion and asthma response in adults and children older than two years of age with asthma; 2) assess the methodological quality of these trials; and 3) determine the effect of MSG ingestion on asthma outcomes. We searched the Cochrane Airways group's Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), and bibliographies of existing trials. Searches were current up to May 2012. We included RCTs that investigated the effect of MSG on chronic asthma in adults and children. Two authors independently extracted, entered and analysed data from included studies. We contacted study authors for additional information. Only two cross-over studies involving 24 adults met the eligibility criteria; the challenge dosages of MSG were 1 g, 5 g and 25 mg/kg. They reported the number of subjects who had a maximum fall in forced expiratory volume in the first second (FEV(1)) greater than 15% or 200 mL after MSG or the control challenge. The pooled data found no statistically significant difference between MSG and placebo. One trial reported the mean change at four hours and maximum fall in FEV(1) over four hours after MSG or the placebo challenge, but found no statistically significant difference between interventions. There were no differences in symptom scores, non-specific bronchial hyper-responsiveness (BHR), eosinophil cationic protein

  3. Metabolomic profiling of urinary changes in mice with monosodium glutamate-induced obesity

    Czech Academy of Sciences Publication Activity Database

    Pelantová, Helena; Bártová, Simona; Anýž, J.; Holubová, Martina; Železná, Blanka; Maletínská, Lenka; Novák, D.; Lacinová, Z.; Šulc, Miroslav; Haluzík, M.; Kuzma, Marek

    2016-01-01

    Roč. 408, č. 2 (2016), s. 567-578 ISSN 1618-2642 R&D Projects: GA ČR GA13-14105S; GA MŠk LO1509 Institutional support: RVO:61388971 ; RVO:61388963 Keywords : Mouse model * Monosodium glutamate (MSG) induced obesity * Diabetes Subject RIV: CE - Biochemistry Impact factor: 3.431, year: 2016

  4. Effect of cholecystokinin on feeding is attenuated in monosodium glutamate obese mice

    Czech Academy of Sciences Publication Activity Database

    Maletínská, Lenka; Toma, Resha Shamas; Pirnik, Z.; Kiss, A.; Slaninová, Jiřina; Haluzík, M.; Železná, Blanka

    2006-01-01

    Roč. 136, č. 1/3 (2006), s. 58-63 ISSN 0167-0115 R&D Projects: GA ČR(CZ) GA303/05/0614 Institutional research plan: CEZ:AV0Z40550506; CEZ:AV0Z50520514 Keywords : monosodium glutamate * obesity * cholecistokinin * feeding behavior Subject RIV: CE - Biochemistry Impact factor: 2.442, year: 2006

  5. Effect of L (+) ascorbic acid and monosodium glutamate concentration on the morphology of calcium carbonate

    Science.gov (United States)

    Saraya, Mohamed El-shahte Ismaiel

    2015-11-01

    In this study, monosodium glutamate and ascorbic acid were used as crystal and growth modifiers to control the crystallization of CaCO3. Calcium carbonate prepared by reacting a mixed solution of Na2CO3 with CaCl2 at ambient temperature, (25 °C), constant Ca++/ CO3- - molar ratio and pH with stirring. The polymorph and morphology of the crystals were characterized using scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), transmission electron microscopy (TEM) and differential scanning calorimetry (DSC). The results indicate that rhombohedral calcite was only formed in water without organic additives, and both calcite and spherical vaterite with various morphologies were produced in the presence of monosodium glutamate. The content of vaterite increased as the monosodium glutamate increased. In addition, spherical vaterite was obtained in the presence of different concentrations of ascorbic acid. The spherical vaterite posses an aggregate shape composed of nano-particles, ranging from 30 to 50 nm as demonstrated by the SEM and TEM analyses. Therefore, the ascorbic stabilizes vaterite and result in nano-particles compared to monosodium glutamate.

  6. The Monosodium Glutamate Story: The Commercial Production of MSG and Other Amino Acids

    Science.gov (United States)

    Ault, Addison

    2004-01-01

    Monosodium glutamate (MSG) is both the basis of a trillion dollar worldwide industry and a presence in the diet of a majority of the inhabitants of the world. Some parts of the "story" of MSG that might be of most interest to chemists, chemistry teachers and their students are presented.

  7. Monosodium glutamate obesity in mice: effect of peripherally administered cholecystokinin on feeding behaviour

    Czech Academy of Sciences Publication Activity Database

    Maletínská, Lenka; Slaninová, Jiřina; Haluzík, M.; Železná, Blanka

    2005-01-01

    Roč. 6, Suppl.1 (2005), s. 60 ISSN 1467-7881. [European Congress on Obesity /14./. 01.06.2005-04.06.2005, Athens] Institutional research plan: CEZ:AV0Z40550506 Keywords : obesity * monosodium glutamate * feeding Subject RIV: CE - Biochemistry

  8. Neonatal monosodium glutamate treatment modifies glutamic acid decarboxylase activity during rat brain postnatal development.

    Science.gov (United States)

    Ureña-Guerrero, Mónica Elisa; López-Pérez, Silvia Josefina; Beas-Zárate, Carlos

    2003-03-01

    Monosodium glutamate (MSG) produces neurodegeneration in several brain regions when it is administered to neonatal rats. From an early embryonic age to adulthood, GABA neurons appear to have functional glutamatergic receptors, which could convert them in an important target for excitotoxic neurodegeneration. Changes in the activity of the GABA synthesizing enzyme, glutamic acid decarboxylase (GAD), have been shown after different neuronal insults. Therefore, this work evaluates the effect of neonatal MSG treatment on GAD activity and kinetics in the cerebral cortex, striatum, hippocampus and cerebellum of the rat brain during postnatal development. Neonatal MSG treatment decreased GAD activity in the cerebral cortex at 21 and 60 postnatal days (PD), mainly due to a reduction in the enzyme affinity (K(m)). In striatum, the GAD activity and the enzyme maximum velocity (V(max)) were increased at PD 60 after neonatal MSG treatment. Finally, in the hippocampus and cerebellum, the GAD activity and V(max) were increased, but the K(m) was found to be lower in the experimental group. The results could be related to compensatory mechanisms from the surviving GABAergic neurons, and suggest a putative adjustment in the GAD isoform expression throughout the development of the postnatal brain, since this enzyme is regulated by the synaptic activity under physiological and/or pathophysiological conditions.

  9. Headache and mechanical sensitization of human pericranial muscles after repeated intake of monosodium glutamate (MSG)

    DEFF Research Database (Denmark)

    Shimada, Akiko; Cairns, B.E.; Vad, N.

    2013-01-01

    A single intake of monosodium glutamate (MSG) may cause headache and increased muscle sensitivity. We conducted a double-blinded, placebo-controlled, crossover study to examine the effect of repeated MSG intake on spontaneous pain, mechanical sensitivity of masticatory muscles, side effects...... pressure were evaluated before and 15, 30, and 50 min after MSG intake. Whole saliva samples were taken before and 30 min after MSG intake to assess glutamate concentrations. Headache occurred in 8/14 subjects during MSG and 2/14 during placebo (P = 0.041). Salivary glutamate concentrations on Day 5 were...

  10. Alteration in some antioxidant enzymes in cardiac tissue upon monosodium glutamate [MSG] administration to adult male mice

    OpenAIRE

    Singh, Kuldip; Pushpa, Ahluwalia

    2005-01-01

    4mg and 8mg monosodium glutamate per gram body weight was administered subcutaneously for 6 consecutive days to normal adult male mice and its effect was seen on 31st day after the last injection on some antioxidant enzymes in heart. A significant dose dependent increase in lipid peroxidation and xanthine oxidase level was observed, whereas the activity of free radical scavenging enzymes such as superoxide dismutase and catalase was decreased in both monosodium glutamate treated groups (Group...

  11. Study of the Protective Effects of Quince (Cydonia Oblonga) Leaf Extract on Fertility Alterations and Gonadal Dysfunction Induced by Monosodium Glutamate in Adult Male Wistar Rats

    OpenAIRE

    Kianifard Davoud; Saiah Gholamreza Vafaei; Rezaee Farhad

    2015-01-01

    Background and Aims: Starting from the cytotoxic effects of monosodium glutamate (MSG), the aim of this study was to evaluate the protective effects of quince leaf extract as natural antioxidant on the reproductive dysfunction induced by monosodium glutamate in rats. Material and methods: Monosodium glutamate was administrated with a dose of 30 and 60 mg/kg and quince leaf extract was administrated with a dose of 500 mg/kg. At the end of study, body and testicular weight measurement, hormonal...

  12. Increased pain and muscle glutamate concentration after single ingestion of monosodium glutamate by myofascial temporomandibular disorders patients.

    Science.gov (United States)

    Shimada, A; Castrillon, E E; Baad-Hansen, L; Ghafouri, B; Gerdle, B; Wåhlén, K; Ernberg, M; Cairns, B E; Svensson, P

    2016-10-01

    A randomized, double-blinded, placebo-controlled study was conducted to investigate if single monosodium glutamate (MSG) administration would elevate muscle/serum glutamate concentrations and affect muscle pain sensitivity in myofascial temporomandibular disorders (TMD) patients more than in healthy individuals. Twelve myofascial TMD patients and 12 sex- and age-matched healthy controls participated in two sessions. Participants drank MSG (150 mg/kg) or NaCl (24 mg/kg; control) diluted in 400 mL of soda. The concentration of glutamate in the masseter muscle, blood plasma and saliva was determined before and after the ingestion of MSG or control. At baseline and every 15 min after the ingestion, pain intensity was scored on a 0-10 numeric rating scale. Pressure pain threshold, pressure pain tolerance (PPTol) and autonomic parameters were measured. All participants were asked to report adverse effects after the ingestion. In TMD, interstitial glutamate concentration was significantly greater after the MSG ingestion when compared with healthy controls. TMD reported a mean pain intensity of 2.8/10 at baseline, which significantly increased by 40% 30 min post MSG ingestion. At baseline, TMD showed lower PPTols in the masseter and trapezius, and higher diastolic blood pressure and heart rate than healthy controls. The MSG ingestion resulted in reports of headache by half of the TMD and healthy controls, respectively. These findings suggest that myofascial TMD patients may be particularly sensitive to the effects of ingested MSG. WHAT DOES THIS STUDY ADD?': Elevation of interstitial glutamate concentration in the masseter muscle caused by monosodium glutamate (MSG) ingestion was significantly greater in myofascial myofascial temporomandibular disorders (TMD) patients than healthy individuals. This elevation of interstitial glutamate concentration in the masseter muscle significantly increased the intensity of spontaneous pain in myofascial TMD patients. © 2016

  13. Study of the Long-Term and Dose Dependent Effects of Methylphenidate and Monosodium Glutamate on the Hormonal Alterations of the Pituitary-Testicular Axis and Sperm Analysis in Adolescence Rats

    Directory of Open Access Journals (Sweden)

    Azad ABDOLLAHZADEH

    2017-05-01

    Full Text Available Methylphenidate is one of the most common medications that used for maintaining alertness and improving of attention which, may lead to increase of the risk of substance abuse in some cases. Monosodium glutamate is a food additive which has toxic effects on human and animal’s tissues.  Due to the various side effects of methylphenidate and monosodium glutamate on the reproductive system, the aim of this study was to evaluate the long-term and dose dependent effects of these compounds on the reproductive system during adolescence through hormonal and sperm analysis. Low and high dose of methylphenidate and monosodium glutamate was administrated to adolescent rats for 60 days. Body and testicular weight measurement, pituitary gonadotropins and testosterone levels assays and sperm analysis was performed on euthanized animals. The results showed that, high dose of methylphenidate and low dose of monosodium glutamate and/or combination form of these two compounds have more effects on body and testicular weight alterations. Low dose of methylphenidate with high dose of monosodium glutamate influenced some alterations in follicle stimulating hormone. The distinct use of methylphenidate and monosodium glutamate led to slight elevation in sperm count but simultaneous use of these compounds led to significant elevation of sperm count. The administration of these compounds had negative effect on sperm motility and viability. It has been concluded that, coadministration of methylphenidate and monosodium glutamate through the influence of brain-pituitary-testicular axis and induction of some hormonal alterations may lead to changes in normal function of reproductive system

  14. Monosodium glutamate alters the response properties of rat trigeminovascular neurons through activation of peripheral NMDA receptors.

    Science.gov (United States)

    O'Brien, Melissa; Cairns, Brian E

    2016-10-15

    Ingestion of monosodium glutamate (MSG) has been shown to cause headaches in healthy individuals and trigger migraine-like headaches in migraine sufferers. We combined immunohistochemistry, in vivo electrophysiology, and laser Doppler recordings of dural vasculature to investigate the effect of systemic administration of MSG on the trigeminovascular pathway. Immunohistochemical analysis confirmed the expression of NMDA receptors on nerve fibers innervating dural blood vessels and excitatory amino acid transporter 2 on dural blood vessels. Systemic administration of MSG (50mg/kg) evoked an increase in ongoing discharge in 5/6 spinal trigeminal subnucleus caudalis (SpVc) neurons with dural input recorded from male and female rats, respectively, as well as lowering their mechanical activation threshold. There were no sex-related differences in these effects of MSG. Neuronal discharge and mechanical sensitization were significantly attenuated by co-injection with the peripherally restricted NMDA receptor antagonist (2R)-amino-5-phosphonovaleric acid (APV) in both sexes. Systemic administration of MSG induced a 24.5% and 20.6% increase in dural flux in male and female rats, respectively. These results suggest that MSG-induced headache is mediated by the activation of peripheral NMDA receptors and subsequent dural vasodilation. Peripheral NMDA receptors are a potential target for the development of new drugs to treat headaches. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  15. [The effect of probiotic therapy on development of experimental obesity in rats caused by monosodium glutamate].

    Science.gov (United States)

    Savcheniuk, O A; Virchenko, O V; Falalieieva, T M; Beregova, T V; Babenko, L P; Lazarenko, L M; Spivak, M Ia

    2014-01-01

    The effect of a mixture of probiotic strains (2:1:1 Lactobacillus casei IMVB-7280, Bifidobacterium animalis VKL, Bifidobacterium animalis VKB) on the development of experimental obesity in rats induced by neonatal administration of monosodium glutamate has been studied. It was shown that in rats of 4 months age, the injection of monosodium glutamate (4 mg/g) at 2, 4, 6, 8, 10 days after birth elicited abdominal obesity and metabolic syndrome. An intermittent administration of a probiotic mixture to rats treated with monosodium prevented the development of obesity. In the group of rats treated with probiotics, anthropometric parameters (weight and body length, Lee index, body mass index) did not differ from the level of intact rats. Visceral fat mass was decreased by probiotics by 38.5% (P < 0.05) compared to rats treated with water. Probiotics improved lipid metabolism: reduced the level of VLDL by 32.2% (P < 0,05), the level of LDL by 30.6% (P < 0.05), increased HDL by 25.7% (P <0,05) compared to obese control rats. Probiotic strains restored the secretion of adipocytes hormones (leptin and adiponectin) to the normal level of intact animals. The results show the effectiveness of probiotics for the prevention of obesity.

  16. Sex-dimorphism in Cardiac Nutrigenomics: effect of Trans fat and/or Monosodium Glutamate consumption

    Directory of Open Access Journals (Sweden)

    Collison Kate S

    2011-11-01

    Full Text Available Abstract Background A paucity of information on biological sex-specific differences in cardiac gene expression in response to diet has prompted this present nutrigenomics investigation. Sexual dimorphism exists in the physiological and transcriptional response to diet, particularly in response to high-fat feeding. Consumption of Trans-fatty acids (TFA has been linked to substantially increased risk of heart disease, in which sexual dimorphism is apparent, with males suffering a higher disease rate. Impairment of the cardiovascular system has been noted in animals exposed to Monosodium Glutamate (MSG during the neonatal period, and sexual dimorphism in the growth axis of MSG-treated animals has previously been noted. Processed foods may contain both TFA and MSG. Methods We examined physiological differences and changes in gene expression in response to TFA and/or MSG consumption compared to a control diet, in male and female C57BL/6J mice. Results Heart and % body weight increases were greater in TFA-fed mice, who also exhibited dyslipidemia (P Gata4, Mef2d and Srebf2. Enrichment of functional Gene Ontology (GO categories were related to transcription, phosphorylation and anatomic structure (P Conclusion Our model identified major changes in the cardiac transcriptional profile of TFA and/or MSG-fed mice compared to controls, which was reflected by significant differences in the physiological profile within the 4 diet groups. Identification of sexual dimorphism in cardiac transcription may provide the basis for sex-specific medicine in the future.

  17. Excitotoxicity triggered by neonatal monosodium glutamate treatment and blood-brain barrier function.

    Science.gov (United States)

    Gudiño-Cabrera, Graciela; Ureña-Guerrero, Monica E; Rivera-Cervantes, Martha C; Feria-Velasco, Alfredo I; Beas-Zárate, Carlos

    2014-11-01

    It is likely that monosodium glutamate (MSG) is the excitotoxin that has been most commonly employed to characterize the process of excitotoxicity and to improve understanding of the ways that this process is related to several pathological conditions of the central nervous system. Excitotoxicity triggered by neonatal MSG treatment produces a significant pathophysiological impact on adulthood, which could be due to modifications in the blood-brain barrier (BBB) permeability and vice versa. This mini-review analyzes this topic through brief descriptions about excitotoxicity, BBB structure and function, role of the BBB in the regulation of Glu extracellular levels, conditions that promote breakdown of the BBB, and modifications induced by neonatal MSG treatment that could alter the behavior of the BBB. In conclusion, additional studies to better characterize the effects of neonatal MSG treatment on excitatory amino acids transporters, ionic exchangers, and efflux transporters, as well as the role of the signaling pathways mediated by erythropoietin and vascular endothelial growth factor in the cellular elements of the BBB, should be performed to identify the mechanisms underlying the increase in neurovascular permeability associated with excitotoxicity observed in several diseases and studied using neonatal MSG treatment. Copyright © 2015 IMSS. Published by Elsevier Inc. All rights reserved.

  18. Resistance exercise reduces memory impairment induced by monosodium glutamate in male and female rats.

    Science.gov (United States)

    Araujo, Paulo Cesar Oliveira; Quines, Caroline Brandão; Jardim, Natália Silva; Leite, Marlon Regis; Nogueira, Cristina Wayne

    2017-07-01

    What is the central question of this study? Monosodium glutamate causes cognitive impairment. Does resistance exercise improve the performance of rats treated with monosodium glutamate? What is the main finding and its importance? Resistance exercise is effective against monosodium glutamate-induced memory impairment in male and female rats. Monosodium glutamate (MSG), a flavour enhancer in diets, causes cognitive impairment in rodents. Exercise has been reported to protect against impairment of memory in humans. In this study, we investigated whether resistance exercise improves the performance of male and female rats treated with MSG in tests of memory and motor co-ordination. Wistar rats received MSG [4 g (kg body weight) -1  day -1 , s.c.] from postnatal day 1 to 10. At postnatal day 60, the animals started a resistance exercise protocol in an 80 deg inclined vertical ladder apparatus and performed it during 7 weeks. Rats performed object recognition and location memory tests. Resistance exercise reduced impairment in motor co-ordination of male and female rats treated with MSG. Resistance exercise was effective against the decrease in exploratory preference in the long-term recognition memory for novel objects of male rats treated with MSG. In MSG-treated female rats, resistance exercise was effective against the decrease in exploratory preference in the novel object location test. The exploratory preference of female rats in the long-term recognition memory test was similar in all groups. The short-term memory was not altered by MSG or resistance exercise in male and female rats. This study demonstrates that MSG affected the memory of male and female rats in different ways. Resistance exercise was effective against the decrease in recognition for male rats and in location memory for female rats treated with MSG. This report demonstrates the beneficial effects of resistance exercise against the prejudice of motor condition and impairment of memory induced

  19. Differential effects of repetitive oral administration of monosodium glutamate on interstitial glutamate concentration and muscle pain sensitivity.

    Science.gov (United States)

    Shimada, Akiko; Baad-Hansen, Lene; Castrillon, Eduardo; Ghafouri, Bijar; Stensson, Niclas; Gerdle, Björn; Ernberg, Malin; Cairns, Brian; Svensson, Peter; Svensson Odont, Peter

    2015-02-01

    The aim of this study was to determine the relationship of high daily monosodium glutamate (MSG) consumption with glutamate concentrations in jaw muscle, saliva, and serum, and muscle pain sensitivity in healthy participants. A randomized, double-blinded, placebo-controlled study was conducted to investigate the effect of repetitive consumption of high-dose MSG on glutamate concentration in the masseter muscles measured by microdialysis and muscle pain sensitivity. In five contiguous experimental daily sessions, 32 healthy participants drank MSG (150 mg/kg) or NaCl (24 mg/kg) diluted with a 400 mL soda. The concentrations of glutamate before and after the ingestion were assessed in dialysate and plasma samples on the first and last days. Saliva glutamate concentration was assessed every day. Pressure pain threshold, pressure pain tolerance, autonomic parameters (heart rate, systolic and diastolic blood pressures) and reported side effects also were assessed. No significant change was noted in the baseline concentration of glutamate in the masseter muscle, blood, or saliva, but the peak concentration in the masseter muscle increased significantly between day 1 and 5. A statistically significant increase in systolic and diastolic blood pressures after MSG administration was observed, as well as a significantly higher frequency of reports of nausea and headache in the MSG group. No robust effect of MSG on muscle sensitivity was found. Interstitial glutamate concentration in the masseter muscle is not highly disturbed by excessive repetitive intake of MSG in healthy man. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Ginger and Propolis Exert Neuroprotective Effects against Monosodium Glutamate-Induced Neurotoxicity in Rats

    Directory of Open Access Journals (Sweden)

    Usama K. Hussein

    2017-11-01

    Full Text Available Central nervous system cytotoxicity is linked to neurodegenerative disorders. The objective of the study was to investigate whether monosodium glutamate (MSG neurotoxicity can be reversed by natural products, such as ginger or propolis, in male rats. Four different groups of Wistar rats were utilized in the study. Group A served as a normal control, whereas group B was orally administered with MSG (100 mg/kg body weight, via oral gavage. Two additional groups, C and D, were given MSG as group B along with oral dose (500 mg/kg body weight of either ginger or propolis (600 mg/kg body weight once a day for two months. At the end, the rats were sacrificed, and the brain tissue was excised and levels of neurotransmitters, ß-amyloid, and DNA oxidative marker 8-OHdG were estimated in the brain homogenates. Further, formalin-fixed and paraffin-embedded brain sections were used for histopathological evaluation. The results showed that MSG increased lipid peroxidation, nitric oxide, neurotransmitters, and 8-OHdG as well as registered an accumulation of ß-amyloid peptides compared to normal control rats. Moreover, significant depletions of glutathione, superoxide dismutase, and catalase as well as histopathological alterations in the brain tissue of MSG-treated rats were noticed in comparison with the normal control. In contrast, treatment with ginger greatly attenuated the neurotoxic effects of MSG through suppression of 8-OHdG and β-amyloid accumulation as well as alteration of neurotransmitter levels. Further improvements were also noticed based on histological alterations and reduction of neurodegeneration in the brain tissue. A modest inhibition of the neurodegenerative markers was observed by propolis. The study clearly indicates a neuroprotective effect of ginger and propolis against MSG-induced neurodegenerative disorders and these beneficial effects could be attributed to the polyphenolic compounds present in these natural products.

  1. Interactive effects of neonatal exposure to monosodium glutamate and aspartame on glucose homeostasis

    Directory of Open Access Journals (Sweden)

    Collison Kate S

    2012-06-01

    Full Text Available Abstract Background Recent evidence suggests that the effects of certain food additives may be synergistic or additive. Aspartame (ASP and Monosodium Glutamate (MSG are ubiquitous food additives with a common moiety: both contain acidic amino acids which can act as neurotransmitters, interacting with NMDA receptors concentrated in areas of the Central Nervous System regulating energy expenditure and conservation. MSG has been shown to promote a neuroendocrine dysfunction when large quantities are administered to mammals during the neonatal period. ASP is a low-calorie dipeptide sweetener found in a wide variety of diet beverages and foods. However, recent reports suggest that ASP may promote weight gain and hyperglycemia in a zebrafish nutritional model. Methods We investigated the effects of ASP, MSG or a combination of both on glucose and insulin homeostasis, weight change and adiposity, in C57BL/6 J mice chronically exposed to these food additives commencing in-utero, compared to an additive-free diet. Pearson correlation analysis was used to investigate the associations between body characteristics and variables in glucose and insulin homeostasis. Results ASP alone (50 mg/Kgbw/day caused an increase in fasting blood glucose of 1.6-fold, together with reduced insulin sensitivity during an Insulin Tolerance Test (ITT P  Conclusions Aspartame exposure may promote hyperglycemia and insulin intolerance. MSG may interact with aspartame to further impair glucose homeostasis. This is the first study to ascertain the hyperglycemic effects of chronic exposure to a combination of these commonly consumed food additives; however these observations are limited to a C57BL/6 J mouse model. Caution should be applied in extrapolating these findings to other species.

  2. Supplementing monosodium glutamate to partial enteral nutrition slows gastric emptying in preterm pigs(1-3).

    Science.gov (United States)

    Bauchart-Thevret, Caroline; Stoll, Barbara; Benight, Nancy M; Olutoye, Oluyinka; Lazar, David; Burrin, Douglas G

    2013-05-01

    Emerging evidence suggests that free glutamate may play a functional role in modulating gastroduodenal motor function. We hypothesized that supplementing monosodium glutamate (MSG) to partial enteral nutrition stimulates gastric emptying in preterm pigs. Ten-day-old preterm, parenterally fed pigs received partial enteral nutrition (25%) as milk-based formula supplemented with MSG at 0, 1.7, 3.0, and 4.3 times the basal protein-bound glutamate intake (468 mg·kg(-1)·d(-1)) from d 4 to 8 of life (n = 5-8). Whole-body respiratory calorimetry and (13)C-octanoic acid breath tests were performed on d 4, 6, and 8. Body weight gain, stomach and intestinal weights, and arterial plasma glutamate and glutamine concentrations were not different among the MSG groups. Arterial plasma glutamate concentrations were significantly higher at birth than after 8 d of partial enteral nutrition. Also at d 8, the significant portal-arterial concentration difference in plasma glutamate was substantial (∼500 μmol/L) among all treatment groups, suggesting that there was substantial net intestinal glutamate absorption in preterm pigs. MSG supplementation dose-dependently increased gastric emptying time and decreased breath (13)CO2 enrichments, (13)CO2 production, percentage of (13)CO2 recovery/h, and cumulative percentage recovery of (13)C-octanoic acid. Circulating glucagon-like peptide-2 (GLP-2) concentration was significantly increased by MSG but was not associated with an increase in intestinal mucosal growth. In contrast to our hypothesis, our results suggest that adding MSG to partial enteral nutrition slows the gastric emptying rate, which may be associated with an inhibitory effect of increased circulating GLP-2.

  3. Supplementing Monosodium Glutamate to Partial Enteral Nutrition Slows Gastric Emptying in Preterm Pigs123

    Science.gov (United States)

    Bauchart-Thevret, Caroline; Stoll, Barbara; Benight, Nancy M.; Olutoye, Oluyinka; Lazar, David; Burrin, Douglas G.

    2013-01-01

    Emerging evidence suggests that free glutamate may play a functional role in modulating gastroduodenal motor function. We hypothesized that supplementing monosodium glutamate (MSG) to partial enteral nutrition stimulates gastric emptying in preterm pigs. Ten-day-old preterm, parenterally fed pigs received partial enteral nutrition (25%) as milk-based formula supplemented with MSG at 0, 1.7, 3.0, and 4.3 times the basal protein-bound glutamate intake (468 mg·kg−1·d−1) from d 4 to 8 of life (n = 5–8). Whole-body respiratory calorimetry and 13C-octanoic acid breath tests were performed on d 4, 6, and 8. Body weight gain, stomach and intestinal weights, and arterial plasma glutamate and glutamine concentrations were not different among the MSG groups. Arterial plasma glutamate concentrations were significantly higher at birth than after 8 d of partial enteral nutrition. Also at d 8, the significant portal-arterial concentration difference in plasma glutamate was substantial (∼500 μmol/L) among all treatment groups, suggesting that there was substantial net intestinal glutamate absorption in preterm pigs. MSG supplementation dose-dependently increased gastric emptying time and decreased breath 13CO2 enrichments, 13CO2 production, percentage of 13CO2 recovery/h, and cumulative percentage recovery of 13C-octanoic acid. Circulating glucagon-like peptide-2 (GLP-2) concentration was significantly increased by MSG but was not associated with an increase in intestinal mucosal growth. In contrast to our hypothesis, our results suggest that adding MSG to partial enteral nutrition slows the gastric emptying rate, which may be associated with an inhibitory effect of increased circulating GLP-2. PMID:23446960

  4. Anorexigenic Lipopeptides Ameliorate Central Insulin Signaling and Attenuate Tau Phosphorylation in Hippocampi of Mice with Monosodium Glutamate-Induced Obesity

    Czech Academy of Sciences Publication Activity Database

    Špolcová, Andrea; Mikulášková, Barbora; Holubová, Martina; Nagelová, Veronika; Pirník, Zdenko; Zemenová, Jana; Haluzík, M.; Železná, Blanka; Galas, M. C.; Maletínská, Lenka

    2015-01-01

    Roč. 45, č. 3 (2015), s. 823-835 ISSN 1387-2877 R&D Projects: GA ČR GAP303/12/0576 Institutional support: RVO:61388963 Keywords : Alzheimer's disease * insulin signaling * liraglutide * monosodium glutamate-obese mice * obesity * pre- diabetes * prolactin-releasing peptide Subject RIV: CE - Biochemistry Impact factor: 3.920, year: 2015

  5. EFFECTS OF MONOSODIUM GLUTAMATE (UMAMI TASTE) WITH AND WITHOUT GUANOSINE 5'-MONOPHOSPHATE ON RAT AUTONOMIC RESPONSES TO MEALS

    NARCIS (Netherlands)

    STEFFENS, AB; LEUVENINK, H; SCHEURINK, AJW

    Monosodium glutamate (MSG) is used as a food additive to improve the taste of food. The effect of MSG on sweet taste is enhanced by guanosine 5'-monophosphate (GMP). Because increased palatability is known to increase the vagally mediated preabsorptive insulin response (PIR), we hypothesized that

  6. A precise temporal dissection of monosodium glutamate-induced apoptotic events in newborn rat retina in vivo.

    Science.gov (United States)

    Dénes, Viktória; Lakk, Mónika; Czotter, Nikoletta; Gábriel, Róbert

    2011-08-01

    Although L-glutamate is the main excitatory neurotransmitter in the retina, excess glutamate level triggers severe neuronal damages. Therefore, monosodium glutamate has been used to probe neurodegenerative mechanisms but precise toxicity schedule is not available in vivo. We report, for the first time, a temporal analysis of apoptotic processes induced by subcutaneously applied monosodium glutamate. We investigated the glutamate triggered subcellular processes over a time scale of 48 h in neonatal retina. We employed immunoblots to measure the level of activated apoptotic factors and immunocytochemistry to reveal the dying cells. Upregulation of active caspase-9 started at 3 h and peaked at 6 h post-injection. Activations of caspase-3, caspase-6 and caspase-7 consistent with their late-phase roles increased at 6 h post-injection. The apoptotic processes were terminated by 24 h post-injection. Caspase 12 and calpain-2 seemed unaffected by subcutaneous monosodium glutamate administration. Uniquely, we found that the ubiquitous calpain-1 is not expressed in newborn rat retina.

  7. Immunohistochemical evaluation of hippocampal CA1 region astrocytes in 10-day-old rats after monosodium glutamate treatment.

    Science.gov (United States)

    Krawczyk, A; Jaworska-Adamu, J; Rycerz, K

    2015-01-01

    High concentration of glutamate (Glu) is excitotoxic for nervous system structures. This may lead to glial reactivity ie. increased expression of glial fibrillary acidic protein (GFAP) and S100β protein, and also to hypertrophy and proliferation of cells which are determined by the presence of Ki-67 antigen. The aim of the study was to analyse the immunoreactivity of the GFAP, S100β and Ki-67 proteins in astrocytes of hippocampal CA1 region in young rats after administration of monosodium glutamate (MSG) at two doses: 2 g/kg b.w. (I group) and 4 g/kg b.w. (II group). In rats from I and II group morphologically altered astrocytes with the GFAP expression were observed in the SLM of the hippocampal CA1 region. The cells had eccentrically located nuclei and on the opposite site of the nuclei there were single or double, long and weakly branched processes. Moreover, in the SLM the increase of the number of GFAP and S100β immunopositive astrocytes and nuclei with Ki-67 expression, in contrary to control individuals, was observed. These results suggest the increased expression of the proteins in early reactions or hyperplasia which, together with cell hypertrophy, indicate late reactivity of astroglia in response to glutamate noxious effect.

  8. The Effect of MSG (Monosodium Glutamate) Addition on The Quality of Yoghurt Frozen Culture Starter Viewed Viability, pH Value and Acidity

    OpenAIRE

    Aris Sri Widati; Abdul Manab; Teguh Hadi Waluyo

    2012-01-01

    The objective of this study was to investigate wether the effect of percentage monosodium glutamat addition on the quality of yoghurt frozen culture starter viewed viability, pH value and acidity.The experimental design used in this study was Randomised Complete Design and the treatment were four levels of monosodium glutamate concentration respectively 0% (without monosodium glutamat) 10%, 15% and 20% from medium. Each treatment were three times replicated. The research result showed that th...

  9. Monosodium glutamate induced testicular toxicity and the possible ameliorative role of vitamin E or selenium in male rats

    Directory of Open Access Journals (Sweden)

    Reham Z. Hamza

    2014-01-01

    Full Text Available Monosodium glutamate (MSG has been recognized as flavor enhancer that adversely affects male reproductive systems. The present study was carried out to evaluate the potential protective role of vitamin E (vit E or selenium against MSG induced oxidative stress and histopathological changes in testis tissues of rats. Mature male Wistar rats weighing 150–200 g BW were allocated to evenly twelve groups each group of ten animals, the first group was maintained as control group, the 2nd, 3rd and 4th groups were administered MSG in three different dose levels (low, medium and high (6, 17.5 and 60 mg/kg BW, the 5th and 6th groups were given vit E in two doses (low and high (150 and 200 mg/kg, the 7th and 8th groups were administered selenium in two doses (low and high (0.25 and 1 mg/kg daily via gavage for a period of 30 days. Meanwhile the 9th and 10th groups were given combinations of MSG (high dose and vit E while, the 11th and 12th groups were given MSG (high dose plus selenium in two recommended doses for each one. Monosodium glutamate caused an elevation in lipid peroxidation level parallel with significant decline in SOD, CAT as well as GPx activities in testis tissues. Administration of vit E or selenium to MSG-treated groups declined lipid peroxidation, increased SOD, CAT, GPx activities. Selenium or vit E significantly reduced MSG induced histopathological changes by the entire restoration of the histological structures and the testicular antioxidant status to great extent in treated rats. In conclusion, supplementation of selenium or vit E could ameliorate the MSG induced testicular toxicity to great extent and reduce the oxidative stress on testis tissues.

  10. Monosodium glutamate stimulates secretion of glucagon-like peptide-1 and reduces postprandial glucose after a lipid-containing meal.

    Science.gov (United States)

    Hosaka, H; Kusano, M; Zai, H; Kawada, A; Kuribayashi, S; Shimoyama, Y; Nagoshi, A; Maeda, M; Kawamura, O; Mori, M

    2012-11-01

    Monosodium l-glutamate (MSG) is known to influence the endocrine system and gastrointestinal (GI) motility. The mechanism of postprandial glycemic control by food in the GI tract is mostly unknown and of great interest. To investigate the effect of MSG on glucose homeostasis, incretin secretion and gastric emptying in humans after a lipid-containing meal. Thirteen healthy male volunteers (mean age, 25.5 years) and with no Helicobcter pylori infection were enrolled. A 400 mL (520 kcal) liquid meal with MSG (2 g, 0.5% wt:vol) or NaCl (control) was ingested in a single-blind placebo-controlled cross-over study. Blood glucose, serum insulin, plasma glucagon, plasma glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide were measured. Gastric emptying was monitored by a 13C acetate breath test. Postprandial symptoms were assessed on a visual analogue scale. The 30-min postprandial glucose concentration was significantly reduced by adding MSG to the test meal. The area under the glucose concentration vs. time curve (0-60 min) was also significantly reduced by adding MSG (40.6 ± 3.51 mg·1 hr/dL with MSG vs. 49.2 ± 3.86 mg·1 hr/dL with NaCl, P = 0.047), whereas, the 30-min postprandial plasma GLP-1 level was significantly increased (58.1 ± 15.8 pmol/L with MSG vs. 13.4 ± 15.8 pmol/L with NaCl, P = 0.035). MSG did not affect the half gastric emptying time or postprandial symptoms. Monosodium l-glutamate improved early postprandial glycaemia after a lipid-containing liquid meal. This effect was not associated with a change in gastric emptying, but was possibly related to stimulation of glucagon-like peptide-1 secretion.

  11. [The influence of long-term monosodium glutamate feeding on the structure of rats pancreas].

    Science.gov (United States)

    Leshchenko, I V; Shevchuk, V H; Falalieieva, T M; Beregova, T V

    2012-01-01

    The influence of prolonged administration of monosodium glutamate (MSG) on pancreas in rats was studied. It was established that 30-days feeding by MSG in the doses 15 to 30 mg/kg (equivalent to 1 and 2 g/person) leads to necrotic, necrobiotic and degenerative changes in exocrine and endocrine cells, leukocytic and lymphoid infiltration, perivascular and interstitial fibrosis, edema and discirculatory disorders. Introduction of sodium glutamate increases the cross-sectional area of nuclei ofexocrine and endocrine cells, indicating intensification of synthetic processes in the cells of the pancreas and reduces the cross-sectional area of exocrine pancreatic cells, which is a sign of stimulation of secretory processes in exocrine cells. The changes described are characteristic of the acute pancreatitis. It is concluded that the maximum daily dose of food supplements containing glutamic acid and its salts should be reviewed because of their adverse effects on the pancreas. It is concluded that the maximum dose of MSG should be reconsidered taking into account its influence on the pancreas.

  12. Headache and mechanical sensitization of human pericranial muscles after repeated intake of monosodium glutamate (MSG).

    Science.gov (United States)

    Shimada, Akiko; Cairns, Brian E; Vad, Nynne; Ulriksen, Kathrine; Pedersen, Anne Marie Lynge; Svensson, Peter; Baad-Hansen, Lene

    2013-01-24

    A single intake of monosodium glutamate (MSG) may cause headache and increased muscle sensitivity. We conducted a double-blinded, placebo-controlled, crossover study to examine the effect of repeated MSG intake on spontaneous pain, mechanical sensitivity of masticatory muscles, side effects, and blood pressure. Fourteen healthy subjects participated in 5 daily sessions for one week of MSG intake (150 mg/kg) or placebo (24 mg/kg NaCl) (randomized, double-blinded). Spontaneous pain, pressure pain thresholds and tolerance levels for the masseter and temporalis muscles, side effects, and blood pressure were evaluated before and 15, 30, and 50 min after MSG intake. Whole saliva samples were taken before and 30 min after MSG intake to assess glutamate concentrations. Headache occurred in 8/14 subjects during MSG and 2/14 during placebo (P = 0.041). Salivary glutamate concentrations on Day 5 were elevated significantly (P < 0.05). Pressure pain thresholds in masseter muscle were reduced by MSG on Day 2 and 5 (P < 0.05). Blood pressure was significantly elevated after MSG (P < 0.040). In conclusion, MSG induced mechanical sensitization in masseter muscle and adverse effects such as headache and short-lasting blood pressure elevation for which tolerance did not develop over 5 days of MSG intake.

  13. Effects of monosodium glutamate supplementation on glutamine metabolism in adult rats.

    Science.gov (United States)

    Boutry, Claire; Bos, Cecile; Matsumoto, Hideki; Even, Patrick; Azzout-Marniche, Dalila; Tome, Daniel; Blachier, Francois

    2011-01-01

    Monosodium glutamate (MSG) is a worldwide used flavor enhancer. Supplemental glutamate may impact physiological functions. The aim of this study was to document the metabolic and physiological consequences of supplementation with 2% MSG (w/w) in rats. After 15 days-supplementation and following the ingestion of a test meal containing 2% MSG, glutamic acid accumulated for 5h in the stomach and for 1h in the small intestine. This coincided with a significant decrease of intestinal glutaminase activity, a marked specific increase in plasma glutamine concentration and a transient increase of plasma insulin concentration. MSG after chronic or acute supplementation had no effect on food intake, body weight, adipose tissue masses, gastric emptying rate, incorporation of dietary nitrogen in gastrointestinal and other tissues, and protein synthesis in intestinal mucosa, liver and muscles. The only significant effects of chronic supplementation were a slightly diminished gastrocnemius muscle mass, increased protein mass in intestinal mucosa and decreased protein synthesis in stomach. It is concluded that MSG chronic supplementation promotes glutamine synthesis in the body but has little effect on the physiological functions examined.

  14. Effect of monosodium glutamate on retinal vessel development and permeability in rats.

    Science.gov (United States)

    Bellhorn, R W; Lipman, D A; Confino, J; Burns, M S

    1981-08-01

    Monosodium glutamate (MSG) administered to neonatal rats on postnatal days 1 to 10 caused a generalized degeneration of the inner retinal layers. MSG administered only on postnatal days 8, 9, 10, and/or 11 caused a retinopathy limited to more peripheral retinal areas corresponding to currently existing regions of immature retinal vessels. Ink-injected retinal vessel studies showed a delay in development of the retinal vessel network but no alterations in vessel patency. Fluorescence microscopic examination of freeze-dried tissues revealed to abnormalities of the blood-retinal barriers to sodium fluorescein. We conclude, as demonstrated by these methods, that MSG retards development of the retinal vessels but does not affect development of the blood-retinal barriers. The retinotoxic effect of MSG apparently results from a mechanism(s) other than a breakdown of the blood-retinal barrier.

  15. Monosodium glutamate inhibits the lymphatic transport of lipids in the rat.

    Science.gov (United States)

    Kohan, Alison B; Yang, Qing; Xu, Min; Lee, Dana; Tso, Patrick

    2016-10-01

    It is not well understood how monosodium glutamate (MSG) affects gastrointestinal physiology, especially regarding the absorption and the subsequent transport of dietary lipids into lymph. Thus far, there is little information about how the ingestion of MSG affects the lipid lipolysis, uptake, intracellular esterification, and formation and secretion of chylomicrons. Using lymph fistula rats treated with the infusion of a 2% MSG solution before a continuous infusion of triglyceride, we show that MSG causes a significant decrease in both triglyceride and cholesterol secretion into lymph. Intriguingly, the diminished lymphatic transport of triglyceride and cholesterol was not caused by an accumulation of these labeled lipids in the intestinal lumen or in the intestinal mucosa. Rather, it is a result of increased portal transport in the animals fed acutely the lipid plus 2% MSG in the lipid emulsion. This is a first demonstration of MSG on intestinal lymphatic transport of lipids. Copyright © 2016 the American Physiological Society.

  16. Sex-dimorphism in Cardiac Nutrigenomics: effect of Trans fat and/or Monosodium Glutamate consumption

    Science.gov (United States)

    2011-01-01

    Background A paucity of information on biological sex-specific differences in cardiac gene expression in response to diet has prompted this present nutrigenomics investigation. Sexual dimorphism exists in the physiological and transcriptional response to diet, particularly in response to high-fat feeding. Consumption of Trans-fatty acids (TFA) has been linked to substantially increased risk of heart disease, in which sexual dimorphism is apparent, with males suffering a higher disease rate. Impairment of the cardiovascular system has been noted in animals exposed to Monosodium Glutamate (MSG) during the neonatal period, and sexual dimorphism in the growth axis of MSG-treated animals has previously been noted. Processed foods may contain both TFA and MSG. Methods We examined physiological differences and changes in gene expression in response to TFA and/or MSG consumption compared to a control diet, in male and female C57BL/6J mice. Results Heart and % body weight increases were greater in TFA-fed mice, who also exhibited dyslipidemia (P females weighed less than males (P males compared to females (P male DEGs were downregulated including Gata4, Mef2d and Srebf2. Enrichment of functional Gene Ontology (GO) categories were related to transcription, phosphorylation and anatomic structure (P males and downregulated in females, including pro-apoptotic histone deacetylase-2 (HDAC2). Sexual dimorphism was also observed in cardiac transcription from MSG-fed animals, with both sexes upregulating approximately 100 DEGs exhibiting sex-specific differences in GO categories. A comparison of cardiac gene expression between all diet combinations together identified a subset of 111 DEGs significant only in males, 64 DEGs significant in females only, and 74 transcripts identified as differentially expressed in response to dietary manipulation in both sexes. Conclusion Our model identified major changes in the cardiac transcriptional profile of TFA and/or MSG-fed mice compared to

  17. Impact of monosodium glutamate and /or gamma irradiation on pregnant rats and their embryos

    International Nuclear Information System (INIS)

    Ibrahim, M.F.; Darwish, M.M.

    2009-01-01

    The purpose of this study is to evaluate the destructive impact of the widely used nutritional flavouring agent, monosodium glutamate (MSG) and/or radiation stress on the female rats mothers and their developing embryos as judged by the maternal biochemical and embryological morphological and histopathological lesions induced. MSG is the sodium salt of glutamic acid, widely used as a food additive and flavour enhancer in modern nutrition. MSG (4 mg/rat) was daily administered subcutaneously to pregnant female rats from the 10 th to the 15 th gestational days during which they were subjected to intermittent radiation dose levels of 0.5 Gy increments delivered every other day up to a cumulative dose of 1.5 Gy whereas investigation has been carried out one day prior to parturition. MSG and radiation dual treatment resulted in increased maternal serum levels of lipid peroxides, total lipids, triglycerides, cholesterol and sodium together with decreased calcium concentrations. consequently, the developing embryos in the uteri, due to their increased sensitivity, showed various teratological and histological impairments . MSG and/or radiation induced effects were detected as growth retardation, malformations, intrauterine death and embryonic resorption. moreover, embryonic histological examination revealed ill-shaped vertebrae with degenerated osteogenic layer together with severely degenerated neurons

  18. Does monosodium glutamate really cause headache? : a systematic review of human studies.

    Science.gov (United States)

    Obayashi, Yoko; Nagamura, Yoichi

    2016-01-01

    Although monosodium glutamate (MSG) is classified as a causative substance of headache in the International Classification of Headache Disorders 3rd edition (ICHD-III beta), there is no literature in which causal relationship between MSG and headache was comprehensively reviewed. We performed systematic review of human studies which include the incidence of headache after an oral administration of MSG. An analysis was made by separating the human studies with MSG administration with or without food, because of the significant difference of kinetics of glutamate between those conditions (Am J Clin Nutr 37:194-200, 1983; J Nutr 130:1002S-1004S, 2000) and there are some papers which report the difference of the manifestation of symptoms after MSG ingestion with or without food (Food Chem Toxicol 31:1019-1035, 1993; J Nutr 125:2891S-2906S, 1995). Of five papers including six studies with food, none showed a significant difference in the incidence of headache except for the female group in one study. Of five papers including seven studies without food, four studies showed a significant difference. Many of the studies involved administration of MSG in solution at high concentrations (>2 %). Since the distinctive MSG is readily identified at such concentrations, these studies were thought not to be properly blinded. Because of the absence of proper blinding, and the inconsistency of the findings, we conclude that further studies are required to evaluate whether or not a causal relationship exists between MSG ingestion and headache.

  19. Dietary supplementation with monosodium glutamate is safe and improves growth performance in postweaning pigs.

    Science.gov (United States)

    Rezaei, Reza; Knabe, Darrell A; Tekwe, Carmen D; Dahanayaka, Sudath; Ficken, Martin D; Fielder, Susan E; Eide, Sarah J; Lovering, Sandra L; Wu, Guoyao

    2013-03-01

    Dietary intake of glutamate by postweaning pigs is markedly reduced due to low feed consumption. This study was conducted to determine the safety and efficacy of dietary supplementation with monosodium glutamate (MSG) in postweaning pigs. Piglets were weaned at 21 days of age to a corn and soybean meal-based diet supplemented with 0, 0.5, 1, 2, and 4 % MSG (n = 25/group). MSG was added to the basal diet at the expense of cornstarch. At 42 days of age (21 days after weaning), blood samples (10 mL) were obtained from the jugular vein of 25 pigs/group at 1 and 4 h after feeding for hematological and clinical chemistry tests; thereafter, pigs (n = 6/group) were euthanized to obtain tissues for histopathological examinations. Feed intake was not affected by dietary supplementation with 0-2 % MSG and was 15 % lower in pigs supplemented with 4 % MSG compared with the 0 % MSG group. Compared with the control, dietary supplementation with 1, 2 and 4 % MSG dose-dependently increased plasma concentrations of glutamate, glutamine, and other amino acids (including lysine, methionine, phenylalanine and leucine), daily weight gain, and feed efficiency in postweaning pigs. At day 7 postweaning, dietary supplementation with 1-4 % MSG also increased jejunal villus height, DNA content, and antioxidative capacity. The MSG supplementation dose-dependently reduced the incidence of diarrhea during the first week after weaning. All variables in standard hematology and clinical chemistry tests, as well as gross and microscopic structures, did not differ among the five groups of pigs. These results indicate that dietary supplementation with up to 4 % MSG is safe and improves growth performance in postweaning pigs.

  20. The significance of excursions above the ADI. Case study: monosodium glutamate.

    Science.gov (United States)

    Walker, R

    1999-10-01

    Monosodium glutamate (MSG) has been allocated an "ADI not specified" by the JECFA, which indicates that no toxicological concerns arise associated with its use as a food additive in accordance with good manufacturing practice (GMP) and for that reason it is not necessary to allocate a numerical ADI. The question in this case, then, is not whether excursions above a numerical ADI might occur but whether high peak intakes might arise which could invalidate the assumption of absence of hazard. Two major issues have arisen in relation to high intakes of MSG: (1) What is the significance of neural damage (focal necrosis in the hypothalamus) seen following high parenteral or intragastric doses of MSG to neonatal animals and is this a particular risk for children? (2) What is the role of MSG in "Chinese Restaurant Syndrome" (flushing, tightness of the chest, difficulty in breathing, etc.) following consumption of Chinese foods? In relation to the first issue, human studies have been crucial in resolving the question. The threshold blood levels associated with neuronal damage in the mouse (most sensitive species) are 100-130 mumol/dl in neonates rising to > 630 mumol/dl in adult animals. In humans, plasma levels of this magnitude have not been recorded even after bolus doses of 150 mg/kg body wt (ca. 10 g for an adult). Additionally, studies in infants have confirmed that the human baby can metabolize glutamate as effectively as adults. It is concluded that blood levels of glutamate + aspartate do not rise significantly even after abuse doses and babies are no more at risk than adults. Intake levels associated with the use of MSG as a food additive and natural levels of glutamic acid in foods therefore do not raise toxicological concerns even at high peak levels of intake. It is not envisaged that use of MSG according to GMP requires the allocation of a numerical ADI. With regard to the second issue, controlled double-blind crossover studies have failed to establish a

  1. The Effect of MSG (Monosodium Glutamate Addition on The Quality of Yoghurt Frozen Culture Starter Viewed Viability, pH Value and Acidity

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    Aris Sri Widati

    2012-02-01

    Full Text Available The objective of this study was to investigate wether the effect of percentage monosodium glutamat addition on the quality of yoghurt frozen culture starter viewed viability, pH value and acidity.The experimental design used in this study was Randomised Complete Design and the treatment were four levels of monosodium glutamate concentration respectively 0% (without monosodium glutamat 10%, 15% and 20% from medium. Each treatment were three times replicated. The research result showed that the difference of monosodium glutamate concentration  did not gave a significant effect (P>0.05 on viability of yoghurt frozen culture starter and acidity of yoghurt made by frozen culture starter but it gave a significant effect (P<0.05 on pH value. It can be concluded that different monosodium glutamate concentration had a different quality on frozen culture starter yoghurt. The addition of monosodium glutamate up to 20% necessarily indicate increase on quality of yoghurt frozen culture starter. Keywords: culture starter yoghurt, freezing, cryoprotectant

  2. Monosodium glutamate derived tricolor fluorescent carbon nanoparticles for cell-imaging application.

    Science.gov (United States)

    Zheng, Nannan; Ding, Sha; Zhou, Xingping

    2016-06-01

    Fluorescent carbon nanoparticle (FCN) is a new type of carbon-based materials. Because of its wide raw material sources, excellent optical properties and good biocompatibility, FCN is getting more and more attentions. However, its synthesis from resources at low cost under mild conditions is still a challenge. Here we report a novel and simple method derived from monosodium glutamate carbonization to make tricolor fluorescent carbon nanoparticles with an average size below 10nm, a high yield up to 35.2% based on the carbon content in the resource, a long life-time of 3.71ns, and a high fluorescence quantum yield up to 51.5% by using quinine sulfate as the standard substance. We discovered that the fluorescent stability of the FCNs was very excellent under UV irradiation for hours in aqueous solutions of pH ranged from 2.0 to 9.0. The cell viability tested under a pretty high concentration of FCNs indicated their safety for biological applications. Based on their high fluorescence quantum efficiency and the advantages mentioned above, these FCNs were then used for cell imaging and exhibited a perfect performance under 3 kinds of excitation bands (UV, blue, and green lights). Thus, they can be practically applied to immune labeling and imaging in vivo in the near future. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. Monosodium glutamate (MSG consumption is associated with urolithiasis and urinary tract obstruction in rats.

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    Amod Sharma

    Full Text Available BACKGROUND: The peritoneal injection of monosodium glutamate (MSG can induce kidney injury in adult rats but the effects of long-term oral intake have not been determined. METHODS: We investigated the kidney histology and function in adult male Wistar rats that were fed ad libitum with a standard rat chow pellet and water with or without the addition of 2 mg/g body weight MSG/day in drinking water (n=10 per group. Both MSG-treated and control animals were sacrificed after 9 months when renal function parameters, blood and urine electrolytes, and tissue histopathology were determined. RESULTS: MSG-treated rats were more prone to kidney stone formation, as represented by the alkaline urine and significantly higher activity product of calcium phosphate. Accordingly, 3/10 MSG-treated rats developed kidney stones over 9 months versus none of the control animals. Further, 2/10 MSG-treated rats but none (0/10 of the controls manifested hydronephrosis. MSG-treated rats had significantly higher levels of serum creatinine and potassium including urine output volume, urinary excretion sodium and citrate compared to controls. In contrast, MSG-treated rats had significantly lower ammonium and magnesium urinary excretion. CONCLUSION: Oral MSG consumption appears to cause alkaline urine and may increase the risks of kidney stones with hydronephrosis in rats. Similar effects in humans must be verified by dedicated studies.

  4. Monosodium glutamate in its anhydrous and monohydrate form: Differentiation by Raman spectroscopies and density functional calculations

    Science.gov (United States)

    Peica, N.; Lehene, C.; Leopold, N.; Schlücker, S.; Kiefer, W.

    2007-03-01

    Monosodium glutamate (MSG), a common flavor enhancer, is detected in aqueous solutions by Raman and surface-enhanced Raman (SERS) spectroscopies at the micromolar level. The presence of different species, such as protonated and unprotonated MSG, is demonstrated by concentration and pH dependent Raman and SERS experiments. In particular, the symmetric bending modes of the amino group and the stretching modes of the carboxy moiety are employed as marker bands. The protonation of the NH 2 group at acidic pH values, for example, is detected in the Raman spectra. From the measured SERS spectra, a strong chemical interaction of MSG with the colloidal particles is deduced and a geometry of MSG adsorbed on the silver surface is proposed. In order to assign the observed Raman bands, calculations employing density functional theory (DFT) were performed. The calculated geometries, harmonic vibrational wavenumbers and Raman scattering activities for both MSG forms are in good agreement with experimental data. The set of theoretical data enables a complete vibrational assignment of the experimentally detected Raman spectra and the differentiation between the anhydrous and monohydrate forms of MSG.

  5. Use of monosodium glutamate by-product in cow diet on performance of lactating dairy cows.

    Science.gov (United States)

    Padunglerk, Achira; Prasanpanich, Somkiert; Kongmun, Phongthorn

    2017-01-01

    Eight multiparous lactating Holstein cows were randomly assigned in a 4 × 4 replicated Latin square design to receive four dietary treatments. The dietary treatments were monosodium glutamate by-product (MSGB) replacement for soybean meal in concentrate at four levels: MSGB replacement at 0, 20, 40 and 60%, respectively. Pangola hay was given on an ad libitum basis. It was found that total dry matter intake, concentrate intake, pangola hay intake and all apparent digestibilities were not different among treatments. Ammonia nitrogen concentration in the rumen at 4 h post-feeding was significantly different, in which the 0% treatment had the highest (P < 0.05) while the 20% treatment had the lowest. Milk fat percentage was the highest (P < 0.05) in the 0% treatment. MSGB replacement at 40% and 60% were shown to be the lowest (P < 0.05) feed cost for milk production, and profitability of milk production was the highest (P < 0.05) for the 60% treatment. Based on this experiment, it could be concluded that MSGB replacement for soybean meal at 20-60% in the feed for dairy cows presented no negative effects on their performances. In addition, it could decrease feed cost 2.9-17.3% and increase milk production profit up to 33.3% in the 60% treatment. © 2016 Japanese Society of Animal Science.

  6. HISTOLOGICAL STUDIES OF THE EFFECTS OF MONOSODIUM GLUTAMATE ON THE INFERIOR COLLICULUS OF ADULT WISTAR RATS.

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    A.O. Eweka.

    2008-01-01

    Full Text Available Histological effects of Monosodium glutamate (MSG commonly used as food additive on the inferior colliculus (IC of adult Wistar rats were carefully studied. The rats of both sexes (n=24, average weight of 185g were randomly assigned into two treatments (n=16 and control (n=8 groups. The rats in the treatment groups received 3g and 6g of MSG thoroughly mixed with their feeds for fourteen days, while the control rats received equal amounts of feeds without MSG added. The rats were fed with growers' mash purchased from Edo Feeds and Flour Mill Ltd, Ewu, Edo State and were given water liberally. The rats were sacrificed on day fifteen of the experiment. The inferior colliculus was carefully dissected out and quickly fixed in 10% formal saline for routine histological study after H&E method.The histological findings after H&E methods indicated that the treated sections of the inferior colliculus showed some cellular degenerative changes, cellular hypertrophy, and autophagic vacuoles with some intercellular vacuolations appearing in the stroma, and some degree of neuronal hypertrophy when compared to the control sections.These findings indicate that MSG consumption may have a deleterious effect on the neurons of the inferior colliculus (IC. MSG may probably have adverse effects on the auditory sensibilities by its deleterious effects on the nerve cells of the IC of adult Wistar rats. It is recommended that further studies aimed at corroborating these observations be carried out.

  7. Does acute or habitual protein deprivation influence liking for monosodium glutamate?

    Science.gov (United States)

    Masic, Una; Yeomans, Martin R

    2017-03-15

    The umami flavour generated by monosodium glutamate (MSG) has been proposed as the marker for the presence of protein in foods. As protein is the most closely regulated macronutrient in the diet, the present study addressed whether acute protein deprivation, habitual protein intake or a combination of the two influenced liking for the taste of MSG. 24 low-restraint male participants (mean age: 22; BMI: 23) consumed either their habitual breakfast (baseline), a low protein breakfast (breakfast meal with low protein milk and milkshake) or a high protein breakfast (breakfast meal with high protein milk and milkshake) on three different days, and then evaluated the acceptability of umami (MSG), salty (NaCl) or sweet (Acesulphame K) tastes at low or high concentrations in a soup context at lunchtime. Participants also completed a habitual protein intake questionnaire (39-item protein Food Frequency Questionnaire). Liking for all tastes was higher on the low than on the high protein day, and NaCl and Acesulphame K were liked less on both protein manipulation days when compared to the no added flavour control. Habitual protein intake was not related to liking for MSG stimuli alone but habitual high protein consumers rated a high concentration of MSG as more pleasant than any other taste when in protein deficit. Overall, these findings suggest that liking for high MSG concentrations may be moderated by nutritional need in high protein consumers. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

  8. Neonatal exposure to monosodium glutamate induces morphological alterations in suprachiasmatic nucleus of adult rat.

    Science.gov (United States)

    Rojas-Castañeda, Julio César; Vigueras-Villaseñor, Rosa María; Chávez-Saldaña, Margarita; Rojas, Patricia; Gutiérrez-Pérez, Oscar; Rojas, Carolina; Arteaga-Silva, Marcela

    2016-02-01

    Neonatal exposure to monosodium glutamate (MSG) induces circadian disorders in several physiological and behavioural processes regulated by the suprachiasmatic nucleus (SCN). The objective of this study was to evaluate the effects of neonatal exposure to MSG on locomotor activity, and on morphology, cellular density and expression of proteins, as evaluated by optical density (OD), of vasopressin (VP)-, vasoactive intestinal polypeptide (VIP)- and glial fibrillary acidic protein (GFAP)-immunoreactive cells in the SCN. Male Wistar rats were used: the MSG group was subcutaneously treated from 3 to 10 days of age with 3.5 mg/g/day. Locomotor activity was evaluated at 90 days of age using 'open-field' test, and the brains were processed for immunohistochemical studies. MSG exposure induced a significant decrease in locomotor activity. VP- and VIP-immunoreactive neuronal densities showed a significant decrease, while the somatic OD showed an increase. Major axes and somatic area were significantly increased in VIP neurons. The cellular and optical densities of GFAP-immunoreactive sections of SCN were significantly increased. These results demonstrated that newborn exposure to MSG induced morphological alterations in SCN cells, an alteration that could be the basis for behavioural disorders observed in the animals. © 2016 The Authors. International Journal of Experimental Pathology © 2016 International Journal of Experimental Pathology.

  9. Protective effects of N-acetylcysteine against monosodium glutamate-induced astrocytic cell death.

    Science.gov (United States)

    Park, Euteum; Yu, Kyoung Hwan; Kim, Do Kyung; Kim, Seung; Sapkota, Kumar; Kim, Sung-Jun; Kim, Chun Sung; Chun, Hong Sung

    2014-05-01

    Monosodium glutamate (MSG) is a flavor enhancer, largely used in the food industry and it was reported to have excitotoxic effects. Higher amounts of MSG consumption have been related with increased risk of many diseases, including Chinese restaurant syndrome and metabolic syndromes in human. This study investigated the protective effects of N-acetylcysteine (NAC) on MSG-induced cytotoxicity in C6 astrocytic cells. MSG (20 mM)-induced reactive oxygen species (ROS) generation and apoptotic cell death were significantly attenuated by NAC (500 μM) pretreatment. NAC effectively inhibited the MSG-induced mitochondrial membrane potential (MMP) loss and intracellular reduced glutathione (GSH) depletion. In addition, NAC significantly attenuated MSG-induced endoplasmic reticulum (ER) stress markers, such as XBP1 splicing and CHOP, PERK, and GRP78 up-regulation. Furthermore, NAC prevented the changes of MSG-induced Bcl-2 expression level. These results suggest that NAC can protect C6 astrocytic cells against MSG-induced oxidative stress, mitochondrial dysfunction, and ER stress. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. Monosodium glutamate in chicken and beef stock cubes using high-performance liquid chromatography.

    Science.gov (United States)

    Demirhan, Buket Er; Demirhan, Burak; Sönmez, Ceren; Torul, Hilal; Tamer, Uğur; Yentür, Gülderen

    2015-01-01

    In this survey monosodium glutamate (MSG) levels in chicken and beef stock cube samples were determined. A total number of 122 stock cube samples (from brands A, B, C, D) were collected from local markets in Ankara, Turkey. High-performance liquid chromatography with diode array detection (HPLC-DAD) was used for quantitative MSG determination. Mean MSG levels (±SE) in samples of A, B, C and D brands were 14.6 ± 0.2 g kg⁻¹, 11.9 ± 0.3 g kg⁻¹, 9.7 ± 0.1 g kg⁻¹ and 7.2 ± 0.1 g kg⁻¹, respectively. Differences between mean levels of brands were significant. Also, mean levels of chicken stock cube samples were lower than in beef stock cubes. Maximum limits for MSG in stock cubes are not specified in the Turkish Food Codex (TFC). Generally the limit for MSG in foods (except some foods) is established as 10 g kg⁻¹ (individually or in combination).

  11. Mixotrophic growth and biochemical analysis of Chlorella vulgaris cultivated with diluted monosodium glutamate wastewater.

    Science.gov (United States)

    Ji, Yan; Hu, Wenrong; Li, Xiuqing; Ma, Guixia; Song, Mingming; Pei, Haiyan

    2014-01-01

    Monosodium glutamate wastewater (MSGW) is a potential medium for microbial cultivation because of containing abundant organic nutrient. This paper seeks to evaluate the feasibility of growing Chlorella vulgaris with MSGW and assess the influence of MSGW concentration on the biomass productivity and biochemical compositions. The MSGW diluted in different concentrations was prepared for microalga cultivation. C. vulgaris growth was greatly promoted with MSGW compared with the inorganic BG11 medium. C. vulgaris obtained the maximum biomass concentration (1.02 g/L) and biomass productivity (61.47 mg/Ld) with 100-time diluted MSGW. The harvested biomass was rich in protein (36.01-50.64%) and low in lipid (13.47-25.4%) and carbohydrate (8.94-20.1%). The protein nutritional quality and unsaturated fatty acids content of algal increased significantly with diluted MSGW. These results indicated that the MSGW is a feasible alternative for mass cultivation of C. vulgaris. Copyright © 2013 Elsevier Ltd. All rights reserved.

  12. Protective effect of Piper longum Linn. on monosodium glutamate induced oxidative stress in rats.

    Science.gov (United States)

    Thomas, Mariyamma; Sujatha, K S; George, Sisilamma

    2009-03-01

    Protective effect of ethanol extract of Piper longum Linn. against monosodium glutamate (MSG) induced toxicity was studied. Rats, orally administered with MSG at a dose of 8 mg/g body weight for 20 consecutive days, showed an increase in liver weight and rate of lipid peroxidation. Glutathione (GSH) in serum, liver and kidney showed decreased concentration. Significant increase was noticed in activities of serum alanine amino transferase (ALT) and aspartate amino transferase (AST), levels of serum triacylglycerol, total cholesterol and urea. Histopathological examination of liver and kidney showed central venous congestion, diffuse degeneration and necrosis of hepatocytes in para cortical and midzonal areas of liver and diffuse cortical tubular degeneration of kidney. Oral administration of ethanol extract of P. longum fruits at 300 mg/kg body weight along with MSG significantly reduced the levels of lipid peroxides in serum, liver and kidney, serum AST activity, serum levels of triacylglycerol and total cholesterol. Though, there was an increase in the level of GSH in tissues it was not significant. However, the treatment failed to reduce the levels of ALT and urea. Examination of tissue sections also exhibited normal histological architecture of both the organs. The present study revealed that administration of P. longum provided significant protection to liver and kidney from the oxidative stress of MSG, though the dose rate was not sufficient to provide a complete protection.

  13. Monosodium glutamate-sensitive hypothalamic neurons contribute to the control of bone mass

    Science.gov (United States)

    Elefteriou, Florent; Takeda, Shu; Liu, Xiuyun; Armstrong, Dawna; Karsenty, Gerard

    2003-01-01

    Using chemical lesioning we previously identified hypothalamic neurons that are required for leptin antiosteogenic function. In the course of these studies we observed that destruction of neurons sensitive to monosodium glutamate (MSG) in arcuate nuclei did not affect bone mass. However MSG treatment leads to hypogonadism, a condition inducing bone loss. Therefore the normal bone mass of MSG-treated mice suggested that MSG-sensitive neurons may be implicated in the control of bone mass. To test this hypothesis we assessed bone resorption and bone formation parameters in MSG-treated mice. We show here that MSG-treated mice display the expected increase in bone resorption and that their normal bone mass is due to a concomitant increase in bone formation. Correction of MSG-induced hypogonadism by physiological doses of estradiol corrected the abnormal bone resorptive activity in MSG-treated mice and uncovered their high bone mass phenotype. Because neuropeptide Y (NPY) is highly expressed in MSG-sensitive neurons we tested whether NPY regulates bone formation. Surprisingly, NPY-deficient mice had a normal bone mass. This study reveals that distinct populations of hypothalamic neurons are involved in the control of bone mass and demonstrates that MSG-sensitive neurons control bone formation in a leptin-independent manner. It also indicates that NPY deficiency does not affect bone mass.

  14. Metabolomic profiling of urinary changes in mice with monosodium glutamate-induced obesity.

    Science.gov (United States)

    Pelantová, Helena; Bártová, Simona; Anýž, Jiří; Holubová, Martina; Železná, Blanka; Maletínská, Lenka; Novák, Daniel; Lacinová, Zdena; Šulc, Miroslav; Haluzík, Martin; Kuzma, Marek

    2016-01-01

    Obesity with related complications represents a widespread health problem. The etiopathogenesis of obesity is often studied using numerous rodent models. The mouse model of monosodium glutamate (MSG)-induced obesity was exploited as a model of obesity combined with insulin resistance. The aim of this work was to characterize the metabolic status of MSG mice by NMR-based metabolomics in combination with relevant biochemical and hormonal parameters. NMR analysis of urine at 2, 6, and 9 months revealed altered metabolism of nicotinamide and polyamines, attenuated excretion of major urinary proteins, increased levels of phenylacetylglycine and allantoin, and decreased concentrations of methylamine in urine of MSG-treated mice. Altered levels of creatine, citrate, succinate, and acetate were observed at 2 months of age and approached the values of control mice with aging. The development of obesity and insulin resistance in 6-month-old MSG mice was also accompanied by decreased mRNA expressions of adiponectin, lipogenetic and lipolytic enzymes and peroxisome proliferator-activated receptor-gamma in fat while mRNA expressions of lipogenetic enzymes in the liver were enhanced. At the age of 9 months, biochemical parameters of MSG mice were normalized to the values of the controls. This fact pointed to a limited predictive value of biochemical data up to age of 6 months as NMR metabolomics confirmed altered urine metabolic composition even at 9 months.

  15. Proteomic analysis of kidney in rats chronically exposed to monosodium glutamate.

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    Amod Sharma

    Full Text Available Chronic monosodium glutamate (MSG intake causes kidney dysfunction and renal oxidative stress in the animal model. To gain insight into the renal changes induced by MSG, proteomic analysis of the kidneys was performed.Six week old male Wistar rats were given drinking water with or without MSG (2 mg/g body weight, n = 10 per group for 9 months. Kidneys were removed, frozen, and stored at -75°C. After protein extraction, 2-D gel electrophoresis was performed and renal proteome profiles were examined with Colloidal Coomassie Brilliant Blue staining. Statistically significant protein spots (ANOVA, p<0.05 with 1.2-fold difference were excised and analyzed by LC-MS. Proteomic data were confirmed by immunohistochemistry and Western blot analyses.The differential image analysis showed 157 changed spots, of which 71 spots were higher and 86 spots were lower in the MSG-treated group compared with those in the control group. Eight statistically significant and differentially expressed proteins were identified: glutathione S-transferase class-pi, heat shock cognate 71 kDa, phosphoserine phosphatase, phosphoglycerate kinase, cytosolic glycerol-3-phosphate dehydrogenase, 2-amino-3-carboxymuconate-6-semialdehyde decarboxylase, α-ketoglutarate dehydrogenase and succinyl-CoA ligase.The identified proteins are mainly related to oxidative stress and metabolism. They provide a valuable clue to explore the mechanism of renal handling and toxicity on chronic MSG intake.

  16. Monosodium glutamate, a food additive, induces depressive-like and anxiogenic-like behaviors in young rats.

    Science.gov (United States)

    Quines, Caroline B; Rosa, Suzan G; Da Rocha, Juliana T; Gai, Bibiana M; Bortolatto, Cristiani F; Duarte, Marta Maria M F; Nogueira, Cristina W

    2014-06-27

    Monosodium glutamate (MSG) has been the target of research due to its toxicological effects. We investigated the depressive- and anxiogenic-like behaviors in rats exposed to neonatal subcutaneous injection of MSG. The involvement of the serotonergic system, by measuring [(3)H] serotonin (5-HT) uptake in cerebral cortices, and the hypothalamic pituitary adrenal (HPA) axis, by determining serum adrenocorticotropic hormone (ACTH) and corticosterone levels, was also examined. Male and female newborn Wistar rats were divided into control and MSG groups, which received, respectively, a daily subcutaneous injection of saline (0.9%) or MSG (4 g/kg/day) from the 1st to 5th postnatal day. The behavioral tests [spontaneous locomotor activity, contextual fear conditioning, and forced swimming test (FST)] were performed from the 60th to 64th postnatal day. MSG-treated animals showed alteration in the spontaneous locomotor activity, an increase in the number of fecal pellets and the number of animal's vocalizations and urine occurrence, and a decrease in the grooming time. The MSG exposure increased the immobility time in the FST and the freezing reaction in the contextual fear conditioning. Additionally, MSG treatment increased the [(3)H]5-HT uptake in the cerebral cortices of rats and induced a deregulation of HPA axis function (by increasing serum ACTH and corticosterone levels). In conclusion MSG-treated rats are more susceptible to develop anxiogenic- and depressive-like behaviors, which could be related to a dysfunction in the serotonergic system. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. Effect of NaCl/Monosodium Glutamate (MSG) Mixture on the Sensorial Properties and Quality Characteristics of Model Meat Products.

    Science.gov (United States)

    Chun, Ji-Yeon; Kim, Byong-Soo; Lee, Jung-Gyu; Cho, Hyung-Yong; Min, Sang-Gi; Choi, Mi-Jung

    2014-01-01

    Sodium chloride is an important ingredient added to most of foods which contributes to flavor enhancement and food preservation but excess intake of sodium chloride may also cause various diseases such as heart diseases, osteoporosis and so on. Therefore, this study was carried out to investigate the effect of monosodium glutamate (MSG) as a salty flavor enhancer on the quality and sensorial properties of the NaCl/MSG complex and actual food system. For characterizing the spray-dried NaCl/MSG complex, surface dimension, morphology, rheology, and saltiness intensity were estimated by increasing MSG (0-2.0%) levels at a fixed NaCl concentration (2.0%). MSG levels had no effect of the characteristics of the NaCl/MSG complex, although the addition of MSG increased the surface dimension of the NaCl/MSG complex significantly (pmeat products (pork patties) were prepared by replacing NaCl with MSG. MSG enhanced the salty flavor, thereby increasing overall acceptability of pork patties. Replacement of NaCl with MSG (sensorial properties of pork patties, although quality deterioration such as high cooking loss was found. Nevertheless, MSG had a potential application in meat product formulation as a salty flavor enhancer or a partial NaCl replacer when meat products were supplemented with binding agents.

  18. Effect of dietary monosodium glutamate on trans fat-induced nonalcoholic fatty liver disease

    Science.gov (United States)

    Collison, Kate S.; Maqbool, Zakia; Saleh, Soad M.; Inglis, Angela; Makhoul, Nadine J.; Bakheet, Razan; Al-Johi, Mohammed; Al-Rabiah, Rana; Zaidi, Marya Z.; Al-Mohanna, Futwan A.

    2009-01-01

    The effects of dietary monosodium glutamate (MSG) on trans-fatty acid (TFA)-induced nonalcoholic fatty liver disease (NAFLD) are addressed in an animal model. We used Affymetrix microarray analysis to investigate hepatic gene expression and the contribution of visceral white adipose tissue (WAT) to diet-induced NAFLD. Trans-fat feeding increased serum leptin, FFA, HDL-cholesterol (HDL-C), and total cholesterol (T-CHOL) levels, while robustly elevating the expression of genes involved in hepatic lipogenesis, including the transcription factor sterol-regulatory element binding protein 1c. Histological examination revealed hepatic macrosteatosis in TFA-fed animals. Conversely, dietary MSG at doses similar to human average daily intake caused hepatic microsteatosis and the expression of β-oxidative genes. Serum triglyceride, FFA, and insulin levels were elevated in MSG-treated animals. The abdominal cavities of TFA- or MSG-treated animals had increased WAT deposition compared with controls. Microarray analysis of WAT gene expression revealed increased lipid biosynthetic gene expression, together with a 50% decrease in the key transcription factor Ppargc1a. A combination of TFA+MSG resulted in the highest levels of serum HDL-C, T-CHOL, and leptin. Microarray analysis of TFA+MSG-treated livers showed elevated expression of markers of hepatic inflammation, lipid storage, cell damage, and cell cycle impairment. TFA+MSG mice also had a high degree of WAT deposition and lipogenic gene expression. Levels of Ppargc1a were further reduced to 25% by TFA+MSG treatment. MSG exacerbates TFA-induced NAFLD. PMID:19001666

  19. Histological changes in kidneys of adult rats treated with Monosodium glutamate: A light microscopic study

    Directory of Open Access Journals (Sweden)

    Singh BR, Ujwal Gajbe, Anil Kumar Reddy, Vandana Kumbhare

    2015-01-01

    Full Text Available Introduction: Monosodium Glutamate (MSG, which is chemically known as AJI-NO-MOTO also familiar as MSG in routine life. MSG is always considered to be a controversial food additive used in the world. It is a natural excitatory neurotransmitter, helps in transmitting the fast synaptic signals in one third of CNS. Liver and kidney play a crucial role in metabolism as well as elimination of MSG from the body. Present study is to detect structural changes in adult rat kidney tissue treated with MSG; observations are done with a light microscope. Materials & Methods: The study was conducted in the department of Anatomy, J.N.M.C, Sawangi (M Wardha. Thirty (30 adult Wistar rats (2-3 months old weighing about (200 ± 20g were used in the current study, animals were divided into three groups (Group – A, B, C. Group A: Control, Group B: 3 mg /gm body weight, Group C: 6 mg /gm body weight, MSG were administered orally daily for 45 days along with the regular diet. Observations & Results: The Mean values of animals weight at the end of experiment (46th day respectively were 251.2 ± 13, 244.4 ± 19.9 and 320 ± 31.1. Early degenerative changes like, Glomerular shrinkage (GSr, loss of brush border in proximal convoluted tubules and Cloudy degeneration was observed in sections of kidney treated with 3 mg/gm body weight of MSG. Animals treated with 6 mg/gm body weight of MSG showed rare changes like interstitial chronic inflammatory infiltrate with vacuolation in some of the glomeruli, and much glomerular shrinkage invaginated by fatty lobules. Conclusion: The effects of MSG on kidney tissues of adult rats revealed that the revelatory changes are directly proportional to the doses of MSG.

  20. Neonatal monosodium glutamate treatment causes obesity, diabetes, and macrovesicular steatohepatitis with liver nodules in DIAR mice.

    Science.gov (United States)

    Tsuneyama, Koichi; Nishida, Takeshi; Baba, Hayato; Taira, Shu; Fujimoto, Makoto; Nomoto, Kazuhiro; Hayashi, Shinichi; Miwa, Shigeharu; Nakajima, Takahiko; Sutoh, Mitsuko; Oda, Emu; Hokao, Ryoji; Imura, Johji

    2014-09-01

    Non-alcoholic steatohepatitis (NASH) is the hepatic manifestation of metabolic syndrome (MS). Monosodium glutamate (MSG)-treated ICR mice is a useful model of MS and NASH, but it shows the different patterns of steatosis from human NASH. Because inbred aged DIAR (ddY, Institute for Animal Reproduction) mice spontaneously show the similar pattern of steatosis as NASH, we analyzed their liver pathology after administering MSG. MSG-treated DIAR mice (DIAR-MSG) and untreated DIAR mice (DIAR-controls) were sacrificed and assessed histopathologically at 29, 32, 40, 48, and 54 weeks of age. The NASH activity score, body mass index, blood glucose level, and oral glucose tolerance test were also assessed. The body mass index and blood glucose levels of DIAR-MSG were significantly higher than controls. The oral glucose tolerance test revealed a type 2 diabetes pattern in DIAR-MSG. The livers of DIAR-MSG mice showed macrovesicular steatosis, lobular inflammation with neutrophils, and ballooning degeneration after 29 weeks. At 54 weeks, mild fibrosis was observed in 5/6 DIAR-MSG and 2/5 DIAR-control mice. In imaging mass spectrometry analysis, cholesterol as well as triglyceride accumulated in the liver of DIAR-MSG mice. Atypical liver nodules were also observed after 32 weeks in DIAR-MSG, some with cellular and structural atypia mimicking human hepatocellular carcinoma. The NASH activity score of DIAR-MSG after 29 weeks was higher than that of control mice, suggesting the development of NASH. DIAR-MSG had NASH-like liver pathology and liver nodules typically associated with MS symptoms. DIAR-MSG provides a valuable animal model to analyze NASH pathogenesis and carcinogenesis. © 2014 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

  1. Adjusting irradiance to enhance growth and lipid production of Chlorella vulgaris cultivated with monosodium glutamate wastewater.

    Science.gov (United States)

    Jiang, Liqun; Ji, Yan; Hu, Wenrong; Pei, Haiyan; Nie, Changliang; Ma, Guixia; Song, Mingming

    2016-09-01

    Light is one of the most important factors affecting microalgae growth and biochemical composition. The influence of illumination on Chlorella vulgaris cultivated with diluted monosodium glutamate wastewater (MSGW) was investigated. Six progressive illumination intensities (0, 30, 90, 150, 200 and 300μmol·m(-2)s(-1)), were used for C. vulgaris cultivation at 25°C. Under 150μmol·m(-2)s(-1), the corresponding specific light intensity of 750×10(-6)μmol·m(-2)s(-1) per cell, algae obtained the maximum biomass concentration (1.46g·L(-1)) on the 7th day, which was 3.5 times of that under 0μmol·m(-2)s(-1), and the greatest average specific growth rate (0.79 d(-1)) in the first 7days. The results showed the importance role of light in mixotrophic growth of C. vulgaris. High light intensities of 200 and 300μmol·m(-2)s(-1) would inhibit microalgae growth to a certain degree. The algal lipid content was the greatest (30.5%) at 150μmol·m(-2)s(-1) light intensity, which was 2.42 times as high as that cultured in dark. The protein content of C. vulgaris decreased at high light intensities of 200 and 300μmol·m(-2)s(-1). The effect of irradiance on carbohydrate content was inversely correlated with that on protein. The available light at an appropriate intensity, not higher than 200μmol·m(-2)s(-1), was feasible for economical cultivation of C. vulgaris in MSGW. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Monosodium Glutamate Dietary Consumption Decreases Pancreatic β-Cell Mass in Adult Wistar Rats.

    Directory of Open Access Journals (Sweden)

    Piyanard Boonnate

    Full Text Available The amount of dietary monosodium glutamate (MSG is increasing worldwide, in parallel with the epidemics of metabolic syndrome. Parenteral administration of MSG to rodents induces obesity, hyperglycemia, hyperlipidemia, insulin resistance, and type 2 diabetes. However, the impact of dietary MSG is still being debated. We investigated the morphological and functional effects of prolonged MSG consumption on rat glucose metabolism and on pancreatic islet histology.Eighty adult male Wistar rats were randomly subdivided into 4 groups, and test rats in each group were supplemented with MSG for a different duration (1, 3, 6, or 9 months, n=20 for each group. All rats were fed ad libitum with a standard rat chow and water. Ten test rats in each group were provided MSG 2 mg/g body weight/day in drinking water and the 10 remaining rats in each group served as non-MSG treated controls. Oral glucose tolerance tests (OGTT were performed and serum insulin measured at 9 months. Animals were sacrificed at 1, 3, 6, or 9 months to examine the histopathology of pancreatic islets.MSG-treated rats had significantly lower pancreatic β-cell mass at 1, 6 and 9 months of study. Islet hemorrhages increased with age in all groups and fibrosis was significantly more frequent in MSG-treated rats at 1 and 3 months. Serum insulin levels and glucose tolerance in MSG-treated and untreated rats were similar at all time points we investigated.Daily MSG dietary consumption was associated with reduced pancreatic β-cell mass and enhanced hemorrhages and fibrosis, but did not affect glucose homeostasis. We speculate that high dietary MSG intake may exert a negative effect on the pancreas and such effect might become functionally significant in the presence or susceptibility to diabetes or NaCl; future experiments will take these crucial cofactors into account.

  3. Cross-fostering reduces obesity induced by early exposure to monosodium glutamate in male rats.

    Science.gov (United States)

    Miranda, Rosiane Aparecida; da Silva Franco, Claudinéia Conationi; de Oliveira, Júlio Cezar; Barella, Luiz Felipe; Tófolo, Laize Peron; Ribeiro, Tatiane Aparecida; Pavanello, Audrei; da Conceição, Ellen Paula Santos; Torrezan, Rosana; Armitage, James; Lisboa, Patrícia Cristina; de Moura, Egberto Gaspar; de Freitas Mathias, Paulo Cezar; Vieira, Elaine

    2017-01-01

    Maternal obesity programmes a range of metabolic disturbances for the offspring later in life. Moreover, environmental changes during the suckling period can influence offspring development. Because both periods significantly affect long-term metabolism, we aimed to study whether cross-fostering during the lactation period was sufficient to rescue a programmed obese phenotype in offspring induced by maternal obesity following monosodium L-glutamate (MSG) treatment. Obesity was induced in female Wistar rats by administering subcutaneous MSG (4 mg/g body weight) for the first 5 days of postnatal life. Control and obese female rats were mated in adulthood. The resultant pups were divided into control second generation (F 2 ) (CTLF 2 ), MSG-treated second generation (F 2 ) (MSGF 2 ), which suckled from their CTL and MSG biological dams, respectively, or CTLF 2 -CR, control offspring suckled by MSG dams and MSGF 2 -CR, MSG offspring suckled by CTL dams. At 120 days of age, fat tissue accumulation, lipid profile, hypothalamic leptin signalling, glucose tolerance, glucose-induced, and adrenergic inhibition of insulin secretion in isolated pancreatic islets were analysed. Maternal MSG-induced obesity led to an obese phenotype in male offspring, characterized by hyperinsulinaemia, hyperglycaemia, hyperleptinaemia, dyslipidaemia, and impaired leptin signalling, suggesting central leptin resistance, glucose intolerance, impaired glucose-stimulated, and adrenergic inhibition of insulin secretion. Cross-fostering normalized body weight, food intake, leptin signalling, lipid profiles, and insulinaemia, but not glucose homeostasis or insulin secretion from isolated pancreatic islets. Our findings suggest that alterations during the lactation period can mitigate the development of obesity and prevent the programming of adult diseases.

  4. Subcutaneous administration of monosodium glutamate to pregnant mice reduces weight gain in pups during lactation.

    Science.gov (United States)

    Park, Ji-Hun; Choi, Tae-Saeng

    2016-04-01

    Administering monosodium glutamate (MSG) to neonatal rodents induces obesity and type 2 diabetes. In addition, several studies have shown that MSG administered to pregnant animals can cross the placenta and reach the foetus. The present study was performed to investigate the effects of administering MSG to pregnant ICR mice on dam and neonatal growth. Pregnant mice were treated with 60 or 120 mg MSG once daily from day 5 of pregnancy to one day before parturition by subcutaneous injection. In addition, the body weights of the neonates were determined until nine weeks of age. The birth weights of neonates were not different between the control and MSG-treated groups. However, MSG treatment resulted in a lower body weight gain of neonates during lactation. In addition, this underweight of the MSG-treated group at weaning returned to normal compared with the control group at five weeks of age. Cross-fostering experiments indicated that the lower body weight gain of neonates in the MSG-treated group during lactation was due to its effects on the dam. Serum prolactin levels and mammary gland development of the mice were examined next to determine the reasons for this lactation problem. Although there were no differences in prolactin levels, morphological analyses of the mammary glands revealed apparent differences, including low numbers and altered phenotype of alveoli, between the control and MSG-treated groups. Taken together, our results show that treating pregnant mice with excess MSG induced lower neonate body weight gain during lactation. © The Author(s) 2015.

  5. Monosodium glutamate intake affect the function of the kidney through NMDA receptor.

    Science.gov (United States)

    Mahieu, Stella; Klug, Maximiliano; Millen, Néstor; Fabro, Ana; Benmelej, Adriana; Contini, Maria Del Carmen

    2016-03-15

    We investigated whether the chronic intake of monosodium glutamate (MSG) with food affects kidney function, and renal response to glycine. We also established if the NMDA receptors are involved in the changes observed. Male Wistar rats (5weeks old) were fed a diet supplemented with MSG (3g/kg b.w./day), five days a week, and spontaneous ingestion of a 1% MSG solution during 16weeks. NaCl rats were fed a diet with NaCl (1g/kg b.w./day) and 0.35% NaCl solution at the same frequency and time. Control group was fed with normal chow and tap water. We utilized clearance techniques to examine glomerular filtration rate (GFR) and cortical renal plasma flow (CRPF) response to glycine and glycine+MK-801 (antagonist NMDA-R), and we determined NMDA-R1 in kidney by immunohistochemistry. The addition of MSG in the diet of rats increased both GFR and CRPF with an increase of absolute sodium reabsorption. However, hyperfiltration was accompanied with a normal response to glycine infusion. Immunostain of kidney demonstrate that the NMDA receptor is upregulated in rats fed with MSG diet. NMDA-R antagonist MK-801 significantly reduced both the GFR and CRPF; however the percentage of reduction was significantly higher in the group MSG. MK-801 also reduces fractional excretion of water, sodium and potassium in the three groups. Renal NMDAR may be conditioned by the addition of MSG in the diet, favoring the hyperfiltration and simultaneously Na retention in the body. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Influence of Monosodium Glutamate on Radiation-Induced Biochemical Alterations in Male Albino Rats

    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 consumption of foods and beverages containing additives has intensely increased over the past decades. Monosodium glutamate (MSG) is one of the main flavor enhancer that can be consumed in high concentrations. Also, human exposure to ionizing radiation (RAD) has become inevitable with its vast application in diagnosis and industry. Humans are frequently exposed to RAD and MSG from various food additives, therapeutic treatments and the environment. Although the use of additives and exposure to RAD in therapeutic treatments are believed to be relatively safe, their combined effects remain unclear. The present study proposed to investigate neurotoxic potentials of exposure to MSG and/or RAD on oxidative stress, neurotransmitters disturbance and metabolic disorders in the rat’s brain tissue. MSG was supplemented daily by gavages to rats at a dose of 450 mg/Kg bwt/day (equivalent to 5 g/day human consumption) for 7 days pre- and 21 days post-exposure to whole body gamma rays at doses of 2 Gy/week up to a total dose of 8 Gy. Exposure to MSG and/or RAD -induced oxidative stress, neurotransmitters disturbance and metabolic disorders. Oxidative stress was manifested by a significant increase in lipid peroxidation product malondialdehyde (MDA) and decrease in the activity of antioxidant enzymes, superoxide dismutase, catalase and glutathione content. The administration of MSG daily during exposure to gamma radiation has potentiated oxidative stress regarding each single treatment. MSG-exposure induced a highly significant decrease of serotonin (P<0.01) and a slight non significant increase (P>0.05) of aspartic and glutamic acids levels while in RAD- group the decrease of serotonin and the increase of amino acids were very highly significant (P<0.001). MSG + RAD-exposure had potentiated the decrease of serotonin and produced an additive effect on the increase of neurotransmitters amino acids. MSG as well as RAD-exposure increased (P<0.05) glucose and insulin levels with

  7. Microscopic Study of Testicular Tissue Structure and Spermatogenesis Following Long Term Dose Dependent Administration of Monosodium Glutamate in Adult Diabetic Rats

    Directory of Open Access Journals (Sweden)

    Kianifard Davoud

    2016-06-01

    Full Text Available Background and aims: Diabetic hyperglycemia leads to structural and functional alterations in body organs including testis. Monosodium glutamate (MSG is a food additive which has toxic effects on human and animal’s tissues. The aim of this study was to evaluate the effects of MSG on diabetic complications of testicular tissue.

  8. No effect on intake and liking of soup enhanced with mono-sodium glutamate and celery powder among elderly people with olfactory and/or gustatory loss

    NARCIS (Netherlands)

    Essed, N.H.; Kleikers, S.M.; Staveren, van W.A.; Kok, F.J.; Graaf, de C.

    2009-01-01

    Mono-sodium glutamate (MSG) and/or flavors may improve palatability and intake in elderly people. Whether this improvement is related to a decline in chemosensory sensitivity is unclear. We examined the effect of flavor-enhanced tomato soup (1,200 mg/l MSG (0.12% MSG) + 3 g/l celery powder) versus

  9. 78 FR 65278 - Monosodium Glutamate From the People's Republic of China, and the Republic of Indonesia...

    Science.gov (United States)

    2013-10-31

    ... Indonesia and the PRC are being, or are likely to be, sold in the United States at less than fair value... from Indonesia and the PRC are being, or likely to be, sold in the United States at less than fair... DEPARTMENT OF COMMERCE International Trade Administration [A-570-992, A-560-826] Monosodium...

  10. Monosodium glutamate neurotoxicity increases beta amyloid in the rat hippocampus: a potential role for cyclic AMP protein kinase.

    Science.gov (United States)

    Dief, Abeer E; Kamha, Eman S; Baraka, Azza M; Elshorbagy, Amany K

    2014-05-01

    Glutamate excitotoxicity and cyclic AMP-activated protein kinase (AMPK) are both recognized as important mediators in neurodegenerative disorders including Alzheimer's disease (AD). To investigate whether oral or subcutaneous monosodium glutamate (MSG) neurotoxicity mimics some features of AD and whether these can be reversed by the AMPK activator Pioglitazone. Male Wistar rats aged 5 weeks were administered oral or subcutaneous MSG for 10 days with or without daily oral Pioglitazone. Two additional groups given only saline orally or subcutaneously acted as controls. At age 10 weeks the rats were subjected to neurobehavioral testing, then sacrificed for measurement of AMPK, β-amyloid and Fas ligand in the hippocampus. Oral and subcutaneous MSG both induced a lowering of hippocampal AMPK by 43% and 31% respectively (P2-fold increase in hippocampal Fas ligand, a mediator of apoptosis (P4-fold and >5-fold in the oral and subcutaneous groups. This was associated with increased latency before crossing to the white half in the black-white alley and before the first rear in the holeboard test, suggesting increased anxiety. Pioglitazone decreased hippocampal β-amyloid accumulation and Fas ligand, but did not ameliorate the neurobehavioural deficits induced by MSG. MSG treatment enhances β-amyloid accumulation in the rat hippocampus. Our results suggest a role for AMPK reduction in mediating the neurotoxic effects of glutamate, including β-amyloid accumulation. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. The feasibility of using complex wastewater from a monosodium glutamate factory to cultivate Spirulina subsalsa and accumulate biochemical composition.

    Science.gov (United States)

    Jiang, Liqun; Pei, Haiyan; Hu, Wenrong; Ji, Yan; Han, Lin; Ma, Guixia

    2015-03-01

    This paper is mainly observations on the growth and biomass accumulation of Spirulina subsalsa in modified Zarrouk medium supplemented with complex wastewater (CW, from a monosodium glutamate factory) in different concentrations. High ammonia in 75% and 100% CW inhibits algae growth, but maximum biomass production (2.86mgL(-1)) was obtained in 25% CW (concentration of CW in medium was 25%). Different CW concentration promoted biomass composition accumulation at different degrees, 41% of protein content in 25% CW and 18% of carbohydrate in 50% CW. In terms of economy, a concentration of 25% CW was suitable for protein production and 50% for lipid and carbohydrate production. These results suggested that CW is a feasible replacement in part for cultivation of S. subsalsa to economize input of water and nutrients. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Dietary consumption of monosodium L-glutamate induces adaptive response and reduction in the life span of Drosophila melanogaster.

    Science.gov (United States)

    Abolaji, Amos O; Olaiya, Charles O; Oluwadahunsi, Oluwagbenga J; Farombi, Ebenezer O

    2017-04-01

    Adaptive response is the ability of an organism to better counterattack stress-induced damage in response to a number of different cytotoxic agents. Monosodium L-glutamate (MSG), the sodium salt of amino acid glutamate, is commonly used as a food additive. We investigated the effects of MSG on the life span and antioxidant response in Drosophila melanogaster (D. melanogaster). Both genders (1 to 3 days old) of flies were fed with diet containing MSG (0.1, 0.5, and 2.5-g/kg diet) for 5 days to assess selected antioxidant and oxidative stress markers, while flies for longevity were fed for lifetime. Thereafter, the longevity assay, hydrogen peroxide (H 2 O 2 ), and reactive oxygen and nitrogen species levels were determined. Also, catalase, glutathione S-transferase and acetylcholinesterase activities, and total thiol content were evaluated in the flies. We found that MSG reduced the life span of the flies by up to 23% after continuous exposure. Also, MSG increased reactive oxygen and nitrogen species and H 2 O 2 generations and total thiol content as well as the activities of catalase and glutathione S-transferase in D. melanogaster (P melanogaster induced adaptive response, but long-term exposure reduced life span of flies. This study may therefore have public health significance in humans, and thus, moderate consumption of MSG is advocated by the authors. Copyright © 2017 John Wiley & Sons, Ltd.

  13. To study the effect of monosodium glutamate on histomorphometry of cortex of kidney in adult albino rats.

    Science.gov (United States)

    Dixit, Shilpi Gupta; Rani, Puja; Anand, Akansha; Khatri, Kamlesh; Chauhan, Renu; Bharihoke, Veena

    2014-03-01

    Thousands of chemicals are being used recently in our new high tech foods like ready to eat Japanese, Chinese, packaged and tinned foods. Most food additives act as either preservatives or flavor enhancers like monosodium glutamate (MSG), a sodium salt of glutamic acid. The present study investigated the effect of intraperitoneally administered MSG on cortex of the kidneys of adult albino Wistar rats and compared with control group. The histomorphometry done by calibrating with ocular micrometer on kidney tissue of control and experimental group revealed a significant difference in glomeruli with increase in length, size of bowman's capsule with an increase in bowman's space. The size of renal tubules could not be compared as the cells of these tubules in experimental group were disintegrated and distorted. In the experimental group (rats treated with 4 mg MSG/g body weight), the cortex of the kidneys developed variable pathological changes, which were patchy in distribution with intervening normal areas. There was distortion of renal cytoarchitecture. Many glomeruli (66.4%) showed hypercellularity, i.e., cellular proliferation of mesangial or endothelial cells and infiltration of inflammatory cells. The capillary membrane showed thickening as was evident on PAS stain. Since MSG, as a food additive, was found to be toxic on various organs of the body by various researchers, it should perhaps be stopped from being used as a food additive. This may be a suggestion which needs validation in human studies.

  14. Monosodium glutamate, disodium inosinate, disodium guanylate, lysine and taurine improve the sensory quality of fermented cooked sausages with 50% and 75% replacement of NaCl with KCl.

    Science.gov (United States)

    dos Santos, Bibiana Alves; Campagnol, Paulo Cezar Bastianello; Morgano, Marcelo Antônio; Pollonio, Marise Aparecida Rodrigues

    2014-01-01

    Fermented cooked sausages were produced by replacing 50% and 75% of NaCl with KCl and adding monosodium glutamate, disodium inosinate, disodium guanylate, lysine and taurine. The manufacturing process was monitored by pH and water activity measurements. The sodium and potassium contents of the resulting products were measured. The color values (L*, a* and b*), texture profiles and sensory profiles were also examined. Replacing 50% and 75% NaCl with KCl depreciated the sensory quality of the products. The reformulated sausages containing monosodium glutamate combined with lysine, taurine, disodium inosinate and disodium guanylate masked the undesirable sensory attributes associated with the replacement of 50% and 75% NaCl with KCl, allowing the production of fermented cooked sausages with good sensory acceptance and approximately 68% sodium reduction. © 2013.

  15. Economical production of poly(γ-glutamic acid) using untreated cane molasses and monosodium glutamate waste liquor by Bacillus subtilis NX-2.

    Science.gov (United States)

    Zhang, Dan; Feng, Xiaohai; Zhou, Zhe; Zhang, Yang; Xu, Hong

    2012-06-01

    The production of poly(γ-glutamic acid) by Bacillus subtilis NX-2 from cane molasses and monosodium glutamate waste liquor (MGWL) was studied for the first time in this work. When batch fermentation was carried out with untreated molasses, 33.6±0.37 g L(-1) PGA was obtained with a productivity of 0.46±0.006 g L(-1) h(-1). In order to minimize the substrate inhibition, fed-batch fermentation was performed with untreated or hydrolyzed molasses in 7.5 L bioreactor, giving 50.2±0.53 and 51.1±0.51 g L(-1) of PGA at 96 h, respectively. Further studies were carried out by using MGWL as another carbon source, resulting in a PGA concentration of 52.1±0.52 g L(-1) with a productivity of 0.54±0.003 g L(-1) h(-1). These results suggest that the low-cost cane molasses and MGWL can be used for the environmental-friendly and economical production of PGA by B. subtilis NX-2. Copyright © 2012 Elsevier Ltd. All rights reserved.

  16. Anorexigenic effect of cholecystokinin is lost but that of CART (cocaine and amphetamine regulated transcript) peptide is preserved in monosodium glutamate obese mice

    Czech Academy of Sciences Publication Activity Database

    Železná, Blanka; Maixnerová, Jana; Matyšková, Resha; Haugvicová, Renata; Blokešová, Darja; Maletínská, Lenka

    2009-01-01

    Roč. 58, č. 5 (2009), s. 717-723 ISSN 0862-8408 R&D Projects: GA ČR GA303/05/0614 Grant - others:GA ČR(CZ) GA305/06/0427 Program:GA Institutional research plan: CEZ:AV0Z40550506; CEZ:AV0Z5020903 Keywords : monosodium glutamate (MSG) obesity * neuropeptide Y (NPY) * cholecystokinin Subject RIV: CC - Organic Chemistry Impact factor: 1.430, year: 2009

  17. Changes in hippocampal synaptic functions and protein expression in monosodium glutamate-treated obese mice during development of glucose intolerance.

    Science.gov (United States)

    Sasaki-Hamada, Sachie; Hojo, Yuki; Koyama, Hajime; Otsuka, Hayuma; Oka, Jun-Ichiro

    2015-05-01

    Glucose is the sole neural fuel for the brain and is essential for cognitive function. Abnormalities in glucose tolerance may be associated with impairments in cognitive function. Experimental obese model mice can be generated by an intraperitoneal injection of monosodium glutamate (MSG; 2 mg/g) once a day for 5 days from 1 day after birth. MSG-treated mice have been shown to develop glucose intolerance and exhibit chronic neuroendocrine dysfunction associated with marked cognitive malfunctions at 28-29  weeks old. Although hippocampal synaptic plasticity is impaired in MSG-treated mice, changes in synaptic transmission remain unknown. Here, we investigated whether glucose intolerance influenced cognitive function, synaptic properties and protein expression in the hippocampus. We demonstrated that MSG-treated mice developed glucose intolerance due to an impairment in the effectiveness of insulin actions, and showed cognitive impairments in the Y-maze test. Moreover, long-term potentiation (LTP) at Schaffer collateral-CA1 pyramidal synapses in hippocampal slices was impaired, and the relationship between the slope of extracellular field excitatory postsynaptic potential and stimulus intensity of synaptic transmission was weaker in MSG-treated mice. The protein levels of vesicular glutamate transporter 1 and GluA1 glutamate receptor subunits decreased in the CA1 region of MSG-treated mice. These results suggest that deficits in glutamatergic presynapses as well as postsynapses lead to impaired synaptic plasticity in MSG-treated mice during the development of glucose intolerance, though it remains unknown whether impaired LTP is due to altered inhibitory transmission. It may be important to examine changes in glucose tolerance in order to prevent cognitive malfunctions associated with diabetes. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  18. Antinociceptive action of diphenyl diselenide in the nociception induced by neonatal administration of monosodium glutamate in rats.

    Science.gov (United States)

    Rosa, Suzan G; Quines, Caroline B; da Rocha, Juliana T; Bortolatto, Cristiani F; Duarte, Thiago; Nogueira, Cristina W

    2015-07-05

    Monosodium glutamate (MSG) is a neuroexcitatory amino acid commonly used as flavoring of foods. MSG neonatal administration to animals leads to behavioral and physiological disorders in adulthood, including increased pain sensitivity. This study aimed to investigate the effect of diphenyl diselenide (PhSe)2, an organoselenium compound with pharmacological properties already documented, on nociception induced by MSG. Newborn Wistar rats received 10 subcutaneous injections of MSG at a dose of 4.0g/kg or saline (once daily). At the 60th day of life, the rats were daily treated with (PhSe)2 (1mg/kg) or vehicle (canola oil) by the intragastric route for 7 days. The behavioral tests (locomotor activity, hot plate, tail-immersion and mechanical allodynia) were carried out. Ex vivo assays were performed in samples of hippocampus to determine Na(+), K(+)-ATPase and Ca(2+)-ATPase activities, cytokine levels and [(3)H]glutamate uptake. The results demonstrated that MSG increased nociception in the hot plate test and in the mechanical allodynia stimulated by Von-Frey hair but did not alter the tail immersion test. (PhSe)2 reversed all nociceptive behaviors altered by MSG. MSG caused an increase in Na(+),K(+)-ATPase and Ca(2+)-ATPase activities and in pro-inflammatory cytokine levels and a decrease in the anti-inflammatory cytokine and in the [(3)H]glutamate uptake. (PhSe)2 was effective in reversing all alterations caused by MSG. The results indicate that (PhSe)2 had a potential antinociceptive and anti-inflammatory action in the MSG model. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. The Monosodium Glutamate Story: The Commercial Production of MSG and Other Amino Acids

    Science.gov (United States)

    Ault, Addison

    2004-03-01

    Examples of the industrial synthesis of pure amino acids are presented. The emphasis is on the synthesis of ( S )-glutamic acid and, to a lesser extent, ( S )-lysine and ( R,S )-methionine. These amino acids account for about 90% of the total world production of amino acids, ( S )-glutamic acid being used as a flavor-enhancing additive (MSG) for the human diet, and ( S )-lysine and ( R,S )-methionine as supplements for the feeding of domestic animals. Examples include chemical, enzymatic, and fermentation synthesis, and two clever continuous processes for the resolution of enantiomers. See Featured Molecules .

  20. Antioxidant Actions Of Irradiated Hibiscus SABDARIFFA L. (KARKADE) Against Monosodium Glutamate-Induced Oxidative Stress In Rats

    International Nuclear Information System (INIS)

    FARAG, M.F.S.; OSMAN, N.N.

    2009-01-01

    Monosodium glutamate (MSG) continues to function as a flavour enhancer in diets. Aqueous extract of dried flowers of irradiated Hibiscus sabdariffa L. (HS), (Karkade), was investigated for its antioxidant action in MSG treated rats. MSG was injected intraperitoneally at a dose of 4 mg/g body weight for 15 days to male Wistar rats. Lipid peroxidation as thiobarbituric acid reactive substances (TBARS) and the antioxidants superoxide dismutase (SOD), catalase (CAT) and reduced glutathione (GSH) were examined in brain, heart, kidney and testes. MSG markedly increases the TBARS formation in rat organs. Meanwhile, it decreased significantly the activities of SOD and CAT in the same examined organs. The GSH level was also reduced due to MSG. In MSG treated rats, simultaneous oral administration of HS water extract (HSAE; 540 mg /kg/day) significantly reduced the MSG mediated increase in TBARS. Moreover, the administered HSAE was effective in ameliorating the changes in the activities of SOD and CAT in the examined organs. It also restored the decrease in GSH content. Overall, these findings are suggestive of the protective and the possible anti oxidative role played by dried flowers of Hibiscus sabdariffa L. against the oxidative damage due to MSG administration to rats.

  1. High dosage of monosodium glutamate causes deficits of the motor coordination and the number of cerebellar Purkinje cells of rats.

    Science.gov (United States)

    Prastiwi, D; Djunaidi, A; Partadiredja, G

    2015-11-01

    Monosodium glutamate (MSG) has been widely used throughout the world as a flavoring agent of food. However, MSG at certain dosages is also thought to cause damage to many organs, including cerebellum. This study aimed at investigating the effects of different doses of MSG on the motor coordination and the number of Purkinje cells of the cerebellum of Wistar rats. A total of 24 male rats aged 4 to 5 weeks were divided into four groups, namely, control (C), T2.5, T3, and T3.5 groups, which received intraperitoneal injection of 0.9% sodium chloride solution, 2.5 mg/g body weight (bw) of MSG, 3.0 mg/g bw of MSG, and 3.5 mg/g bw of MSG, respectively, for 10 consecutive days. The motor coordination of the rats was examined prior and subsequent to the treatment. The number of cerebellar Purkinje cells was estimated using physical fractionator method. It has been found that the administration of MSG at a dosage of 3.5 mg/g bw, but not at lower dosages, caused a significant decrease of motor coordination and the estimated total number of Purkinje cells of rats. There was also a significant correlation between motor coordination and the total number of Purkinje cells. © The Author(s) 2015.

  2. Effect of different doses of monosodium glutamate on the thyroid follicular cells of adult male albino rats: a histological study.

    Science.gov (United States)

    Khalaf, Hanaa A; Arafat, Eetmad A

    2015-01-01

    Monosodium glutamate (MSG) is a major flavor enhancer used as a food additive. The present study investigates the effects of different doses of MSG on the morphometric and histological changes of the thyroid gland. 28 male albino rats were used. The rats were divided into four groups: group I control, group II, III and IV treated with MSG (0.25 g/kg, 3 g/kg, 6 g/kg daily for one month) respectively. The thyroid glands were dissected out and prepared for light and electron microscopic examination. Light microscopic examination of thyroid gland of group II revealed increase in follicular epithelial height. Groups III & IV showed decrease in the follicular diameter and irregularity in the shape of some follicles with discontinuity of basement membrane. Follicular hyperplasia was detected in some follicles with appearance of multiple pyknotic nuclei in follicular and interfollicular cells and multiple exfoliated cells in the colloid. In addition, areas of loss of follicular pattern were appeared in group IV. Immunohistochemical examination of BCL2 immunoexpression of the thyroid glands of groups III & IV reveals weak positive reaction in the follicular cells cytoplasm. Ultrathin sections examination of groups III & IV revealed follicular cells with irregular hyperchromatic nuclei, marked dilatation of rER and increased lysosomes with areas of short or lost apical microvilli. In addition, vacuolation of mitochondria was detected in group IV. The results displayed that MSG even at low doses is capable of producing alterations in the body weights and thyroid tissue function and histology.

  3. Monosodium glutamate (MSG intake is associated with the prevalence of metabolic syndrome in a rural Thai population

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    Insawang Tonkla

    2012-06-01

    Full Text Available Abstract Background Epidemiology and animal models suggest that dietary monosodium glutamate (MSG may contribute to the onset of obesity and the metabolic syndrome. Methods Families (n = 324 from a rural area of Thailand were selected and provided MSG as the sole source for the use in meal preparation for 10 days. Three hundred forty-nine subjects aged 35–55 years completed the study and were evaluated for energy and nutrient intake, physical activity, and tobacco smoking. The prevalence of overweight and obesity (BMI ≥ 25 kg/m2, insulin resistance (HOMA-IR >3, and the metabolic syndrome (ATP III criteria were evaluated according to the daily MSG intake. Results The prevalence of the metabolic syndrome was significantly higher in the tertile with the highest MSG intake. Further, every 1 g increase in MSG intake significantly increased the risk of having the metabolic syndrome (odds ratio 1.14, 95% confidence interval-CI- 1.12 - 1.28 or being overweight (odds ratio 1.16, 95% CI 1.04 - 1.29, independent of the total energy intake and the level of physical activity. Conclusion Higher amounts of individual MSG consumption are associated with the risk of having the metabolic syndrome and being overweight independent of other major determinants.

  4. HISTOLOGICAL STUDIES OF THE EFFECTS OF MONOSODIUM GLUTAMATE ON THE MEDIAL GENICULATE BODY OF ADULT WISTAR RATS

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    A.O.Eweka

    2007-01-01

    Full Text Available Histological effects of Monosodium glutamate (MSG commonly used as food additive on the medial geniculate body (MGB of adult wistar rats were carefully studied. The rats of both sexes (n=24, average weight of 185g were randomly assigned into two treatments (n=16 and control (n=8 groups.The rats in the treatment groups received 3g and 6g of MSG thoroughly mixed with their feeds for fourteen days, while the control rats received equal amounts of feeds without MSG added. The rats were fed with grower's mash purchased from Edo Feeds and Flour Mill Ltd, Ewu, Edo State and were given water liberally. The rats were sacrificed on day fifteen of the experiment. The medial geniculate body was carefully dissected out and quickly fixed in 10% formal saline for routine histological study after H&E method.The histological findings after H&E methods indicated that the treated sections of the medial geniculate body showed some cellular degenerative changes, autophagic vacuoles with some vacuolations appearing in the stroma, and some degree of neuronal hypertrophy when compared to the control sections. These findings indicate that MSG consumption may have a deleterious effect on the neurons of the medial geniculate body (MGB. MSG may probably have adverse effects on the auditory sensibilities by its deleterious effects on the nerve cells of the MGB of adult wistar rats. It is recommended that further studies aimed at corroborating these observations be carried out.

  5. Progressive Depletion of Rough Endoplasmic Reticulum in Epithelial Cells of the Small Intestine in Monosodium Glutamate Mice Model of Obesity

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    Kazuhiko Nakadate

    2016-01-01

    Full Text Available Chronic obesity is a known risk factor for metabolic syndrome. However, little is known about pathological changes in the small intestine associated with chronic obesity. This study investigated cellular and subcellular level changes in the small intestine of obese mice. In this study, a mouse model of obesity was established by early postnatal administration of monosodium glutamate. Changes in body weight were monitored, and pathological changes in the small intestine were evaluated using hematoxylin-eosin and Nissl staining and light and electron microscopy. Consequently, obese mice were significantly heavier compared with controls from 9 weeks of age. Villi in the small intestine of obese mice were elongated and thinned. There was reduced hematoxylin staining in the epithelium of the small intestine of obese mice. Electron microscopy revealed a significant decrease in and shortening of rough endoplasmic reticulum in epithelial cells of the small intestine of obese mice compared with normal mice. The decrease in rough endoplasmic reticulum in the small intestine epithelial cells of obese mice indicates that obesity starting in childhood influences various functions of the small intestine, such as protein synthesis, and could impair both the defense mechanism against invasion of pathogenic microbes and nutritional absorption.

  6. Environmental enrichment improved cognitive deficits more in peri-adolescent than in adult rats after postnatal monosodium glutamate treatment.

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    Madhavadas, S; Subramanian, S; Kutty, B M

    2017-12-01

    Exposure to enriched environment (EE) is known to promote sensory, cognitive, and motor stimulation with intensified levels of novelty and complexity. In this study, we investigated the positive regulatory effect of short-term exposure to EE on establishing functional recovery in monosodium glutamate (MSG)-induced obese rats. Unless treated, MSG rats exhibited peripheral insulin resistance, cognitive deficits, and a reduction in the total hippocampal volume with decreased neuron count in the DG, CA3, and CA1 subfields. These MSG rats were exposed to short-term EE for 15 days for a period of 6 h/day, beginning either at 45 or at 75 days of age. EE exposure has improved insulin sensitivity, yielded a significant increase in total hippocampal volume along with increase in neuron number in the CA1 subfield of the hippocampus in both age groups. However, as assessed by radial arm maze task, which relies upon the positive reinforcement to test spatial memory, and the Barnes maze task, which utilizes an aversive learning strategy, a complete recovery of cognitive function could be achieved in 2-month-old rats only and not among 3-month-old rats, thus highlighting the importance of critical window period for EE interventions in restoring the memory functions. These results suggest the therapeutic potential of EE paradigm in prevention of cognitive disorders.

  7. Effect of Monosodium Glutamate and L-Carnitine on Density and Structure of Granular Cells of Cerebellum in Rat

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    Mojdeh Fatahzadeh

    2018-04-01

    Full Text Available Abstract Background: Monosodium glutamate (MSG is a widely-used flavor enhancer and stabilizer in ready-made or packaged foods. The excessive use of MSG has been shown to increase oxidative stress in different regions of the brain. In this study, the neuroprotective effect of L-carnitine was investigated against MSG intoxication in granular cell of cerebellum in rats. Materials and Methods: 48 adult male Wistar rats were randomly divided into 6 groups: the control, sham (normal saline treated, MSG (3%, L-Carnitine200, MSG+L-Carnitine100 and MSG+L-Carnitine200. After 30 days of treatment, through transcardialy perfusion, the rats were sacrificed and histopathological analyses were conducted on cerebellum. Results: The results indicated that the density of granular cells in cerebellar folium IV, V and VI of rats in the MSG group had significantly decreased in comparison to that of the control and sham groups. Furthermore, the MSG+L-Carnitine200 group showed the higher density of granular cells compared with the MSG group in the three folia. Conclusion: Treatment with L-Carnitine could protect the granular cells in cerebellum against MSG intoxication in rats.

  8. Beta-galactosidase staining in the nucleus of the solitary tract of Fos-Tau-LacZ mice is unaffected by monosodium glutamate taste stimulation.

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    Jennifer M Stratford

    Full Text Available Fos-Tau-LacZ (FTL transgenic mice are used to visualize the anatomical connectivity of neurons that express c-Fos, an immediate early gene, in response to activation. In contrast to typical c-Fos protein expression, which is localized to the nucleus of stimulated neurons, activation of the c-Fos gene results in beta galactosidase (β-gal expression throughout the entire cytoplasm of activated cells in FTL mice; thereby making it possible to discern the morphology of c-Fos expressing cells. This can be an especially important tool in brain areas in which function may be related to cell morphology, such as the primary taste/viscerosensory brainstem nucleus of the solitary tract (nTS. Thus, to further characterize FTL activity in the brain, the current study quantified both β-gal enzymatic activity as well as c-Fos protein expression in the nTS under a variety of experimental conditions (no stimulation, no stimulation with prior overnight food and water restriction, monosodium glutamate taste stimulation, and monosodium glutamate taste stimulation with perfusion 5 h post stimulation. Contrary to previous research, we found that β-gal activity (both labeled cell bodies and overall number of labeled pixels was unchanged across all experimental conditions. However, traditional c-Fos protein activity (both cell bodies and number of activated pixels varied significantly across experimental conditions, with the greatest amount of c-Fos protein label found in the group that received monosodium glutamate taste stimulation. Interestingly, although many c-Fos positive cells were also β-gal positive in the taste stimulated group, some c-Fos protein labeled cells were not co-labeled with β-gal. Together, these data suggest that β-gal staining within the nTS reflects a stable population of β-gal- positive neurons whose pattern of expression is unaffected by experimental condition.

  9. Beta-galactosidase staining in the nucleus of the solitary tract of Fos-Tau-LacZ mice is unaffected by monosodium glutamate taste stimulation.

    Science.gov (United States)

    Stratford, Jennifer M; Thompson, John A

    2014-01-01

    Fos-Tau-LacZ (FTL) transgenic mice are used to visualize the anatomical connectivity of neurons that express c-Fos, an immediate early gene, in response to activation. In contrast to typical c-Fos protein expression, which is localized to the nucleus of stimulated neurons, activation of the c-Fos gene results in beta galactosidase (β-gal) expression throughout the entire cytoplasm of activated cells in FTL mice; thereby making it possible to discern the morphology of c-Fos expressing cells. This can be an especially important tool in brain areas in which function may be related to cell morphology, such as the primary taste/viscerosensory brainstem nucleus of the solitary tract (nTS). Thus, to further characterize FTL activity in the brain, the current study quantified both β-gal enzymatic activity as well as c-Fos protein expression in the nTS under a variety of experimental conditions (no stimulation, no stimulation with prior overnight food and water restriction, monosodium glutamate taste stimulation, and monosodium glutamate taste stimulation with perfusion 5 h post stimulation). Contrary to previous research, we found that β-gal activity (both labeled cell bodies and overall number of labeled pixels) was unchanged across all experimental conditions. However, traditional c-Fos protein activity (both cell bodies and number of activated pixels) varied significantly across experimental conditions, with the greatest amount of c-Fos protein label found in the group that received monosodium glutamate taste stimulation. Interestingly, although many c-Fos positive cells were also β-gal positive in the taste stimulated group, some c-Fos protein labeled cells were not co-labeled with β-gal. Together, these data suggest that β-gal staining within the nTS reflects a stable population of β-gal- positive neurons whose pattern of expression is unaffected by experimental condition.

  10. Biochemical Alterations during the Obese-Aging Process in Female and Male Monosodium Glutamate (MSG-Treated Mice

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    René J. Hernández-Bautista

    2014-06-01

    Full Text Available Obesity, from children to the elderly, has increased in the world at an alarming rate over the past three decades, implying long-term detrimental consequences for individual’s health. Obesity and aging are known to be risk factors for metabolic disorder development, insulin resistance and inflammation, but their relationship is not fully understood. Prevention and appropriate therapies for metabolic disorders and physical disabilities in older adults have become a major public health challenge. Hence, the aim of this study was to evaluate inflammation markers, biochemical parameters and glucose homeostasis during the obese-aging process, to understand the relationship between obesity and health span during the lifetime. In order to do this, the monosodium glutamate (MSG obesity mice model was used, and data were evaluated at 4, 8, 12, 16 and 20 months in both female and male mice. Our results showed that obesity was a major factor contributing to premature alterations in MSG-treated mice metabolism; however, at older ages, obesity effects were attenuated and MSG-mice became more similar to normal mice. At a younger age (four months old, the Lee index, triglycerides, total cholesterol, TNF-α and transaminases levels increased; while adiponectin decreased and glucose tolerance and insulin sensitivity levels were remarkably altered. However, from 16 months old-on, the Lee index and TNF-α levels diminished significantly, while adiponectin increased, and glucose and insulin homeostasis was recovered. In summary, MSG-treated obese mice showed metabolic changes and differential susceptibility by gender throughout life and during the aging process. Understanding metabolic differences between genders during the lifespan will allow the discovery of specific preventive treatment strategies for chronic diseases and functional decline.

  11. Glycine regulates the production of pro-inflammatory cytokines in lean and monosodium glutamate-obese mice.

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    Alarcon-Aguilar, F J; Almanza-Perez, Julio; Blancas, Gerardo; Angeles, Selene; Garcia-Macedo, Rebeca; Roman, Ruben; Cruz, Miguel

    2008-12-03

    Fat tissue plays an important role in the regulation of inflammatory processes. Increased visceral fat has been associated with a higher production of cytokines that triggers a low-grade inflammatory response, which eventually may contribute to the development of insulin resistance. In the present study, we investigated whether glycine, an amino acid that represses the expression in vitro of pro-inflammatory cytokines in Kupffer and 3T3-L1 cells, can affect in vivo cytokine production in lean and monosodium glutamate-induced obese mice (MSG/Ob mice). Our data demonstrate that glycine treatment in lean mice suppressed TNF-alpha transcriptional expression in fat tissue, and serum protein levels of IL-6 were suppressed, while adiponectin levels were increased. In MSG/Ob mice, glycine suppressed TNF-alpha and IL-6 gene expression in fat tissue and significantly reduced protein levels of IL-6, resistin and leptin. To determine the role of peroxisome proliferator-activated receptor-gamma (PPAR-gamma) in the modulation of this inflammatory response evoked by glycine, we examined its expression levels in fat tissue. Glycine clearly increased PPAR-gamma expression in lean mice but not in MSG/Ob mice. Finally, to identify alterations in glucose metabolism by glycine, we also examined insulin levels and other biochemical parameters during an oral glucose tolerance test. Glycine significantly reduced glucose tolerance and raised insulin levels in lean but not in obese mice. In conclusion, our findings suggest that glycine suppresses the pro-inflammatory cytokines production and increases adiponectin secretion in vivo through the activation of PPAR-gamma. Glycine might prevent insulin resistance and associated inflammatory diseases.

  12. Consumption of monosodium glutamate in relation to incidence of overweight in Chinese adults: China Health and Nutrition Survey (CHNS).

    Science.gov (United States)

    He, Ka; Du, Shufa; Xun, Pengcheng; Sharma, Sangita; Wang, Huijun; Zhai, Fengying; Popkin, Barry

    2011-06-01

    It has been hypothesized that monosodium glutamate (MSG), a flavor enhancer, is positively associated with weight gain, which influences energy balance through the disruption of the hypothalamic signaling cascade of leptin action. The objective was to examine the longitudinal association between MSG consumption and incidence of overweight. Data were collected from the China Health and Nutrition Survey (CHNS), a prospective open-cohort, ongoing nationwide health and nutrition survey, consisting of 10,095 apparently healthy Chinese adults aged 18-65 y at entry from 1991 to 2006. Diet, including MSG and other condiments, was assessed with a weighed food inventory in combination with three 24-h recalls. Incident overweight was defined as a body mass index (BMI; in kg/m(2)) ≥ 25 or ≥23 based on World Health Organization recommendations for Asian populations. Multilevel mixed-effects models were constructed to estimate change in BMI, and Cox regression models with gamma shared frailty were used to determine the incidence of overweight. The mean follow-up was 5.5 y. The cumulative mean (±SD) MSG intake of 2.2 ± 1.6 g/d was positively associated with BMI after adjustment for potential confounders and cluster effects at different levels (individual, household, and community). The adjusted hazard ratio of overweight was 1.33 (95% CI: 1.01, 1.75; P for trend total energy intake, and other major lifestyle factors. MSG consumption was positively, longitudinally associated with overweight development among apparently healthy Chinese adults. Additional studies are needed to elucidate mechanisms of action and to establish causal inference.

  13. Cognitive and biochemical effects of monosodium glutamate and aspartame, administered individually and in combination in male albino mice.

    Science.gov (United States)

    Abu-Taweel, Gasem M; A, Zyadah M; Ajarem, Jamaan S; Ahmad, Mohammad

    2014-01-01

    The present study was designed to investigate the in vivo effects of monosodium glutamate (MSG) and aspartame (ASM) individually and in combination on the cognitive behavior and biochemical parameters like neurotransmitters and oxidative stress indices in the brain tissue of mice. Forty male Swiss albino mice were randomly divided into four groups of ten each and were exposed to MSG and ASM through drinking water for one month. Group I was the control and was given normal tap water. Groups II and III received MSG (8 mg/kg) and ASM (32 mg/kg) respectively dissolved in tap water. Group IV received MSG and ASM together in the same doses. After the exposure period, the animals were subjected to cognitive behavioral tests in a shuttle box and a water maze. Thereafter, the animals were sacrificed and the neurotransmitters and oxidative stress indices were estimated in their forebrain tissue. Both MSG and ASM individually as well as in combination had significant disruptive effects on the cognitive responses, memory retention and learning capabilities of the mice in the order (MSG+ASM)>ASM>MSG. Furthermore, while MSG and ASM individually were unable to alter the brain neurotransmitters and the oxidative stress indices, their combination dose (MSG+ASM) decreased significantly the levels of neurotransmitters (dopamine and serotonin) and it also caused oxidative stress by increasing the lipid peroxides measured in the form of thiobarbituric acid-reactive substances (TBARS) and decreasing the level of total glutathione (GSH). Further studies are required to evaluate the synergistic effects of MSG and ASM on the neurotransmitters and oxidative stress indices and their involvement in cognitive dysfunctions. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. Consumption of monosodium glutamate in relation to incidence of overweight in Chinese adults: China Health and Nutrition Survey (CHNS)123

    Science.gov (United States)

    Du, Shufa; Xun, Pengcheng; Sharma, Sangita; Wang, Huijun; Zhai, Fengying; Popkin, Barry

    2011-01-01

    Background: It has been hypothesized that monosodium glutamate (MSG), a flavor enhancer, is positively associated with weight gain, which influences energy balance through the disruption of the hypothalamic signaling cascade of leptin action. Objective: The objective was to examine the longitudinal association between MSG consumption and incidence of overweight. Design: Data were collected from the China Health and Nutrition Survey (CHNS), a prospective open-cohort, ongoing nationwide health and nutrition survey, consisting of 10,095 apparently healthy Chinese adults aged 18–65 y at entry from 1991 to 2006. Diet, including MSG and other condiments, was assessed with a weighed food inventory in combination with three 24-h recalls. Incident overweight was defined as a body mass index (BMI; in kg/m2) ≥ 25 or ≥23 based on World Health Organization recommendations for Asian populations. Multilevel mixed-effects models were constructed to estimate change in BMI, and Cox regression models with gamma shared frailty were used to determine the incidence of overweight. Results: The mean follow-up was 5.5 y. The cumulative mean (±SD) MSG intake of 2.2 ± 1.6 g/d was positively associated with BMI after adjustment for potential confounders and cluster effects at different levels (individual, household, and community). The adjusted hazard ratio of overweight was 1.33 (95% CI: 1.01, 1.75; P for trend < 0.01) for participants in the highest quintile of MSG intake compared with those in the lowest quintile after adjustment for age, physical activity, total energy intake, and other major lifestyle factors. Conclusions: MSG consumption was positively, longitudinally associated with overweight development among apparently healthy Chinese adults. Additional studies are needed to elucidate mechanisms of action and to establish causal inference. PMID:21471280

  15. Anorexigenic lipopeptides ameliorate central insulin signaling and attenuate tau phosphorylation in hippocampi of mice with monosodium glutamate-induced obesity.

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    Špolcová, Andrea; Mikulášková, Barbora; Holubová, Martina; Nagelová, Veronika; Pirnik, Zdenko; Zemenová, Jana; Haluzík, Martin; Železná, Blanka; Galas, Marie-Christine; Maletínská, Lenka

    2015-01-01

    Numerous epidemiological and experimental studies have demonstrated that patients who suffer from metabolic disorders, such as type 2 diabetes mellitus (T2DM) or obesity, have higher risks of cognitive dysfunction and of Alzheimer's disease (AD). Impaired insulin signaling in the brain could contribute to the formation of neurofibrillary tangles, which contain an abnormally hyperphosphorylated tau protein. This study aimed to determine whether potential tau hyperphosphorylation could be detected in an obesity-induced pre-diabetes state and whether anorexigenic agents could affect this state. We demonstrated that 6-month-old mice with monosodium glutamate (MSG) obesity, which represent a model of obesity-induced pre-diabetes, had increased tau phosphorylation at Ser396 and Thr231 in the hippocampus compared with the controls, as determined by western blots. Two weeks of subcutaneous treatment with a lipidized analog of prolactin-releasing peptide (palm-PrRP31) or with the T2DM drug liraglutide, which both had a central anorexigenic effect, resulted in increased phosphorylation of the insulin cascade kinases PDK1 (Ser241), Akt (Thr308), and GSK-3β (Ser9). Furthermore, these drugs attenuated phosphorylation at Ser396, Thr231, and Thr212 of tau and of the primary tau kinases in the hippocampi of 6-month-old MSG-obese mice. We identified tau hyperphosphorylation in the obesity-induced pre-diabetes state in MSG-obese mice and demonstrated the beneficial effects of palm-PrRP31 and liraglutide, both of known central anorexigenic effects, on hippocampal insulin signaling and on tau phosphorylation.

  16. (p-ClPhSe)2Reduces Hepatotoxicity Induced by Monosodium Glutamate by Improving Mitochondrial Function in Rats.

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    Quines, Caroline B; Chagas, Pietro M; Hartmann, Diane; Carvalho, Nélson R; Soares, Félix A; Nogueira, Cristina W

    2017-09-01

    It is has been demonstrated that mitochondrial dysfunction, oxidative stress, and chronic inflammatory process are associated with progress of morbid obesity in human patients. For this reason, the searching for safe and effective antiobesity drugs has been the subject of intense research. In this context, the organic selenium compounds have attracted much attention due to their pharmacological properties, such as antihyperglycemic, antioxidant, and anti-inflammatory. The aim of this study was to evaluate the hepatoprotective action of p-chloro-diphenyl diselenide (p-ClPhSe) 2 , an organic selenium compound, in a model of obesity induced by monosodium glutamate (MSG) administration in rats. Wistar rats were treated during the first ten postnatal days with MSG (4 g/kg by subcutaneous injections) and received (p-ClPhSe) 2 (10 mg/kg, intragastrically) from 90th to 97th postnatal day. Mitochondrial function, purine content and the levels of proteins involved in apoptotic (poly [ADP-ribose] polymerase [PARP]) and inflammatory processes (inducible nitric oxide synthases [iNOS] and p38) were determined in the liver of rats. The present study, demonstrated that postnatal administration of MSG to male rats induced a mitochondrial dysfunction, accompanied by oxidative stress and an increase in the ADP levels, without altering the efficiency of phosphorylation in the liver of adult rats. Furthermore, the MSG administration also induces hepatotoxicity, through an increase in PARP, iNOS, and p38 levels. (p-ClPhSe) 2 treatment had beneficial effects against mitochondrial dysfunction, oxidative stress, and modulated protein markers of apoptosis and inflammation in the liver of MSG-treated rats. J. Cell. Biochem. 118: 2877-2886, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  17. The effects of additives on the crystal habit of monosodium L-glutamate monohydrate

    Science.gov (United States)

    Sano, Chiaki; Nagashima, Nobuya; Kawakita, Tetsuya; Iitaka, Yoichi

    1990-01-01

    The effects of various amino acids and organic acids on the habit of MSG crystals have been investigated. The addition of L-alanine (L-Ala) and L-lysine (L-Lys) made the MSG crystals short and thick, but D-glutamic acid (D-Glu), γ-amino butylic acid (γ-ABA) and L-pyrrolidone carboxylic acid (L-PCA) made the crystals long and thin. HPLC analysis of the end and the side faces of the MSG crystals grown with the additives revealed that the concentrations of L-Lys and L-Ala were higher at the end faces than at the side faces; but those of D-Glu, γ-ABA and L-PCA were higher at the side faces than at the end faces. The facts indicate that habit modifications of the MSG crystals, brought about in the presence of these additives, are due to stereo-selective adsorption of the additives on the crystal faces. Finally, the cause leading to the differences in adsorption of the additives on the crystal faces of MSG is discussed in relation to the stacking density of L-Glu molecules and Na ions on each face using the results of the X-ray structure analysis.

  18. Potent protection of ferulic acid against excitotoxic effects of maternal intragastric administration of monosodium glutamate at a late stage of pregnancy on developing mouse fetal brain.

    Science.gov (United States)

    Yu, Lijian; Zhang, Yongping; Ma, Rundi; Bao, Li; Fang, Juanzhi; Yu, Tingxi

    2006-04-01

    The present study was conducted to investigate a possible protection of ferulic acid against excitotoxic effects of maternal intragastric (ig) administration of monosodium glutamate (MSG) at a late stage of pregnancy on developing mouse fetal brain. [(3)H]-labeled glutamate was used as radiotracer to study the effect of ferulic acid on distribution of MSG in mouse fetal brain. MSG dissolved in distilled water (2.0 g/kg body weight, 640 kBq of [(3)H]glutamate/mouse, ig) or/and sodium ferulate (SF) (20, 40, 80 mg/kg body weight, ip), was given to pregnant mice at 17-19 days; the distribution of [(3)H] glutamate in the mouse fetal brains was measured at 30, 60, 90, 120 min after administration of MSG or/and SF. Maternal mice were given MSG (1.0, 2.0, 4.0 g/kg body weight, ig) or/and SF (20, 40, 80 mg/kg body weight, ip) simultaneously at 17-19 days of pregnancy, and then behavioral tests and histopathological observations were used to analyze glutamate-induced functional and morphological changes of the brains of their offspring, and Western blot analysis was performed for examining expressions of bcl-2 and caspase-3. The results showed that SF obviously inhibited the uptake of labeled glutamate in fetal brain. In addition, SF countered the effects of MSG on behavior, histopathology, genetic toxicity, and expression of apoptosis-related gene. The results suggest that ferulic acid is a novel competitive N-methyl-D-aspartate (NMDA) receptor antagonist and neuroprotector. In conclusion, maternal administration of ferulic acid has potent protective effects against glutamate-induced neurotoxicity in their filial mice.

  19. Comparison of the Obesity Phenotypes Related to Monosodium Glutamate Effect on Arcuate Nucleus and/or the High Fat Diet Feeding in C57BL/6 and NMRI Mice

    Czech Academy of Sciences Publication Activity Database

    Matyšková, Resha; Maletínská, Lenka; Maixnerová, Jana; Pirnik, Z.; Kiss, A.; Železná, Blanka

    2008-01-01

    Roč. 57, č. 5 (2008), s. 727-734 ISSN 0862-8408 R&D Projects: GA ČR GA303/05/0614 Institutional research plan: CEZ:AV0Z40550506 Keywords : C57BL/6 * NMRI * mouse * monosodium glutamate obesity Subject RIV: CC - Organic Chemistry Impact factor: 1.653, year: 2008

  20. Biochemical Studies on the Effect of Monosodium Glutamate and Omega 3 Fatty Acids in Gamma-Irradiated Rats

    International Nuclear Information System (INIS)

    Shedid, S.M.E.

    2014-01-01

    The consumption of foods and beverages containing additives has intensely increased over the past decades. Monosodium glutamate (MSG) is one of the main flavor enhancer that can be consumed in high concentrations. Also, human exposure to ionizing radiation (RAD) has become inevitable with its vast application in diagnosis and industry. Although the use of additives and exposure to RAD in therapeutic treatments are believed to be relatively safe their combined effect remain unclear. The objective of this work was to evaluate the role of fish oil (FO); rich in the omega-3 fatty acids eicosapentaenoic (EPA) and docosahexaenoic (DHA), on some biochemical alterations induced by exposure to MSG, RAD and MSG+RAD. Male albino rats were divided into 8 groups and treated in parallel: 1-Control, 2-FO: received FO (400 mg/Kg/day), 3-MSG: received MSG (450 mg/Kg/day), 4- FO+MSG: received FO with MSG, 5-RAD: whole body irradiated with 2Gy/week up to 8Gy, 6-FO+RAD: received FO daily during RAD exposure, 7- MSG+RAD: received MSG daily during RAD exposure. 8- FO+MSG+RAD: received FO daily during MSG+RAD exposure. Exposure to RAD and/or MSG induced oxidative stress evidenced by increased malondialdehyde (marker of lipid peroxidation), and protein carbonyl (marker of protein oxidation) associated to decreased superoxide dismutase, catalase and glutathione peroxidase activities and glutathione content (antioxidant biomarkers). Alteration in neurotransmitters was noted by a decrease in the level of serotonin (inhibitory neurotransmitter) and increased aspartic and glutamic acids (excitatory amino acids) though this increase was not recorded after exposure to MSG alone. The level of omega-3 fatty acids EPA and DHA was decreased. Furthermore, exposure to RAD and/or MSG elevate serum glucose, insulin, triglycerides, total cholesterol, and low-density lipoprotein cholesterol and decreased high-density lipoprotein cholesterol though this decrease was not observed after MSG exposure alone

  1. Curcumin Protects against Monosodium Glutamate Neurotoxicity and Decreasing NMDA2B and mGluR5 Expression in Rat Hippocampus

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    Rania M. Khalil

    2016-08-01

    Full Text Available Background: Monosodium glutamate (MSG is a flavor enhancer used in food industries. MSG is well documented to induce neurotoxicity. Curcumin (CUR reportedly possesses beneficial effects against various neurotoxic insults. Hence, this present study has been designed to evaluate the neuroprotective effect of curcumin on MSG-induced neurotoxicity in rats. Methods: Thirty-two male Wister rats were divided into four groups (n=8: Control group, MSG group, CUR group and MSG + CUR group. CUR (Curcumin 150 mg/kg, orally was given day after day for four weeks along with MSG (4 mg/kg, orally. After 4 weeks, rats were sacrificed and brain hippocampus was isolated immediately on ice. Inflammatory marker TNFα and acetylcholinesterase (AChE activity (marker for cholinergic function were estimated. Gene expressions of metabotropic glutamate receptor 5 (mGluR5 and N-methyl-D-aspartate receptor 2B (NMDA2B along with glutamate concentration were assessed. Results: Treatment with CUR significantly attenuated AChE activity and TNFα in MSG-treated animals. The anti-inflammatory properties of CUR may be responsible for this observed neuroprotective action. A possible role of CUR to attenuate both glutamate level and gene expression of NMDA2B and mGLUR5 in brain hippocampus was established when compared to MSG group. Conclusion: We concluded that CUR as flavor enhancer protects against MSG-induced neurotoxicity in rats.

  2. The effects of black garlic on the working memory and pyramidal cell number of medial prefrontal cortex of rats exposed to monosodium glutamate.

    Science.gov (United States)

    Nurmasitoh, Titis; Sari, Dwi Cahyani Ratna; Partadiredja, Ginus

    2017-12-27

    Monosodium glutamate-induced exitotoxicity causes oxidative stress in many brain areas, including the medial prefrontal cortex. The ethanolic garlic (Allium sativum) extract is considered as a neuroprotective substance. The present study aimed at investigating the effects of the ethanolic fermented garlic extract on the working memory and the pyramidal cell number of the medial prefrontal cortex of adolescent male Wistar rats exposed to monosodium glutamate (MSG). Twenty-five rats were randomly divided into five groups. The C- group was given 0.9% NaCl solution. The C + group was given 2 mg/g bw of MSG. The T1, T2, and T3 groups were given MSG and garlic extract (0.0125, 0.025, and 0.05 mg/g bw, respectively). All treatments were conducted for 10 days. The working memory capability of the rats was measured using Y-maze test. The total number of pyramidal cells of the medial prefrontal cortex was estimated using physical fractionator method. The working memory performances of the T1, T2, and T3 groups were significantly better than that of the C + group. There were no significant differences between groups in the estimated total number of pyramidal cell of medial prefrontal cortex. The MSG may not cause the death of neurons, but it may modify neuronal architectures that are sufficient to disrupt memory functions. Black garlic may play a role as an antioxidant agent that prevents the prefrontal cortex from glutamate-induced oxidative stress. It is concluded that the ethanolic fermented garlic extract prevented the working memory impairment following MSG administration.

  3. Monosodium Glutamate Toxicity

    African Journals Online (AJOL)

    Dr Olaleye

    functions of the cerebral cortex and the memory storage functions of the hippocampus may be disrupted (Snell, 2006). MSG-induced injury of these neural .... eliminate olfactory bias and allowed to dry before introducing a fresh animal. Sample collection and histological preparation ; On day 15 of the experiment, after ...

  4. Comparison of the Tastes of L-Alanine and Monosodium Glutamate in C57BL/6J Wild Type and T1r3 Knockout Mice.

    Science.gov (United States)

    Eddy, Meghan C; Eschle, Benjamin K; Delay, Eugene R

    2017-09-01

    Previous research showed that L-alanine and monosodium L-glutamate elicit similar taste sensations in rats. This study reports the results of behavioral experiments designed to compare the taste capacity of C57BL/6J wild type and T1r3- mice for these 2 amino acids. In conditioned taste aversion (CTA) experiments, wild-type mice exhibited greater sensitivity than knockout mice for both L-amino acids, although knockout mice were clearly able to detect both amino acids at 50 mM and higher concentrations. Generalization of CTA between L-alanine and L-glutamate was bidirectionally equivalent for both mouse genotypes, indicating that both substances elicited similar tastes in both genotypes. This was verified by the discrimination experiments in which both mouse genotypes performed at or near chance levels at 75 and 150 mM. Above 150 mM, discrimination performance improved, suggesting the taste qualities of the 2 L-amino acids are not identical. No differences between knockout and wild-type mice in discrimination ability were detected. These results indicate that while the T1r3 receptor is important for tasting L-alanine and L-glutamate, other receptors are also important for tasting these amino acids. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  5. Studies on the influences of. gamma. -ray irradiation upon food additives, (6). Radiolysis of monosodium glutamate due to. gamma. -ray irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Hamada, M. (Shimonoseki Univ. of Fisheries, Yamaguchi (Japan)); Gohya, Y.; Ishio, S.

    1981-08-01

    The effect of ..gamma..-ray irradiation on monosodium glutamate (MSG) in aqueous solution and in ''kamaboko'' was investigated to evaluate the rate of decomposition of MSG and to elucidate the safety of the decomposed products, under the concentration of 106.9 mmol/l aqueous solution and 1% content of MSG in ''kamaboko''. In aqueous solution, MSG was decomposed by ..gamma..-ray irradiation, and G value was estimated to be 1.24. The decomposition of MSG resulted from deamination reaction was estimated to be 40% of the total decomposition. Glutamic acid content decreased as the dose of ..gamma..-ray increased in MSG-enriched ''kamaboko'', while it increased as the dose of ..gamma..-ray increased in MSG-free ''kamaboko''. Glutamic acid was liberated from the protein in ''kamaboko'', therefore the apparent decomposition rate of MSG in ''kamaboko'' was regarded as lower than actual.

  6. Choline chloride (ChCl) and monosodium glutamate (MSG)-based green solvents from optimized cactus malic acid for biomass delignification.

    Science.gov (United States)

    Yiin, Chung Loong; Quitain, Armando T; Yusup, Suzana; Uemura, Yoshimitsu; Sasaki, Mitsuru; Kida, Tetsuya

    2017-11-01

    This work aimed to develop an efficient microwave-hydrothermal (MH) extraction of malic acid from abundant natural cactus as hydrogen bond donor (HBD) whereby the concentration was optimized using response surface methodology. The ideal process conditions were found to be at a solvent-to-feed ratio of 0.008, 120°C and 20min with 1.0g of oxidant, H 2 O 2 . Next generation environment-friendly solvents, low transition temperature mixtures (LTTMs) were synthesized from cactus malic acid with choline chloride (ChCl) and monosodium glutamate (MSG) as hydrogen bond acceptors (HBAs). The hydrogen-bonding interactions between the starting materials were determined. The efficiency of the LTTMs in removing lignin from oil palm biomass residues, empty fruit bunch (EFB) was also evaluated. The removal of amorphous hemicellulose and lignin after the pretreatment process resulted in an enhanced digestibility and thermal degradability of biomass. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Effects of chronic dietary exposure to monosodium glutamate on feeding behavior, adiposity, gastrointestinal motility, and cardiovascular function in healthy adult rats.

    Science.gov (United States)

    López-Miranda, V; Soto-Montenegro, M L; Uranga-Ocio, J A; Vera, G; Herradón, E; González, C; Blas, C; Martínez-Villaluenga, M; López-Pérez, A E; Desco, M; Abalo, R

    2015-11-01

    Monosodium glutamate (MSG) is a flavor-enhancer widely used as a food additive. However, its safe dietary concentration and its toxicity, including its possible implication in the recent metabolic syndrome pandemia, is still a controversial issue. Therefore, a deep knowledge of its effects upon regular dietary use is needed. Our aim was to evaluate the effects of chronic exposure to MSG on feeding behavior, abdominal fat, gastrointestinal motility, and cardiovascular function in rats. Two groups of adult male Wistar rats were used: control and treated with MSG (4 g/L in drinking water) for 6 weeks. Different functional parameters were determined and the histological structure was analyzed in tissues of interest. Compared to control animals, chronic MSG increased water intake but did not modify food ingestion or body weight gain. Neither the abdominal fat volume nor the fat fraction, measured by magnetic resonance imaging, was modified by MSG. Monosodium glutamate did not alter general gastrointestinal motility, but significantly increased the colonic response to mechanical stimulation. It slightly reduced endothelium-dependent relaxation in aorta, without significantly modifying any other cardiovascular parameters. No significant histological alterations were detected in salivary glands, intestinal wall, aorta, heart, and kidney. Chronic treatment with MSG in the adult rat increased water intake. This supports its potential to improve acceptance of low-fat regimens and to increase hydration in the elderly and sportspeople, often at risk of dehydration. Changes in colonic contractility and cardiovascular function could have some long-term repercussions warranting further research. © 2015 John Wiley & Sons Ltd.

  8. Mutual diffusion coefficients of L-glutamic acid and monosodium L-glutamate in aqueous solutions at T = 298.15 K

    International Nuclear Information System (INIS)

    Ribeiro, Ana C.F.; Rodrigo, M.M.; Barros, Marisa C.F.; Verissimo, Luis M.P.; Romero, Carmen; Valente, Artur J.M.; Esteso, Miguel A.

    2014-01-01

    Highlights: • Interdiffusion coefficients of L-glutamic acid and sodium L-glutamate were measured. • The L-glutamic acid behaves as a monoprotic weak acid. • The sodium L-glutamate shows a symmetrical 1:1 non-associated behaviour. • Limiting diffusion coefficients and ionic conductivities were estimated. • Diffusion coefficients were discussed on the basis of the Onsager–Fuoss equations. - Abstract: Mutual diffusion coefficient values for binary aqueous solutions of both L-glutamic acid (H 2 Glu) and sodium L-glutamate (NaHGlu) were measured with the Taylor dispersion technique, at T = 298.15 K, and concentrations ranging from (0.001 to 0.100) mol · dm −3 . The results were discussed on the basis of the Onsager–Fuoss and the Nernst theoretical equations, by considering the H 2 Glu as a weak acid (monoprotic acid, with K 2 = 5.62 · 10 −5 ). The smaller values found for the acid with respect to those of the salt, confirm this association hypothesis. From the diffusion coefficient values at infinitesimal concentration, limiting ionic conductivities as well as the hydrodynamic radius of the hydrogen glutamate ion (HGlu − ) were derived and analyzed in terms of the chain methylene groups. The effect of different phenomena, such as association or complexation, were also taken into consideration and discussed. Values for the dissociation degree for H 2 Glu were also estimated

  9. Optimization of the production of poly-γ-glutamic acid by Bacillus amyloliquefaciens C1 in solid-state fermentation using dairy manure compost and monosodium glutamate production residues as basic substrates.

    Science.gov (United States)

    Yong, Xiaoyu; Raza, Waseem; Yu, Guanghui; Ran, Wei; Shen, Qirong; Yang, Xingming

    2011-08-01

    Poly-γ-glutamic acid (γ-PGA) is a polymer with uses in foods, cosmetics, medicine and agriculture. The medium for the production of γ-PGA by Bacillusamyloliquefaciens C1 was optimized by response surface methodology using agro-industrial wastes in solid-state fermentation (SSF). The optimal SSF medium (20g substrates with 50% initial moisture) for producing γ-PGA was determined to contain 5.51g dairy manure compost, 1.91g soybean cake, 0.57g corn flour, 2.15g monosodium glutamate production residues, 1.5g wheat bran, 0.5g rapeseed cake, 0.1g citric acid, 0.05g MgSO(4)·7H(2)O and 0.03g MnSO(4)·H(2)O. In this medium the strain produced up to 0.0437g γ-PGA per gram of substrates when cultured for 48h at 37°C. SDS-PAGE showed that the molecular weight of the γ-PGA was more than 130kDa. Due to the high-yields observed and the low-cost nature of the optimal medium, this study indicates a possibility to establish economical large-scale production of γ-PGA. Copyright © 2011 Elsevier Ltd. All rights reserved.

  10. Changes in the expression level of MAPK pathway components induced by monosodium glutamate-administration produce neuronal death in the hippocampus from neonatal rats.

    Science.gov (United States)

    Rivera-Carvantes, Martha Catalina; Jarero-Basulto, José Jaime; Feria-Velasco, Alfredo Ignacio; Beas-Zárate, Carlos; Navarro-Meza, Mónica; González-López, Mariana Berenice; Gudiño-Cabrera, Graciela; García-Rodríguez, Julio Cesar

    2017-12-04

    Excessive Glutamate (Glu) release may trigger excitotoxic cellular death by the activation of intracellular signaling pathways that transduce extracellular signals to the cell nucleus, which determines the onset of a death program. One such signaling pathway is the mitogen-activated protein kinases (MAPK), which is involved in both survival and cell death. Experimental evidences from the use of specific inhibitors supports the participation of some MAPK pathway components in the excitotoxicity mechanism, but the complete process of this activation, which terminates in cell damage and death, is not clearly understood. The present work, we investigated the changes in the expression level of some MAPK-pathway components in hippocampal excitotoxic cell death in the neonatal rats using an experimental model of subcutaneous monosodium glutamate (MSG) administration on postnatal days (PD) 1, 3, 5 and 7. Data were collected at different ages through PD 14. Cell viability was evaluated using fluorescein diacetate mixed with propidium iodide (FDA-PI), and the Nissl-staining technique was used to evaluate histological damage. Transcriptional changes were also investigated in 98 components of the MAPK pathway that are associated with cell damage. These results are an evidence of that repetitive use of MSG, in neonatal rats, induces cell damage-associated transcriptional changes of MAPK components, that might reflect a differential stage of both biochemical and molecular brain maturation. This work also suggests that some of the proteins evaluated such as phosphorylated retinoblastoma (pRb) protein, which was up-regulated, could regulate the response to excitotoxic through modulation of the process of re-entry into the cell cycle in the hippocampus of rats treated with MSG. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  11. Effect of Nigella Sativa Extract on Inflammatory Cells, Interleukin-10, Interferon-γ and Histological of Kidney in Monosodium Glutamate-Induced Rats

    Directory of Open Access Journals (Sweden)

    Abdalrauf A Mahmud Yousif

    2016-04-01

    Full Text Available There is considerable evidence, suggest that, consumption of food additives monosodium glutamate (MSG, a flavor enhancer was unhealthy. Herbal medicine Nigella sativa (NS has antioxidant properties able to cure the toxic induced by MSG. This study aimed to evaluate the risks of excessive use of MSG and to study the role of NS to inhibit inflammation and renal damage. Treated rats (twenty four male wistar rats were divided into six group and analyzed by measuring the cells in blood, interleukin-10, interferon-γ serum levels by ELISA method and remove kidneys for histological examination. Histological of kidney for all groups except control, were showed different abnormalities include congestion of some blood vessels, hemorrhage between tubules, widening in the renal tubules, revealed severe dilatation of Bowman's capsule and shrinkage of glomeruli, and areas of huge vacuole, were observed compared with control. Interleukin-10 was reduced in Groups 2,3,4 and 5, whereas increase in NS group compared with control. Interferon-γ was increased in groups 2,3,4 and reduced in groups 5,6 compared with control. Eosinophil was increased in groups 2,5 and reduced in groups 3,4, 6 compared with control. This present study showed that administration of MSG to rats induced many changes effects on inflammatory cells, cytokines and histological of kidneys. NS has benefit in blood parameters, whereas harmful on kidney at these doses.

  12. The alpha/beta-adrenergic receptor blocker arotinolol activates the thermogenesis of brown adipose tissue in monosodium-L-glutamate-induced obese mice.

    Science.gov (United States)

    Yoshida, T; Sakane, N; Wakabayashi, Y; Yoshioka, K; Umekawa, T; Kondo, M

    1994-05-01

    We have found previously that arotinolol, an alpha/beta-adrenergic blocker, increases blood flow in brown adipose tissue (BAT) in a similar extent as BRL 26830A, a beta 3-adrenoceptor agonist. We tested the hypothesis that arotinolol activates thermogenesis in BAT, leading to weight loss in monosodium-L-glutamate-induced (MSG-induced) obese mice and saline-treated controls. Six weeks of standard animal feed (CE-2) containing arotinolol hydrochloride (350 mg/kg CE-2), which reduced mean blood pressure in MSG-treated mice, significantly increased the mitochondrial protein content in BAT, and activated the specific and total binding of guanosine-5'-diphosphate (GDP) in BAT mitochondria, leading to a reduction of obesity in both MSG- and saline-treated mice vs. the control groups fed with CE-2 diet alone. However, six weeks of CE-2 diet containing propranolol hydrochloride (525 mg/kg CE-2) a non-selective beta-blocker, markedly reduced the specific and total binding of GDP in BAT mitochondria, leading to weight gain in both MSG- and saline-treated mice. These findings support the hypothesis, that arotinolol activates BAT thermogenesis, leading to weight loss.

  13. Estradiol target neurons in the hypothalamic arcuate nucleus and lateral ventromedial nucleus of young adult, reproductively senescent, and monosodium glutamate-lesioned female golden hamsters

    International Nuclear Information System (INIS)

    Blaha, G.C.; Lamperti, A.A.

    1983-01-01

    Histoautoradiographic methods were used to assess estrogen target neurons in the hypothalamic arcuate nucleus (ARC) and ventromedial nucleus, lateral portion (LVM), comparing young adult and aged female golden hamsters. A subgroup of young adult females had ARC lesions induced by monosodium glutamate at neonatal day 8. All were ovariectomized to remove endogenous estrogens. Controls were given nonradioactive estradiol. After 3 H-estradiol ( 3 H-E2) was injected intravenously, hypothalami were removed, frozen, and processed for histoautoradiography. In the ARC and LVM the ratio of 3 H-E2 labelled neurons to total neurons counted was significantly lower in the older animals. Young females with ARC lesions had very few 3 H-E2 labelled neurons remaining in the ARC but had a normal complement in the LVM. Although 3 H-E2 labelled ARC neurons were notably decreased in old females, those ARC neurons that were labelled in the old had virtually the same frequency distribution of the labelling index as in the young, suggesting no change in the average estrogen uptake per target cell

  14. The Neuroprotective Effect of Dark Chocolate in Monosodium Glutamate-Induced Nontransgenic Alzheimer Disease Model Rats: Biochemical, Behavioral, and Histological Studies.

    Science.gov (United States)

    Madhavadas, Sowmya; Kapgal, Vijaya Kumar; Kutty, Bindu M; Subramanian, Sarada

    2016-01-01

    The vulnerability to oxidative stress and cognitive decline continue to increase during both normal and pathological aging. Dietary changes and sedentary life style resulting in mid-life obesity and type 2 diabetes, if left uncorrected, further add to the risk of cognitive decline and Alzheimer disease (AD) in the later stages of life. Certain antioxidant agents such as dietary polyphenols, taken in adequate quantities, have been suggested to improve the cognitive processes. In this study, we examined the effect of oral administration of dark chocolate (DC) containing 70% cocoa solids and 4% total polyphenol content for three months at a dose of 500 mg/Kg body weight per day to 17-month-old monosodium glutamate treated obese Sprague-Dawley rats, earlier characterized as a nontransgenic AD (NTAD) rat model after reversal of obesity, diabetes, and consequent cognitive impairments. The results demonstrated that DC reduced the hyperglycemia, inhibited the cholinesterase activity in the hippocampal tissue homogenates, and improved the cognitive performance in spatial memory related Barnes maze task. Histological studies revealed an increase in cell volume in the DC treated rats in the CA3 region of the hippocampus. These findings demonstrated the benefits of DC in enhancing cognitive function and cholinergic activity in the hippocampus of the aged NTAD rats while correcting their metabolic disturbances.

  15. The fifth dimension of the taste in Spirulina platensis feed. Study on the influence of monosodium glutamate in the development and composition of the Spirulina platensis algae

    Directory of Open Access Journals (Sweden)

    Ştefan MANEA

    2010-12-01

    Full Text Available Food additives have become a way of life, creating pleasure and food request. But from the point of view of health promotion, it is necessary to demonstrate the risks and find out new possibilities for a good sensorial aspect of the food. This would apply especially in the case of long-term consumption, or in some particular conditions (allergies to different ingredients which appear more often to consumers. Cheap products are manufactured by using E-dangerous. The explanation is simple: the natural E extracted from various fruits and vegetables are very expensive. The study wants to demonstrate that the monosodium glutamate (MSG into the culture medium of plantscan affect their healthiness. Spirulina platensis has the same type of amino acids as humans and this is why it has been chosen as an experiment plant. Four samples obtained from the Spirulina’s culturemedium were studied: one blank and three with 0.2%, 0.4% and respectively 0.6% MSG in the culture medium. The mineral content was evaluated using the Atomic Absorption Spectroscopy (AAS and a rapid increase of calcium and magnesium content was registered for the sample with the biggest amount of MSG. The structure of the filaments and the cells appearance were evaluated microscopically. There were changes identified in the structure after three days of cultivating. Also, the sample with 0.6% MSG presented dead cells and the ones which were still alive had profound changes in form and structure.

  16. Lycopene modulates cholinergic dysfunction, Bcl-2/Bax balance, and antioxidant enzymes gene transcripts in monosodium glutamate (E621) induced neurotoxicity in a rat model.

    Science.gov (United States)

    Sadek, Kadry; Abouzed, Tarek; Nasr, Sherif

    2016-04-01

    The effect of monosodium glutamate (MSG) on brain tissue and the relative ability of lycopene to avert these neurotoxic effects were investigated. Thirty-two male Wistar rats were distributed into 4 groups: group I, untreated (placebo); group II, injected with MSG (5 mg·kg(-1)) s.c.; group III, gastrogavaged with lycopene (10 mg·kg(-1)) p.o.; and group IV received MSG with lycopene with the same mentioned doses for 30 days. The results showed that MSG induced elevation in lipid peroxidation marker and perturbation in the antioxidant homeostasis and increased the levels of brain and serum cholinesterase (ChE), total creatine phosphokinase (CPK), creatine phosphokinase isoenzymes BB (CPK-BB), and lactate dehydrogenase (LDH). Glutathione S-transferase (GST), superoxide dismutase (SOD), and catalase (CAT) activities and gene expression were increased and glutathione content was reduced in the MSG-challenged rats, and these effects were ameliorated by lycopene. Furthermore, MSG induced apoptosis in brain tissues reflected in upregulation of pro-apoptotic Bax while lycopene upregulated the anti-apoptotic Bcl-2. Our results indicate that lycopene appears to be highly effective in relieving the toxic effects of MSG by inhibiting lipid peroxidation and inducing modifications in the activity of cholinesterase and antioxidant pathways. Interestingly, lycopene protects brain tissue by inhibiting apoptosis signaling induced by MSG.

  17. Both dietary supplementation with monosodium L-glutamate and fat modify circulating and tissue amino acid pools in growing pigs, but with little interactive effect.

    Directory of Open Access Journals (Sweden)

    Zemeng Feng

    Full Text Available The Chinese population has undergone rapid transition to a high-fat diet. Furthermore, monosodium L-glutamate (MSG is widely used as a daily food additive in China. Little information is available on the effects of oral MSG and dietary fat supplementation on the amino acid balance in tissues. The present study aimed to determine the effects of both dietary fat and MSG on amino acid metabolism in growing pigs, and to assess any possible interactions between these two nutrients.Four iso-nitrogenous and iso-caloric diets (basal diet, high fat diet, basal diet with 3% MSG and high fat diet with 3% MSG were provided to growing pigs. The dietary supplementation with fat and MSG used alone and in combination were found to modify circulating and tissue amino acid pools in growing pigs. Both dietary fat and MSG modified the expression of gene related to amino acid transport in jejunum.Both dietary fat and MSG clearly influenced amino acid content in tissues but in different ways. Both dietary fat and MSG enhance the absorption of amino acids in jejunum. However, there was little interaction between the effects of dietary fat and MSG.

  18. The use of concentrated monosodium glutamate wastewater as a conditioning agent for adjusting acidity and minimizing ammonia volatilization in livestock manure composting.

    Science.gov (United States)

    Liu, Li; Kong, Haimin; Lu, Beibei; Wang, Jibing; Xie, Yuan; Fang, Ping

    2015-09-15

    In this study, concentrated monosodium glutamate waste (CMGW) was proposed as a conditioning agent to adjust acidity and decrease ammonia (NH3) volatilization in thermophilic aerobic composting based on two incubation experiments. The results showed that with the addition of CMGW, NH3 volatilization of compost mixture under high temperature phase decreased significantly and pH met the current national standard within 5.5-8.5. When CMGW dosage increased to 2% (v/w), the decrease in NH3 volatilization was as high as 78.9%. This effect was enhanced by repeated application of CMGW. Furthermore, although the electrical conductivity increased with the application of CMGW, both the germination index and the microbial respiration of compost mixture implied that CMGW had no negative effects on the maturity of compost, instead, a comprehensive maturity might be accelerated. It was concluded that CMGW was an optional conditioning agent for thermophilic aerobic composting of livestock manure in regards to adjusting acidity and preventing nitrogen loss from NH3 volatilization. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. Estradiol target neurons in the hypothalamic arcuate nucleus and lateral ventromedial nucleus of young adult, reproductively senescent, and monosodium glutamate-lesioned female golden hamsters

    Energy Technology Data Exchange (ETDEWEB)

    Blaha, G.C.; Lamperti, A.A.

    1983-09-01

    Histoautoradiographic methods were used to assess estrogen target neurons in the hypothalamic arcuate nucleus (ARC) and ventromedial nucleus, lateral portion (LVM), comparing young adult and aged female golden hamsters. A subgroup of young adult females had ARC lesions induced by monosodium glutamate at neonatal day 8. All were ovariectomized to remove endogenous estrogens. Controls were given nonradioactive estradiol. After /sup 3/H-estradiol (/sup 3/H-E2) was injected intravenously, hypothalami were removed, frozen, and processed for histoautoradiography. In the ARC and LVM the ratio of /sup 3/H-E2 labelled neurons to total neurons counted was significantly lower in the older animals. Young females with ARC lesions had very few /sup 3/H-E2 labelled neurons remaining in the ARC but had a normal complement in the LVM. Although /sup 3/H-E2 labelled ARC neurons were notably decreased in old females, those ARC neurons that were labelled in the old had virtually the same frequency distribution of the labelling index as in the young, suggesting no change in the average estrogen uptake per target cell.

  20. Hepatotoxic effects of low dose oral administration of monosodium ...

    African Journals Online (AJOL)

    The present study is aimed at investigating the potentials of low concentration administration of monosodium glutamate in inducing hepatotoxic effects in male albino rats. Thus, monosodium glutamate at a dose of 5 mg/kg of body weight was administered to adult male albino rats by oral intubation. Treatment was daily for ...

  1. Polyphenol-rich extract of Syzygium cumini leaf dually improves peripheral insulin sensitivity and pancreatic islet function in monosodium L-glutamate-induced obese rats

    Directory of Open Access Journals (Sweden)

    Jonas Rodrigues Sanches

    2016-03-01

    Full Text Available Syzygium cumini (L. Skeels (Myrtaceae has been traditionally used to treat a number of illnesses. Ethnopharmacological studies have particularly addressed antidiabetic and metabolic-related effects of extracts prepared from its different parts, especially seed and pulp-fruit, however there is a lack of studies on phytochemical profile and biological properties of its leaf. As there is considerable interest in bioactive compounds to treat metabolic syndrome and its clustered risk factors, we sought to characterize the metabolic effects of hydroethanolic extract of S. cumini leaf (HESc on lean and monosodium L-glutamate (MSG-induced obese rats. HPLC-MS/MS characterization of the HESc polyphenolic profile, at 254 nm, identified 15 compounds pertaining to hydrolysable tannin and flavanol subclasses. At 60 days of age, both groups were randomly assigned to receive HESc (500 mg/kg or vehicle for 30 days. At the end of treatment, obese+HESc exhibited significantly lower body weight gain, body mass index, and white adipose tissue mass, compared to obese rats receiving vehicle. Obese rats treated with HESc showed a 2-fold increase in lipolytic activity in the periepididymal fat pad, as well as, brought triglyceride levels in serum, liver and skeletal muscle back to levels close those found in lean animals. Furthermore, HESc also improved hyperinsulinemia and insulin resistance in obese+HESc rats, which resulted in partial reversal of glucose intolerance, as compared to obese rats. HESc had no effect in lean rats. Assessment of ex vivo glucose-stimulated insulin secretion showed HESc potentiated pancreatic function in islets isolated from both lean and obese rats treated with HESc. In addition, HESc (10 – 1000 ug/mL increased glucose stimulated insulin secretion from both isolated rat islets and INS-1E beta cells. These data demonstrate that S. cumini leaf improved peripheral insulin sensitivity via stimulating/modulating beta cell insulin release

  2. The Effect of Nigella Sativa Extract on Alpha-ketoglutarate Activity and Histopathologic Changes on Rat Liver Induced by Monosodium Glutamate

    Directory of Open Access Journals (Sweden)

    Ala Sh Emhemed Eshami

    2015-09-01

    Full Text Available Monosodium glutamate (MSG is a commonly used food additive and found in most soups, fish, and processed meat. The use of MSG in food is growing. However, the fear of consuming MSG has increased in the last few years due to the adverse reactions and toxicity in the liver. Nigella sativa (NS is used as traditional medicine for the treatment of many diseases. It has been extensively investigated in recent years due to its notable pharmacological properties such as inhibit oxidative stress. The present study was undertaken to investigate the effect of different doses of Nigella Sativa on alpha KGDH activity and liver histology of MSG-induced rats. The animals (n=30 were grouped into A (control, B (treated with MSG 1g/kg.bw , C (treated with MSG 1g/kg.bw and NS 0.1 g/kg.bw, D (treated with MSG 1g/kg.bw and NS 0.2 g/kg.bw, E (treated with MSG 1g/kg.bw and NS 0.4 g/kg.bw and F (given a daily NS extract 0.2 g/kg.bw. Alpha KGDH activity was investigated using ELISA method and liver histopathology by light microscope. The MSG treatment increased Alpha KGDH activity and disturbed liver architecture, hemorrhage in the central veins, areas of necrosis, vacuolation and increased inflammatory cells infiltration. The condition was normalized by treatment NS on dose 0.2 and 0.4 g/kg.bw. The findings showed that the administration of MSG increases alpha KGDH and induces damage in liver tissue. Nigella sativa extract can reduce alpha KGDH and prevent liver damage caused by MSG.

  3. Benefits of L-alanine or L-arginine supplementation against adiposity and glucose intolerance in monosodium glutamate-induced obesity.

    Science.gov (United States)

    Araujo, Thiago R; Freitas, Israelle N; Vettorazzi, Jean F; Batista, Thiago M; Santos-Silva, Junia C; Bonfleur, Maria L; Balbo, Sandra L; Boschero, Antonio C; Carneiro, Everardo M; Ribeiro, Rosane A

    2017-09-01

    L-alanine (Ala) and L-arginine (Arg) have been reported to regulate pancreatic β-cell physiology and to prevent body fat accumulation in diet-induced obesity. Here, we assessed growth and adiposity parameters, glucose tolerance, insulin secretion and the expression of insulin and nutrient-regulated proteins in monosodium glutamate (MSG)-obese mice supplemented with either Ala or Arg. Male newborn C57Bl/6 mice received a daily subcutaneous injection of MSG or saline solution (CTL group), during the first 6 days of life. From 30 to 90 days of age, MSG and CTL mice received or not 2.55 % Ala (CAla or MArg groups) or 1.51 % Arg-HCl (CArg or MArg groups) in their drinking water. Adult MSG mice displayed higher adiposity associated with lower phosphorylation of the adipogenic enzyme, ACC, in adipose tissue. Glucose intolerance in MSG mice was linked to lower insulin secretion and to lower expression of IRβ in adipose tissue, as well as AS160 phosphorylation in skeletal muscle. Perigonadal fat depots were smaller in Ala and Arg mice, while retroperitoneal fat pads were decreased by Ala supplementation only. Both Ala and Arg improved fed-state glycemia as well as IRβ and pAS160 content, but only Ala led to improved glucose tolerance and insulin secretion. Adipostatic signals were increased in MAla mice, as indicated by enhanced AMPK phosphorylation and pACC content in fat depots. Ala supplementation led to more pronounced metabolic improvements compared to Arg, possibly due to suppression of lipogenesis through activation of the AMPK/ACC pathway.

  4. The endocrine disrupting potential of monosodium glutamate (MSG) on secretion of the glucagon-like peptide-1 (GLP-1) gut hormone and GLP-1 receptor interaction.

    Science.gov (United States)

    Shannon, Maeve; Green, Brian; Willars, Gary; Wilson, Jodie; Matthews, Natalie; Lamb, Joanna; Gillespie, Anna; Connolly, Lisa

    2017-01-04

    Monosodium glutamate (MSG) is a suspected obesogen with epidemiological evidence positively correlating consumption to increased body mass index and higher prevalence of metabolic syndrome. ELISA and high content analysis (HCA) were employed to examine the disruptive effects of MSG on the secretion of enteroendocrine hormone glucagon-like peptide-1 (GLP-1) and GLP-1 receptor (GLP-1R), respectively. Following 3h MSG exposure of the enteroendocrine pGIP/neo: STC-1 cell line model (500μg/ml) significantly increased GLP-1 secretion (1.8 fold; P≤0.001), however, 72h exposure (500μg/ml) caused a 1.8 fold decline (P≤0.05). Also, 3h MSG exposure (0.5-500μg/ml) did not induce any cytotoxicity (including multiple pre-lethal markers) but 72h exposure at 250-500μg/ml, decreased cell number (11.8-26.7%; P≤0.05), increased nuclear area (23.9-29.8%; P≤0.001) and decreased mitochondrial membrane potential (13-21.6%; P≤0.05). At 500μg/ml, MSG increased mitochondrial mass by 16.3% (P≤0.01). MSG did not agonise or antagonise internalisation of the GLP-1R expressed recombinantly in U2OS cells, following GLP-1 stimulation. In conclusion, 72h exposure of an enteroendocrine cell line at dietary levels of MSG, results in pre-lethal cytotoxicity and decline in GLP-1 secretion. These adverse events may play a role in the pathogenesis of obesity as outlined in the obesogen hypothesis by impairing GLP-1 secretion, related satiety responses and glucose-stimulated insulin release. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  5. Persistent enhancement of ethanol drinking following a monosodium glutamate-substitution procedure in C57BL6/J and DBA/2J mice.

    Science.gov (United States)

    McCool, Brian A; Chappell, Ann M

    2014-02-01

    Inbred mouse strains such as C57BL/6J (B6) and DBA/2J (D2) and related strains have been used extensively to help identify genetic controls for a number of ethanol-related behaviors, including acute intoxication and sensitivity to repeated exposures. The disparate ethanol drinking behaviors of B6 mice expressing high-drinking/preference and D2 mice expressing low-drinking/preference have yielded considerable insight into the heritable control of alcohol drinking. However, the B6-high and D2-low drinking phenotypes are contrasted with ethanol-conditioned reward-like behaviors, which are robustly expressed by D2 mice and considerably less expressed by B6 mice. This suggests that peripheral factors, chiefly ethanol taste, may help drive ethanol drinking by these and related strains, which complicates mouse genetic studies designed to understand the relationships between reward-related behaviors and ethanol drinking. Traditional approaches such as the sucrose/saccharin-substitution procedure that normally accentuate ethanol drinking in rodents have had limited success in low drinking/preferring mice such as the D2 line. This may be due to allelic variations of the sweet taste receptor subunit, expressed by many ethanol low-drinking/preferring strains, which would limit the utility of these types of substitution approaches. We have recently shown (McCool & Chappell, 2012) that monosodium glutamate (MSG), the primary component of umami taste, can be used in a substitution procedure to initiate ethanol drinking in both B6 and D2 mice that greatly surpasses that initiated by a more traditional sucrose-substitution procedure. In this study, we show that ethanol drinking initiated by MSG substitution in D2 mice, but not sucrose substitution, can persist for several weeks following removal of the flavor. These findings further illustrate the utility of MSG substitution to initiate ethanol drinking in distinct mouse strains. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. Altered cytochrome P450 activities and expression levels in the liver and intestines of the monosodium glutamate-induced mouse model of human obesity.

    Science.gov (United States)

    Tomankova, Veronika; Liskova, Barbora; Skalova, Lenka; Bartikova, Hana; Bousova, Iva; Jourova, Lenka; Anzenbacher, Pavel; Ulrichova, Jitka; Anzenbacherova, Eva

    2015-07-15

    Cytochromes P450 (CYPs) are enzymes present from bacteria to man involved in metabolism of endogenous and exogenous compounds incl. drugs. Our objective was to assess whether obesity leads to changes in activities and expression of CYPs in the mouse liver, small intestine and colon. An obese mouse model with repeated injection of monosodium glutamate (MSG) to newborns was used. Controls were treated with saline. All mice were sacrificed at 8 months. In the liver and intestines, levels of CYP mRNA and proteins were analyzed using RT-PCR and Western blotting. Activities of CYP enzymes were measured with specific substrates of human orthologous forms. At the end of the experiment, body weight, plasma insulin and leptin levels as well as the specific content of hepatic CYP enzymes were increased in obese mice. Among CYP enzymes, hepatic CYP2A5 activity, protein and mRNA expression increased most significantly in obese animals. Higher activities and protein levels of hepatic CYP2E1 and 3A in the obese mice were also found. No or a weak effect on CYPs 2C and 2D was observed. In the small intestine and colon, no changes of CYP enzymes were detected except for increased expression of CYP2E1 and decreased expression of CYP3A mRNAs in the colon of the obese mice. Results of our study suggest that the specific content and activities of some liver CYP enzymes (especially CYP2A5) can be increased in obese mice. Higher activity of CYP2A5 (CYP2A6 human ortholog) could lead to altered metabolism of drug substrates of this enzyme (valproic acid, nicotine, methoxyflurane). Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Homeostatic effect of p-chloro-diphenyl diselenide on glucose metabolism and mitochondrial function alterations induced by monosodium glutamate administration to rats.

    Science.gov (United States)

    Quines, Caroline B; Rosa, Suzan G; Chagas, Pietro M; da Rocha, Juliana T; Dobrachinski, Fernando; Carvalho, Nélson R; Soares, Félix A; da Luz, Sônia C Almeida; Nogueira, Cristina W

    2016-01-01

    The metabolic syndrome is a group of metabolic alterations considered a worldwide public health problem. Organic selenium compounds have been reported to have many different pharmacological actions, such as anti-hypercholesterolemic and anti-hyperglycemic. The aim of this study was to evaluate the effect of p-chloro-diphenyl diselenide (p-ClPhSe)2, an organic selenium compound, in a model of obesity induced by monosodium glutamate (MSG) administration in rats. The rats were treated during the first ten postnatal days with MSG and received (p-ClPhSe)2 (10 mg/kg, intragastrically) from 45th to 51 th postnatal day. Glucose, lipid and lactate levels were determined in plasma of rats. Glycogen levels and activities of tyrosine aminotransferase, hexokinase, citrate synthase and glucose-6-phosphatase (G-6-Pase) were determined in livers of rats. Renal G-6-Pase activity was also determined. The purine content [Adenosine triphosphate (ATP), adenosine diphosphate (ADP) and adenosine monophosphate] and mitochondrial functionality in the liver were also investigated. p-(ClPhSe)2 did not alter the reduction in growth performance and in the body weight caused by MSG but reduced epididymal fat deposition of rats. p-(ClPhSe)2 restored glycemia, triglycerides, cholesterol and lactate levels as well as the glucose metabolism altered in rats treated with MSG. p-(ClPhSe)2 restored hepatic mitochondrial dysfunction and the decrease in citrate synthase activity and ATP and ADP levels caused by MSG in rats. In summary, (p-ClPhSe)2 had homeostatic effects on glucose metabolism and mitochondrial function alterations induced by MSG administration to rats.

  8. Peripheral CB1 Receptor Neutral Antagonist, AM6545, Ameliorates Hypometabolic Obesity and Improves Adipokine Secretion in Monosodium Glutamate Induced Obese Mice

    Directory of Open Access Journals (Sweden)

    Haiming Ma

    2018-03-01

    Full Text Available Effect of peripheral cannabinoid receptor 1 (CB1R blockade by AM6545 in the monosodium glutamate (MSG-induced hypometabolic and hypothalamic obesity was observed, and the impact on intraperitoneal adipose tissue and adipokines was investigated. The MSG mice is characterized by excessive abdominal obesity, and combined with dyslipidemia and insulin resistance. 3-Week AM6545 treatment dose-dependently decreased the body weight, intraperitoneal fat mass, and rectified the accompanied dyslipidemia include elevated serum triglyceride, total cholesterol, free fatty acids, and lowered LDLc level. Glucose intolerance and hyperinsulinemia were also alleviated. But AM6545 didn’t affect the food-intake consistently through the experiment. In line with the reduction on fat mass, the size of adipocyte was reduced markedly. Most interestingly, AM6545 showed significant improvement on levels of circulating adipokines including lowering leptin, asprosin and TNFα, and increasing HMW adiponectin. Correspondingly, dysregulated gene expression of lipogenesis, lipolysis, and adipokines in the adipose tissue were nearly recovered to normal level after AM6545 treatment. Additionally, western blot analysis revealed that AM6545 corrected the elevated CB1R and PPARγ protein expression, while increased the key energy uncoupling protein UCP1 expression in adipose tissue. Taken together, the current study indicates that AM6545 induced a comprehensive metabolic improvement in the MSG mice including counteracting the hypometabolic and hypothalamic obesity, and improving the accompanied dyslipidemia and insulin resistance. One key underlying mechanism is related to ameliorate on the metabolic deregulation of adipose tissue, the synthesis and secretion of adipokines were thus rectified, and finally the catabolism was increased and the anabolism was reduced in intraperitoneal adipose tissue. Findings from this study will provide the valuable information about peripheral CB1R

  9. Diphenyl diselenide ameliorates monosodium glutamate induced anxiety-like behavior in rats by modulating hippocampal BDNF-Akt pathway and uptake of GABA and serotonin neurotransmitters.

    Science.gov (United States)

    Rosa, Suzan Gonçalves; Quines, Caroline Brandão; Stangherlin, Eluza Curte; Nogueira, Cristina Wayne

    2016-03-01

    Monosodium glutamate (MSG), a flavor enhancer used in food, administered to neonatal rats causes neuronal lesions and leads to anxiety when adulthood. We investigated the anxiolytic-like effect of diphenyl diselenide (PhSe)2 and its mechanisms on anxiety induced by MSG. Neonatal male and female Wistar rats received a subcutaneous injection of saline (0.9%) or MSG (4 g/kg/day) from the 1st to 10th postnatal day. At 60 days of life, the rats received (PhSe)2 (1mg/kg/day) or vehicle by the intragastric route for 7 days. The spontaneous locomotor activity (LAM), elevated plus maze test (EPM) and contextual fear conditioning test (CFC) as well as neurochemical ([(3)H]GABA and [(3)H]5-HT uptake) and molecular analyses (Akt and p-Akt and BDNF levels) were carried out after treatment with (PhSe)2. Neonatal exposure to MSG increased all anxiogenic parameters in LAM, EPM and CFC tests. MSG increased GABA and 5-HT uptake in hippocampus of rats, without changing uptake in cerebral cortex. The levels of BDNF and p-Akt were reduced in hippocampus of rats treated with MSG. The administration of (PhSe)2 to rats reversed all behavioral anxiogenic parameters altered by MSG. The increase in hippocampal GABA and 5-HT uptake induced by MSG was reversed by (PhSe)2. (PhSe)2 reversed the reduction in hippocampal BDNF and p-Akt levels induced by MSG. In conclusion, the anxiolytic-like action of (PhSe)2 in rats exposed to MSG during their neonatal period is related to its modulation of hippocampal GABA and 5-HT uptake as well as the BDNF-Akt pathway. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Monosodium L-glutamate in soup reduces subsequent energy intake from high-fat savoury food in overweight and obese women.

    Science.gov (United States)

    Miyaki, Takashi; Imada, Toshifumi; Hao, Susan Shuzhen; Kimura, Eiichiro

    2016-01-14

    The umami seasoning, monosodium L-glutamate (MSG), has been shown to increase satiety in normal body weight adults, although the results have not been consistent. The satiety effect of MSG in overweight and obese adults has not been examined yet. The objective of the present study was to investigate the effect of MSG in a vegetable soup on subsequent energy intakes as well as food selection in overweight and obese adult women without eating disorders. A total of sixty-eight overweight and obese women (BMI range: 25·0-39·9 kg/m²), otherwise healthy, were recruited to our study. A fixed portion (200 ml) of control vegetable soup or the same soup with added MSG (0·5 g/100 ml) was provided 10 min before an ad libitum lunch and an ad libitum snack in the mid-afternoon. The control soup had equivalent amount of Na to the soup with added MSG. Energy intakes at the ad libitum lunch and ad libitum snack time after the soup preload were assessed using a randomised, double-blind, two-way cross-over design. The soup with MSG in comparison with the control soup resulted in significantly lower consumption of energy at lunch. The addition of MSG in the soup also reduced energy intake from high-fat savoury foods. The soup with MSG showed lower but no significant difference in energy intake at mid-afternoon. The addition of umami seasoning MSG in a vegetable soup may decrease subsequent energy intake in overweight and obese women who do not have eating disorders.

  11. Altered behavior of adult obese rats by monosodium l-glutamate neonatal treatment is related to hypercorticosteronemia and activation of hypothalamic ERK1 and ERK2.

    Science.gov (United States)

    Guimarães, Ernesto da Silveira Goulart; de Caires Júnior, Luiz Carlos; Musso, Camila Manso; Macedo de Almeida, Mariana; Gonçalves, Cássio Francisco; Pettersen, Klaus Grossi; Paes, Santiago Tavares; González Garcia, Raúl Marcel; de Freitas Mathias, Paulo Cesar; Torrezan, Rosana; Mourao-Júnior, Carlos Alberto; Andreazzi, Ana Eliza

    2017-04-01

    Obesity is a metabolic and hormonal disorder with serious social and psychological impacts. There is a close relationship among obesity, neuroendocrine homeostasis and behavioral patterns. However, few data are available in the literature regarding this subject. This study assessed behavior and memory of adult obese rats by monosodium l-glutamate (MSG) neonatal treatment or highly palatable dietary treatment. MSG obesity was induced by subcutaneous injections of MSG (4 mg/g) during the first 5 days of life (Ob-MSG); control group (C-MSG), received saline solution equimolar. Both groups were fed with commercial chow. To induce dietary obesity, 21-day-old rats were assigned to two experimental diets: highly palatable diet (Ob-Diet) and control diet (C-Diet) composed of commercial chow. Ninety-day-old animals were submitted to behavioral assessment by the open-field test and short- and long-term memory by the object recognition test. Biometric variables were obtained, the Lee index was calculated and mass of retroperitoneal and perigonadal fat pads was measured. Furthermore, an altered behavioral profile was investigated by quantification of plasmatic corticosterone, expression, and activity of hypothalamic extracellular signal-regulated kinase protein (ERK) 1 and 2. Increased Lee index and fat pads were observed in Ob-MSG and Ob-Diet groups. Ob-MSG presented a higher level of anxiety and impaired long-term memory compared to C-MSG, while there was no difference between Ob-Diet and C-Diet. The Ob-MSG group presented a higher level of plasmatic corticosterone and increased phosphorylation of hypothalamic ERK1 and 2. Both treatments induced obesity but only Ob-MSG showed altered behavioral parameters, which is related to increased concentration of corticosterone and hypothalamic ERK1 and 2 activation.

  12. Diphenyl diselenide elicits antidepressant-like activity in rats exposed to monosodium glutamate: A contribution of serotonin uptake and Na(+), K(+)-ATPase activity.

    Science.gov (United States)

    Quines, Caroline B; Rosa, Suzan G; Velasquez, Daniela; Da Rocha, Juliana T; Neto, José S S; Nogueira, Cristina W

    2016-03-15

    Depression is a disorder with symptoms manifested at the psychological, behavioral and physiological levels. Monosodium glutamate (MSG) is the most widely used additive in the food industry; however, some adverse effects induced by this additive have been demonstrated in experimental animals and humans, including functional and behavioral alterations. The aim of this study was to investigate the possible antidepressant-like effect of diphenyl diselenide (PhSe)2, an organoselenium compound with pharmacological properties already documented, in the depressive-like behavior induced by MSG in rats. Male and female newborn Wistar rats were divided in control and MSG groups, which received, respectively, a daily subcutaneous injection of saline (0.9%) or MSG (4g/kg/day) from the 1st to 5th postnatal day. At 60th day of life, animals received (PhSe)2 (10mg/kg, intragastrically) 25min before spontaneous locomotor and forced swimming tests (FST). The cerebral cortices of rats were removed to determine [(3)H] serotonin (5-HT) uptake and Na(+), K(+)-ATPase activity. A single administration of (PhSe)2 was effective against locomotor hyperactivity caused by MSG in rats. (PhSe)2 treatment protected against the increase in the immobility time and a decrease in the latency for the first episode of immobility in the FST induced by MSG. Furthermore, (PhSe)2 reduced the [(3)H] 5-HT uptake and restored Na(+), K(+)-ATPase activity altered by MSG. In the present study a single administration of (PhSe)2 elicited an antidepressant-like effect and decrease the synaptosomal [(3)H] 5-HT uptake and an increase in the Na(+), K(+)-ATPase activity in MSG-treated rats. Copyright © 2015 Elsevier B.V. All rights reserved.

  13. Protective Role of Co-administration of Vitamin D in Monosodium Glutamate Induced Obesity in Female Rats.

    Science.gov (United States)

    Nandan, Padmanabha; Nayanatara, Arun Kumar; Poojary, Roopesh; Bhagyalakshmi, K; Nirupama, M; Kini, Rekha D

    2018-02-01

    Obesity in females is an emerging health problem. The consumption of MSG has been considered as a risk factor for obesity. The tastemakers in Chinese and fast foods, such as fish sauce and soy sauce, contain very high levels of glutamate. The deficiency of Vitamin D is associated with obesity and metabolic syndrome. Therefore, the present study aimed to determine the effect of co-administration of Vitamin D on body weight control in MSG-induced obese rats. Eighteen adult female Wistar rats were randomly divided into three groups equally. The first group (Group I) was treated with saline served as the control; the second group (Group II) received a daily oral dose of 5 g/kg Body weight of MSG; the third group (Group III) received the same dose of MSG along with calcitriol (0.2 mcg/kg BW) for 15 days. The body weight, food, and water intake were measured. MSG treated rats showed a significant increase (P body weight, food, and water intake but significant decrease (P body weight gain in MSG-induced obese rats. Active agents in Vitamin D are useful for the prevention and treatment of obesity. Foods tested with high glutamate levels can be fortified with minute quantities of calcitriol to combat the adverse effects without compromising on the taste of the food processed. The fortification of junk foods might also combat largely prevalent Vitamin D deficiency in India. Copyright © 2018 National Medical Association. Published by Elsevier Inc. All rights reserved.

  14. KB-R7943 reduces 4-aminopyridine-induced epileptiform activity in adult rats after neuronal damage induced by neonatal monosodium glutamate treatment.

    Science.gov (United States)

    Hernandez-Ojeda, Mariana; Ureña-Guerrero, Monica E; Gutierrez-Barajas, Paola E; Cardenas-Castillo, Jazmin A; Camins, Antoni; Beas-Zarate, Carlos

    2017-05-09

    Neonatal monosodium glutamate (MSG) treatment triggers excitotoxicity and induces a degenerative process that affects several brain regions in a way that could lead to epileptogenesis. Na + /Ca 2+ exchangers (NCX1-3) are implicated in Ca 2+ brain homeostasis; normally, they extrude Ca 2+ to control cell inflammation, but after damage and in epilepsy, they introduce Ca 2+ by acting in the reverse mode, amplifying the damage. Changes in NCX3 expression in the hippocampus have been reported immediately after neonatal MSG treatment. In this study, the expression level of NCX1-3 in the entorhinal cortex (EC) and hippocampus (Hp); and the effects of blockade of NCXs on the seizures induced by 4-Aminopyridine (4-AP) were analysed in adult rats after neonatal MSG treatment. KB-R7943 was applied as NCXs blocker, but is more selective to NCX3 in reverse mode. Neonatal MSG treatment was applied to newborn male rats at postnatal days (PD) 1, 3, 5, and 7 (4 g/kg of body weight, s.c.). Western blot analysis was performed on total protein extracts from the EC and Hp to estimate the expression level of NCX1-3 proteins in relative way to the expression of β-actin, as constitutive protein. Electrographic activity of the EC and Hp were acquired before and after intracerebroventricular (i.c.v.) infusion of 4-AP (3 nmol) and KB-R7943 (62.5 pmol), alone or in combination. All experiments were performed at PD60. Behavioural alterations were also recorder. Neonatal MSG treatment significantly increased the expression of NCX3 protein in both studied regions, and NCX1 protein only in the EC. The 4-AP-induced epileptiform activity was significantly higher in MSG-treated rats than in controls, and KB-R7943 co-administered with 4-AP reduced the epileptiform activity in more prominent way in MSG-treated rats than in controls. The long-term effects of neonatal MSG treatment include increases on functional expression of NCXs (mainly of NCX3) in the EC and Hp, which seems to contribute to

  15. Teratogenicity and brain aromatase-induction of monosodium ...

    African Journals Online (AJOL)

    Teratogenicity and brain aromatase-induction of monosodium glutamate in estrogen-responsive mosaic transgenic zebra fish Danio rerio. Tamer Said Abdelkader, Chang Seo-Na, Kim Tae-Hyun, Song Juha, Kim Dongso, Jae-Hak Park ...

  16. Amelioration of Behavioural, Biochemical, and Neurophysiological Deficits by Combination of Monosodium Glutamate with Resveratrol/Alpha-Lipoic Acid/Coenzyme Q10 in Rat Model of Cisplatin-Induced Peripheral Neuropathy

    Directory of Open Access Journals (Sweden)

    Naini Bhadri

    2013-01-01

    Full Text Available Cisplatin or cis-diamminedichloroplatinum (II (CDDP is a cytotoxic chemotherapeutic agent with dose-dependent peripheral neuropathy as a foremost side effect characterised by ataxia, pain, and sensory impairment. Cumulative drug therapy of CDDP is known to produce severe oxidative damage. It mainly targets and accumulates in dorsal root ganglia that in turn cause damage resulting in secondary nerve fibre axonopathy. In the present study, we investigated the neuroprotective effect of the combination of monosodium glutamate (MSG with three individual antioxidants, that is, resveratrol, alpha-lipoic acid (ALA, and coenzyme Q10 (CoQ10, in cisplatin (2 mg/kg i.p. twice weekly induced peripheral neuropathy in rats. After 8 weeks of treatment the degree of neuroprotection was determined by measuring behavioral and electrophysiological properties and sciatic nerve lipid peroxidation, as well as glutathione and catalase levels. The results suggested that pretreatment with the combination of MSG (500 mg/kg/day po with resveratrol (10 mg/kg/day i.p. or ALA (20 mg/kg/day i.p. or CoQ10 (10 mg/kg weekly thrice i.p. exhibited neuroprotective effect. The maximum neuroprotection of MSG was observed in the combination with resveratrol.

  17. In-capillary derivatization with o-phthalaldehyde in the presence of 3-mercaptopropionic acid for the simultaneous determination of monosodium glutamate, benzoic acid, and sorbic acid in food samples via capillary electrophoresis with ultraviolet detection.

    Science.gov (United States)

    Aung, Hnin-Pwint; Pyell, Ute

    2016-06-03

    For the rapid simultaneous determination of monosodium glutamate (MSG), benzoic acid (BA), and sorbic acid (SA) in canned food and other processed food samples, we developed a method that combines in-capillary derivatization with separation by capillary electrophoresis. This method employs the rapid derivatization of MSG with o-phthalaldehyde (OPA) in the presence of 3-mercaptopropionic acid (3-MPA) and enables the detection of the resulting OPA-MSG derivative and of non-derivatized BA and SA at 230nm. The composition of the background electrolyte and the parameters of derivatization and separation are as follows: 25mM borax containing 5mM OPA and 6mM 3-MPA, separation voltage 25mV, injection at 30mbar for 20s, and column temperature 25°C. Because of the high reaction rate and suitably adapted effective electrophoretic mobilities, band broadening due to the derivatization reaction at the start of the separation process is kept to a minimum. The optimized method is validated with respect to LOD, LOQ, linearity, recovery, and precision. This method can be applied to real samples such as soy, fish, oyster and sweet and sour chili sauces after application of appropriate clean-up steps. Mechanisms of zone broadening and zone focusing are discussed showing the validity of the employed theoretical approach regarding the dependence of the peak shape for OPA-MSG on the concentration of MSG in the sample. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. A novel glutamate transport system in poly(γ-glutamic acid)-producing strain Bacillus subtilis CGMCC 0833.

    Science.gov (United States)

    Wu, Qun; Xu, Hong; Zhang, Dan; Ouyang, Pingkai

    2011-08-01

    Bacillus subtilis CGMCC 0833 is a poly(γ-glutamic acid) (γ-PGA)-producing strain. It has the capacity to tolerate high concentration of extracellular glutamate and to utilize glutamate actively. Such a high uptake capacity was owing to an active transport system for glutamate. Therefore, a specific transport system for L-glutamate has been observed in this strain. It was a novel transport process in which glutamate was symported with at least two protons, and an inward-directed sodium gradient had no stimulatory effect on it. K(m) and V(m) for glutamate transport were estimated to be 67 μM and 152 nmol⁻¹ min⁻¹ mg⁻¹ of protein, respectively. The transport system showed structural specificity and stereospecificity and was strongly dependent on extracellular pH. Moreover, it could be stimulated by Mg²⁺, NH₄⁺, and Ca²⁺. In addition, the glutamate transporter in this strain was studied at the molecular level. As there was no important mutation of the transporter protein, it appeared that the differences of glutamate transporter properties between this strain and other B. subtilis strains were not due to the differences of the amino acid sequence and the structure of transporter protein. This is the first extensive report on the properties of glutamate transport system in γ-PGA-producing strain.

  19. The effects of black garlic ethanol extract on the spatial memory and estimated total number of pyramidal cells of the hippocampus of monosodium glutamate-exposed adolescent male Wistar rats.

    Science.gov (United States)

    Hermawati, Ery; Sari, Dwi Cahyani Ratna; Partadiredja, Ginus

    2015-09-01

    Monosodium glutamate (MSG) is believed to exert deleterious effects on various organs, including the hippocampus, likely via the oxidative stress pathway. Garlic (Alium sativum L.), which is considered to possess potent antioxidant activity, has been used as traditional remedy for various ailments since ancient times. We have investigated the effects of black garlic, a fermented form of garlic, on spatial memory and estimated the total number of pyramidal cells of the hippocampus in adolescent male Wistar rats treated with MSG. Twenty-five rats were divided into five groups: C- group, which received normal saline; C+ group, which was exposed to 2 mg/g body weight (bw) of MSG; three treatment groups (T2.5, T5, T10), which were treated with black garlic extract (2.5, 5, 10 mg/200 g bw, respectively) and MSG. The spatial memory test was carried out using the Morris water maze (MWM) procedure, and the total number of pyramidal cells of the hippocampus was estimated using the physical disector design. The groups treated with black garlic extract were found to have a shorter path length than the C- and C+ groups in the escape acquisition phase of the MWM test. The estimated total number of pyramidal cells in the CA1 region of the hippocampus was higher in all treated groups than that of the C+ group. Based on these results, we conclude that combined administration of black garlic and MSG may alter the spatial memory functioning and total number of pyramidal neurons of the CA1 region of the hippocampus of rats.

  20. Effect of osmotic dehydration of olives as pre-fermentation treatment and partial substitution of sodium chloride by monosodium glutamate in the fermentation profile of Kalamata natural black olives.

    Science.gov (United States)

    Bonatsou, Stamatoula; Iliopoulos, Vasilis; Mallouchos, Athanasios; Gogou, Eleni; Oikonomopoulou, Vasiliki; Krokida, Magdalini; Taoukis, Petros; Panagou, Efstathios Z

    2017-05-01

    This study examined the effect of osmotic dehydration of Kalamata natural black olives as pre-fermentation treatment in combination with partial substitution of NaCl by monosodium glutamate (MSG) on the fermentation profile of olives. Osmotic dehydration was undertaken by immersing the olives in 70% (w/w) glucose syrup overnight at room temperature. Further on, three different mixtures of NaCl and MSG with/without prior osmotic dehydration of olives were investigated, namely (i) 6.65% NaCl - 0.35% MSG (5% substitution), (ii) 6.30% NaCl - 0.70% MSG (10% substitution), (iii) 5.95% NaCl - 1.05% MSG (15% substitution), and (iv) 7% NaCl without osmotic dehydration (control treatment). Changes in the microbial association (lactic acid bacteria [LAB], yeasts, Enterobacteriaceae), pH, titratable acidity, organic acids, sugars, and volatile compounds in the brine were analyzed for a period of 4 months. The final product was subjected to sensory analysis and the content of MSG in olives was determined. Results demonstrated that osmotic dehydration of olives prior to brining led to vigorous lactic acid processes as indicated by the obtained values of pH (3.7-4.1) and acidity (0.7-0.8%) regardless of the amount of MSG used. However, in non-osmotically dehydrated olives, the highest substitution level of MSG resulted in a final pH (4.5) that was beyond specification for this type of olives. MSG was degraded in the brines being almost completely converted to γ-aminobutyric acid (GABA) at the end of fermentation. Finally, the sensory assessment of fermented olives with/without osmotic dehydration and at all levels of MSG did not show any deviation compared to the control treatment. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Efeito da vagotomia troncular em ratos injetados na fase neonatal com glutamato monossódico: estudo biométrico Effect of vagotomy in rats neonatally injected with monosodium glutamate: biometry study

    Directory of Open Access Journals (Sweden)

    Fernando de Souza

    2001-03-01

    lesion could cause neuroendocrine obesity. Hypothalamic obesity could be reproduced through ventromedial hypothalamic lesion in animals and attenuated that by subdiafragmatic vagotomy (VT. VT decreased food intake and insulinemia. Injection of monosodium glutamate (MSG neonatally in rats produces adiposity, hyperphagia, without weight gain because it injures arcuate nucleus of the hypothalamus, site of growth hormone releasing hormone production. The purpose of this paper is to evaluate the MSG effect on weight, stature, Lee index (3 square root body weight/nasoanal length, gonadal fat (GF and food intake in rats and the VT effect on these parameters. Fifty-two male Wistar rats were used, divided into two groups of twenty-six animals each. SALINA group was subcutaneously injected with saline solution 12.5% (1.25 mg/g body weight/dayly/5days and MSG group was injected with MSG solution 24% (4 mg/g body weight/dayly/5 days, after the rats were born, in the posterior cervical region without adverse reaction. On the 30th day of life, the animals were divided into four groups and submitted to operation, sham operated groups (LAPSAL and LAPMSG and vagotomized groups (VTSAL and VTMSG. On operation day, weight, nasoanal length (NAL and Lee index were obtained. Food intake were obtained from the 30th day until 90th day. On 90th day, the animals were sacrificed and weight, NAL, Lee index and GF were obtained. Statistic analysis was performed by the Student’s t test. NAL was smaller and Lee index was greater in MSG group than in SALINA group on the 30th day. Weight gain and NAL were smaller and Lee index and GF were greater on the 90th day, and food intake from the 30th to 90th day period was greater in LAPMSG group than in LAPSAL group. Weight gain, Lee index and GF were smaller and NAL trended smaller in VTMSG group than in LAPMSG group on the 90th day. Food intake from the 30th to 60th day period was smaller and trended greater from the 60th to 90th day period in VTMSG group

  2. Metabolic fate and function of dietary glutamate in the gut

    Science.gov (United States)

    Glutamate is a major constituent of dietary protein and is also consumed in many prepared foods as an additive in the form of monosodium glutamate. Evidence from human and animal studies indicates that glutamate is a major oxidative fuel for the gut and that dietary glutamate is extensively metabol...

  3. Emerging aspects of dietary glutamate metabolism in the developing gut

    Science.gov (United States)

    Glutamate is a major constituent of dietary protein and is also consumed in many prepared foods as a flavour additive in the form of monosodium glutamate (MSG). Evidence from human and animal studies indicates that glutamate is the major oxidative fuel for the gut and that dietary glutamate is exten...

  4. Protective effect of naringenin on glutamate-induced neurotoxicity in cultured hippocampal cells

    Directory of Open Access Journals (Sweden)

    Xu Xiao-Hui

    2015-01-01

    Full Text Available Monosodium glutamate induces excitotoxicity in the central nervous system through hyperactivation of both ionotropic and metabotropic glutamate receptors, which leads to neuronal cell death. In this study, we investigated the neuroprotective effects of naringenin on excitotoxicity induced by glutamate in primary hippocampal neurons of neonatal mice. The expression levels of apoptosis-inducing proteins and as well as ischemic factors were observed by Western blot analysis. Immunocytochemistry and morphometric analysis of hippocampal cells with or without glutamate and naringenin treatment were performed. We observed that naringenin regulated Erk1/2 and Akt phosphorylation and reduced the demise of dendrites due to glutamate exposure in cultured hippocampal neurons. Furthermore, naringenin induced the brain-derived neurotrophic factor and other neuroprotective cytokines, and markedly improved the survival rates of the neurons 24 h following glutamate exposure. The observed results suggest that the naturally occurring bioflavonoid (naringenin exerts neuroprotective effects via highly specific molecular targets in neurons.

  5. Monosodium glutamate: Potentials at inducing prostate pathologies ...

    African Journals Online (AJOL)

    ONOS

    2010-09-06

    Sep 6, 2010 ... Busch C, Hanssen TA, Wagener CO, Brink B (2002). Down-regulation of CEACAM1 in human prostate cancer: correlation with loss of cell polarity, increased proliferation rate, and Gleason grade 3 to 4 transition. Hum. Pathol. 33: 290-298. Choi DM (1988). Calcium mediated neurotoxicity; relationship to ...

  6. CHARACTERIZATION OF A BINDING PROTEIN-DEPENDENT GLUTAMATE TRANSPORT-SYSTEM OF RHODOBACTER-SPHAEROIDES

    NARCIS (Netherlands)

    Jacobs, M.H J; Driessen, A.J.M.; Konings, W.N

    The mechanism of L-glutamate uptake was studied in Rhodobacter sphaeroides. Uptake of L-glutamate is mediated by a high-affinity (K-t of 1.2 mu M), shock-sensitive transport system that is inhibited by vanadate and dependent on the internal pH. From the shock fluid, an L-glutamate-binding protein

  7. Characterization of a Binding Protein-Dependent Glutamate Transport System of Rhodobacter sphaeroides

    NARCIS (Netherlands)

    Jacobs, Mariken H.J.; Driessen, Arnold J.M.; Konings, Wil N.

    1995-01-01

    The mechanism of L-glutamate uptake was studied in Rhodobacter sphaeroides. Uptake of L-glutamate is mediated by a high-affinity (Kt of 1.2 µM), shock-sensitive transport system that is inhibited by vanadate and dependent on the internal pH. From the shock fluid, an L-glutamate-binding protein was

  8. Evaluation of body growth and myoenteric neurons of Wistar rats after neonatal treatment with monosodium glutamate = Avaliação do crescimento corporal e dos neurônios mioentéricos de ratos Wistar após tratamento neonatal com glutamato monossódico

    Directory of Open Access Journals (Sweden)

    Fernando Carlos Sousa

    2007-01-01

    Full Text Available This work aimed at evaluating how the neonatal treatment withmonosodium glutamate reflects on body parameters and on myoenteric neurons of Wistar rats. Male rats were injected with monosodium glutamate during the first five postnatal days. Body growth was recorded until the age of 90 days, when the animals were killed.Fasting plasma glucose, caloric density and weight of organs were assayed. Gastric and duodenal whole-mounts stained with NADH diaphorase were observed for neuronal numbers and sizes. Growth, relative weight of organs and testicular caloric density of theinjected rats were smaller than those of the controls, while their Lee index and relative fat content were greater. The number of duodenal neurons and the mean size of gastric neurons were smaller in the injected animals. These results are discussed in light of theendocrine, autonomic and behavioral changes stemming from the lesion of the hypothalamic arcuate nucleus by monosodium glutamate.Este trabalho objetivou avaliar como o tratamento neonatal com glutamato monossódico se reflete em parâmetros corporais e nos neurônios mioentéricos de ratos Wistar. Ratos machos foram injetados com glutamato monossódico durante os primeiros 5 dias após o nascimento. O crescimento corporal foi registrado até os 90 dias, quando os animais foram sacrificados. Glicose plasmática de jejum, densidade calórica e peso dos órgãos foram avaliados. Preparados de membrana gástricos e duodenais corados com NADH-diaforase foramobservados quanto a número e tamanho dos neurônios. Crescimento, peso relativo dos órgãos e densidade calórica testicular dos ratos injetados foram menores que nos controles, enquanto o índice de Lee e o conteúdo relativo de gordura foram maiores. O número de neurônios duodenais e o tamanho médio dos neurônios gástricos foram menores nosanimais injetados. Esses resultados são discutidos à luz das alterações endócrinas, autonômicas e comportamentais

  9. Pharmacology of Glutamate Transport in the CNS: Substrates and Inhibitors of Excitatory Amino Acid Transporters (EAATs) and the Glutamate/Cystine Exchanger System x c -

    Science.gov (United States)

    Bridges, Richard J.; Patel, Sarjubhai A.

    As the primary excitatory neurotransmitter in the mammalian CNS, l-glutamate participates not only in standard fast synaptic communication, but also contributes to higher order signal processing, as well as neuropathology. Given this variety of functional roles, interest has been growing as to how the extracellular concentrations of l-glutamate surrounding neurons are regulated by cellular transporter proteins. This review focuses on two prominent systems, each of which appears capable of influencing both the signaling and pathological actions of l-glutamate within the CNS: the sodium-dependent excitatory amino acid transporters (EAATs) and the glutamate/cystine exchanger, system x c - (Sx c -). While the family of EAAT subtypes limit access to glutamate receptors by rapidly and efficiently sequestering l-glutamate in neurons and glia, Sxc - provides a route for the export of glutamate from cells into the extracellular environment. The primary intent of this work is to provide an overview of the inhibitors and substrates that have been developed to delineate the pharmacological specificity of these transport systems, as well as be exploited as probes with which to selectively investigate function. Particular attention is paid to the development of small molecule templates that mimic the structural properties of the endogenous substrates, l-glutamate, l-aspartate and l-cystine and how strategic control of functional group position and/or the introduction of lipophilic R-groups can impact multiple aspects of the transport process, including: subtype selectivity, inhibitory potency, and substrate activity.

  10. Dietary glutamate will not affect pain in fibromyalgia

    NARCIS (Netherlands)

    Geenen, R.; Janssens, E.L.; Jacobs, J.W.G.; Staveren, van W.A.

    2004-01-01

    Injection of glutamate into the masseter muscle has been suggested-to evoke an increase in intensity of and sensitivity to pain. A case study showed that a diet low in monosodium glutamate (MSG) might accomplish pain relief in fibromyalgia (FM). To clarify the possible pain-modulating effect of

  11. Cutaneous and electrically evoked glutamate signaling in the adult rat somatosensory system.

    Science.gov (United States)

    Onifer, Stephen M; Quintero, Jorge E; Gerhardt, Greg A

    2012-07-15

    Glutamate neurotransmission plays critical roles in normal central nervous system (CNS) function, neurodegenerative diseases, and neurotrauma. We determined whether glutamate signaling could be evoked within the anesthetized normal adult rat CNS with clinically relevant peripheral stimulation and recorded (at >1Hz) with glutamate-sensitive, ceramic microelectrode arrays (MEAs). Basal glutamate levels and both forelimb cutaneous and electrical stimulation-evoked glutamate release were measured within the cuneate nucleus, a relay of the mammalian dorsal columns somatosensory system. The MEAs with triangular, sharp-point tips were more effective at tissue penetration than the flat, blunt tips. Basal glutamate levels of 2.1±4.4μM (mean±SD, n=10 animals) were detected from 150μm to 1200μm below the brainstem dorsal surface. Cutaneous evoked glutamate signals showed an amplitude of 1.1±1.1μM and a duration of 7.3±6.5s (26 signals, n=6). Electrically evoked signals, like cutaneous ones, were both rapid and slowly rising. Electrically evoked signals, especially those evoked by stimulation trains, were more reproducible and had an amplitude of 1.2±1.4μM, duration of 19.4±17.3s, and latency from stimulus onset of 21.3±21.5s (25 signals, n=4). In contrast to cutaneous stimulation, glutamate signals evoked by electrical stimulation had longer durations and were recorded primarily in the middle and ventral cuneate nuclei. Importantly, both cutaneous and electrical stimulation of the contralateral forelimb and hindlimbs did not evoke glutamate signaling. With the use of MEAs, these results show, for the first time, somatosensory-pathway specific changes in glutamate levels during peripheral cutaneous and electrical stimulation. Copyright © 2012 Elsevier B.V. All rights reserved.

  12. Deletion of glutamate dehydrogenase 1 (Glud1) in the central nervous system affects glutamate handling without altering synaptic transmission

    DEFF Research Database (Denmark)

    Frigerio, Francesca; Karaca, Melis; De Roo, Mathias

    2012-01-01

    Glutamate dehydrogenase (GDH), encoded by GLUD1, participates in the breakdown and synthesis of glutamate, the main excitatory neurotransmitter. In the CNS, besides its primary signaling function, glutamate is also at the crossroad of metabolic and neurotransmitter pathways. Importance of brain G...

  13. Glutamate Transport System as a Novel Therapeutic Target in Chronic Pain

    DEFF Research Database (Denmark)

    Gegelashvili, Georgi; Bjerrum, Ole Jannik

    2017-01-01

    The vast majority of peripheral neurons sensing noxious stimuli and conducting pain signals to the dorsal horn of the spinal cord utilize glutamate as a chemical transmitter of excitation. High-affinity glutamate transporter subtypes GLAST/EAAT1, GLT1/EAAT2, EAAC1/EAAT3, and EAAT4, differentially...... pain treatment. However, design and development of new analgesics based on the modulation of glutamate uptake will require more precise knowledge of molecular mechanisms underlying physiological or aberrant functioning of this transport system in the spinal cord.......The vast majority of peripheral neurons sensing noxious stimuli and conducting pain signals to the dorsal horn of the spinal cord utilize glutamate as a chemical transmitter of excitation. High-affinity glutamate transporter subtypes GLAST/EAAT1, GLT1/EAAT2, EAAC1/EAAT3, and EAAT4, differentially...... expressed on sensory neurons, postsynaptic spinal interneurons, and neighboring glia, ensure fine modulation of glutamate neurotransmission in the spinal cord. The glutamate transport system seems to play important roles in molecular mechanisms underlying chronic pain and analgesia. Downregulation...

  14. Quantitative autoradiographic distribution of L-[3H]glutamate-binding sites in rat central nervous system

    International Nuclear Information System (INIS)

    Greenamyre, J.T.; Young, A.B.; Penney, J.B.

    1984-01-01

    Quantitative autoradiography was used to determine the distribution of L-[3H]glutamate-binding sites in the rat central nervous system. Autoradiography was carried out in the presence of Cl- and Ca2+ ions. Scatchard plots and Hill coefficients of glutamate binding suggested that glutamate was interacting with a single population of sites having a K-D of about 300 nM and a capacity of 14.5 pmol/mg of protein. In displacement studies, ibotenate also appeared to bind to a single class of non-interacting sites with a KI of 28 microM. However, quisqualate displacement of [3H]glutamate binding revealed two well-resolved sites with KIS of 12 nM and 114 microM in striatum. These sites were unevenly distributed, representing different proportions of specific glutamate binding in different brain regions. The distribution of glutamate-binding sites correlated very well with the projection areas of putative glutamatergic pathways. This technique provides an extremely sensitive assay which can be used to gather detailed pharmacological and anatomical information about L-[3H]glutamate binding in the central nervous system

  15. Autoradiographic characterization of L-[3H]glutamate binding sites in the central nervous system

    International Nuclear Information System (INIS)

    Greenamyre, J.T.

    1986-01-01

    A quantitative autoradiographic technique was developed to study L-[ 3 H[glutamate binding in sections of central nervous system tissue. This technique circumvented some problems associated with conventional receptor binding methodologies and allowed direct assessment of regional distribution, numbers and affinities of glutamate binding sites. The sensitivity and high degree of anatomical resolution attainable by autoradiography obviated the need for pooled samples of microdissected specimens. Under assay conditions, [ 4 H]glutamate bound rapidly and reversibly to sections of rat brain and was not metabolized appreciably. The distribution of glutamate binding sites corresponded to the projection areas of putative glutamatergic pathways. Thus, there was heavy glutamate binding in regions where there is evidence for glutamatergic innervation and little binding in nuclei which apparently do not receive glutamatergic input. Scatchard and Hill plots suggested that glutamate was interacting with a single population of sites; however, competition studies revealed binding site heterogeneity. Anatomical and pharmacological evidence suggested that the NMDA-, high affinity quisqualate-, and kainate-sensitive glutamate binding sites may correspond to physiologically-defined NMDA, quisqualate and kainate receptors

  16. Pharmacological Treatment of Glutamate Excitotoxicity Following Traumatic Brain Injury

    Science.gov (United States)

    2009-01-14

    In 1969, Olney found that subcutaneous injection of monosodium glutamate resulted in necrotic brain lesions in the hypothalamus of newborn mice...Thesis: "Pharmacological Treatment of Glutamate Excitotoxicity Following Traumatic Brain Injury" Name of Candidate: Michael Doh Molecular & Cell...TYPE 3. DATES COVERED 00-00-2009 to 00-00-2009 4. TITLE AND SUBTITLE Pharmacological Treatment Of Glutamate Excitotoxicity Following Traumatic

  17. HISTOLOGI SEL PIRAMIDAL HIPOKAMPUS TIKUS PUTIH PASCA PENGHENTIAN PAJANAN MONOSODIUM GLUTAMAT PERORAL

    Directory of Open Access Journals (Sweden)

    Buddy Dayono

    2015-07-01

    Full Text Available Abstract: Histology Of Hippocampal Pyramidal Cells Rats After Cessation Of Oral Administration Monosodium Glutamate. The aim of this study was to determine the histological of hippocampal pyramidal cells adult male Wistar rats (Rattus norvegicus after cessation of oral administration monosodium glutamate. This is true experimental study. This study used 27 rats and divided into 9 groups with simple random sampling. Data were analyzed using One-way ANOVA followed by LSD and Kruskal Wallis Test followed by Mann-Whitney Test. There were no significant differences in the mean number of pyramidal cells degeneration between treatment groups (P (p≥0,05. There were significant differences in the mean number of normal pyramidal cells between treatment groups (P (p<0,05. Keywords: monosodium glutamate (MSG, regeneration, pyramidal cells. Abstrak : Histologi Sel Pyramidal Hipokampus Tikus Putih Pasca Penghentian Pajanan Monosodium Glutamate Peroral. Penelitian ini bertujuan untuk mengetahui gambaran histologis sel piramidal hipokampus tikus putih (Rattus norvegicus jantan dewasa strain wistar pasca penghentian pajanan MSG peroral. penelitian ini menggunakan desain true experiment. Penelitian ini menggunakan 27 tikus dan dibagi 9 kelompok. Sampel dipilih dengan metode simple random sampling. Data dianalisa menggunakan one-way anova dilanjutkan LSD dan Kruskal Wallis Test dilanjutkan Mann-Whitney Test. Hasil menunjukkan bahwa tidak ada perbedaan bermakna rerata jumlah sel piramidal rusak pada seluruh kelompok perlakuan (P pada hari yang berbeda (p≥0,05. Terdapat perbedaan bermakna rerata jumlah sel piramidal normal pada seluruh kelompok perlakuan (P pada hari yang berbeda (p<0,05. Kata kunci: monosodium glutamat (MSG, regenerasi, sel pyramidal

  18. [Imbalance of system of glutamin - glutamic acid in the placenta and amniotic fluid at placental insufficiency].

    Science.gov (United States)

    Pogorelova, T N; Gunko, V O; Linde, V A

    2014-01-01

    Metabolism of glutamine and glutamic acid has been investigated in the placenta and amniotic fluid under conditions of placental insufficiency. The development of placental insufficiency is characterized by the increased content of glutamic acid and a decrease of glutamine in both placenta and amniotic fluid. These changes changes were accompanied by changes in the activity of enzymes involved in the metabolism of these amino acids. There was a decrease in glutamate dehydrogenase activity and an increase in glutaminase activity with the simultaneous decrease of glutamine synthetase activity. The compensatory decrease in the activity of glutamine keto acid aminotransferase did not prevent a decrease in the glutamine level. The impairments in the system glutamic acid-glutamine were more pronounced during the development of premature labor.

  19. The oxidative stress-inducible cystine/glutamate antiporter, system x (c) (-) : cystine supplier and beyond.

    Science.gov (United States)

    Conrad, Marcus; Sato, Hideyo

    2012-01-01

    The oxidative stress-inducible cystine/glutamate exchange system, system x (c) (-) , transports one molecule of cystine, the oxidized form of cysteine, into cells and thereby releases one molecule of glutamate into the extracellular space. It consists of two protein components, the 4F2 heavy chain, necessary for membrane location of the heterodimer, and the xCT protein, responsible for transport activity. Previously, system x (c) (-) has been regarded to be a mere supplier of cysteine to cells for the synthesis of proteins and the antioxidant glutathione (GSH). In that sense, oxygen, electrophilic agents, and bacterial lipopolysaccharide trigger xCT expression to accommodate with increased oxidative stress by stimulating GSH biosynthesis. However, emerging evidence established that system x (c) (-) may act on its own as a GSH-independent redox system by sustaining a redox cycle over the plasma membrane. Hallmarks of this cycle are cystine uptake, intracellular reduction to cysteine and secretion of the surplus of cysteine into the extracellular space. Consequently, increased levels of extracellular cysteine provide a reducing microenvironment required for proper cell signaling and communication, e.g. as already shown for the mechanism of T cell activation. By contrast, the enhanced release of glutamate in exchange with cystine may trigger neurodegeneration due to glutamate-induced cytotoxic processes. This review aims to provide a comprehensive picture from the early days of system x (c) (-) research up to now.

  20. On-chip microfluidic systems for determination of L-glutamate based on enzymatic recycling of substrate

    DEFF Research Database (Denmark)

    Laiwattanapaisal, W.; Yakovleva, J.; Bengtsson, Martin

    2009-01-01

    Two microfluidic systems have been developed for specific analysis of L-glutamate in food based on substrate recycling fluorescence detection. L-glutamate dehydrogenase and a novel enzyme, D-phenylglycine aminotransferase, were covalently immobilized on (i) the surface of silicon microchips conta...

  1. Kinetic Properties of a Phosphate-Bond-Driven Glutamate-Glutamine Transport System in Streptococcus lactis and Streptococcus cremoris

    NARCIS (Netherlands)

    POOLMAN, B; SMID, EJ; KONINGS, WN

    In Streptococcus lactis ML3 and Streptococcus cremoris Wg2 the uptake of glutamate and glutamine is mediated by the same transport system, which has a 30-fold higher affinity for glutamine than for glutamate at pH 6.0. The apparent affinity constant for transport (KT) of glutamine is 2.5 ± 0.3 μM,

  2. Behavioral deficits in adult rats treated neonatally with glutamate

    Czech Academy of Sciences Publication Activity Database

    Hliňák, Zdeněk; Gandalovičová, D.; Krejčí, I.

    2005-01-01

    Roč. 27, č. 3 (2005), s. 465-473 ISSN 0892-0362 R&D Projects: GA MZd(CZ) NF6474 Institutional research plan: CEZ:AV0Z5011922 Keywords : neonatal treatment * monosodium glutamate * long-term effect Subject RIV: ED - Physiology Impact factor: 1.940, year: 2005

  3. Histochemical Studies of the Effects of Monosodium Glutamate on ...

    African Journals Online (AJOL)

    Uche

    trauma, dietary deficiencies and hereditary factors acting alone or in a complex interaction with environmental factors, cause diseases. 2. The safety of MSG‟s ... depression, Parkinson‟s disease, Alzheimer‟s disease, Huntington‟s disease, and amyotrophic lateral sclerosis. 12. The liver is the largest glandular organ of ...

  4. Histological Studies of the Effects of Monosodium Glutamate on the ...

    African Journals Online (AJOL)

    Uche

    hereditary factors acting alone or in a multifarious interaction with environmental factors, cause diseases. ... several ailments including epilepsy stroke and depression. 8, 9. The ovary is a paired, egg-producing reproductive organ found in female organisms. The ovaries also functions in the production of various steroid and.

  5. Effect of monosodium glutamate and aspartame on behavioral and ...

    African Journals Online (AJOL)

    sunny t

    2016-04-13

    Apr 13, 2016 ... sacrificed and the neurotransmitters and oxidative stress parameters were estimated in their forebrain ..... and amygdala regions which play an important role in the onset of symptoms as upset of their ..... impair memory retention and damage hypothalamic neurons in adult mice. Toxicol. Lett. 115:117-125.

  6. The effect of monosodium glutamate (MSG) on blood glucose in ...

    African Journals Online (AJOL)

    The animals were grouped into two: groups A (control) and B (Test B1 and Test B2). Group A received water and feed (grower's mash) with grass supplementation. Group B (Test B1 and B2) received 3.33mg/ml and 6.66mg/ml of MSG respectively at libitum. At the end of each week, fasting blood glucose levels were ...

  7. Monosodium glutamate induced testicular lesions in rats (histological study

    Directory of Open Access Journals (Sweden)

    Aisha D. Alalwani

    2014-12-01

    Conclusions: MSG may have some deleterious effects on the testes of Wistar rats and by extension may contribute to the causes of male infertility. Thus, it is important to reconsider the usage of MSG as a flavor enhancer.

  8. Effect of the oral administration of monosodium glutamate during pregnancy and breast-feeding in the offspring of pregnant Wistar rats Efeito da administração de glutamato monossódico durante a gestação e amamentação na prole de ratas Wistar prenhes

    Directory of Open Access Journals (Sweden)

    Vinicius von Diemen

    2010-02-01

    Full Text Available PURPOSE: Determine the effects of the MSG (monosodium glutamate in the offspring of pregnant rats through the comparison of the weight, NAL (nasal-anal length and IL (Index of Lee at birth and with 21 days of life. METHODS: Pregnant Wistar rats and their offspring were divided into 3 groups: GC, G10 and G20. Each of the groups received 0%, 10% and 20% of MSG, respectively from coupling until the end of the weaning period. RESULTS: Neither weight nor NAL were different among the groups at birth. The group G20 at birth had an IL lower than the group GC (pOBJETIVO: Avaliar o efeito do glutamato monossódico (GMS nos fetos de ratas prenhes por meio da comparação do peso, comprimento nasal-anal (CNA e índice de Lee (IL ao nascimento e com 21 dias de vida. MÉTODOS: Foram utilizadas ratas prenhes da linhagem Wistar distribuídas em três grupos: grupo controle (GC, G10 e G20. Estes, respectivamente, foram alimentados com ração contendo 0, 10 e 20% de GMS desde o período de acasalamento até o final da amamentação. RESULTADOS: O peso e o CNA não foram diferentes entre os grupos ao nascimento. O grupo G20, ao nascimento, teve IL menor que o grupo GC (p < 0,05 e, aos 21 dias de vida, apresentou peso e CNA menores que o grupo G10, o qual foi menor que o GC (p < 0,01. O grupo G20, aos 21 dias de vida, teve IL semelhante aos outros dois grupos. O percentual de ganho de peso do nascimento ao 21º dia de vida foi menor no G20 em relação aos outros dois grupos (p < 0,01. O grupo G20 teve percentual de aumento de CNA do nascimento ao 21º dia de vida menor que o grupo G10, e este menor que o grupo GC (p < 0,01. CONCLUSÕES: O GMS nas concentrações de 10 e 20% na ração de ratas prenhes Wistar apresentou uma relação dose-dependente nas variáveis peso e CNA. Houve diminuição no padrão de ganho de peso e de aumento de CNA do nascimento ao 21º dia de vida com uso de GMS. O IL na prole do grupo G20 aumentou em relação ao do grupo GC após 3

  9. The glutamate and the immune systems: new targets for the pharmacological treatment of OCD.

    Science.gov (United States)

    Marazziti, Donatella; Albert, Umberto; Mucci, Federico; Piccinni, Armando

    2017-11-08

    In the last decades the pharmacological treatment of obsessive-compulsive disorder (OCD) has been significantly promoted by the effectiveness of selective serotonin (5-HT) reuptake inhibitors (SSRIs) and the subsequent development of the 5-HT hypothesis of OCD. However, since a large majority of patients (between 40% and 60 %) do not respond to SSRIs or strategies based on the modulation of the 5-HT system, it is now essential to search for other possible therapeutic targets. The aim of this paper was to review current literature through a PubMed and Google Scholar search of novel hypotheses and related compounds for the treatment of OCD, with a special focus on the glutammate and the immune systems. The literature would indicate that glutamate, the main excitatory neurotransmitter, might play an important role in the pathophysiology of OCD. In addition, a series of clinical study would also support the potential efficacy of drugs modulating the glutamate system. The role of the immune system alterations in OCD in both children and adults needs to be more deeply elucidated. In children, it has been widely described a subtype of OCD resulting from infections driven by group A streptococcus β-hemolitic and belonging to the so-called "pediatric autoimmune neuropsychiatric disorders associated with streptococcus" (PANDAS). In adults, available findings are meager and controversial, although interesting. The glutamate and the immune systems represent two intriguing topics of research that hold promises of development of open novel treatment strategies in OCD. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  10. Efficient bioconversion of L-glutamate to γ-aminobutyric acid by Lactobacillus brevis resting cells.

    Science.gov (United States)

    Shi, Xiufeng; Chang, Chuanyou; Ma, Shenxi; Cheng, Yibing; Zhang, Jun; Gao, Qiang

    2017-05-01

    This work investigated the efficient bioconversion process of L-glutamate to GABA by Lactobacillus brevis TCCC 13007 resting cells. The optimal bioconversion system was composed of 50 g/L 48 h cultivated wet resting cells, 0.1 mM pyridoxal phosphate in glutamate-containing 0.6 M citrate buffer (pH 4.5) and performed at 45 °C and 180 rpm. By 10 h bioconversion at the ratio of 80 g/L L-glutamic acid to 240 g/L monosodium glutamate, the final titer of GABA reached 201.18 g/L at the molar bioconversion ratio of 99.4 %. This process presents a potential for industrial and commercial applications and also offers a promising feasibility of continuous GABA production coupled with fermentation. Besides, the built kinetics model revealed that the optimum operating conditions were 45 °C and pH 4.5, and the bioconversion kinetics at low ranges of substrate concentration (0 < S < 80 g/L) was assumed to follow the classical Michaelis-Menten equation.

  11. Nanofiber mat spinal cord dressing-released glutamate impairs blood-spinal cord barrier

    Directory of Open Access Journals (Sweden)

    Dorota Sulejczak

    2016-12-01

    Full Text Available An excessive glutamate level can result in excitotoxic damage and death of central nervous system (CNS cells, and is involved in the pathogenesis of many CNS diseases. It may also be related to a failure of the blood-spinal cord barrier (BSCB. This study was aimed at examining the effects of extended administration of monosodium glutamate on the BSCB and spinal cord cells in adult male Wistar rats. The glutamate was delivered by subarachnoidal application of glutamate-carrying electrospun nanofiber mat dressing at the lumbar enlargement level. Half of the rats with the glutamate-loaded mat application were treated systemically with the histone deacetylase inhibitor valproic acid. A group of intact rats and a rat group with subarachnoidal application of an ‘empty’ (i.e., carrying no glutamate nanofiber mat dressing served as controls. All the rats were euthanized three weeks later and lumbar fragments of their spinal cords were harvested for histological, immunohistochemical and ultrastructural studies. The samples from controls revealed normal parenchyma and BSCB morphology, whereas those from rats with the glutamate-loaded nanofiber mat dressing showed many intraparenchymal microhemorrhages of variable sizes. The capillaries in the vicinity of the glutamate-carrying dressing (in the meninges and white matter alike were edematous and leaky, and their endothelial cells showed degenerative changes: extensive swelling, enhanced vacuo­lization and the presence of vascular intraluminal projections. However, endothelial tight junctions were generally well preserved. Some endothelial cells were dying by necrosis or apoptosis. The adjacent parenchyma showed astrogliosis with astrocytic hypertrophy and swelling of perivascular astrocytic feet. Neurons in the parenchyma revealed multiple symptoms of degeneration, including, inter alia, perikaryal, dendritic and axonal swelling, and destruction of organelles. All the damage symptoms were slightly less

  12. Nanofiber mat spinal cord dressing-released glutamate impairs blood-spinal cord barrier.

    Science.gov (United States)

    Sulejczak, Dorota; Taraszewska, Anna; Chrapusta, Stanisław J; Dziewulska, Dorota; Nakielski, Paweł; Rafałowska, Janina

    2016-01-01

    An excessive glutamate level can result in excitotoxic damage and death of central nervous system (CNS) cells, and is involved in the pathogenesis of many CNS diseases. It may also be related to a failure of the blood-spinal cord barrier (BSCB). This study was aimed at examining the effects of extended administration of monosodium glutamate on the BSCB and spinal cord cells in adult male Wistar rats. The glutamate was delivered by subarachnoidal application of glutamate-carrying electrospun nanofiber mat dressing at the lumbar enlargement level. Half of the rats with the glutamate-loaded mat application were treated systemically with the histone deacetylase inhibitor valproic acid. A group of intact rats and a rat group with subarachnoidal application of an 'empty' (i.e., carrying no glutamate) nanofiber mat dressing served as controls. All the rats were euthanized three weeks later and lumbar fragments of their spinal cords were harvested for histological, immunohistochemical and ultrastructural studies. The samples from controls revealed normal parenchyma and BSCB morphology, whereas those from rats with the glutamate-loaded nanofiber mat dressing showed many intraparenchymal microhemorrhages of variable sizes. The capillaries in the vicinity of the glutamate-carrying dressing (in the meninges and white matter alike) were edematous and leaky, and their endothelial cells showed degenerative changes: extensive swelling, enhanced vacuo-lization and the presence of vascular intraluminal projections. However, endothelial tight junctions were generally well preserved. Some endothelial cells were dying by necrosis or apoptosis. The adjacent parenchyma showed astrogliosis with astrocytic hypertrophy and swelling of perivascular astrocytic feet. Neurons in the parenchyma revealed multiple symptoms of degeneration, including, inter alia, perikaryal, dendritic and axonal swelling, and destruction of organelles. All the damage symptoms were slightly less severe in the rats

  13. Targeting glutamate system for novel antipsychotic approaches: relevance for residual psychotic symptoms and treatment resistant schizophrenia.

    Science.gov (United States)

    de Bartolomeis, Andrea; Sarappa, Chiara; Magara, Salvatore; Iasevoli, Felice

    2012-05-05

    Antipsychotics are the mainstay of schizophrenia treatment. However, approximately one third of schizophrenic patients do not respond or respond poorly to antipsychotics. Therefore, there is a need for new approaches that can improve schizophrenia treatment significantly. Promising strategies arise from the modulation of glutamatergic system, according to its proposed involvement in schizophrenia pathogenesis. In this review, we critically updated preclinical and clinical data on the modulation of glutamate N-methyl-D-aspartate (NMDA) receptor activity by NMDA-Rs co-agonists, glycine transporters inhibitors, AMPAkines, mGluR5 agonists, NMDA-Rs partial agonists. We focused on: 1) preclinical results in animal models mimicking the pathophysiology of psychosis, mainly believed to be responsible of negative and cognitive symptoms, and predicting antipsychotic-like activity of these compounds; and 2) clinical efficacy in open-label and double-blind trials. Albeit promising preclinical findings for virtually all compounds, clinical efficacy has not been confirmed for D-cycloserine. Contrasting evidence has been reported for glycine and D-serine, that may however have a role as add-on agents. More promising results in humans have been found for glycine transporter inhibitors. AMPAkines appear to be beneficial as pro-cognitive agents, while positive allosteric modulators of mGluR5 have not been tested in humans. Memantine has been proposed in early stages of schizophrenia, as it may counteract the effects of glutamate excitotoxicity correlated to high glutamate levels, slowing the progression of negative symptoms associated to more advanced stages of the illness. Copyright © 2012 Elsevier B.V. All rights reserved.

  14. Novel expression patterns of metabotropic glutamate receptor 6 in the zebrafish nervous system.

    Directory of Open Access Journals (Sweden)

    Ying-Yu Huang

    Full Text Available The metabotropic glutamate receptor 6 (mGluR6 or GRM6 belongs to the class III of the metabotropic glutamate receptor family. It is the only known mGluR that mediates direct synaptic transmission in the nervous system and is thought to mediate the ON-response in the ON-pathway of the vertebrate retina. Phylogenetic and gene structure analysis indicated that the zebrafish genome harbours two mglur6 paralogs, mglur6a and mglur6b. Besides expression in the inner nuclear layer and distinct regions in the brain, both mglur6 paralogs are expressed in ganglion cells of the retina, an expression pattern which can also be observed in the downstream effector molecules gnaoa and gnaob. This unexpected expression pattern is consistent with immunohistological labeling using a peptide antibody specific for the mGluR6b paralog. These expression patterns contradict the existing view that mGluR6 is solely located on ON-bipolar cells where it functions in signal transmission. Consistent with expression in ON-bipolar cells, we report a decreased b-wave amplitude in the electroretinogram after morpholino-based downregulation of mGluR6b, showing a function in the ON response. Our data suggest more widespread functions of mGluR6 mediated signaling in the central nervous system, possibly including sign reversing synapses in the inner retina.

  15. Dietary protein restriction causes modification in aluminum-induced alteration in glutamate and GABA system of rat brain

    Directory of Open Access Journals (Sweden)

    Chatterjee Ajay K

    2003-02-01

    Full Text Available Abstract Background Alteration of glutamate and γ-aminobutyrate system have been reported to be associated with neurodegenerative disorders and have been postulated to be involved in aluminum-induced neurotoxicity as well. Aluminum, an well known and commonly exposed neurotoxin, was found to alter glutamate and γ-aminobutyrate levels as well as activities of associated enzymes with regional specificity. Protein malnutrition also reported to alter glutamate level and some of its metabolic enzymes. Thus the region-wise study of levels of brain glutamate and γ-aminobutyrate system in protein adequacy and inadequacy may be worthwhile to understand the mechanism of aluminum-induced neurotoxicity. Results Protein restriction does not have any significant impact on regional aluminum and γ-aminobutyrate contents of rat brain. Significant interaction of dietary protein restriction and aluminum intoxication to alter regional brain glutamate level was observed in the tested brain regions except cerebellum. Alteration in glutamate α-decarboxylase and γ-aminobutyrate transaminase activities were found to be significantly influenced by interaction of aluminum intoxication and dietary protein restriction in all the tested brain regions. In case of regional brain succinic semialdehyde content, this interaction was significant only in cerebrum and thalamic area. Conclusion The alterations of regional brain glutamate and γ-aminobutyrate levels by aluminum are region specific as well as dependent on dietary protein intake. The impact of aluminum exposure on the metabolism of these amino acid neurotransmitters are also influenced by dietary protein level. Thus, modification of dietary protein level or manipulation of the brain amino acid homeostasis by any other means may be an useful tool to find out a path to restrict amino acid neurotransmitter alterations in aluminum-associated neurodisorders.

  16. Glutamate-induced obesity leads to decreased sperm reserves and acceleration of transit time in the epididymis of adult male rats

    OpenAIRE

    Fernandes, Glaura S. A.; Arena, Arielle C. [UNESP; Campos, Kleber E.; Volpato, Gustavo T.; Anselmo-Franci, Janete A.; Damasceno, Débora Cristina [UNESP; Kempinas, Wilma G. [UNESP

    2012-01-01

    Abstract Background Given the established fact that obesity interferes with male reproductive functions, the present study aimed to evaluate sperm production in the testis and storage in the epididymis in a glutamate-induced model of obesity. Methods Male rats were treated neonatally with monosodium glutamate (MSG) at doses of 4 mg/kg subcutaneously, or with saline...

  17. Polyamines Are Critical for the Induction of the Glutamate Decarboxylase-dependent Acid Resistance System in Escherichia coli *

    Science.gov (United States)

    Chattopadhyay, Manas K.; Tabor, Herbert

    2013-01-01

    As part of our studies on the biological functions of polyamines, we have used a mutant of Escherichia coli that lacks all the genes for polyamine biosynthesis for a global transcriptional analysis on the effect of added polyamines. The most striking early response to the polyamine addition is the increased expression of the genes for the glutamate-dependent acid resistance system (GDAR) that is important for the survival of the bacteria when passing through the acid environment of the stomach. Not only were the two genes for glutamate decarboxylases (gadA and gadB) and the gene for glutamate-γ-aminobutyrate antiporter (gadC) induced by the polyamine addition, but the various genes involved in the regulation of this system were also induced. We confirmed the importance of polyamines for the induction of the GDAR system by direct measurement of glutamate decarboxylase activity and acid survival. The effect of deletions of the regulatory genes on the GDAR system and the effects of overproduction of two of these genes were also studied. Strikingly, overproduction of the alternative σ factor rpoS and of the regulatory gene gadE resulted in very high levels of glutamate decarboxylase and almost complete protection against acid stress even in the absence of any polyamines. Thus, these data show that a major function of polyamines in E. coli is protection against acid stress by increasing the synthesis of glutamate decarboxylase, presumably by increasing the levels of the rpoS and gadE regulators. PMID:24097985

  18. Metabotropic glutamate receptors in glial cells

    NARCIS (Netherlands)

    D'Antoni, Simona; Berretta, Antonio; Bonaccorso, Carmela Maria; Bruno, Valeria; Aronica, Eleonora; Nicoletti, Ferdinando; Catania, Maria Vincenza

    2008-01-01

    Glutamate is the major excitatory neurotransmitter in the mammalian central nervous system (CNS) and exerts its actions via a number of ionotropic glutamate receptors/channels and metabotropic glutamate (mGlu) receptors. In addition to being expressed in neurons, glutamate receptors are expressed in

  19. L-Glutamic acid production by Bacillus spp. isolated from vegetable ...

    African Journals Online (AJOL)

    Administrator

    2011-06-15

    Jun 15, 2011 ... monosodium salt as a flavor enhancer in foods (Kikunae,. 2008). L-Glutamic acid has been produced from quite a large number of carbon and nitrogen sources by fermen- tation using different bacterial .... ammonium nitrate, urea, ammonium chloride, potassium nitrate, alanine and asparagines at 0.2% ...

  20. Regulation of the Glutamate-Glutamine Transport System by Intracellular pH in Streptococcus lactis

    NARCIS (Netherlands)

    POOLMAN, B; HELLINGWERF, KJ; KONINGS, WN

    Various methods of manipulation of the intracellular pH in Streptococcus lactis result in a unique relationship between the rate of glutamate and glutamine transport and the cytoplasmic pH. The initial rate of glutamate uptake by S. lactis cells increases more than 30-fold when the intracellular pH

  1. Effects of introducing theanine or glutamic acid core to tralopyril on systemicity and insecticidal activity.

    Science.gov (United States)

    Yang, Wen; Chen, Yao; Zhang, Ying; Gao, Xiu-Bing; Zhou, Yu-Feng

    2017-09-01

    Tralopyril was the active agent of a pro-insecticide chlorfenapyr. To simultaneously solve the problems of the phytotoxicity and non-systemic insecticidal activity of tralopyril, four new tralopyril conjugates containing theanine or glutamic acid moieties were designed and synthesized. Their phytotoxicity to tea shoot, phloem systemicity, and insecticidal activity were evaluated. Phytotoxic symptoms were not observed after the tea shoots were exposed to the four conjugates at concentrations of 2mM. The phloem mobility test on Ricinus communis L. seedlings confirmed that all four conjugates were mobile in the sieve tubes. Results of insecticidal activity against the third-instar larvae of Plutella xylostella showed that only conjugate 20 exhibited activity with an LC 50 value of 0.5882±0.0504mM. After root application to tea seedlings, conjugate 20 showed obviously systemic insecticidal activity against Dendrothrips minowai Priesner, while chlorfenapyr showed no attribute of that. A new conjugate as potential phloem mobile pro-insecticide candidate was provided and so a novel strategy of pro-insecticide for improved phloem systemicity was proposed. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Glutamate receptor agonists

    DEFF Research Database (Denmark)

    Vogensen, Stine Byskov; Greenwood, Jeremy R; Bunch, Lennart

    2011-01-01

    The neurotransmitter (S)-glutamate [(S)-Glu] is responsible for most of the excitatory neurotransmission in the central nervous system. The effect of (S)-Glu is mediated by both ionotropic and metabotropic receptors. Glutamate receptor agonists are generally a-amino acids with one or more...... stereogenic centers due to strict requirements in the agonist binding pocket of the activated state of the receptor. By contrast, there are many examples of achiral competitive antagonists. The present review addresses how stereochemistry affects the activity of glutamate receptor ligands. The review focuses...... mainly on agonists and discusses stereochemical and conformational considerations as well as biostructural knowledge of the agonist binding pockets, which is useful in the design of glutamate receptor agonists. Examples are chosen to demonstrate how stereochemistry not only determines how the agonist...

  3. Pro-psychotic effects of synthetic cannabinoids: interactions with central dopamine, serotonin, and glutamate systems.

    Science.gov (United States)

    Fantegrossi, William E; Wilson, Catheryn D; Berquist, Michael D

    2018-02-01

    An association between marijuana use and schizophrenia has been noted for decades, and the recent emergence of high-efficacy synthetic cannabinoids (SCBs) as drugs of abuse has lead to a growing number of clinical reports of persistent psychotic effects in users of these substances. The mechanisms underlying SCB-elicited pro-psychotic effects is unknown, but given the ubiquitous neuromodulatory functions of the endocannabinoid system, it seems likely that agonist actions at cannabinoid type-1 receptors (CB1Rs) might modulate the functions of other neurotransmitter systems known to be involved in schizophrenia. The present review surveys what is currently known about the interactions of CB1Rs with dopamine, serotonin, and glutamate systems, because all three of those neurotransmitters are well-established in the pathophysiology of schizophrenia and psychosis. Identification of molecular mechanisms underlying the pro-psychotic effects of SCB drugs of abuse may establish certain classes of these substances as particularly dangerous, guiding regulations to control availability of these drugs. Likewise, an understanding of the pharmacological interactions which lead to schizophrenia and psychosis subsequent to SCB exposure might guide the development of novel therapies to treat afflicted users.

  4. Expression of group III metabotropic glutamate receptors in the reproductive system of male mice.

    Science.gov (United States)

    Marciniak, Marcin; Chruścicka, Barbara; Lech, Tomasz; Burnat, Grzegorz; Pilc, Andrzej

    2016-03-01

    Although the presence of metabotropic glutamate (mGlu) receptors in the central nervous system is well documented, they have recently been found in peripheral and non-neuronal tissues. In the present study we investigated the expression of group III mGlu receptors in the reproductive system of male mice. Reverse transcription-polymerase chain reaction analysis revealed the presence of mGlu6, mGlu7 and mGlu8 (but not mGlu4) receptor transcripts in testes and epididymides from adult mice. In addition, expression of mGlu6 (Grm6) and mGlu8 receptor (Grm8) mRNA was detected in spermatozoa isolated from the vas deferens. The vas deferens was found to contain only mGlu7 receptor (Grm7) mRNA, which was particularly intense in 21-day-old male mice. In penile homogenates, only the mGlu7 receptor signal was detected. Genetic ablation of the mGlu7 receptor in males led to fertility disorders manifested by decreased insemination capability as well as deterioration of sperm parameters, particularly sperm motility, vitality, sperm membrane integrity and morphology, with a simultaneous increase in sperm concentration. These results indicate that constitutively expressed mGlu receptors in the male reproductive system may play an important role in ejaculation and/or erection processes, as well as in the formation and maturation of spermatozoa.

  5. PENGETAHUAN DAN PERILAKU KONSUMSI MAHASISWA PUTRA TINGKAT PERSIAPAN BERSAMA IPB TENTANG MONOSODIUM GLUTAMAT DAN KEAMANANNYA

    Directory of Open Access Journals (Sweden)

    Made Mita Dwi Saraswati

    2013-10-01

    Full Text Available ABSTRACTThe aim of this study was to analyze the knowledge and consumption behaviour of the first year boy students of IPB on Monosodium Glutamate (MSG and its safety. Data were collected using self administered questionnaire. Questionnaires were given to the students through cooperation with one of internal club in IPB’s Dormitory. There were 1 324 questionnaires that were given, but only 808 questionnaires were collected back and 24 of them not filled out completely. Thus there were 784 questionnaires that qualified to be research data. Knowledge on MSG and its safety was classified into 3 levels of knowledge, such as low (80% of total score. The results showed that most students have low level of knowledge on the MSG (81.4% and it’s safety (94.3%. However, most of them frequently consume foods containing MSG (39—86%. Level of knowledge on MSG is not correlated to consumption behavior of MSG (p>0.05.Key words: consumption behavior, knowledge, Monosodium Glutamate (MSGABSTRAKPenelitian ini bertujuan untuk menganalisis pengetahuan dan perilaku mahasiswa putra Tingkat Persiapan Bersama (TPB IPB tentang Monosodium Glutamat (MSG dan keamanannya. Data penelitian diperoleh melalui kuesioner yang diisi sendiri oleh mahasiswa putra. Penyebaran kuesioner dilakukan melalui kerjasama dengan salah satu klub internal Asrama Putra TPB. Kuesioner survei diberikan kepada seluruh mahasiswa putra, yaitu sebanyak 1 324 orang. Jumlah mahasiswa yang mengisi kuesioner adalah 808 orang, namun 24 orang diantara- nya tidak mengisi kuesioner dengan lengkap sehingga diperoleh 784 orang sebagai subjek dalam penelitian ini. Tingkat pengetahuan tentang MSG dan keamanannya diklasifikasikan menjadi tiga, yaitu tingkat pengetahuan kurang (skor total80%. Hasil penelitian menunjukkan bahwa sebagian besar mahasiswa putra mempunyai tingkat pengetahuan yang rendah tentang MSG (81.4% dan keamanan MSG (94.3%, namun sebagian besar dari mereka (39—86% juga sering mengonsumsi

  6. Glutamate receptors

    DEFF Research Database (Denmark)

    Kristensen, Anders S; Geballe, Matthew T; Snyder, James P

    2006-01-01

    Fast excitatory synaptic transmission in the CNS relies almost entirely on the neurotransmitter glutamate and its family of ion channel receptors. An appreciation of the coupling between agonist binding and channel opening has advanced rapidly during the past five years, largely as a result of ne...

  7. Effects of glutamate decarboxylase and gamma-aminobutyric acid (GABA) transporter on the bioconversion of GABA in engineered Escherichia coli.

    Science.gov (United States)

    Le Vo, Tam Dinh; Kim, Tae Wan; Hong, Soon Ho

    2012-05-01

    Gamma-aminobutyric acid (GABA) is a non-essential amino acid and a precursor of pyrrolidone, a monomer of nylon 4. GABA can be biosynthesized through the decarboxylation of L: -glutamate by glutamate decarboxylase. In this study, the effects of glutamate decarboxylase (gadA, gadB), glutamate/GABA antiporter (gadC) and GABA aminotransferase (gabT) on GABA production were investigated in Escherichia coli. Glutamate decarboxylase was overexpressed alone or with the glutamate/GABA antiporter to enhance GABA synthesis. GABA aminotransferase, which redirects GABA into the TCA cycle, was knock-out mutated. When gadB and gadC were co-overexpressed in the gabT mutant strain, a final GABA concentration of 5.46 g/l was obtained from 10 g/l of monosodium glutamate (MSG), which corresponded to a GABA yield of 89.5%.

  8. HISTOLOGI KORTEKS SEREBRI TIKUS PUTIH JANTAN GALUR WISTAR SETELAH PENGHENTIAN PAJANAN MONOSODIUM GLUTAMAT (MSG

    Directory of Open Access Journals (Sweden)

    Muhammad Hadi Arwani

    2015-11-01

    Full Text Available Abstract: Histology Of Cortex Celebrity Male Wistar Rats (Rattus norvegicus After Cessation Exposure Of Monosodium Glutamate (MSG. The aim of this study was to determine the reparation or the regeneration pyramidal cells in cortex after cessation exposure of MSG. This is an experimental study used 27 male Wistar rats and divided into 3 large groups (K(+, K(-, and P. The variables data was observed in the tenth field of view the cortex celebrity with a magnification of 40x objective lens and the data was determined the average of it. Data were analyzed using Kruskal Wallis followed by Mann Whitney. Results show that the Exposure to MSG for a minimum of 28 days resulted from no significant change (p>0,05 in the account of normal pyramidal cells and the account of damaged pyramidal cells. Abstrak : Gambaran Histologikorteks Serebri Tikus Putih (Rattus norvegicus Jantan Galur Wistar Setelah Penghentian Pajanan Monosodium Glutamat (MSG. Penelitian ini bertujuan untuk mengetahui adanya perbaikan atau regenerasi sel piramidal di korteks serebri setelah penghentian pajanan toksik MSG pada tikus. Penelitian ini merupakan penelitian eksperimental menggunakan 27 ekor tikus jantan galur wistar yang dibagi menjadi 3 kelompok besar (K(+, K(-, dan P. Data diamati pada 10 lapang pandang korteks dengan perbesaran lensa objektif 40x dan dicari reratanya. Data kemudian dianalisa menggunakan uji Kruskall Wallis yang dilanjutkan dengan Mann Whitney Test. Hasil penelitian menunjukkan bahwa pajanan MSG selama minimal 28 hari tidak mengakibatkan perubahan secara signifikan (p>0,05 jumlah sel piramidal normaldan jumlah sel piramidal rusak.

  9. PENGARUH PEMBERIAN MONOSODIUM GLUTAMAT TERHADAP KADAR HORMON ESTRADIOL DAN KADAR HORMON PROGESTERON PADA TIKUS PUTIH BETINA (Rattus norvegicus

    Directory of Open Access Journals (Sweden)

    andri ani

    2018-03-01

    Full Text Available Perubahan pola demografi di negara maju dan negara berkembang, angka kejadian infertilitas di negara maju dilaporkan sekitar 5%-8% dan di negara berkembang sekitar 30%.WHO memperkirakan sekitar 8%-10% atau sekitar 50-80 juta pasangan suami istri di seluruh dunia mengalami masalah infertilitas, sehingga membuat infertilitas menjadi masalah mendesak. Untuk itu diperlukan pengendalian infertilitas, salah satunya adalah kewaspadaan perubahan gaya hidup, perubahan ini juga mempengaruhi pola konsumsi makanan dengan lebih banyak mengkonsumsi jenis makanan cepat saji yang banyak mengandung zat aditif (penyedap rasa. Penelitian ini bertujuan untuk mengetahui pengaruh pemberian monosodium glutamate terhadap kadar hormon estradiol dan kadar hormon progesteron pada tikus putih betina ( Rattus norvegicus .Penelitian ini menggunakan metode pendekatan post test only control group design, terhadap tikus putih betina dengan berat 200 – 250 gr. Sampel terdiri dari 24 ekor tikus yang dibagi 4 kelompok yaitu kelompok kontrol ( K , perlakuan I, II dan III . Kelompok perlakuan diberikan monosodium glutamat dengan dosis masing-masing : 45 mg, 54 mg dan 63 mg setiap hari diberikan peroral yang dilarutkan dengan aquabides 2 ml selama 20 hari yang dimulai pada awal fase proestrus. Setelah 20 hari perlakuan tikus di korbankan dan diambil darahnya. Pemeriksaan kadar hormone estradiol dan progesteron menggunakan Elisa Spectrophotometer.  Kemudian hasilnya dianalisa dengan menggunakan One Way ANOVA dan dilanjutkan dengan uji Multiple Comparison jenis Bonferroni.Hasil penelitian pemberian  monosodium glutamat dengan dosis 45 mg/ ekor/ hari, 54 mg/ekor/ hari dan 63 mg/ ekor /hari dapat menurunkan kadar hormon estradiol tikus putih betina (Rattus norvegicus secara signifikan. Dan pemberian monosodium glutamate dengan dosis 45 mg/ ekor/ hari dapat menurunkan kadar hormon progesteron tikus putih betina (Rattus norvegicus walaupun tidak berpengaruh secara signifikan , dan pada

  10. GANGGUAN SPERMATOGENESIS SETELAH PEMBERIAN MONOSODIUM GLUTAMAT PADA MENCIT (MUS MUSCULUS L.

    Directory of Open Access Journals (Sweden)

    A.A.SG.A SUKMANINGSIH

    2011-12-01

    Full Text Available This study was conducted to investigate the effect of monosodium glutamate (MSG on spermatogenesis of male experimental mice.using 32 twelve-week old mice. They were divided randomly into 4 groups, each group consisted of 8 mice. One group was used as control, three groups were used as treatment, which received 1.5 mg/g body weight/day, 3 mg/g body weight/day and 4.5 mg/g body weight/day of MSG solution in destilled water for 35 days. The result showed that MSG treatment led to disturbance on spermatogenesis by reduction in some of the parameter studied. There was a significant (p 0.05.

  11. A Pulsed Electromagnetic Field Protects against Glutamate-Induced Excitotoxicity by Modulating the Endocannabinoid System in HT22 Cells.

    Science.gov (United States)

    Li, Xin; Xu, Haoxiang; Lei, Tao; Yang, Yuefan; Jing, Da; Dai, Shuhui; Luo, Peng; Xu, Qiaoling

    2017-01-01

    Glutamate-induced excitotoxicity is common in the pathogenesis of many neurological diseases. A pulsed electromagnetic field (PEMF) exerts therapeutic effects on the nervous system, but its specific mechanism associated with excitotoxicity is still unknown. We investigated the role of PEMF exposure in regulating glutamate-induced excitotoxicity through the endocannabinoid (eCB) system. PEMF exposure improved viability of HT22 cells after excitotoxicity and reduced lactate dehydrogenase release and cell death. An eCB receptor 1 (CB1R) specific inhibitor suppressed the protective effects of PEMF exposure, even though changes in CB1R expression were not observed. Elevation of N-arachidonylethanolamide (AEA) and 2-arachidonylglycerol (2-AG) following PEMF exposure indicated that the neuroprotective effects of PEMF were related to modulation of the eCB metabolic system. Furthermore, CB1R/ERK signaling was shown to be an important downstream pathway of PEMF in regulating excitotoxicity. These results suggest that PEMF exposure leads to neuroprotective effects against excitotoxicity by facilitating the eCB/CB1R/ERK signaling pathway. Therefore, PEMF may be a potential physical therapeutic technique for preventing and treating neurological diseases.

  12. The effects of reactants ratios, reaction temperatures and times on Maillard reaction products of the L-ascorbic acid/L-glutamic acid system

    Directory of Open Access Journals (Sweden)

    Yong-Yan ZHOU

    2016-01-01

    Full Text Available Abstract The transformation law of the Maillard reaction products with three different reactants ratios - equimolar reactants, excess L-glutamic acid and excess L-ascorbic acid reaction respectively, five different temperatures, and different time conditions for the L-ascorbic acid / L-glutamic acid system were investigated. Results showed that, the increase of the reaction time and temperature led to the increase of the browning products, uncoloured intermediate products, as well as aroma compounds. Compared with the equimolar reaction system, the excess L-ascorbic acid reaction system produced more browning products and uncoloured intermediate products, while the aroma compounds production remained the same. In the excess L-glutamic acid system, the uncoloured intermediate products increased slightly, the browning products remained the same, while the aroma compounds increased.

  13. Glutamate transporters combine transporter- and channel-like features

    NARCIS (Netherlands)

    Slotboom, DJ; Konings, WN; Lolkema, JS

    2001-01-01

    Glutamate transporters in the mammalian central nervous system have a unique position among secondary transport proteins as they exhibit glutamate-gated chloride-channel activity in addition to glutamate-transport activity. In this article, the available data on the structure of the glutamate

  14. Elevated systemic glutamic acid level in the non-obese diabetic mouse is Idd linked and induces beta cell apoptosis.

    Science.gov (United States)

    Banday, Viqar Showkat; Lejon, Kristina

    2017-02-01

    Although type 1 diabetes (T1D) is a T-cell-mediated disease in the effector stage, the mechanism behind the initial beta cell assault is less understood. Metabolomic differences, including elevated levels of glutamic acid, have been observed in patients with T1D before disease onset, as well as in pre-diabetic non-obese diabetic (NOD) mice. Increased levels of glutamic acid damage both neurons and beta cells, implying that this could contribute to the initial events of T1D pathogenesis. We investigated the underlying genetic factors and consequences of the increased levels of glutamic acid in NOD mice. Serum glutamic acid levels from a (NOD×B6)F 2 cohort (n = 182) were measured. By genome-wide and Idd region targeted microsatellite mapping, genetic association was detected for six regions including Idd2, Idd4 and Idd22. In silico analysis of potential enzymes and transporters located in and around the mapped regions that are involved in glutamic acid metabolism consisted of alanine aminotransferase, glutamic-oxaloacetic transaminase, aldehyde dehydrogenase 18 family, alutamyl-prolyl-tRNA synthetase, glutamic acid transporters GLAST and EAAC1. Increased EAAC1 protein expression was observed in lysates from livers of NOD mice compared with B6 mice. Functional consequence of the elevated glutamic acid level in NOD mice was tested by culturing NOD. Rag2 -/- Langerhans' islets with glutamic acid. Induction of apoptosis of the islets was detected upon glutamic acid challenge using TUNEL assay. Our results support the notion that a dysregulated metabolome could contribute to the initiation of T1D. We suggest that targeting of the increased glutamic acid in pre-diabetic patients could be used as a potential therapy. © 2016 John Wiley & Sons Ltd.

  15. Gambaran Histologi Regenerasi Hati Pasca Penghentian Pajanan Monosodium Glutamat pada Tikus Wistar

    Directory of Open Access Journals (Sweden)

    Heryanto Andreas

    2015-09-01

    (28, 42, and 56 days. 1 positivecontrol goup were given akuades for 28, 42, and 56 days; 1st, 2nd, and 3rdst,  negative control goup weregiven 5 mg/gBW/day of MSG for for 28, 42, and 56 days; 1st, 2nd, and 3 treatment goup were given 5mg/gBW/day of MSG for 28, 42, and 56 days, then stopped for 0, 14, and 28 days. Measured variablewere liver damage degree. One Way ANOVA data analysis found a significant difference (p<0.05and there was no significant difference between positive control and regeneration treatment goup day 14th (p>0.05 and regeneration treatment group day 28thrd2nd3, and 3rd (p>0.05. MSG exposure causes liver damage and liver regeneration occurs after 14 days cessation of MSG exposure. Keywords: monosodium glutamate (MSG, regeneration, liver damage

  16. Enhanced succinic acid production under acidic conditions by introduction of glutamate decarboxylase system in E. coli AFP111.

    Science.gov (United States)

    Wu, Mingke; Li, Xiaozhan; Guo, Shunfeng; Lemma, Wubliker Dessie; Zhang, Wenming; Ma, Jiangfeng; Jia, Honghua; Wu, Hao; Jiang, Min; Ouyang, Pingkai

    2017-04-01

    Biological synthesis of succinic acid at low pH values was favored since it not only decreased investment cost but also simplified downstream purification process. In this study, the feasibility of using glutamate decarboxylase system to improve succinic acid production of Escherichia coli AFP111, a succinate-producing candidate with mutations in pfl, ldhA, and ptsG, under acidic conditions was investigated. By overexpressing gadBC operon in AFP111, a recombinant named as BA201 (AFP111/pMD19T-gadBC) was constructed. Fermentation at pH 5.6 showed that 30 g L -1 glucose was consumed and 26.58 g L -1 succinic acid was produced by BA201, which was 1.22- and 1.32-fold higher than that by the control BA200 (AFP111/pMD19T) containing the empty vector. Analysis of intracellular enzymes activities and ATP concentrations revealed that the activities of key enzymes involved in glucose uptake and products synthesis and intracellular ATP levels were all increased after overexpression of gadBC which were benefit for cell metabolism under weak acidic conditions. To further improve the succinic acid titer by recombinant BA201 at pH 5.6, the extracellular glutamate concentration was optimized and the final succinic acid titer increased 20.4% to 32.01 g L -1 . Besides, the fermentation time was prolonged by repetitive fermentation and additional 15.78 g L -1 succinic acid was produced by recovering cells into fresh medium. The results here demonstrated a potential strategy of overexpressing gadBC for increased succinic acid production of E. coli AFP111 under weak acidic conditions.

  17. Adsorption of biometals to monosodium titanate in biological environments

    Energy Technology Data Exchange (ETDEWEB)

    HOBBS, D.T.; MESSER, R. L. W.; LEWIS, J. B.; CLICK, D. R. LOCKWOOD, P. E.; WATAHA, J. C.

    2005-06-06

    Monosodium titanate (MST) is an inorganic sorbent/ion exchanger developed for the removal of radionuclides from nuclear wastes. We investigated the ability of MST to bind Cd(II), Hg(II), or Au(III) to establish the utility of MST for applications in environmental decontamination or medical therapy (drug delivery). Adsorption isotherms for MST were determined at pH 7-7.5 in water or phosphate-buffered saline. The extent of metal binding was determined spectroscopically by measuring the concentrations of the metals in solution before and after contact with the MST. Cytotoxic responses to MST were assessed using THP1 monocytes and succinate dehydrogenase activity. Monocytic activation by MST was assessed by TNF{alpha} secretion (ELISA) with or without lipopolysaccharide (LPS) activation. MST sorbed Cd(II), Hg(II), and Au(III) under conditions similar to that in physiological systems. MST exhibited the highest affinity for Cd(II) followed by Hg(II) and Au (III). MST (up to 100 mg/L) exhibited only minor (< 25% suppression of succinate dehydrogenase) cytotoxicity and did not trigger TNF{alpha} secretion nor modulate LPS-induced TNF{alpha} secretion from monocytes. MST exhibits high affinity for biometals with no significant biological liabilities in these introductory studies. MST deserves further scrutiny as a substance with the capacity to decontaminate biological environments or deliver metals in a controlled fashion.

  18. Effect of parenteral glutamate treatment on the localization of neurotransmitters in the mediobasal hypothalamus

    Energy Technology Data Exchange (ETDEWEB)

    Walaas, I.; Fonnum, F.

    1978-01-01

    The localization of cholinergic, aminergic and amino acid-ergic neurones in the mediobasal hypothalamus has been studied in normal rat brain and in brains where neurones in nucleus arcuatus were destroyed by repeated administration of 2 mg/g body weight monosodium glutamate to newborn animals. In normal animals acetylcholinesterase staining, choline acetyltransferase and aromatic L-amino acid decarboxylase were concentrated in the median eminence and the arcuate nucleus. Glutamate decarboxylase was concentrated at the boundary between the ventromedial and the arcuate nuclei, with lower activity in the arcuate nucleus and very low activity in the median eminence. Nucleus arcuatus contained an intermediate level of high affinity glutamate uptake. In the lesioned animals, there were significant decreases in choline acetyltransferase, acetylcholinesterase staining and glutamate decarboxylase in the median eminence, whereas choline acetyltransferase activity and acetylcholinesterase staining, but not glutamate decarboxylase activity, were decreased in nucleus arcuatus. Aromatic L-amino acid decarboxylase was unchanged in all regions studied. The high affinity uptakes of glutamate, dopamine and noradrenaline, and the endogenous amino acid levels were also unchanged in the treated animals. The results indicate the existence of acetylcholine- and GABA-containing elements in the tuberoinfundibular tract. They further indicate that the dopamine cells in the arcuate nucleus are less sensitive to the toxic effect of glutamate than other cell types, possibly because they contain less glutamate receptors.

  19. Biosynthetic preparation of L-[13C]- and [15N]glutamate by Brevibacterium flavum

    International Nuclear Information System (INIS)

    Walker, T.E.; London, R.E.

    1987-01-01

    The biosynthesis of isotopically labeled L-glutamic acid by the microorganism Brevibacterium flavum was studied with a variety of carbon-13-enriched precursors. The purpose of this study was twofold: (i) to develop techniques for the efficient preparation of labeled L-glutamate with a variety of useful labeling patterns which can be used for other metabolic studies, and (ii) to better understand the metabolic events leading to label scrambling in these strains. B. flavum, which is used commercially for the production of monosodium glutamate, has the capability of utilizing glucose or acetate as a sole carbon source, and important criterion from the standpoint of developing labeling strategies. Unfortunately, singly labeled glucose precursors lead to excessive isotopic dilution which reduces their usefulness. Studies with [3- 13 C]pyruvate indicate that this problem can in principle be overcome by using labeled three-carbon precursors; however, conditions could not be found which would lead to an acceptable yield of isotopically labeled L-glutamate. In contrast, [1- 13 C]- or [2- 13 C]acetate provides relatively inexpensive, readily available precursors for the production of selectively labeled, high enriched L-glutamate. The preparation of L-[ 15 N]glutamate from [ 15 N]ammonium sulfate was carried out and is a very effective labeling strategy. Analysis of the isotopic distribution in labeled glutamate provides details about the metabolic pathways in these interesting organisms

  20. A survey of free glutamic acid in foods using a robust LC-MS/MS method.

    Science.gov (United States)

    Cebi, Nur; Dogan, Canan Ekinci; Olgun, Elmas Oktem; Sagdic, Osman

    2018-05-15

    An effective and simultaneous liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was used with the aim of quantifying monosodium glutamate (MSG) in foodstuffs, such as chips, taste cubes, sauces and soups. The results were linear (R 2  = 1), with very low LOD and LOQ values, 1.0 µg/kg, 5.0 µg/kg, respectively. Excellent repeatability and reproducibility were also achieved. This highly sensitive and robust LC-MS/MS technique was applied successfully for the detection and quantification of MSG in a wide variety of foodstuffs. MSG contents ranged from 0.01 g/100 g to 15.39 g/100 g in food samples. Importantly, determination of free glutamic acid in the daily diet could also prevent various side effects associated with consumption of excess free glutamic acid. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Regulation of Synaptic Transmission by Ambient Extracellular Glutamate

    OpenAIRE

    FEATHERSTONE, DAVID E.; SHIPPY, SCOTT A.

    2007-01-01

    Many neuroscientists assume that ambient extracellular glutamate concentrations in the nervous system are biologically negligible under nonpathological conditions. This assumption is false. Hundreds of studies over several decades suggest that ambient extracellular glutamate levels in the intact mammalian brain are ~0.5 to ~5 μM. This has important implications. Glutamate receptors are desensitized by glutamate concentrations significantly lower than needed for receptor activation; 0.5 to 5 μ...

  2. Antimutagenic Effect of Hibiscus sabdariffa L. Aqueous Extract on Rats Treated with Monosodium Glutamate.

    Science.gov (United States)

    Gheller, Ana Carla Guidini Valentini; Kerkhoff, Jacqueline; Vieira Júnior, Gerardo Magela; de Campos, Kleber Eduardo; Sugui, Marina Mariko

    2017-01-01

    Hibiscus sabdariffa L. is a plant of the Malvaceae family, commonly known as roselle. H. sabdariffa is known to contain antioxidant, cholesterol-lowering, antiobesity, insulin resistance reduction, antihypertensive, and skin cancer chemopreventive properties. This study evaluated the effects of H. sabdariffa aqueous extract against cyclophosphamide (CPA, 25 mg/Kg) induced damage to DNA in male Wistar rats by micronucleus test. Samples of H. sabdariffa calyx were obtained in the municipality of Barra do Garças, Mato Grosso, Brazil. The aqueous extract was prepared by infusion and each animal received a daily dose of 400 mg/Kg by gavage for 15 consecutive days of treatment. The presence of anthocyanins was confirmed by ferric chloride test and phenolic compounds using high-performance liquid chromatography, with emphasis on the identification of rutin. The animals were sacrificed by deepening of anaesthesia to obtain bone marrow and determination of the frequency of micronucleated polychromatic erythrocytes. The group treated with the aqueous extract of H. sabdariffa revealed a 91% reduction in micronucleus frequency when compared with the positive control group. Under the conditions tested, H. sabdariffa L. presented a protective effect to CPA-induced damage to DNA of the treated animals, and it is a potential candidate as a chemopreventive agent against carcinogenesis.

  3. 78 FR 57881 - Monosodium Glutamate from China and Indonesia; Institution of Antidumping and Countervailing Duty...

    Science.gov (United States)

    2013-09-20

    ... than fair value and alleged to be subsidized by the Governments of China and Indonesia. Unless the... duties will each be collectively allocated one hour within which to make an oral presentation at the... investigations. Parties may file written testimony in connection with their presentation at the conference no...

  4. Antimutagenic Effect of Hibiscus sabdariffa L. Aqueous Extract on Rats Treated with Monosodium Glutamate

    Directory of Open Access Journals (Sweden)

    Ana Carla Guidini Valentini Gheller

    2017-01-01

    Full Text Available Hibiscus sabdariffa L. is a plant of the Malvaceae family, commonly known as roselle. H. sabdariffa is known to contain antioxidant, cholesterol-lowering, antiobesity, insulin resistance reduction, antihypertensive, and skin cancer chemopreventive properties. This study evaluated the effects of H. sabdariffa aqueous extract against cyclophosphamide (CPA, 25 mg/Kg induced damage to DNA in male Wistar rats by micronucleus test. Samples of H. sabdariffa calyx were obtained in the municipality of Barra do Garças, Mato Grosso, Brazil. The aqueous extract was prepared by infusion and each animal received a daily dose of 400 mg/Kg by gavage for 15 consecutive days of treatment. The presence of anthocyanins was confirmed by ferric chloride test and phenolic compounds using high-performance liquid chromatography, with emphasis on the identification of rutin. The animals were sacrificed by deepening of anaesthesia to obtain bone marrow and determination of the frequency of micronucleated polychromatic erythrocytes. The group treated with the aqueous extract of H. sabdariffa revealed a 91% reduction in micronucleus frequency when compared with the positive control group. Under the conditions tested, H. sabdariffa L. presented a protective effect to CPA-induced damage to DNA of the treated animals, and it is a potential candidate as a chemopreventive agent against carcinogenesis.

  5. Antimutagenic Effect of Hibiscus sabdariffa L. Aqueous Extract on Rats Treated with Monosodium Glutamate

    OpenAIRE

    Gheller, Ana Carla Guidini Valentini; Kerkhoff, Jacqueline; Vieira Júnior, Gerardo Magela; Campos, Kleber Eduardo de; Sugui, Marina Mariko

    2017-01-01

    Hibiscus sabdariffa L. is a plant of the Malvaceae family, commonly known as roselle. H. sabdariffa is known to contain antioxidant, cholesterol-lowering, antiobesity, insulin resistance reduction, antihypertensive, and skin cancer chemopreventive properties. This study evaluated the effects of H. sabdariffa aqueous extract against cyclophosphamide (CPA, 25?mg/Kg) induced damage to DNA in male Wistar rats by micronucleus test. Samples of H. sabdariffa calyx were obtained in the municipality o...

  6. A pilot integrative genomics study of GABA and glutamate neurotransmitter systems in suicide, suicidal behavior, and major depressive disorder.

    Science.gov (United States)

    Yin, Honglei; Pantazatos, Spiro P; Galfalvy, Hanga; Huang, Yung-Yu; Rosoklija, Gorazd B; Dwork, Andrew J; Burke, Ainsley; Arango, Victoria; Oquendo, Maria A; Mann, John J

    2016-04-01

    Gamma-amino butyric acid (GABA) and glutamate are the major inhibitory and excitatory neurotransmitters in the mammalian central nervous system, respectively, and have been associated with suicidal behavior and major depressive disorder (MDD). We examined the relationship between genotype, brain transcriptome, and MDD/suicide for 24 genes involved in GABAergic and glutamatergic signaling. In part 1 of the study, 119 candidate SNPs in 24 genes (4 transporters, 4 enzymes, and 16 receptors) were tested for associations with MDD and suicidal behavior in 276 live participants (86 nonfatal suicide attempters with MDD and 190 non-attempters of whom 70% had MDD) and 209 postmortem cases (121 suicide deaths of whom 62% had MDD and 88 sudden death from other causes of whom 11% had MDD) using logistic regression adjusting for sex and age. In part 2, RNA-seq was used to assay isoform-level expression in dorsolateral prefrontal cortex of 59 postmortem samples (21 with MDD and suicide, 9 MDD without suicide, and 29 sudden death non-suicides and no psychiatric illness) using robust regression adjusting for sex, age, and RIN score. In part 3, SNPs with subthreshold (uncorrected) significance levels below 0.05 for an association with suicidal behavior and/or MDD in part 1 were tested for eQTL effects in prefrontal cortex using the Brain eQTL Almanac (www.braineac.org). No SNPs or transcripts were significant after adjustment for multiple comparisons. However, a protein coding transcript (ENST00000414552) of the GABA A receptor, gamma 2 (GABRG2) had lower brain expression postmortem in suicide (P = 0.01) and evidence for association with suicide death (P = 0.03) in a SNP that may be an eQTL in prefrontal cortex (rs424740, P = 0.02). These preliminary results implicate GABRG2 in suicide and warrant further investigation and replication in larger samples. © 2016 Wiley Periodicals, Inc.

  7. Effect of sludge solids to mono-sodium titanate (MST) ratio on MST-treated sludge

    International Nuclear Information System (INIS)

    Saito, H.H.

    1999-01-01

    The Salt Disposition Systems Engineering Team has selected two cesium removal technologies for further development to replace the In-Tank Precipitation process: small tank tetraphenylborate (TPB) precipitation and crystalline silicotitanate (CST) ion exchange. In the CST ion exchange process, incoming salt solution from storage tanks containing entrained sludge solids is pretreated with monosodium titanate (MST) to adsorb strontium and plutonium. The resulting slurry is filtered using a cross-flow filter, with the permeate sent forward to CST ion exchange columns for cesium removal prior to conversion into Class A grout at the Saltstone Facility. The MST and sludge solids are to be sent for vitrification at the Defense Waste Processing Facility (DWPF). The High Level Waste Division (HLWD) requested that the Waste Processing Technology Section (WPTS) study varying the insoluble sludge solids to MST ratio to determine the relative impact of sludge and MST on filter performance. The purpose of this study was not for an exhaustive comprehensive search for an optimized insoluble sludge solids to monosodium titanate (MST) ratio, but as a scoping study to identify any effects of having an excess of either material. This document reports the results obtained

  8. Metabotropic glutamate receptor subtype 7 has critical roles in regulation of the endocrine system and social behaviours.

    Science.gov (United States)

    Masugi-Tokita, M; Yoshida, T; Kageyama, S; Kawata, M; Kawauchi, A

    2018-03-01

    Metabotropic glutamate receptor subtype 7 (mGluR7) is one of the group III mGluRs, which are negatively coupled to adenylate cyclase via Gi/Go proteins and localised to presynaptic active zones of the mammalian central nervous system. We previously reported that mGluR7 is essential for intermale aggression and amygdala-dependent fear learning. To elucidate the role of mGluR7 in the neuroendocrine system, we performed biochemical analyses and found a significant reduction of testosterone levels in mGluR7 knockout (KO) mice. Testosterone replacement restored intermale aggressive behaviour in castrated wild-type mice to the level of gonadally intact wild-type mice. However, given the same dosage of testosterone replacement, mGluR7 KO mice showed almost no aggressive behaviour. These results indicate that reduction of plasma testosterone is unrelated to the deficit in intermale aggression in mGluR7 KO mice. Social investigating behaviour of intact mGluR7 KO mice also differed from that of wild-type mice; e.g. the KO mice showing less frequent anogenital sniffing and more frequent grooming behaviour. Testosterone replacement increased anogenital sniffing and grooming behaviour in castrated mGluR7 KO mice, while the differences were still present between castrated wild-type mice and KO mice after both underwent testosterone replacement. These results imply that reduction of plasma testosterone may partially inhibit social investigating behaviours in intact mGluR7 KO mice. Furthermore, castrated mGluR7 KO mice have smaller seminal vesicles than those of castrated wild-type mice, although seminal vesicle weights were normal in intact mice. These observations suggest that, besides testicular testosterone, some other hormone levels may be dysregulated in mGluR7 KO mice, and indicate a critical role of mGluR7 in the endocrine system. Taken together, our findings demonstrate that mGluR7 is essential for the regulation of the endocrine system, in addition to innate behaviours

  9. Role of spinal cord glutamate transporter during normal sensory transmission and pathological pain states

    Directory of Open Access Journals (Sweden)

    Stephens Robert L

    2005-10-01

    Full Text Available Abstract Glutamate is a neurotransmitter critical for spinal excitatory synaptic transmission and for generation and maintenance of spinal states of pain hypersensitivity via activation of glutamate receptors. Understanding the regulation of synaptically and non-synaptically released glutamate associated with pathological pain is important in exploring novel molecular mechanisms and developing therapeutic strategies of pathological pain. The glutamate transporter system is the primary mechanism for the inactivation of synaptically released glutamate and the maintenance of glutamate homeostasis. Recent studies demonstrated that spinal glutamate transporter inhibition relieved pathological pain, suggesting that the spinal glutamate transporter might serve as a therapeutic target for treatment of pathological pain. However, the exact function of glutamate transporter in pathological pain is not completely understood. This report will review the evidence for the role of the spinal glutamate transporter during normal sensory transmission and pathological pain conditions and discuss potential mechanisms by which spinal glutamate transporter is involved in pathological pain.

  10. Dual-energy CT (DECT) imaging of tophi and monosodium urate deposits in a patient with longstanding anorexia nervosa

    DEFF Research Database (Denmark)

    Weihe, Johan Petur; Birger Morillon, Melanie; Lambrechtsen, Jess

    Dual-energy CT (DECT) imaging of tophi and monosodium urate deposits in a patient with longstanding anorexia nervosa......Dual-energy CT (DECT) imaging of tophi and monosodium urate deposits in a patient with longstanding anorexia nervosa...

  11. Effects of added glutamate on liking for novel food flavors.

    Science.gov (United States)

    Prescott, John

    2004-04-01

    Adding glutamate to foods increases their umami quality, their acceptability and their consumption. The functional significance of this palatability is unclear. Other highly palatable substances, e.g. sugar and fats, also increase liking for novel flavors with which they are repeatedly paired, especially when ingested. This is thought to reflect the rewarding effects of sugar and fat energy, post-ingestion. To determine if a liking for novel flavors can also be conditioned using glutamate, 44 subjects rated 10 ml samples of three novel soups for liking and familiarity, both before and after seven daily exposures to each of two soup flavors-one with added monosodium l-glutamate (MSG) (0.5% w/w; MSG+) and one without (MSG-). During exposure, subjects received either a 250 ml bowl of soup (Consume group) or a 10 ml sample (Taste group). There were no significant differences as a function of samples or groups, despite some trends for changes in liking to be higher in the consumed MSG+ condition. In a second experiment, 69 subjects were divided into three groups (Consume MSG+; Consume MSG-; Taste MSG+) in which they received nine exposures to one novel soup flavor. The Consume MSG+ group showed a significantly greater increase in liking than either the Consume MSG- or the Taste MSG+ groups, which did not differ. Changes in familiarity ratings reflected amount consumed, not MSG content. Pairing glutamate with a novel flavor can condition liking for that flavor. While post-ingestive effects of glutamate may be rewarding, flavor conditioning cannot be ruled out.

  12. [Glutamate signaling and neural plasticity].

    Science.gov (United States)

    Watanabe, Masahiko

    2013-07-01

    Proper functioning of the nervous system relies on the precise formation of neural circuits during development. At birth, neurons have redundant synaptic connections not only to their proper targets but also to other neighboring cells. Then, functional neural circuits are formed during early postnatal development by the selective strengthening of necessary synapses and weakening of surplus connections. Synaptic connections are also modified so that projection fields of active afferents expand at the expense of lesser ones. We have studied the molecular mechanisms underlying these activity-dependent prunings and the plasticity of synaptic circuitry using gene-engineered mice defective in the glutamatergic signaling system. NMDA-type glutamate receptors are critically involved in the establishment of the somatosensory pathway ascending from the brainstem trigeminal nucleus to the somatosensory cortex. Without NMDA receptors, whisker-related patterning fails to develop, whereas lesion-induced plasticity occurs normally during the critical period. In contrast, mice lacking the glutamate transporters GLAST or GLT1 are selectively impaired in the lesion-induced critical plasticity of cortical barrels, although whisker-related patterning itself develops normally. In the developing cerebellum, multiple climbing fibers initially innervating given Purkinje cells are eliminated one by one until mono-innervation is achieved. In this pruning process, P/Q-type Ca2+ channels expressed on Purkinje cells are critically involved by the selective strengthening of single main climbing fibers against other lesser afferents. Therefore, the activation of glutamate receptors that leads to an activity-dependent increase in the intracellular Ca2+ concentration plays a key role in the pruning of immature synaptic circuits into functional circuits. On the other hand, glutamate transporters appear to control activity-dependent plasticity among afferent fields, presumably through adjusting

  13. Extensive neuroadaptive changes in cortical gene-transcript expressions of the glutamate system in response to repeated intermittent MDMA administration in adolescent rats

    Directory of Open Access Journals (Sweden)

    Malki Rana

    2008-04-01

    Full Text Available Abstract Background Many studies have focused on the implication of the serotonin and dopamine systems in neuroadaptive responses to the recreational drug 3,4-methylenedioxy-metamphetamine (MDMA. Less attention has been given to the major excitatory neurotransmitter glutamate known to be implicated in schizophrenia and drug addiction. The aim of the present study was to investigate the effect of repeated intermittent MDMA administration upon gene-transcript expression of the glutamate transporters (EAAT1, EAAT2-1, EAAT2-2, the glutamate receptor subunits of AMPA (GluR1, GluR2, GluR3, the glutamate receptor subunits of NMDA (NR1, NR2A and NR2B, as well as metabotropic glutamate receptors (mGluR1, mGluR2, mGluR3, mGluR5 in six different brain regions. Adolescent male Sprague Dawley rats received MDMA at the doses of 3 × 1 and 3 × 5 mg/kg/day, or 3× vehicle 3 hours apart, every 7th day for 4 weeks. The gene-transcript levels were assessed using real-time PCR validated with a range of housekeeping genes. Results The findings showed pronounced enhancements in gene-transcript expression of GluR2, mGluR1, mGluR5, NR1, NR2A, NR2B, EAAT1, and EAAT2-2 in the cortex at bregma +1.6. In the caudate putamen, mRNA levels of GluR3, NR2A, and NR2B receptor subunits were significantly increased. In contrast, the gene-transcript expression of GluR1 was reduced in the hippocampus. In the hypothalamus, there was a significant increase of GluR1, GluR3, mGluR1, and mGluR3 gene-transcript expressions. Conclusion Repeated intermittent MDMA administration induces neuroadaptive changes in gene-transcript expressions of glutamatergic NMDA and AMPA receptor subunits, metabotropic receptors and transporters in regions of the brain regulating reward-related associative learning, cognition, and memory and neuro-endocrine functions.

  14. The Lathyrus excitotoxin β-N-oxalyl-L-α,β-diaminopropionic acid is a substrate of the L-cystine/L-glutamate exchanger system xc-

    International Nuclear Information System (INIS)

    Warren, Brady A.; Patel, Sarjubhai A.; Nunn, Peter B.; Bridges, Richard J.

    2004-01-01

    β-N-Oxalyl-L-α-β-diaminopropionic acid (β-L-ODAP) is an unusual amino acid present in seeds of plants from the Lathyrus genus that is generally accepted as the causative agent underlying the motor neuron degeneration and spastic paraparesis in human neurolathyrism. Much of the neuropathology produced by β-L-ODAP appears to be a direct consequence of its structural similarities to the excitatory neurotransmitter L-glutamate and its ability to induce excitotoxicity as an agonist of non-NMDA receptors. Its actions within the CNS are, however, not limited to non-NMDA receptors, raising the likely possibility that the anatomical and cellular specificity of the neuronal damage observed in neurolathyrism may result from the cumulative activity of β-L-ODAP at multiple sites. Accumulating evidence suggests that system x c - , a transporter that mediates the exchange of L-cystine and L-glutamate, is one such site. In the present work, two distinct approaches were used to define the interactions of β-L-ODAP with system x c - : Traditional radiolabel-uptake assays were employed to quantify inhibitory activity, while fluorometrically coupled assays that follow the exchange-induced efflux of L-glutamate were used to assess substrate activity. In addition to confirming that β-L-ODAP is an effective competitive inhibitor of system x c - , we report that the compound exhibits a substrate activity comparable to that of the endogenous substrate L-cystine. The ability of system x c - to transport and accumulate β-L-ODAP identifies additional variables that could influence its toxicity within the CNS, including the ability to limit its access to EAA receptors by clearing the excitotoxin from the extracellular synaptic environment, as well as serving as a point of entry through which β-L-ODAP could have increased access to intracellular targets

  15. 21 CFR 582.4521 - Monosodium phosphate derivatives of mono- and diglycerides of edible fats or oils, or edible fat...

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Monosodium phosphate derivatives of mono- and... Monosodium phosphate derivatives of mono- and diglycerides of edible fats or oils, or edible fat-forming fatty acids. (a) Product. Monosodium phosphate derivatives of mono- and diglycerides of edible fats or...

  16. Poly - (l) - glutamic acid drug delivery system for the intravesical therapy of bladder cancer using WGA as targeting moiety.

    Science.gov (United States)

    Apfelthaler, C; Anzengruber, M; Gabor, F; Wirth, M

    2017-06-01

    In the management of bladder cancer, surgical resection of the tumour is usually followed by intravesical instillation of immunomodulatives and/or chemotherapeutics. The purpose of this local intravesical therapy is to eliminate residual malignant cells after surgical intervention. The main limitation of a localised adjuvant therapy is the insufficient concentration of the active pharmaceutical ingredient (API) in malignant cells due to the unique structure of the human urothelium making it an exclusively hard to overcome barrier in the human body. Different strategies such as electromotive drug administration or local hyperthermia are employed to ameliorate intravesical drug uptake. Previous studies on biorecognitive targeting showed promising results for lectin-, especially wheat germ agglutinin (WGA), mediated drug delivery. Here, we present a targeted conjugate that provides enough binding sites for a possible API as well as high cytoadhesive and cytoinvasive potential. The conjugate should comprise the following components: First WGA, as the targeting moiety, second poly-l-glutamic acid (PGA) as a polymeric backbone providing more than 300 possible binding sites for an API and third fluorescein cadaverine (Fc), a fluorescent dye we coupled to PGA rendering the conjugate traceable. After purification via size exclusion chromatography (SEC) the WGA containing and therefore binding conjugate was isolated from the reaction mix. In flow-cytometric and fluorimetric experiments with single cells and cell monolayers, respectively, binding and internalisation of the conjugate representing a high molecular weight (>100kDa) could be demonstrated. Fluorescent PGA without the WGA component showed neither binding nor internalisation potential. Microscopic colocalization studies with cell monolayers and single cells confirmed the cytoadhesive and cytoinvasive potential of the WGA containing conjugate. In accordance with the results of specificity studies the interaction

  17. 21 CFR 184.1521 - Monosodium phosphate derivatives of mono- and diglycerides.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Monosodium phosphate derivatives of mono- and... derivatives of mono- and diglycerides. (a) Monosodium phophate derivatives of mono- and diglycerides are composed of glyceride derivatives formed by reacting mono- and diglycerides that are derived from edible...

  18. Glutamate release from platelets: exocytosis versus glutamate transporter reversal.

    Science.gov (United States)

    Kasatkina, Ludmila A; Borisova, Tatiana A

    2013-11-01

    Platelets express neuronal and glial glutamate transporters EAAT 1-3 in the plasma membrane and vesicular glutamate transporters VGLUT 1,2 in the membrane of secretory granules. This study is focused on the assessment of non-exocytotic glutamate release, that is, the unstimulated release, heteroexchange and glutamate transporter reversal in platelets. Using the glutamate dehydrogenase assay, the absence of unstimulated release of endogenous glutamate from platelets was demonstrated, even after inhibition of glutamate transporters and cytoplasmic enzyme glutamine synthetase by dl-threo-β-benzyloxyaspartate and methionine sulfoximine, respectively. Depolarization of the plasma membrane by exposure to elevated [K(+)] did not induce the release of glutamate from platelets that was shown using the glutamate dehydrogenase assay and radiolabeled l-[(14)C]glutamate. Glutamate efflux by means of heteroexchange with transportable inhibitor of glutamate transporters dl-threo-β-hydroxyaspartate (dl-THA) was not observed. Furthermore, the protonophore cyanide-p-trifluoromethoxyphenyl-hydrazon (FCCP) and inhibitor of V-type H(+)-ATPase bafilomycin A1 also failed to stimulate the release of glutamate from platelets. However, exocytotic release of glutamate from secretory granules in response to thrombin stimulation was not prevented by elevated [K(+)], dl-THA, FCCP and bafilomycin A1. In contrast to nerve terminals, platelets cannot release glutamate in a non-exocytotic manner. Heteroexchange, transporter-mediated and unstimulated release of glutamate are not inherent to platelets. Therefore, platelets may be used as a peripheral marker/model for the analysis of glutamate uptake by brain nerve terminals only (direct function of transporters), whereas the mechanisms of glutamate release are different in platelets and nerve terminals. Glutamate is released by platelets exclusively by means of exocytosis. Also, reverse function of vesicular glutamate transporters of platelets is

  19. Biosynthetic preparation of L-(/sup 13/C)- and (/sup 15/N)glutamate by Brevibacterium flavum

    Energy Technology Data Exchange (ETDEWEB)

    Walker, T.E.; London, R.E.

    1987-01-01

    The biosynthesis of isotopically labeled L-glutamic acid by the microorganism Brevibacterium flavum was studied with a variety of carbon-13-enriched precursors. The purpose of this study was twofold: (i) to develop techniques for the efficient preparation of labeled L-glutamate with a variety of useful labeling patterns which can be used for other metabolic studies, and (ii) to better understand the metabolic events leading to label scrambling in these strains. B. flavum, which is used commercially for the production of monosodium glutamate, has the capability of utilizing glucose or acetate as a sole carbon source, and important criterion from the standpoint of developing labeling strategies. Unfortunately, singly labeled glucose precursors lead to excessive isotopic dilution which reduces their usefulness. Studies with (3-/sup 13/C)pyruvate indicate that this problem can in principle be overcome by using labeled three-carbon precursors; however, conditions could not be found which would lead to an acceptable yield of isotopically labeled L-glutamate. In contrast, (1-/sup 13/C)- or (2-/sup 13/C)acetate provides relatively inexpensive, readily available precursors for the production of selectively labeled, high enriched L-glutamate. The preparation of L-(/sup 15/N)glutamate from (/sup 15/N)ammonium sulfate was carried out and is a very effective labeling strategy. Analysis of the isotopic distribution in labeled glutamate provides details about the metabolic pathways in these interesting organisms.

  20. Glutamate affects the production of epoxyeicosanoids within the brain: The up-regulation of brain CYP2J through the MAPK-CREB signaling pathway.

    Science.gov (United States)

    Liu, Mingzhou; Zhu, Quanfei; Wu, Jinhua; Yu, Xuming; Hu, Mingbai; Xie, Xianfei; Yang, Zheqiong; Yang, Jing; Feng, Yu-Qi; Yue, Jiang

    2017-04-15

    Glutamate is the major excitatory neurotransmitter in the brain, and chronic glutamate excitotoxicity has been thought to be involved in numerous neurodegenerative diseases. We investigated the effects of glutamate at concentrations lower than the usual extrasynaptic concentrations on the production of epoxyeicosanoids mediated by brain CYP2J. Glutamate increased CYP2J2 mRNA levels in astrocytes in a dose-dependent manner, while an antagonist of the metabotropic glutamate receptor subtype 5 (mGlu5 receptor) attenuated the glutamate-induced increases in CYP2J2 levels by glutamate. Glutamate increased the binding of cAMP response element-binding protein (CREB) with the CYP2J2 promoter, and the inhibition of the MAPK signaling pathway (ERK1/2, p38, and JNK) decreased the binding of CREB with the CYP2J2 promoter following the glutamate treatment. CREB activated the CYP2J2 promoter located at -1522 to -1317bp, and CREB overexpression significantly increased CYP2J2 mRNA levels. The CYP2J2 and mGlu5 mRNA levels were higher in the frontal cortex, hippocampus, cerebellum, and brainstem in adult rats that received a subcutaneous injection of monosodium l-glutamate at 1, 3, 5, and 7days of age. The data from the partial least-squares-discriminant analysis showed the epoxyeicosanoid profile of the hippocampus from the cerebellum, brain stem, and frontal cortex. The sum of the epoxyeicosatrienoic acids (EETs) and dihydroxyeicosatrienoic acids (DHETs) was increased by 1.16-fold, 1.18-fold, and 1.19-fold in the frontal cortex, cerebellum, and brain stem, respectively, in rats treated with monosodium l-glutamate compared with the control group. The results suggest that brain CYP2J levels and CYP2J-mediated epoxyeicosanoid production can be regulated by extrasynaptic glutamate. The glutamate receptors expressed in astrocytes may mediate the regulation of drug-metabolizing enzymes and the metabolome of endogenous substances by glutamate. Copyright © 2017 Elsevier B.V. All rights

  1. Riluzole and gabapentinoids activate glutamate transporters to facilitate glutamate-induced glutamate release from cultured astrocytes

    OpenAIRE

    Yoshizumi, Masaru; Eisenach, James. C.; Hayashida, Ken-ichiro

    2011-01-01

    We have recently demonstrated that the glutamate transporter activator riluzole paradoxically enhanced glutamate-induced glutamate release from cultured astrocytes. We further showed that both riluzole and the α2δ subunit ligand gabapentin activated descending inhibition in rats by increasing glutamate receptor signaling in the locus coeruleus and hypothesized that these drugs share common mechanisms to enhance glutamate release from astrocytes. In the present study, we examined the effects o...

  2. Efficient gamma-aminobutyric acid bioconversion by employing synthetic complex between glutamate decarboxylase and glutamate/GABA antiporter in engineered Escherichia coli.

    Science.gov (United States)

    Le Vo, Tam Dinh; Ko, Ji-seun; Park, Si Jae; Lee, Seung Hwan; Hong, Soon Ho

    2013-08-01

    Gamma-aminobutyric acid (GABA) is a precursor of one of the most promising heat-resistant biopolymers, Nylon-4, and can be produced by the decarboxylation of monosodium glutamate (MSG). In this study, a synthetic protein complex was applied to improve the GABA conversion in engineered Escherichia coli. Complexes were constructed by assembling a single protein-protein interaction domain SH3 to the glutamate decarboxylase (GadA and GadB) and attaching a cognate peptide ligand to the glutamate/GABA antiporter (GadC) at the N-terminus, C-terminus, and the 233rd amino acid residue. When GadA and GadC were co-overexpressed via the C-terminus complex, a GABA concentration of 5.65 g/l was obtained from 10 g/l MSG, which corresponds to a GABA yield of 93 %. A significant increase of the GABA productivity was also observed where the GABA productivity increased 2.5-fold in the early culture period due to the introduction of the synthetic protein complex. The GABA pathway efficiency and GABA productivity were enhanced by the introduction of the complex between Gad and glutamate/GABA antiporter.

  3. [Preparation of leucine-methyl glutamate-glutamic acid copolymers].

    Science.gov (United States)

    Pan, S; Shi, F; Huang, L; Zhou, Q; Lin, Z; Yi, W

    1997-06-01

    The method for preparing leucine-methyl glutamate-glutamic acid copolymer was studied. In the first place benzyl glutamate and methyl glutamate were synthesized respectively. Then N-carboxy anhydrides (NCA) of leucine, benzyl glutamate or methyl glutamate were prepared in a closed container by phosgene-toluene solution method. After copolymerization the copolymers were debenzylated and demethylated by anhydrous hydrogen bromide. The free carboxyl group mole content in side chains of the copolymer was controlled by various standing periods following bubbling HBr. Analysis of infrared spectrogram and ultraviolet asorbance of copolymers indicated that this procedure resulted in the loss of almost all benzyl groups and some methyl groups.

  4. Glutamate monitoring in vitro and in vivo: recent progress in the field of glutamate biosensors

    DEFF Research Database (Denmark)

    Rieben, Nathalie Ines; Rose, Nadia Cherouati; Martinez, Karen Laurence

    2009-01-01

    Glutamate is the major excitatory neurotransmitter in the mammalian central nervous system. It is involved in numerous important brain functions such as learning, memory and cognition, as well as the development and plasticity of the central nervous system. In order to ensure efficient signal...... transmission, glutamate is highly compartmentalized. Prolonged elevated extracellular levels of glutamate have been shown to be excitotoxic with the result of neuronal cell death ultimately. Furthermore, alterations in glutamate levels have been shown to be linked to several neurodegenerative disorders...... such as Alzheimer's, Parkinson's and Huntington's diseases, as well as ischemic stroke and amyotrophic lateral sclerosis. Accurate measurement of glutamate levels in vitro and in vivo for a better understanding of the physiological and pathological role of glutamate in neurotransmission has remained challenging...

  5. Activation of the Glutamic Acid-Dependent Acid Resistance System in Escherichia coli BL21(DE3) Leads to Increase of the Fatty Acid Biotransformation Activity.

    Science.gov (United States)

    Woo, Ji-Min; Kim, Ji-Won; Song, Ji-Won; Blank, Lars M; Park, Jin-Byung

    The biosynthesis of carboxylic acids including fatty acids from biomass is central in envisaged biorefinery concepts. The productivities are often, however, low due to product toxicity that hamper whole-cell biocatalyst performance. Here, we have investigated factors that influence the tolerance of Escherichia coli to medium chain carboxylic acid (i.e., n-heptanoic acid)-induced stress. The metabolic and genomic responses of E. coli BL21(DE3) and MG1655 grown in the presence of n-heptanoic acid indicated that the GadA/B-based glutamic acid-dependent acid resistance (GDAR) system might be critical for cellular tolerance. The GDAR system, which is responsible for scavenging intracellular protons by catalyzing decarboxylation of glutamic acid, was inactive in E. coli BL21(DE3). Activation of the GDAR system in this strain by overexpressing the rcsB and dsrA genes, of which the gene products are involved in the activation of GadE and RpoS, respectively, resulted in acid tolerance not only to HCl but also to n-heptanoic acid. Furthermore, activation of the GDAR system allowed the recombinant E. coli BL21(DE3) expressing the alcohol dehydrogenase of Micrococcus luteus and the Baeyer-Villiger monooxygenase of Pseudomonas putida to reach 60% greater product concentration in the biotransformation of ricinoleic acid (i.e., 12-hydroxyoctadec-9-enoic acid (1)) into n-heptanoic acid (5) and 11-hydroxyundec-9-enoic acid (4). This study may contribute to engineering E. coli-based biocatalysts for the production of carboxylic acids from renewable biomass.

  6. Activation of the Glutamic Acid-Dependent Acid Resistance System in Escherichia coli BL21(DE3 Leads to Increase of the Fatty Acid Biotransformation Activity.

    Directory of Open Access Journals (Sweden)

    Ji-Min Woo

    Full Text Available The biosynthesis of carboxylic acids including fatty acids from biomass is central in envisaged biorefinery concepts. The productivities are often, however, low due to product toxicity that hamper whole-cell biocatalyst performance. Here, we have investigated factors that influence the tolerance of Escherichia coli to medium chain carboxylic acid (i.e., n-heptanoic acid-induced stress. The metabolic and genomic responses of E. coli BL21(DE3 and MG1655 grown in the presence of n-heptanoic acid indicated that the GadA/B-based glutamic acid-dependent acid resistance (GDAR system might be critical for cellular tolerance. The GDAR system, which is responsible for scavenging intracellular protons by catalyzing decarboxylation of glutamic acid, was inactive in E. coli BL21(DE3. Activation of the GDAR system in this strain by overexpressing the rcsB and dsrA genes, of which the gene products are involved in the activation of GadE and RpoS, respectively, resulted in acid tolerance not only to HCl but also to n-heptanoic acid. Furthermore, activation of the GDAR system allowed the recombinant E. coli BL21(DE3 expressing the alcohol dehydrogenase of Micrococcus luteus and the Baeyer-Villiger monooxygenase of Pseudomonas putida to reach 60% greater product concentration in the biotransformation of ricinoleic acid (i.e., 12-hydroxyoctadec-9-enoic acid (1 into n-heptanoic acid (5 and 11-hydroxyundec-9-enoic acid (4. This study may contribute to engineering E. coli-based biocatalysts for the production of carboxylic acids from renewable biomass.

  7. Glutamate Transporters in the Blood-Brain Barrier

    DEFF Research Database (Denmark)

    Helms, Hans Christian Cederberg; Nielsen, Carsten Uhd; Waagepetersen, Helle Sønderby

    2017-01-01

    The amino acid L-glutamate serves a number of roles in the central nervous system, being an excitatory neurotransmitter, metabolite, and building block in protein synthesis. During pathophysiological events, where L-glutamate homeostasis cannot be maintained, the increased brain interstitial fluid...... studies have demonstrated blood-to-brain transport of L-glutamate, at least during pathological events. A number of studies have shown that brain endothelial cells express excitatory amino acid transporters, which may account for abluminal concentrative uptake of L-glutamate into the capillary endothelial...... concentration of L-glutamate causes excitotoxicity. A tight control of the brain interstitial fluid L-glutamate levels is therefore imperative, in order to maintain optimal neurotransmission and to avoid such excitotoxicity. The blood-brain barrier, i.e., the endothelial lining of the brain capillaries...

  8. Exposure to Enriched Environment Decreases Neurobehavioral Deficits Induced by Neonatal Glutamate Toxicity

    Directory of Open Access Journals (Sweden)

    Peter Kiss

    2013-09-01

    Full Text Available Environmental enrichment is a popular strategy to enhance motor and cognitive performance and to counteract the effects of various harmful stimuli. The protective effects of enriched environment have been shown in traumatic, ischemic and toxic nervous system lesions. Monosodium glutamate (MSG is a commonly used taste enhancer causing excitotoxic effects when given in newborn animals. We have previously demonstrated that MSG leads to a delay in neurobehavioral development, as shown by the delayed appearance of neurological reflexes and maturation of motor coordination. In the present study we aimed at investigating whether environmental enrichment is able to decrease the neurobehavioral delay caused by neonatal MSG treatment. Newborn pups were treated with MSG subcutaneously on postnatal days 1, 5 and 9. For environmental enrichment, we placed rats in larger cages, supplemented with different toys that were altered daily. Normal control and enriched control rats received saline treatment only. Physical parameters such as weight, day of eye opening, incisor eruption and ear unfolding were recorded. Animals were observed for appearance of reflexes such as negative geotaxis, righting reflexes, fore- and hindlimb grasp, fore- and hindlimb placing, sensory reflexes and gait. In cases of negative geotaxis, surface righting and gait, the time to perform the reflex was also recorded daily. For examining motor coordination, we performed grid walking, footfault, rope suspension, rota-rod, inclined board and walk initiation tests. We found that enriched environment alone did not lead to marked alterations in the course of development. On the other hand, MSG treatment caused a slight delay in reflex development and a pronounced delay in weight gain and motor coordination maturation. This delay in most signs and tests could be reversed by enriched environment: MSG-treated pups kept under enriched conditions showed no weight retardation, no reflex delay in

  9. The possible interaction of dopamine system in nucleus accumbens shell and glutamate system of prelimbic region on locomotor activity in rat

    Directory of Open Access Journals (Sweden)

    Hatam Ahmadi

    2013-06-01

    Full Text Available Background: Nucleus accumbens (NAc and prefrontal cortex (PFC dopaminergic and glutamatergic systems are involved in regulating of locomotor activity behaviors. This study has investigated the interaction of NAc shell dopaminergic system and prelimbic glutamatergic systems in regulating locomotor activity and related parameters. Methods: The aim of this study was the effect the drugs injection interaction in the brain of male Wistar rats on locomotor activity and related parameters, in the order of this purpose, open field apparatus that automatically recorded locomotor activity was employed. Unilateral intra-cerebral injection of drugs was done. Results: Unilateral intra-prelimbic injection of D-AP7 (N-methyl-D-aspartic acid= NMDA receptor antagonist; 0.25, 0.5 and 1μg/μl did not alter locomotor activity behaviors. However, infusion of NMDA (0.9μg/μl in this region increased locomotor activity (P<0.01, whereas decreased rearing (P<0.01 and grooming (P<0.01 which was blocked by D-AP7 (0.25μg/μl (P<0.01. Moreover, unilateral infusion of SCH23390 (dopamine D1 receptor antagonist; 0.25, 0.5 and 1μg/μl into the left NAc shell did not alter locomotor activity. However, injection of SKF38393 (dopamine D1 receptor agonist; 4μg/μl into the left NAc shell increased locomotor activity (P<0.05 which was blocked by SCH23390 (0.25μg/μl (P<0.01. Furthermore, the subthreshold dose infusion of SCH23390 (0.25μg/μl into the left NAc shell reduced the effect of intra- prelimbic NMDA on locomotor activity (P<0.01. In addition, intra-NAc shell administration of the subthreshold dose of SKF38393 (1μg/μl potentiated the middle dose (P<0.05, whereas decreased the higher dose of intra-left prelimbic NMDA response (P<0.05 on locomotor activity. Conclusion: The results suggested a modulatory effect of the NAc shell dopaminergic system on increased locomotor activity by activating glutamate system in prelimbic.

  10. Glutamate receptor agonists

    DEFF Research Database (Denmark)

    Vogensen, Stine Byskov; Greenwood, Jeremy R; Bunch, Lennart

    2011-01-01

    stereogenic centers due to strict requirements in the agonist binding pocket of the activated state of the receptor. By contrast, there are many examples of achiral competitive antagonists. The present review addresses how stereochemistry affects the activity of glutamate receptor ligands. The review focuses...... mainly on agonists and discusses stereochemical and conformational considerations as well as biostructural knowledge of the agonist binding pockets, which is useful in the design of glutamate receptor agonists. Examples are chosen to demonstrate how stereochemistry not only determines how the agonist...

  11. Glutamate oxidation in astrocytes: Roles of glutamate dehydrogenase and aminotransferases.

    Science.gov (United States)

    McKenna, Mary C; Stridh, Malin H; McNair, Laura F; Sonnewald, Ursula; Waagepetersen, Helle S; Schousboe, Arne

    2016-12-01

    The cellular distribution of transporters and enzymes related to glutamate metabolism led to the concept of the glutamate-glutamine cycle. Glutamate is released as a neurotransmitter and taken up primarily by astrocytes ensheathing the synapses. The glutamate carbon skeleton is transferred back to the presynaptic neurons as the nonexcitatory amino acid glutamine. The cycle was initially thought to function with a 1:1 ratio between glutamate released and glutamine taken up by neurons. However, studies of glutamate metabolism in astrocytes have shown that a considerable proportion of glutamate undergoes oxidative degradation; thus, quantitative formation of glutamine from the glutamate taken up is not possible. Oxidation of glutamate is initiated by transamination catalyzed by an aminotransferase, or oxidative deamination catalyzed by glutamate dehydrogenase (GDH). We discuss methods available to elucidate the enzymes that mediate this conversion. Methods include pharmacological tools such as the transaminase inhibitor aminooxyacetic acid, studies using GDH knockout mice, and siRNA-mediated knockdown of GDH in astrocytes. Studies in brain slices incubated with [ 15 N]glutamate demonstrated activity of GDH in astrocytes in situ. These results, in conjunction with reports in the literature, support the conclusion that GDH is active in astrocytes both in culture and in vivo and that this enzyme plays a significant role in glutamate oxidation. Oxidative metabolism of glutamate, primarily mediated by GDH, but also by transamination by aspartate aminotransferase, provides considerably more energy than is required to maintain the activity of the high-affinity glutamate transporters needed for efficient removal of glutamate from the synaptic cleft. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  12. Curcumin-Protected PC12 Cells Against Glutamate-Induced Oxidative Toxicity

    OpenAIRE

    Chang, Chi-Huang; Chen, Hua-Xin; Yü, George; Peng, Chiung-Chi; Peng, Robert Y.

    2014-01-01

    Glutamate is a major excitatory neurotransmitter present in the central nervous system. The glutamate/cystine antiporter system xc– connects the antioxidant defense with neurotransmission and behaviour. Overactivation of ionotropic glutamate receptors induces neuronal death, a pathway called excitotoxicity. Glutamate-induced oxidative stress is a major contributor to neurodegenerative diseases including cerebral ischemia, Alzheimer’s and Huntington’s disease. Curcuma has a wide spectrum of bi...

  13. Glutamate-system defects behind psychiatric manifestations in a familial hemiplegic migraine type 2 disease-mutation mouse model

    DEFF Research Database (Denmark)

    Bøttger, Pernille; Glerup, Simon; Gesslein, Bodil

    2016-01-01

    )) phenocopy several FHM2-relevant disease traits e.g., by mimicking mood depression and OCD. In vitro studies showed impaired glutamate uptake in hippocampal mixed astrocyte-neuron cultures from α2(G301R/G301R) E17 embryonic mice, and moreover, induction of cortical spreading depression (CSD) resulted......Migraine is a complex brain disorder, and understanding the complexity of this prevalent disease could improve quality of life for millions of people. Familial Hemiplegic Migraine type 2 (FHM2) is a subtype of migraine with aura and co-morbidities like epilepsy/seizures, cognitive impairments...... and psychiatric manifestations, such as obsessive-compulsive disorder (OCD). FHM2 disease-mutations locate to the ATP1A2 gene encoding the astrocyte-located α2-isoform of the sodium-potassium pump (α2Na(+)/K(+)-ATPase). We show that knock-in mice heterozygous for the FHM2-associated G301R-mutation (α2(+/G301R...

  14. Phase IV testing of monosodium titanate adsorption with radioactive waste

    Energy Technology Data Exchange (ETDEWEB)

    Hobbs, D.T.

    1999-12-08

    Testing examined the extent and rate of strontium, plutonium, uranium, and neptunium removal from radioactive waste solutions at 4.5M and 7.5M in Na concentration by adsorption onto monosodium titanate (MST) at 0.2 g/L. Results indicate that the extents and rates of strontium, plutonium, and neptunium removal in radioactive waste solutions agree well with those previously measured using simulated waste solutions. Uranium removal in the 7.5M Na radioactive waste solution proved similar to that observed with simulated waste solutions. Uranium removal in the 4.5M Na radioactive waste solution proved lower than expected from previous simulant tests. The authors conclude that MST adsorption data obtained from simulated waste solutions provide reliable predictions for use in facility design and flowsheet modeling studies in the Salt Disposition Alternatives program.

  15. Glutamate oxidation in astrocytes: Roles of glutamate dehydrogenase and aminotransferases

    DEFF Research Database (Denmark)

    McKenna, Mary C; Stridh, Malin H; McNair, Laura Frendrup

    2016-01-01

    to the presynaptic neurons as the nonexcitatory amino acid glutamine. The cycle was initially thought to function with a 1:1 ratio between glutamate released and glutamine taken up by neurons. However, studies of glutamate metabolism in astrocytes have shown that a considerable proportion of glutamate undergoes...... the enzymes that mediate this conversion. Methods include pharmacological tools such as the transaminase inhibitor aminooxyacetic acid, studies using GDH knockout mice, and siRNA-mediated knockdown of GDH in astrocytes. Studies in brain slices incubated with [15N]glutamate demonstrated activity of GDH......The cellular distribution of transporters and enzymes related to glutamate metabolism led to the concept of the glutamate–glutamine cycle. Glutamate is released as a neurotransmitter and taken up primarily by astrocytes ensheathing the synapses. The glutamate carbon skeleton is transferred back...

  16. Application of a glutamate microsensor to brain tissue

    NARCIS (Netherlands)

    Oldenziel, Weite Hendrik

    2006-01-01

    The amino acid l-glutamate is one of the most important neurotransmitters in the central nervous system (CNS). It is involved in many physiological processes and consequently in the pathophysiology of several psychiatric, neurological and neurodegenerative disorders. Therefore, glutamate is an

  17. Glutamate receptors in NG2-glial cells: gene profiling and functional changes after ischemic brain injury

    OpenAIRE

    Waloschková, Eliška

    2017-01-01

    Glutamate is the main excitatory neurotransmitter in the mammalian brain and its transmission is responsible for higher brain functions, such as learning, memory and cognition. Glutamate action is mediated by a variety of glutamate receptors, though their properties were until now studied predominantly in neurons. Glutamate receptors are expressed also in NG2-glia, however their role under physiological conditions as well as in pathological states of the central nervous system is not fully un...

  18. Chronic glutamate toxicity in neurodegenerative diseases-what is the evidence?

    Directory of Open Access Journals (Sweden)

    Pamela eMaher

    2015-12-01

    Full Text Available Together with aspartate, glutamate is the major excitatory neurotransmitter in the brain. Glutamate binds and activates both ligand-gated ion channels (ionotropic glutamate receptors and a class of G-protein coupled receptors (metabotropic glutamate receptors. Although the intracellular glutamate concentration in the brain is in the millimolar range, the extracellular glutamate concentration is kept in the low micromolar range by the action of excitatory amino acid transporters that import glutamate and aspartate into astrocytes and neurons. Excess extracellular glutamate may lead to excitotoxicity in vitro and in vivo in acute insults like ischemic stroke via the overactivation of ionotropic glutamate receptors. In addition, chronic excitotoxicity has been hypothesized to play a role in numerous neurodegenerative diseases including amyotrophic lateral sclerosis, Alzheimer’s disease and Huntington’s disease. Based on this hypothesis, a good deal of effort has been devoted to develop and test drugs that either inhibit glutamate receptors or decrease extracellular glutamate. In this review, we provide an overview of the different pathways that are thought to lead to an over-activation of the glutamatergic system and glutamate toxicity in neurodegeneration. In addition, we summarize the available experimental evidence for glutamate toxicity in animal models of neurodegenerative diseases.

  19. Glucose replaces glutamate as energy substrate to fuel glutamate uptake in glutamate dehydrogenase-deficient astrocytes.

    Science.gov (United States)

    Pajęcka, Kamilla; Nissen, Jakob D; Stridh, Malin H; Skytt, Dorte M; Schousboe, Arne; Waagepetersen, Helle S

    2015-07-01

    Cultured astrocytes treated with siRNA to knock down glutamate dehydrogenase (GDH) were used to investigate whether this enzyme is important for the utilization of glutamate as an energy substrate. By incubation of these cells in media containing different concentrations of glutamate (range 100-500 µM) in the presence or in the absence of glucose, the metabolism of these substrates was studied by using tritiated glutamate or 2-deoxyglucose as tracers. In addition, the cellular contents of glutamate and ATP were determined. The astrocytes were able to maintain physiological levels of ATP regardless of the expression level of GDH and the incubation condition, indicating a high degree of flexibility with regard to regulatory mechanisms involved in maintaining an adequate energy level in the cells. Glutamate uptake was found to be increased in these cells when exposed to increasing levels of extracellular glutamate independently of the GDH expression level. Moreover, increased intracellular glutamate content was observed in the GDH-deficient cells after a 2-hr incubation in the presence of 100 µM glutamate. It is significant that GDH-deficient cells exhibited an increased utilization of glucose in the presence of 250 and 500 µM glutamate, monitored as an increase in the accumulation of tritiated 2-deoxyglucose-6-phosphate. These findings underscore the importance of the expression level of GDH for the ability to utilize glutamate as an energy source fueling its own energy-requiring uptake. © 2015 Wiley Periodicals, Inc.

  20. Evidence for synergistic control of glutamate biosynthesis by glutamate dehydrogenases and glutamate in Bacillus subtilis.

    Science.gov (United States)

    Stannek, Lorena; Thiele, Martin J; Ischebeck, Till; Gunka, Katrin; Hammer, Elke; Völker, Uwe; Commichau, Fabian M

    2015-09-01

    In the Gram-positive bacterium, Bacillus subtilis glutamate is synthesized by the glutamine synthetase and the glutamate synthase (GOGAT). During growth with carbon sources that exert carbon catabolite repression, the rocG glutamate dehydrogenase (GDH) gene is repressed and the transcription factor GltC activates the expression of the GOGAT encoding gltAB genes. In the presence of amino acids of the glutamate family, the GDH RocG is synthesized and the enzyme prevents GltC from binding to DNA. The dual control of glutamate biosynthesis allows the efficient utilization of the available nutrients. Here we provide genetic and biochemical evidence that, like RocG, also the paralogous GDH GudB can inhibit the transcription factor GltC, thereby controlling glutamate biosynthesis. Contradictory previous observations show that high level of GDH activity does not result in permanent inhibition of GltC. By controlling the intracellular levels of glutamate through feeding with exogenous arginine, we observed that the GDH-dependent control of GltC and thus expression of the gltAB genes inversely correlates with the glutamate pool. These results suggest that the B. subtilis GDHs RocG and GudB in fact act as glutamate sensors. In conclusion, the GDH-mediated control of glutamate biosynthesis seems to depend on the intracellular glutamate concentration. © 2015 Society for Applied Microbiology and John Wiley & Sons Ltd.

  1. Glutamate and Neurotrophic Factors in Neuronal Plasticity and Disease

    Science.gov (United States)

    Mattson, Mark P.

    2008-01-01

    Glutamate’s role as a neurotransmitter at synapses has been known for 40 years, but glutamate has since been shown to regulate neurogenesis, neurite outgrowth, synaptogenesis and neuron survival in the developing and adult mammalian nervous system. Cell surface glutamate receptors are coupled to Ca2+ influx and release from endoplasmic reticulum stores which causes rapid (kinase- and protease-mediated) and delayed (transcription-dependent) responses that change the structure and function of neurons. Neurotrophic factors and glutamate interact to regulate developmental and adult neuroplasticity. For example, glutamate stimulates the production of brain-derived neurotrophic factor (BDNF) which, in turn, modifies neuronal glutamate sensitivity, Ca2+ homeostasis and plasticity. Neurotrophic factors may modify glutamate signalling directly, by changing the expression of glutamate receptor subunits and Ca2+-regulating proteins, and also indirectly by inducing the production of antioxidant enzymes, energy-regulating proteins and anti-apoptotic Bcl2 family members. Excessive activation of glutamate receptors, under conditions of oxidative and metabolic stress, may contribute to neuronal dysfunction and degeneration in diseases ranging from stroke and Alzheimer’s disease to psychiatric disorders. By enhancing neurotrophic factor signalling, environmental factors such as exercise and dietary energy restriction, and chemicals such as antidepressants may optimize glutamatergic signalling and protect against neurological disorders. PMID:19076369

  2. A review of glutamate's role in traumatic brain injury mechanisms

    Science.gov (United States)

    Good, Cameron H.

    2013-05-01

    Glutamate is the primary excitatory neurotransmitter used by the central nervous system (CNS) for synaptic communication, and its extracellular concentration is tightly regulated by glutamate transporters located on nearby astrocytes. Both animal models and human clinical studies have demonstrated elevated glutamate levels immediately following a traumatic brain event, with the duration and severity of the rise corresponding to prognosis. This rise in extracellular glutamate likely results from a combination of excessive neurotransmitter release from damaged neurons and down regulation of uptake mechanisms in local astrocytes. The immediate results of a traumatic event can lead to necrotic tissue in severely injured regions, while prolonged increases in excitatory transmission can cause secondary excitotoxic injury through activation of delayed apoptotic pathways. Initial TBI animal studies utilized a variety of broad glutamate receptor antagonists to successfully combat secondary injury mechanisms, but unfortunately this same strategy has proven inconclusive in subsequent human trials due to deleterious side effects and heterogeneity of injuries. More recent treatment strategies have utilized specific glutamate receptor subunit antagonists in an effort to minimize side effects and have shown promising results. Future challenges will be detecting the concentration and kinetics of the glutamate rise following injury, determining which patient populations could benefit from antagonist treatment based on their extracellular glutamate concentrations and when drugs should be administered to maximize efficacy.

  3. Phosphene perception is due to the ultra-weak photon emission produced in various parts of the visual system: glutamate in the focus.

    Science.gov (United States)

    Császár, Noémi; Scholkmann, Felix; Salari, Vahid; Szőke, Henrik; Bókkon, István

    2016-04-01

    Phosphenes are experienced sensations of light, when there is no light causing them. The physiological processes underlying this phenomenon are still not well understood. Previously, we proposed a novel biopsychophysical approach concerning the cause of phosphenes based on the assumption that cellular endogenous ultra-weak photon emission (UPE) is the biophysical cause leading to the sensation of phosphenes. Briefly summarized, the visual sensation of light (phosphenes) is likely to be due to the inherent perception of UPE of cells in the visual system. If the intensity of spontaneous or induced photon emission of cells in the visual system exceeds a distinct threshold, it is hypothesized that it can become a conscious light sensation. Discussing several new and previous experiments, we point out that the UPE theory of phosphenes should be really considered as a scientifically appropriate and provable mechanism to explain the physiological basis of phosphenes. In the present paper, we also present our idea that some experiments may support that the cortical phosphene lights are due to the glutamate-related excess UPE in the occipital cortex.

  4. Glucose replaces glutamate as energy substrate to fuel glutamate uptake in glutamate dehydrogenase-deficient astrocytes

    DEFF Research Database (Denmark)

    Pajęcka, Kamilla; Nissen, Jakob D; Stridh, Malin H

    2015-01-01

    Cultured astrocytes treated with siRNA to knock down glutamate dehydrogenase (GDH) were used to investigate whether this enzyme is important for the utilization of glutamate as an energy substrate. By incubation of these cells in media containing different concentrations of glutamate (range 100......-500 µM) in the presence or in the absence of glucose, the metabolism of these substrates was studied by using tritiated glutamate or 2-deoxyglucose as tracers. In addition, the cellular contents of glutamate and ATP were determined. The astrocytes were able to maintain physiological levels of ATP...... regardless of the expression level of GDH and the incubation condition, indicating a high degree of flexibility with regard to regulatory mechanisms involved in maintaining an adequate energy level in the cells. Glutamate uptake was found to be increased in these cells when exposed to increasing levels...

  5. Non-woven nanofiber mats - a new perspective for experimental studies of the central nervous system?

    Science.gov (United States)

    Rafalowska, Janina; Sulejczak, Dorota; Chrapusta, Stanisław J; Gadamski, Roman; Taraszewska, Anna; Nakielski, Paweł; Kowalczyk, Tomasz; Dziewulska, Dorota

    2014-01-01

    (Sub)chronic local drug application is clearly superior to systemic administration, but may be associated with substantial obstacles, particularly regarding the applications to highly sensitive central nervous system (CNS) structures that are shielded from the outer environment by the blood-brain barrier. Violation of the integrity of the barrier and CNS tissues by a permanently implanted probe or cannula meant for prolonged administration of drugs into specific CNS structures can be a severe confounding factor because of the resulting inflammatory reactions. In this study, we tested the utility of a novel way for (sub)chronic local delivery of highly active (i.e., used in very low amounts) drugs to the rat spinal cord employing a non-woven nanofiber mat dressing. To this end, we compared the morphology and motoneuron ( + ) counts in spinal cord cervical and lumbar segments between rats with glutamate-loaded nanofiber mats applied to the lumbar enlargement and rats with analogical implants carrying no glutamate. Half of the rats with glutamate-loaded implants were given daily valproate treatment to test its potential for counteracting the detrimental effects of glutamate excess. The mats were prepared in-house by electrospinning of an emulsion made of a solution of the biocompatible and biodegradable poly(L-lactide-co-caprolactone) polymer in a mixture of organic solvents, an aqueous phase with or without monosodium glutamate, and sodium dodecyl sulfate as an emulsifier; the final glutamate content was 1.4 µg/mg of the mat. Three weeks after mat implantation there was no inflammation or considerable damage of the spinal cord motoneuron population in the rats with the subarachnoid dressing of a glutamate-free mat, whereas the spinal cords of the rats with glutamate-loaded nanofiber mats showed clear symptoms of excitotoxic damage and a substantial increase in dying/damaged motoneuron numbers in both segments studied. The rats given systemic valproate

  6. Micelles Based on Biodegradable Poly(L-glutamic acid)-b-Polylactide with Paramagnetic Gd Ions Chelated to the Shell Layer as a Potential Nanoscale MRI-Visible Delivery System

    OpenAIRE

    Zhang, Guodong; Zhang, Rui; Wen, Xiaoxia; Li, Li; Li, Chun

    2007-01-01

    There is much interest in the development of nanoscale drug delivery system with MRI visibility to optimize the delivery efficiency and therapeutic efficacy under image guidance. Here we report on the successful fabrication of nanoscale micelles based on biodegradable poly(L-glutamic acid)-b-polylactide (PG-b-PLA) block copolymer with paramagnetic Gd3+ ions chelated to their shell. (PG-b-PLA) was synthesized by sequential polymerization reactions: anionic polymerization of L-lactide followed ...

  7. Impact of soil organic carbon on monosodium methyl arsenate (MSMA) sorption and species transformation.

    Science.gov (United States)

    Ou, Ling; Gannon, Travis W; Polizzotto, Matthew L

    2017-11-01

    Monosodium methyl arsenate (MSMA), a common arsenical herbicide, is a major contributor of anthropogenic arsenic (As) to the environment. Uncertainty about controls on MSMA fate and the rates and products of MSMA species transformation limits effective MSMA regulation and management. The main objectives of this research were to quantify the kinetics and mechanistic drivers of MSMA species transformation and removal from solution by soil. Laboratory MSMA incubation studies with two soils and varying soil organic carbon (SOC) levels were conducted. Arsenic removal from solution was more extensive and faster in sandy clay loam incubations than sand incubations, but for both systems, As removal was biphasic, with initially fast removal governed by sorption, followed by slower As removal limited by species transformation. Dimethylarsinic acid was the dominant product of species transformation at first, but inorganic As(V) was the ultimate transformation product by experiment ends. SOC decreased As removal and enhanced As species transformation, and SOC content had linear relationships with As removal rates (R 2  = 0.59-0.95) for each soil and reaction phase. These results reveal the importance of edaphic conditions on inorganic As production and overall mobility of As following MSMA use, and such information should be considered in MSMA management and regulatory decisions. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Involvement of serotonergic system in the effect of a metabotropic glutamate 5 receptor antagonist in the novelty-suppressed feeding test

    Directory of Open Access Journals (Sweden)

    Kenichi Fukumoto

    2015-01-01

    Full Text Available The blockade of metabotropic glutamate 5 (mGlu5 receptor has been reported to exert antidepressant effects in several animal models. We previously reported that both ketamine and an mGlu5 receptor antagonist exerted an effect in a novelty-suppressed feeding (NSF test, and that the effect of ketamine may be mediated through an α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA receptor-dependent increase in serotonergic transmission. However, the involvement of the serotonergic system in the effect of mGlu5 receptor antagonists in the NSF test is not well understood. Therefore, we examined the roles of the serotonergic system in the effect of an mGlu5 receptor antagonist, 6-methyl-2-(phenylethynylpyridine hydrochloride (MPEP, in the NSF test in mice. The administration of MPEP significantly shortened the latency to feed, which was not attenuated by the AMPA receptor antagonist, 2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzo[f]quinoxaline-7-sulfonamide (NBQX. The effect of MPEP was abolished by the tryptophan hydroxylase inhibitor, para-chlorophenylalanine (PCPA. Moreover, the effect of MPEP was blocked by a serotonin (5-HT2A/2C receptor antagonist, ritanserin, but not by a 5-HT1A receptor antagonist, N-{2-[4-(2-methoxyphenyl-1-piperazinyl]ethyl}-N-(2-pyridynyl cyclohexane-carboxamide (WAY100635. These results suggest that the effect of an mGlu5 receptor antagonist may be mediated by the serotonergic system, including the stimulation of the 5-HT2A/2C receptor, in an AMPA receptor-independent manner in the NSF test.

  9. Involvement of serotonergic system in the effect of a metabotropic glutamate 5 receptor antagonist in the novelty-suppressed feeding test.

    Science.gov (United States)

    Fukumoto, Kenichi; Chaki, Shigeyuki

    2015-01-01

    The blockade of metabotropic glutamate 5 (mGlu5) receptor has been reported to exert antidepressant effects in several animal models. We previously reported that both ketamine and an mGlu5 receptor antagonist exerted an effect in a novelty-suppressed feeding (NSF) test, and that the effect of ketamine may be mediated through an α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor-dependent increase in serotonergic transmission. However, the involvement of the serotonergic system in the effect of mGlu5 receptor antagonists in the NSF test is not well understood. Therefore, we examined the roles of the serotonergic system in the effect of an mGlu5 receptor antagonist, 6-methyl-2-(phenylethynyl)pyridine hydrochloride (MPEP), in the NSF test in mice. The administration of MPEP significantly shortened the latency to feed, which was not attenuated by the AMPA receptor antagonist, 2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzo[f]quinoxaline-7-sulfonamide (NBQX). The effect of MPEP was abolished by the tryptophan hydroxylase inhibitor, para-chlorophenylalanine (PCPA). Moreover, the effect of MPEP was blocked by a serotonin (5-HT)2A/2C receptor antagonist, ritanserin, but not by a 5-HT1A receptor antagonist, N-{2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl}-N-(2-pyridynyl) cyclohexane-carboxamide (WAY100635). These results suggest that the effect of an mGlu5 receptor antagonist may be mediated by the serotonergic system, including the stimulation of the 5-HT2A/2C receptor, in an AMPA receptor-independent manner in the NSF test. Copyright © 2014 Japanese Pharmacological Society. Production and hosting by Elsevier B.V. All rights reserved.

  10. Glutamic acid as anticancer agent: An overview

    OpenAIRE

    Dutta, Satyajit; Ray, Supratim; Nagarajan, K.

    2013-01-01

    The objective of the article is to highlight various roles of glutamic acid like endogenic anticancer agent, conjugates to anticancer agents, and derivatives of glutamic acid as possible anticancer agents. Besides these emphases are given especially for two endogenous derivatives of glutamic acid such as glutamine and glutamate. Glutamine is a derivative of glutamic acid and is formed in the body from glutamic acid and ammonia in an energy requiring reaction catalyzed by glutamine synthase. I...

  11. Glutamate mechanisms underlying opiate memories

    NARCIS (Netherlands)

    Peters, J.; de Vries, T.J.

    2012-01-01

    As the major excitatory neurotransmitter in the brain, glutamate plays an undisputable integral role in opiate addiction. This relates, in part, to the fact that addiction is a disorder of learning and memory, and glutamate is required for most types of memory formation. As opiate addiction

  12. Micelles based on biodegradable poly(L-glutamic acid)-b-polylactide with paramagnetic Gd ions chelated to the shell layer as a potential nanoscale MRI-visible delivery system.

    Science.gov (United States)

    Zhang, Guodong; Zhang, Rui; Wen, Xiaoxia; Li, Li; Li, Chun

    2008-01-01

    There is much interest in the development of a nanoscale drug delivery system with MRI visibility to optimize the delivery efficiency and therapeutic efficacy under image guidance. Here we report on the successful fabrication of nanoscale micelles based on biodegradable poly( L-glutamic acid)- b-polylactide (PG- b-PLA) block copolymer with paramagnetic Gd3+ ions chelated to their shell. PG- b-PLA was synthesized by sequential polymerization reactions: anionic polymerization of L-lactide followed by ring-opening polymerization of benzyl glutamate N-carboxylic anhydride. The metal chelator p-aminobenzyldiethylenetriaminepenta(acetic acid) (DTPA) was readily conjugated to the side chain carboxylic acids of poly( L-glutamic acid). The resulting copolymer formed spherical micelles in aqueous solution with an average diameter of 230 nm at pH 7.4. The size of PG(DTPA)- b-PLA micelles decreased with increasing pH value. DTPA-Gd chelated to the shell layer of the micelles exhibited significantly higher spin-lattice relaxivity (r1) than a small-molecular-weight MRI contrast agent, indicating that water molecules could readily access the Gd ions in the micelles. Because of the presence of multiple carboxylic acid functional groups in the shell layer, polymeric micelles based on biodegradable PG(DTPA-Gd)- b-PLA may be a suitable platform for the development of MRI-visible, targeted nanoscale drug delivery systems.

  13. Elevated AT1 protein but lower angiotensin II binding in adipose tissue of rats with monosodium glutamate-induced obesity

    Czech Academy of Sciences Publication Activity Database

    Pintérová, L.; Železná, Blanka; Macho, L.; Ježová, D.; Zórad, Š.

    2001-01-01

    Roč. 25, Suppl. 3 (2001), s. S22 ISSN 0307-0565. [International Symposium on Obesity and Hypertension. 25.10.2001-27.10.2001, Berlin] Institutional research plan: CEZ:AV0Z5052915 Subject RIV: EB - Genetics ; Molecular Biology

  14. PENGARUH PEMBERIAN MONOSODIUM GLUTAMAT (MSG PADA TIKUS JANTAN (Rattus Norvegicus TERHADAP FSH DAN LH

    Directory of Open Access Journals (Sweden)

    Zulkarnain Edward

    2010-09-01

    Bonferroni.Hasil penelitian yang diperoleh bahwa pemberian MSG dengan dosis 4800 mg/kgbb/hari, 7200 mg/kgbb/hari dan 9600 mg/kgbb/hari menunjukkan pengaruh yang bermakna terhadap penurunan kadar FSH (p=0,000 dan LH (p=0,000, namun pada uji Multiple Comparissons Bonferroni didapatkan antar kelompok pada FSH belum menunjukan pengaruh yang bermakna (p˃0,05 sedangkan pada LH antar kelompok perlakuan, antara P1, P2 tidak didapatkan perbedaan yangARTIKEL PENELITIAN161bermakna (p˃0,05, P1 dan P3 didapatkan perbedaan yang bermakna (p˂0,05 dan P2 dengan P3 didapatkan perbedaan yang bermakna (p˂0,05.Penelitian ini menyimpulkan bahwa pemberian MSG terhadap tikus jantan dapat menurunkan kadar FSH dan LH. Disarankan untuk dilakukan penelitian lanjutan untuk mendapatkan dosis minimal yang dapat memberikan perubahan kadar FSH dan LH.Kata kunci : MSG, FSH, LHAbstractThe progress of information and technology gave the influence in society and life styles, included the change of goods and provision system, which become more prefered to fast food, meal packaged and preserved, then firmly sells and found in traditional market and swalayan. The continously use of additional substance firmly seems everywhere, one of them is something used as flavoring, L-Glutamat acid which used in a mineral salt that is Monosodium Glutamat (MSG. Many kinds of MSG brand known by people as ajinomoto, vetsin, micin, sasa, miwon, etc.MSG is a mineral salt of monosodium with glutamat acid that firmly used as the food flavoring for appetizer. The distribution of MSG causing the hormonal interference for the animal trial, which the glutamat ion in portal sirculation will effect the hipotalamus in producting the GnRH which were next would effected the anterior hypofise in producting the FSH and LH. The FSH function is to do working for seminiferus tubular espeially for sertoli cells to increase the spermatogenesis, then LH functioned to Leydig to control the testosteron secretion.This research experimently done with

  15. Substrate and Cation Binding Mechanism of Glutamate Transporter Homologs

    NARCIS (Netherlands)

    Jensen, Sonja

    2017-01-01

    Glutamate transporters and their homologs are membrane proteins that transport glutamate and aspartate together with sodium ions and/or protons. Human glutamate transporters remove the neurotransmitter glutamate after signal transmission. Therefore, glutamate transporters play a great role in

  16. Phase I Technical Report for the Engineering of Monosodium Titanate

    International Nuclear Information System (INIS)

    NASH, CHARLES

    2004-01-01

    Monosodium titanate (MST) is an inorganic adsorbent that effectively removes strontium, plutonium, uranium, and other trace elements from alkaline salt supernate. Current plans use the MST in batch contact processes to treat Savannah River Site (SRS) waste solutions that require 90Sr and actinide removal to meet low level disposal criteria. More effective use of MST may be realized if the MST could be engineered into a form suitable for a continuous treatment process such as an adsorption column. The main benefits of column operation are (1) enhanced loading due to equilibration with feed adsorbate levels versus product levels, and (2) a small footprint relative to that of a batch contact tank. The current baseline MST material features particles of nominally 0.5-35 micron in size, which are much too fine for use in an adsorption column. An extensive review of the literature and consultation with technical experts identified candidate methods to produce engineered forms of MST. From this list a review team selected five candidate methods for further study. Laboratory syntheses at Savannah River National Laboratory (SRNL) and offsite produced representative samples for characterization and performance testing. Testing identified two suitable methods. The two methods include internal gelation, which is patented technology of Oak Ridge National Laboratory, and internal hydrolysis, a method in which the MST is produced within a porous substrate. A commercial sodium titanate, SrTreat(R), produced by Fortum Engineering (Finland), demonstrated good performance as well although plutonium removal kinetics appeared much slower than observed for the other engineered MST materials

  17. Monosodium urate crystals induce oxidative stress in human synoviocytes.

    Science.gov (United States)

    Zamudio-Cuevas, Yessica; Martínez-Flores, Karina; Fernández-Torres, Javier; Loissell-Baltazar, Yahir A; Medina-Luna, Daniel; López-Macay, Ambar; Camacho-Galindo, Javier; Hernández-Díaz, Cristina; Santamaría-Olmedo, Mónica G; López-Villegas, Edgar Oliver; Oliviero, Francesca; Scanu, Anna; Cerna-Cortés, Jorge Francisco; Gutierrez, Marwin; Pineda, Carlos; López-Reyes, Alberto

    2016-05-21

    Gout is the most common inflammatory arthropathy of metabolic origin and it is characterized by intense inflammation, the underlying mechanisms of which are unknown. The aim of this study was to evaluate the oxidative stress in human fibroblast-like synoviocytes (FLS) exposed to monosodium urate (MSU) crystals, which trigger an inflammatory process. Human FLS isolated from synovial tissue explants were stimulated with MSU crystals (75 μg/mL) for 24 h. Cellular viability was evaluated by crystal violet staining, apoptosis was assessed using Annexin V, and the cellular content of reactive oxygen species (ROS) and nitrogen species (RNS) (O2 (-), H2O2, NO) was assessed with image-based cytometry and fluorometric methods. In order to determine protein oxidation levels, protein carbonyls were detected through oxyblot analysis, and cell ultrastructural changes were assessed by transmission electron microscopy. The viability of FLS exposed to MSU crystals decreased by 30 % (P crystals exhibited a 2.1-fold increase in H2O2 content and a 1.5-fold increase in O2 (-) and NO levels. Oxyblots revealed that the spots obtained from FLS protein lysates exposed to MSU crystals exhibited protein carbonyl immunoreactivity, which reflects the presence of oxidatively modified proteins. Concomitantly, MSU crystals triggered the induction of changes in the morphostructure of FLS, such as the thickening and discontinuity of the endoplasmic reticulum, and the formation of vacuoles and misfolded glycoproteins. Our results prove that MSU crystals induce the release of ROS and RNS in FLS, subsequently oxidizing proteins and altering the cellular oxidative state of the endoplasmic reticulum, which results in FLS apoptosis.

  18. Glutamic acid and its derivatives: candidates for rational design of anticancer drugs.

    Science.gov (United States)

    Ali, Imran; Wani, Waseem A; Haque, Ashanul; Saleem, Kishwar

    2013-05-01

    Throughout the history of human civilizations, cancer has been a major health problem. Its treatment has been interesting but challenging to scientists. Glutamic acid and its derivative glutamine are known to play interesting roles in cancer genesis, hence, it was realized that structurally variant glutamic acid derivatives may be designed and developed and, might be having antagonistic effects on cancer. The present article describes the state-of-art of glutamic acid and its derivatives as anticancer agents. Attempts have been made to explore the effectivity of drug-delivery systems based on glutamic acid for the delivery of anticancer drugs. Moreover, efforts have also been made to discuss the mechanism of action of glutamic acid derivatives as anticancer agents, clinical applications of glutamic acid derivatives, as well as recent developments and future perspectives of glutamic acid drug development have also been discussed.

  19. Preservation of glutamic acid-iron chelate into montmorillonite to efficiently degrade Reactive Blue 19 in a Fenton system under sunlight irradiation at neutral pH

    Science.gov (United States)

    Huang, Zhujian; Wu, Pingxiao; Gong, Beini; Yang, Shanshan; Li, Hailing; Zhu, Ziao; Cui, Lihua

    2016-05-01

    To further enhance the visible light responsive property and the chemical stability of Fe/clay mineral catalysts, glutamic acid-iron chelate intercalated montmorillonite (G-Fe-Mt) was developed. The physiochemical properties of G-Fe-Mt were investigated by X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), UV-vis diffuse reflectance spectroscopy (DRS), etc. The results showed that glutamic acid-iron chelates were successfully intercalated into the gallery of montmorillonite and the intercalated glutamic acid-iron chelate molecules were well preserved. The product G-Fe-Mt displayed excellent catalytic performance in heterogeneous photo-Fenton reaction under sunlight irradiation at acidic and neutral pH values. The chelation and the visible light responsiveness of glutamic acid produce a synergistic effect leading to greatly enhanced sunlight-Fenton reaction catalyzed by the heterogeneous G-Fe-Mt under neutral pH. G-Fe-Mt is a promising catalyst for advanced oxidation processes.

  20. Preservation of glutamic acid-iron chelate into montmorillonite to efficiently degrade Reactive Blue 19 in a Fenton system under sunlight irradiation at neutral pH

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Zhujian [College of Natural Resources and Environment, South China Agricultural University, Guangzhou 510642 (China); Wu, Pingxiao, E-mail: pppxwu@scut.edu.cn [School of Environment and Energy, South China University of Technology, Guangzhou Higher Education Mega Centre, Guangzhou 510006 (China); The Key Lab of Pollution Control and Ecosystem Restoration in Industry Clusters, Ministry of Education, Guangzhou 510006 (China); Gong, Beini; Yang, Shanshan; Li, Hailing [School of Environment and Energy, South China University of Technology, Guangzhou Higher Education Mega Centre, Guangzhou 510006 (China); Zhu, Ziao; Cui, Lihua [College of Natural Resources and Environment, South China Agricultural University, Guangzhou 510642 (China)

    2016-05-01

    Graphical abstract: - Highlights: • G–Fe chelate molecules were well preserved into montmorillonite. • The product shows an excellent catalytic activity under sunlight at neutral pH value. • G–Fe–Mt is a promising catalyst for advanced oxidation processes. - Abstract: To further enhance the visible light responsive property and the chemical stability of Fe/clay mineral catalysts, glutamic acid-iron chelate intercalated montmorillonite (G–Fe–Mt) was developed. The physiochemical properties of G–Fe–Mt were investigated by X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), UV–vis diffuse reflectance spectroscopy (DRS), etc. The results showed that glutamic acid-iron chelates were successfully intercalated into the gallery of montmorillonite and the intercalated glutamic acid-iron chelate molecules were well preserved. The product G–Fe–Mt displayed excellent catalytic performance in heterogeneous photo-Fenton reaction under sunlight irradiation at acidic and neutral pH values. The chelation and the visible light responsiveness of glutamic acid produce a synergistic effect leading to greatly enhanced sunlight-Fenton reaction catalyzed by the heterogeneous G–Fe–Mt under neutral pH. G–Fe–Mt is a promising catalyst for advanced oxidation processes.

  1. Glutamic acid as anticancer agent: An overview.

    Science.gov (United States)

    Dutta, Satyajit; Ray, Supratim; Nagarajan, K

    2013-10-01

    The objective of the article is to highlight various roles of glutamic acid like endogenic anticancer agent, conjugates to anticancer agents, and derivatives of glutamic acid as possible anticancer agents. Besides these emphases are given especially for two endogenous derivatives of glutamic acid such as glutamine and glutamate. Glutamine is a derivative of glutamic acid and is formed in the body from glutamic acid and ammonia in an energy requiring reaction catalyzed by glutamine synthase. It also possesses anticancer activity. So the transportation and metabolism of glutamine are also discussed for better understanding the role of glutamic acid. Glutamates are the carboxylate anions and salts of glutamic acid. Here the roles of various enzymes required for the metabolism of glutamates are also discussed.

  2. Glutamate and GABA uptake by cerebellar granule and glial cell enriched populations

    International Nuclear Information System (INIS)

    Campbell, G.L.; Shank, R.P.

    1978-01-01

    The results of a study on the uptake of glutamate and GABA by the granule and glial cell enriched populations are reported. They demonstrate that the granule cells vigorously accumulate glutamate but not GABA, whereas the glial cell enriched fraction takes up both amino acids quite rapidly. An unexpected and significant finding is that both cell populations take up glutamate by two distinct high-affinity transport systems as well as a low-affinity system. (Auth.)

  3. Inhibition of the Mitochondrial Glutamate Carrier SLC25A22 in Astrocytes Leads to Intracellular Glutamate Accumulation

    Directory of Open Access Journals (Sweden)

    Emmanuelle Goubert

    2017-05-01

    Full Text Available The solute carrier family 25 (SLC25 drives the import of a large diversity of metabolites into mitochondria, a key cellular structure involved in many metabolic functions. Mutations of the mitochondrial glutamate carrier SLC25A22 (also named GC1 have been identified in early epileptic encephalopathy (EEE and migrating partial seizures in infancy (MPSI but the pathophysiological mechanism of GC1 deficiency is still unknown, hampered by the absence of an in vivo model. This carrier is mainly expressed in astrocytes and is the principal gate for glutamate entry into mitochondria. A sufficient supply of energy is essential for the proper function of the brain and mitochondria have a pivotal role in maintaining energy homeostasis. In this work, we wanted to study the consequences of GC1 absence in an in vitro model in order to understand if glutamate catabolism and/or mitochondrial function could be affected. First, short hairpin RNA (shRNA designed to specifically silence GC1 were validated in rat C6 glioma cells. Silencing GC1 in C6 resulted in a reduction of the GC1 mRNA combined with a decrease of the mitochondrial glutamate carrier activity. Then, primary astrocyte cultures were prepared and transfected with shRNA-GC1 or mismatch-RNA (mmRNA constructs using the Neon® Transfection System in order to target a high number of primary astrocytes, more than 64%. Silencing GC1 in primary astrocytes resulted in a reduced nicotinamide adenine dinucleotide (Phosphate (NAD(PH formation upon glutamate stimulation. We also observed that the mitochondrial respiratory chain (MRC was functional after glucose stimulation but not activated by glutamate, resulting in a lower level of cellular adenosine triphosphate (ATP in silenced astrocytes compared to control cells. Moreover, GC1 inactivation resulted in an intracellular glutamate accumulation. Our results show that mitochondrial glutamate transport via GC1 is important in sustaining glutamate homeostasis in

  4. Blood glutamate scavenging: Insight into neuro protection

    OpenAIRE

    Leibowitz, A; Boyko, M; Shapira, Y; Zlotnik, A

    2012-01-01

    Brain insults are characterized by a multitude of complex processes, of which glutamate release plays a major role. Deleterious excess of glutamate in the brain's extracellular fluids stimulates glutamate receptors, which in turn lead to cell swelling, apoptosis, and neuronal death. These exacerbate neurological outcome. Approaches aimed at antagonizing the astrocytic and glial glutamate receptors have failed to demonstrate clinical benefit. Alternatively, eliminating excess glutamate from br...

  5. Blood Glutamate Scavenging: Insight into Neuroprotection

    OpenAIRE

    Leibowitz, Akiva; Boyko, Matthew; Shapira, Yoram; Zlotnik, Alexander

    2012-01-01

    Brain insults are characterized by a multitude of complex processes, of which glutamate release plays a major role. Deleterious excess of glutamate in the brain’s extracellular fluids stimulates glutamate receptors, which in turn lead to cell swelling, apoptosis, and neuronal death. These exacerbate neurological outcome. Approaches aimed at antagonizing the astrocytic and glial glutamate receptors have failed to demonstrate clinical benefit. Alternatively, eliminating excess glutamate from br...

  6. Regulation of glutamate dehydrogenase in Bacillus subtilis.

    OpenAIRE

    Kane, J F; Wakim, J; Fischer, R S

    1981-01-01

    The activity of the nicotinamide adenine dinucleotide-dependent glutamate dehydrogenase in Bacillus subtilis was influenced by the carbon source, but not the nitrogen source, in the growth medium. The highest specific activity for this enzyme was found when B. subtilis was grown in a minimal or rich medium that contained glutamate as the carbon source. It is proposed that glutamate dehydrogenase serves a catabolic function in the metabolism of glutamate, is induced by glutamate, and is subjec...

  7. Regulation of glutamate dehydrogenase in Bacillus subtilis.

    Science.gov (United States)

    Kane, J F; Wakim, J; Fischer, R S

    1981-01-01

    The activity of the nicotinamide adenine dinucleotide-dependent glutamate dehydrogenase in Bacillus subtilis was influenced by the carbon source, but not the nitrogen source, in the growth medium. The highest specific activity for this enzyme was found when B. subtilis was grown in a minimal or rich medium that contained glutamate as the carbon source. It is proposed that glutamate dehydrogenase serves a catabolic function in the metabolism of glutamate, is induced by glutamate, and is subject to catabolite repression. PMID:6118356

  8. Methods for antagonizing glutamate neurotoxicity.

    Science.gov (United States)

    Choi, D W

    1990-01-01

    Recent evidence suggests that glutamate-induced neuronal damage may contribute importantly to neuronal death in several neurological diseases, including cerebral hypoxia-ischemia. This review outlines a range of measures that might be used to protect neurons from such excitotoxic damage. The organizing thesis is a speculative consideration of glutamate neurotoxicity as a sequential three-stage process--induction, amplification, and expression--each perhaps specifically amenable to therapeutic interference. Overstimulation of glutamate receptors likely induces the intracellular accumulation of several substances, including Ca2+, Na+, inositol-1,4,5-trisphosphate, and diacylglycerol. Blockade of this induction might be accomplished most easily by antagonizing postsynaptic glutamate receptors, but also might be accomplished by reducing glutamate release from presynaptic terminals, or improving glutamate clearance from synaptic clefts. Following induction, several steps may importantly amplify the resultant rise in intracellular free Ca2+, and promote the spread of excessive excitation to other circuit neurons. Protective strategies operative at this level might include blockade of additional Ca2+ influx, blockade of Ca2+ release from intracellular stores, and interference with the mechanisms coupling glutamate receptor stimulation to lasting enhancements of excitatory synaptic efficacy. Following amplification, toxic levels of intracellular free Ca2+ might trigger destructive cascades bearing direct responsibility for resultant neuronal degeneration--the expression of excitotoxicity. The most important cascades to block may be those related to the activation of catabolic enzymes, and the generation of free radicals. Broad consideration of possible methods for antagonizing glutamate neurotoxicity may be needed to develop therapies with the greatest efficacy, and least adverse consequences for brain function.

  9. Glutamate receptor ligands

    DEFF Research Database (Denmark)

    Guldbrandt, Mette; Johansen, Tommy N; Frydenvang, Karla Andrea

    2002-01-01

    Homologation and substitution on the carbon backbone of (S)-glutamic acid [(S)-Glu, 1], as well as absolute stereochemistry, are structural parameters of key importance for the pharmacological profile of (S)-Glu receptor ligands. We describe a series of methyl-substituted 2-aminoadipic acid (AA...... or slightly lower potencies than (S)-AA [e.g., EC(50) = 76 microM for (2S,4S)-4-methyl-AA (5a) as compared to EC(50) = 35 microM for (S)-AA]. The position of the methyl substituent had a profound effect on the observed pharmacology, whereas the absolute stereochemistry at the methylated carbon atom had a very......) analogs, and the synthesis, stereochemistry, and enantiopharmacology of 3-methyl-AA (4a-d), 4-methyl-AA (5a-d), 5-methyl-AA (6a-d), and (E)-Delta(4)-5-methyl-AA (7a and 7b) are reported. The compounds were resolved using chiral HPLC and the configurational assignments of the enantiomers were based on X...

  10. Activation of a7 Nicotinic Acetylcholine Receptors Prevents Monosodium Iodoacetate-Induced Osteoarthritis in Rats

    Directory of Open Access Journals (Sweden)

    Yuan Liu

    2015-01-01

    Full Text Available Background/Aims: Although some evidence suggests that the prevalence of osteoarthritis (OA is lower in smokers compared to nonsmokers, the mechanisms of nicotine-induced protection remain unclear. Stimulation of the a7 nicotinic acetylcholine receptor (a7-nAChR appears to be a critical mechanism underlying the anti-inflammatory potential of cholinergic agonists in immune cells. The inhibition of secreted inflammatory molecules and the subsequent inflammatory processes have been proposed as a novel strategy for the treatment of OA. The objective of the present study was to determine whether nicotine-induced protection in a monosodium iodoacetate (MIA rat model of OA occurs via a7-nAChR-mediated inhibition of chondrocytes. Methods: Both in vivo (MIA and in vitro (MIA; Interleukin-1ß, IL-1ß models of OA were used to investigate the roles and the possible mechanisms whereby a7-nAChRs protect against knee joint degradation. Multiple experimental approaches, including macroscopic, histological analysis, chondrocyte cell cultures, confocal microscopy, and western blotting, were employed to elucidate the mechanisms of a7-nAChR-mediated protection. Results: Systemic administration of nicotine alleviated MIA-induced joint degradation. The protective effects of nicotine were abolished by administration of the a7-nAChR-selective antagonist methyllycaconitine (MLA. In primary cultured rat chondrocytes, pretreatment with nicotine suppressed both p38, extracellular regulated kinase (Erk 1/2 and c-Jun-N-terminal kinase (JNK mitogen-activated protein kinases (MAPK phosphorylation and phosphorylated nuclear factor-kappa B (NF-κB p65 activation induced by MIA- or IL-1ß, and these effects were also reversed by MLA. Conclusion: Taken together, our results suggest that activation a7-nAChRs is an important mechanism underlying the protective effects of nicotine.

  11. Microbial-driven arsenic cycling in rice paddies amended with monosodium methanearsonate

    Science.gov (United States)

    Maguffin, S. C.; McClung, A.; Rohila, J. S.; Derry, L. A.; Huang, R.; Reid, M. C.

    2017-12-01

    Rice consumption is the second largest contributor to human arsenic exposure worldwide and is linked to many serious diseases. Because rice is uniquely adapted for agricultural production under flooded soils, arsenic species solubilized in such environments can be effectively transported into plant tissue via root transporters. Through this process, both inorganic and organic (methylated) arsenic species can accumulate to problematic concentrations and may affect grain yield as well as crop value. The distribution of these species in plant tissue is determined by arsenic sources, as well as enzymatic redox and methylation-demethylation reactions in soils and pore water. Historic use of organoarsenic-based pesticides in US agriculture may provide an enduring source of arsenic in rice paddies. However, it is unclear how persistent these organic species are in the adsorbed phase or how available they remain to rice cultivars throughout the growing season. We conducted a field experiment in a 2x2 factorial design examining the effects of irrigation methods (continuous flooding and alternate wetting and drying) and monosodium methanearsonate (MSMA) application on the abundance and speciation of arsenic in pore water, soil, and rice plant tissues. We monitored arsenic speciation and partitioning between these reservoirs at semi-weekly to semi-monthly frequencies. Pore water arsenic speciation was determined using LC-ICP-MS, and X-ray absorption near-edge structure (XANES) analysis was employed to speciate the arsenic within solid-phase soil and plant tissue throughout the growing season. These data help clarify the role of two irrigation methods and MSMA amendments for arsenic bioavailability and speciation in rice. Furthermore, the study illuminates the significance of microbial metabolism in the reapportionment of arsenic within the soil-plant-water system and its impact on arsenic levels in rice grains.

  12. Morphine Protects Spinal Cord Astrocytes from Glutamate-Induced Apoptosis via Reducing Endoplasmic Reticulum Stress

    Directory of Open Access Journals (Sweden)

    Chao Zhang

    2016-10-01

    Full Text Available Glutamate is not only a neurotransmitter but also an important neurotoxin in central nervous system (CNS. Chronic elevation of glutamate induces both neuronal and glial cell apoptosis. However, its effect on astrocytes is complex and still remains unclear. In this study, we investigated whether morphine, a common opioid ligand, could affect glutamate-induced apoptosis in astrocytes. Primary cultured astrocytes were incubated with glutamate in the presence/absence of morphine. It was found that morphine could reduce glutamate-induced apoptosis of astrocytes. Furthermore, glutamate activated Ca2+ release, thereby inducing endoplasmic reticulum (ER stress in astrocytes, while morphine attenuated this deleterious effect. Using siRNA to reduce the expression of κ-opioid receptor, morphine could not effectively inhibit glutamate-stimulated Ca2+ release in astrocytes, the protective effect of morphine on glutamate-injured astrocytes was also suppressed. These results suggested that morphine could protect astrocytes from glutamate-induced apoptosis via reducing Ca2+ overload and ER stress pathways. In conclusion, this study indicated that excitotoxicity participated in the glutamate mediated apoptosis in astrocytes, while morphine attenuated this deleterious effect via regulating Ca2+ release and ER stress.

  13. Glutamine and glutamate as vital metabolites

    Directory of Open Access Journals (Sweden)

    Newsholme P.

    2003-01-01

    Full Text Available Glucose is widely accepted as the primary nutrient for the maintenance and promotion of cell function. This metabolite leads to production of ATP, NADPH and precursors for the synthesis of macromolecules such as nucleic acids and phospholipids. We propose that, in addition to glucose, the 5-carbon amino acids glutamine and glutamate should be considered to be equally important for maintenance and promotion of cell function. The functions of glutamine/glutamate are many, i.e., they are substrates for protein synthesis, anabolic precursors for muscle growth, they regulate acid-base balance in the kidney, they are substrates for ureagenesis in the liver and for hepatic and renal gluconeogenesis, they act as an oxidative fuel for the intestine and cells of the immune system, provide inter-organ nitrogen transport, and act as precursors of neurotransmitter synthesis, of nucleotide and nucleic acid synthesis and of glutathione production. Many of these functions are interrelated with glucose metabolism. The specialized aspects of glutamine/glutamate metabolism of different glutamine-utilizing cells are discussed in the context of glucose requirements and cell function.

  14. Effects of Bee Venom on Glutamate-Induced Toxicity in Neuronal and Glial Cells

    OpenAIRE

    Lee, Sang Min; Yang, Eun Jin; Choi, Sun-Mi; Kim, Seon Hwy; Baek, Myung Gi; Jiang, Jing Hua

    2012-01-01

    Bee venom (BV), which is extracted from honeybees, is used in traditional Korean medical therapy. Several groups have demonstrated the anti-inflammatory effects of BV in osteoarthritis both in vivo and in vitro. Glutamate is the predominant excitatory neurotransmitter in the central nervous system (CNS). Changes in glutamate release and uptake due to alterations in the activity of glutamate transporters have been reported in many neurodegenerative diseases, including Parkinson's disease, Alzh...

  15. Group I Metabotropic Glutamate Receptors

    DEFF Research Database (Denmark)

    Erichsen, Julie Ladeby; Blaabjerg, Morten; Bogetofte Thomasen, Helle

    2015-01-01

    is, however, needed to realise their therapeutic potential. Glutamate and group I metabotropic glutamate receptors (mGluRs) affect proliferation and survival of rodent NSCs both during embryonic and postnatal development. To investigate the role of group I mGluRs (mGluR1 and mGluR5) on human NSCs, we...... differentiated an immortalized, forebrain-derived stem cell line in the presence or absence of glutamate and with addition of either the group I mGluR agonist DHPG or the selective antagonists; MPEP (mGluR5) and LY367385 (mGluR1). Characterization of differentiated cells revealed that both mGluR1 and mGluR5 were...... present on the cells. Addition of glutamate to the growth medium significantly increased cell proliferation and reduced cell death, resulting in increased cell numbers. In the presence of glutamate, selective activation of group I mGluRs reduced gliogenesis, whereas selective inhibition of group I m...

  16. Buffer-free production of gamma-aminobutyric acid using an engineered glutamate decarboxylase from Escherichia coli.

    Science.gov (United States)

    Kang, Taek Jin; Ho, Ngoc Anh Thu; Pack, Seung Pil

    2013-08-15

    Escherichia coli glutamate decarboxylase (GAD) converts glutamate into γ-aminobutyric acid (GABA) through decarboxylation using proton as a co-substrate. Since GAD is active only at acidic conditions even though pH increases as the reaction proceeds, the conventional practice of using this enzyme involved the use of relatively high concentration of buffers, which might complicate the downstream purification steps. Here we show by simulation and experiments that the free acid substrate, glutamic acid, rather than its monosodium salt can act as a substrate and buffer at the same time. This yielded the buffer- and salt-free synthesis of GABA conveniently in a batch mode. Furthermore, we engineered GAD to hyper active ones by extending or reducing the length of the enzyme by just one residue at its C-terminus. Through the buffer-free reaction with engineered GAD, we could synthesize 1M GABA in 3h, which can be translated into a space-time yield of 34.3g/L/h. Copyright © 2013 Elsevier Inc. All rights reserved.

  17. Methylphenidate Increases Glutamate Uptake in Bergmann Glial Cells.

    Science.gov (United States)

    Guillem, Alain M; Martínez-Lozada, Zila; Hernández-Kelly, Luisa C; López-Bayghen, Esther; López-Bayghen, Bruno; Calleros, Oscar A; Campuzano, Marco R; Ortega, Arturo

    2015-11-01

    Glutamate, the main excitatory transmitter in the vertebrate brain, exerts its actions through the activation of specific membrane receptors present in neurons and glial cells. Over-stimulation of glutamate receptors results in neuronal death, phenomena known as excitotoxicity. A family of glutamate uptake systems, mainly expressed in glial cells, removes the amino acid from the synaptic cleft preventing an excessive glutamatergic stimulation and thus neuronal damage. Autism spectrum disorders comprise a group of syndromes characterized by impaired social interactions and anxiety. One or the most common drugs prescribed to treat these disorders is Methylphenidate, known to increase dopamine extracellular levels, although it is not clear if its sedative effects are related to a plausible regulation of the glutamatergic tone via the regulation of the glial glutamate uptake systems. To gain insight into this possibility, we used the well-established model system of cultured chick cerebellum Bergmann glia cells. A time and dose-dependent increase in the activity and protein levels of glutamate transporters was detected upon Methylphenidate exposure. Interestingly, this increase is the result of an augmentation of both the synthesis as well as the insertion of these protein complexes in the plasma membrane. These results favour the notion that glial cells are Methylphenidate targets, and that by these means could regulate dopamine turnover.

  18. DNA nanopore translocation in glutamate solutions

    NARCIS (Netherlands)

    Plesa, C.; Van Loo, N.; Dekker, C.

    2015-01-01

    Nanopore experiments have traditionally been carried out with chloride-based solutions. Here we introduce silver/silver-glutamate-based electrochemistry as an alternative, and study the viscosity, conductivity, and nanopore translocation characteristics of potassium-, sodium-, and lithium-glutamate

  19. Ceftriaxone modulates uptake activity of glial glutamate transporter-1 against global brain ischemia in rats.

    Science.gov (United States)

    Hu, Yu-Yan; Xu, Jing; Zhang, Min; Wang, Dan; Li, Li; Li, Wen-Bin

    2015-01-01

    Ceftriaxone(Cef) selectively increases the expression of glial glutamate transporter-1 (GLT-1), which was thought to be neuroprotective in some circumstances. However, the effect of Cef on glutamate uptake of GLT-1 was mostly assayed using in vitro studies such as primary neuron/astrocyte cultures or brain slices. In addition, the effect of Cef on neurons in different ischemic models was still discrepant. Therefore, this study was undertaken to observe the effect of Cef on neurons in global brain ischemia in rats, and especially to provide direct evidence of the up-regulation of GLT-1 uptake for glutamate contributing to the neuronal protection of Cef against brain ischemia. Neuropathological evaluation indicated that administration of Cef, especially pre-treatment protocols, significantly prevented delayed neuronal death in hippocampal CA1 subregion normally induced by global brain ischemia. Simultaneously, pre-administration of Cef significantly up-regulated the expression of GLT-1. Particularly, GLT-1 uptake assay with (3) H-glutamate in living cells from adult rats showed that up-regulation in glutamate uptake accompanied up-regulated GLT-1 expression. Inhibition of GLT-1 by antisense oligodeoxynucleotides or dihydrokainate significantly inhibited the Cef-induced up-regulation in GLT-1 uptake and the neuroprotective effect against global ischemia. Thus, we may conclude that Cef protects neurons against global brain ischemia via up-regulation of the expression and glutamate uptake of GLT-1. Glutamate uptake by glial glutamate transporter-1 (GLT-1) is the principal way to regulate extracellular glutamate homeostasis in central nervous system. Over-accumulation of glutamate results in excitotoxicity and injures neurons after cerebral ischemia. Ceftriaxone up-regulates GLT-1 expression and uptake of glutamate, diminishes the excitotoxicity of glutamate and then protects neurons against global brain ischemia. © 2014 International Society for Neurochemistry.

  20. 21 CFR 582.1516 - Monopotassium glutamate.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Monopotassium glutamate. 582.1516 Section 582.1516 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Additives § 582.1516 Monopotassium glutamate. (a) Product. Monopotassium glutamate. (b) Conditions of use...

  1. 21 CFR 182.1516 - Monopotassium glutamate.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Monopotassium glutamate. 182.1516 Section 182.1516 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD... Substances § 182.1516 Monopotassium glutamate. (a) Product. Monopotassium glutamate. (b) Conditions of use...

  2. 21 CFR 182.1500 - Monoammonium glutamate.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Monoammonium glutamate. 182.1500 Section 182.1500 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD... Substances § 182.1500 Monoammonium glutamate. (a) Product. Monoammonium glutamate. (b) Conditions of use...

  3. 21 CFR 582.1500 - Monoammonium glutamate.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Monoammonium glutamate. 582.1500 Section 582.1500 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Additives § 582.1500 Monoammonium glutamate. (a) Product. Monoammonium glutamate. (b) Conditions of use...

  4. Glutamate esters as agents for cholescintigraphy

    International Nuclear Information System (INIS)

    Colombetti, L.

    1976-01-01

    Several sup(99m)Tc-labelled aldehyde glutamate complexes having similar pharmacological properties as sup(99m)Tc-pyridoxylidene glutamate have been prepared. The dynamic behaviour of these compounds in dogs and rabbits was studied using a digital computer and scintillation camera. The aldehyde-glutamate complex promises to be a useful agent for the dynamic study of hepatic and biliary function

  5. Ciprofloxacin triggered glutamate production by Corynebacterium glutamicum.

    Science.gov (United States)

    Lubitz, Dorit; Wendisch, Volker F

    2016-10-07

    Corynebacterium glutamicum is a well-studied bacterium which naturally overproduces glutamate when induced by an elicitor. Glutamate production is accompanied by decreased 2-oxoglutatate dehydrogenase activity. Elicitors of glutamate production by C. glutamicum analyzed to molecular detail target the cell envelope. Ciprofloxacin, an inhibitor of bacterial DNA gyrase and topoisomerase IV, was shown to inhibit growth of C. glutamicum wild type with concomitant excretion of glutamate. Enzyme assays showed that 2-oxoglutarate dehydrogenase activity was decreased due to ciprofloxacin addition. Transcriptome analysis revealed that this inhibitor of DNA gyrase increased RNA levels of genes involved in DNA synthesis, repair and modification. Glutamate production triggered by ciprofloxacin led to glutamate titers of up to 37 ± 1 mM and a substrate specific glutamate yield of 0.13 g/g. Even in the absence of the putative glutamate exporter gene yggB, ciprofloxacin effectively triggered glutamate production. When C. glutamicum wild type was cultivated under nitrogen-limiting conditions, 2-oxoglutarate rather than glutamate was produced as consequence of exposure to ciprofloxacin. Recombinant C. glutamicum strains overproducing lysine, arginine, ornithine, and putrescine, respectively, secreted glutamate instead of the desired amino acid when exposed to ciprofloxacin. Ciprofloxacin induced DNA synthesis and repair genes, reduced 2-oxoglutarate dehydrogenase activity and elicited glutamate production by C. glutamicum. Production of 2-oxoglutarate could be triggered by ciprofloxacin under nitrogen-limiting conditions.

  6. 21 CFR 182.1045 - Glutamic acid.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Glutamic acid. 182.1045 Section 182.1045 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN....1045 Glutamic acid. (a) Product. Glutamic acid. (b) [Reserved] (c) Limitations, restrictions, or...

  7. GABA and glutamate uptake and metabolism in retinal glial (Müller cells

    Directory of Open Access Journals (Sweden)

    Andreas eBringmann

    2013-04-01

    Full Text Available Müller cells, the principal glial cells of the retina, support the synaptic activity by the uptake and metabolization of extracellular neurotransmitters. Müller cells express uptake and exchange systems for various neurotransmitters including glutamate and -aminobutyric acid (GABA. Müller cells remove the bulk of extracellular glutamate in the inner retina and contribute to the glutamate clearance around photoreceptor terminals. By the uptake of glutamate, Müller cells are involved in the shaping and termination of the synaptic activity, particularly in the inner retina. Reactive Müller cells are neuroprotective, e.g., by the clearance of excess extracellular glutamate, but may also contribute to neuronal degeneration by a malfunctioning or even reversal of glial glutamate transporters, or by a downregulation of the key enzyme, glutamine synthetase. This review summarizes the present knowledge about the role of Müller cells in the clearance and metabolization of extracellular glutamate and GABA. Some major pathways of GABA and glutamate metabolism in Müller cells are described; these pathways are involved in the glutamate-glutamine cycle of the retina, in the defense against oxidative stress via the production of glutathione, and in the production of substrates for the neuronal energy metabolism.

  8. Coupling of glutamate and glucose uptake in cultured Bergmann glial cells.

    Science.gov (United States)

    Mendez-Flores, Orquidia G; Hernández-Kelly, Luisa C; Suárez-Pozos, Edna; Najimi, Mustapha; Ortega, Arturo

    2016-09-01

    Glutamate, the main excitatory neurotransmitter in the vertebrate brain, exerts its actions through specific membrane receptors present in neurons and glial cells. Over-stimulation of glutamate receptors results in neuronal death, phenomena known as excitotoxicity. A family of sodium-dependent, glutamate uptake transporters mainly expressed in glial cells, removes the amino acid from the synaptic cleft preventing neuronal death. The sustained sodium influx associated to glutamate removal in glial cells, activates the sodium/potassium ATPase restoring the ionic balance, additionally, glutamate entrance activates glutamine synthetase, both events are energy demanding, therefore glia cells increase their ATP expenditure favouring glucose uptake, and triggering several signal transduction pathways linked to proper neuronal glutamate availability, via the glutamate/glutamine shuttle. To further characterize these complex transporters interactions, we used the well-established model system of cultured chick cerebellum Bergmann glia cells. A time and dose-dependent increase in the activity, plasma membrane localization and protein levels of glucose transporters was detected upon d-aspartate exposure. Interestingly, this increase is the result of a protein kinase C-dependent signaling cascade. Furthermore, a glutamate-dependent glucose and glutamate transporters co-immunoprecipitation was detected. These results favour the notion that glial cells are involved in glutamatergic neuronal physiology. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Secretory phospholipase A2-mediated neuronal cell death involves glutamate ionotropic receptors

    DEFF Research Database (Denmark)

    Kolko, Miriam; de Turco, Elena B; Diemer, Nils Henrik

    2002-01-01

    ]Arachidonic acid release induced by both sPLA and glutamate was partially blocked by MK-801, indicating that the glutamate-NMDA-cPLA pathway contributes to sPLA -induced arachidonic acid release. Systemic administration of MK-801 to rats that had sPLA injected into the right striatum significantly decreased...

  10. EVALUATING THE NMDA-GLUTAMATE RECEPTOR AS A SITE OF ACTION FOR TOLUENE, IN VIVO

    Science.gov (United States)

    In vitro, toluene disrupts the function of NMDA-glutamate receptors, indicating that effects on NMDA receptor function may contribute to toluene neurotoxicity. NMDA-glutamate receptors are widely present in the visual system and contribute to pattern-elicited visual evoked potent...

  11. The glutamate/GABA-glutamine cycle

    DEFF Research Database (Denmark)

    Bak, Lasse K; Schousboe, Arne; Waagepetersen, Helle S

    2006-01-01

    or GABA from neurons and subsequent uptake into astrocytes. In return, astrocytes release glutamine to be taken up into neurons for use as neurotransmitter precursor. In this review, the basic properties of the glutamate/GABA-glutamine cycle will be discussed, including aspects of transport and metabolism...... of intercellular transfer of ammonia produced in neurons (when glutamine is deamidated to glutamate) and utilized in astrocytes (for amidation of glutamate) when the glutamate/GABA-glutamine cycle is operating. A main objective of this review is to endorse the view that the glutamate/GABA-glutamine cycle must...

  12. Metabotropic glutamate receptor 5 may be involved in macrophage plasticity

    Directory of Open Access Journals (Sweden)

    Lali Shanshiashvili

    Full Text Available Abstract Background Macrophages are a functionally heterogeneous cell population and depending on microenvironments they polarize in two main groups: M1 and M2. Glutamic acid and glutamate receptors may participate in the regulation of macrophage plasticity. To investigate the role of glutamatergic systems in macrophages physiology, we performed the transfection of mGluR5 cDNAs into RAW-264.7 cells. Results Comparative analysis of modified (RAW-mGluR5 macrophages and non-modified macrophages (RAW-macrophages has shown that the RAW-mGluR5 macrophages absorbed more glutamate than control cells and the amount of intracellular glutamate correlated with the expression of excitatory amino acid transporters -2 (EAAT-2. Besides, our results have shown that RAW-mGluR5 macrophages expressed a higher level of peroxisome proliferator-activated receptor γ (PPAR-γ and secreted more IL-10, high mobility group box 1 proteins (HMGB1 and Galectin-3 than control RAW-macrophages. Conclusions We propose that elevation of intracellular glutamate and expression of mGluR5 may initiate the metabolic rearrangement in macrophages that could contribute to the formation of an immunosuppressive phenotype.

  13. Zinc and glutamate dehydrogenase in putative glutamatergic brain structures.

    Science.gov (United States)

    Wolf, G; Schmidt, W

    1983-01-01

    A certain topographic parallelism between the distribution of histochemically (TIMM staining) identified zinc and putative glutamatergic structures in the rat brain was demonstrated. Glutamate dehydrogenase as a zinc containing protein is in consideration to be an enzyme synthesizing transmitter glutamate. In a low concentration range externally added zinc ions (10(-9) to 10(-7) M) induced an increase in the activity of glutamate dehydrogenase (GDH) originating from rat hippocampal formation, neocortex, and cerebellum up to 142.4%. With rising molarity of Zn(II) in the incubation medium, the enzyme of hippocampal formation and cerebellum showed a biphasic course of activation. Zinc ions of a concentration higher than 10(-6) M caused a strong inhibition of GDH. The effect of Zn(II) on GDH originating from spinal ganglia and liver led only to a decrease of enzyme activity. These results are discussed in connection with a functional correlation between zinc and putatively glutamatergic system.

  14. The involvement of glutamate in the pathophysiology of depression.

    Science.gov (United States)

    Palucha, A; Pilc, A

    2005-05-01

    In spite of more than 40 years of thorough studies, conventional antidepressants still have many limitations that hinder the effective treatment of depression. It seems that a breakthrough in the therapy of depression will require going beyond a monoamine-based theory of depression. Converging lines of evidence indicate that the glutamatergic system might be a promising target for a novel antidepressant therapy. Both ionotropic glutamate receptor ligands (functional NMDA receptor antagonists and AMPA receptor potentiators) and compounds acting at metabotropic glutamate receptors (mGluRs; group I mGluR antagonists, group II antagonists and group III agonists) produce antidepressant-like activity in several preclinical and some clinical studies. In this review, current knowledge and crucial hypotheses concerning the role of glutamate in the pathophysiology of depression are discussed. 2005 Prous Science. All rights reserved

  15. Fate of glutamate carbon and nitrogen in isolated guinea-pig kidney-cortex tubules. Evidence for involvement of glutamate dehydrogenase in glutamine sythesis from glutamate.

    OpenAIRE

    Baverel, G; Genoux, C; Forissier, M; Pellet, M

    1980-01-01

    1. The pathways and the fate of glutamate carbon and nitrogen were investigated in isolated guinea-pig kidney-cortex tubules. 2. At low glutamate concentration (1 mM), the glutamate carbon skeleton was either completely oxidized or converted into glutamine. At high glutamate concentration (5 mM), glucose, lactate and alanine were additional products of glutamate metabolism. 3. At neither concentration of glutamate was there accumulation of ammonia. 4. Nitrogen-balance calculations and the rel...

  16. Glutamate Receptors in Neuroinflammatory Demyelinating Disease

    Directory of Open Access Journals (Sweden)

    2006-01-01

    Full Text Available Multiple sclerosis (MS is a chronic demyelinating disease of the human central nervous system (CNS. The condition predominantly affects young adults and is characterised by immunological and inflammatory changes in the periphery and CNS that contribute to neurovascular disruption, haemopoietic cell invasion of target tissues, and demyelination of nerve fibres which culminate in neurological deficits that relapse and remit or are progressive. The main features of MS can be reproduced in the inducible animal counterpart, experimental autoimmune encephalomyelitis (EAE. The search for new MS treatments invariably employs EAE to determine drug activity and provide a rationale for exploring clinical efficacy. The preclinical development of compounds for MS has generally followed a conventional, immunotherapeutic route. However, over the past decade, a group of compounds that suppress EAE but have no apparent immunomodulatory activity have emerged. These drugs interact with the N-methyl-D-aspartate (NMDA and α -amino-3-hydroxy-5-isoxazolepropionic acid (AMPA/kainate family of glutamate receptors reported to control neurovascular permeability, inflammatory mediator synthesis, and resident glial cell functions including CNS myelination. The review considers the importance of the glutamate receptors in EAE and MS pathogenesis. The use of receptor antagonists to control EAE is also discussed together with the possibility of therapeutic application in demyelinating disease.

  17. The neuroprotective effects of tocotrienol rich fraction and alpha tocopherol against glutamate injury in astrocytes

    Directory of Open Access Journals (Sweden)

    Thilaga Rati Selvaraju

    2014-11-01

    Full Text Available Tocotrienol rich fraction (TRF is an extract of palm oil, which consists of 25% alpha tocopherol (α-TCP and 75% tocotrienols. TRF has been shown to possess potent antioxidant, anti-inflammatory, anticancer, neuroprotection, and cholesterol lowering activities. Glutamate is the main excitatory amino acid neurotransmitter in the central nervous system of mammalian, which can be excitotoxic, and it has been suggested to play a key role in neurodegenerative disorders like Parkinson’s and Alzheimer’s diseases. In this present study, the effects of vitamin E (TRF and α-TCP in protecting astrocytes against glutamate injury were elucidated. Astrocytes induced with 180 mM of glutamate lead to significant cell death. However, glutamate mediated cytotoxicity was diminished via pre and post supplementation of TRF and α-TCP. Hence, vitamin E acted as a potent antioxidant agent in recovering mitochondrial injury due to elevated oxidative stress, and enhanced better survivability upon glutamate toxicity.  

  18. Bacterial-Derived Polymer Poly-γ-Glutamic Acid (γ-PGA)-Based Micro/Nanoparticles as a Delivery System for Antimicrobials and Other Biomedical Applications

    Science.gov (United States)

    Khalil, Ibrahim R.; Burns, Alan T. H.; Radecka, Iza; Kowalczuk, Marek; Khalaf, Tamara; Adamus, Grazyna; Johnston, Brian; Khechara, Martin P.

    2017-01-01

    In the past decade, poly-γ-glutamic acid (γ-PGA)-based micro/nanoparticles have garnered remarkable attention as antimicrobial agents and for drug delivery, owing to their controlled and sustained-release properties, low toxicity, as well as biocompatibility with tissue and cells. γ-PGA is a naturally occurring biopolymer produced by several gram-positive bacteria that, due to its biodegradable, non-toxic and non-immunogenic properties, has been used successfully in the medical, food and wastewater industries. Moreover, its carboxylic group on the side chains can offer an attachment point to conjugate antimicrobial and various therapeutic agents, or to chemically modify the solubility of the biopolymer. The unique characteristics of γ-PGA have a promising future for medical and pharmaceutical applications. In the present review, the structure, properties and micro/nanoparticle preparation methods of γ-PGA and its derivatives are covered. Also, we have highlighted the impact of micro/nanoencapsulation or immobilisation of antimicrobial agents and various disease-related drugs on biodegradable γ-PGA micro/nanoparticles. PMID:28157175

  19. Hippocampal glutamate is increased and associated with risky drinking in young adults with major depression.

    Science.gov (United States)

    Hermens, Daniel F; Chitty, Kate M; Lee, Rico Sc; Tickell, Ashleigh; Haber, Paul S; Naismith, Sharon L; Hickie, Ian B; Lagopoulos, Jim

    2015-11-01

    Risky drinking in young people is harmful, highly prevalent and often complicated by comorbid mental health problems that compound alcohol-induced impairment. The hippocampus and the glutamate system have been implicated in the pathophysiology of alcoholism and depression. This study aimed to determine whether risky drinking is associated with glutamate levels recorded within the hippocampus of young adults with major depression. Sixty-three young persons with major depression (22.1±3.1 years; 65% female) and 38 healthy controls were recruited. Participants completed the alcohol use disorder identification test and underwent proton magnetic resonance spectroscopy to measure in vivo glutamate levels within the hippocampus following a period of at least 48h of abstinence. Young adults with depression had significantly increased hippocampal glutamate levels and a positive association between the level of alcohol use and glutamate. Regression analysis revealed that higher levels of hippocampal glutamate were predicted by having increased levels of risky drinking and depression. Small sample sizes for testing diagnosis by risky drinking interaction and use of creatine ratios rather than the absolute concentrations of glutamate. The hippocampus is a critical region; given its role in learning and memory as well as mood regulation, and the neurochemical changes observed in this study may precede structural changes, which are commonly observed in both depression and alcohol misuse. These findings suggest that young adults with major depression who engage in risky drinking may be at increased risk of glutamate excitotoxicity. Copyright © 2015 Elsevier B.V. All rights reserved.

  20. Characterization of the venom from the spider, Araneus gemma: search for a glutamate antagonist

    International Nuclear Information System (INIS)

    Early, S.L.

    1985-01-01

    Venom from three spiders, Argiope aurantia, Neoscona arabesca, and Araneus gemma have been shown to inhibit the binding of L-[ 3 H]glutamate to both GBP and synaptic membranes. The venom from Araneus gemma was shown to be the most potent of the three venoms in inhibiting the binding of L-[ 3 H]glutamate to GBP. Therefore, Araneus gemma venom was selected for further characterization. Venom from Araneus gemma appeared to contain two factors which inhibit the binding of L-[ 3 H]glutamate to GBP and at least one factor that inhibits L-glutamate-stimulated 35 SCN flux. Factor I is thought to be L-glutamic acid, based on: (1) its similar mobility to glutamic acid in thin-layer chromatography and amino acid analysis, (2) the presence of fingerprint molecular ion peaks for glutamate in the mass spectrum for the methanol:water (17:1) extract and for the fraction from the HPLC-purification of the crude venom, and (3) its L-glutamate-like interaction with the sodium-dependent uptake system. Factor II appears to be a polypeptide, possibly 21 amino acids in length, and does not appear to contain any free amino groups or tryptophan. While the venom does not appear to contain any indoleamines, three catecholamines (epinephrine, epinine, dopamine) and one catecholamine metabolite (DOPAC) were detected

  1. SORPTION BEHAVIOR OF MONOSODIUM TITANATE AND AMORPHOUS PEROXOTITANATE MATERIALS UNDER WEAKLY ACIDIC CONDITIONS

    Energy Technology Data Exchange (ETDEWEB)

    Hobbs, D.; Elvington, M.; Click, D.

    2009-11-11

    Inorganic, titanate-based sorbents are tested with respect to adsorption of a variety of sorbates under weakly acidic conditions (pH 3). Specifically, monosodium titanate (MST) and amorphous peroxotitanate (APT) sorption characteristics are initially probed through a screening process consisting of a pair of mixed metal solutions containing a total of 29 sorbates including alkali metals, alkaline earth metals, transition metals, metalloids and nonmetals. MST and APT sorption characteristics are further analyzed individually with chromium(III) and cadmium(II) using a batch method at ambient laboratory temperature, varying concentrations of the sorbents and sorbates and contact times. Maximum sorbate loadings are obtained from the respective adsorption isotherms.

  2. Introduction to the Glutamate-Glutamine Cycle

    DEFF Research Database (Denmark)

    Sonnewald, Ursula; Schousboe, Arne

    2016-01-01

    The term 'glutamate-glutamine cycle' was coined several decades ago based on the observation that using certain (14)C-labeled precursors for studies of brain metabolism the specific radioactivity of glutamine generated from glutamate was higher than that of glutamate, its immediate precursor....... This is metabolically impossible unless it is assumed that at least two distinct pools of these amino acids exist. This combined with the finding that the enzyme synthesizing glutamine from glutamate was expressed in astrocytes but not in neurons formed the basis of the notion that a cycle must exist in which glutamate...... released from neurons is transported into astrocytes, converted to glutamine which is subsequently returned to neurons and converted to glutamate by an enzyme the activity of which is much higher in neurons than in astrocytes. Originally this cycle was supposed to function in a stoichiometric fashion...

  3. Introduction to the Glutamate-Glutamine Cycle

    DEFF Research Database (Denmark)

    Sonnewald, Ursula; Schousboe, Arne

    2016-01-01

    . This is metabolically impossible unless it is assumed that at least two distinct pools of these amino acids exist. This combined with the finding that the enzyme synthesizing glutamine from glutamate was expressed in astrocytes but not in neurons formed the basis of the notion that a cycle must exist in which glutamate......The term 'glutamate-glutamine cycle' was coined several decades ago based on the observation that using certain (14)C-labeled precursors for studies of brain metabolism the specific radioactivity of glutamine generated from glutamate was higher than that of glutamate, its immediate precursor...... released from neurons is transported into astrocytes, converted to glutamine which is subsequently returned to neurons and converted to glutamate by an enzyme the activity of which is much higher in neurons than in astrocytes. Originally this cycle was supposed to function in a stoichiometric fashion...

  4. Prefrontal changes in the glutamate-glutamine cycle and neuronal/glial glutamate transporters in depression with and without suicide

    NARCIS (Netherlands)

    Zhao, J.; Verwer, R.W.H.; van Wamelen, D.J.; Qi, X.R.; Gao, S.F.; Lucassen, P.J.; Swaab, D.F.

    2016-01-01

    There are indications for changes in glutamate metabolism in relation to depression or suicide. The glutamate-glutamine cycle and neuronal/glial glutamate transporters mediate the uptake of the glutamate and glutamine. The expression of various components of the glutamate-glutamine cycle and the

  5. The glutamate/neutral amino acid transporter family SLC1: molecular, physiological and pharmacological aspects.

    Science.gov (United States)

    Kanai, Yoshikatsu; Hediger, Matthias A

    2004-02-01

    The solute carrier family 1 (SLC1) includes five high-affinity glutamate transporters, EAAC1, GLT-1, GLAST, EAAT4 and EAAT5 (SLC1A1, SLC1A2, SLC1A3, SLC1A6, and SLC1A7, respectively) as well as the two neutral amino acid transporters, ASCT1 and ASCT2 (SLC1A4 and ALC1A5, respectively). Although each of these transporters have similar predicted structures, they exhibit distinct functional properties which are variations of a common transport mechanism. The high-affinity glutamate transporters mediate transport of l-Glu, l-Asp and d-Asp, accompanied by the cotransport of 3 Na(+) and 1 H(+), and the countertransport of 1 K(+), whereas ASC transporters mediate Na(+)-dependent exchange of small neutral amino acids such as Ala, Ser, Cys and Thr. The unique coupling of the glutamate transporters allows uphill transport of glutamate into cells against a concentration gradient. This feature plays a crucial role in protecting neurons against glutamate excitotoxicity in the central nervous system. During pathological conditions, such as brain ischemia (e.g. after a stroke), however, glutamate exit can occur due to "reversed glutamate transport", which is caused by a reversal of the electrochemical gradients of the coupling ions. Selective inhibition of the neuronal glutamate transporter EAAC1 (SLC1A1) may be of therapeutic interest to block glutamate release from neurons during ischemia. On the other hand, upregulation of the glial glutamate transporter GLT1 (SLC1A2) may help protect motor neurons in patients with amyotrophic lateral sclerosis (ALS), since loss of function of GLT1 has been associated with the pathogenesis of certain forms of ALS.

  6. Evidence for a role of glutamate as an efferent transmitter in taste buds

    Directory of Open Access Journals (Sweden)

    Anderson Catherine B

    2010-06-01

    Full Text Available Abstract Background Glutamate has been proposed as a transmitter in the peripheral taste system in addition to its well-documented role as an umami taste stimulus. Evidence for a role as a transmitter includes the presence of ionotropic glutamate receptors in nerve fibers and taste cells, as well as the expression of the glutamate transporter GLAST in Type I taste cells. However, the source and targets of glutamate in lingual tissue are unclear. In the present study, we used molecular, physiological and immunohistochemical methods to investigate the origin of glutamate as well as the targeted receptors in taste buds. Results Using molecular and immunohistochemical techniques, we show that the vesicular transporters for glutamate, VGLUT 1 and 2, but not VGLUT3, are expressed in the nerve fibers surrounding taste buds but likely not in taste cells themselves. Further, we show that P2X2, a specific marker for gustatory but not trigeminal fibers, co-localizes with VGLUT2, suggesting the VGLUT-expressing nerve fibers are of gustatory origin. Calcium imaging indicates that GAD67-GFP Type III taste cells, but not T1R3-GFP Type II cells, respond to glutamate at concentrations expected for a glutamate transmitter, and further, that these responses are partially blocked by NBQX, a specific AMPA/Kainate receptor antagonist. RT-PCR and immunohistochemistry confirm the presence of the Kainate receptor GluR7 in Type III taste cells, suggesting it may be a target of glutamate released from gustatory nerve fibers. Conclusions Taken together, the results suggest that glutamate may be released from gustatory nerve fibers using a vesicular mechanism to modulate Type III taste cells via GluR7.

  7. Antiarthritic effect of polar extract of Curcuma longa on Monosodium Iodoacetate induced osteoarthritis in rats.

    Science.gov (United States)

    Murugan, Sasikumar; Bethapudi, Bharathi; Purusothaman, Divya; Raja, Prasanna; Velusami, Chandrasekaran Chinampudur

    2018-01-26

    Curcuma longa Linn, "the golden spice" is a common spice used in southern Asia and Middle East countries. It has a history of ethnopharmacological use for its various functional activities like antiseptic, anti-inflammatory, antioxidant, antimicrobial, anticancer and so on. To investigate the effects of polar extract of C. longa (PCL) against monosodium iodoacetate (MIA) induced osteoarthritis in rat and to compare with curcuminoids, which are contemporarily believed to be the only active phytochemicals of C. longa for relieving pain in osteoarthritis. Degenerative osteoarthritis in rats was induced by intra-articular injection of monosodium iodoacetate (MIA) in right knee. PCL or curcuminoids or tramadol was administered orally on the 5th day post MIA injection to rats. Weight bearing capacity and percentage inhibition of nociception of PCL treated groups were determined and compared with curcuminoids and tramadol (reference drug). In addition, gene expression of type II collagen and matrix metalloproteinases (MMP) in joint cartilage was measured by Reverse transcription polymerase chain reaction. PCL significantly decreased the difference in weight distribution between left and right limb in a dose dependent manner. Anti-arthritic activity of PCL is evident from gene expression analysis, significantly up regulating type II collagen gene (COL2A1) and down regulating MMP-3 and MMP-7. Polysaccharide extract of Curcuma longa showed beneficial effects on joints by exhibiting equilibrium between catabolism and anabolism of joint cartilage. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  8. Growth patterns of monosodium urate monohydrate (gouty and urinary) crystals in gel: An in vitro study.

    Science.gov (United States)

    Ahmed, Salman; Hasan, Muhammad Mohtasheemul; Mahmood, Zafar Alam

    2017-11-01

    Monosodium urate monohydrate crystals are deposited in peripheral joints causing gout and elicit an intense localized inflammatory attack whereas in collecting ducts and medullary interstitium as a urinary calculi which causes dysuria, nausea and hematuria. The purpose of present study is to observe possible growth patterns of monosodium urate monohydrate crystals. The crystals were grown in test tubes by single diffusion gel technique and were observed at 7th, 14th, 21st, 28th and 40th day. Needle and spherulite type crystals were observed at 14th day, while arboresque, crystal sheaves, densely branched, dumbbell, mushroom type spherulites, plumose and hexagonal prismatic crystals were observed for the first time. After 40th day complete spherulites were observed with their aggregates. The crystals were characterized by Scanning Electron Microscopy, Energy-Dispersive X-ray and Fourier Transform infra Red spectroscopies. The pattern of MSUM will be helpful to determine the role of different natural products in the modulation, inhibition or promotion of these crystals by affecting the shape, size, transparency, approximate number and total mass of growing crystals. In case of inhibition or modulation it will be helpful for evaluation the prophylactic management whereas the promotion of the crystal will give an idea about the risk factors of gout and kidney stones.

  9. Desensitization of metabotropic glutamate receptors in neuronal cultures

    NARCIS (Netherlands)

    Catania, M. V.; Aronica, E.; Sortino, M. A.; Canonico, P. L.; Nicoletti, F.

    1991-01-01

    Preexposure of cultured cerebellar neurons to glutamate reduced the stimulation of polyphosphoinositide (PPI) hydrolysis induced by subsequent addition of glutamate without affecting the response to the muscarinic receptor agonist carbamylcholine. Desensitization of glutamate-stimulated PPI

  10. On the potential role of glutamate transport in mental fatigue

    Directory of Open Access Journals (Sweden)

    Hansson Elisabeth

    2004-11-01

    Full Text Available Abstract Mental fatigue, with decreased concentration capacity, is common in neuroinflammatory and neurodegenerative diseases, often appearing prior to other major mental or physical neurological symptoms. Mental fatigue also makes rehabilitation more difficult after a stroke, brain trauma, meningitis or encephalitis. As increased levels of proinflammatory cytokines are reported in these disorders, we wanted to explore whether or not proinflammatory cytokines could induce mental fatigue, and if so, by what mechanisms. It is well known that proinflammatory cytokines are increased in major depression, "sickness behavior" and sleep deprivation, which are all disorders associated with mental fatigue. Furthermore, an influence by specific proinflammatory cytokines, such as interleukin (IL-1, on learning and memory capacities has been observed in several experimental systems. As glutamate signaling is crucial for information intake and processing within the brain, and due to the pivotal role for glutamate in brain metabolism, dynamic alterations in glutamate transmission could be of pathophysiological importance in mental fatigue. Based on this literature and observations from our own laboratory and others on the role of astroglial cells in the fine-tuning of glutamate neurotransmission we present the hypothesis that the proinflammatory cytokines tumor necrosis factor-α, IL-1β and IL-6 could be involved in the pathophysiology of mental fatigue through their ability to attenuate the astroglial clearance of extracellular glutamate, their disintegration of the blood brain barrier, and effects on astroglial metabolism and metabolic supply for the neurons, thereby attenuating glutamate transmission. To test whether our hypothesis is valid or not, brain imaging techniques should be applied with the ability to register, over time and with increasing cognitive loading, the extracellular concentrations of glutamate and potassium (K+ in humans suffering from

  11. On the potential role of glutamate transport in mental fatigue.

    Science.gov (United States)

    Rönnbäck, Lars; Hansson, Elisabeth

    2004-11-04

    Mental fatigue, with decreased concentration capacity, is common in neuroinflammatory and neurodegenerative diseases, often appearing prior to other major mental or physical neurological symptoms. Mental fatigue also makes rehabilitation more difficult after a stroke, brain trauma, meningitis or encephalitis. As increased levels of proinflammatory cytokines are reported in these disorders, we wanted to explore whether or not proinflammatory cytokines could induce mental fatigue, and if so, by what mechanisms.It is well known that proinflammatory cytokines are increased in major depression, "sickness behavior" and sleep deprivation, which are all disorders associated with mental fatigue. Furthermore, an influence by specific proinflammatory cytokines, such as interleukin (IL)-1, on learning and memory capacities has been observed in several experimental systems. As glutamate signaling is crucial for information intake and processing within the brain, and due to the pivotal role for glutamate in brain metabolism, dynamic alterations in glutamate transmission could be of pathophysiological importance in mental fatigue. Based on this literature and observations from our own laboratory and others on the role of astroglial cells in the fine-tuning of glutamate neurotransmission we present the hypothesis that the proinflammatory cytokines tumor necrosis factor-alpha, IL-1beta and IL-6 could be involved in the pathophysiology of mental fatigue through their ability to attenuate the astroglial clearance of extracellular glutamate, their disintegration of the blood brain barrier, and effects on astroglial metabolism and metabolic supply for the neurons, thereby attenuating glutamate transmission. To test whether our hypothesis is valid or not, brain imaging techniques should be applied with the ability to register, over time and with increasing cognitive loading, the extracellular concentrations of glutamate and potassium (K+) in humans suffering from mental fatigue. At

  12. Relative contributions of presystemic and systemic peptidases to oral exposure of a novel metabotropic glutamate 2/3 receptor agonist (LY404039) after oral administration of prodrug pomaglumetad methionil (LY2140023).

    Science.gov (United States)

    Annes, William F; Long, Amanda; Witcher, Jennifer W; Ayan-Oshodi, Mosun A; Knadler, Mary Pat; Zhang, Wei; Mitchell, Malcolm I; Cornelissen, Karen; Hall, Stephen D

    2015-01-01

    Pomaglumetad methionil (LY2140023) is the prodrug of a novel metabotropic glutamate 2/3 receptor agonist (LY404039) being investigated for the treatment of schizophrenia. Using accelerator mass spectrometry (AMS) and an intravenous (i.v.) radiolabeled tracer approach, the absolute bioavailability of the prodrug and the extent of its conversion to active moiety (LY404039) were estimated at presystemic (intestinal/first pass) and systemic sites after simultaneous oral and i.v. dosing in healthy subjects. The mean absolute bioavailability of prodrug (80 mg oral) was 0.68. On the basis of these data and a previous radiolabeled mass balance study in which no prodrug was recovered in feces, we concluded that 0.32 of the dose is converted to active drug in the intestinal tract. The fraction of prodrug converted to active moiety was approximately 1, indicating complete conversion of the prodrug that reaches the systemic circulation to the active moiety. Prodrug (80 mg oral and 100 μg i.v.) and active moiety (100 μg i.v.) were well tolerated in healthy subjects. Thus, the absolute bioavailability of prodrug LY2140023 and the fraction converted presystemically and systemically to active moiety LY404039 were estimated simultaneously using radiolabeled tracer microdosing and AMS. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

  13. The effect of pH and ADP on ammonia affinity for human glutamate dehydrogenases

    DEFF Research Database (Denmark)

    Zaganas, Ioannis; Pajecka, Kamilla; Nielsen, Camilla Wendel

    2013-01-01

    Glutamate dehydrogenase (GDH) uses ammonia to reversibly convert α-ketoglutarate to glutamate using NADP(H) and NAD(H) as cofactors. While GDH in most mammals is encoded by a single GLUD1 gene, humans and other primates have acquired a GLUD2 gene with distinct tissue expression profile. The two h...... of the kidney during systemic acidosis. The reverse could apply for conditions of local or systemic hyperammonemia or alkalosis....

  14. Glutamate synthase: An archaeal horizontal gene transfer?

    Indian Academy of Sciences (India)

    (GOGAT) which is a key enzyme in ammonia assimilation in bacteria, algae and plants. It catalyzes the reductive transamidation of amido nitrogen from glutamine to 2-oxoglutarate to form two molecules of glutamate (Temple et al 1998). Glutamate synthases differ according to their molecular weights, subunit compositions, ...

  15. Modeling of glutamate-induced dynamical patterns

    DEFF Research Database (Denmark)

    Faurby-Bentzen, Christian Krefeld; Zhabotinsky, A.M.; Laugesen, Jakob Lund

    2009-01-01

    Based on established physiological mechanisms, the paper presents a detailed computer model, which supports the hypothesis that temporal lobe epilepsy may be caused by failure of glutamate reuptake from the extracellular space. The elevated glutamate concentration causes an increased activation o...

  16. Glutamate Fermentation-2: Mechanism of L-Glutamate Overproduction in Corynebacterium glutamicum.

    Science.gov (United States)

    Hirasawa, Takashi; Wachi, Masaaki

    The nonpathogenic coryneform bacterium, Corynebacterium glutamicum, was isolated as an L-glutamate-overproducing microorganism by Japanese researchers and is currently utilized in various amino acid fermentation processes. L-Glutamate production by C. glutamicum is induced by limitation of biotin and addition of fatty acid ester surfactants and β-lactam antibiotics. These treatments affect the cell surface structures of C. glutamicum. After the discovery of C. glutamicum, many researchers have investigated the underlying mechanism of L-glutamate overproduction with respect to the cell surface structures of this organism. Furthermore, metabolic regulation during L-glutamate overproduction by C. glutamicum, particularly, the relationship between central carbon metabolism and L-glutamate biosynthesis, has been investigated. Recently, the role of a mechanosensitive channel protein in L-glutamate overproduction has been reported. In this chapter, mechanisms of L-glutamate overproduction by C. glutamicum have been reviewed.

  17. Competitive inhibition of glutamate dehydrogenase reaction.

    Science.gov (United States)

    Choudhury, Rajarshi; Punekar, Narayan S

    2007-06-12

    Irrespective of their pyridine nucleotide specificity, all glutamate dehydrogenases share a common chemical mechanism that involves an enzyme bound 'iminoglutarate' intermediate. Three compounds, structurally related to this intermediate, were tested for the inhibition of purified NADP-glutamate dehydrogenases from two Aspergilli, as also the bovine liver NAD(P)-glutamate dehydrogenase. 2-Methyleneglutarate, closely resembling iminoglutarate, was a potent competitive inhibitor of the glutamate dehydrogenase reaction. This is the first report of a non-aromatic structure with a better glutamate dehydrogenase inhibitory potency than aryl carboxylic acids such as isophthalate. A suitably located 2-methylene group to mimic the iminium ion could be exploited to design inhibitors of other amino acid dehydrogenases.

  18. Nitrogen in dietary glutamate is utilized exclusively for the synthesis of amino acids in the rat intestine.

    Science.gov (United States)

    Nakamura, Hidehiro; Kawamata, Yasuko; Kuwahara, Tomomi; Torii, Kunio; Sakai, Ryosei

    2013-01-01

    Although previous studies have shown that virtually the entire carbon skeleton of dietary glutamate (glutamate-C) is metabolized in the gut for energy production and amino acid synthesis, little is known regarding the fate of dietary glutamate nitrogen (glutamate-N). In this study, we hypothesized that dietary glutamate-N is an effective nitrogen source for amino acid synthesis and investigated the fate of dietary glutamate-N using [(15)N]glutamate. Fischer male rats were given hourly meals containing [U-(13)C]- or [(15)N]glutamate. The concentration and isotopic enrichment of several amino acids were measured after 0-9 h of feeding, and the net release of each amino acid into the portal vein was calculated. Most of the dietary glutamate-C was metabolized into CO(2), lactate, or alanine (56, 13, and 12% of the dietary input, respectively) in the portal drained viscera (PDV). Most of the glutamate-N was utilized for the synthesis of other amino acids such as alanine and citrulline (75 and 3% of dietary input, respectively) in the PDV, and only minor amounts were released into the portal vein in the form of ammonia and glutamate (2 and 3% of the dietary input, respectively). Substantial incorporation of (15)N into systemic amino acids such as alanine, glutamine, and proline, amino acids of the urea cycle, and branched-chain amino acids was also evident. These results provide quantitative evidence that dietary glutamate-N distributes extensively to amino acids synthesized in the PDV and, consequently, to circulating amino acids.

  19. GDH-Dependent Glutamate Oxidation in the Brain Dictates Peripheral Energy Substrate Distribution

    Directory of Open Access Journals (Sweden)

    Melis Karaca

    2015-10-01

    Full Text Available Glucose, the main energy substrate used in the CNS, is continuously supplied by the periphery. Glutamate, the major excitatory neurotransmitter, is foreseen as a complementary energy contributor in the brain. In particular, astrocytes actively take up glutamate and may use it through oxidative glutamate dehydrogenase (GDH activity. Here, we investigated the significance of glutamate as energy substrate for the brain. Upon glutamate exposure, astrocytes generated ATP in a GDH-dependent way. The observed lack of glutamate oxidation in brain-specific GDH null CnsGlud1−/− mice resulted in a central energy-deprivation state with increased ADP/ATP ratios and phospho-AMPK in the hypothalamus. This induced changes in the autonomous nervous system balance, with increased sympathetic activity promoting hepatic glucose production and mobilization of substrates reshaping peripheral energy stores. Our data reveal the importance of glutamate as necessary energy substrate for the brain and the role of central GDH in the regulation of whole-body energy homeostasis.

  20. Effects of Bee Venom on Glutamate-Induced Toxicity in Neuronal and Glial Cells

    Directory of Open Access Journals (Sweden)

    Sang Min Lee

    2012-01-01

    Full Text Available Bee venom (BV, which is extracted from honeybees, is used in traditional Korean medical therapy. Several groups have demonstrated the anti-inflammatory effects of BV in osteoarthritis both in vivo and in vitro. Glutamate is the predominant excitatory neurotransmitter in the central nervous system (CNS. Changes in glutamate release and uptake due to alterations in the activity of glutamate transporters have been reported in many neurodegenerative diseases, including Parkinson's disease, Alzheimer's disease, and amyotrophic lateral sclerosis. To assess if BV can prevent glutamate-mediated neurotoxicity, we examined cell viability and signal transduction in glutamate-treated neuronal and microglial cells in the presence and absence of BV. We induced glutamatergic toxicity in neuronal cells and microglial cells and found that BV protected against cell death. Furthermore, BV significantly inhibited the cellular toxicity of glutamate, and pretreatment with BV altered MAP kinase activation (e.g., JNK, ERK, and p38 following exposure to glutamate. These findings suggest that treatment with BV may be helpful in reducing glutamatergic cell toxicity in neurodegenerative diseases.

  1. Glutamate Metabolism in Brain Structures in Experimental Hemorrhagic Shock

    Directory of Open Access Journals (Sweden)

    V. N. Jakovlev

    2017-01-01

    Full Text Available Purpose. To study glutamate metabolism characteristics in phylogenetically different parts of the mammalian brain in experimentally induced hemorrhagic shock (HS in cats.Material and methods. Experiments were performed on 76 cats. HS was induced by intermittent bloodletting from femoral artery at a rate of 10ml/kg•10 minutes, with the average volume of 24±0.8 ml/kg. The bloodletting was discontinued after arterial pressure (BP drop to 60.0±1.5 mmHg. We studied ammonia, glutamate (Gt, and α-ketoglutarate (α-KG levels and glutaminase (GS and glutamate dehydrogenase (GDG activity in specimens harvested from phylogenetically different parts of the brain (cortex, limbic system, diencephalon, and medulla oblongata.Results. In intact animals, the peak GDG activity was found in the medulla oblongata (phylogenetically the oldest part of the brain and the peak GS activity was registered in the sensorimotor cortex (phylogenetically the youngest part of the brain; the glutaminase activity did not depend on the phylogenetic age of brain structures.In the case of HS, Gt metabolism changes began in the sensorimotor cortex manifested by decreased GS activity, which progresses by the 70th minute of the post%hemorrhagic period (PHP accompanied by delayed increase in the GDG and glutaminase activity, as well as Gt accumulation. In the limbic system and diencephalon the Gt metabolism was changing (impaired glutamine synthesis, stimuled Gt synthesis with glutamine desamidization and α%KG amination when developed by the 70th minute of the PHP. Similarly to sensorimotor cortex, changes were associated with Gt accumulation. During the agony, α%KG deficiency developed in all parts of the brain as a result of its increased contribution to Gt synthesis. At the same period of time, in the sensorimotor cortex, limbic system and diencephalon the Gt synthesis from glutamine was stimulated, however, the Gt contribution tothe formation of glutamine was decreased. The

  2. A radiometric microassay for glutamic acid decarboxylase

    International Nuclear Information System (INIS)

    Maderdrut, J.L.; North Carolina Univ., Chapel Hill

    1979-01-01

    A simple method for purifying L-[ 3 H] glutamic acid and incubation conditions suitable for estimating L-glutamic acid decarboxylase activity are described. Routine and recycled cation-exchange procedure for separating γ-aminobutyric acid from L-glutamate are outlined and compared. Recycling increases the sensitivity of the cation-exchange method by 6-7 fold. L-Glutamate decarboxylase activity can be measured reliably in samples of embryonic neural tissue having wet-weights of approximately 1 μg. The cation-exchange method is compared with the anion-exchange and CO 2 -trapping methods. L-Glutamate decarboxylase activity has been detected in the lumbar spinal cord of the chick embryo at Day 21/4 (stage 14) using the cation-exchange method. This is 5-6 days earlier than L-glutamate decarboxylase activity has been detected in embryonic neural tissue by previous investigators. L-Glutamate decarboxylase is present in the lumbar spinal cord at least as early as the birth of the first lumbar spinal cord neurons and at least 1-2 days before the initiation of synaptogenesis. (author)

  3. CHARACTERIZATION OF MODIFIED MONOSODIUM TITANATE - AN IMPROVED SORBENT FOR STRONTIUM AND ACTINIDE SEPARATIONS

    Energy Technology Data Exchange (ETDEWEB)

    Hobbs, D.; Taylor-Pashow, K.; Missimer, D.

    2010-12-21

    High-level nuclear waste produced from fuel reprocessing operations at the Savannah River Site (SRS) requires pretreatment to remove {sup 134,137}Cs, {sup 90}Sr, and alpha-emitting radionuclides (i.e., actinides) prior to disposal onsite as low level waste. An inorganic sorbent, monosodium titanate (MST), is currently used to remove {sup 90}Sr and alpha-emitting radionuclides, while a caustic-side solvent extraction process is used for removing {sup 134,137}Cs. A new peroxotitanate material, modified MST, or mMST, has recently been developed and has shown increased removal kinetics and capacity for {sup 90}Sr and alpha-emitting radionuclides compared to the current baseline material, MST. This paper describes recent results focused on further characterization of this material.

  4. Chronic effects of arsenic on American red crayfish, Procambarus clarkii, exposed to monosodium methanearsonate (MSMA) herbicide

    Energy Technology Data Exchange (ETDEWEB)

    Naqvi, S.M. (Southern Univ., Baton Rouge, LA (USA)); Flagge, C.T. (Bay De Noc Community College, Escanaba, MI (USA))

    1990-07-01

    Bioaccumulative and biomagnifying effects of arsenic on crayfish have been reported. However, no work has been done on the chronic effects of this heavy metal on crayfish populations. There is a great concern for MSMA (Monosodium Methanearsonate) herbicide in the vicinity of natural waters due to its high water solubility and bioaccumulative potential. American red crayfish (Procambarus clarkii) account for 98% of the annual crayfish harvest in North America. Those pesticides which have greater water solubility (i.e. MSMA) than other less soluble compounds may cause higher mortalities of aquatic organisms, or cause adverse chronic effects if the non-target animals are sublethally exposed. This work was conducted in the laboratory to assess the possible chronic effects of arsenic on crayfish.

  5. AMPK Activation Affects Glutamate Metabolism in Astrocytes

    DEFF Research Database (Denmark)

    Voss, Caroline Marie; Pajęcka, Kamilla; Stridh, Malin H

    2015-01-01

    acid (TCA) cycle was studied using high-performance liquid chromatography analysis supplemented with gas chromatography-mass spectrometry technology. It was found that AMPK activation had profound effects on the pathways involved in glutamate metabolism since the entrance of the glutamate carbon...... skeleton into the TCA cycle was reduced. On the other hand, glutamate uptake into the astrocytes as well as its conversion to glutamine catalyzed by glutamine synthetase was not affected by AMPK activation. Interestingly, synthesis and release of citrate, which are hallmarks of astrocytic function, were...

  6. Glutamate Receptor Stimulation Up-Regulates Glutamate Uptake in Human Müller Glia Cells.

    Science.gov (United States)

    López-Colomé, Ana María; López, Edith; Mendez-Flores, Orquidia G; Ortega, Arturo

    2016-07-01

    Glutamate, the main excitatory amino acid in the vertebrate retina, is a well know activator of numerous signal transduction pathways, and has been critically involved in long-term synaptic changes acting through ionotropic and metabotropic glutamate receptors. However, recent findings underlining the importance of intensity and duration of glutamate stimuli for specific neuronal responses, including excitotoxicity, suggest a crucial role for Na(+)-dependent glutamate transporters, responsible for the removal of this neurotransmitter from the synaptic cleft, in the regulation of glutamate-induced signaling. Transporter proteins are expressed in neurons and glia cells, albeit most of glutamate uptake occurs in the glial compartment. Within the retina, Müller glia cells are in close proximity to glutamatergic synapses and participate in the recycling of glutamate through the glutamate/glutamine shuttle. In this context, we decided to investigate a plausible role of glutamate as a regulatory signal for its own transport in human retinal glia cells. To this end, we determined [(3)H]-D-aspartate uptake in cultures of spontaneously immortalized human Müller cells (MIO-M1) exposed to distinct glutamatergic ligands. A time and dose-dependent increase in the transporter activity was detected. This effect was dependent on the activation of the N-methyl D-aspartate subtype of glutamate receptors, due to a dual effect: an increase in affinity and an augmented expression of the transporter at the plasma membrane, as established via biotinylation experiments. Furthermore, a NMDA-dependent association of glutamate transporters with the cystoskeletal proteins ezrin and glial fibrillary acidic protein was also found. These results add a novel mediator of the glutamate transporter modulation and further strengthen the notion of the critical involvement of glia cells in synaptic function.

  7. Relationship between glutamate dysfunction and symptoms and cognitive function in psychosis

    Directory of Open Access Journals (Sweden)

    Kate eMerritt

    2013-11-01

    Full Text Available The glutamate hypothesis of schizophrenia, proposed over two decades ago, originated following the observation that administration of drugs that block NMDA glutamate receptors, such as ketamine, could induce schizophrenia–like symptoms. Since then, this hypothesis has been extended to describe how glutamate abnormalities may disturb brain function and underpin psychotic symptoms and cognitive impairments. The glutamatergic system is now a major focus for the development of new compounds in schizophrenia. Relationships between regional brain glutamate function and symptom severity can be investigated using proton magnetic resonance spectroscopy (1H-MRS to estimate levels of glutamatergic metabolites in vivo. Here we briefly review the 1H-MRS studies that have explored relationships between glutamatergic metabolites, symptoms and cognitive function in clinical samples. While some of these studies suggest that more severe symptoms may be associated with elevated glutamatergic function in the anterior cingulate, studies in larger patient samples selected on the basis of symptom severity are required.

  8. Construction of a potentiometric glutamate biosensor for determination of glutamate in some real samples.

    Science.gov (United States)

    Y Lmaz, Demet; Karaku, Emine

    2011-12-01

    The potentiometric glutamate biosensor based on ammonium-selective poly(vinylchloride) (PVC) membrane electrode was constructed by chemically immobilizing glutamate oxidase. Ammonium ions produced after an enzymatic reaction were determined potentiometrically. We determined the optimum working conditions of the biosensor such as buffer concentration, buffer pH, lifetime, response time, linear working range, kinetic constants (K(m) and V(max)) of glutamate oxidase enzyme used for biosensor construction values, and other response characteristics. Additionally, glutamate assay in some real samples such as chicken bullion, healthy human serum, and commercial multipower amino acid mixture were also successfully carried out. The results showed good agreement with previously reported values.

  9. Glutamate stimulation of (/sup 3/H)dopamine release from dissociated cell cultures of rat ventral mesencephalon

    Energy Technology Data Exchange (ETDEWEB)

    Mount, H.; Welner, S.; Quirion, R.; Boksa, P.

    1989-04-01

    In dissociated cell cultures of fetal rat ventral mesencephalon preloaded with (3H)dopamine, glutamate (10(-5)-10(-3) M) stimulated the release of (3H)dopamine. Glutamate stimulation of (3H)dopamine release was Ca2+ dependent and was blocked by the glutamate antagonist, cis-2,3-piperidine dicarboxylic acid. Glutamate stimulation of (3H)dopamine release was not due to glutamate neurotoxicity because (1) glutamate did not cause release of a cytosolic marker, lactate dehydrogenase, and (2) preincubation of cultures with glutamate did not impair subsequent ability of the cells to take up or release (3H)dopamine. Thus, these dissociated cell cultures appear to provide a good model system to characterize glutamate stimulation of dopamine release. Release of (3H)dopamine from these cultures was stimulated by veratridine, an activator of voltage-sensitive Na+ channels, and this stimulation was blocked by tetrodotoxin. However, glutamate-stimulated (3H)dopamine release was not blocked by tetrodotoxin or Zn2+. Substitution of NaCl in the extracellular medium by sucrose, LiCl, or Na2SO4 had no effect on glutamate stimulation of (3H)dopamine release; however, release was inhibited when NaCl was replaced by choline chloride or N-methyl-D-glucamine HCl. Glutamate-stimulated (3H)-dopamine release was well maintained (60-82% of control) in the presence of Co2+, which blocks Ca2+ action potentials, and was unaffected by the local anesthetic, lidocaine. These results are discussed in terms of the receptor and ionic mechanisms involved in the stimulation of dopamine release by excitatory amino acids.

  10. Mechanism for the activation of glutamate receptors

    Science.gov (United States)

    Scientists at the NIH have used a technique called cryo-electron microscopy to determine a molecular mechanism for the activation and desensitization of ionotropic glutamate receptors, a prominent class of neurotransmitter receptors in the brain and spina

  11. Biobased synthesis of acrylonitrile from glutamic acid

    NARCIS (Netherlands)

    Notre, le J.E.L.; Scott, E.L.; Franssen, M.C.R.; Sanders, J.P.M.

    2011-01-01

    Glutamic acid was transformed into acrylonitrile in a two step procedure involving an oxidative decarboxylation in water to 3-cyanopropanoic acid followed by a decarbonylation-elimination reaction using a palladium catalyst

  12. Temperature-sensitive glutamate dehydrogenase mutants of Salmonella typhimurium.

    OpenAIRE

    Dendinger, S M; Brenchley, J E

    1980-01-01

    Mutants of Salmonella typhimurium defective in glutamate dehydrogenase activity were isolated in parent strains lacking glutamate synthase activity by localizcd mutagenesis or by a general mutagenesis combined with a cycloserine enrichment for glutamate auxotrophs. Two mutants with temperature-sensitive phenotypes had glutamate dehydrogenase activities that were more thermolabile than that of an isogenic control strain. Eight other mutants had less than 10% of the wild-type glutamate dehydrog...

  13. Asiatic acid, a pentacyclic triterpene in Centella asiatica, attenuates glutamate-induced cognitive deficits in mice and apoptosis in SH-SY5Y cells

    Science.gov (United States)

    Xu, Min-fang; Xiong, Yu-yun; Liu, Jian-kang; Qian, Jin-jun; Zhu, Li; Gao, Jing

    2012-01-01

    Aim: To investigate whether asiatic acid (AA), a pentacyclic triterpene in Centella asiatica, exerted neuroprotective effects in vitro and in vivo, and to determine the underlying mechanisms. Methods: Human neuroblastoma SH-SY5Y cells were used for in vitro study. Cell viability was determined with the MTT assay. Hoechst 33342 staining and flow cytometry were used to examine the apoptosis. The mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) were measured using fluorescent dye. PGC-1α and Sirt1 levels were examined using Western blotting. Neonatal mice were given monosodium glutamate (2.5 mg/g) subcutaneously at the neck from postnatal day (PD) 7 to 13, and orally administered with AA on PD 14 daily for 30 d. The learning and memory of the mice were evaluated with the Morris water maze test. HE staining was used to analyze the pyramidal layer structure in the CA1 and CA3 regions. Results: Pretreatment of SH-SY5Y cells with AA (0.1–100 nmol/L) attenuated toxicity induced by 10 mmol/L glutamate in a concentration-dependent manner. AA 10 nmol/L significantly decreased apoptotic cell death and reduced reactive oxygen species (ROS), stabilized the mitochondrial membrane potential (MMP), and promoted the expression of PGC-1α and Sirt1. In the mice models, oral administration of AA (100 mg/kg) significantly attenuated cognitive deficits in the Morris water maze test, and restored lipid peroxidation and glutathione and the activity of SOD in the hippocampus and cortex to the control levels. AA (50 and 100 mg/kg) also attenuated neuronal damage of the pyramidal layer in the CA1 and CA3 regions. Conclusion: AA attenuates glutamate-induced cognitive deficits of mice and protects SH-SY5Y cells against glutamate-induced apoptosis in vitro. PMID:22447225

  14. Posterior hypothalamus glutamate infusion decreases pentylenetetrazol-induced seizures of male rats through hippocampal histamine increase.

    Science.gov (United States)

    Arzhang, Atieh; Elahdadi Salmani, Mahmoud; Lashkarbolouki, Taghi; Goudarzi, Iran

    2017-07-01

    Seizures are epileptic manifestations that are intrinsically modulated through different neurotransmitters and receptor systems. Although glutamate increases excitation and hence seizures, it activates other systems which could potentially terminate seizures. Histamine originates from neurons of the posterior hypothalamus (PH) and can mediate anticonvulsant properties, but the effect of local PH glutamate on hippocampal histamine content is unknown. Therefore, in this study, the effect of PH glutamate and the involvement of hippocampal histamine in pentylenetetrazol (PTZ) induced seizure activity was studied. OX2R antagonist (TCS OX2 29, 40nmol/1μl, intra-PH), AMPA/Kainate receptor antagonist (CNQX, 3mM, intra-PH) and glutamate (1mM) were injected bilaterally into PH using stereotaxic surgery. The intravenous PTZ infusion model was used to generate behavioral convulsions and the amount of hippocampal histamine content was then measured using a biochemical method. Administration of glutamate into PH decreased both seizure stage and the duration of tonic-clonic convulsion (TCC) with increasing TCC latency and hippocampal histamine content. Blocking OX2Rs alone or coinhibition of OX2Rs and AMPA/kainate receptors reversed these effects by increasing both seizure stage and TCC duration, and by decreasing both latency and consequent histamine content. Our findings suggest that glutamate administration into PH may control seizures (stages and duration) through increasing the hippocampal histamine content. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Pharmacological or genetic orexin 1 receptor inhibition attenuates MK-801 induced glutamate release in mouse cortex

    Directory of Open Access Journals (Sweden)

    Leah eAluisio

    2014-05-01

    Full Text Available The orexin/hypocretin neuropeptides are produced by a cluster of neurons within the lateral posterior hypothalamus and participate in neuronal regulation by activating their receptors (OX1 and OX2 receptors. The orexin system projects widely through the brain and functions as an interface between multiple regulatory systems including wakefulness, energy balance, stress, reward and emotion. Recent studies have demonstrated that orexins and glutamate interact at the synaptic level and that orexins facilitate glutamate actions. We tested the hypothesis that orexins modulate glutamate signaling via OX1 receptors by monitoring levels of glutamate in frontal cortex of freely moving mice using enzyme coated biosensors under inhibited OX1 receptor conditions. MK-801, an NMDA receptor antagonist, was administered subcutaneously (0.178 mg/kg to indirectly disinhibit pyramidal neurons and therefore increase cortical glutamate release. In wild-type mice, pretreatment with the OX1 receptor antagonist GSK-1059865 (10 mg/kg S.C. which had no effect by itself, significantly attenuated the cortical glutamate release elicited by MK-801. OX1 receptor knockout mice had a blunted glutamate release response to MK-801 and exhibited about half of the glutamate release observed in wild-type mice in agreement with the data obtained with transient blockade of OX1 receptors. These results indicate that pharmacological (transient or genetic (permanent inhibition of the OX1 receptor similarly interfere with glutamatergic function in the cortex. Selectively targeting the OX1 receptor with an antagonist may normalize hyperglutamatergic states and thus may represent a novel therapeutic strategy for the treatment of various psychiatric disorders associated with hyperactive states.

  16. Intracellular synthesis of glutamic acid in Bacillus methylotrophicus SK19.001, a glutamate-independent poly(γ-glutamic acid)-producing strain.

    Science.gov (United States)

    Peng, Yingyun; Zhang, Tao; Mu, Wanmeng; Miao, Ming; Jiang, Bo

    2016-01-15

    Bacillus methylotrophicus SK19.001 is a glutamate-independent strain that produces poly(γ-glutamic acid) (γ-PGA), a polymer of D- and L-glutamic acids that possesses applications in food, the environment, agriculture, etc. This study was undertaken to explore the synthetic pathway of intracellular L- and D-glutamic acid in SK19.001 by investigating the effects of tricarboxylic acid cycle intermediates and different amino acids as metabolic precursors on the production of γ-PGA and analyzing the activities of the enzymes involved in the synthesis of L- and D-glutamate. Tricarboxylic acid cycle intermediates and amino acids could participate in the synthesis of γ-PGA via independent pathways in SK19.001. L-Aspartate aminotransferase, L-glutaminase and L-glutamate synthase were the enzymatic sources of L-glutamate. Glutamate racemase was responsible for the formation of D-glutamate for the synthesis of γ-PGA, and the synthetase had stereoselectivity for glutamate substrate. The enzymatic sources of L-glutamate were investigated for the first time in the glutamate-independent γ-PGA-producing strain, and multiple enzymatic sources of L-glutamate were verified in SK19.001, which will benefit efforts to improve production of γ-PGA with metabolic engineering strategies. © 2015 Society of Chemical Industry.

  17. Escherichia coli O157:H7 Glutamate- and Arginine-dependent Acid Resistance Systems Protect Against Oxidative Stress During Extreme Acid Challenge

    Science.gov (United States)

    To investigate the protection that several known Escherichia coli O157:H7 acid resistance systems provide against oxidative stress, the addition of diamide or hydrogen peroxide were used concomitant with acid challenge at pH 2.5 to determine bacterial survival. Diamide and hydrogen peroxide both de...

  18. Silicon Wafer-Based Platinum Microelectrode Array Biosensor for Near Real-Time Measurement of Glutamate in Vivo

    Directory of Open Access Journals (Sweden)

    Nigel T. Maidment

    2008-08-01

    Full Text Available Using Micro-Electro-Mechanical-Systems (MEMS technologies, we have developed silicon wafer-based platinum microelectrode arrays (MEAs modified with glutamate oxidase (GluOx for electroenzymatic detection of glutamate in vivo. These MEAs were designed to have optimal spatial resolution for in vivo recordings. Selective detection of glutamate in the presence of the electroactive interferents, dopamine and ascorbic acid, was attained by deposition of polypyrrole and Nafion. The sensors responded to glutamate with a limit of detection under 1μM and a sub-1-second response time in solution. In addition to extensive in vitro characterization, the utility of these MEA glutamate biosensors was also established in vivo. In the anesthetized rat, these MEA glutamate biosensors were used for detection of cortically-evoked glutamate release in the ventral striatum. The MEA biosensors also were applied to the detection of stress-induced glutamate release in the dorsal striatum of the freely-moving rat.

  19. Neuronal Glud1 (glutamate dehydrogenase 1) over-expressing mice: increased glutamate formation and synaptic release, loss of synaptic activity, and adaptive changes in genomic expression.

    Science.gov (United States)

    Michaelis, E K; Wang, X; Pal, R; Bao, X; Hascup, K N; Wang, Y; Wang, W-T; Hui, D; Agbas, A; Choi, I-Y; Belousov, A; Gerhardt, G A

    2011-09-01

    Glutamate dehydrogenase 1 (GLUD1) is a mitochondrial enzyme expressed in all tissues, including brain. Although this enzyme is expressed in glutamatergic pathways, its function as a regulator of glutamate neurotransmitter levels is still not well defined. In order to gain an understanding of the role of GLUD1 in the control of glutamate levels and synaptic release in mammalian brain, we generated transgenic (Tg) mice that over-express this enzyme in neurons of the central nervous system. The Tg mice have increased activity of GLUD, as well as elevated levels and increased synaptic and depolarization-induced release of glutamate. These mice suffer age-associated losses of dendritic spines, nerve terminals, and neurons. The neuronal losses and dendrite structural changes occur in select regions of the brain. At the transcriptional level in the hippocampus, cells respond by increasing the expression of genes related to neurite growth and synapse formation, indications of adaptive or compensatory responses to the effects of increases in the release and action of glutamate at synapses. Because these Tg mice live to a relatively old age they are a good model of the effects of a "hyperglutamatergic" state on the aging process in the nervous system. The mice are also useful in defining the molecular pathways affected by the over-activation of GLUD in glutamatergic neurons of the brain and spinal cord. Copyright © 2011 Elsevier Ltd. All rights reserved.

  20. Essential roles of aspartate aminotransferase 1 and vesicular glutamate transporters in β-cell glutamate signaling for incretin-induced insulin secretion.

    Directory of Open Access Journals (Sweden)

    Naoya Murao

    Full Text Available Incretins (GLP-1 and GIP potentiate insulin secretion through cAMP signaling in pancreatic β-cells in a glucose-dependent manner. We recently proposed a mechanistic model of incretin-induced insulin secretion (IIIS that requires two critical processes: 1 generation of cytosolic glutamate through the malate-aspartate (MA shuttle in glucose metabolism and 2 glutamate transport into insulin granules by cAMP signaling to promote insulin granule exocytosis. To directly prove the model, we have established and characterized CRISPR/Cas9-engineered clonal mouse β-cell lines deficient for the genes critical in these two processes: aspartate aminotransferase 1 (AST1, gene symbol Got1, a key enzyme in the MA shuttle, which generates cytosolic glutamate, and the vesicular glutamate transporters (VGLUT1, VGLUT2, and VGLUT3, gene symbol Slc17a7, Slc17a6, and Slc17a8, respectively, which participate in glutamate transport into secretory vesicles. Got1 knockout (KO β-cell lines were defective in cytosolic glutamate production from glucose and showed impaired IIIS. Unexpectedly, different from the previous finding that global Slc17a7 KO mice exhibited impaired IIIS from pancreatic islets, β-cell specific Slc17a7 KO mice showed no significant impairment in IIIS, as assessed by pancreas perfusion experiment. Single Slc17a7 KO β-cell lines also retained IIIS, probably due to compensatory upregulation of Slc17a6. Interestingly, triple KO of Slc17a7, Slc17a6, and Slc17a8 diminished IIIS, which was rescued by exogenously introduced wild-type Slc17a7 or Slc17a6 genes. The present study provides direct evidence for the essential roles of AST1 and VGLUTs in β-cell glutamate signaling for IIIS and also shows the usefulness of the CRISPR/Cas9 system for studying β-cells by simultaneous disruption of multiple genes.

  1. Diet-induced and monosodium-glutamate obesity in mice: Relationship among neuropeptide Y, CART peptide and cholecystokinin in feeding behavior

    Czech Academy of Sciences Publication Activity Database

    Železná, Blanka; Matyšková, Resha; Maixnerová, Jana; Haugvicová, Renata; Blokešová, Darja; Maletínská, Lenka

    2007-01-01

    Roč. 88, č. 4 (2007), s. 557 ISSN 0006-3525. [American Peptide Society Symposium /20./. 26.06.2007-30.06.2007, Montreal] Institutional research plan: CEZ:AV0Z40550506; CEZ:AV0Z50200510 Keywords : cocaine and amphetamine regulated transcript peptide * cholecystokinin Subject RIV: CE - Biochemistry

  2. Elevated AT1 receptor protein but lower angiotensin II-binding in adipose tissue of rats with monosodium glutamate-induced obesity

    Czech Academy of Sciences Publication Activity Database

    Pinterová, L.; Železná, Blanka; Ficková, M.; Macho, L.; Križanová, O.; Ježová, D.; Zórad, Š.

    2001-01-01

    Roč. 33, č. 12 (2001), s. 708-12 ISSN 0018-5043 R&D Projects: GA ČR GA204/99/1453 Grant - others:VEGA(SK) VEGA 2/7213; VEGA(SK) VEGA 2/6084; VEGA(SK) VEGA 2/7158 Keywords : AT1 receptor * fat tissue * MSG rat Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 1.910, year: 2001

  3. Regional regulation of glutamate signaling during cuprizone-induced demyelination in the brain.

    Science.gov (United States)

    Azami Tameh, Abolfazl; Clarner, Tim; Beyer, Cordian; Atlasi, Mohammad Ali; Hassanzadeh, Gholamreza; Naderian, Homayoun

    2013-10-01

    Glutamate excitotoxicity is associated with a wide range of neurodegenerative disorders and also seems to be involved in the pathology of demyelinating disorders such as multiple sclerosis (MS). Cuprizone-induced toxic demyelination shows clear characteristics of MS such as demyelination and axonal damage without the involvement of the innate immune system. In this study, we have evaluated glutamate signaling during cuprizone-induced demyelination in the white and gray matter of mouse brain by studying the expression of ionotropic and metabotropic glutamate-receptors and -transporters by Affymetrix gene array analysis, followed by real-time PCR and western blot analysis. Cellular localization of glutamate transporters was investigated by fluorescence double-labeling experiments. Comparing white and gray matter areas, the expression of glutamate receptors was region-specific. Among NMDA receptor subunits, NR2A was up-regulated in the demyelinated corpus callosum (CC), whereas the metabotropic glutamate receptor mGluR2 was down-regulated in demyelinated gray matter. Glutamate-aspartate transporter (GLAST) co-localizing with GFAP(+) astrocytes was increased in both demyelinated CC and telencephalic cortex, whereas Slc1a4 transporter was up-regulated only in CC. Our data indicate that cuprizone treatment affects glutamate-receptors and -transporters differently in gray and white matter brain areas revealing particularly regulation of GLAST and Slc1a4 compared with other genes. This might have an important influence on brain-region selective sensitivity to neurotoxic compounds and the progression of demyelination as has been reported for MS and other demyelinating neurological diseases. Copyright © 2013 Elsevier GmbH. All rights reserved.

  4. Biochemical evidence that L-glutamate is a neurotransmitter of primary vagal afferent nerve fibers

    International Nuclear Information System (INIS)

    Perrone, M.H.

    1981-01-01

    To determine in rat if vagal afferent fibers projecting into the intermediate one third of the nucleus tractus solitarius (NTS), the site of termination of baroafferents, utilize glutamate as a neurotransmitter, the high-affinity uptake of [ 3 H]L-glutamate and content of glutamate were analyzed in micropunches of rat brain stem. The intermediate NTS contains a high-affinity synaptosomal uptake system for [ 3 H]L-glutamate that is greater in capacity than that in areas adjacent to the NTS; it is almost two-fold higher than uptake in medial septum and nucleus accumbens and equal to that of hippocampal regions purportedly containing a rich glutamatergic innervation. Unilateral ablation of the nodose ganglion (i.e. cells of origin of vagal afferents) resulted, within 24 h in a prolonged significant reduction, to 56% of control, of [ 3 H]L-glutamate uptake, bilaterally in the NTS. The reduction of Na + -dependent synaptosomal uptake of [ 3 H]L-glutamate, resulted from a decrease in Vsub(max) without change in the Ksub(m) of the process, was anatomically restricted to the intermediate NTS, and was not associated with changes in [ 3 H]GABA uptake. The content of glutamate in the NTS was significantly (P < 0.01) decreased by 30% 7 days following unilateral extirpation of the nodose ganglion without changes in the concentrations of aspartate, glycine, glutamine, or GABA. A population of vagal afferent fibers projecting to NTS are glutamatergic. The results are consistent with the hypothesis obtained by physiological and pharmacological techniques that glutamate is a neurotransmitter of baroafferents. (Auth.)

  5. The structure and function of glutamate receptors: Mg2+ block to X-ray diffraction.

    Science.gov (United States)

    Mayer, Mark L

    2017-01-01

    Experiments on the action of glutamate on mammalian and amphibian nervous systems started back in the 1950s but decades passed before it became widely accepted that glutamate was the major excitatory neurotransmitter in the CNS. The pace of research greatly accelerated in the 1980s when selective ligands that identified glutamate receptor subtypes became widely available, and voltage clamp techniques, coupled with rapid perfusion, began to resolve the unique functional properties of what cloning subsequently revealed to be a large family of receptors with numerous subtypes. More recently the power of X-ray crystallography and cryo-EM has been applied to the study of glutamate receptors, revealing their atomic structures, and the conformational changes that underlie their gating. In this review I summarize the history of this field, viewed through the lens of a career in which I spent 3 decades working on the structure and function of glutamate receptor ion channels. This article is part of the Special Issue entitled 'Ionotropic glutamate receptors'. Published by Elsevier Ltd.

  6. The application of glutamic acid alpha-decarboxylase for the valorization of glutamic acid

    NARCIS (Netherlands)

    Lammens, T.M.; Biase, De Daniela; Franssen, M.C.R.; Scott, E.L.; Sanders, J.P.M.

    2009-01-01

    Glutamic acid is an important constituent of waste streams from biofuels production. It is an interesting starting material for the synthesis of nitrogen containing bulk chemicals, thereby decreasing the dependency on fossil fuels. On the pathway from glutamic acid to a range of molecules, the

  7. The Degradation of 14C-Glutamic Acid by L-Glutamic Acid Decarboxylase.

    Science.gov (United States)

    Dougherty, Charles M; Dayan, Jean

    1982-01-01

    Describes procedures and semi-micro reaction apparatus (carbon dioxide trap) to demonstrate how a particular enzyme (L-Glutamic acid decarboxylase) may be used to determine the site or sites of labeling in its substrate (carbon-14 labeled glutamic acid). Includes calculations, solutions, and reagents used. (Author/SK)

  8. Isocitrate Dehydrogenase and Glutamate Synthesis in Acetobacter suboxydans1

    Science.gov (United States)

    Greenfield, Seymour; Claus, G. W.

    1969-01-01

    Acetobacter suboxydans is an obligate aerobe for which an operative tricarboxylic acid cycle has not been demonstrated. Glutamate synthesis has been reported to occur by mechanisms other than those utilizing isocitrate dehydrogenase, a tricarboxylic acid cycle enzyme not previously detected in this organism. We have recovered α-ketoglutarate and glutamate from a system containing citrate, nicotinamide adenine dinucleotide (NAD), a divalent cation, pyridoxal phosphate, an amino donor, and dialyzed, cell-free extract. Aconitase activity was readily detected in these extracts, but isocitrate dehydrogenase activity, measured by NAD reduction, was masked by a cyanide-resistant, particulate, reduced NAD oxidase. Isocitrate dehydrogenase activity could be demonstrated after centrifuging the extracts at 150,000 × g for 3 hr and treating the supernatant fluid with 2-heptyl-4-hydroxyquinoline N-oxide. It is concluded that A. suboxydans can utilize the conventional tricarboxylic acid cycle enzymes to convert citrate to α-ketoglutarate which can then undergo a transamination to glutamate. Images PMID:5361215

  9. A Novel Amperometric Glutamate Biosensor Based on Glutamate Oxidase Adsorbed on Silicalite

    Science.gov (United States)

    Soldatkina, O. V.; Soldatkin, O. O.; Kasap, B. Ozansoy; Kucherenko, D. Yu.; Kucherenko, I. S.; Kurc, B. Akata; Dzyadevych, S. V.

    2017-04-01

    In this work, we developed a new amperometric biosensor for glutamate detection using a typical method of glutamate oxidase (GlOx) immobilization via adsorption on silicalite particles. The disc platinum electrode ( d = 0.4 mm) was used as the amperometric sensor. The procedure of biosensor preparation was optimized. The main parameters of modifying amperometric transducers with a silicalite layer were determined along with the procedure of GlOx adsorption on this layer. The biosensors based on GlOx adsorbed on silicalite demonstrated high sensitivity to glutamate. The linear range of detection was from 2.5 to 450 μM, and the limit of glutamate detection was 1 μM. It was shown that the proposed biosensors were characterized by good response reproducibility during hours of continuous work and operational stability for several days. The developed biosensors could be applied for determination of glutamate in real samples.

  10. Glutamate-induced obesity leads to decreased sperm reserves and acceleration of transit time in the epididymis of adult male rats.

    Science.gov (United States)

    Fernandes, Glaura Sa; Arena, Arielle C; Campos, Kleber E; Volpato, Gustavo T; Anselmo-Franci, Janete A; Damasceno, Débora C; Kempinas, Wilma G

    2012-12-05

    Given the established fact that obesity interferes with male reproductive functions, the present study aimed to evaluate sperm production in the testis and storage in the epididymis in a glutamate-induced model of obesity. Male rats were treated neonatally with monosodium glutamate (MSG) at doses of 4 mg/kg subcutaneously, or with saline solution (control group), on postnatal days 2, 4, 6, 8 and 10. On day 120, obesity was confirmed by the Lee index in all MSG-treated rats. After this, all animals from the two experimental groups were anesthetized and killed to evaluate body and reproductive organ weights, sperm parameters, plasma hormone levels (FSH, LH and testosterone), testicular and epididymal histo-morphometry and histopathology. Significant reductions in absolute and relative weights of testis, epididymis, prostate and seminal vesicle were noted in MSG-treated animals. In these same animals plasma testosterone and follicle-stimulating hormone (FSH) concentrations were decreased, as well as sperm counts in the testis and epididymis and seminiferous epithelium height and tubular diameter. The sperm transit time was accelerated in obese rats. However, the number of Sertoli cells per seminiferous tubule and stereological findings on the epididymis were not markedly changed by obesity. Neonatal MSG-administered model of obesity lowers sperm production and leads to a reduction in sperm storage in the epididymis of adult male rats. The acceleration of sperm transit time can have implications for the sperm quality of these rats.

  11. Glutamate-induced obesity leads to decreased sperm reserves and acceleration of transit time in the epididymis of adult male rats

    Directory of Open Access Journals (Sweden)

    Fernandes Glaura SA

    2012-12-01

    Full Text Available Abstract Background Given the established fact that obesity interferes with male reproductive functions, the present study aimed to evaluate sperm production in the testis and storage in the epididymis in a glutamate-induced model of obesity. Methods Male rats were treated neonatally with monosodium glutamate (MSG at doses of 4 mg/kg subcutaneously, or with saline solution (control group, on postnatal days 2, 4, 6, 8 and 10. On day 120, obesity was confirmed by the Lee index in all MSG-treated rats. After this, all animals from the two experimental groups were anesthetized and killed to evaluate body and reproductive organ weights, sperm parameters, plasma hormone levels (FSH, LH and testosterone, testicular and epididymal histo-morphometry and histopathology. Results Significant reductions in absolute and relative weights of testis, epididymis, prostate and seminal vesicle were noted in MSG-treated animals. In these same animals plasma testosterone and follicle-stimulating hormone (FSH concentrations were decreased, as well as sperm counts in the testis and epididymis and seminiferous epithelium height and tubular diameter. The sperm transit time was accelerated in obese rats. However, the number of Sertoli cells per seminiferous tubule and stereological findings on the epididymis were not markedly changed by obesity. Conclusions Neonatal MSG-administered model of obesity lowers sperm production and leads to a reduction in sperm storage in the epididymis of adult male rats. The acceleration of sperm transit time can have implications for the sperm quality of these rats.

  12. Chronic, systemic treatment with a metabotropic glutamate receptor 5 antagonist produces anxiolytic-like effects and reverses abnormal firing activity of projection neurons in the basolateral nucleus of the amygdala in rats with bilateral 6-OHDA lesions.

    Science.gov (United States)

    Chen, Li; Liu, Jian; Ali, Umar; Gui, Zhen Hua; Hou, Chen; Fan, Ling Ling; Wang, Yong; Wang, Tao

    2011-02-28

    Although 2-methyl-6-(phenylethynyl)-pyridine (MPEP), a selective metabotropic glutamate receptor 5 antagonist, improves the motor symptoms of Parkinson's disease (PD), the effects of MPEP on the psychiatric symptom of PD and the mechanism involved are still unclear. In the present study, we examined the effects of MPEP in anxiolytic-like behavior and firing activity of projection neurons in the basolateral nucleus of the amygdala (BLA) in rats with 6-hydroxydopamine (6-OHDA) injected bilaterally into dorsal striatum. Rats were divided into three groups, sham-operated group, 6-OHDA lesion with vehicle treatment group and 6-OHDA lesion with MPEP treatment group. Injection of 6-OHDA (10.5 μg) into the dorsal striatum produced 31.5% loss of tyrosine hydroxylase immunoreactive (TH-ir) neurons in the SNpc. The 6-OHDA-lesioned rats showed anxiety behavior and the firing rate of BLA projection neurons decreased significantly compared with sham-operated rats, and no difference was found in the firing pattern of these neurons. Whereas chronic, systemic treatment of MPEP (3 mg/kg/day, i.p.; 14 days) attenuated loss of TH-ir neurons, produced anxiolytic-like effect and normalized the abnormal firing rate of projection neurons of the BLA in rats with the bilateral lesions. Systemic administration of cumulative apomorphine (10-160 μg/kg, i.v.) inhibited the firing rate of BLA projection neurons in sham-operated, 6-OHDA lesion with vehicle-treated and MPEP-treated rats, but the 6-OHDA lesion decreased the response of BLA projection neurons to apomorphine stimulation, while MPEP reversed the reactivity of these neurons. These data demonstrate that the partial lesion of the nigrostriatal pathway causes anxiety symptom and decreases firing rate of BLA projection neurons in the rat. Furthermore, chronic, systemic MPEP treatment has the neuroprotective and anxiolytic-like effects, and reverses the abnormal firing rate of BLA projection neurons, suggesting that MPEP has important

  13. Vitamin C Protects Chondrocytes against Monosodium Iodoacetate-Induced Osteoarthritis by Multiple Pathways.

    Science.gov (United States)

    Chiu, Pu-Rong; Hu, Yu-Chen; Huang, Tzu-Ching; Hsieh, Bau-Shan; Yeh, Jou-Pei; Cheng, Hsiao-Ling; Huang, Li-Wen; Chang, Kee-Lung

    2016-12-27

    Osteoarthritis (OA) is the most prevalent joint disease. Dietary intake of vitamin C relates to a reduction in cartilage loss and OA. This study examined the efficacy of vitamin C to prevent OA with the in vitro chondrosarcoma cell line (SW1353) and the in vivo monosodium iodoacetate (MIA)-induced OA rat. Results demonstrated that, in SW1353 cells, treatment with 5 μM MIA inhibited cell growth and increased oxidative stress, apoptosis, and proteoglycan loss. In addition, the expression levels of the pro-inflammatory cytokines IL-6, IL-17A, and TNF-α and matrix metalloproteinases (MMPs) MMP-1, MMP-3, and MMP-13 were increased. All of these MIA-induced changes could be prevented with treatment of 100 μM vitamin C. In an animal model, intra-articular injection of MIA-induced cartilage degradation resembled the pathological changes of OA, and treatment of vitamin C could lessen these changes. Unexpectedly, vitamin C's effects did not strengthen with the increasing dosage, while the 100 mg/kg dosage was more efficient than the 200 or 300 mg/kg dosages. Vitamin C possessed multiple capacities for prevention of OA progress, including a decrease in apoptosis and in the expression of pro-inflammatory cytokines and MMPs in addition to the well-known antioxidation.

  14. Monosodium Urate Crystals Generate Nuclease-Resistant Neutrophil Extracellular Traps via a Distinct Molecular Pathway.

    Science.gov (United States)

    Chatfield, Simon M; Grebe, Kathrin; Whitehead, Lachlan W; Rogers, Kelly L; Nebl, Thomas; Murphy, James M; Wicks, Ian P

    2018-03-01

    Neutrophil extracellular traps (NETs) and the cell death associated with it (NETosis) have been implicated in numerous diseases. Mechanistic studies of NETosis have typically relied on nonphysiological stimuli, such as PMA. The human disease of gout is caused by monosodium urate (MSU) crystals. We observed that DNA consistent with NETs is present in fluid from acutely inflamed joints of gout patients. NETs also coat the crystals found in uninflamed tophi of chronic gout patients. We developed a quantitative, live cell imaging assay, which measures the key features of NETosis, namely, cell death and chromatin decondensation. We show that MSU and other physiologically relevant crystals induce NETosis through a molecular pathway that is distinct from PMA and Candida hyphae. Crystals interact with lysosomes to induce NADPH oxidase-independent cell death, with postmortem chromatin decondensation mediated by neutrophil elastase. The resulting MSU-induced NETs are enriched for actin and are resistant to serum and DNase degradation. These findings demonstrate a distinct physiological NETosis pathway in response to MSU crystals, which coats MSU crystals in DNA that persists in tissues as gouty tophi. Copyright © 2018 by The American Association of Immunologists, Inc.

  15. Effects of Tribulus terrestris on monosodium iodoacetate‑induced osteoarthritis pain in rats.

    Science.gov (United States)

    Park, Young Jin; Cho, Young-Rak; Oh, Joa Sub; Ahn, Eun-Kyung

    2017-10-01

    Tribulus terrestris L. (T. terrestris) has been used as a traditional medicine for the treatment of diuretic, lithontriptic, edema and urinary infections. Previous studies have indicated that it is effective in improving inflammation by regulating tumor necrosis factor‑α (TNF)‑α, interleukin (IL)‑6, IL‑10, nitric oxide (NO) and cyclooxygenase (COX)‑2. However, the effects and mechanism of action of T. terrestris on osteoarthritis (OA) remain unknown. Therefore, the present study aimed to evaluate the effects of the ethanolic extract of T. terrestris (ETT) in a monosodium iodoacetate (MIA)‑induced OA animal model. OA was induced in LEW/SSNHSD rats by intra‑articular injection of MIA. Morphometric changes and parameters of the tibial trabecular bone were determined using micro‑computed tomography. The molecular mechanisms of ETT in OA were investigated using reverse transcription‑polymerase chain reaction, western blotting and gelatin zymogram analysis. Treatment with ETT attenuated MIA‑induced OA, and this effect was mediated by the downregulation of NO synthase 2, COX‑2, TNF‑α and IL‑6. Furthermore, the ETT‑mediated attenuation of OA was also dependent on the expression of matrix metalloproteinases‑2 and ‑9. The results of the current study indicate that further evaluation of the mechanisms underlying the attenuation of MIA‑induced OA by ETT are required, and may support the development of ETT as a potential therapeutic agent for the treatment of inflammatory diseases such as OA.

  16. Effects of Tribulus terrestris on monosodium iodoacetate-induced osteoarthritis pain in rats

    Science.gov (United States)

    Park, Young Jin; Cho, Young-Rak; Oh, Joa Sub; Ahn, Eun-Kyung

    2017-01-01

    Tribulus terrestris L. (T. terrestris) has been used as a traditional medicine for the treatment of diuretic, lithontriptic, edema and urinary infections. Previous studies have indicated that it is effective in improving inflammation by regulating tumor necrosis factor-α (TNF)-α, interleukin (IL)-6, IL-10, nitric oxide (NO) and cyclooxygenase (COX)-2. However, the effects and mechanism of action of T. terrestris on osteoarthritis (OA) remain unknown. Therefore, the present study aimed to evaluate the effects of the ethanolic extract of T. terrestris (ETT) in a monosodium iodoacetate (MIA)-induced OA animal model. OA was induced in LEW/SSNHSD rats by intra-articular injection of MIA. Morphometric changes and parameters of the tibial trabecular bone were determined using micro-computed tomography. The molecular mechanisms of ETT in OA were investigated using reverse transcription-polymerase chain reaction, western blotting and gelatin zymogram analysis. Treatment with ETT attenuated MIA-induced OA, and this effect was mediated by the downregulation of NO synthase 2, COX-2, TNF-α and IL-6. Furthermore, the ETT-mediated attenuation of OA was also dependent on the expression of matrix metalloproteinases-2 and −9. The results of the current study indicate that further evaluation of the mechanisms underlying the attenuation of MIA-induced OA by ETT are required, and may support the development of ETT as a potential therapeutic agent for the treatment of inflammatory diseases such as OA. PMID:28849084

  17. The structure of glutamate transporters shows channel-like features

    NARCIS (Netherlands)

    Slotboom, DJ; Konings, WN; Lolkema, JS

    2001-01-01

    Neuronal and glial glutamate transporters remove the excitatory neurotransmitter glutamate from the synaptic cleft and thus prevent neurotoxicity, The proteins belong to a large family of secondary transporters, which includes transporters from a variety of bacterial, archaeal and eukaryotic

  18. Calcium pyrophosphate crystal deposition: the effect of monosodium urate and apatite crystals in a kinetic study using a gelatin matrix model.

    Science.gov (United States)

    Mandel, G S; Halverson, P B; Mandel, N S

    1988-06-01

    The kinetics of calcium pyrophosphate dihydrate (CPPD) crystal growth was studied by allowing calcium and pyrophosphate (PPi-4) ions to diffuse through a denatured collagen matrix (biological grade gelatin) in the presence of either monosodium urate monohydrate (MSU) or hydroxyapatite (HA) crystals. In this in vitro model system, MSU crystals significantly altered the kinetics of PPi-4 ionic diffusion through the gelatin matrix by allowing the [PPi-4] gradient to fall off much more rapidly, suggesting an increased level of scavenging of PPi-4 ions into crystalline materials. Even more significantly, the presence of MSU crystals markedly influenced the crystal growth morphology of triclinic CPPD, producing that observed in vivo. A large number of epitaxially dimensional matches between MSU and triclinic (t) and monoclinic (m) CPPD were identified, suggesting that MSU crystals can epitaxially induce CPPD crystal growth. This finding supports the hypothesis that the association of urate gout and CPPD crystal deposition disease is based on the nucleating potential of MSU crystals for CPPD crystal growth. In contrast, the HA crystal structure did not appear to serve as a nucleating agent for CPPD crystals. However, HA crystals did serve as effective traps for PPi-4 ions and their presence led to more stable CPPD crystal growth.

  19. Glutamate and dopamine in schizophrenia: an update for the 21st century

    Science.gov (United States)

    Howes, Oliver; McCutcheon, Rob; Stone, James

    2016-01-01

    The glutamate and dopamine hypotheses are leading theories of the pathoaetiology of schizophrenia. Both were initially based on indirect evidence from pharmacological studies supported by post-mortem findings, but have since been substantially advanced by new lines of evidence from in vivo imaging studies. This review provides an up- date on the latest findings on dopamine and glutamate abnormalities in schizophrenia, focusing on the in vivo neuroimaging studies in patients and clinical high risk groups, and considers their implications for understanding the biology and treatment of schizophrenia. These findings have refined both the dopamine and glutamate hypotheses, enabling greater anatomical and functional specificity, and have been complemented by preclinical evidence showing how the risk factors for schizophrenia impact on the dopamine and glutamate systems. The implications of this new evidence for understanding the development and treatment of schizophrenia are considered, and the gaps in current knowledge highlighted. Finally the evidence for an integrated model of the interactions between the glutamate and dopamine systems is reviewed, and future directions discussed. PMID:25586400

  20. Effects of blockade of sodium-dependent glutamate transporters on brain metabolism

    International Nuclear Information System (INIS)

    Moussa, C.E.-H.; Rae, C.; Bubb, W.A.; Blacar, V.J.

    2002-01-01

    Full text: L-Glutamic acid is the major excitatory amino acid in the CNS. Termination of the glutamatergic transmission and the clearance of excessive and neurotoxic glutamate are achieved by high affinity Na + -dependent uptake transporters. A number of neurodegenerative diseases have been imputed to failure of the Na + -dependent transport system, including motor neuron disease. In this study we examined the effects of blockade of glutamate transporters on the metabolism of guinea pig cortical brain slices (350 μm thickness). 13 C-NMR spectroscopy revealed a significant decrease (p 13 C label (flux) into individual isotopomers in the presence of LCCGIII (50 μM), a transportable glutamate uptake inhibitor. However, a significant increase in metabolic flux and fractional enrichment of metabolites was observed in the presence of 5 μM LCCG III. This is indicative of a mild stimulatory effect on metabolism due to inhibition of the transporters. A non-transportable blocker of glutamate transport, a,e-MPDC, produced a significant increase in metabolic fluxes and fractional enrichment of isotopomers, but had no effects on total metabolite pool sizes, in the presence of both 5 μM and 50 μM a,e-MPDC. Both 5 μM and 50 μM Lt-PDC increased the total metabolite pool sizes and the metabolic flux. These results suggest that blockade of glutamate transport lead to an increase of metabolic rate, which in turn may increase the rate of the glutamate-glutamine cycle and neurotransmitter release and, thus, produce neurotoxicity. Copyright (2002) Australian Neuroscience Society

  1. Glutamate released spontaneously from astrocytes sets the threshold for synaptic plasticity.

    Science.gov (United States)

    Bonansco, Christian; Couve, Alejandro; Perea, Gertrudis; Ferradas, Carla Á; Roncagliolo, Manuel; Fuenzalida, Marco

    2011-04-01

    Astrocytes exhibit spontaneous calcium oscillations that could induce the release of glutamate as gliotransmitter in rat hippocampal slices. However, it is unknown whether this spontaneous release of astrocytic glutamate may contribute to determining the basal neurotransmitter release probability in central synapses. Using whole-cell recordings and Ca(2+) imaging, we investigated the effects of the spontaneous astrocytic activity on neurotransmission and synaptic plasticity at CA3-CA1 hippocampal synapses. We show here that the metabolic gliotoxin fluorocitrate (FC) reduces the amplitude of evoked excitatory postsynaptic currents and increases the paired-pulse facilitation, mainly due to the reduction of the neurotransmitter release probability and the synaptic potency. FC also decreased intracellular Ca(2+) signalling and Ca(2+) -dependent glutamate release from astrocytes. The addition of glutamine rescued the effects of FC over the synaptic potency; however, the probability of neurotransmitter release remained diminished. The blockage of group I metabotropic glutamate receptors mimicked the effects of FC on the frequency of miniature synaptic responses. In the presence of FC, the Ca(2+) chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N ',N '-tetra-acetate or group I metabotropic glutamate receptor antagonists, the excitatory postsynaptic current potentiation induced by the spike-timing-dependent plasticity protocol was blocked, and it was rescued by delivering a stronger spike-timing-dependent plasticity protocol. Taken together, these results suggest that spontaneous glutamate release from astrocytes contributes to setting the basal probability of neurotransmitter release via metabotropic glutamate receptor activation, which could be operating as a gain control mechanism that regulates the threshold of long-term potentiation. Therefore, endogenous astrocyte activity provides a novel non-neuronal mechanism that could be critical for transferring information in

  2. 21 CFR 182.1047 - Glutamic acid hydrochloride.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Glutamic acid hydrochloride. 182.1047 Section 182.1047 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... Food Substances § 182.1047 Glutamic acid hydrochloride. (a) Product. Glutamic acid hydrochloride. (b...

  3. Neuroexcitatory amino acids: 4-methylene glutamic acid derivatives : Short Communication.

    Science.gov (United States)

    Receveur, J M; Roumestant, M L; Viallefont, P

    1995-12-01

    A short synthesis of 4-methylene glutamic acid was achieved. Under thermal conditions the corresponding anhydride reacted with 2,3 dimethylbutadiene to afford the corresponding DIELS-ALDER adduct in good yield. L-4-methylene glutamic acid essentially acts on glutamate metabotropic receptors and is as potent as L-Glu in producing IPs.

  4. Glutamate excitoxicity is the key molecular mechanism which is influenced by body temperature during the acute phase of brain stroke.

    Science.gov (United States)

    Campos, Francisco; Pérez-Mato, María; Agulla, Jesús; Blanco, Miguel; Barral, David; Almeida, Angeles; Brea, David; Waeber, Christian; Castillo, José; Ramos-Cabrer, Pedro

    2012-01-01

    Glutamate excitotoxicity, metabolic rate and inflammatory response have been associated to the deleterious effects of temperature during the acute phase of stroke. So far, the association of temperature with these mechanisms has been studied individually. However, the simultaneous study of the influence of temperature on these mechanisms is necessary to clarify their contributions to temperature-mediated ischemic damage. We used non-invasive Magnetic Resonance Spectroscopy to simultaneously measure temperature, glutamate excitotoxicity and metabolic rate in the brain in animal models of ischemia. The immune response to ischemia was measured through molecular serum markers in peripheral blood. We submitted groups of animals to different experimental conditions (hypothermia at 33°C, normothermia at 37°C and hyperthermia at 39°C), and combined these conditions with pharmacological modulation of glutamate levels in the brain through systemic injections of glutamate and oxaloacetate. We show that pharmacological modulation of glutamate levels can neutralize the deleterious effects of hyperthermia and the beneficial effects of hypothermia, however the analysis of the inflammatory response and metabolic rate, demonstrated that their effects on ischemic damage are less critical than glutamate excitotoxity. We conclude that glutamate excitotoxicity is the key molecular mechanism which is influenced by body temperature during the acute phase of brain stroke.

  5. Influence of Glutamic Acid on the Properties of Poly(xylitol glutamate sebacate Bioelastomer

    Directory of Open Access Journals (Sweden)

    Weifu Dong

    2013-11-01

    Full Text Available In order to further improve the biocompatibility of xylitol based poly(xylitol sebacate (PXS bioelastomer, a novel kind of amino acid based poly(xylitol glutamate sebacate (PXGS has been successfully prepared in this work by melt polycondensation of xylitol, N-Boc glutamic acid and sebacic acid. Differential scanning calorimetry (DSC results indicated the glass-transition temperatures could be decreased by feeding N-Boc glutamic acid. In comparison to PXS, PXGS exhibited comparable tensile strength and much higher elongation at break at the same ratio of acid/xylitol. The introduction of glutamic acid increased the hydrophilicity and in vitro degradation rate of the bioelastomer. It was found that PXGS exhibited excellent properties, such as tensile properties, biodegradability and hydrophilicity, which could be easily tuned by altering the feeding monomer ratios. The amino groups in the PXGS polyester side chains are readily functionalized, thus the biomelastomers can be considered as potential biomaterials for biomedical application.

  6. L-glutamate Receptor In Paramecium

    Science.gov (United States)

    Bernal-Martínez, Juan; Ortega-Soto, Arturo

    2004-09-01

    Behavioral, electrophysiological and biochemical experiments were performed in order to establish the presence of a glutamate receptor in the ciliate Paramecium. It was found that an AMPA/KA receptor is functionally expressed in Paramecium and that this receptor is immunologically and fillogenetically related to the AMPA/KA receptor present in vertebrates.

  7. Glutamate mediated astrocytic filtering of neuronal activity.

    Directory of Open Access Journals (Sweden)

    Gilad Wallach

    2014-12-01

    Full Text Available Neuron-astrocyte communication is an important regulatory mechanism in various brain functions but its complexity and role are yet to be fully understood. In particular, the temporal pattern of astrocyte response to neuronal firing has not been fully characterized. Here, we used neuron-astrocyte cultures on multi-electrode arrays coupled to Ca2+ imaging and explored the range of neuronal stimulation frequencies while keeping constant the amount of stimulation. Our results reveal that astrocytes specifically respond to the frequency of neuronal stimulation by intracellular Ca2+ transients, with a clear onset of astrocytic activation at neuron firing rates around 3-5 Hz. The cell-to-cell heterogeneity of the astrocyte Ca2+ response was however large and increasing with stimulation frequency. Astrocytic activation by neurons was abolished with antagonists of type I metabotropic glutamate receptor, validating the glutamate-dependence of this neuron-to-astrocyte pathway. Using a realistic biophysical model of glutamate-based intracellular calcium signaling in astrocytes, we suggest that the stepwise response is due to the supralinear dynamics of intracellular IP3 and that the heterogeneity of the responses may be due to the heterogeneity of the astrocyte-to-astrocyte couplings via gap junction channels. Therefore our results present astrocyte intracellular Ca2+ activity as a nonlinear integrator of glutamate-dependent neuronal activity.

  8. Glutamate Mediated Astrocytic Filtering of Neuronal Activity

    Science.gov (United States)

    Herzog, Nitzan; De Pittà, Maurizio; Jacob, Eshel Ben; Berry, Hugues; Hanein, Yael

    2014-01-01

    Neuron-astrocyte communication is an important regulatory mechanism in various brain functions but its complexity and role are yet to be fully understood. In particular, the temporal pattern of astrocyte response to neuronal firing has not been fully characterized. Here, we used neuron-astrocyte cultures on multi-electrode arrays coupled to Ca2+ imaging and explored the range of neuronal stimulation frequencies while keeping constant the amount of stimulation. Our results reveal that astrocytes specifically respond to the frequency of neuronal stimulation by intracellular Ca2+ transients, with a clear onset of astrocytic activation at neuron firing rates around 3-5 Hz. The cell-to-cell heterogeneity of the astrocyte Ca2+ response was however large and increasing with stimulation frequency. Astrocytic activation by neurons was abolished with antagonists of type I metabotropic glutamate receptor, validating the glutamate-dependence of this neuron-to-astrocyte pathway. Using a realistic biophysical model of glutamate-based intracellular calcium signaling in astrocytes, we suggest that the stepwise response is due to the supralinear dynamics of intracellular IP3 and that the heterogeneity of the responses may be due to the heterogeneity of the astrocyte-to-astrocyte couplings via gap junction channels. Therefore our results present astrocyte intracellular Ca2+ activity as a nonlinear integrator of glutamate-dependent neuronal activity. PMID:25521344

  9. Amperometric L-glutamate biosensor based on bacterial cell-surface displayed glutamate dehydrogenase

    Energy Technology Data Exchange (ETDEWEB)

    Liang, Bo [Laboratory for Biosensing, Key Laboratory of Biofuels, and Shandong Provinicial Key Laboratory of Energy Genetics, Qingdao Institute of Bioenergy & Bioprocess Technology, Chinese Academy of Sciences, 189 Songling Road, Qingdao 266101 (China); University of Chinese Academy of Sciences, 19A Yuquan Road, Beijing 100049 (China); Zhang, Shu [Laboratory for Biosensing, Key Laboratory of Biofuels, and Shandong Provinicial Key Laboratory of Energy Genetics, Qingdao Institute of Bioenergy & Bioprocess Technology, Chinese Academy of Sciences, 189 Songling Road, Qingdao 266101 (China); Key Laboratory of Marine Chemistry Theory and Technology of Ministry of Education, Ocean University of China, 238 Songling Road, Qingdao 266100 (China); Lang, Qiaolin [Laboratory for Biosensing, Key Laboratory of Biofuels, and Shandong Provinicial Key Laboratory of Energy Genetics, Qingdao Institute of Bioenergy & Bioprocess Technology, Chinese Academy of Sciences, 189 Songling Road, Qingdao 266101 (China); Song, Jianxia; Han, Lihui [Key Laboratory of Marine Chemistry Theory and Technology of Ministry of Education, Ocean University of China, 238 Songling Road, Qingdao 266100 (China); Liu, Aihua, E-mail: liuah@qibebt.ac.cn [Laboratory for Biosensing, Key Laboratory of Biofuels, and Shandong Provinicial Key Laboratory of Energy Genetics, Qingdao Institute of Bioenergy & Bioprocess Technology, Chinese Academy of Sciences, 189 Songling Road, Qingdao 266101 (China); University of Chinese Academy of Sciences, 19A Yuquan Road, Beijing 100049 (China)

    2015-07-16

    Highlights: • E. coli surface-dispalyed Gldh exhibiting excellent enzyme activity and stability. • Sensitive amperometric biosensor for glutamate using Gldh-bacteria and MWNTs. • The glutamate biosensor exhibited high specificity and stability. - Abstract: A novel L-glutamate biosensor was fabricated using bacteria surface-displayed glutamate dehydrogenase (Gldh-bacteria). Here the cofactor NADP{sup +}-specific dependent Gldh was expressed on the surface of Escherichia coli using N-terminal region of ice nucleation protein (INP) as the anchoring motif. The cell fractionation assay and SDS-PAGE analysis indicated that the majority of INP-Gldh fusion proteins were located on the surface of cells. The biosensor was fabricated by successively casting polyethyleneimine (PEI)-dispersed multi-walled carbon nanotubes (MWNTs), Gldh-bacteria and Nafion onto the glassy carbon electrode (Nafion/Gldh-bacteria/PEI-MWNTs/GCE). The MWNTs could not only significantly lower the oxidation overpotential towards NAPDH, which was the product of NADP{sup +} involving in the oxidation of glutamate by Gldh, but also enhanced the current response. Under the optimized experimental conditions, the current–time curve of the Nafion/Gldh-bacteria/PEI-MWNTs/GCE was performed at +0.52 V (vs. SCE) by amperometry varying glutamate concentration. The current response was linear with glutamate concentration in two ranges (10 μM–1 mM and 2–10 mM). The low limit of detection was estimated to be 2 μM glutamate (S/N = 3). Moreover, the proposed biosensor is stable, specific, reproducible and simple, which can be applied to real samples detection.

  10. Strontium D-Glutamate Hexahydrate and Strontium Di(hydrogen L-glutamate) Pentahydrate

    DEFF Research Database (Denmark)

    Christgau, Stephan; Odderhede, Jette; Stahl, Kenny

    2005-01-01

    Sr(C5H7NO4)] center dot 6H(2)O, ( I), and [Sr(C5H8NO4)(2)] center dot 5H(2)O, (II), both crystallize with similar strontium - glutamate - water layers. In ( I), the neutral layers are connected through hydrogen bonds by water molecules, while in ( II), the positively charged layers are connected...... through hydrogen bonds and electrostatic interactions by interleaving layers of hydrogen glutamate anions and water molecules....

  11. ¹³C-metabolic enrichment of glutamate in glutamate dehydrogenase mutants of Saccharomyces cerevisiae.

    Science.gov (United States)

    Tang, Yijin; Sieg, Alex; Trotter, Pamela J

    2011-10-20

    Glutamate dehydrogenases (GDH) interconvert α-ketoglutarate and glutamate. In yeast, NADP-dependent enzymes, encoded by GDH1 and GDH3, are reported to synthesize glutamate from α-ketoglutarate, while an NAD-dependent enzyme, encoded by GDH2, catalyzes the reverse. Cells were grown in acetate/raffinose (YNAceRaf) to examine the role(s) of these enzymes during aerobic metabolism. In YNAceRaf the doubling time of wild type, gdh2Δ, and gdh3Δ cells was comparable at ∼4 h. NADP-dependent GDH activity (Gdh1p+Gdh3p) in wild type, gdh2Δ, and gdh3Δ was decreased ∼80% and NAD-dependent activity (Gdh2p) in wild type and gdh3Δ was increased ∼20-fold in YNAceRaf as compared to glucose. Cells carrying the gdh1Δ allele did not divide in YNAceRaf, yet both the NADP-dependent (Gdh3p) and NAD-dependent (Gdh2p) GDH activity was ∼3-fold higher than in glucose. Metabolism of [1,2-(13)C]-acetate and analysis of carbon NMR spectra were used to examine glutamate metabolism. Incorporation of (13)C into glutamate was nearly undetectable in gdh1Δ cells, reflecting a GDH activity at glutamate carbons indicates a decreased rate of glutamate biosynthesis from acetate in gdh2Δ and gdh3Δ strains as compared to wild type. Further, the relative complexity of (13)C-isotopomers at early time points was noticeably greater in gdh3Δ as compared to wild type and gdh2Δ cells. These in vivo data show that Gdh1p is the primary GDH enzyme and Gdh2p and Gdh3p play evident roles during aerobic glutamate metabolism. Copyright © 2010 Elsevier GmbH. All rights reserved.

  12. Amperometric L-glutamate biosensor based on bacterial cell-surface displayed glutamate dehydrogenase.

    Science.gov (United States)

    Liang, Bo; Zhang, Shu; Lang, Qiaolin; Song, Jianxia; Han, Lihui; Liu, Aihua

    2015-07-16

    A novel L-glutamate biosensor was fabricated using bacteria surface-displayed glutamate dehydrogenase (Gldh-bacteria). Here the cofactor NADP(+)-specific dependent Gldh was expressed on the surface of Escherichia coli using N-terminal region of ice nucleation protein (INP) as the anchoring motif. The cell fractionation assay and SDS-PAGE analysis indicated that the majority of INP-Gldh fusion proteins were located on the surface of cells. The biosensor was fabricated by successively casting polyethyleneimine (PEI)-dispersed multi-walled carbon nanotubes (MWNTs), Gldh-bacteria and Nafion onto the glassy carbon electrode (Nafion/Gldh-bacteria/PEI-MWNTs/GCE). The MWNTs could not only significantly lower the oxidation overpotential towards NAPDH, which was the product of NADP(+) involving in the oxidation of glutamate by Gldh, but also enhanced the current response. Under the optimized experimental conditions, the current-time curve of the Nafion/Gldh-bacteria/PEI-MWNTs/GCE was performed at +0.52 V (vs. SCE) by amperometry varying glutamate concentration. The current response was linear with glutamate concentration in two ranges (10 μM-1 mM and 2-10 mM). The low limit of detection was estimated to be 2 μM glutamate (S/N=3). Moreover, the proposed biosensor is stable, specific, reproducible and simple, which can be applied to real samples detection. Copyright © 2015 Elsevier B.V. All rights reserved.

  13. Reciprocal regulation between taurine and glutamate response via Ca2+- dependent pathways in retinal third-order neurons

    Directory of Open Access Journals (Sweden)

    Bulley Simon

    2010-08-01

    Full Text Available Abstract Although taurine and glutamate are the most abundant amino acids conducting neural signals in the central nervous system, the communication between these two neurotransmitters is largely unknown. This study explores the interaction of taurine and glutamate in the retinal third-order neurons. Using specific antibodies, both taurine and taurine transporters were localized in photoreceptors and Off-bipolar cells, glutamatergic neurons in retinas. It is possible that Off-bipolar cells release juxtaposed glutamate and taurine to activate the third-order neurons in retina. The interaction of taurine and glutamate was studied in acutely dissociated third-order neurons in whole-cell patch-clamp recording and Ca2+ imaging. We find that taurine effectively reduces glutamate-induced Ca2+ influx via ionotropic glutamate receptors and voltage-dependent Ca2+ channels in the neurons, and the effect of taurine was selectively inhibited by strychnine and picrotoxin, but not GABA receptor antagonists, although GABA receptors are present in the neurons. A CaMKII inhibitor partially reversed the effect of taurine, suggesting that a Ca2+/calmodulin-dependent pathway is involved in taurine regulation. On the other hand, a rapid influx of Ca2+ through ionotropic glutamate receptors could inhibit the amplitude and kinetics of taurine-elicited currents in the third-order neurons, which could be controlled with intracellular application of BAPTA a fast Ca2+ chelator. This study indicates that taurine is a potential neuromodulator in glutamate transmission. The reciprocal inhibition between taurine and glutamate in the postsynaptic neurons contributes to computation of visual signals in the retinal neurons.

  14. Genetic differences in the modulation of accumbal glutamate and γ-amino butyric acid levels after cocaine-induced reinstatement.

    Science.gov (United States)

    Miguéns, Miguel; Botreau, Fanny; Olías, Oscar; Del Olmo, Nuria; Coria, Santiago M; Higuera-Matas, Alejandro; Ambrosio, Emilio

    2013-07-01

    The Lewis (LEW) and Fischer 344 (F344) inbred rat strains are frequently used to study the role of genetic factors in vulnerability to drug addiction and relapse. Glutamate and γ-amino butyric acid (GABA) transmission are significantly altered after cocaine-induced reinstatement, although whether LEW and F344 rats differ in their accumbal glutamate and GABA responsiveness to cocaine-induced reinstatement remains unknown. To investigate this, we measured by in vivo microdialysis extracellular glutamate and GABA levels in the core division of the nucleus accumbens after extinction of cocaine self-administration and during cocaine-induced reinstatement (7.5mg/kg, i.p.) in these two strains of rats. No strain differences were evident in cocaine self-administration or extinction behavior, although cocaine priming did induce a higher rate of lever pressing in LEW compared with F344 rats. After extinction, F344 rats that self-administered cocaine had less GABA than the saline controls, while the glutamate levels remained constant in both strains. There was more accumbal glutamate after cocaine priming in LEW rats that self-administered cocaine, while GABA levels were unaffected. By contrast, GABA increased transiently in F344 rats that self-administered cocaine, while glutamate levels were unaltered. In F344 saline controls, cocaine priming provoked contrasting effects in glutamate and GABA levels, inducing a delayed increase in glutamate and a delayed decrease in GABA levels. These amino acids were unaffected by cocaine priming in LEW saline rats. Together, these results suggest that genetic differences in cocaine-induced reinstatement reflect different responses of the accumbal GABA and glutamate systems to cocaine priming. © 2011 The Authors, Addiction Biology © 2011 Society for the Study of Addiction.

  15. Identification of monosodium urate crystal deposits in patients with asymptomatic hyperuricemia using dual-energy CT

    Science.gov (United States)

    Smith, Stacy E; Garg, Rajesh; Lu, Fengxin; Wohlfahrt, Alyssa; Campos, Anarosa; Vanni, Kathleen; Yu, Zhi; Solomon, Daniel H; Kim, Seoyoung C

    2018-01-01

    Objectives Dual-energy CT (DECT) scan is a sensitive and specific tool used to visualise and quantify monosodium urate (MSU) crystal deposits in the joints. Few studies have examined MSU crystal deposits in patients with asymptomatic hyperuricemia (ie, hyperuricemia in the absence of gout) using DECT. Methods We conducted a prospective, non-interventional cross-sectional study to detect MSU crystal deposits on DECT scans among patients with asymptomatic hyperuricemia. We also examined patient factors associated with subclinical MSU crystal deposits. Out of 130 subjects aged ≥40 years with metabolic syndrome screened for serum uric acid (sUA) levels ≥6.5 mg/dL, 46 underwent a foot/ankle DECT scan. Results The mean age of the study participants was 62 (±8) years, 41% were men and the mean sUA level was 7.8 (±1.0) mg/dL. Seven (15%) of 46 patients had MSU crystal deposits on DECT with a mean total volume of 0.13 (±0.14) cm3. In the univariable logistic regression analysis, older age had a significant association with presence of MSU crystal deposits (OR 1.20, 95% CI 1.03 to 1.39), but sUA did not (OR 1.36, 95% CI 0.63 to 2.95). In the univariable analysis, sUA levels showed a trend towards a modest linear association (β=0.11, P=0.09) with total volume of MSU crystal deposits. Conclusions Fifteen per cent of patients with asymptomatic hyperuricemia had subclinical MSU crystal deposits on foot/ankle DECT scans. Older age, but not sUA, was significantly associated with presence of subclinical MSU crystal deposits among patients with asymptomatic hyperuricemia. Clinical significance of these subclinical MSU crystal deposits needs to be determined. PMID:29556417

  16. Invariant Natural Killer T Cells Ameliorate Monosodium Urate Crystal-Induced Gouty Inflammation in Mice

    Directory of Open Access Journals (Sweden)

    Jie Wang

    2017-12-01

    Full Text Available Gout is an inflammatory arthritis caused by deposition of intra-articular monosodium urate (MSU crystal. Previous studies have focused on resident macrophage, infiltrating monocyte, and neutrophil responses to MSU crystal; yet the mechanisms of cellular changes and the potential involvement of other regulatory immune cells remain largely unknown. Invariant natural killer T (iNKT cells, an innate type of T cell, are involved in the development of various inflammatory diseases. Here, we investigate the role of iNKT cells in MSU crystal-induced gouty inflammation. MSU crystal-induced inflammatory profiles in an air-pouch model were examined in iNKT-deficient CD1d knockout (KO and wild-type (WT control mice. To explore potential mechanisms of iNKT cell regulation of gouty inflammation, we cocultured CD4+ or CD4−iNKT cells with bone marrow-derived macrophages (BMDMs. We found that iNKT cells quickly migrated to the site of inflammation upon MSU crystal stimulation in WT mice. The total number of infiltrating cells in CD1d KO mice, especially neutrophils, was dramatically increased at 6 and 12 h (P < 0.01 post-MSU crystal challenge, compared with WT controls. BMDMs cocultured with CD4+iNKT cells produced less tumor necrosis factor-α and expressed higher levels of M2 macrophage markers, including Clec7a, Pdcd1Ig2, and interleukin-4 (P < 0.01, compared with BMDMs cocultured with CD4−iNKT cells or conventional CD4+ T cells. CD4+iNKT cells are one of the key regulators of MSU crystal-induced gouty inflammation through the control of macrophage polarization. iNKT cells may serve as a new therapeutic target for gout.

  17. Microbial production of poly-γ-glutamic acid.

    Science.gov (United States)

    Sirisansaneeyakul, Sarote; Cao, Mingfeng; Kongklom, Nuttawut; Chuensangjun, Chaniga; Shi, Zhongping; Chisti, Yusuf

    2017-09-05

    Poly-γ-glutamic acid (γ-PGA) is a natural, biodegradable and water-soluble biopolymer of glutamic acid. This review is focused on nonrecombinant microbial production of γ-PGA via fermentation processes. In view of its commercial importance, the emphasis is on L-glutamic acid independent producers (i.e. microorganisms that do not require feeding with the relatively expensive amino acid L-glutamic acid to produce γ-PGA), but glutamic acid dependent production is discussed for comparison. Strategies for improving production, reducing costs and using renewable feedstocks are discussed.

  18. Repeated Administration of Cigarette Smoke Condensate Increases Glutamate Levels and Behavioral Sensitization

    Directory of Open Access Journals (Sweden)

    In Soo Ryu

    2018-03-01

    Full Text Available Nicotine, a nicotinic acetylcholine receptor agonist, produces the reinforcing effects of tobacco dependence by potentiating dopaminergic and glutamatergic neurotransmission. Non-nicotine alkaloids in tobacco also contribute to dependence by activating the cholinergic system. However, glutamatergic neurotransmission in the dorsal striatum associated with behavioral changes in response to cigarette smoking has not been investigated. In this study, the authors investigated alterations in glutamate levels in the rat dorsal striatum related to behavioral alterations after repeated administration of cigarette smoke condensate (CSC using the real-time glutamate biosensing and an open-field behavioral assessment. Repeated administration of CSC including 0.4 mg nicotine (1.0 mL/kg/day, subcutaneous for 14 days significantly increased extracellular glutamate concentrations more than repeated nicotine administration. In parallel with the hyperactivation of glutamate levels, repeated administration of CSC-evoked prolonged hypersensitization of psychomotor activity, including locomotor and rearing activities. These findings suggest that the CSC-induced psychomotor activities are closely associated with the elevation of glutamate concentrations in the rat dorsal striatum.

  19. A selective review of glutamate pharmacological therapy in obsessive–compulsive and related disorders

    Directory of Open Access Journals (Sweden)

    Grados MA

    2015-04-01

    Full Text Available Marco A Grados,1 Elizabeth B Atkins,2 Gabriela I Kovacikova,3 Erin McVicar4 1Division of Child and Adolescent Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD, 2Department of Psychology, Smith College, Northampton, MA, 3Department of Psychology, Wellesley College, Wellesley, MA, 4Susquehanna University, Selinsgrove, PA, USA Abstract: Glutamate, an excitatory central nervous system neurotransmitter, is emerging as a potential alternative pharmacological treatment when compared to gamma-aminobutyric acid (GABA-, dopamine-, and serotonin-modulating treatments for neuropsychiatric conditions. The pathophysiology, animal models, and clinical trials of glutamate modulation are explored in disorders with underlying inhibitory deficits (cognitive, motor, behavioral including obsessive–compulsive disorder, attention deficit hyperactivity disorder, Tourette syndrome, trichotillomania, excoriation disorder, and nail biting. Obsessive–compulsive disorder, attention deficit hyperactivity disorder, and grooming disorders (trichotillomania and excoriation disorder have emerging positive data, although only scarce controlled trials are available. The evidence is less supportive for the use of glutamate modulators in Tourette syndrome. Glutamate-modulating agents show promise in the treatment of disorders of inhibition. Keywords: glutamate, obsessive–compulsive disorder, attention deficit hyperactivity disorder, trichotillomania, excoriation disorder, modulation

  20. Glutamate uptake is important for osmoregulation and survival in the rice pathogen Burkholderia glumae.

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    Yongsung Kang

    Full Text Available Bacteria exhibit an optimal growth rate in culture media with sufficient nutrients at an optimal temperature and pH. In addition, the concentration of solutes plays a critical role in bacterial growth and survival. Glutamate is known to be a major anionic solute involved in osmoregulation and the bacterial cell's response to changes in solute concentration. To determine how glutamate uptake is involved in osmoregulation in the rice bacterial pathogen Burkholderia glumae BGR1, we mutated the gltI gene encoding a periplasmic substrate binding protein of a glutamate transport system to abolish glutamate uptake, and monitored the growth of the gltI null mutant in Luria-Bertani medium. We found that the gltI null mutant showed a slower growth rate than the wild-type strain and experienced hyperosmotic stress resulting in water loss from the cytoplasm in stationary phase. When the incubation time was extended, the mutant population collapsed due to the hyperosmotic stress. The gltI null mutant exhibited loss of adaptability under both hypoosmotic and hyperosmotic stresses. The growth rate of the gltI null mutant was restored to the level of wild-type growth by exogenous addition of glycine betaine to the culture medium, indicating that glycine betaine is a compatible solute in B. glumae. These results indicate that glutamate uptake from the environment plays a key role in osmoregulation in B. glumae.

  1. Tetrodotoxin effects in the stimulated acetylcholine release by agonist of glutamate in mice striatum tissue

    International Nuclear Information System (INIS)

    Paes, Paulo Cesar de Arruda; Camillo, Maria A.P.; Rogero, Jose Roberto; Troncone, Lanfranco R.P.

    2002-01-01

    The toxins of animal venoms have been used as important tools for biochemical studies of physiological and pathological processes of diverse systems. In this work we used the action of tetrodotoxin on sodium channels to map the localization of glutamate receptors in cholinergic neurons from striatum tissue of rats. All glutamate receptors are exciting, so they promote the release of other neurotransmitters. In this work we focus on acetylcholine. The localization of glutamate receptor, on the soma or on the excitatory terminal, may contribute for a better understanding of its function. For this work we applied the in vitro method of tritiated neurotransmitter release. The agonists of glutamate receptors chosen were glutamic acid 500μM, NMDA 100μM, kainic acid 300μM, quisqualic acid 300μM and AMPA 1mM. In the first part of the assay the basal and stimulated releases were measured and in the second, the same protocol was performed in the presence of tetrodotoxin 1μM. The reductions observed in basal and stimulated release in the presence of tetrodotoxin suggested that the receptors type AMPA and NMDA were located in soma of cholinergic cell preferentially and the other ones presented a more equilibrate distribution among the axons and the soma. (author)

  2. Inhibitors of glutamate dehydrogenase block sodium-dependent glutamate uptake in rat brain membranes

    Directory of Open Access Journals (Sweden)

    Brendan S Whitelaw

    2013-09-01

    Full Text Available We recently found evidence for anatomic and physical linkages between the astroglial Na+-dependent glutamate transporters (GLT-1/EAAT2 and GLAST/EAAT1 and mitochondria. In these same studies, we found that the glutamate dehydrogenase (GDH inhibitor, epigallocatechin-monogallate (EGCG, inhibits both glutamate oxidation and Na+-dependent glutamate uptake in astrocytes. In the present study, we extend this finding by exploring the effects of EGCG on Na+-dependent L-[3H]-glutamate (Glu uptake in crude membranes (P2 prepared from rat brain cortex. In this preparation, uptake is almost exclusively mediated by GLT-1. EGCG inhibited L-[3H]-Glu uptake in cortical membranes with an IC50 value of 230 µM. We also studied the effects of two additional inhibitors of GDH, hexachlorophene (HCP and bithionol (BTH. Both of these compounds also caused concentration-dependent inhibition of glutamate uptake in cortical membranes. Pre-incubating with HCP for up to 15 min had no greater effect than that observed with no pre-incubation, showing that the effects occur rapidly. HCP decreased the Vmax for glutamate uptake without changing the Km, consistent with a non-competitive mechanism of action. EGCG, HCP, and BTH also inhibited Na+-dependent transport of D-[3H]-aspartate (Asp, a non-metabolizable substrate, and [3H]-γ-aminobutyric acid (GABA. In contrast to the forebrain, glutamate uptake in crude cerebellar membranes (P2 is likely mediated by GLAST (EAAT1. Therefore, the effects of these compounds were examined in cerebellar membranes. In this region, none of these compounds had any effect on uptake of either L-[3H]-Glu or D-[3H]-Asp, but they all inhibited [3H]-GABA uptake. Together these studies suggest that GDH is preferentially required for glutamate uptake in forebrain as compared to cerebellum, and GDH may be required for GABA uptake as well. They also provide further evidence for a functional linkage between glutamate transport and mitochondria.

  3. Microsensors for in vivo Measurement of Glutamate in Brain Tissue

    Directory of Open Access Journals (Sweden)

    Miranda van der Zeyden

    2008-11-01

    Full Text Available Several immobilized enzyme-based electrochemical biosensors for glutamate detection have been developed over the last decade. In this review, we compare first and second generation sensors. Structures, working mechanisms, interference prevention, in vitro detection characteristics and in vivo performance are summarized here for those sensors that have successfully detected brain glutamate in vivo. In brief, first generation sensors have a simpler structure and are faster in glutamate detection. They also show a better sensitivity to glutamate during calibration in vitro. For second generation sensors, besides their less precise detection, their fabrication is difficult to reproduce, even with a semi-automatic dip-coater. Both generations of sensors can detect glutamate levels in vivo, but the reported basal levels are different. In general, second generation sensors detect higher basal levels of glutamate compared with the results obtained from first generation sensors. However, whether the detected glutamate is indeed from synaptic sources is an issue that needs further attention.

  4. Glutamate Efflux at the Blood-Brain Barrier

    DEFF Research Database (Denmark)

    Cederberg-Helms, Hans Christian; Uhd-Nielsen, Carsten; Brodin, Birger

    2014-01-01

    L-Glutamate is considered the most important excitatory amino acid in the mammalian brain. Strict control of its concentration in the brain interstitial fluid is important to maintain neurotransmission and avoid excitotoxicity. The role of astrocytes in handling L-glutamate transport and metabolism...... is well known, however endothelial cells may also play an important role through mediating brain-to-blood L-glutamate efflux. Expression of excitatory amino acid transporters has been demonstrated in brain endothelial cells of bovine, human, murine, rat and porcine origin. These can account for high...... affinity concentrative uptake of L-glutamate from the brain interstitial fluid into the capillary endothelial cells. The mechanisms in between L-glutamate uptake in the endothelial cells and L-glutamate appearing in the blood are still unclear and may involve a luminal transporter for L-glutamate...

  5. The Challenge of Interpreting Glutamate-Receptor Ion-Channel Structures.

    Science.gov (United States)

    Mayer, Mark L

    2017-11-21

    Ion channels activated by glutamate mediate excitatory synaptic transmission in the central nervous system. Similar to other ligand-gated ion channels, their gating cycle begins with transitions from a ligand-free closed state to glutamate-bound active and desensitized states. In an attempt to reveal the molecular mechanisms underlying gating, numerous structures for glutamate receptors have been solved in complexes with agonists, antagonists, allosteric modulators, and auxiliary proteins. The embarrassingly rich library of structures emerging from this work reveals very dynamic molecules with a more complex conformational spectrum than anticipated from functional studies. Unanticipated conformations solved for complexes with competitive antagonists and a lack of understanding of the structural basis for ion channel subconductance states further highlight challenges that have yet to be addressed. Published by Elsevier Inc.

  6. Automatic production of 13NH3 and L-[13N] glutamate ready for intravenous injection

    International Nuclear Information System (INIS)

    Suzuki, K.; Tamate, K.

    1984-01-01

    A system has been developed for the automatic production of 13 NH 3 and L-[ 13 N]glutamate for i.v. injection. Up to 250 mCi of 13 NH 3 and 60 mCi of L-[ 13 N]glutamate were produced at radiochemical purities of 99.9% with the equipment. The required times were 8.2 and 17.5 min, respectively. Pyrogen and glutamate dehydrogenase (GDH) were not detected in the product. The solution was obtained without any sterile procedure other than the filtration with an autoclaved ultrafilter (NMWL = 10,000) assembly at the final production stage. Penetration ratios through the filter were -6 and 2 x 10 -7 of the order of 6 x 10 -7 for GDH and E. Coli endotoxin, respectively. A new 47 mm diameter filter holder with a small dead volume (approx. 0.6 mL) was devised for easy assembly of the sterilized filter. (author)

  7. Glutamate alteration of glutamic acid decarboxylase (GAD) in GABAergic neurons: the role of cysteine proteases.

    Science.gov (United States)

    Monnerie, Hubert; Le Roux, Peter D

    2008-09-01

    Brain cell vulnerability to neurologic insults varies greatly, depending on their neuronal subpopulation. Among cells that survive a pathological insult such as ischemia or brain trauma, some may undergo morphological and/or biochemical changes that could compromise brain function. We previously reported that surviving cortical GABAergic neurons exposed to glutamate in vitro displayed an NMDA receptor (NMDAR)-mediated alteration in the levels of the GABA synthesizing enzyme glutamic acid decarboxylase (GAD65/67) [Monnerie, H., Le Roux, P., 2007. Reduced dendrite growth and altered glutamic acid decarboxylase (GAD) 65- and 67-kDa isoform protein expression from mouse cortical GABAergic neurons following excitotoxic injury in vitro. Exp. Neurol. 205, 367-382]. In this study, we examined the mechanisms by which glutamate excitotoxicity caused a change in cortical GABAergic neurons' GAD protein levels. Removing extracellular calcium prevented the NMDAR-mediated decrease in GAD protein levels, measured using Western blot techniques, whereas inhibiting calcium entry through voltage-gated calcium channels had no effect. Glutamate's effect on GAD protein isoforms was significantly attenuated by preincubation with the cysteine protease inhibitor N-Acetyl-L-Leucyl-L-Leucyl-L-norleucinal (ALLN). Using class-specific protease inhibitors, we observed that ALLN's effect resulted from the blockade of calpain and cathepsin protease activities. Cell-free proteolysis assay confirmed that both proteases were involved in glutamate-induced alteration in GAD protein levels. Together these results suggest that glutamate-induced excitotoxic stimulation of NMDAR in cultured cortical neurons leads to altered GAD protein levels from GABAergic neurons through intracellular calcium increase and protease activation including calpain and cathepsin. Biochemical alterations in surviving cortical GABAergic neurons in various disease states may contribute to the altered balance between excitation

  8. Neuronal Activity and Glutamate Uptake Decrease Mitochondrial Mobility in Astrocytes and Position Mitochondria Near Glutamate Transporters

    Science.gov (United States)

    Jackson, Joshua G.; O'Donnell, John C.; Takano, Hajime; Coulter, Douglas A.

    2014-01-01

    Within neurons, mitochondria are nonuniformly distributed and are retained at sites of high activity and metabolic demand. Glutamate transport and the concomitant activation of the Na+/K+-ATPase represent a substantial energetic demand on astrocytes. We hypothesized that mitochondrial mobility within astrocytic processes might be regulated by neuronal activity and glutamate transport. We imaged organotypic hippocampal slice cultures of rat, in which astrocytes maintain their highly branched morphologies and express glutamate transporters. Using time-lapse confocal microscopy, the mobility of mitochondria within individual astrocytic processes and neuronal dendrites was tracked. Within neurons, a greater percentage of mitochondria were mobile than in astrocytes. Furthermore, they moved faster and farther than in astrocytes. Inhibiting neuronal activity with tetrodotoxin (TTX) increased the percentage of mobile mitochondria in astrocytes. Mitochondrial movement in astrocytes was inhibited by vinblastine and cytochalasin D, demonstrating that this mobility depends on both the microtubule and actin cytoskeletons. Inhibition of glutamate transport tripled the percentage of mobile mitochondria in astrocytes. Conversely, application of the transporter substrate d-aspartate reversed the TTX-induced increase in the percentage of mobile mitochondria. Inhibition of reversed Na+/Ca2+ exchange also increased the percentage of mitochondria that were mobile. Last, we demonstrated that neuronal activity increases the probability that mitochondria appose GLT-1 particles within astrocyte processes, without changing the proximity of GLT-1 particles to VGLUT1. These results imply that neuronal activity and the resulting clearance of glutamate by astrocytes regulate the movement of astrocytic mitochondria and suggest a mechanism by which glutamate transporters might retain mitochondria at sites of glutamate uptake. PMID:24478345

  9. Modafinil attenuates reinstatement of cocaine seeking: role for cystine-glutamate exchange and metabotropic glutamate receptors.

    Science.gov (United States)

    Mahler, Stephen V; Hensley-Simon, Megan; Tahsili-Fahadan, Pouya; LaLumiere, Ryan T; Thomas, Charles; Fallon, Rebecca V; Kalivas, Peter W; Aston-Jones, Gary

    2014-01-01

    Modafinil may be useful for treating stimulant abuse, but the mechanisms by which it acts to do so are unknown. Indeed, a primary effect of modafinil is to inhibit dopamine transport, which typically promotes rather than inhibits motivated behavior. Therefore, we examined the role of nucleus accumbens extracellular glutamate and the group II metabotropic glutamate receptor (mGluR2/3) in modafinil effects. One group of rats was trained to self-administer cocaine for 10 days and extinguished, then given priming injections of cocaine to elicit reinstatement. Modafinil (300 mg/kg, intraperitoneal) inhibited reinstated cocaine seeking (but did not alter extinction responding by itself), and this effect was prevented by pre-treatment with bilateral microinjections of the mGluR2/3 antagonist LY-341495 (LY) into nucleus accumbens core. No reversal of modafinil effects was seen after unilateral accumbens core LY, or bilateral LY in the rostral pole of accumbens. Next, we sought to explore effects of modafinil on extracellular glutamate levels in accumbens after chronic cocaine. Separate rats were administered non-contingent cocaine, and after 3 weeks of withdrawal underwent accumbens microdialysis. Modafinil increased extracellular accumbens glutamate in chronic cocaine, but not chronic saline-pre-treated animals. This increase was prevented by reverse dialysis of cystine-glutamate exchange or voltage-dependent calcium channel antagonists. Voltage-dependent sodium channel blockade partly attenuated the increase in glutamate, but mGluR1 blockade did not. We conclude that modafinil increases extracellular glutamate in nucleus accumbens from glial and neuronal sources in cocaine-exposed rats, which may be important for its mGluR2/3-mediated antirelapse properties. © 2012 The Authors, Addiction Biology © 2012 Society for the Study of Addiction.

  10. Developmental expression of glutamate transporters and glutamate dehydrogenase in astrocytes of the postnatal rat hippocampus.

    Science.gov (United States)

    Kugler, Peter; Schleyer, Verena

    2004-01-01

    Glutamate is the major excitatory transmitter in the CNS and plays distinct roles in a number of developmental events. Its extracellular concentration, which mediates these activities, is regulated by glutamate transporters in glial cells and neurons. In the present study, we have used nonradioactive in situ hybridization, immunocytochemistry, and immunoblotting to show the cellular and regional expression of the high-affinity glutamate transporters GLAST (EAAT1) and generic GLT1 (EAAT2; glial form of GLT1) in the rat hippocampus during postnatal development (P1-60). The results of transporter expression were compared with the localization and activity pattern of glutamate dehydrogenase (GDH), an important glutamate-metabolizing enzyme. The study showed that both transporters and GDH were demonstrable at P1 (day of birth). The expression of GLAST (detected by in situ hybridization and immunocytochemistry) in the early postnatal development was higher than GLT1. Thereafter, the expression of both transporters increased, showing adult levels at between P20 and P30 (detected by in situ hybridization and immunoblotting). At these time points, the expression of GLT1 appeared to be significantly higher than the GLAST expression. GLT1 and GLAST proteins were demonstrable only in astrocytes. The increase of GDH activities (steepest increase from P5-P8), which were localized preferentially in astrocytes, was in agreement with the increase of transporter expression, preferentially with that of GLT1. These observations suggest that the extent of glutamate transporter expression and of glutamate-metabolizing GDH activity in astrocytes is intimately correlated with the formation of glutamatergic synapses in the developing hippocampus. 2004 Wiley-Liss, Inc.

  11. Glutamate receptor antagonists with the potential for migraine treatment.

    Science.gov (United States)

    Ferrari, Anna; Rustichelli, Cecilia; Baraldi, Carlo

    2017-12-01

    Preclinical, clinical, and other (e.g., genetic) evidence support the concept that migraine susceptibility may at least partially result from a glutamatergic system disorder. Therefore, the receptors of the glutamatergic system are considered relatively new targets for investigational drugs to treat migraine. Investigational and established glutamate receptor antagonists (GluRAs) have been shown to possess antinociceptive properties in preclinical models of trigeminovascular nociception and have been evaluated in clinical trials. This review focuses on preclinical and clinical studies of GluRAs for the treatment of migraine. Areas covered: A PubMed database search (from 1987 to December 2016) and a review of published studies on GluRAs in migraine were conducted. Expert opinion: All published clinical trials of investigational GluRAs have been unsuccessful in establishing benefit for acute migraine treatment. Clinical trial results contrast with the preclinical data, suggesting that glutamate (Glu) does not play a decisive role after the attack has already been triggered. These antagonists may instead be useful for migraine prophylaxis. Improving patient care requires further investigating and critically analyzing the role of Glu in migraine, designing experimental models to study more receptors and their corresponding antagonists, and identifying biomarkers to facilitate trials designed to target specific subgroups of migraine patients.

  12. Functional and structural remodeling of glutamate synapses in prefrontal and frontal cortex induced by behavioral stress

    Directory of Open Access Journals (Sweden)

    Laura eMusazzi

    2015-04-01

    Full Text Available Increasing evidence has shown that the pathophysiology of neuropsychiatric disorders, including mood disorders, is associated with abnormal function and regulation of the glutamatergic system. Consistently, preclinical studies on stress-based animal models of pathology showed that glucocorticoids and stress exert crucial effects on neuronal excitability and function, especially in cortical and limbic areas. In prefrontal and frontal cortex, acute stress was shown to induce enhancement of glutamate release/transmission dependent on activation of corticosterone receptors. Although the mechanisms whereby stress affects glutamate transmission have not yet been fully understood, it was shown that synaptic, non-genomic action of corticosterone is required to increase the readily releasable pool of glutamate vesicles but is not sufficient to enhance transmission in prefrontal and frontal cortex. Slower, partly genomic mechanisms are probably necessary for the enhancement of glutamate transmission induced by stress.Combined evidence has suggested that the changes in glutamate release and transmission are responsible for the dendritic remodeling and morphological changes induced by stress and it has been argued that sustained alterations of glutamate transmission may play a key role in the long-term structural/functional changes associated with mood disorders in patients. Intriguingly, modifications of the glutamatergic system induced by stress in the prefrontal cortex seem to be biphasic. Indeed, while the fast response to stress suggests an enhancement in the number of excitatory synapses, synaptic transmission and working memory, long-term adaptive changes -including those consequent to chronic stress- induce opposite effects. Better knowledge of the cellular effectors involved in this biphasic effect of stress may be useful to understand the pathophysiology of stress-related disorders, and open new paths for the development of therapeutic approaches.

  13. Anhydrous thallium hydrogen L-glutamate: polymer networks formed by sandwich layers of oxygen-coordinated thallium ions cores shielded by hydrogen L-glutamate counterions.

    Science.gov (United States)

    Bodner, Thomas; Wirnsberger, Bianca; Albering, Jörg; Wiesbrock, Frank

    2011-11-07

    Anhydrous thallium hydrogen L-glutamate [Tl(L-GluH)] crystallizes from water (space group P2(1)) with a layer structure in which the thallium ions are penta- and hexacoordinated exclusively by the oxygen atoms of the γ-carboxylate group of the hydrogen L-glutamate anions to form a two-dimensional coordination polymer. The thallium-oxygen layer is composed of Tl(2)O(2) and TlCO(2) quadrangles and is only 3 Å high. Only one hemisphere of the thallium ions participates in coordination, indicative of the presence of the 6s(2) lone pair of electrons. The thallium-oxygen assemblies are shielded by the hydrogen l-glutamate anions. Only the carbon atom of the α-carboxylate group deviates from the plane spanned by the thallium ions, the γ-carboxylate groups and the proton bearing carbon atoms, which are in trans conformation. Given the abundance of L-glutamic and L-aspartic acid in biological systems on the one hand and the high toxicity of thallium on the other hand, it is worth mentioning that the dominant structural motifs in the crystal structure of [Tl(L-GluH)] strongly resemble their corresponding analogues in the crystalline phase of [K(L-AspH)(H(2)O)(2)].

  14. The Glutamine-Glutamate/GABA Cycle

    DEFF Research Database (Denmark)

    Walls, Anne B; Waagepetersen, Helle S; Bak, Lasse Kristoffer

    2015-01-01

    The operation of a glutamine-glutamate/GABA cycle in the brain consisting of the transfer of glutamine from astrocytes to neurons and neurotransmitter glutamate or GABA from neurons to astrocytes is a well-known concept. In neurons, glutamine is not only used for energy production and protein...... synthesis, as in other cells, but is also an essential precursor for biosynthesis of amino acid neurotransmitters. An excellent tool for the study of glutamine transfer from astrocytes to neurons is [(14)C]acetate or [(13)C]acetate and the glial specific enzyme inhibitors, i.e. the glutamine synthetase...... inhibitor methionine sulfoximine and the tricarboxylic acid cycle (aconitase) inhibitors fluoro-acetate and -citrate. Acetate is metabolized exclusively by glial cells, and [(13)C]acetate is thus capable when used in combination with magnetic resonance spectroscopy or mass spectrometry, to provide...

  15. Binding thermodynamics of a glutamate transporter homologue

    Science.gov (United States)

    Reyes, Nicolas; Oh, SeCheol; Boudker, Olga

    2013-01-01

    Glutamate transporters catalyze concentrative uptake of the neurotransmitter into glial cells and neurons. Their transport cycle involves binding and release of the substrate on the extra- and intracellular sides of the plasma membranes, and translocation of the substrate-binding site across the lipid bilayers. The energy of the ionic gradients, mainly sodium, fuels the cycle. Here, we used a cross-linking approach to trap a glutamate transporter homologue from Pyrococcus horikoshii in key conformational states with substrate-binding site facing either the extracellular or intracellular sides of the membrane to study their binding thermodynamics. We show that the chemical potential of sodium ions in solution is exclusively coupled to substrate binding and release, and not to substrate translocation. Despite the structural symmetry, the binding mechanisms are distinct on the opposite sides of the membrane and more complex than the current models suggest. PMID:23563139

  16. Glutamate dehydrogenase (RocG) in Bacillus licheniformis WX-02: Enzymatic properties and specific functions in glutamic acid synthesis for poly-γ-glutamic acid production.

    Science.gov (United States)

    Tian, Guangming; Wang, Qin; Wei, Xuetuan; Ma, Xin; Chen, Shouwen

    2017-04-01

    Poly-γ-glutamic acid (γ-PGA), a natural biopolymer, is widely used in cosmetics, medicine, food, water treatment, and agriculture owing to its features of moisture sequestration, cation chelation, non-toxicity and biodegradability. Intracellular glutamic acid, the substrate of γ-PGA, is a limiting factor for high yield in γ-PGA production. Bacillus subtilis and Bacillus licheniformis are both important γ-PGA producing strains, and B. subtilis synthesizes glutamic acid in vivo using the unique GOGAT/GS pathway. However, little is known about the glutamate synthesis pathway in B. licheniformis. The aim of this work was to characterize the glutamate dehydrogenase (RocG) in glutamic acid synthesis from B. licheniformis with both in vivo and in vitro experiments. By re-directing the carbon flux distribution, the rocG gene deletion mutant WX-02ΔrocG produced intracellular glutamic acid with a concentration of 90ng/log(CFU), which was only 23.7% that of the wild-type WX-02 (380ng/log(CFU)). Furthermore, the γ-PGA yield of mutant WX-02ΔrocG was 5.37g/L, a decrease of 45.3% compared to the wild type (9.82g/L). In vitro enzymatic assays of RocG showed that RocG has higher affinity for 2-oxoglutarate than glutamate, and the glutamate synthesis rate was far above degradation. This is probably the first study to reveal the glutamic acid synthesis pathway and the specific functions of RocG in B. licheniformis. The results indicate that γ-PGA production can be enhanced through improving intracellular glutamic acid synthesis. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. In vivo monitoring of extracellular glutamate in the brain with a microsensor

    NARCIS (Netherlands)

    Oldenziel, Weite Hendrik; Dijkstra, G; Cremers, T.I.F.H.; Westerink, B.H.C.

    2006-01-01

    Recent discoveries have revealed that glutamatergic neurotransmission in the central nervous system is mediated by a dynamic interplay between neurons and astrocytes. To enhance our understanding of this process, the study of extracellular glutamate is crucial. At present, microdialysis is the most

  18. Bovine neuronal vesicular glutamate transporter activity is inhibited by ergovaline and other ergopeptines

    Science.gov (United States)

    L-Glutamate (Glu) is the major excitatory neurotransmitter responsible for neurotransmission in the vertebrate central nervous system, including the gastrointestinal tract (GIT) of cattle. Vesicular Glu transporters VGLUT1 and VGLUT2 concentrate (50 mM) Glu (Km = 1 to 4 mM) into synaptic vesicles (S...

  19. Selective Negative Allosteric Modulation Of Metabotropic Glutamate Receptors - A Structural Perspective of Ligands and Mutants

    DEFF Research Database (Denmark)

    Harpsøe, Kasper; Isberg, Vignir; Tehan, Benjamin G

    2015-01-01

    The metabotropic glutamate receptors have a wide range of modulatory functions in the central nervous system. They are among the most highly pursued drug targets, with relevance for several neurological diseases, and a number of allosteric modulators have entered clinical trials. However, so far ...

  20. Enrichment of Thermophilic Syntrophic Anaerobic Glutamate-Degrading Consortia using a Dialysis Membrane Reactor

    NARCIS (Netherlands)

    Plugge, C.M.; Stams, A.J.M.

    2002-01-01

    A dialysis cultivation system was used to enrich slow-growing moderately thermophilic anaerobic bacteria at high cell densities. Bicarbonate buffered mineral salts medium with 5 mM glutamate as the sole carbon and energy source was used and the incubation temperature was 55 degrees C. The reactor

  1. Synaptically evoked glutamate transporter currents in Spinal Dorsal Horn Astrocytes

    Directory of Open Access Journals (Sweden)

    Dougherty Patrick M

    2009-07-01

    Full Text Available Abstract Background Removing and sequestering synaptically released glutamate from the extracellular space is carried out by specific plasma membrane transporters that are primarily located in astrocytes. Glial glutamate transporter function can be monitored by recording the currents that are produced by co-transportation of Na+ ions with the uptake of glutamate. The goal of this study was to characterize glutamate transporter function in astrocytes of the spinal cord dorsal horn in real time by recording synaptically evoked glutamate transporter currents. Results Whole-cell patch clamp recordings were obtained from astrocytes in the spinal substantia gelatinosa (SG area in spinal slices of young adult rats. Glutamate transporter currents were evoked in these cells by electrical stimulation at the spinal dorsal root entry zone in the presence of bicuculline, strychnine, DNQX and D-AP5. Transporter currents were abolished when synaptic transmission was blocked by TTX or Cd2+. Pharmacological studies identified two subtypes of glutamate transporters in spinal astrocytes, GLAST and GLT-1. Glutamate transporter currents were graded with stimulus intensity, reaching peak responses at 4 to 5 times activation threshold, but were reduced following low-frequency (0.1 – 1 Hz repetitive stimulation. Conclusion These results suggest that glutamate transporters of spinal astrocytes could be activated by synaptic activation, and recording glutamate transporter currents may provide a means of examining the real time physiological responses of glial cells in spinal sensory processing, sensitization, hyperalgesia and chronic pain.

  2. Effect of diet composition and mixture of selected food additives on the erythrocytic system and iron metabolism in peripheral blood of male rats.

    Science.gov (United States)

    Sadowska, Joanna; Kuchlewska, Magdalena

    2011-01-01

    Metabolic processes of food additives which are "exogenous xenobiotics" are catalysed, primarily, by enzymes located in microsomes of hepatocytes affiliated to P-450 cytochrome superfamily, containing iron. The aim of the study was to investigate the effect of diet composition and selected food additives on the erythrocyte system and iron metabolism in peripheral blood of male rats. The experiment was carried out on 30 male rats sorted into three equinumerous groups. For drinking animals received pure, settled tap water, animals from group III were receiving additionally an aqueous solution of sodium (nitrate), potassium nitrite, benzoic acid, sorbic acid and monosodium glutamate. Ascertained a significant effect of changes in diet composition on the increase in hematocrit marker value and the count of red blood cells in blood of animals examined. Used food additives diminished hemoglobin concentration, hematocrit value and red blood cell count, diminishing also iron concentration in serum, the total iron binding capacity and transferrin saturation with iron. Analysis of the results allowed ascertain adverse changes in values of the erythrocytic system markers, occurring under the influence of the applied mixture of food additives. Used food additives change the iron metabolism, most likely from the necessity of applied xenobiotics biotransformation by heme-containing monoxygenases of P-450 cytochrome.

  3. Glutamate production from ammonia via glutamate dehydrogenase 2 activity supports cancer cell proliferation under glutamine depletion.

    Science.gov (United States)

    Takeuchi, Yukiko; Nakayama, Yasumune; Fukusaki, Eiichiro; Irino, Yasuhiro

    2018-01-01

    Cancer cells rapidly consume glutamine as a carbon and nitrogen source to support proliferation, but the cell number continues to increase exponentially after glutamine is nearly depleted from the medium. In contrast, cell proliferation rates are strongly depressed when cells are cultured in glutamine-free medium. How cancer cells survive in response to nutrient limitation and cellular stress remains poorly understood. In addition, rapid glutamine catabolism yields ammonia, which is a potentially toxic metabolite that is secreted into the extracellular space. Here, we show that ammonia can be utilized for glutamate production, leading to cell proliferation under glutamine-depleted conditions. This proliferation requires glutamate dehydrogenase 2, which synthesizes glutamate from ammonia and α-ketoglutarate and is expressed in MCF7 and T47D cells. Our findings provide insight into how cancer cells survive under glutamine deprivation conditions and thus contribute to elucidating the mechanisms of tumor growth. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Astrocytes and Glutamate Homoeostasis in Alzheimer's Disease: A Decrease in Glutamine Synthetase, But Not in Glutamate Transporter-1, in the Prefrontal Cortex

    Directory of Open Access Journals (Sweden)

    Magdalena Kulijewicz-Nawrot

    2013-09-01

    Full Text Available Astrocytes control tissue equilibrium and hence define the homoeostasis and function of the CNS (central nervous system. Being principal homoeostatic cells, astroglia are fundamental for various forms of neuropathology, including AD (Alzheimer's disease. AD is a progressive neurodegenerative disorder characterized by the loss of cognitive functions due to specific lesions in mnesic-associated regions, including the mPFC (medial prefrontal cortex. Here, we analyzed the expression of GS (glutamine synthetase and GLT-1 (glutamate transporter-1 in astrocytes in the mPFC during the progression of AD in a triple-transgenic mouse model (3xTg-AD. GS is an astrocyte-specific enzyme, responsible for the intracellular conversion of glutamate into glutamine, whereas the removal of glutamate from the extracellular space is accomplished mainly by astroglia-specific GLT-1. We found a significant decrease in the numerical density (Nv, cells/mm3 of GS-positive astrocytes from early to middle ages (1–9 months; at the age of 1 month by 17%, 6 months by 27% and 9 months by 27% when compared with control animals in parallel with a reduced expression of GS (determined by Western blots, which started at the age of 6 months and was sustained up to 12 months of age. We did not, however, find any changes in the expression of GLT-1, which implies an intact glutamate uptake mechanism. Our results indicate that the decrease in GS expression may underlie a gradual decline in the vital astrocyte-dependent glutamate–glutamine conversion pathway, which in turn may compromise glutamate homoeostasis, leading towards failures in synaptic connectivity with deficient cognition and memory.

  5. siRNA knock down of glutamate dehydrogenase in astrocytes affects glutamate metabolism leading to extensive accumulation of the neuroactive amino acids glutamate and aspartate.

    Science.gov (United States)

    Skytt, Dorte M; Klawonn, Anna M; Stridh, Malin H; Pajęcka, Kamilla; Patruss, Yasar; Quintana-Cabrera, Ruben; Bolaños, Juan P; Schousboe, Arne; Waagepetersen, Helle S

    2012-09-01

    Glutamate is the most abundant excitatory neurotransmitter in the brain and astrocytes are key players in sustaining glutamate homeostasis. Astrocytes take up the predominant part of glutamate after neurotransmission and metabolism of glutamate is necessary for a continuous efficient removal of glutamate from the synaptic area. Glutamate may either be amidated by glutamine synthetase or oxidatively metabolized in the mitochondria, the latter being at least to some extent initiated by oxidative deamination by glutamate dehydrogenase (GDH). To explore the particular importance of GDH for astrocyte metabolism we have knocked down GDH in cultured cortical astrocytes employing small interfering RNA (siRNA) achieving a reduction of the enzyme activity by approximately 44%. The astrocytes were incubated for 2h in medium containing either 1.0mM [(15)NH(4)(+)] or 100 μM [(15)N]glutamate. For those exposed to [(15)N]glutamate an additional 100 μM was added after 1h. Metabolic mapping was performed from isotope incorporation measured by mass spectrometry into relevant amino acids of cell extracts and media. The contents of the amino acids were measured by HPLC. The (15)N incorporation from [(15)NH(4)(+)] into glutamate, aspartate and alanine was decreased in astrocytes exhibiting reduced GDH activity. However, the reduced GDH activity had no effect on the cellular contents of these amino acids. This supports existing in vivo and in vitro studies that GDH is predominantly working in the direction of oxidative deamination and not reductive amination. In contrast, when exposing the astrocytes to [(15)N]glutamate, the reduced GDH activity led to an increased (15)N incorporation into glutamate, aspartate and alanine and a large increase in the content of glutamate and aspartate. Surprisingly, this accumulation of glutamate and net-synthesis of aspartate were not reflected in any alterations in either the glutamine content or labeling, but a slight increase in mono labeling of

  6. From the Cover: Glutamate antagonists limit tumor growth

    Science.gov (United States)

    Rzeski, Wojciech; Turski, Lechoslaw; Ikonomidou, Chrysanthy

    2001-05-01

    Neuronal progenitors and tumor cells possess propensity to proliferate and to migrate. Glutamate regulates proliferation and migration of neurons during development, but it is not known whether it influences proliferation and migration of tumor cells. We demonstrate that glutamate antagonists inhibit proliferation of human tumor cells. Colon adenocarcinoma, astrocytoma, and breast and lung carcinoma cells were most sensitive to the antiproliferative effect of the N-methyl-D-aspartate antagonist dizocilpine, whereas breast and lung carcinoma, colon adenocarcinoma, and neuroblastoma cells responded most favorably to the -amino-3-hydroxy-5-methyl-4-isoxazole-propionate antagonist GYKI52466. The antiproliferative effect of glutamate antagonists was Ca2+ dependent and resulted from decreased cell division and increased cell death. Morphological alterations induced by glutamate antagonists in tumor cells consisted of reduced membrane ruffling and pseudopodial protrusions. Furthermore, glutamate antagonists decreased motility and invasive growth of tumor cells. These findings suggest anticancer potential of glutamate antagonists.

  7. [Determination of glutamic acid in biological material by capillary electrophoresis].

    Science.gov (United States)

    Narezhnaya, E; Krukier, I; Avrutskaya, V; Degtyareva, A; Igumnova, E A

    2015-01-01

    The conditions for the identification and determination of Glutamic acid by capillary zone electrophoresis without their preliminary derivatization have been optimized. The effect of concentration of buffer electrolyte and pH on determination of Glutamic acid has been investigated. It is shown that the 5 Mm borate buffer concentration and a pH 9.15 are optimal. Quantitative determination of glutamic acid has been carried out using a linear dependence between the concentration of the analyte and the area of the peak. The accuracy and reproducibility of the determination are confirmed by the method "introduced - found". Glutamic acid has been determined in the placenta homogenate. The duration of analysis doesn't exceed 30 minutes. The results showed a decrease in the level of glutamic acid in cases of pregnancy complicated by placental insufficiency compared with the physiological, and this fact allows to consider the level of glutamic acid as a possible marker of complicated pregnancy.

  8. Bidirectional regulation of thermotaxis by glutamate transmissions in Caenorhabditis elegans.

    Science.gov (United States)

    Ohnishi, Noriyuki; Kuhara, Atsushi; Nakamura, Fumiya; Okochi, Yoshifumi; Mori, Ikue

    2011-04-06

    In complex neural circuits of the brain, massive information is processed with neuronal communication through synaptic transmissions. It is thus fundamental to delineate information flows encoded by various kinds of transmissions. Here, we show that glutamate signals from two distinct sensory neurons bidirectionally affect the same postsynaptic interneuron, thereby producing the opposite behaviours. EAT-4/VGLUT (vesicular glutamate transporter)-dependent glutamate signals from AFD thermosensory neurons inhibit the postsynaptic AIY interneurons through activation of GLC-3/GluCl inhibitory glutamate receptor and behaviourally drive migration towards colder temperature. By contrast, EAT-4-dependent glutamate signals from AWC thermosensory neurons stimulate the AIY neurons to induce migration towards warmer temperature. Alteration of the strength of AFD and AWC signals led to significant changes of AIY activity, resulting in drastic modulation of behaviour. We thus provide an important insight on information processing, in which two glutamate transmissions encoding opposite information flows regulate neural activities to produce a large spectrum of behavioural outputs.

  9. Protective effects of peel and seed extracts of Citrus aurantium on glutamate-induced cytotoxicity in PC12 cell line

    Directory of Open Access Journals (Sweden)

    Azar Hosseini

    2016-10-01

    Full Text Available Oxidative stress and apoptosis contribute to neuronal degeneration in many neurodegenerative diseases such as Alzheimer’s disease. Glutamate is a major excitatory neurotransmitter in the central nervous system (CNS and is considered responsible for the pathogenesis of many neurological disorders. Reactive oxygen species (ROS production is thought to be involved in glutamate-induced apoptosis process. In this study, the neuroprotective effects of Citrus aurantium in the glutamate-induced rat’s adrenal pheochromocytoma cell line (PC12 cells were investigated. The cell viability and apoptotic cell death were measured using MTT and propidium iodine (PI-staining methods, respectively. In addition, intracellular ROS and malondialdehyde (MDA levels were determined by fluorometric methods. The results showed that glutamate cytotoxicity in PC12 cells was accompanied by an increment of MDA content, ROS generation, and apoptotic induction. However, pretreatment with peel and seed extracts of C. aurantium significantly reduced MDA content, ROS generation, and apoptotic cells. All these findings indicated that C. aurantium protected PC12 cells against glutamate-induced apoptosis by inhibiting ROS production. Therefore, the present study supports that C. aurantium extracts possess neuroprotective effects against glutamate-induced toxicity in PC12 cell line. The protective effect of C. aurantium might be attributed to its antioxidant properties.

  10. Protective effects of peel and seed extracts of Citrus aurantium on glutamate-induced cytotoxicity in PC12 cell line.

    Science.gov (United States)

    Hosseini, A; Sadeghnia, H R; Rajabian, A

    2016-01-01

    Oxidative stress and apoptosis contribute to neuronal degeneration in many neurodegenerative diseases such as Alzheimer's disease. Glutamate is a major excitatory neurotransmitter in the central nervous system (CNS) and is considered responsible for the pathogenesis of many neurological disorders. Reactive oxygen species (ROS) production is thought to be involved in glutamate-induced apoptosis process. In this study, the neuroprotective effects of Citrus aurantium in the glutamate-induced rat's adrenal pheochromocytoma cell line (PC12 cells) were investigated. The cell viability and apoptotic cell death were measured using MTT and propidium iodine (PI)-staining methods, respectively. In addition, intracellular ROS and malondialdehyde (MDA) levels were determined by fluorometric methods. The results showed that glutamate cytotoxicity in PC12 cells was accompanied by an increment of MDA content, ROS generation, and apoptotic induction. However, pretreatment with peel and seed extracts of C. aurantium significantly reduced MDA content, ROS generation, and apoptotic cells. All these findings indicated that C. aurantium protected PC12 cells against glutamate-induced apoptosis by inhibiting ROS production. Therefore, the present study supports that C. aurantium extracts possess neuroprotective effects against glutamate-induced toxicity in PC12 cell line. The protective effect of C. aurantium might be attributed to its antioxidant properties.

  11. Biochemical evidence for glutamate as a transmitter in hippocampal efferents to the basal forebrain and hypothalamus in the rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Walaas, I.; Fonnum, F.

    1980-01-01

    The effects of bilateral transection of the fornix bundle on the high affinity uptake of glutamate and on the amino acid content in several nuclei of rat forebrain and hypothalamus were studied in order to investigate the possible role of glutamate as a transmitter of these fibres. This lesion decreased the high affinity uptake of L-glutamate by 60 to 70% in the mammillary body and lateral septum, and by 40 to 50% in the anterior diagonal band nucleus, the bed nucleus of the stria terminalis, the mediobasal hypothalamus and the nucleus accumbens. The content of endogenous glutamate in samples dissected from freeze-dried tissue also decreased significantly in these regions. Endogenous aspartate was slightly decreased in the anterior diagonal band nucleus and the mammillary body, but unchanged in the other regions. No significant changes were seen in the levels of serine, ..gamma..-aminobutyric acid, glutamine and taurine, except for an increase in glutamine and taurine in the bed nucleus of the stria terminalis. The high affinity uptake of ..gamma..-aminobutyric acid, tested in the bed nucleus of the stria terminalis, the mediobasal hypothalamus and the mammillary body, was unchanged after the lesion. The results indicate that allocortical efferents innervating subcortial nuclei through the fornix might use glutamate as a transmitter. The study further supports the concept that glutamate plays an important role as transmitter of several different corticofugal fibre systems in mammalian brain.

  12. Relationship between Increase in Astrocytic GLT-1 Glutamate Transport and Late-LTP

    Science.gov (United States)

    Pita-Almenar, Juan D.; Zou, Shengwei; Colbert, Costa M.; Eskin, Arnold

    2012-01-01

    Na[superscript +]-dependent high-affinity glutamate transporters have important roles in the maintenance of basal levels of glutamate and clearance of glutamate during synaptic transmission. Interestingly, several studies have shown that basal glutamate transport displays plasticity. Glutamate uptake increases in hippocampal slices during early…

  13. Control of Amygdala Circuits by 5-HT Neurons via 5-HT and Glutamate Cotransmission.

    Science.gov (United States)

    Sengupta, Ayesha; Bocchio, Marco; Bannerman, David M; Sharp, Trevor; Capogna, Marco

    2017-02-15

    The serotonin (5-HT) system and the amygdala are key regulators of emotional behavior. Several lines of evidence suggest that 5-HT transmission in the amygdala is implicated in the susceptibility and drug treatment of mood disorders. Therefore, elucidating the physiological mechanisms through which midbrain 5-HT neurons modulate amygdala circuits could be pivotal in understanding emotional regulation in health and disease. To shed light on these mechanisms, we performed patch-clamp recordings from basal amygdala (BA) neurons in brain slices from mice with channelrhodopsin genetically targeted to 5-HT neurons. Optical stimulation of 5-HT terminals at low frequencies (≤1 Hz) evoked a short-latency excitation of BA interneurons (INs) that was depressed at higher frequencies. Pharmacological analysis revealed that this effect was mediated by glutamate and not 5-HT because it was abolished by ionotropic glutamate receptor antagonists. Optical stimulation of 5-HT terminals at higher frequencies (10-20 Hz) evoked both slow excitation and slow inhibition of INs. These effects were mediated by 5-HT because they were blocked by antagonists of 5-HT 2A and 5-HT 1A receptors, respectively. These fast glutamate- and slow 5-HT-mediated responses often coexisted in the same neuron. Interestingly, fast-spiking and non-fast-spiking INs displayed differential modulation by glutamate and 5-HT. Furthermore, optical stimulation of 5-HT terminals did not evoke glutamate release onto BA principal neurons, but inhibited these cells directly via activation of 5-HT 1A receptors and indirectly via enhanced GABA release. Collectively, these findings suggest that 5-HT neurons exert a frequency-dependent, cell-type-specific control over BA circuitry via 5-HT and glutamate co-release to inhibit the BA output. SIGNIFICANCE STATEMENT The modulation of the amygdala by serotonin (5-HT) is important for emotional regulation and is implicated in the pathogenesis and treatment of affective disorders

  14. Bidirectional regulation of thermotaxis by glutamate transmissions in Caenorhabditis elegans

    OpenAIRE

    Ohnishi, Noriyuki; Kuhara, Atsushi; Nakamura, Fumiya; Okochi, Yoshifumi; Mori, Ikue

    2011-01-01

    In complex neural circuits of the brain, massive information is processed with neuronal communication through synaptic transmissions. It is thus fundamental to delineate information flows encoded by various kinds of transmissions. Here, we show that glutamate signals from two distinct sensory neurons bidirectionally affect the same postsynaptic interneuron, thereby producing the opposite behaviours. EAT-4/VGLUT (vesicular glutamate transporter)-dependent glutamate signals from AFD thermosenso...

  15. Comparison between oral and intra-articular antinociceptive effect of dexketoprofen and tramadol combination in monosodium iodoacetate-induced osteoarthritis in rats.

    Science.gov (United States)

    Cialdai, Cecilia; Giuliani, Sandro; Valenti, Claudio; Tramontana, Manuela; Maggi, Carlo Alberto

    2013-08-15

    Dexketoprofen and tramadol, alone or in combination, were evaluated after oral or intra-articular administration on knee osteoarthritis nociception induced by intra-articular (i.ar.) monosodium iodoacetate (MIA, 1 mg/25 µl) in the rat right knee while the left knee received saline (25 µl). Seven days after MIA treatment, dexketoprofen, tramadol, their combination or the vehicle were administered. Nociception was evaluated as alteration in hind limb weight distribution with Incapacitance tester at different time-points after drug administration. Oral dexketoprofen (0.1-1 mg/kg) or tramadol (0.5-5 mg/kg) induced maximal antinociception at 1 and 5 mg/kg, respectively. Their combination dose-dependently increased the intensity and duration of antinociception, that was additive and lasted up to 3 days. Also the intra-articular administration of dexketoprofen or tramadol (10-100 µg/25 µl) inhibited MIA-induced nociception, and the combination of the lower doses (10 µg/25 µl) produced a long lasting more than additive antinociceptive effect indicating a synergistic interaction between the two drugs. This effect was significantly reduced by naloxone (10 μg/25 μl, i.ar.) co-administered with both compounds. The intra-articular administration of both drugs at 10 µg/25 µl in the contralateral control knee joint provoked a marked synergistic antinociceptive effect indicating significant systemic diffusion through synovial membrane. The oral or intra-articular combination of dexketoprofen and tramadol produced additive or synergistic antinociceptive effects, respectively, in the model of MIA-induced osteoarthritis in rats, that might allow to obtain therapeutic advantages with lower side effects. © 2013 Elsevier B.V. All rights reserved.

  16. Physical and functional interaction of NCX1 and EAAC1 transporters leading to glutamate-enhanced ATP production in brain mitochondria.

    Directory of Open Access Journals (Sweden)

    Simona Magi

    Full Text Available Glutamate is emerging as a major factor stimulating energy production in CNS. Brain mitochondria can utilize this neurotransmitter as respiratory substrate and specific transporters are required to mediate the glutamate entry into the mitochondrial matrix. Glutamate transporters of the Excitatory Amino Acid Transporters (EAATs family have been previously well characterized on the cell surface of neuronal and glial cells, representing the primary players for glutamate uptake in mammalian brain. Here, by using western blot, confocal microscopy and immunoelectron microscopy, we report for the first time that the Excitatory Amino Acid Carrier 1 (EAAC1, an EAATs member, is expressed in neuronal and glial mitochondria where it participates in glutamate-stimulated ATP production, evaluated by a luciferase-luciferin system. Mitochondrial metabolic response is counteracted when different EAATs pharmacological blockers or selective EAAC1 antisense oligonucleotides were used. Since EAATs are Na(+-dependent proteins, this raised the possibility that other transporters regulating ion gradients across mitochondrial membrane were required for glutamate response. We describe colocalization, mutual activity dependency, physical interaction between EAAC1 and the sodium/calcium exchanger 1 (NCX1 both in neuronal and glial mitochondria, and that NCX1 is an essential modulator of this glutamate transporter. Only NCX1 activity is crucial for such glutamate-stimulated ATP synthesis, as demonstrated by pharmacological blockade and selective knock-down with antisense oligonucleotides. The EAAC1/NCX1-dependent mitochondrial response to glutamate may be a general and alternative mechanism whereby this neurotransmitter sustains ATP production, since we have documented such metabolic response also in mitochondria isolated from heart. The data reported here disclose a new physiological role for mitochondrial NCX1 as the key player in glutamate-induced energy production.

  17. Display of alpha-amylase on the surface of Corynebacterium glutamicum cells by using NCgl1221 as the anchoring protein, and production of glutamate from starch.

    Science.gov (United States)

    Yao, Wenjuan; Chu, Chunli; Deng, Xiaozhao; Zhang, Yun; Liu, Miao; Zheng, Pu; Sun, Zhihao

    2009-10-01

    We developed a new cell surface display system in Corynebacterium glutamicum based on the C-terminally truncated NCgl1221 anchor protein to increase L-glutamate production from starch directly. The C-terminally truncated NCgl1221 protein is a mutant NCgl1221 and leads to the constitutive export of L-glutamate. The N terminus of alpha-amylase (AmyA) was fused to truncated NCgl1221, and the resulting fusion protein was expressed on the cell surface by IPTG induction. Localization of the fusion protein was confirmed by immunofluorescence microscopy and flow cytometric analysis. The results of L-glutamate fermentation showed that the soluble starch was utilized to grow and produce L-glutamate by the recombinant strain displaying AmyA. The amount of soluble starch was reduced from 30.0 +/- 2.8 to 4.5 +/- 0.7 g/l under non-inducing condition and from 50.0 +/- 2.4 to 12.5 +/- 1.1 g/l under biotin limitation in 36 h. The glutamate concentration in the medium was transiently increased in 14 h under no induction, while under biotin-limiting condition, glutamate production was continuously elevated during fermentation. The amount of glutamate reached 19.3 +/- 2.1 g/l after 26 h of fermentation with biotin limitation, which was greater than that produced by the strain using PgsA, one of the poly-gamma-glutamate synthetase complexes, as the anchor protein under the same condition. Therefore, the truncated NCgl1221 anchor protein has more advantages than the PgsA anchor protein in glutamate fermentation because truncated NCgl1221 leads to the constitutive export of L-glutamate without any treatments.

  18. Inhibition of breast cancer-cell glutamate release with sulfasalazine limits cancer-induced bone pain.

    Science.gov (United States)

    Ungard, Robert G; Seidlitz, Eric P; Singh, Gurmit

    2014-01-01

    Cancer in bone is frequently a result of metastases from distant sites, particularly from the breast, lung, and prostate. Pain is a common and often severe pathological feature of cancers in bone, and is a significant impediment to the maintenance of quality of life of patients living with bone metastases. Cancer cell lines have been demonstrated to release significant amounts of the neurotransmitter and cell-signalling molecule l-glutamate via the system xC(-) cystine/glutamate antiporter. We have developed a novel mouse model of breast cancer bone metastases to investigate the impact of inhibiting cancer cell glutamate transporters on nociceptive behaviour. Immunodeficient mice were inoculated intrafemorally with the human breast adenocarcinoma cell line MDA-MB-231, then treated 14days later via mini-osmotic pumps inserted intraperitoneally with sulfasalazine, (S)-4-carboxyphenylglycine, or vehicle. Both sulfasalazine and (S)-4-carboxyphenylglycine attenuated in vitro cancer cell glutamate release in a dose-dependent manner via the system xC(-) transporter. Animals treated with sulfasalazine displayed reduced nociceptive behaviours and an extended time until the onset of behavioural evidence of pain. Animals treated with a lower dose of (S)-4-carboxyphenylglycine did not display this reduction in nociceptive behaviour. These results suggest that a reduction in glutamate secretion from cancers in bone with the system xC(-) inhibitor sulfasalazine may provide some benefit for treating the often severe and intractable pain associated with bone metastases. Copyright © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  19. In situ measurement of glutamate concentrations in the periportal, intermediate, and pericentral zones of rat liver

    NARCIS (Netherlands)

    Geerts, W. J.; Jonker, A.; Boon, L.; Meijer, A. J.; Charles, R.; van Noorden, C. J.; Lamers, W. H.

    1997-01-01

    We developed a quantitative histochemical assay for measurement of local glutamate concentrations in cryostat sections of rat liver. Deamination of glutamate by glutamate dehydrogenase (GDH) was coupled to the production of formazan and formazan precipitation was used for colorimetric visualization.

  20. Identification and characterization of a bacterial glutamic peptidase.

    Science.gov (United States)

    Jensen, Kenneth; Østergaard, Peter R; Wilting, Reinhard; Lassen, Søren F

    2010-12-01

    Glutamic peptidases, from the MEROPS family G1, are a distinct group of peptidases characterized by a catalytic dyad consisting of a glutamate and a glutamine residue, optimal activity at acidic pH and insensitivity towards the microbial derived protease inhibitor, pepstatin. Previously, only glutamic peptidases derived from filamentous fungi have been characterized. We report the first characterization of a bacterial glutamic peptidase (pepG1), derived from the thermoacidophilic bacteria Alicyclobacillus sp. DSM 15716. The amino acid sequence identity between pepG1 and known fungal glutamic peptidases is only 24-30% but homology modeling, the presence of the glutamate/glutamine catalytic dyad and a number of highly conserved motifs strongly support the inclusion of pepG1 as a glutamic peptidase. Phylogenetic analysis places pepG1 and other putative bacterial and archaeal glutamic peptidases in a cluster separate from the fungal glutamic peptidases, indicating a divergent and independent evolution of bacterial and fungal glutamic peptidases. Purification of pepG1, heterologously expressed in Bacillus subtilis, was performed using hydrophobic interaction chromatography and ion exchange chromatography. The purified peptidase was characterized with respect to its physical properties. Temperature and pH optimums were found to be 60°C and pH 3-4, in agreement with the values observed for the fungal members of family G1. In addition, pepG1 was found to be pepstatin-insensitive, a characteristic signature of glutamic peptidases. Based on the obtained results, we suggest that pepG1 can be added to the MEROPS family G1 as the first characterized bacterial member.

  1. Identification and characterization of a bacterial glutamic peptidase

    Directory of Open Access Journals (Sweden)

    Jensen Kenneth

    2010-12-01

    Full Text Available Abstract Background Glutamic peptidases, from the MEROPS family G1, are a distinct group of peptidases characterized by a catalytic dyad consisting of a glutamate and a glutamine residue, optimal activity at acidic pH and insensitivity towards the microbial derived protease inhibitor, pepstatin. Previously, only glutamic peptidases derived from filamentous fungi have been characterized. Results We report the first characterization of a bacterial glutamic peptidase (pepG1, derived from the thermoacidophilic bacteria Alicyclobacillus sp. DSM 15716. The amino acid sequence identity between pepG1 and known fungal glutamic peptidases is only 24-30% but homology modeling, the presence of the glutamate/glutamine catalytic dyad and a number of highly conserved motifs strongly support the inclusion of pepG1 as a glutamic peptidase. Phylogenetic analysis places pepG1 and other putative bacterial and archaeal glutamic peptidases in a cluster separate from the fungal glutamic peptidases, indicating a divergent and independent evolution of bacterial and fungal glutamic peptidases. Purification of pepG1, heterologously expressed in Bacillus subtilis, was performed using hydrophobic interaction chromatography and ion exchange chromatography. The purified peptidase was characterized with respect to its physical properties. Temperature and pH optimums were found to be 60°C and pH 3-4, in agreement with the values observed for the fungal members of family G1. In addition, pepG1 was found to be pepstatin-insensitive, a characteristic signature of glutamic peptidases. Conclusions Based on the obtained results, we suggest that pepG1 can be added to the MEROPS family G1 as the first characterized bacterial member.

  2. Rat odontoblasts may use glutamate to signal dentin injury.

    Science.gov (United States)

    Cho, Yi Sul; Ryu, Chang Hyun; Won, Jong Hwa; Vang, Hue; Oh, Seog Bae; Ro, Jin Young; Bae, Yong Chul

    2016-10-29

    Accumulating evidence indicates that odontoblasts act as sensor cells, capable of triggering action potentials in adjacent pulpal nociceptive axons, suggesting a paracrine signaling via a currently unknown mediator. Since glutamate can mediate signaling by non-neuronal cells, and peripheral axons may express glutamate receptors (GluR), we hypothesized that the expression of high levels of glutamate, and of sensory receptors in odontoblasts, combined with an expression of GluR in adjacent pulpal axons, is the morphological basis for odontoblastic sensory signaling. To test this hypothesis, we investigated the expression of glutamate, the thermo- and mechanosensitive ion channels transient receptor potential vanilloid 1 (TRPV1), transient receptor potential ankyrin 1 (TRPA1), and TWIK-1-related K+channel (TREK-1), and the glutamate receptor mGluR5, in a normal rat dental pulp, and following dentin injury. We also examined the glutamate release from odontoblast in cell culture. Odontoblasts were enriched with glutamate, at the level as high as in adjacent pulpal axons, and showed immunoreactivity for TRPV1, TRPA1, and TREK-1. Pulpal sensory axons adjacent to odontoblasts expressed mGluR5. Both the levels of glutamate in odontoblasts, and the expression of mGluR5 in nearby axons, were upregulated following dentin injury. The extracellular glutamate concentration was increased significantly after treating of odontoblast cell line with calcium permeable ionophore, suggesting glutamate release from odontoblasts. These findings lend morphological support to the hypothesis that odontoblasts contain glutamate as a potential neuroactive substance that may activate adjacent pulpal axons, and thus contribute to dental pain and hypersensitivity. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  3. TAILORING INORGANIC SORBENTS FOR SRS STRONTIUM AND ACTINIDE SEPARATIONS: OPTIMIZED MONOSODIUM TITANATE PHASE II FINAL REPORT

    International Nuclear Information System (INIS)

    Hobbs, D; Thomas Peters, T; Michael Poirier, M; Mark Barnes, M; Major Thompson, M; Samuel Fink, S

    2007-01-01

    This document provides a final report of Phase II testing activities for the development of a modified monosodium titanate (MST) that exhibits improved strontium and actinide removal characteristics compared to the baseline MST material. The activities included determining the key synthesis conditions for preparation of the modified MST, preparation of the modified MST at a larger scale by a commercial vendor, demonstration of the strontium and actinide removal characteristics with actual tank waste supernate and measurement of filtration characteristics. Key findings and conclusions include the following. Testing evaluated three synthetic methods and eleven process parameters for the optimum synthesis conditions for the preparation on an improved form of MST. We selected the post synthesis method (Method 3) for continued development based on overall sorbate removal performance. We successfully prepared three batches of the modified MST using Method 3 procedure at a 25-gram scale. The laboratory prepared modified MST exhibited increased sorption kinetics with simulated and actual waste solutions and similar filtration characteristics to the baseline MST. Characterization of the modified MST indicated that the post synthesis treatment did not significantly alter the particle size distribution, but did significantly increase the surface area and porosity compared to the original MST. Testing indicated that the modified MST exhibits reduced affinity for uranium compared to the baseline MST, reducing risk of fissile loading. Shelf-life testing indicated no change in strontium and actinide performance removal after storing the modified MST for 12-months at ambient laboratory temperature. The material releases oxygen during the synthesis and continues to offgas after the synthesis at a rapidly diminishing rate until below a measurable rate after 4 months. Optima Chemical Group LLC prepared a 15-kilogram batch of the modified MST using the post synthesis procedure (Method

  4. Flavonoids of Inula britannica protect cultured cortical cells from necrotic cell death induced by glutamate.

    Science.gov (United States)

    Kim, So Ra; Park, Mi Jung; Lee, Mi Kyeong; Sung, Sang Hyun; Park, Eun Jung; Kim, Jinwoong; Kim, Sun Yeou; Oh, Tae H; Markelonis, George J; Kim, Young Choong

    2002-04-01

    We previously reported 12 antioxidative flavonoids isolated from the n-BuOH extract of Inula britannica (Asteraceae). This prompted us to investigate further whether these flavonoids also showed antioxidative activity upon live cells grown in a culture system. Among the 12 flavonoids tested, only patuletin, nepetin, and axillarin protected primary cultures of rat cortical cells from oxidative stress induced by glutamate. These flavonoids exerted significant neuroprotective activity when they were administered either before or after the glutamate insult. Treatment with these flavonoids maintained the activities of such antioxidant enzymes as catalase, glutathione-peroxidase, and glutathione reductase, all of which play important roles in the antioxidative defense mechanism. Moreover, these three flavonoids also attenuated significant drops in glutathione induced by glutamate which is a routine concomitant of oxidative stress by inhibiting glutathione diminution. Accordingly, these flavonoids did not stimulate the synthesis of glutathione. With regard to structure-activity relationships, our results indicated that the 6-methoxyl group in the A ring and the 3', 4'-hydroxyl groups in the B ring are crucial for the protection against the oxidative stress; glycosylation greatly reduced their protective activities. Collectively, these results indicated that patuletin, nepetin, and axillarin strongly protect primary cultured neurons against glutamate-induced oxidative stress.

  5. Permanent uncoupling of male-specific CYP2C11 transcription/translation by perinatal glutamate

    Energy Technology Data Exchange (ETDEWEB)

    Banerjee, Sarmistha; Das, Rajat Kumar; Giffear, Kelly A.; Shapiro, Bernard H., E-mail: shapirob@vet.upenn.edu

    2015-04-01

    Perinatal exposure of rats and mice to the typically reported 4 mg/g bd wt dose of monosodium glutamate (MSG) results in a complete block in GH secretion as well as obesity, growth retardation and a profound suppression of several cytochrome P450s, including CYP2C11, the predominant male-specific isoform — all irreversible effects. In contrast, we have found that a lower dose of the food additive, 2 mg/g bd wt on alternate days for the first 9 days of life results in a transient neonatal depletion of plasma GH, a subsequent permanent overexpression of CYP2C11 as well as subnormal (mini) GH pulse amplitudes in an otherwise normal adult masculine episodic GH profile. The overexpressed CYP2C11 was characterized by a 250% increase in mRNA, but only a 40 to 50% increase in CYP2C11 protein and its catalytic activity. Using freshly isolated hepatocytes as well as primary cultures exposed to the masculine-like episodic GH profile, we observed normal induction, activation, nuclear translocation and binding to the CYP2C11 promoter of the GH-dependent signal transducers required for CYP2C11 transcription. The disproportionately lower expression levels of CYP2C11 protein were associated with dramatically high expression levels of an aberrant, presumably nontranslated CYP2C11 mRNA, a 200% increase in CYP2C11 ubiquitination and a 70–80% decline in miRNAs associated, at normal levels, with a suppression of CYP2C expression. Whereas the GH-responsiveness of CYP2C7 and CYP2C6 as well as albumin was normal in the MSG-derived hepatocytes, the abnormal expression of CYP2C11 was permanent and irreversible. - Highlights: • A “low” neonatal dose of MSG causes an immediate but transient growth hormone depletion. • Adult circulating growth hormone contains mini pulses in an otherwise male profile. • CYP2C11 is permanently overexpressed > 250%; CYP2C6, 2C7 and albumin remain normal. • The bulk of the overexpressed CYP2C11 mRNA consists of an intron-retained form. • SOCS2

  6. Permanent uncoupling of male-specific CYP2C11 transcription/translation by perinatal glutamate

    International Nuclear Information System (INIS)

    Banerjee, Sarmistha; Das, Rajat Kumar; Giffear, Kelly A.; Shapiro, Bernard H.

    2015-01-01

    Perinatal exposure of rats and mice to the typically reported 4 mg/g bd wt dose of monosodium glutamate (MSG) results in a complete block in GH secretion as well as obesity, growth retardation and a profound suppression of several cytochrome P450s, including CYP2C11, the predominant male-specific isoform — all irreversible effects. In contrast, we have found that a lower dose of the food additive, 2 mg/g bd wt on alternate days for the first 9 days of life results in a transient neonatal depletion of plasma GH, a subsequent permanent overexpression of CYP2C11 as well as subnormal (mini) GH pulse amplitudes in an otherwise normal adult masculine episodic GH profile. The overexpressed CYP2C11 was characterized by a 250% increase in mRNA, but only a 40 to 50% increase in CYP2C11 protein and its catalytic activity. Using freshly isolated hepatocytes as well as primary cultures exposed to the masculine-like episodic GH profile, we observed normal induction, activation, nuclear translocation and binding to the CYP2C11 promoter of the GH-dependent signal transducers required for CYP2C11 transcription. The disproportionately lower expression levels of CYP2C11 protein were associated with dramatically high expression levels of an aberrant, presumably nontranslated CYP2C11 mRNA, a 200% increase in CYP2C11 ubiquitination and a 70–80% decline in miRNAs associated, at normal levels, with a suppression of CYP2C expression. Whereas the GH-responsiveness of CYP2C7 and CYP2C6 as well as albumin was normal in the MSG-derived hepatocytes, the abnormal expression of CYP2C11 was permanent and irreversible. - Highlights: • A “low” neonatal dose of MSG causes an immediate but transient growth hormone depletion. • Adult circulating growth hormone contains mini pulses in an otherwise male profile. • CYP2C11 is permanently overexpressed > 250%; CYP2C6, 2C7 and albumin remain normal. • The bulk of the overexpressed CYP2C11 mRNA consists of an intron-retained form. • SOCS2

  7. Novel Inhibitors Complexed with Glutamate Dehydrogenase

    Science.gov (United States)

    Li, Ming; Smith, Christopher J.; Walker, Matthew T.; Smith, Thomas J.

    2009-01-01

    Mammalian glutamate dehydrogenase (GDH) is a homohexameric enzyme that catalyzes the reversible oxidative deamination of l-glutamate to 2-oxoglutarate using NAD(P)+ as coenzyme. Unlike its counterparts from other animal kingdoms, mammalian GDH is regulated by a host of ligands. The recently discovered hyperinsulinism/hyperammonemia disorder showed that the loss of allosteric inhibition of GDH by GTP causes excessive secretion of insulin. Subsequent studies demonstrated that wild-type and hyperinsulinemia/hyperammonemia forms of GDH are inhibited by the green tea polyphenols, epigallocatechin gallate and epicatechin gallate. This was followed by high throughput studies that identified more stable inhibitors, including hexachlorophene, GW5074, and bithionol. Shown here are the structures of GDH complexed with these three compounds. Hexachlorophene forms a ring around the internal cavity in GDH through aromatic stacking interactions between the drug and GDH as well as between the drug molecules themselves. In contrast, GW5074 and bithionol both bind as pairs of stacked compounds at hexameric 2-fold axes between the dimers of subunits. The internal core of GDH contracts when the catalytic cleft closes during enzymatic turnover. None of the drugs cause conformational changes in the contact residues, but all bind to key interfaces involved in this contraction process. Therefore, it seems likely that the drugs inhibit enzymatic turnover by inhibiting this transition. Indeed, this expansion/contraction process may play a major role in the inter-subunit communication and allosteric regulation observed in GDH. PMID:19531491

  8. Influence of the glutamic acid content of the diet on the catabolic rate of labelled glutamic acid in rats. 3

    International Nuclear Information System (INIS)

    Simon, O.; Wilke, A.; Bergner, H.

    1984-01-01

    Mal rats received during a 8 days experimental feeding period diets with different contents in glutamic acid. The daily feed intake was restricted to the energy maintenance level of 460 kJ/kg/sup 0.75/. The diet contained a mixture of L-amino acids corresponding to the pattern of egg protein except glutamic acid. Glutamic acid was added successively at 10 levels (0 to 14.8 % of dry matter) and the resulting diets were fed to groups of 4 animals each. At the end of the experimental feeding period 14 C- and 15 N-labelled glutamic acid were applied by intragastric infusion. CO 2 and 14 CO 2 excretion was measured during the following 4 hours and the urinary N and 15 N excretion during the following 24 hours. The CO 2 excretion decreased from 53 to 44 mmol CO 2 /100g body weight with increasing levels of dietary glutamic acid. This change seems to result from the increasing proportion of amino acids as an energetic fuel. While the amount of oxidized glutamic acid increased with increasing supplements of glutamic acid the relative 14 CO 2 excretion decreased from 57 to 48 % of the applied radioactivity. The urinary 15 N excretion during 24 hours was 31 % of the given amount of 15 N if no glutamic acid was included in the diet. This proportion increased successively up to 52 % in the case of the highest supply of glutamic acid. Because the total N excretion increased at the same extent as the 15 N excretion a complete mixing of the NH 2 groups resulting from glutamic acid due to desamination with the ammonia pool was assumed. No correlation between glutamic acid content of the diet and specific radioactivity of CO 2 or atom-% 15 N excess of urinary N was observed. (author)

  9. probing the cob(ii)alamin conductor hypothesis with glutamate ...

    African Journals Online (AJOL)

    dell

    Glutamate mutase activity was also demonstrated upon incubation of GlmS and E with 3',5'- ... overproduced in E.coli (Huhta et al. 2001,. Huhta et ..... Biochemistry. 37: 9704-9715. Buckel W 2001 Unusual enzymes involved in five pathways of glutamate fermentation. Appl. Microbiol. Biotechnol. 57: 263-273. Buckel W and ...

  10. Microscopic picture of the aqueous solvation of glutamic acid

    NARCIS (Netherlands)

    Leenders, E.J.M.; Bolhuis, P.G.; Meijer, E.J.

    2008-01-01

    We present molecular dynamics simulations of glutamic acid and glutamate solvated in water, using both density functional theory (DFT) and the Gromos96 force field. We focus on the microscopic aspects of the solvation−particularly on the hydrogen bond structures and dynamics−and investigate the

  11. Some Properties of Glutamate Dehydrogenase from the Marine Red ...

    African Journals Online (AJOL)

    Keywords: ammonia assimilation, glutamate dehydrogenase, GDH, Gracilaria sordida, red alga, enzyme activity. Glutamate dehydrogenases (GDH, EC ... Anabolic functions could be assimilation of ammonia released during photorespiration and synthesis of N-rich transport compounds. Western Indian Ocean Journal of ...

  12. Surface grafting of poly(L-glutamates). 3. Block copolymerization

    NARCIS (Netherlands)

    Wieringa, RH; Siesling, EA; Werkman, PJ; Vorenkamp, EJ; Schouten, AJ

    2001-01-01

    This paper describes for the first time the synthesis of surface-grafted AB-block copolypeptides, consisting of poly(gamma -benzyl L-glutamate) (PBLG) as the A-block and poly(gamma -methyl L-glutamate) (PMLG) as the B-block. Immobilized primary amine groups of (,gamma -aminopropyl)triethoxysilane

  13. 21 CFR 522.1125 - Hemoglobin glutamer-200 (bovine).

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Hemoglobin glutamer-200 (bovine). 522.1125 Section... (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.1125 Hemoglobin glutamer-200 (bovine). (a) Specifications. Each 125 milliliter bag contains 13...

  14. Electrochemical Synthesis of Polypyrrole Layers Doped with Glutamic Ions

    NARCIS (Netherlands)

    Meteleva-Fischer, Yulia V.; Von Hauff, Elizabeth; Parisi, Juergen

    2009-01-01

    Electrochemically synthesized polypyrrole thin films doped with glutamic ions were investigated as interesting materials for potential use as molecularly selective surfaces. Pyrrole and glutamate interact in aqueous solution, resulting in the formation of a prominent band at 240 nm in the absorption

  15. Astrocytes revisited: concise historic outlook on glutamate homeostasis and signaling

    Science.gov (United States)

    Parpura, Vladimir; Verkhratsky, Alexei

    2012-01-01

    Astroglia is a main type of brain neuroglia, which includes many cell sub-types that differ in their morphology and physiological properties and yet are united by the main function, which is the maintenance of brain homeostasis. Astrocytes employ a variety of mechanisms for communicating with neuronal networks. The communication mediated by neurotransmitter glutamate has received a particular attention. Glutamate is de novo synthesized exclusively in astrocytes; astroglia-derived glutamine is the source of glutamate for neurons. Glutamate is released from both neurons and astroglia through exocytosis, although various other mechanisms may also play a role. Glutamate-activated specific receptors trigger excitatory responses in neurons and astroglia. Here we overview main properties of glutamatergic transmission in neuronal-glial networks and identify some future challenges facing the field. PMID:23275317

  16. Production of poly-γ-glutamic acid by a thermotolerant glutamate-independent strain and comparative analysis of the glutamate dependent difference.

    Science.gov (United States)

    Zeng, Wei; Chen, Guiguang; Guo, Ye; Zhang, Bin; Dong, Mengna; Wu, Yange; Wang, Jun; Che, Zhiqun; Liang, Zhiqun

    2017-11-25

    Poly-γ-glutamic acid (γ-PGA) is a promising microbial polymer with wide applications in industry, agriculture and medicine. In this study, a novel glutamate-independent γ-PGA producing strain with thermotolerant characteristics was isolated and identified as Bacillus subtilis GXG-5, then its product was also characterized. The fermentation process was optimized by single-factor tests, and results showed that high temperature (50 °C) was especially suitable for the γ-PGA production by GXG-5. The γ-PGA yield reached 19.50 ± 0.75 g/L with substrate conversion efficiency of 78% at 50 °C in 10 L fermentor. Comparison of GXG-5 and GXA-28 (glutamate-dependent strain) under respective optimal fermentation conditions, the γ-PGA yield of GXG-5 was 19.0% higher than that of GXA-28, and GXG-5 was also superior to GXA-28 in the availability of carbon sources and substrates. Furthermore, the glutamate dependent difference between GXA-28 and GXG-5 was analyzed by genomic sequencing, results indicated that genes related to the glutamate dependent difference mainly involved in carbohydrate transport and metabolism and amino acid metabolism, and 13 genes related to γ-PGA synthesis were mutated in GXG-5. This study provided a potential glutamate-independent strain to replace glutamate-dependent strain for γ-PGA production, and shared novel information for understanding the glutamate dependent difference at the genomic level.

  17. Glutamate increases toxicity of inorganic lead in GT1-7 neurons: partial protection induced by flunarizine

    Energy Technology Data Exchange (ETDEWEB)

    Loikkanen, Jarkko; Vaehaekangas, Kirsi H. [Department of Pharmacology and Toxicology, University of Kuopio, PO Box 1627, 70211, Kuopio (Finland); Naarala, Jonne [Department of Environmental Sciences, University of Kuopio, PO Box 1627, 70211, Kuopio (Finland); Savolainen, Kai M. [Department of Industrial Hygiene and Toxicology, Finnish Institute of Occupational Health, Topeliuksenkatu 41 aA, 00250, Helsinki (Finland)

    2003-12-01

    Recent studies point to an interaction between the glutamatergic neurotransmitter system and inorganic lead (Pb) neurotoxicity. Pb (1-100 {mu}M) evoked cytotoxicity over the period of 72 h in mouse hypothalamic GT1-7 neurons. Glutamate (0.1 or 1 mM) on its own did not have any effect on cell viability. However, 1 mM glutamate clearly increased Pb-induced cell death at 48 and 72 h. Although flunarizine (0.1-10 {mu}M), an antagonist of L- and T-type voltage-sensitive calcium channels (VSCCs), partially protected from the cytotoxicity induced by co-exposure to Pb (10 or 100 {mu}M) and glutamate (1 mM), it had no protective effect on cytotoxicity induced by Pb alone. The flunarizine-induced protection was dependent on time and observed only at 48 h. Neither verapamil, an antagonist of L-type VSCCs, nor DIDS, an inhibitor of anion exchange, at non-toxic concentrations (0.1-10 {mu}M) had any effect on cytotoxicity induced by Pb alone or together with glutamate at any studied time point. Co-exposure to Pb and glutamate also resulted in more prominent production of reactive oxygen species (ROS) than either of the compounds alone. Interestingly, we observed an increase in intracellular glutathione (GSH) levels in cells exposed to micromolar concentrations of Pb. Glutamate decreased the levels of intracellular GSH and also partially reduced the Pb-induced increase in GSH levels. These results suggest that the interaction of glutamate and Pb results in increased neuronal cell death via mechanisms that involve an increase in ROS production, a decrease in intracellular GSH defense against oxidative stress and probably T-type VSCCs. (orig.)

  18. Agmatine protects against cell damage induced by NMDA and glutamate in cultured hippocampal neurons.

    Science.gov (United States)

    Wang, Wei-Ping; Iyo, Abiye H; Miguel-Hidalgo, Javier; Regunathan, Soundar; Zhu, Meng-Yang

    2006-04-21

    Agmatine is a polyamine and has been considered as a novel neurotransmitter or neuromodulator in the central nervous system. In the present study, the neuroprotective effect of agmatine against cell damage caused by N-methyl-D-aspartate (NMDA) and glutamate was investigated in cultured rat hippocampal neurons. Lactate dehydrogenase (LDH) activity assay, beta-tubulin III immunocytochemical staining and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate (dUTP) nick end-labeling (TUNEL) assay were conducted to detect cell damage. Exposure of 12-day neuronal cultures of rat hippocampus to NMDA or glutamate for 1 h caused a concentration-dependent neurotoxicity, as indicated by the significant increase in released LDH activities. Addition of 100 microM agmatine into media ablated the neurotoxicity induced by NMDA or glutamate, an effect also produced by the specific NMDA receptor antagonist dizocilpine hydrogen maleate (MK801). Arcaine, an analog of agmatine with similar structure as agmatine, fully prevented the NMDA- or glutamate-induced neuronal damage. Spermine and putrescine, the endogenous polyamine and metabolic products of agmatine without the guanidine moiety of agmatine, failed to show this effect, indicating a structural relevance for this neuroprotection. Immunocytochemical staining and TUNEL assay confirmed the findings in the LDH measurement. That is, agmatine and MK801 markedly attenuated NMDA-induced neuronal death and significantly reduced TUNEL-positive cell numbers induced by exposure of cultured hippocampal neurons to NMDA. Taken together, these results demonstrate that agmatine can protect cultured hippocampal neurons from NMDA- or glutamate-induced excitotoxicity, through a possible blockade of the NMDA receptor channels or a potential anti-apoptotic property.

  19. Vitamin E-Mediated Modulation of Glutamate Receptor Expression in an Oxidative Stress Model of Neural Cells Derived from Embryonic Stem Cell Cultures

    Directory of Open Access Journals (Sweden)

    Afifah Abd Jalil

    2017-01-01

    Full Text Available Glutamate is the primary excitatory neurotransmitter in the central nervous system. Excessive concentrations of glutamate in the brain can be excitotoxic and cause oxidative stress, which is associated with Alzheimer’s disease. In the present study, the effects of vitamin E in the form of tocotrienol-rich fraction (TRF and alpha-tocopherol (α-TCP in modulating the glutamate receptor and neuron injury markers in an in vitro model of oxidative stress in neural-derived embryonic stem (ES cell cultures were elucidated. A transgenic mouse ES cell line (46C was differentiated into a neural lineage in vitro via induction with retinoic acid. These cells were then subjected to oxidative stress with a significantly high concentration of glutamate. Measurement of reactive oxygen species (ROS was performed after inducing glutamate excitotoxicity, and recovery from this toxicity in response to vitamin E was determined. The gene expression levels of glutamate receptors and neuron-specific enolase were elucidated using real-time PCR. The results reveal that neural cells derived from 46C cells and subjected to oxidative stress exhibit downregulation of NMDA, kainate receptor, and NSE after posttreatment with different concentrations of TRF and α-TCP, a sign of neurorecovery. Treatment of either TRF or α-TCP reduced the levels of ROS in neural cells subjected to glutamate-induced oxidative stress; these results indicated that vitamin E is a potent antioxidant.

  20. Chronic noise stress-induced alterations of glutamate and gamma-aminobutyric acid and their metabolism in the rat brain.

    Science.gov (United States)

    Kazi, Amajad Iqbal; Oommen, Anna

    2014-01-01

    Chronic stress induces neurochemical changes that include neurotransmitter imbalance in the brain. Noise is an environmental factor inducing stress. Chronic noise stress affects monoamine neurotransmitter systems in the central nervous system. The effect on other excitatory and inhibitory neurotransmitter systems is not known. The aim was to study the role of chronic noise stress on the glutamatergic and gamma-aminobutyric acid (GABA)ergic systems of the brain. Female Wistar rats (155 ± 5 g) were unintentionally exposed to noise due to construction (75-95 db, 3-4 hours/day, 5 days a week for 7-8 weeks) in the vicinity of the animal care facility. Glutamate/GABA levels and their metabolic enzymes were evaluated in different rat brain regions (cortex, hippocampus, striatum, and cerebellum) and compared with age and gender matched nonexposed rats. Chronic noise stress decreased glutamate levels and glutaminase activity 27% and 33% in the cortex, 15% and 24% in the cerebellum. Glutamate levels increased 10% in the hippocampus, 28% in striatum and glutaminase activity 15% in striatum. Glutamine synthetase activity increased significantly in all brain regions studied, that is, cortex, hippocampus, striatum, and cerebellum (P Noise stress-increased GABA levels and glutamate alpha decarboxylase activity 20% and 45% in the cortex, 13% and 28% in the hippocampus respectively. GABA levels and glutamate alpha decarboxylase activity decreased 15% and 14%, respectively in the striatum. GABA transaminase activity was significantly reduced in the cortex (55%), hippocampus (17%), and cerebellum (33%). Chronic noise stress differentially affected glutamatergic and GABAergic neurotransmitter systems in the rat brain, which may alter glutamate and GABA neurotransmission.

  1. Glutamate-induced glutamate release: A proposed mechanism for calcium bursting in astrocytes

    Science.gov (United States)

    Larter, Raima; Craig, Melissa Glendening

    2005-12-01

    Here we present a new model for the generation of complex calcium-bursting patterns in astrocytes, a type of brain cell recently implicated in a variety of neural functions including memory formation. The model involves two positive feedback processes, in which the key feedback species are calcium ion and glutamate. The latter is the most abundant excitatory neurotransmitter in the brain and has been shown to be involved in bidirectional communication between astrocytes and nearby neurons. The glutamate feedback process considered here is shown to be critical for the generation of complex bursting oscillations in the astrocytes and to, perhaps, code for information which may be passed from neuron to neuron via the astrocyte. These processes may be involved in memory storage and formation as well as in mechanisms which lead to dynamical diseases such as epilepsy.

  2. Calcium regulates glutamate dehydrogenase and poly-γ-glutamic acid synthesis in Bacillus natto.

    Science.gov (United States)

    Meng, Yonghong; Dong, Guiru; Zhang, Chen; Ren, Yuanyuan; Qu, Yuling; Chen, Weifeng

    2016-04-01

    To study the effect of Ca(2+) on glutamate dehydrogenase (GDH) and its role in poly-γ-glutamic acid (γ-PGA) synthesis in Bacillus natto HSF 1410. When the concentration of Ca(2+) varied from 0 to 0.1 g/l in the growth medium of B. natto HSF 1410, γ-PGA production increased from 6.8 to 9.7 g/l, while GDH specific activity and NH4Cl consumption improved from 183 to 295 U/mg and from 0.65 to 0.77 g/l, respectively. GDH with α-ketoglutarate as substrate primarily used NADPH as coenzyme with a K m of 0.08 mM. GDH was responsible for the synthesis of endogenous glutamate. The specific activity of GDH remained essentially unchanged in the presence of CaCl2 (0.05-0.2 g/l) in vitro. However, the specific activity of GDH and its expression was significantly increased by CaCl2 in vivo. Therefore, the regulation of GDH and PGA synthesis by Ca(2+) is an intracellular process. Calcium regulation may be an effective approach for producing γ-PGA on an industrial scale.

  3. TAILORING INORGANIC SORBENTS FOR SRS STRONTIUM AND ACTINIDE SEPARATIONS: MODIFIED MONOSODIUM TITANATE PHASE III FINAL REPORT

    Energy Technology Data Exchange (ETDEWEB)

    Taylor-Pashow, K.; Hobbs, D.

    2010-09-01

    This document provides a final report of Phase III testing activities for the development of modified monosodium titanate (mMST), which exhibits improved strontium and actinide removal characteristics compared to the baseline MST material. The activities included characterization of the crystalline phases present at varying temperatures, solids settling characteristics, quantification of the peroxide content; evaluation of the post-synthesis gas release under different conditions; the extent of desorption of {sup 85}Sr, Np, and Pu under washing conditions; and the effects of age and radiation on the performance of the mMST. Key findings and conclusions include the following. The peroxide content of several mMST samples was determined using iodometric titration. The peroxide content was found to decrease with age or upon extended exposure to elevated temperature. A loss of peroxide was also measured after exposure of the material to an alkaline salt solution similar in composition to the simulated waste solution. To determine if the loss of peroxide with age affects the performance of the material, Sr and actinide removal tests were conducted with samples of varying age. The oldest sample (4 years and 8 months) did show lower Sr and Pu removal performance. When compared to the youngest sample tested (1 month), the oldest sample retained only 15% of the DF for Pu. Previous testing with this sample indicated no decrease in Pu removal performance up to an age of 30 months. No loss in Np removal performance was observed for any of the aged samples, and no uptake of uranium occurred at the typical sorbent loading of 0.2 g/L. Additional testing with a uranium only simulant and higher mMST loading (3.0 g/L) indicated a 10% increase of uranium uptake for a sample aged 3 years and 8 months when compared to the results of the same sample measured at an age of 1 year and 5 months. Performance testing with both baseline-MST and mMST that had been irradiated in a gamma source to

  4. Glutamate and GABA in appetite regulation

    Directory of Open Access Journals (Sweden)

    Teresa Cardoso Delgado

    2013-08-01

    Full Text Available Appetite is regulated by a coordinated interplay between gut, adipose tissue and brain. A primary site for the regulation of appetite is the hypothalamus where interaction between orexigenic neurons, expressing Neuropeptide Y/Agouti-related protein, and anorexigenic neurons, expressing Pro-opiomelanocortin cocaine/Amphetamine-related transcript, controls energy homeostasis. Within the hypothalamus, several peripheral signals have been shown to modulate the activity of these neurons, including the orexigenic peptide ghrelin and the anorexigenic hormones insulin and leptin. In addition to the accumulated knowledge on neuropeptide signaling, presence and function of amino acid neurotransmitters in key hypothalamic neurons brought a new light into appetite regulation. Therefore, the principal aim of this review will be to describe the current knowledge of the role of amino acid neurotransmitters in the mechanism of neuronal activation during appetite regulation and the associated neuronal-astrocytic metabolic coupling mechanisms.Glutamate and GABA dominate synaptic transmission in the hypothalamus and administration of their receptors agonists into hypothalamic nuclei stimulates feeding. By using 13C High-Resolution Magic Angle Spinning Nuclear Magnetic Resonance spectroscopy based analysis, the Cerdán group has shown that increased neuronal firing in mice hypothalamus, as triggered by appetite during the feeding-fasting paradigm, may stimulate the use of lactate as neuronal fuel leading to increased astrocytic glucose consumption and glycolysis. Moreover, fasted mice showed increased hypothalamic [2-13C]GABA content, which may be explained by the existence of GABAergic neurons in key appetite regulation hypothalamic nuclei. Interestingly, increased [2-13C]GABA concentration in the hypothalamus of fasted animals appears to result mainly from reduction in GABA metabolizing pathways, rather than increased GABA synthesis by augmented activity of the

  5. Potentiation of lead-induced cell death in PC12 cells by glutamate: Protection by N-acetylcysteine amide (NACA), a novel thiol antioxidant

    International Nuclear Information System (INIS)

    Penugonda, Suman; Mare, Suneetha; Lutz, P.; Banks, William A.; Ercal, Nuran

    2006-01-01

    Oxidative stress has been implicated as an important factor in many neurological diseases. Oxidative toxicity in a number of these conditions is induced by excessive glutamate release and subsequent glutamatergic neuronal stimulation. This, in turn, causes increased generation of reactive oxygen species (ROS), oxidative stress, excitotoxicity, and neuronal damage. Recent studies indicate that the glutamatergic neurotransmitter system is involved in lead-induced neurotoxicity. Therefore, this study aimed to (1) investigate the potential effects of glutamate on lead-induced PC12 cell death and (2) elucidate whether the novel thiol antioxidant N-acetylcysteine amide (NACA) had any protective abilities against such cytotoxicity. Our results suggest that glutamate (1 mM) potentiates lead-induced cytotoxicity by increased generation of ROS, decreased proliferation (MTS), decreased glutathione (GSH) levels, and depletion of cellular adenosine-triphosphate (ATP). Consistent with its ability to decrease ATP levels and induce cell death, lead also increased caspase-3 activity, an effect potentiated by glutamate. Exposure to glutamate and lead elevated the cellular malondialdehyde (MDA) levels and phospholipase-A 2 (PLA 2 ) activity and diminished the glutamine synthetase (GS) activity. NACA protected PC12 cells from the cytotoxic effects of glutamate plus lead, as evaluated by MTS assay. NACA reduced the decrease in the cellular ATP levels and restored the intracellular GSH levels. The increased levels of ROS and MDA in glutamate-lead treated cells were significantly decreased by NACA. In conclusion, our data showed that glutamate potentiated the effects of lead-induced PC12 cell death by a mechanism involving mitochondrial dysfunction (ATP depletion) and oxidative stress. NACA had a protective role against the combined toxic effects of glutamate and lead by inhibiting lipid peroxidation and scavenging ROS, thus preserving intracellular GSH

  6. Evidence for glutamate as a neuroglial transmitter within sensory ganglia.

    Science.gov (United States)

    Kung, Ling-Hsuan; Gong, Kerui; Adedoyin, Mary; Ng, Johnson; Bhargava, Aditi; Ohara, Peter T; Jasmin, Luc

    2013-01-01

    This study examines key elements of glutamatergic transmission within sensory ganglia of the rat. We show that the soma of primary sensory neurons release glutamate when depolarized. Using acute dissociated mixed neuronal/glia cultures of dorsal root ganglia (DRG) or trigeminal ganglia and a colorimetric assay, we show that when glutamate uptake by satellite glial cells (SGCs) is inhibited, KCl stimulation leads to simultaneous increase of glutamate in the culture medium. With calcium imaging we see that the soma of primary sensory neurons and SGCs respond to AMPA, NMDA, kainate and mGluR agonists, and selective antagonists block this response. Using whole cell patch-clamp technique, inward currents were recorded from small diameter (ganglion preparation) in response to local application of the above glutamate receptor agonists. Following a chronic constriction injury (CCI) of either the inferior orbital nerve or the sciatic nerve, glutamate expression increases in the trigeminal ganglia and DRG respectively. This increase occurs in neurons of all diameters and is present in the somata of neurons with injured axons as well as in somata of neighboring uninjured neurons. These data provides additional evidence that glutamate can be released within the sensory ganglion, and that the somata of primary sensory neurons as well as SGCs express functional glutamate receptors at their surface. These findings, together with our previous gene knockdown data, suggest that glutamatergic transmission within the ganglion could impact nociceptive threshold.

  7. Posttranslational Modification Biology of Glutamate Receptors and Drug Addiction

    Directory of Open Access Journals (Sweden)

    Li-Min eMao

    2011-03-01

    Full Text Available Posttranslational covalent modifications of glutamate receptors remain a hot topic. Early studies have established that this family of receptors, including almost all ionotropic and metabotropic glutamate receptor subtypes, undergoes active phosphorylation at serine, threonine, or tyrosine residues on their intracellular domains. Recent evidence identifies several glutamate receptor subtypes to be direct substrates for palmitoylation at cysteine residues. Other modifications such as ubiquitination and sumoylation at lysine residues also occur to certain glutamate receptors. These modifications are dynamic and reversible in nature and are regulatable by changing synaptic inputs. The regulated modifications significantly impact the receptor in many ways, including interrelated changes in biochemistry (synthesis, subunit assembling and protein-protein interactions, subcellular redistribution (trafficking, endocytosis, synaptic delivery and clustering, and physiology, usually associated with changes in synaptic plasticity. Glutamate receptors are enriched in the striatum and cooperate closely with dopamine to regulate striatal signaling. Emerging evidence shows that modification processes of striatal glutamate receptors are sensitive to addictive drugs, such as psychostimulants (cocaine and amphetamines. Altered modifications are believed to be directly linked to enduring receptor/synaptic plasticity and drug-seeking. This review summarizes several major types of modifications of glutamate receptors and analyzes the role of these modifications in striatal signaling and in the pathogenesis of psychostimulant addiction.

  8. Role of aminotransferases in glutamate metabolism of human erythrocytes

    Energy Technology Data Exchange (ETDEWEB)

    Ellinger, James J. [University of Wisconsin-Madison, Department of Biochemistry (United States); Lewis, Ian A. [Princeton University, Lewis-Sigler Institute for Integrative Genomics (United States); Markley, John L., E-mail: markley@nmrfam.wisc.edu [University of Wisconsin-Madison, Department of Biochemistry (United States)

    2011-04-15

    Human erythrocytes require a continual supply of glutamate to support glutathione synthesis, but are unable to transport this amino acid across their cell membrane. Consequently, erythrocytes rely on de novo glutamate biosynthesis from {alpha}-ketoglutarate and glutamine to maintain intracellular levels of glutamate. Erythrocytic glutamate biosynthesis is catalyzed by three enzymes, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and glutamine aminohydrolase (GA). Although the presence of these enzymes in RBCs has been well documented, the relative contributions of each pathway have not been established. Understanding the relative contributions of each biosynthetic pathway is critical for designing effective therapies for sickle cell disease, hemolytic anemia, pulmonary hypertension, and other glutathione-related disorders. In this study, we use multidimensional {sup 1}H-{sup 13}C nuclear magnetic resonance (NMR) spectroscopy and multiple reaction mode mass spectrometry (MRM-MS) to measure the kinetics of de novo glutamate biosynthesis via AST, ALT, and GA in intact cells and RBC lysates. We show that up to 89% of the erythrocyte glutamate pool can be derived from ALT and that ALT-derived glutamate is subsequently used for glutathione synthesis.

  9. GLT-1-Dependent Disruption of CNS Glutamate Homeostasis and Neuronal Function by the Protozoan Parasite Toxoplasma gondii.

    Directory of Open Access Journals (Sweden)

    Clément N David

    2016-06-01

    Full Text Available The immune privileged nature of the CNS can make it vulnerable to chronic and latent infections. Little is known about the effects of lifelong brain infections, and thus inflammation, on the neurological health of the host. Toxoplasma gondii is a parasite that can infect any mammalian nucleated cell with average worldwide seroprevalence rates of 30%. Infection by Toxoplasma is characterized by the lifelong presence of parasitic cysts within neurons in the brain, requiring a competent immune system to prevent parasite reactivation and encephalitis. In the immunocompetent individual, Toxoplasma infection is largely asymptomatic, however many recent studies suggest a strong correlation with certain neurodegenerative and psychiatric disorders. Here, we demonstrate a significant reduction in the primary astrocytic glutamate transporter, GLT-1, following infection with Toxoplasma. Using microdialysis of the murine frontal cortex over the course of infection, a significant increase in extracellular concentrations of glutamate is observed. Consistent with glutamate dysregulation, analysis of neurons reveal changes in morphology including a reduction in dendritic spines, VGlut1 and NeuN immunoreactivity. Furthermore, behavioral testing and EEG recordings point to significant changes in neuronal output. Finally, these changes in neuronal connectivity are dependent on infection-induced downregulation of GLT-1 as treatment with the ß-lactam antibiotic ceftriaxone, rescues extracellular glutamate concentrations, neuronal pathology and function. Altogether, these data demonstrate that following an infection with T. gondii, the delicate regulation of glutamate by astrocytes is disrupted and accounts for a range of deficits observed in chronic infection.

  10. Dysfunctional TCA-Cycle Metabolism in Glutamate Dehydrogenase Deficient Astrocytes.

    Science.gov (United States)

    Nissen, Jakob D; Pajęcka, Kamilla; Stridh, Malin H; Skytt, Dorte M; Waagepetersen, Helle S

    2015-12-01

    Astrocytes take up glutamate in the synaptic area subsequent to glutamatergic transmission by the aid of high affinity glutamate transporters. Glutamate is converted to glutamine or metabolized to support intermediary metabolism and energy production. Glutamate dehydrogenase (GDH) and aspartate aminotransferase (AAT) catalyze the reversible reaction between glutamate and α-ketoglutarate, which is the initial step for glutamate to enter TCA cycle metabolism. In contrast to GDH, AAT requires a concomitant interconversion of oxaloacetate and aspartate. We have investigated the role of GDH in astrocyte glutamate and glucose metabolism employing siRNA mediated knock down (KD) of GDH in cultured astrocytes using stable and radioactive isotopes for metabolic mapping. An increased level of aspartate was observed upon exposure to [U-(13) C]glutamate in astrocytes exhibiting reduced GDH activity. (13) C Labeling of aspartate and TCA cycle intermediates confirmed that the increased amount of aspartate is associated with elevated TCA cycle flux from α-ketoglutarate to oxaloacetate, i.e. truncated TCA cycle. (13) C Glucose metabolism was elevated in GDH deficient astrocytes as observed by increased de novo synthesis of aspartate via pyruvate carboxylation. In the absence of glucose, lactate production from glutamate via malic enzyme was lower in GDH deficient astrocytes. In conclusions, our studies reveal that metabolism via GDH serves an important anaplerotic role by adding net carbon to the TCA cycle. A reduction in GDH activity seems to cause the astrocytes to up-regulate activity in pathways involved in maintaining the amount of TCA cycle intermediates such as pyruvate carboxylation as well as utilization of alternate substrates such as branched chain amino acids. © 2015 Wiley Periodicals, Inc.

  11. In vitro evidence for the brain glutamate efflux hypothesis

    DEFF Research Database (Denmark)

    Helms, Hans Christian; Madelung, Rasmus; Waagepetersen, Helle Sønderby

    2012-01-01

    -glutamate homeostasis. Transendothelial transport- and accumulation studies of (3) H-L-glutamate, (3) H-L-aspartate, and (3) H-D-aspartate in an electrically tight bovine endothelial/rat astrocyte blood-brain barrier coculture model were performed. After 6 days in culture, the endothelium displayed transendothelial......The concentration of the excitotoxic amino acid, L-glutamate, in brain interstitial fluid is tightly regulated by uptake transporters and metabolism in astrocytes and neurons. The aim of this study was to investigate the possible role of the blood-brain barrier endothelium in brain L...

  12. Clearance of glutamate inside the synapse and beyond.

    Science.gov (United States)

    Bergles, D E; Diamond, J S; Jahr, C E

    1999-06-01

    The heated debate over the level of postsynaptic receptor occupancy by transmitter has not been extinguished - indeed, new evidence is fanning the flames. Recent experiments using two-photon microscopy suggest that the concentration of glutamate in the synaptic cleft does not attain levels previously suggested. In contrast, recordings from glial cells and studies of extrasynaptic receptor activation indicate that significant quantities of glutamate escape from the cleft following exocytosis. Determining the amount of glutamate efflux from the synaptic cleft and the distance it diffuses is critical to issues of synaptic specificity and the induction of synaptic plasticity.

  13. Stereostructure-activity studies on agonists at the AMPA and kainate subtypes of ionotropic glutamate receptors

    DEFF Research Database (Denmark)

    Johansen, Tommy N; Greenwood, Jeremy R; Frydenvang, Karla Andrea

    2003-01-01

    (S)-Glutamic acid (Glu), the major excitatory neurotransmitter in the central nervous system, operates through ionotropic as well as metabotropic receptors and is considered to be involved in certain neurological disorders and degenerative brain diseases that are currently without any satisfactory...... design of ligands, especially for the AMPA and kainate subtypes of ionotropic Glu receptors. This mini-review will focus on structure-activity relationships on AMPA and kainate receptor agonists with special emphasis on stereochemical and three-dimensional aspects....

  14. Stability and visible absorption of glutamic acid complexes with uranyl and neodymium ions

    International Nuclear Information System (INIS)

    Petit-Ramel, M.M.; Mosoni, L.

    1982-01-01

    The stability constants of the complexes of uranyl and neodymium ions with glutanic acid are determined pH-metrically in 0.1 M NaClO 4 solution at 25 0 C. In both cases protonated complexes are formed in significant concentrations. A new MA c