Science.gov

Sample records for monosodium glutamate msg-obese

  1. Surgical removal of visceral fat decreases plasma free fatty acid and increases insulin sensitivity on liver and peripheral tissue in monosodium glutamate (MSG)-obese rats.

    PubMed

    Kim, Y W; Kim, J Y; Lee, S K

    1999-10-01

    In order to evaluate the role of visceral and subcutaneous fat tissue in insulin sensitivity and lipid metabolism, we measured the fasting levels of plasma free fatty acid (FFA) and insulin, glucose disappearance rate (Rd), and hepatic glucose production rate (HGP) after surgical removal of visceral (VF) or subcutaneous (SF) fat tissue in monosodium glutamate-obese (MSG-Ob) rats. Monosodium glutamate obesity was induced in rats by neonatal injection of MSG. Surgery to remove fat was done at 15 weeks of age. The experiments were done four weeks after the surgery. MSG-Ob rats showed increased levels of FFA, insulin, and HGP and decreased Rd compared to normal rats. In the VF group, the FFA level and HGP were decreased to normal values, Rd was partially normalized, but the level of insulin did not change significantly compared to MSG-Ob. In the SF group, FFA and Rd were partially normalized, but HGP was not suppressed significantly compared to MSG-Ob. These results suggest that visceral fat affects the insulin sensitivity of liver and FFA concentration more than subcutaneous fat; however, no significant difference was shown on whole body insulin sensitivity and fasting insulin concentration. PMID:10576150

  2. Genotoxicity of monosodium glutamate.

    PubMed

    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. PMID:26929995

  3. The PPARalpha/gamma dual agonist chiglitazar improves insulin resistance and dyslipidemia in MSG obese rats.

    PubMed

    Li, Ping-Ping; Shan, Song; Chen, Yue-Teng; Ning, Zhi-Qiang; Sun, Su-Juan; Liu, Quan; Lu, Xian-Ping; Xie, Ming-Zhi; Shen, Zhu-Fang

    2006-07-01

    1. The aim of this study was to investigate the capacity of chiglitazar to improve insulin resistance and dyslipidemia in monosodium L-glutamate (MSG) obese rats and to determine whether its lipid-lowering effect is mediated through its activation of PPARalpha. 2. Chiglitazar is a PPARalpha/gamma dual agonist. 3. The compound improved impaired insulin and glucose tolerance; decreased plasma insulin level and increased the insulin sensitivity index and decreased HOMA index. Euglycemic hyperinsulinemic clamp studies showed chiglitazar increased the glucose infusion rate in MSG obese rats. 4. Chiglitazar inhibited alanine gluconeogenesis, lowered the hepatic glycogen level in MSG obese rats. Like rosiglitazone, chiglitazar promoted the differentiation of adipocytes and decreased the maximal diameter of adipocytes. In addition, chiglitazar decreased the fibrosis and lipid accumulation in the islets and increased the size of islets. 5. Chiglitazar reduced plasma triglyceride, total cholesterol (TCHO), nonesterified fatty acids (NEFA) and low density lipoprotein-cholesterol levels; lowered hepatic triglyceride and TCHO contents; decreased muscular NEFA level. Unlike rosiglitazone, chiglitazar showed significant increase of mRNA expression of PPARalpha, CPT1, BIFEZ, ACO and CYP4A10 in the liver of MSG obese rats. 6. These data suggest that PPARalpha/gamma coagonist, such as chiglitazar, affect lipid homeostasis with different mechanisms from rosiglitazone, chiglitazar may have better effects on lipid homeostasis in diabetic patients than selective PPARgamma agonists. PMID:16751799

  4. Anorexigenic effect of cholecystokinin is lost but that of CART (Cocaine and Amphetamine Regulated Transcript) peptide is preserved in monosodium glutamate obese mice.

    PubMed

    Zelezná, B; Maixnerová, J; Matysková, R; Haugvicová, R; Blokesová, D; Maletínská, L

    2009-01-01

    Monosodium glutamate (MSG) treatment of neonatal mice results in a selective damage to the arcuate nucleus (ARC) and development of obesity with increased adiposity at sustained body weight in the adulthood. Feeding pattern of the MSG obese mice is unusual. Our previous results showed that after 24-h fasting, MSG mice consumed negligible amount of food in several hours and therefore, it was impossible to register the effect of peptides attenuating food intake such as cholecystokinin (CCK) or cocaine- and amphetamine-regulated transcript (CART) peptide. To overcome this problem, two findings were used: firstly, orexigenic effect of neuropeptide Y (NPY) was attenuated both by CCK or CART peptide in lean fed mice and secondly, orexigenic effect of NPY was preserved in fed rats with MSG obesity. In this study, short-term food intake in fed lean and MSG obese C57BL/6 male mice was measured after simultaneous central administration of orexigenic NPY with either CART peptide or peripherally administered CCK. Anorexigenic action of exogenous CART peptide was preserved in MSG obese mice. On the other hand, satiety effect of exogenous CCK was completely lost in MSG obese mice. In conclusion, effective leptin signaling in ARC is necessary for satiety effect of CCK. PMID:19093718

  5. [A preliminary study on the mechanism of impaired beta cell function in monosodium glutamate obese rat with insulin resistance].

    PubMed

    Liu, Shuai-Nan; Liu, Quan; Shen, Zhu-Fang

    2008-11-01

    This study is to evaluate beta cell function and investigate the mechanism of impaired pancreatic islet beta cell function in monosodium glutamate (MSG) obese rat with insulin resistance, an animal model of metabolic syndrome. Insulin tolerance test was used to screen MSG obese rats with insulin resistance. Blood concentrations of glucose, triglyceride, total cholesterol and insulin were determined. Beta cell function was assessed with hyperglycemic clamp technique. The morphological alterations in pancreas and changes of islet beta cell mass were evaluated by hematoxylin-eosin (HE) and Gomori aldehyde fuchsin staining. Lipid, oxidative stress relevant factors, nitric oxide (NO) level and activity of ATPase in pancreas and pancreatic mitochondrial were tested. The MSG obese rats with insulin resistance could be validated as a typical metabolic syndrome animal model possessing increased fasting plasma triglycerides and insulin (P < 0. 001), markedly decreased weight indices of pancreas and impaired glucose-stimulated insulin secretion. Hematoxylin-eosin (HE) and Gomori aldehyde fuchsin staining showed increased adipocytes and fibroplasia deposition in pancreas and reduced beta cell mass. The increased contents of triglyceride and NO level, the decreased SOD levels and activities of total ATPase (P < 0.001), Na+-K+-ATPase (P < 0.001) and Ca2+-Mg2+-ATPase (P < 0.01) were observed in pancreas and its mitochondria versus normal rat. The study demonstrates that accumulation of lipids in pancreas could lead to increased systemic indicators of inflammation, such as NO, which may influence the activities of several kinds of ATPase in cell membranes and interfere the ion transport, substance metabolism and energy production in pancreas. Finally the MSG obese rats characterized with metabolic syndrome displayed an impairment of beta cell function. PMID:19239028

  6. Renal sympathetic nerve activity is increased in monosodium glutamate induced hyperadipose rats.

    PubMed

    da Silva Mattos, Alexandro Márcio; Xavier, Carlos Henrique; Karlen-Amarante, Marlusa; da Cunha, Natália Veronez; Fontes, Marco Antonio Peliky; Martins-Pinge, Marli Cardoso

    2012-08-01

    The literature suggests that both obesity and hypertension are associated with increased sympathetic nerve activity. In the present study we evaluated the renal sympathetic nerve activity (RSNA), mean arterial pressure (MAP) and heart rate (HR) in hyperadipose rats induced by neonatal administration of monosodium glutamate (MSG). Neonatal Wistar male rats were injected with MSG (4 mg/g body weight ID) or equimolar saline (control) for 5 days. At 90th day, all rats were anesthetized (urethane 1.4 g/kg) and prepared for MAP, HR and renal sympathetic nerve activity recordings. The anesthetized MSG rats presented baseline hypertension and increased baseline RSNA compared with control. Our results suggest the involvement of the renal sympathetic nervous system in the physiopathology of the MSG obesity. PMID:22705582

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

    PubMed

    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. PMID:25624414

  8. Altered baroreflex and autonomic modulation in monosodium glutamate-induced hyperadipose rats.

    PubMed

    Karlen-Amarante, Marlusa; da Cunha, Natália Veronez; de Andrade, Ozahyr; de Souza, Hugo Celso Dutra; Martins-Pinge, Marli Cardoso

    2012-10-01

    We aimed to examine the cardiovascular function by tonic and baroreflex alterations in obese rats induced by monosodium glutamate (MSG). Neonatal male Wistar rats were injected with MSG (4 mg/g body weight) or equimolar saline (control, C). At 90 days, all rats were anesthetized for catheterization of the femoral artery for mean arterial pressure (MAP) and heart rate (HR) recordings in the conscious state. After baseline, we performed IV treatment with hexamethonium (25 mg/kg), or atropine (1 mg/kg) or propranolol (3 mg/kg). We also performed the spectral analysis of heart rate variability (HRV) and baroreflex sensitivity. Baseline comparison showed that obese rats are hypertensive compared with control (C=110±2 mmHg; MSG=: 123±3 mmHg, P<0.05). After ganglionic blockade with hexamethonium the differences in MAP between control and obese rats disappeared. Beta adrenergic blockade with propranolol induced a greater decrease in heart rate compared with control. The analysis of HRV showed that obese rats have increased modulation by both components of the autonomic nervous system compared with control rats. The baroreflex gain showed increased sensitivity for the parasympathetic component in the obese rats (C=-2.41±0.25; MSG=-3.34±0.23 bpm/mmHg) compared with control. Our data suggest that both components of autonomic cardiac tonus and the parasympathetic component of the baroreflex sensitivity are increased in the MSG obese rat. It is possible that the parasympathetic alterations observed in these MSG obese rats may have originated from central areas of cardiovascular control. PMID:22554831

  9. Current clinical findings on monosodium glutamate.

    PubMed

    Livingstone, V H

    1981-07-01

    Monosodium glutamate (MSG) is a common and widely used food additive which has been passed as GRAS (generally recognized as safe) by the American Food and Drug Administration. However, it may have a significant adverse effect on certain individuals; the physician must be able to recognize the symptoms of MSG sensitivity, otherwise known as "Chinese Restaurant Syndrome". This article reviews current findings on MSG. PMID:21289773

  10. Effects of fibre-enriched diets on tissue lipid profiles of MSG obese rats.

    PubMed

    Rotimi, O A; Olayiwola, I O; Ademuyiwa, O; Balogun, E A

    2012-11-01

    In order to investigate the influence of some fibre-enriched diets on tissue lipids in an animal model of obesity induced by the administration of monosodium glutamate (MSG), obese rats were fed diets containing 30% of Acha, Cassava, Maize and Plantain for five weeks and weight gain, feed intake and lee index were recorded. The lipid profiles of plasma, erythrocytes, kidney, heart and liver as well as hepatic 3-hydroxyl-3-methylglutaryl-CoA (HMG-CoA) reductase activity were measured. The diets significantly (p<0.05) reduced weight gain and lee index in the obese rats. Obesity-induced increase in plasma and erythrocytes lipid levels was significantly (p<0.05) reduced by these diets. MSG-induced obesity also resulted in a significant increase (p<0.05) in hepatic cholesterol level which was reduced by the diets. MSG-obesity was characterised by a significant (p<0.05) increase in cholesterol, triacylglycerol and phospholipids in kidney and this was reversed by the diets except Maize which did not reverse the increased cholesterol level. Only Acha reversed the obesity-induced increase in heart cholesterol and phospholipids. The increased activity of hepatic HMG-CoA reductase associated with obesity was also significantly (p<0.05) reduced by the diets. In conclusion, dyslipidemia associated with MSG-induced obesity could be attenuated by consumption of fibre-enriched diets. PMID:22898616

  11. The safety evaluation of monosodium glutamate.

    PubMed

    Walker, R; Lupien, J R

    2000-04-01

    L-Glutamic acid and its ammonium, calcium, monosodium and potassium salts were evaluated by the Joint FAO/WHO Expert Committee on Food Additives (JECFA) in 1988. The Committee noted that intestinal and hepatic metabolism results in elevation of levels in systemic circulation only after extremely high doses given by gavage (>30mg/kg body weight). Ingestion of monosodium glutamate (MSG) was not associated with elevated levels in maternal milk, and glutamate did not readily pass the placental barrier. Human infants metabolized glutamate similarly to adults. Conventional toxicity studies using dietary administration of MSG in several species did not reveal any specific toxic or carcinogenic effects nor were there any adverse outcomes in reproduction and teratology studies. Attention was paid to central nervous system lesions produced in several species after parenteral administration of MSG or as a consequence of very high doses by gavage. Comparative studies indicated that the neonatal mouse was most sensitive to neuronal injury; older animals and other species (including primates) were less so. Blood levels of glutamate associated with lesions of the hypothalamus in the neonatal mouse were not approached in humans even after bolus doses of 10 g MSG in drinking water. Because human studies failed to confirm an involvement of MSG in "Chinese Restaurant Syndrome" or other idiosyncratic intolerance, the JECFA allocated an "acceptable daily intake (ADI) not specified" to glutamic acid and its salts. No additional risk to infants was indicated. The Scientific Committee for Food (SCF) of the European Commission reached a similar evaluation in 1991. The conclusions of a subsequent review by the Federation of American Societies for Experimental Biology (FASEB) and the Federal Drug Administration (FDA) did not discount the existence of a sensitive subpopulation but otherwise concurred with the safety evaluation of JECFA and the SCF. PMID:10736380

  12. 78 FR 76321 - Monosodium Glutamate From China and Indonesia

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-17

    ... Register of September 20, 2013 (78 FR 57881). The conference was held in Washington, DC, on October 23... COMMISSION Monosodium Glutamate From China and Indonesia Determinations On the basis of the record \\1... injured by reason of imports from China and Indonesia of monosodium glutamate, provided for in...

  13. Does monosodium glutamate cause flushing (or merely "glutamania")?

    PubMed

    Wilkin, J K

    1986-08-01

    Monosodium glutamate is widely regarded as the provocative agent in the "Chinese restaurant syndrome," of which flushing is regarded as part of the reaction. Six subjects were monitored by laser Doppler velocimetry for changes in facial cutaneous blood flow during challenge with monosodium glutamate and its cyclization product, pyroglutamate. Additionally, records of patients challenged with monosodium glutamate in the laboratory were reviewed. No flushing was provoked among the twenty-four people tested, eighteen of whom gave a positive history of Chinese restaurant syndrome flushing. These results indicate that monosodium glutamate-provoked flushing, if it exists at all, must be rare. Monosodium glutamate and its cyclization product, pyroglutamate, may provoke edema and associated symptoms. PMID:3745527

  14. Monosodium glutamate 'allergy': menace or myth?

    PubMed

    Williams, A N; Woessner, K M

    2009-05-01

    Monosodium glutamate (MSG) is a salt form of a non-essential amino acid commonly used as a food additive for its unique flavour enhancing qualities. Since the first description of the 'Monosodium glutamate symptom complex', originally described in 1968 as the 'Chinese restaurant syndrome', a number of anecdotal reports and small clinical studies of variable quality have attributed a variety of symptoms to the dietary ingestion of MSG. Descriptions of MSG-induced asthma, urticaria, angio-oedema, and rhinitis have prompted some to suggest that MSG should be an aetiologic consideration in patients presenting with these conditions. This review prevents a critical review of the available literature related to the possible role of MSG in the so-called 'Chinese restaurant syndrome' and in eliciting asthmatic bronchospasm, urticaria, angio-oedema, and rhinitis. Despite concerns raised by early reports, decades of research have failed to demonstrate a clear and consistent relationship between MSG ingestion and the development of these conditions. PMID:19389112

  15. Reproductive alterations in hyperinsulinemic but normoandrogenic MSG obese female rats.

    PubMed

    Gaspar, Renato Simões; Benevides, Renata Ohana Alves; Fontelles, João Lucas de Lima; Vale, Caroline Castro; França, Lucas Martins; Barros, Paulo de Tarso Silva; Paes, Antonio Marcus de Andrade

    2016-05-01

    Obesity and metabolic syndrome are the common causes of reproductive and fertility disorders in women. In particular, polycystic ovary syndrome, which is clinically characterized by hyperandrogenism, oligo/anovulation, and polycystic ovarian morphology, has been increasingly associated with metabolic disorders. However, given the broad interplay between metabolic and reproductive functions, this remains a field of intense research. In this study, we investigated the effect of monosodium l-glutamate (MSG)-induced obesity on reproductive biology of female rats. Newborn female rats were subcutaneously injected with MSG (4g/kg/day) or equiosmolar saline (CTR) each 2 days up to postnatal day (pnd) 10. On pnd 60, estrous cycle was evaluated using vaginal smears twice a day for 15 days, which showed MSG rats to be oligocyclic. Thereafter, animals were killed on estrous phase for blood and tissue collection. MSG rats had increased body mass, accumulation of retroperitoneal and visceral fat pads, and visceral adipocyte hypertrophy compared with CTR rats. MSG rats were also dyslipidemic and hyperinsulinemic but were normoglycemic and normoandrogenic. Ovarian morphology analysis showed that MSG rats had a two-fold decrease in oocyte count but a six-fold increase on ovarian follicular cysts, along with a higher number of total primordial and atretic follicles. Moreover, MSG rats had a four-fold increase in anti-Müllerian hormone immunohistochemical staining on antral follicles. Taken together, data presented here characterize MSG obesity as a unique model to study the metabolic pathways underlying reproductive disorders in the absence of overactivated hypothalamic-pituitary-gonadal axis. PMID:26952035

  16. Monosodium L-glutamate-induced asthma.

    PubMed

    Allen, D H; Delohery, J; Baker, G

    1987-10-01

    Ingested chemicals, including aspirin and sulfites, are becoming increasingly recognized as provokers of acute severe asthma. In order to investigate the asthma-provoking potential of the widely used flavor enhancer, monosodium L-glutamate (MSG), we challenged 32 subjects with asthma, a number of whom gave histories of severe asthma after Chinese restaurant meals or similarly spiced meals. The subjects received an additive-free diet for 5 days before challenge and were challenged in hospital, after an overnight fast, with 500 mg capsules of MSG. They were challenged in a single-blind, placebo-controlled fashion with increasing doses of MSG from 0.5 gm to 5.0 gm. Thirteen subjects reacted. Seven subjects (group 1) developed asthma and symptoms of the Chinese restaurant syndrome 1 to 2 hours after ingestion of MSG. Six subjects (group 2) did not develop symptoms of Chinese restaurant syndrome, and their asthma developed 6 to 12 hours after ingestion of MSG. These challenge studies confirm that MSG can provoke asthma. The reaction to MSG is dose dependent and may be delayed up to 12 hours, making recognition difficult for both patient and physician. PMID:3312372

  17. The efficacy of probiotics for monosodium glutamate-induced obesity: dietology concerns and opportunities for prevention

    PubMed Central

    2014-01-01

    Introduction Obesity becomes endemic today. Monosodium glutamate was proved as obesogenic food additive. Probiotics are discussed to impact on obesity development. Aims and objectives The aim was to study the effects of probiotics on the development of monosodium glutamate (MSG)-induced obesity in rats. Material and methods We included 45 Wistar male rats and divided into three groups (n = 15). Newborn rats of group 1 (control) received subcutaneously 8 μl/g saline. Group 2 received 3 to 4 mg/g MSG subcutaneously on the second, fourth, sixth, eighth and tenth day of life. Within 4 months after birth, rats were on a standard diet. Group 3 received an aqueous solution of probiotics mixture (2:1:1 Lactobacillus casei IMVB-7280, Bifidobacterium animalis VKL, B. animalis VKB) at the dose of 5 × 109 CFU/kg (50 mg/kg) intragastrically. Administration of probiotics was started at the age of 4 weeks just after weaning and continued for 3 months during 2-week courses. Group 2 received intragastrically 2.5 ml/kg water. Organometric and biochemical parameters in all groups of rats were analyzed over 4 months. The concentration of adiponectin was determined in serum, and leptin - in adipose tissue. Results Administration of MSG led to the development of obesity in rats; body weight had increased by 7.9% vs controls (p < 0.05); body length had increased by 5.4% (p < 0.05). Body mass index and Lee index and visceral fat mass had increased (p < 0.001). Under the neonatal injection of MSG, the concentration of total cholesterol, triglycerides, VLDL cholesterol and LDL cholesterol significantly increased (p < 0.001), in comparison with controls. Adipose-derived hormones changed in MSG obesity rats: adiponectin decreased by 58.8% (p < 0.01), and leptin concentration in adipose tissue had increased by 74.7% (p < 0.01). The probiotic therapy of rats from group 3 prevented obesity development. Parameters of rats treated with probiotic mixture did not differ from that in

  18. Recombinant murine fibroblast growth factor 21 ameliorates obesity-related inflammation in monosodium glutamate-induced obesity rats.

    PubMed

    Wang, Wen-Fei; Li, Si-Ming; Ren, Gui-Ping; Zheng, Wei; Lu, Yu-Jia; Yu, Yin-Hang; Xu, Wen-Juan; Li, Tian-He; Zhou, Li-Hong; Liu, Yan; Li, De-Shan

    2015-05-01

    The aim of this study is to investigate the role of FGF21 in obesity-related inflammation in livers of monosodium glutamate (MSG)-induced obesity rats. The MSG rats were injected with recombinant murine fibroblast growth factor 21(FGF21) or equal volumes of vehicle. Metabolic parameters including body weight, Lee's index, food intake, visceral fat and liver weight, intraperitoneal glucose tolerance, glucose, and lipid levels were dynamically measured at specific time points. Liver function and routine blood test were also analyzed. Further, systemic inflammatory cytokines such as glucose transporter 1 (GLUT-1), leptin, TNF-α, and IL-6 mRNAs were determined by real-time PCR. FGF21 independently decreased body weight and whole-body fat mass without reducing food intake in the MSG rats. FGF21 reduced blood glucose level, Lee's index, visceral fat, and liver weight, and improved glucose tolerance, lipid metabolic spectrum, and hepatic steatosis in the MSG-obesity rats. Liver function parameters including AST, ALT, ALP, TP, T.Bili, and D.Bili levels significantly reduced in the FGF21-treated obesity rats compared to the controls. Further, FGF21 ameliorated the total and differential white blood cell (WBC) count, serum C-reactive protein (CRP), IL-6, and TNF-α levels in adipose tissues of the obesity rats, suggesting inflammation amelioration in the in the obesity rats by FGF21. FGF21 improves multiple metabolic disorders and ameliorates obesity-related inflammation in the MSG-induced obesity rats. PMID:25306889

  19. Monosodium glutamate is not likely to be genotoxic.

    PubMed

    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. PMID:27372553

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

    PubMed Central

    Hernández-Bautista, René J.; Alarcón-Aguilar, Francisco J.; Escobar-Villanueva, María Del C.; Almanza-Pérez, Julio C.; Merino-Aguilar, Héctor; Konigsberg Fainstein, Mina; López-Diazguerrero, Norma E.

    2014-01-01

    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. PMID:24979131

  1. Biochemical alterations during the obese-aging process in female and male monosodium glutamate (MSG)-treated mice.

    PubMed

    Hernández-Bautista, René J; Alarcón-Aguilar, Francisco J; Del C Escobar-Villanueva, María; Almanza-Pérez, Julio C; Merino-Aguilar, Héctor; Fainstein, Mina Konigsberg; López-Diazguerrero, Norma E

    2014-01-01

    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. PMID:24979131

  2. Vagotomy ameliorates islet morphofunction and body metabolic homeostasis in MSG-obese rats.

    PubMed

    Lubaczeuski, C; Balbo, S L; Ribeiro, R A; Vettorazzi, J F; Santos-Silva, J C; Carneiro, E M; Bonfleur, M L

    2015-05-01

    The parasympathetic nervous system is important for β-cell secretion and mass regulation. Here, we characterized involvement of the vagus nerve in pancreatic β-cell morphofunctional regulation and body nutrient homeostasis in 90-day-old monosodium glutamate (MSG)-obese rats. Male newborn Wistar rats received MSG (4 g/kg body weight) or saline [control (CTL) group] during the first 5 days of life. At 30 days of age, both groups of rats were submitted to sham-surgery (CTL and MSG groups) or subdiaphragmatic vagotomy (Cvag and Mvag groups). The 90-day-old MSG rats presented obesity, hyperinsulinemia, insulin resistance, and hypertriglyceridemia. Their pancreatic islets hypersecreted insulin in response to glucose but did not increase insulin release upon carbachol (Cch) stimulus, despite a higher intracellular Ca(2+) mobilization. Furthermore, while the pancreas weight was 34% lower in MSG rats, no alteration in islet and β-cell mass was observed. However, in the MSG pancreas, increases of 51% and 55% were observed in the total islet and β-cell area/pancreas section, respectively. Also, the β-cell number per β-cell area was 19% higher in MSG rat pancreas than in CTL pancreas. Vagotomy prevented obesity, reducing 25% of body fat stores and ameliorated glucose homeostasis in Mvag rats. Mvag islets demonstrated partially reduced insulin secretion in response to 11.1 mM glucose and presented normalization of Cch-induced Ca(2+) mobilization and insulin release. All morphometric parameters were similar among Mvag and CTL rat pancreases. Therefore, the higher insulin release in MSG rats was associated with greater β-cell/islet numbers and not due to hypertrophy. Vagotomy improved whole body nutrient homeostasis and endocrine pancreatic morphofunction in Mvag rats. PMID:25714886

  3. Mechanisms underlying hypertriglyceridemia in rats with monosodium L-glutamate-induced obesity: evidence of XBP-1/PDI/MTP axis activation.

    PubMed

    França, Lucas Martins; Freitas, Larissa Nara Costa; Chagas, Vinicyus Teles; Coêlho, Caio Fernando Ferreira; Barroso, Wermerson Assunção; Costa, Graciomar Conceição; Silva, Lucilene Amorim; Debbas, Victor; Laurindo, Francisco Rafael Martins; Paes, Antonio Marcus de Andrade

    2014-01-10

    Non-alcoholic fatty liver disease (NAFLD) is intimately associated with insulin resistance and hypertriglyceridemia, whereas many of the mechanisms underlying this association are still poorly understood. In the present study, we investigated the relationship between microsomal triglyceride transfer protein (MTP) and markers of endoplasmic reticulum (ER) stress in the liver of rats subjected to neonatal monosodium L-glutamate (MSG)-induced obesity. At age 120 days old, the MSG-obese animals exhibited hyperglycemia, hypertriglyceridemia, insulin resistance, and liver steatosis, while the control (CTR) group did not. Analysis using fast protein liquid chromatography of the serum lipoproteins revealed that the triacylglycerol content of the very low-density lipoprotein (VLDL) particles was twice as high in the MSG animals compared with the CTR animals. The expression of ER stress markers, GRP76 and GRP94, was increased in the MSG rats, promoting a higher expression of X-box binding protein 1 (XBP-1), protein disulfide isomerase (PDI), and MTP. As the XBP-1/PDI/MTP axis has been suggested to represent a significant lipogenic mechanism in the liver response to ER stress, our data indicate that hypertriglyceridemia and liver steatosis occurring in the MSG rats are associated with increased MTP expression. PMID:24333444

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

    PubMed Central

    Jinap, Selamat; Hajeb, Parvaneh; Karim, Roslina; Norliana, Sarian; Yibadatihan, Simayi; Abdul-Kadir, Razak

    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 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. PMID:27356909

  5. Monosodium Glutamate Intake, Dietary Patterns and Asthma in Chinese Adults

    PubMed Central

    Shi, Zumin; Yuan, Baojun; Wittert, Gary A.; Pan, Xiaoqun; Dai, Yue; Adams, Robert; Taylor, Anne W.

    2012-01-01

    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. PMID:23240044

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  7. HPA axis and vagus nervous function are involved in impaired insulin secretion of MSG-obese rats.

    PubMed

    Miranda, Rosiane A; Torrezan, Rosana; de Oliveira, Júlio C; Barella, Luiz F; da Silva Franco, Claudinéia C; Lisboa, Patrícia C; Moura, Egberto G; Mathias, Paulo C F

    2016-07-01

    Neuroendocrine dysfunctions such as the hyperactivity of the vagus nerve and hypothalamus-pituitary-adrenal (HPA) axis greatly contribute to obesity and hyperinsulinemia; however, little is known about these dysfunctions in the pancreatic β-cells of obese individuals. We used a hypothalamic-obesity model obtained by neonatal treatment with monosodium l-glutamate (MSG) to induce obesity. To assess the role of the HPA axis and vagal tonus in the genesis of hypercorticosteronemia and hyperinsulinemia in an adult MSG-obese rat model, bilateral adrenalectomy (ADX) and subdiaphragmatic vagotomy (VAG) alone or combined surgeries (ADX-VAG) were performed. To study glucose-induced insulin secretion (GIIS) and the cholinergic insulinotropic process, pancreatic islets were incubated with different glucose concentrations with or without oxotremorine-M, a selective agonist of the M3 muscarinic acetylcholine receptor (M3AChR) subtype. Protein expression of M3AChR in pancreatic islets, corticosteronemia, and vagus nerve activity was also evaluated. Surgeries reduced 80% of the body weight gain. Fasting glucose and insulin were reduced both by ADX and ADX-VAG, whereas VAG was only associated with hyperglycemia. The serum insulin post-glucose stimulation was lower in all animals that underwent an operation. Vagal activity was decreased by 50% in ADX rats. In the highest glucose concentration, both surgeries reduced GIIS by 50%, whereas ADX-VAG decreased by 70%. Additionally, M3AChR activity was recovered by the individual surgeries. M3AChR protein expression was reduced by ADX. Both the adrenal gland and vagus nerve contribute to the hyperinsulinemia in the MSG model, although adrenal is more crucial as it appears to modulate parasympathetic activity and M3AChR expression in obesity. PMID:27113853

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

    PubMed

    Sharma, Amod

    2015-01-01

    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. PMID:26493866

  9. The role of ascorbic acid and monosodium glutamate in thymocyte apoptosis.

    PubMed

    Pavlovic, V; Sarac, M

    2010-01-01

    The studies on experimental animals have confirmed toxic effect of monosodium glutamate in different organs, mainly manifested by increased oxidative stress and cytotoxicity, strongly correlated with numerous diseases. Continuous intake of this flavor enhancer in modern nutrition also resulted with toxic effects on human health, known as Chinese restaurant syndrome. The reference data about influence of monosodium glutamate on the cells of the immune system or primary immune organs and possible protective effects of specific antioxidants are still largely unknown. This review summarizes recently known facts about the role of monosodium glutamate in the cells of the immune system, especially in thymocytes. Also, in this review many new data on positive effects of ascorbic acid on immune system and the mechanisms of its protective influence on thymocytes are discussed (Tab. 1, Ref. 52). PMID:20635684

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

    ERIC Educational Resources Information Center

    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.

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

    NASA Astrophysics Data System (ADS)

    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.

  12. EFFECTS OF PERINATAL MONOSODIUM GLUTAMATE ADMINISTRATIONON VISUAL EVOKED POTENTIALS OF JUVENILE AND ADULT RATS

    EPA Science Inventory

    Administration of high doses of monosodium glutamate (MSG) to rats during the first postnatal week results in severe losses of retinal ganglion cells and interneurons in the retina. his study was conducted to determine what effect this severe retinal damage would have upon the on...

  13. Monosodium L-glutamate: its pharmacology and role in the Chinese restaurant syndrome.

    PubMed

    Schaumburg, H H; Byck, R; Gerstl, R; Mashman, J H

    1969-02-21

    Monosodium L-glutamate is the cause of the Chinese restaurant syndrome and can precipitate headaches. In appropriate doses it causes burning sensations, facial pressure, and chest pain. These are pharmacological effects obeying a dose-effect relationship. There is considerable variation in oral threshold does among individuals. PMID:5764480

  14. Prenatal monosodium glutamate (MSG) treatment given through the mother's diet causes behavioral deficits in rat offspring.

    PubMed

    Frieder, B; Grimm, V E

    1984-04-01

    The present study reports various developmental and behavioral changes in the offspring of rat dams that received monosodium glutamate (MSG) in the drinking water all through the second and third trimesters of pregnancy. Three main effects were observed in the MSG exposed offspring: (1) juvenile obesity; (2) reduced general activity levels; (3) a specific type of learning disability in discrimination learning involving choice between simultaneously present positive and negative stimuli. PMID:6541212

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

    PubMed

    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. PMID:25007523

  16. Learned taste aversions induced by high doses of monosodium L-glutamate.

    PubMed

    Vogel, J R; Nathan, B A

    1975-01-01

    Learned taste aversions, as measured by increased time to complete 100 licks of a sweetened condensed milk solution, were demonstrated by laboratory rats 4 days after consumption of the milk solution paired with high oral doses of monosodium 1-glutamate (MSG). The hesitancy of the rats to consume milk on the test session cannot be simply attributed to direct action of the drug on motivation (e.g., hunger) or to drug debilitation. MSG has been reported to occasionally cause aversive effects in humans (Chinese restaurant syndrome), and the present experiments demonstrate that the effects of MSG are aversive to laboratory rats as well. PMID:1208638

  17. [Oxidative stress development in the tissues of salivary glands of rats in conditions of monosodium glutamate-induced obesity].

    PubMed

    Hordiienko, L P; Berehova, T V; Neporada, K S; Falalieieva, T M

    2014-01-01

    Pathogenic mechanisms of damage of salivary glands under obesity are an insufficiently studied problem of modem medicine. On experimental model of obesity induced by monosodium glutamate, free-radical processes and antioxidant defense system were studied in the tissues of salivary glands of rats. Under experimental obesity induced by monosodium glutamate there is a significant increase of the content of thio-barbituric acid reactive substances and a significant decrease in the activity of superoxide dismutase and catalase. Thus, it indicates to the misbalance of prooxidant and antioxidant systems and the development of oxidative stress. PMID:25335241

  18. Production of a newly isolated Paenibacillus polymyxa biocontrol agent using monosodium glutamate wastewater and potato wastewater.

    PubMed

    Gu, Likun; Bai, Zhihui; Jin, Bo; Zhang, Jianyun; Li, Wenying; Zhuang, Guoqiang; Zhang, Hongxun

    2010-01-01

    A phyllosphere bacterial strain EBL-06 was isolated from wheat leaves. The morphology, cultural characteristics, phospholipid fatty acids, physiological and antagonistic fungus activities of this strain were investigated. A phylogenetic tree was constructed by comparing with the published 16S rDNA sequences of the relevant bacteria. The results showed that the isolate EBL-06 was a strain of Paenibacillus polymyxa; this strain performed a high level of antagonistic fungus activity toward a broad spectrum of phytopathogens, such as Botrytis cinerea, Cladosporium cucumerinum, Fusarium spp. The isolate EBL-06 can grow well using monosodium glutamate wastewater (MGW) and potato wastewater (PW) as culture medium. The maximum yield of 6.5 x 10(9) CFU/mL of the isolate EBL-06 anti-fungus biocontrol agent was reached in 15 hr cultivation at 28 degrees C, pH 6.0-7.5 using the mixture of MGW and PW (1:9). PMID:21174972

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

    PubMed

    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. PMID:27189588

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

    PubMed

    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. [Characterization of an experimental model of monosodium- glutamate-induced convulsions in the amphibian Bufo spp].

    PubMed

    Alfaro, F; Blas, O; Gutiérrez-Padilla, R; Feria-Velasco, A

    1990-01-01

    In previous reports, Feria-Velasco et al. characterized an experimental model of convulsions in rats induced by monosodium glutamate (MSG) with evaluation of the motor behavior and neurochemical parameters. In the present work, MSG injected in toads (Bufo spp) reproduced the model of convulsions with some peculiarities. The electrocorticographic recordings in toads after MSG injection were similar to those obtained in rats after administration of convulsant agents. Most of the toads injected with MSG (81.8%) showed convulsions preceded by an episode of stereotyped movements and signs of hyperexcitability. Latency for convulsions and frequency of convulsive episodes were similar to what has been reported in rats injected with MSG. However, the duration of convulsive period was larger than that seen in rats, and no deaths were recorded in toads. The peculiar feature of amphibia regarding their cerebral structures and their blood-brain barrier (BBB) make the amphibian model, an interesting and valuable one in studying experimentally induced convulsions, as well as the role of BBB in these phenomena. PMID:1669233

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

    NASA Technical Reports Server (NTRS)

    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.

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

    NASA Astrophysics Data System (ADS)

    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.

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

    PubMed

    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. PMID:26799547

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

    PubMed

    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. PMID:26945164

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

    PubMed

    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. PMID:26043886

  7. Condensation of supersaturated water vapor on charged/neutral nanoparticles of glucose and monosodium glutamate.

    PubMed

    Chen, Chin-Cheng; Tao, Chun-Ju; Cheng, Hsiu-Chin

    2002-11-01

    The effects of size, charge, dissolution, and dissociation on the condensation of supersaturated water vapor on monodisperse nanoparticles of glucose and monosodium glutamate (MSG) were investigated in a flow cloud chamber (FCC). The dependence of the critical supersaturation, S(cr), on particle size in the range of 30 to 90 nm and on temperature in the range of 10 to 50 degrees C were determined experimentally. The results show that the experimental S(cr) decreases with increasing particle size at a rate in reasonable agreement with the predictions of the Kohler and Volmer theories of nucleation for soluble particles, but decreases with increasing temperature at a rate higher than the prediction of the Volmer theory. The dissociation of MSG into ions lowers the experimental S(cr) to a value smaller than that for the more soluble glucose, agreeing with predictions. The experimental S(cr) is smaller than the predictions of both theories, and the discrepancy cannot be fully explained by the reductions in surface tension due to the dissolution of particles and curvature dependence. The condensation of supersaturated vapor on singly positively charged particles with diameters of 30, 60, and 90 nm was also examined, and no obvious charge effect on S(cr) was observed. PMID:12702381

  8. Monosodium L-glutamate: a double-blind study and review.

    PubMed

    Tarasoff, L; Kelly, M F

    1993-12-01

    71 healthy subjects were treated with placebos and monosodium L-glutamate (MSG) doses of 1.5, 3.0 and 3.15 g/person, which represented a body mass-adjusted dose range of 0.015-0.07 g/kg body weight before a standardized breakfast over 5 days. The study used a rigorous randomized double-blind crossover design that controlled for subjects who had MSG after-tastes. Capsules and specially formulated drinks were used as vehicles for placebo and MSG treatments. Subjects mostly had no responses to placebo (86%) and MSG (85%) treatments. Sensations, previously attributed to MSG, did not occur at a significantly higher rate than did those elicited by placebo treatment. A significant (P < 0.05) negative correlation between MSG dose and after-effects was found. The profound effect of food in negating the effects of large MSG doses was demonstrated. The common practice of extrapolating food-free experimental results to 'in use' situations was called into question. An exhaustive review of previous methodologies identified the strong taste of MSG as the factor invalidating most 'blind' and 'double-blind' claims by previous researchers. The present study led to the conclusion that 'Chinese Restaurant Syndrome' is an anecdote applied to a variety of postprandial illnesses; rigorous and realistic scientific evidence linking the syndrome to MSG could not be found. PMID:8282275

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

    PubMed

    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. PMID:24556569

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

    PubMed

    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. PMID:26577083

  11. Intragastric monosodium L-glutamate stimulates motility of upper gut via vagus nerve in conscious dogs.

    PubMed

    Toyomasu, Yoshitaka; Mochiki, Erito; Yanai, Mitsuhiro; Ogata, Kyoichi; Tabe, Yuichi; Ando, Hiroyuki; Ohno, Tetsuro; Aihara, Ryuusuke; Zai, Hiroaki; Kuwano, Hiroyuki

    2010-04-01

    Monosodium l-glutamate (MSG) is a substance known to produce the umami taste. Recent studies indicate that MSG also stimulates a variety of activities in the gastrointestinal tract through its receptor in the gut, but no study has reported the activity in conscious large experimental animals. The aim of our study was to investigate whether direct intragastric MSG stimulates gut motility and to identify the mechanism in conscious dogs. Contractile response to intraluminal injection of MSG was studied in the fed and fasted states by means of chronically implanted force transducers. MSG (5, 15, 45, and 90 mM/kg) dissolved in water was injected into the stomach and duodenum in normal and vagotomized dogs. MSG solution was administered into the stomach before feeding, and gastric emptying was evaluated. Several inhibitors of gastrointestinal motility (atropine, hexamethonium, and granisetron) were injected intravenously before MSG administration to the stomach. The effect of MSG was investigated in Pavlov (vagally innervated corpus pouch), Heidenhain (vagally denervated corpus pouch), and antral pouch (vagally innervated) dogs. Upper gut motility was significantly increased by intragastric MSG but not significantly stimulated by intraduodenal MSG. Intragastric MSG (45 mM/kg) stimulated postprandial motility and accelerated gastric emptying. MSG-induced contractions were inhibited by truncal vagotomy, atropine, hexamethonium, and granisetron. Gut motility was increased by intrapouch injection of MSG in the Pavlov pouch, but it was not affected in the Heidenhain or antral pouch dogs. We conclude that intragastric MSG stimulates upper gut motility and accelerates gastric emptying. The sensory structure of MSG is present in the gastric corpus, and the signal is mediated by the vagus nerve. PMID:20071606

  12. Effects of bezafibrate in nonalcoholic steatohepatitis model mice with monosodium glutamate-induced metabolic syndrome.

    PubMed

    Sasaki, Yoshiyuki; Shimada, Tsutomu; Iizuka, Seiichi; Suzuki, Wataru; Makihara, Hiroko; Teraoka, Ryutaro; Tsuneyama, Koichi; Hokao, Ryoji; Aburada, Masaki

    2011-07-15

    Recently, we reported that monosodium glutamate-treated mice (MSG mice) developed severe hyperlipidemia and diabetes mellitus and several complications of obesity. MSG mice acquired fatty livers and subsequently underwent changes that are characteristic of nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH). In the present study, the effects of bezafibrate on obesity, diabetes mellitus, and NAFLD/NASH were examined in MSG mice. A single dose of MSG (4 mg/g) was administered subcutaneously to neonatal male mice within 24h of birth. Bezafibrate was mixed into the normal feed for 8 weeks. The weight and body mass index of MSG mice increased significantly despite the unchanged intake of food. Triglyceride and total cholesterol levels in blood, visceral adipose tissue, and interscapular adipose tissue rose significantly. In the livers of MSG mice, moderate centrilobular microvesicular steatosis, ballooning degeneration with Mallory bodies, and scattered infiltration of neutrophils and lymphocytes were observed. Centrilobular hepatocytes were 4-hydroxynonenal-positive in MSG mice. Bezafibrate ameliorated the severity of diabetes mellitus, hyperinsulinemia, and hyperlipidemia. Adiponectin and leptin concentrations in blood improved, and the accumulation of visceral fat was inhibited. The expression of acyl-CoA oxidase, a beta-oxidation gene, and carnitine palmitoyl transferase, which regulates lipid metabolism, increased markedly on administration of bezafibrate. The liver pathology in MSG mice also improved with bezafibrate; specifically, macro- and microvesicles in hepatocytes nearly disappeared, and NAFLD activity score improved. It is concluded that bezafibrate inhibits the accumulation of visceral fat, following amelioration of hyperlipidemia, in MSG-induced obese mice, due to improvements in diabetes mellitus, fatty liver, and NAFLD. PMID:21549692

  13. GLUT4 protein is differently modulated during development of obesity in monosodium glutamate-treated mice.

    PubMed

    de Carvalho Papa, Paula; Vargas, Alessandra Martins; da Silva, José Luciano Tavares; Nunes, Maria Tereza; Machado, Ubiratan F

    2002-09-01

    The aim of the present study was to investigate the GLUT4 protein expression during the development of obesity in monosodium glutamate- (MSG) treated mice. Control (C) and neonatally MSG-treated 2-month-old (2-mo), 4-month-old (4-mo) and 7-month-old (7-mo) mice were analyzed. Anthropometric data, basal glycemia and insulinemia were measured; and the GLUT4 protein was assessed by Western blotting in white adipose tissue (WAT), skeletal muscle gastrocnemius (SM) and heart (H). Compared to age-matched C mice, the 2-mo and 4-mo MSG mice were already obese, but metabolically they showed increased or preserved whole-body insulin sensitivity, respectively. At these ages they showed unchanged total GLUT4 content in SM and H. However, in plasma membrane fraction from WAT, the MSG showed increased GLUT4 content at both 2- (by 60%) and 4-month (by 45%) of age. When the GLUT4 protein was expressed by unit of adipocyte surface area the protein amount was increased by 36 and 220% in 2-mo and 4-mo MSG mice, respectively. At 7 months of age, obesity was fully established in MSG mice, showing a strongly insulin resistant condition. Additionally, in the 7-mo MSG-mice the GLUT4 protein was reduced in SM (by 40%), H (by 28%), PM and M fractions of WAT (by approximately 70%), and PM expressed by unit of adipocyte surface area (by 92%). The data demonstrate that early, during the accelerated development of obesity in MSG-treated mice, the GLUT4 content was increased in WAT, and that may play a key role in the development of obesity. Later on, when obesity is fully established, the GLUT4 protein was reduced in SM, heart and WAT, and that may be involved in the insulin resistance present in this condition. PMID:12175706

  14. Drug-metabolizing and antioxidant enzymes in monosodium L-glutamate obese mice.

    PubMed

    Matoušková, Petra; Bártíková, Hana; Boušová, Iva; Levorová, Lucie; Szotáková, Barbora; Skálová, Lenka

    2015-02-01

    The prevalence of obesity is rapidly increasing across the world. Physiologic alterations associated with obesity are known to alter enzyme expression and/or activities. As drug-metabolizing and antioxidant enzymes serve as defense system against potentially toxic compounds, their modulation might have serious consequences. In this work, we studied selected antioxidant and drug-metabolizing enzymes (DME) in monosodium glutamate-mouse model of obesity. Specific activities, protein, and mRNA expressions of these enzymes in liver as well as in small intestine were compared in obese male mice and in their lean counterparts. Furthermore, expression of the NF-E2-related factor 2 (Nrf2) and its relation to obesity were tested. Obtained results showed that obesity affects expression and/or activities of some DME and antioxidant enzymes. In obese mice, upregulation of UDP-glucuronosyltransferases 1A (UGT1A), NAD(P)H:quinone oxidoreductase 1 (NQO1), nuclear transcription factor Nrf2, and downregulation of some isoforms of glutathione S-transferases (GST) were observed. Most of these changes were tissue and/or isoform specific. NQO1 seems to be regulated transcriptionally via Nrf2, but other enzymes might be regulated post-transcriptionally and/or post-translationally. Enhanced expression of Nrf2 in livers of obese mice is expected to play a role in protective adaptation. In contrast, elevated activities of NQO1 and UGT1A may cause alterations in drug pharmacokinetics in obese individuals. Moreover, decreased capacity of GST in obese animals indicates potentially reduced antioxidant defense and weaker chemoprotection. PMID:25473020

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

    PubMed Central

    Boonnate, Piyanard; Waraasawapati, Sakda; Hipkaeo, Wiphawi; Pethlert, Supattra; Sharma, Amod; Selmi, Carlo; Prasongwattana, Vitoon; Cha’on, Ubon

    2015-01-01

    Background 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. Methods 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. Results 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. Conclusion 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. PMID:26121281

  16. Effects of CB1 receptor blockade on monosodium glutamate induced hypometabolic and hypothalamic obesity in rats.

    PubMed

    Chen, Wei; Chen, Zhenhua; Xue, Nina; Zheng, Zhibing; Li, Song; Wang, Lili

    2013-08-01

    Effects of cannabinoid receptor 1 (CB1R) blockade were observed by comparing 9-day and 6-week SR141716 treatments in monosodium glutamate (MSG)-induced hypometabolic and hypothalamic obesity (HO) in rats for the first time and molecular mechanisms were investigated. Compared with normal rats, the MSG rats display typical symptoms of the metabolic syndrome, i.e., excessive abdominal obesity, hypertriglyceridemia, hyperinsulinemia, insulin resistance, and hepatic steatosis, but with lower food intake. Although both the 9-day and 6-week treatments with the specific CB1R antagonist SR141716 effectively lowered body weight, intraperitoneal adipose tissue mass, serum triglyceride (TG), and insulin level, the effect of chronic treatment is more impressive. Moreover, serum cholesterol, free fatty acids (FFA), fasted and postprandial blood glucose, and insulin insensitivity were more effectively improved by 6-week exposure to SR141716, whereas hypophagia was only effective within the initial 2 weeks. In addition, hepatic steatosis as well as hepatic and adipocyte morphology was improved. Western blot analysis revealed that the markedly increased CB1R expression and decreased insulin receptor (INR) expression in liver and adipose tissues were effectively corrected by SR141716. Consistent with this, deregulated gene expression of lipogenesis and lipolysis as well as glucose metabolic key enzymes were also restored by SR141716. In conclusion, based on present data we found that: (1) alteration of the hypothalamus in MSG rats leads to a lower expression of INR in crucially insulin-targeted tissues and hyperinsulinemia that was reversed by SR141716, (2) the abnormally increased expression of CB1R in liver and adipose tissues plays a vital role in the pathophysiological process of MSG rats, and (3) chronic CB1R blockade leads to a sustained improvement of the metabolic dysfunctions of MSG rats. PMID:23620336

  17. [Pathological changes in hepatocytes of mice with obesity-induced type 2 diabetes by monosodium glutamate].

    PubMed

    Nakadate, Kazuhiko; Motojima, Kento; Kamata, Sumito; Yoshida, Testuro; Hikita, Masaaki; Wakamatsu, Hisanori

    2014-01-01

    Type 2 diabetes caused by chronic obesity is a major lifestyle-related disease. The present study aimed to determine the pathological changes in hepatocytes in chronic obesity. To develop our type 2 diabetes mouse model, we induced chronic obesity to mice by monosodium glutamate. By overeating, the mice significantly increased their body weight compared with age-matched healthy animals. To analyze the pathological changes in hepatocytes of chronic obesity before preclinical stage of type 2 diabetes, the mice were analyzed by hematoxylin-eosin staining of tissue sections at 15 w of age. In these mice, we observed eosin-negative accumulations of hepatocytes around central veins in the hepatic lobule. By Oil-Red O staining, the eosin-negative granules were identified in the lipid droplets. We then ascertained whether these lipid droplets of hepatocytes in the obese mice could be modified by diet. After 24 h of diet restriction, the lipid droplets of hepatocytes in the obese mice were swollen. Furthermore, after 48 h of the diet restriction, the lipid droplets continued swelling and the autophagy-like structures that were found in the healthy mice under the same condition in the obese mice were not observed. These results suggest that the obese mice might have delayed energy metabolism, which might have influenced the mechanisms of hepatocytes. These findings provide new insight into the functional changes in chronic obesity-induced type 2 diabetes and it is possible that the pathological feature make a contribution to promise the target of pharmacological therapy. PMID:24989474

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

    PubMed

    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. PMID:27484967

  19. Chronobiological variations in the convulsive effect of monosodium L-glutamate when administered to adult rats.

    PubMed

    Feria-Velasco, A; Feria-Cuevas, Y; Gutiérrez-Padilla, R

    1995-01-01

    Monosodium L-glutamate (MSG) when administered intraperitoneally (i.p.) to rodents induces convulsions and has been used as a model to study various aspects of status epilepticus of multifocal origin. There are circadian variations of susceptibility to convulsions induced by various factors in some animal species. The aim of this work was to learn whether the convulsive effect of MSG in rats would vary when the drug is given at different times of the day. Three subgroups of Wistar rats were given i.p. 5 mg/g MSG at 07:00, 15:00 and 23:00 h, whereas two groups of rats divided into three subgroups of five animals each were used as controls, also being injected at 07:00, 15:00 and 23:00 h. One group was injected with NaCI solution, equimolar to that of MSG (eqNaCI); the other was injected with physiological saline solution (PSS) in proportional volumes to those of the experimental group. Motor behavior was recorded for 4 h following injections in the three groups of animals. Neither signs of brain hyperexcitability, nor convulsions appeared in animals injected with PSS or eqNaCl. With MSG, no variations were seen in the latency period when data from the three subgroups studied were compared among them. Duration of convulsive period when rats were injected at 07:00 h was shorter than that seen at 15:00 and 23:00 h. No significant variations were seen in total number of convulsive episodes in the three subgroups, while the number of seizures per hour and their intensity were significantly greater when animals were injected at 07:00 h than those seen when rats were studied at 15:00 and 23:00 h. Nearly 70% of animals injected at 07:00 h died in status epilepticus, whereas no deaths were recorded in animals injected at 15:00 and 23:00 h. Results could be explained in terms of variations of physiological processes at both the brain and extracerebral tissues involved in MSG metabolism and cerebral excitability, related to circadian rhythms. PMID:8845636

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

    PubMed

    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. PMID:26812818

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

    PubMed

    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. PMID:25621725

  2. No effects of monosodium glutamate consumption on the body weight or composition of adult rats and mice.

    PubMed

    Tordoff, Michael G; Aleman, Tiffany R; Murphy, Michelle C

    2012-10-10

    Monosodium glutamate (MSG) is pervasively consumed as a flavor enhancer so there are important implications to understanding its physiological actions, particularly its effects on body weight. Previous studies suggest that MSG increases, decreases, or has no effect on the body weight of rodents. However, most of these studies involved administration of MSG to immature rodents and consequently may not be relevant for understanding human obesity. We report here five experiments in which we measured the body weights of a total of 32 groups of 10-12 adult rats or mice given various diets to eat and MSG to eat or drink. We found no evidence that MSG influenced body weight, energy intake, or body composition. To the extent that experiments in rodents illuminate mechanisms involved in human obesity and body weight control, our results suggest that MSG is unlikely to be a useful anti-obesity supplement but neither is it responsible for exacerbating obesity. PMID:22868067

  3. Monosodium glutamate-induced asthma: study of the potential risk of 30 asthmatics and review of the literature.

    PubMed

    Moneret-Vautrin, D A

    1987-01-01

    Monosodium glutamate is a physiological nutrient, and food additive used as a taste enhancer. Several cases of intolerance to MSG in patients with asthma and with a Chinese Restaurant Syndrome have been published. A high dose of 2.5 g was tested in 6 healthy controls and 30 asthmatics (7: allergic asthma; 15: intrinsic asthma with intolerance to aspirin; 8: intrinsic asthma with aspirin intolerance, intolerance to alcohol or to food additives). Two patients presented with a mild bronchospasm, occurring 6 to 10 hours after the ingestion. Different mechanisms are discussed. A cholinergic mechanism might be incriminated, either due to stimulation of the synthesis of acetylcholine, or due to a vagal reflex elicited by a reflux esophagitis. However, a high vagal hyperreactivity seems to be needed for the occurrence of asthma. It is concluded that a very small subset of patients with intrinsic asthma might present with an intolerance to MSG if high doses are consumed. PMID:3331265

  4. Swim training of monosodium L-glutamate-obese mice improves the impaired insulin receptor tyrosine phosphorylation in pancreatic islets.

    PubMed

    Miranda, Rosiane Aparecida; Branco, Renato Chaves Souto; Gravena, Clarice; Barella, Luiz Felipe; da Silva Franco, Claudinéia Conationi; Andreazzi, Ana Eliza; de Oliveira, Júlio Cezar; Picinato, Maria Cecília; de Freitas Mathias, Paulo Cezar

    2013-06-01

    The goal of the present study was to investigate changes on glucose homoeostasis and of the insulin receptor (IR) and insulin receptor substrate-1 (IRS-1) signalling in pancreatic islets from MSG-obese mice submitted to or not submitted to swim training. Swim training of 90-day-old MSG mice was used to evaluate whether signalling pathways of the IR and IRS-1 in islets are involved with the insulin resistance and glucose intolerance observed in this obese animal model. The results showed that IR tyrosine phosphorylation (pIR) was reduced by 42 % in MSG-obese mice (MSG, 6.7 ± 0.2 arbitrary units (a.u.); control, 11.5 ± 0.4 a.u.); on the other hand, exercise training increased pIR by 76 % in MSG mice without affecting control mice (MSG, 11.8 ± 0.3; control, 12.8 ± 0.2 a.u.). Although the treatment with MSG increased IRS-1 tyrosine phosphorylation (pIRS-1) by 96 % (MSG, 17.02 ± 0.6; control, 8.7 ± 0.2 a.u.), exercise training also increased it in both groups (control, 13.6 ± 0.1; MSG, 22.2 ± 1.1 a.u.). Current research shows that the practice of swim training increases the tyrosine phosphorylation of IRS-1 which can modulate the effect caused by obesity in insulin receptors. PMID:22983867

  5. 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.

    PubMed

    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. PMID:24008059

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

    PubMed

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

    2015-07-01

    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. PMID:25841878

  7. Gastric emptying and duodenal motility upon intake of a liquid meal with monosodium glutamate in healthy subjects

    PubMed Central

    Teramoto, Hidemi; Shimizu, Toshiyasu; Yogo, Hideto; Nishimiya, Yuuta; Hori, Shinji; Kosugi, Takashi; Nakayama, Shinsuke

    2014-01-01

    Abstract Glutamate is thought to serve as a special signal for gut functions. We investigated the effects of monosodium l‐glutamate (MSG) on gastric emptying and duodenal motility. Ten healthy male volunteers underwent rapid magnetic resonance imaging (MRI) of the abdomen. Coronal images were successively acquired after ingestion of liquid meal (200 kcal in 200 mL: 9 g protein, 28.4 g carbohydrate, 5.6 g fat, 370 mg Na+) with and without 0.5% MSG. During the acquisition of MRI, participants breathed freely. In all participants, the gastric residual volume gradually decreased to 80.1 ± 14.2% without MSG and to 75.9 ± 14.3% with MSG after 60 min (P = 0.45 between the groups, n = 10). In two of 10 participants, gastric emptying slowed down significantly, whereas in the remaining eight participants, gastric residual volume decreased to 84.0 ± 13.1% without MSG, and to 73.0 ± 14.6% with MSG after 60 min (P = 0.015, n = 8). There was no difference in the shape of the stomach between groups. In four of the eight participants responding positively to MSG, the duodenum wall was sufficiently identified to quantify the motions. The inclusion of MSG enhanced duodenal motility, judging from changes in (1) the magnitude of the duodenal area, (2) the center of gravity, and (3) the mean velocity of the wall motions. The third parameter most significantly indicated the excitatory effect of l‐glutamate on duodenum motility (~ three‐ to sevenfold increase during 60 min, P < 0.05, n = 4). These results suggest that MSG accelerates gastric emptying by facilitating duodenal motility, at least in subjects with positive responses to MSG. PMID:24744869

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

    PubMed

    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. PMID:25851080

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

    NASA Astrophysics Data System (ADS)

    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 .

  10. Protective Effect of Calendula officinalis L. Flowers Against Monosodium Glutamate Induced Oxidative Stress and Excitotoxic Brain Damage in Rats.

    PubMed

    Shivasharan, B D; Nagakannan, P; Thippeswamy, B S; Veerapur, V P

    2013-07-01

    Monosodium glutamate (MSG) is a popular flavour enhancer used in food industries; however, excess MSG is neurotoxic. Oxidative stress is well documented in MSG induced neurotoxicity. The compounds having antioxidant and anti-inflammatory properties reportedly possess beneficial effects against various neurotoxic insults. Calendula officinalis Linn. flower extract (COE) is known for its potent antioxidant and anti-inflammatory activities. Hence, this present study has been designed to evaluate the neuroprotective effect of COE on MSG-induced neurotoxicity in rats. Adult Wistar rats were administered systemically for 7 days with MSG and after one h of MSG injection, rats were treated with COE (100 and 200 mg/kg) orally. At the end the treatment period, animals were assessed for locomotor activity and were sacrificed; brains were isolated for estimation of LPO, GSH, CAT, TT, GST, Nitrite and histopathological studies. MSG caused a significant alteration in animal behavior, oxidative defense (raised levels of LPO, nitrite concentration, depletion of antioxidant levels) and hippocampal neuronal histology. Treatment with COE significantly attenuated behavioral alterations, oxidative stress, and hippocampal damage in MSG-treated animals. Hence, this study demonstrates that COE protects against MSG-induced neurotoxicity in rats. The antioxidant and anti-inflammatory properties of COE may be responsible for its observed neuroprotective action. PMID:24426226

  11. Quercetin ameliorates glucose and lipid metabolism and improves antioxidant status in postnatally monosodium glutamate-induced metabolic alterations.

    PubMed

    Seiva, Fábio R F; Chuffa, Luiz Gustavo A; Braga, Camila Pereira; Amorim, João Paulo A; Fernandes, Ana Angélica H

    2012-10-01

    We reported the effects of quercetin on metabolic and hormonal profile as well as serum antioxidant activities in a model of MSG (monosodium glutamate)-induced obesity. Rats were divided into 4 groups: MSG group, submitted to neonatal treatment with high doses of MSG, administrated subcutaneously during 10 days, from 2 day-old; control groups, which received the same volume of saline. After completing 30 day-old, these groups were subdivided into 4 groups: control and MSG groups treated and non-treated with quercetin at doses of 75 mg/kg body weight (i.p.) over 42 days. BW gain and food consumption were higher in MSG treated rats and quercetin significantly reduced BW by 25%. While MSG increased triacylglycerol, total cholesterol and fractions, and reduced HDL concentrations, administration of quercetin normalized HDL-cholesterol and reduced others lipids. Insulin, leptin, glucose and creatinine levels were raised in MSG-treated rats and reduced after quercetin treatment. Alanine transaminase, aspartate transaminase, lactate dehydrogenase and alkaline phosphatase activities were lower after MSG-quercetin combination compared to rats given only MSG. MSG-quercetin combination augmented total protein and urea levels as well as glutathione peroxidase and superoxide dismutase activities in contrast to MSG-treated animals. Quercetin normalized serum lipid and glucose profile and minimized the MSG-related toxic effects, which was associated to its antioxidant properties. PMID:22809473

  12. Serological and Histological Examination of a Nonalcoholic Steatohepatitis Mouse Model Created via the Administration of Monosodium Glutamate

    PubMed Central

    Takai, Atsuko; Kajiyama, Yusuke; Sugiura, Anna; Negishi, Masatsugu; Miyakawa, Hiroshi

    2014-01-01

    The administration of monosodium glutamate (MSG) to mice induces hepatic steatosis and inflammation. In this study, we investigated the metabolic features of MSG-treated mice and the histological changes that occur in their livers and adipose tissue. MSG mice were prepared by subcutaneously injecting MSG into newborn C57BL/6J male mice. The control mice were subcutaneously injected with saline. Another group of mice was fed a methionine- and choline-deficient diet (MCD). Compared with the control mice, the MSG mice had higher serum levels of insulin and cholesterol than the control mice, whereas the opposite was true for the MCD mice. Microvesicular steatosis and inflammatory cell infiltration were detected in both the MSG and MCD mouse livers. Enlarged adipocytes and crown-like structures were observed in the epididymal fat of the MSG mice, whereas neither of these features was seen in the MCD mice. Flow cytometric analysis revealed increased frequencies of monocytes and M1 macrophages in the livers and epididymal fat tissue of the MSG mice, respectively. The MSG mice exhibited the characteristic liver histopathology of nonalcoholic steatohepatitis (NASH) as well as metabolic syndrome-like features, which suggested that MSG mice are a better model of human NASH than MCD mice.

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

    PubMed

    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. PMID:25697849

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

    PubMed

    Nakadate, Kazuhiko; Motojima, Kento; Hirakawa, Tomoya; Tanaka-Nakadate, Sawako

    2016-01-01

    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. PMID:27437400

  15. Heterogeneous Nucleation of n-Butanol Vapor on Submicrometer Charged and Neutral Particles of Lactose and Monosodium Glutamate.

    PubMed

    Chen; Tao; Shu

    2000-04-01

    Condensation of a supersaturated vapor of n-butanol on monodisperse submicrometer particles of lactose and monosodium glutamate is investigated in a flow cloud chamber (FCC). The dependence of critical supersaturation S(cr) on the particle size in the range 30 to 90 nm is experimentally examined. The results show that the size dependence of S(cr) qualitatively agrees with that predicted by the Fletcher version of the Volmer theory of heterogeneous nucleation, but to a lesser degree. The experimental S(cr) is smaller than the theoretical prediction even with the line tension and surface diffusion taken into account, and they induce heterogeneous nucleation better than perfectly wetted particles. The discrepancy can not be fully accounted for by the effects of line tension and surface diffusion and the existing theory concerning the curvature-dependent surface tension. The condensation on single positive-charged particles of diameter 30, 60, and 90 nm is also examined. A lowering of S(cr) at an efficiency much larger than the prediction by Volmer's theory for ion-induced nucleation is observed, and the charge effect fades away as particle size increases. Copyright 2000 Academic Press. PMID:10708489

  16. Stability of monosodium glutamate in green table olives and pickled cucumbers as a function of packing conditions and storage time.

    PubMed

    de Castro, Antonio; Sánchez, Antonio Higinio; Beato, Víctor Manuel; Casado, Francisco Javier; Montaño, Alfredo

    2014-01-01

    The effects of different packing conditions and storage times on the stability of monosodium glutamate (MSG) added to two different fermented vegetables (Spanish-type green table olives and pickled cucumbers) were studied. Factors such as packaging material (glass bottle versus plastic pouch), heat treatment (pasteurisation versus non-pasteurisation), and the presence or not of a preservative compound (potassium sorbate) were considered. The MSG content of pickled cucumbers was stable for up to 1 year of storage in all packing conditions studied. The MSG content also remained stable in pasteurised green table olives. On the contrary, MSG was extensively degraded (>75% degradation) after 54 weeks of storage in unpasteurised green olives with a higher degradation rate in glass bottles compared with plastic pouches. In the presence of potassium sorbate, MSG was also considerably degraded in olives packed in plastic pouches (>50% degradation), but hardly degraded in glass bottles. The results indicate that MSG degradation in olives is due to the action of both lactic acid bacteria and yeasts, with the formation of γ-aminobutyric acid as the major end-product. PMID:24720705

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

    PubMed Central

    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. PMID:26884820

  18. Monosodium L-glutamate and dietary fat exert opposite effects on the proximal and distal intestinal health in growing pigs.

    PubMed

    Feng, Zemeng; Li, Tiejun; Wu, Chunli; Tao, Lihua; Blachier, Francois; Yin, Yulong

    2015-04-01

    The Chinese population has undergone rapid transition to a high-fat diet. Furthermore, monosodium L-glutamate (MSG) is widely used as a flavour enhancer in China. Previous studies have reported that high-fat diet modifies intestinal metabolism and physiology. However, little information is available on the effects of oral MSG on intestine, and no study focus on the interaction of dietary fat and MSG for intestinal health. The aim of the present study was to evaluate the effects of MSG and dietary fat on intestinal health in growing pigs, and to try to identify possible interactions between these 2 nutrients for such effects. A total of 32 growing pigs were used and fed with 4 isonitrogenous and isocaloric diets (basal diet, high-fat diet, basal diet with 3% MSG and high fat diet with 3% MSG). Parameters related to reactive oxygen species metabolism, epithelial morphology, pro-inflammation factors and tight junction protein expression and several species of intestinal microbe were measured. Overall, dietary fat and MSG had detrimental effects on several of the physiological and inflammatory parameters measured in the proximal intestine, while exerting beneficial effects on the distal intestine in growing pigs, with generally antagonistic effects. These results may be of particular relevance for nutritional concerns in patients with intestinal diseases. PMID:25781200

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

    PubMed Central

    Nakadate, Kazuhiko; Motojima, Kento; Hirakawa, Tomoya; Tanaka-Nakadate, Sawako

    2016-01-01

    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. PMID:27437400

  20. Review of alleged reaction to monosodium glutamate and outcome of a multicenter double-blind placebo-controlled study.

    PubMed

    Geha, R S; Beiser, A; Ren, C; Patterson, R; Greenberger, P A; Grammer, L C; Ditto, A M; Harris, K E; Shaughnessy, M A; Yarnold, P R; Corren, J; Saxon, A

    2000-04-01

    Monosodium glutamate (MSG) has a long history of use in foods as a flavor enhancer. In the United States, the Food and Drug Administration has classified MSG as generally recognized as safe (GRAS). Nevertheless, there is an ongoing debate exists concerning whether MSG causes any of the alleged reactions. A complex of symptoms after ingestion of a Chinese meal was first described in 1968. MSG was suggested to trigger these symptoms, which were referred to collectively as Chinese Restaurant Syndrome. Numerous reports, most of them anecdotal, were published after the original observation. Since then, clinical studies have been performed by many groups, with varying degrees of rigor in experimental design ranging from uncontrolled open challenges to double-blind, placebo controlled (DBPC) studies. Challenges in subjects who reported adverse reactions to MSG have included relatively few subjects and have failed to show significant reactions to MSG. Results of surveys and of clinical challenges with MSG in the general population reveal no evidence of untoward effects. We recently conducted a multicenter DBPC challenge study in 130 subjects (the largest to date) to analyze the response of subjects who report symptoms from ingesting MSG. The results suggest that large doses of MSG given without food may elicit more symptoms than a placebo in individuals who believe that they react adversely to MSG. However, the frequency of the responses was low and the responses reported were inconsistent and were not reproducible. The responses were not observed when MSG was given with food. PMID:10736382

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

    PubMed

    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. PMID:24556450

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

    PubMed

    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. PMID:22104770

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

    PubMed

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

    2008-12-01

    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. PMID:18930730

  4. Effects of ad libitum ingestion of monosodium glutamate on weight gain in C57BL6/J mice.

    PubMed

    Ren, Xueying; Ferreira, Jozélia G; Yeckel, Catherine W; Kondoh, Takashi; de Araujo, Ivan E

    2011-01-01

    Although the umami compound monosodium glutamate (MSG) is a widely used flavor enhancer, controversy still persists regarding the effects of MSG intake on body weight. It has been claimed, in particular, that chronic MSG intake may result in excessive body weight gain and obesity. In this study we assessed the effects of chronic (16 weeks) ad libitum MSG on body weight and metabolism of C57BL6/J mice. Adult male mice were divided in four experimental groups and fed with either a low-fat (LF) or high-fat (HF) diet and with either two bottles of plain water or one bottle containing 1% MSG and another one containing water according to a factorial design. Mice were monitored weekly for body weight and food/fluid intake for 15 weeks. At the end of the experiments, the circulating levels of leptin, insulin, total protein, total cholesterol, triglyceride, blood urea nitrogen, and non-esterified fatty acids were also analyzed. Our results show that MSG intake did not influence body weight in either LF or HF groups. Interestingly, although animals overall displayed strong preferences for MSG against water, preferences were relatively higher in LF compared to HF group. Consistent with the body weight data, while significant differences in leptin, insulin, total cholesterol, and non-esterified fatty acids were found between HF and LF groups, such an effect was not influenced by MSG intake. Finally, indirect calorimetry measurements revealed similar energy expenditure levels between animals being presented water only and MSG only. In summary, our data does not support the notion that ad libitum MSG intake should trigger the development of obesity or other metabolic abnormalities. PMID:21389726

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

    PubMed Central

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

    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 (p<0.05). Furthermore, the effect of MSG on enhancing the salty flavor was not observed in the solution of the NaCl/MSG complex. In the case of an actual food system, model meat 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 (<1.0%) did not result in negative 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. PMID:26761490

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

    PubMed

    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 (p<0.05). Furthermore, the effect of MSG on enhancing the salty flavor was not observed in the solution of the NaCl/MSG complex. In the case of an actual food system, model meat 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 (<1.0%) did not result in negative 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. PMID:26761490

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

    NASA Astrophysics Data System (ADS)

    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.

  8. Sex differences in brain cholinergic activity in MSG-obese rats submitted to exercise.

    PubMed

    Sagae, Sara Cristina; Grassiolli, Sabrina; Raineki, Charlis; Balbo, Sandra Lucinei; Marques da Silva, Ana Carla

    2011-11-01

    Obesity is an epidemic disease most commonly caused by a combination of increased energy intake and lack of physical activity. The cholinergic system has been shown to be involved in the regulation of food intake and energy expenditure. Moreover, physical exercise promotes a reduction of fat pads and body mass by increasing energy expenditure, but also influences the cholinergic system. The aim of this study is to evaluate the interaction between physical exercise (swimming) and central cholinergic activity in rats treated with monosodium glutamate (MSG, a model for obesity) during infancy. Our results show that MSG treatment is able to induce obesity in male and female rats. Specifically, MSG-treated rats presented a reduced body mass and nasoanal length, and increased perigonadal and retroperitoneal fat pads in relation to the body mass. Physical exercise was able to reduce body mass in both male and female rats, but did not change the fat pads in MSG-treated rats. Increased food intake was only seen in MSG-treated females submitted to exercise. Cholinergic activity was increased in the cortex of MSG-treated females and physical exercise was able to reduce this activity. Thalamic cholinergic activity was higher in sedentary MSG-treated females and exercised MSG-treated males. Hypothalamic cholinergic activity was higher in male and female MSG-treated rats, and was not reduced by exercise in the 2 sexes. Taken together, these results show that MSG treatment and physical exercise have different effects in the cholinergic activity of males and females. PMID:22039988

  9. Impaired muscarinic type 3 (M3) receptor/PKC and PKA pathways in islets from MSG-obese rats.

    PubMed

    Ribeiro, Rosane Aparecida; Balbo, Sandra Lucinei; Roma, Letícia Prates; Camargo, Rafael Ludemann; Barella, Luiz Felipe; Vanzela, Emerielle Cristine; de Freitas Mathias, Paulo Cesar; Carneiro, Everardo Magalhães; Boschero, Antonio Carlos; Bonfleur, Maria Lúcia

    2013-07-01

    Monosodium glutamate-obese rats are glucose intolerant and insulin resistant. Their pancreatic islets secrete more insulin at increasing glucose concentrations, despite the possible imbalance in the autonomic nervous system of these rats. Here, we investigate the involvement of the cholinergic/protein kinase (PK)-C and PKA pathways in MSG β-cell function. Male newborn Wistar rats received a subcutaneous injection of MSG (4 g/kg body weight (BW)) or hyperosmotic saline solution during the first 5 days of life. At 90 days of life, plasma parameters, islet static insulin secretion and protein expression were analyzed. Monosodium glutamate rats presented lower body weight and decreased nasoanal length, but had higher body fat depots, glucose intolerance, hyperinsulinemia and hypertrigliceridemia. Their pancreatic islets secreted more insulin in the presence of increasing glucose concentrations with no modifications in the islet-protein content of the glucose-sensing proteins: the glucose transporter (GLUT)-2 and glycokinase. However, MSG islets presented a lower secretory capacity at 40 mM K(+) (P < 0.05). The MSG group also released less insulin in response to 100 μM carbachol, 10 μM forskolin and 1 mM 3-isobutyl-1-methyl-xantine (P < 0.05, P < 0.0001 and P < 0.01). These effects may be associated with a the decrease of 46 % in the acetylcholine muscarinic type 3 (M3) receptor, and a reduction of 64 % in PKCα and 36 % in PKAα protein expressions in MSG islets. Our data suggest that MSG islets, whilst showing a compensatory increase in glucose-induced insulin release, demonstrate decreased islet M3/PKC and adenylate cyclase/PKA activation, possibly predisposing these prediabetic rodents to the early development of β-cell dysfunction. PMID:23652999

  10. [Effect of long-term monosodium glutamate administration on structure and functional state of the stomach and body weight in rats].

    PubMed

    Falalieieva, T M; Kukhars'kyĭ, V M; Berehova, T V

    2010-01-01

    The influence of prolonged administration of monosodium glutamate (MSG) on basal gastric acid secretion, body weight and gastric mucosa in rats was studied. We found that 10-, 20-, 30-days feeding by MSG in doses 15 to 30 mg/kg (equivalent to I and 2 g/person) leads to erosive and ulcerative lesions of the gastric mucosa and an increased secretion of hydrochloric acid and an increased body weight. It is concluded that the stimulating effect of MSG on the basal secretion of hydrochloric acid in the stomach may be implicated in the pathogenesis of a number of acid-dependent diseases. An excessive consumption of MSG can cause a "Chinese Restaurant Syndrome" and gastritis, gastric and duodenal ulcers. Therefore, the maximum dose of MSG should be reconsidered taking into account its influence on the secretory capacity of the stomach. We also conclude that prolonged, excessive and systemic consumption of MSG causes obesity. PMID:20968043

  11. Both Dietary Supplementation with Monosodium L-Glutamate and Fat Modify Circulating and Tissue Amino Acid Pools in Growing Pigs, but with Little Interactive Effect

    PubMed Central

    Feng, Zemeng; Zhou, Xiaoli; Wu, Fei; Yao, Kang; Kong, Xiangfeng; Li, Tiejun; Blachier, Francois; Yin, Yulong

    2014-01-01

    Background 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. Methods and Results 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. Conclusions 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. PMID:24465415

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

    PubMed

    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. PMID:26900785

  13. Long-term ingestion of monosodium L-glutamate did not induce obesity, dyslipidemia or insulin resistance: a two-generation study in mice.

    PubMed

    Nakamura, Hidehiro; Kawamata, Yasuko; Kuwahara, Tomomi; Smriga, Miro; Sakai, Ryosei

    2013-01-01

    The use of monosodium glutamate (MSG) as a flavor enhancer spans more than 100 y and there are many studies indicating the safety of general use of MSG. Recently, however, Collison et al. (2010) reported a two-generation study with a low dose of MSG that caused abdominal obesity, insulin resistance and dyslipidemia in mice. Due to public health concerns over metabolic syndrome, their report merits careful analysis. The present study attempted to repeat the Collison et al. findings. Groups of male or female C57BL/6J mice were fed a control diet or one supplemented with high-fructose corn syrup (HFCS) at a level of 20%. Drinking water control was provided or treatment groups were given 0.064% MSG solution (w/v). Diets and MSG administration continued throughout mating and during gestation and lactation periods. To further investigate the effects of ingestion of MSG, the offspring were continued on the same dosing conditions until they reached 32 wk of age. MSG administration in mice fed a normal or a HFCS diet throughout gestation and for 32 wk after birth, did not affect growth, girth size, abdominal fat weight or body composition. This study reports that MSG did not trigger insulin resistance, dyslipidemia or hepatic steatosis, regardless of the diet, not reproducing the results of the above-mentioned study (Collison et al., 2010). PMID:23727643

  14. Neuroendocrine, metabolic, and immune functions during the acute phase response of inflammatory stress in monosodium L-glutamate-damaged, hyperadipose male rat.

    PubMed

    Castrogiovanni, Daniel; Gaillard, Rolf C; Giovambattista, Andrés; Spinedi, Eduardo

    2008-01-01

    In rats, neonatal treatment with monosodium L-glutamate (MSG) induces several metabolic and neuroendocrine abnormalities, which result in hyperadiposity. No data exist, however, regarding neuroendocrine, immune and metabolic responses to acute endotoxemia in the MSG-damaged rat. We studied the consequences of MSG treatment during the acute phase response of inflammatory stress. Neonatal male rats were treated with MSG or vehicle (controls, CTR) and studied at age 90 days. Pituitary, adrenal, adipo-insular axis, immune, metabolic and gonadal functions were explored before and up to 5 h after single sub-lethal i.p. injection of bacterial lipopolysaccharide (LPS; 150 microg/kg). Our results showed that, during the acute phase response of inflammatory stress in MSG rats: (1) the corticotrope-adrenal, leptin, insulin and triglyceride responses were higher than in CTR rats, (2) pro-inflammatory (TNFalpha) cytokine response was impaired and anti-inflammatory (IL-10) cytokine response was normal, and (3) changes in peripheral estradiol and testosterone levels after LPS varied as in CTR rats. These data indicate that metabolic and neroendocrine-immune functions are altered in MSG-damaged rats. Our study also suggests that the enhanced corticotrope-corticoadrenal activity in MSG animals could be responsible, at least in part, for the immune and metabolic derangements characterizing hypothalamic obesity. PMID:18382067

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

    PubMed

    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. PMID:26164271

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

    SciTech Connect

    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.

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

    PubMed

    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. PMID:26673833

  18. Supplementing chicken broth with monosodium glutamate reduces energy intake from high fat and sweet snacks in middle-aged healthy women.

    PubMed

    Imada, Toshifumi; Hao, Susan Shuzhen; Torii, Kunio; Kimura, Eiichiro

    2014-08-01

    Monosodium L-glutamate (MSG) and inosine monophosphate-5 (IMP) are flavor enhancers for umami taste. However, their effects on appetite and food intake are not well-researched. The objective of the current study was to test their additions in a broth preload on subsequent appetite ratings, energy intake and food choice. Eighty-six healthy middle-aged women with normal body weight received three preload conditions on 3 test days 1 week apart - a low-energy chicken flavor broth (200 ml) as the control preload, and broths with added MSG alone (0.5 g/100 ml, MSG broth) or in combination with IMP (0.05 g/100 ml) (MSG+ broth) served as the experimental conditions. Fifteen minutes after preload administration subjects were provided an ad libitum testing meal which consisted of 16 snacks varying in taste and fat content. MSG and MSG+ enhanced savory taste and broth properties of liking and pleasantness. In comparison with control, the MSG preload resulted in less consumption of total energy, as well as energy from sweet and high-fat snacks. Furthermore, MSG broth preload reduced added sugar intake. These findings were not observed after MSG+ preload. Appetite ratings were not different across the three preloads. Results suggest a potential role of MSG addition to a low-energy broth preload in subsequent energy intake and food choice. This trial was registered at clinicaltrials.gov as NCT01761045. PMID:24768895

  19. Physical exercise introduced after weaning enhances pancreatic islet responsiveness to glucose and potentiating agents in adult MSG-obese rats.

    PubMed

    Ribeiro, R A; Bonfleur, M L; Vanzela, E C; Zotti, A I; Scomparin, D X; Boschero, A C; Balbo, S L

    2014-08-01

    Physical exercise represents an alternative way to prevent and/or ameliorate chronic metabolic diseases. Disruption of sympathetic nervous system (SNS) activity contributes to adiposity in obese subjects. Here, we verified the preventive effect of swimming training upon adiposity, adrenal catecholamine storage, and pancreatic islet function in obese monosodium glutamate (MSG)-treated rats. Male neonatal Wistar rats received MSG (4 mg/g body weight) during the first 5 days of life and, at weaning, half of the rats were submitted to swimming training, 30 min/day, 3 days a week, until 90 days of age (exercised rats: MSGex). Half of the rats were used as controls (sedentary group, MSGsd). Exercise training (ET) decreased insulinemia and fat deposition in MSGex, and increased adrenal catecholamine content, compared with MSGsd rats. Insulinemia during the ivGTT was lower in MSGex rats, despite a lack of difference in glycemia. Swimming training enhanced insulin release in islets challenged by 2.8-8.3 mmol/l glucose, whereas, at supraphysiological glucose concentrations (11.1-16.7 mmol/l), MSGex islets secreted less insulin than MSGsd. No differences in insulin secretion were observed following l-arginine (Arg) or K(+) stimuli. In contrast, islets from MSGex rats secreted more insulin when exposed to carbachol (100 μmol/l), forskolin (10 μmol/l), or IBMX (1 mmol/l) at 8.3 mmol/l glucose. Additionally, MSGex islets presented a better epinephrine inhibition upon insulin release. These results demonstrate that ET prevented the onset of obesity in MSG rats, probably by enhancing adrenal catecholamine levels. ET ameliorates islet responsiveness to several compounds, as well as insulin peripheral action. PMID:24554535

  20. Low fish oil intake improves insulin sensitivity, lipid profile and muscle metabolism on insulin resistant MSG-obese rats

    PubMed Central

    2011-01-01

    Background Obesity is commonly associated with diabetes, cardiovascular diseases and cancer. The purpose of this study was to determinate the effect of a lower dose of fish oil supplementation on insulin sensitivity, lipid profile, and muscle metabolism in obese rats. Methods Monosodium glutamate (MSG) (4 mg/g body weight) was injected in neonatal Wistar male rats. Three-month-old rats were divided in normal-weight control group (C), coconut fat-treated normal weight group (CO), fish oil-treated normal weight group (FO), obese control group (Ob), coconut fat-treated obese group (ObCO) and fish oil-treated obese group (ObFO). Obese insulin-resistant rats were supplemented with fish oil or coconut fat (1 g/kg/day) for 4 weeks. Insulin sensitivity, fasting blood biochemicals parameters, and skeletal muscle glucose metabolism were analyzed. Results Obese animals (Ob) presented higher Index Lee and 2.5 fold epididymal and retroperitoneal adipose tissue than C. Insulin sensitivity test (Kitt) showed that fish oil supplementation was able to maintain insulin sensitivity of obese rats (ObFO) similar to C. There were no changes in glucose and HDL-cholesterol levels amongst groups. Yet, ObFO revealed lower levels of total cholesterol (TC; 30%) and triacylglycerol (TG; 33%) compared to Ob. Finally, since exposed to insulin, ObFO skeletal muscle revealed an increase of 10% in lactate production, 38% in glycogen synthesis and 39% in oxidation of glucose compared to Ob. Conclusions Low dose of fish oil supplementation (1 g/kg/day) was able to reduce TC and TG levels, in addition to improved systemic and muscle insulin sensitivity. These results lend credence to the benefits of n-3 fatty acids upon the deleterious effects of insulin resistance mechanisms. PMID:21526994

  1. Polyphenol-Rich Extract of Syzygium cumini Leaf Dually Improves Peripheral Insulin Sensitivity and Pancreatic Islet Function in Monosodium L-Glutamate-Induced Obese Rats.

    PubMed

    Sanches, Jonas R; França, Lucas M; Chagas, Vinicyus T; Gaspar, Renato S; Dos Santos, Kayque A; Gonçalves, Luciana M; Sloboda, Deborah M; Holloway, Alison C; Dutra, Richard P; Carneiro, Everardo M; Cappelli, Ana Paula G; Paes, Antonio Marcus de A

    2016-01-01

    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 twofold 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 μg/mL) increased glucose stimulated insulin secretion from both isolated rat islets and INS-1E β-cells. These data demonstrate that S. cumini leaf improved peripheral insulin sensitivity via stimulating/modulating β-cell insulin release, which was associated

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

    PubMed

    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. PMID:26455957

  3. Taste perception of monosodium glutamate and inosine monophosphate by 129P3/J and C57BL/6ByJ mice.

    PubMed

    Murata, Yuko; Beauchamp, Gary K; Bachmanov, Alexander A

    2009-10-19

    Our previous studies have shown that in long-term two-bottle preference tests, mice from the C57BL/6ByJ (B6) inbred strain drink more monosodium glutamate (MSG) and inosine monophosphate (IMP) than mice from the 129P3/J (129) inbred strain. The goal of this study was to examine whether this variation in consumption could be attributed to strain differences in perception of the taste quality of MSG and IMP. We developed a conditioned taste aversion (CTA) in B6 and 129 mice to 100 mM MSG or 10 mM IMP and used a brief-access taste assay to examine CTA generalization. B6 and 129 mice did not differ in the generalization patterns following CTA to MSG: mice from both strains generalized CTA from MSG to NaCl. In contrast, strain differences in the generalization patterns were evident following the CTA to IMP: while mice from both strains generalized CTA from IMP to MSG, 129 mice tended to have stronger CTA generalization to saccharin and d-tryptophan, both of which are perceived as sweet by humans. These data suggest that the strain differences in MSG consumption are not due to variation in perception of the taste quality of MSG. Instead, the differential intake of IMP likely reflects strain differences in the way the taste quality of IMP is perceived. Our data suggest that mice perceive MSG and IMP as complex taste stimuli: some taste components are shared between these two substances, but their relative intensity seems to be different for MSG and IMP. The amiloride-sensitive salt taste component is more prevalent in MSG than in IMP taste, and in B6 compared with 129 mice. PMID:19666040

  4. Polyphenol-Rich Extract of Syzygium cumini Leaf Dually Improves Peripheral Insulin Sensitivity and Pancreatic Islet Function in Monosodium L-Glutamate-Induced Obese Rats

    PubMed Central

    Sanches, Jonas R.; França, Lucas M.; Chagas, Vinicyus T.; Gaspar, Renato S.; dos Santos, Kayque A.; Gonçalves, Luciana M.; Sloboda, Deborah M.; Holloway, Alison C.; Dutra, Richard P.; Carneiro, Everardo M.; Cappelli, Ana Paula G.; Paes, Antonio Marcus de A.

    2016-01-01

    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 twofold 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 μg/mL) increased glucose stimulated insulin secretion from both isolated rat islets and INS-1E β-cells. These data demonstrate that S. cumini leaf improved peripheral insulin sensitivity via stimulating/modulating β-cell insulin release, which was associated

  5. Effect of trans-fat, fructose and monosodium glutamate feeding on feline weight gain, adiposity, insulin sensitivity, adipokine and lipid profile.

    PubMed

    Collison, Kate S; Zaidi, Marya Z; Saleh, Soad M; Inglis, Angela; Mondreal, Rhea; Makhoul, Nadine J; Bakheet, Razan; Burrows, Joey; Milgram, Norton W; Al-Mohanna, Futwan A

    2011-07-01

    The incidence of obesity and type 2 diabetes mellitus (T2DM) is increasing, and new experimental models are required to investigate the diverse aspects of these polygenic diseases, which are intimately linked in terms of aetiology. Feline T2DM has been shown to closely resemble human T2DM in terms of its clinical, pathological and physiological features. Our aim was to develop a feline model of diet-induced weight gain, adiposity and metabolic deregulation, and to examine correlates of weight and body fat change, insulin homeostasis, lipid profile, adipokines and clinical chemistry, in order to study associations which may shed light on the mechanism of diet-induced metabolic dysregulation. We used a combination of partially hydrogenated vegetable shortening and high-fructose corn syrup to generate a high-fat-high-fructose diet. The effects of this diet were compared with an isoenergetic standard chow, either in the presence or absence of 1.125 % dietary monosodium glutamate (MSG). Dual-energy X-ray absorptiometry body imaging and a glucose tolerance test were performed. The present results indicate that dietary MSG increased weight gain and adiposity, and reduced insulin sensitivity (P < 0.05), whereas high-fat-high-fructose feeding resulted in elevated cortisol and markers of liver dysfunction (P < 0.01). The combination of all three dietary constituents resulted in lower insulin levels and elevated serum β-hydroxybutyrate and cortisol (P < 0.05). This combination also resulted in a lower first-phase insulin release during glucose tolerance testing (P < 0.001). In conclusion, markers of insulin deregulation and metabolic dysfunction associated with adiposity and T2DM can be induced by dietary factors in a feline model. PMID:21429276

  6. Sub-chronic concomitant ingestion of L-arginine and monosodium glutamate improves feed efficiency, lipid metabolism and antioxidant capacity in male Wistar rats.

    PubMed

    Egbuonu, Anthony C Cemaluk

    2012-03-15

    The use of L-arginine (ARG) is common in supplements, whereas, Monosodium Glutamate (MSG) is widely used as flavor enhancing food additive. Thus, ARG and MSG may be present together in human diets, warranting this study aimed at investigating the effect of concomitant ingestion of ARG and MSG on some biochemical indices in male rats. Twelve male albino rats were grouped into three (n = 4) and concomitantly exposed to 0:0, 20:5 and 60:15 mg kg(-1) of ARG:MSG. Exposure was peroral and every twenty four h for 28 days. ARG plus MSG treatment caused a significant (p < or = 0.05) increase in Feed Efficiency (FE) (Low dose: 5.23 +/- 22%; High dose: 5.60 +/- 11%), whereas, it decreased (p < or = 0.05) the serum Total Cholesterol (T-Chol) (low dose: 80.83 +/- 0.11 mg/100 mL, high dose: 92.55 +/- 0.14 mg/100 mL), triacylglycerol (TAG) (low dose: 179.91 +/- 0.09 mg/100 mL, high dose: 119.77 +/- 0.32 mg/100 mL) and malondialdehyde (MDA) (low dose: 5.00 +/- 0.07 mg/100 mL, high dose: 24.36 +/- 0.10 mg/100 mL) concentrations of the rats in a dose dependent manner. However, (at the high dose) the increase in Body Weight (BW) (0.08 +/- 0.07 kg), Feed Intake (FI) (0.40 +/- 0.03 kg) and Water Intake (WI) (0.65 +/- 0.18 L) induced by ARG plus MSG exposure was not significant (p < or = 0.05), suggesting non treatment related effect on these routine parameters. However, exposure to ARG plus MSG may significantly improve feed efficiency, lipid metabolism and antioxidant capacity in the male rats. PMID:24175428

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

    PubMed

    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. PMID:26738966

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

    PubMed

    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. PMID:26293481

  9. Neonatal monosodium glutamate treatment counteracts circadian arrhythmicity induced by phase shifts of the light-dark cycle in female and male Siberian hamsters.

    PubMed

    Prendergast, Brian J; Onishi, Kenneth G; Zucker, Irving

    2013-07-12

    Studies of rats and voles suggest that distinct pathways emanating from the anterior hypothalamic-retrochiasmatic area and the mediobasal hypothalamic arcuate nucleus independently generate ultradian rhythms (URs) in hormone secretion and behavior. We evaluated the hypothesis that destruction of arcuate nucleus (ARC) neurons, in concert with dampening of suprachiasmatic nucleus (SCN) circadian rhythmicity, would compromize the generation of ultradian rhythms (URs) of locomotor activity. Siberian hamsters retain-->of both sexes treated neonatally with monosodium glutamate (MSG) that destroys ARC neurons were subjected in adulthood to a circadian disrupting phase-shift protocol (DPS) that produces SCN arrhythmia. MSG treatments induced hypogonadism and obesity, retain-->and markedly reduced the size of the optic chiasm and optic nerves. MSG-treated hamsters exhibited normal entrainment to the light-dark cycle, but MSG treatretain-->ment counteracted the circadian arrhythmicity induced by the DPS protocol: only 6% of retain-->MSG-treated hamsters exhibited circadian arrhythmia, whereas 50% of control hamsters were circadian disrupted. In MSG-treated hamsters that retained circadian rhythmicity after DPS treatment, quantitative parameters of URs appeared normal, but in the two MSG-treated hamsters that became circadian arrhythmic after DPS, both dark-phase and light-phase URs were abolished. Although preliminary, these data are consistent with reports in voles suggesting that the combined disruption of SCN and ARC function impairs the expression of behavioral URs. The data also suggest that light thresholds for entrainment of circadian rhythms may be lower than those required to disrupt circadian organization. PMID:23701725

  10. New frontiers in gut nutrient sensor research: monosodium L-glutamate added to a high-energy, high-protein liquid diet promotes gastric emptying: a possible therapy for patients with functional dyspepsia.

    PubMed

    Kusano, Motoyasu; Zai, Hiroaki; Hosaka, Hiroko; Shimoyama, Yasuyuki; Nagoshi, Atsuto; Maeda, Masaki; Kawamura, Osamu; Mori, Masatomo

    2010-01-01

    Functional dyspepsia is a clinical syndrome that features abdominal symptoms centered in the upper abdomen without an organic basis. Three possible mechanisms of gastric dysfunction could be related to functional dyspepsia: 1) delayed gastric emptying, 2) impaired gastric accommodation to food intake, and 3) hypersensitivity to gastric distention. Delayed gastric emptying has been suggested to lead to prolonged antral distension that causes dyspeptic symptoms. Delayed gastric emptying is therefore a focal point of debate about anorexia caused by dyspepsia, and prokinetic agents are often administered in Japan for its treatment. Recently, we found that addition of monosodium L-glutamate (MSG) to a high-energy liquid diet rich in casein promoted gastric emptying in healthy men. Therefore, another potential method to improve delayed gastric emptying could be enhancement of chemosensors that activate the autonomic nervous system innervating the gastrointestinal tract. In conclusion, enrichment with glutamate promoted gastric emptying after intake of a high-protein meal, suggesting that free glutamate is important for protein digestion and that MSG may be helpful for management of delayed gastric emptying in patients with functional dyspepsia. PMID:20093786

  11. 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.

    PubMed

    Aung, Hnin-Pwint; Pyell, Ute

    2016-06-01

    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. PMID:27156753

  12. Monosodium glutamate neonatal intoxication associated with obesity in adult stage is characterized by chronic inflammation and increased mRNA expression of peroxisome proliferator-activated receptors in mice.

    PubMed

    Roman-Ramos, Ruben; Almanza-Perez, Julio C; Garcia-Macedo, Rebeca; Blancas-Flores, Gerardo; Fortis-Barrera, Angeles; Jasso, Edgar I; Garcia-Lorenzana, Mario; Campos-Sepulveda, Alfonso E; Cruz, Miguel; Alarcon-Aguilar, Francisco J

    2011-06-01

    The monosodium glutamate (MSG) neonatal administration in mice provides a model of obesity with impaired glucose tolerance (IGT) and insulin resistance. However, the inflammatory profile of cytokines produced from fat tissue and its relationship to the metabolic dysfunction induced by MSG have not yet been revealed. The aim of this study was to establish the inflammatory profile attributed to MSG by measuring the expression of adipokines in visceral fat and serum of 19-week-old mice as well as the peroxisome proliferator-activated receptors alpha and gamma (PPARα and γ). Some metabolic and biochemical parameters were also quantified. The MSG increased mRNA expression of interleukin-6 (IL-6), tumour necrosis factor-alpha (TNFα), resistin and leptin, but adiponectin did not exhibit any changes. In addition, impaired glucose tolerance, increased levels of insulin, resistin and leptin were observed in serum. Both PPARα and PPARγ were activated in MSG-induced obese mice, which might explain its inflammatory profile. However, liver transaminases were severely depressed, indicating that MSG may also induce liver injury, contributing to inflammation. The MSG neonatal neuro-intoxication in mice may thus provide a model of obesity and inflammation characterized by the dual activation of PPARα and PPARγ, which might offer new insights into the mechanism of inflammatory diabetes in obesity leading to steatohepatitis, as well as a suitable model to study the role of new therapeutic agents to prevent or reduce insulin resistance, the inflammatory state and liver steatosis. PMID:21205225

  13. The effects of black garlic (Allium sativum L.) ethanol extract on the estimated total number of Purkinje cells and motor coordination of male adolescent Wistar rats treated with monosodium glutamate.

    PubMed

    Aminuddin, M; Partadiredja, G; Sari, D C R

    2015-03-01

    A number of studies have indicated that monosodium glutamate (MSG) might cause negative effects on the nervous system, including in the cerebellum. Garlic (Allium sativum) has long been known as a flavouring agent and a traditional remedy for various illnesses. The present study aimed at investigating the effects of garlic on the motor coordination and the number of Purkinje cells present in rats treated with MSG. A total of 25 male Wistar rats aged 4 to 5 weeks old were used in this study and were divided into five groups, namely a negative control (C-) group, which received 0.9 % NaCl solution, a positive control (C+) group, which received MSG, and three treated groups, which received 2 mg/g bw of MSG and 2.5 mg (T2.5), 5 mg (T5), or 10 mg (T10) of black garlic solution per oral administration (per 200 g bw), respectively. All treatments were carried out for 10 days. Upon the end of the treatment, the motor performance of all rats were tested using the rotarod apparatus. The rats were subsequently sacrificed, and the cerebella of the rats were processed for stereological analyses. It has been found that the number of Purkinje cells of the cerebella of all treated groups were significantly higher than that of the group treated with MSG only. No changes in motor coordination function were observed as a result of MSG treatment. PMID:24737450

  14. 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.

    PubMed

    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. PMID:25422084

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  17. Effect of the umami peptides on the ligand binding and function of rat mGlu4a receptor might implicate this receptor in the monosodium glutamate taste transduction

    PubMed Central

    Monastyrskaia, Katherine; Lundstrom, Kenneth; Plahl, Doris; Acuna, Gonzalo; Schweitzer, Christophe; Malherbe, Pari; Mutel, Vincent

    1999-01-01

    The effect of several metabotropic ligands and di- or tripeptides were tested on the binding of [3H]-L(+)-2-amino-4-phosphonobutyric acid ([3H]-L-AP4) on rat mGlu4 receptor. For selected compounds, the functional activity was determined on this receptor using the guanosine-5′[γ-35S]-thiotriphosphate [γ-35S]-GTP binding assay.Using the scintillation proximity assay, [3H]-L-AP4 saturation analysis gave binding parameters KD and Bmax values of 150 nM and 9.3 pmoles mg−1 protein, respectively. The specific binding was inhibited concentration-dependently by several mGlu receptor ligands, and their rank order of affinity was established.Several peptides inhibited the [3H]-L-AP4 binding with the following rank order of potency: glutamate-glutamate>glutamate-glutamate-leucine=aspartate - glutamate>>glutamate - glutamate-aspartate>lactoyl-glutamate>>aspartate-aspartate. Aspartate-phenylalanine-methyl ester (aspartame) was inactive up to 1 mM and guanosine-5′-monophosphate and inosine-5′-monophosphate were inactive up to 100 μM.The [γ-35S]-GTP binding functional assay was used to determine the agonist activities of the different compounds. For the rat mGlu4 agonists, L-AP4 and L-glutamate, the correlation between their occupancy and activation of the receptor was close to one. The peptides, Glu-Glu, Asp-Glu and Glu-Glu-Asp failed to stimulate the [γ-35S]-GTP binding at receptor occupancy greater than 80% and Glu-Glu-Leu appeared to be a weak partial agonist. These peptides did not elicit a clear dose-dependent umami perception. However, Glu-lac showed a good correlation between its potency to stimulate the [γ-35S]-GTP binding and its affinity for displacement of [3H]-L-AP4 binding. These data are in agreement with the peptide taste assessment in human subjects, which showed that the acid derivatives of glutamate had characteristics similar to umami. PMID:10556940

  18. The Crystallization of Monosodium Urate

    PubMed Central

    Martillo, Miguel A.; Nazzal, Lama; Crittenden, Daria B.

    2014-01-01

    Gout is a common crystal-induced arthritis, in which monosodium urate (MSU) crystals precipitate within joints and soft tissues and elicit an inflammatory response. The causes of elevated serum urate and the inflammatory pathways activated by MSU crystals have been well studied, but less is known about the processes leading to crystal formation and growth. Uric acid, the final product of purine metabolism, is a weak acid that circulates as the deprotonated urate anion under physiologic conditions, and combines with sodium ions to form MSU. MSU crystals are known to have a triclinic structure, in which stacked sheets of purine rings form the needle-shaped crystals that are observed microscopically. Exposed, charged crystal surfaces are thought to allow for interaction with phospholipid membranes and serum factors, playing a role in the crystal-mediated inflammatory response. While hyperuricemia is a clear risk factor for gout, local factors have been hypothesized to play a role in crystal formation, such as temperature, pH, mechanical stress, cartilage components, and other synovial and serum factors. Interestingly, several studies suggest that MSU crystals may drive the generation of crystal-specific antibodies that facilitate future MSU crystallization. Here, we review MSU crystal biology, including a discussion of crystal structure, effector function, and factors thought to play a role in crystal formation. We also briefly compare MSU biology to that of uric acid stones causing nephrolithasis, and consider the potential treatment implications of MSU crystal biology. PMID:24357445

  19. ANALYSIS OF HARRELL MONOSODIUM TITANATE LOT #071311

    SciTech Connect

    Taylor-Pashow, K.

    2011-10-04

    Monosodium titanate (MST) for use in the Actinide Removal Process (ARP) must be qualified and verified in advance. A single qualification sample for each batch of material is sent to SRNL for analysis, as well as a statistical sampling of verification samples. The Harrell Industries Lot No.071311 qualification and 12 verification samples met all the requirements in the specification indicating the material is acceptable for use in the process.

  20. Analysis of Harrell Monosodium Titanate Lot #46000824120

    SciTech Connect

    Taylor-Pashow, K. M.L.

    2013-01-23

    Monosodium titanate (MST) for use in the Actinide Removal Process (ARP) must be qualified and verified in advance. A single qualification sample for each batch of material is sent to SRNL for analysis, as well as a statistical sampling of verification samples. The Harrell Industries Lot #46000824120 qualification and the 16 verification samples failed to meet the specification for weight percent solids. All of the pails sampled and tested contained less than 15 wt % MST solids.

  1. Analysis of Harrell Monosodium Titanate Lot #46000908120

    SciTech Connect

    Taylor-Pashow, K. M.L.

    2013-01-23

    Monosodium titanate (MST) for use in the Actinide Removal Process (ARP) must be qualified and verified in advance. A single qualification sample for each batch of material is sent to SRNL for analysis, as well as a statistical sampling of verification samples. The Harrell Industries Lot #46000908120 qualification and the 16 verification samples failed to meet the specification for weight percent solids. All of the pails sampled and tested contained less than 15 wt % MST solids.

  2. ANALYSIS OF HARRELL MONOSODIUM TITANATE LOT #46000619120

    SciTech Connect

    Taylor-Pashow, K.

    2012-09-06

    Monosodium titanate (MST) for use in the Actinide Removal Process (ARP) must be qualified and verified in advance. A single qualification sample for each batch of material is sent to SRNL for analysis, as well as a statistical sampling of verification samples. The Harrell Industries Lot #46000619120 qualification and the 13 verification samples met each of the selected specification requirements that were tested and, consequently, the material is acceptable for use in the ARP process.

  3. ANALYSIS OF HARRELL MONOSODIUM TITANATE LOT #052511

    SciTech Connect

    Taylor-Pashow, K.

    2011-08-22

    Monosodium titanate (MST) for use in the Actinide Removal Process (ARP) must be qualified and verified in advance. A single qualification sample for each batch of material is sent to SRNL for analysis, as well as a statistical sampling of verification samples. The Harrell Industries Lot No.052511 qualification and 14 verification samples met all the requirements in the specification indicating the material is acceptable for use in the process.

  4. ANALYSIS OF HARRELL MONOSODIUM TITANATE LOT #46000524120

    SciTech Connect

    Taylor-Pashow, K.

    2012-08-29

    Monosodium titanate (MST) for use in the Actinide Removal Process (ARP) must be qualified and verified in advance. A single qualification sample for each batch of material is sent to SRNL for analysis, as well as a statistical sampling of verification samples. The Harrell Industries Lot No.46000524120 qualification and the 14 verification samples met each of the selected specification requirements that were tested and, consequently, the material is acceptable for use in the ARP process.

  5. Intragastric administration of glutamate increases REM sleep in rats.

    PubMed

    Datta, Karuna; Kumar, Deependra; Mallick, Hruda Nanda

    2013-10-01

    Monosodium glutamate, a umami taste substance is commonly used flavor enhancer. The effect of intragastric administration of 1.5 ml of 0.12M monosodium glutamate on sleep-wake was studied in 10 adult male Wistar rats. Sleep-wake parameters were recorded through chronically implanted electroencephalogram, electrooculogram and electromyogram electrodes using a digital recording system (BIOPAC system Inc. BSL PRO 36, USA). The sleep-wake was recorded for 6h after the intragastric administration of either glutamate or saline. Sleep-wake stages were analyzed as wake, slow wave sleep and REM sleep. Compared to saline, intragastric administration of glutamate significantly increased REM sleep duration and episode frequency. REM sleep duration was increased in all the three 2h bins, 10:00-12:00 h (p=0.037), 12:00-14:00 h (p=0.037) and 14:00-16:00 h (p=0.007). The slow wave sleep and total sleep time were not affected. It is concluded that intragastric glutamate administration increases REM sleep. PMID:24055576

  6. Glutamate. Its applications in food and contribution to health.

    PubMed

    Jinap, S; Hajeb, P

    2010-08-01

    This article reviews application of glutamate in food and its benefits and role as one of the common food ingredients used. Monosodium glutamate is one of the most abundant naturally occurring amino acids which frequently added as a flavor enhancer. It produced a unique taste that cannot be provided by other basic taste (saltiness, sourness, sweetness and bitterness), referred to as a fifth taste (umami). Glutamate serves some functions in the body as well, serving as an energy source for certain tissues and as a substrate for glutathione synthesis. Glutamate has the potential to enhance food intake in older individuals and dietary free glutamate evoked a visceral sensation from the stomach, intestine and portal vein. Small quantities of glutamate used in combination with a reduced amount of table salt during food preparation allow for far less salt to be used during and after cooking. Because glutamate is one of the most intensely studied food ingredients in the food supply and has been found safe, the Joint Expert Committee on Food Additives of the United Nations Food and Agriculture Organization and World Health Organization placed it in the safest category for food additives. Despite a widespread belief that glutamate can elicit asthma, migraine headache and Chinese Restaurant Syndrome (CRS), there are no consistent clinical data to support this claim. In addition, findings from the literature indicate that there is no consistent evidence to suggest that individuals may be uniquely sensitive to glutamate. PMID:20470841

  7. Flavor Preferences Conditioned by Dietary Glutamate.

    PubMed

    Ackroff, Karen; Sclafani, Anthony

    2016-07-01

    Our understanding of the molecular basis of umami taste and its appetitive qualities has been greatly aided by studies in laboratory rodents. This review describes methods for testing responses to the prototypical umami substance monosodium glutamate (MSG) in rodents. Two techniques, forced exposure to MSG and 2-bottle choice tests with ascending concentrations, were used to evaluate the responses to the taste of umami itself, and 2 other methods used oral or postoral MSG to modify the responses to other flavors. Intake and preference for MSG are enhanced in mice by experience with MSG and with other nutrients with positive postoral effects. In addition, flavor preferences are enhanced in mice and rats by gastric or intestinal MSG infusions via an associative learning process. Even mice with an impaired or absent ability to taste MSG can learn to prefer a flavor added to an MSG solution, supporting the notion that glutamate acts postorally. The more complex flavor of dashi seasoning, which includes umami substances (inosinate, glutamate), is attractive to rodents, but dashi does not condition flavor preferences. Details of the postoral glutamate detection process and the nature of the signal involved in learned preferences are still uncertain but probably involve gastric or intestinal sensors or both and vagal transmission. Some findings suggest that postoral glutamate effects may enhance food preferences in humans, but this requires further study. PMID:27422522

  8. ANALYSIS OF HARRELL MONOSODIUM TITANATE LOT 46000824120

    SciTech Connect

    Taylor-Pashow, K.

    2014-04-09

    Monosodium titanate (MST) for use in the Actinide Removal Process (ARP) must be qualified and verified in advance. A single qualification sample for each batch of material is sent to SRNL for analysis, as well as a statistical sampling of verification samples. The original Harrell Industries Lot #46000824120 qualification and 16 verification samples received in September 2012 failed to meet the specification for weight percent solids. All of the pails sampled and tested contained less than 15 wt % MST solids. The lot was returned to the vendor, and in February 2014 a new qualification sample and set of 14 verification samples were received from this lot. The new lot met each of the selected specification requirements that were tested and, consequently, the material is acceptable for use in the ARP process.

  9. ANALYSIS OF HARRELL MONOSODIUM TITANATE LOT 46000908120

    SciTech Connect

    Taylor-Pashow, K.

    2014-04-09

    Monosodium titanate (MST) for use in the Actinide Removal Process (ARP) must be qualified and verified in advance. A single qualification sample for each batch of material is sent to SRNL for analysis, as well as a statistical sampling of verification samples. The original Harrell Industries Lot #46000908120 qualification and 16 verification samples received in October 2012 failed to meet the specification for weight percent solids. All of the pails sampled and tested contained less than 15 wt % MST solids. The lot was returned to the vendor, and in February 2014 a new qualification sample and set of 16 verification samples were received from this lot. The new lot met each of the selected specification requirements that were tested and, consequently, the material is acceptable for use in the ARP process.

  10. ANALYSIS OF HARRELL MONOSODIUM TITANATE LOT #120111

    SciTech Connect

    Shehee, T.

    2012-02-21

    Monosodium titanate (MST) for use in the Actinide Removal Process (ARP) must be qualified and verified in advance. A single qualification sample for each batch of material is sent to SRNL for analysis, as well as a statistical sampling of verification samples. The Harrell Industries Lot No.120111 qualification and the first 12 verification samples met all the requirements in the specification indicating the material is acceptable for use in the process. Analyses of Pail 125 verification sample fails the criteria for solids content and has measurably lower pH, density, and total bottle weight. The verification sample for Pail 125 was retested for weight percent solids after checking that all of the solids had been suspended. The sample again failed to meet acceptance criteria. SRNL recommends accepting Pails 1 through 120. Pails 121 through 125 should be rejected and returned to the vendor.

  11. Extracellular expression of glutamate decarboxylase B in Escherichia coli to improve gamma-aminobutyric acid production.

    PubMed

    Zhao, Anqi; Hu, Xiaoqing; Li, Ye; Chen, Cheng; Wang, Xiaoyuan

    2016-12-01

    Escherichia coli overexpressing glutamate decarboxylase GadB can produce gamma-aminobutyric acid with addition of monosodium glutamate. The yield and productivity of gamma-aminobutyric acid might be significantly improved if the overexpressed GadB in E. coli cells can be excreted outside, where it can directly transforms monosodium glutamate to gamma-aminobutyric acid. In this study, GadB was fused to signal peptides TorA or PelB, respectively, and overexpressed in E. coli BL21(DE3). It was found that TorA could facilitate GadB secretion much better than PelB. Conditions for GadB secretion and gamma-aminobutyric acid production were optimized in E. coli BL21(DE3)/pET20b-torA-gadB, leading the secretion of more than half of the overexpressed GadB. Fed-batch fermentation for GadB expression and gamma-aminobutyric acid production of BL21(DE3)/pET20b-torA-gadB was sequentially performed in one fermenter; 264.4 and 313.1 g/L gamma-aminobutyric acid were obtained with addition of monosodium glutamate after 36 and 72 h, respectively. PMID:27549808

  12. ANALYSIS OF HARRELL MONOSODIUM TITANATE LOT #03031

    SciTech Connect

    Taylor-Pashow, K.

    2011-05-16

    Monosodium titanate (MST) for use in the Actinide Removal Process (ARP) must be qualified and verified in advance. A single qualification sample for each batch of material is sent to SRNL for analysis, as well as a statistical sampling of verification samples. The Harrell Industries Lot 030311 qualification and 9 verification samples met all the requirements in the specification indicating the material is acceptable for use in the process. Harrell Industries is under contract with Savannah River Remediation to provide MST for use in the Actinide Removal Process (ARP). A 500-mL qualification sample for Lot 030311 was sent to the Savannah River National Laboratory (SRNL) to confirm the material meets the requirements specified in the purchase specification. The vendor is also obligated to send verification samples from {approx}10% or more of the pails of MST product for each lot (distributed roughly evenly through the entire lot of pails). For the verification of this lot, Harrell Industries sent 9 samples, one each from pails 1, 5, 15, 20, 25, 30, 40, 45, and 55 of 59 total pails.

  13. ANALYSIS OF HARRELL MONOSODIUM TITANATE LOT #050411

    SciTech Connect

    Taylor-Pashow, K.

    2011-06-28

    Harrell Industries is under contract with Savannah River Remediation to provide Monosodium titanate (MST) for use in the Actinide Removal Process (ARP). A 500-mL qualification sample for Lot 050411 was sent to the Savannah River National Laboratory (SRNL) to confirm the material meets the requirements specified in the purchase specification. The vendor is also obligated to send verification samples from {approx}10% or more of the pails of MST product for each lot (distributed roughly evenly through the entire lot of pails). For the verification of this lot, Harrell Industries sent 12 samples, one each from pails No.1, 10, 20, 30, 40, 60, 70, 80, 90, 100, 110, and 120 of 120 total pails. MST for use in the Actinide Removal Process (ARP) must be qualified and verified in advance. A single qualification sample for each batch of material is sent to SRNL for analysis, as well as a statistical sampling of verification samples. The Harrell Industries Lot 050411 qualification and 12 verification samples met all the requirements in the specification indicating the material is acceptable for use in the process.

  14. ANALYSIS OF HARRELL MONOSODIUM TITANATE LOT #081811

    SciTech Connect

    Taylor-Pashow, K.; Fink, S.

    2011-10-28

    Monosodium titanate (MST) for use in the Actinide Removal Process (ARP) must be qualified and verified in advance. A single qualification sample for each batch of material is sent to SRNL for analysis, as well as a statistical sampling of verification samples. The Harrell Industries Lot No.081811 qualification and 12 verification samples met all the requirements in the specification, with the possible exception of the geometric standard deviation for particle size. Two subsamples from the qualification sample were analyzed, giving results of 3.82 and 3.28, respectively, for the geometric standard deviation. The specification is {le}3.5. The results for both samples met the remaining particle size specifications, i.e. <10 vol% below 0.8 {mu}m and <1 vol% above 37 {mu}m. Filtration behavior of the current batch is expected to be near that of recent batches. SRNL recommends acceptance of this material. SRNL also recommends performing a statistical review of particle size data for the MST lots from this vendor to assess whether an improved material specification is appropriate.

  15. Fissile solubility and monosodium titanate loading tests

    SciTech Connect

    Hobbs, D.T.; Fleischman, S.D.

    1993-02-12

    The solubilities of plutonium and uranium have been determined for alkaline salt solutions having compositions which bound those which will be processed in the In-Tank Precipitation (ITP) process. Loadings of plutonium and uranium onto monosodium titanate (MST) have been determined at temperatures bounding those expected to occur during ITP and using a salt solution which was determined to have the maximum solubility for uranium and plutonium. Fissile loadings increase with decreasing amounts of MST in contact with the salt solutions saturated in plutonium and uranium. At MST concentrations bounding those which are planned for the ITP process, expressions for the maximum loadings (wt %) are determined to be 0.29 - 0.20x[MST] for plutonium and 1.8 - 0.29x[MST] for uranium, where [MST] is the concentration of MST in grams/liter. These expressions are valid over the range of MST concentrations from 0.05 to 0.51 g/L and temperatures of 17{degrees}--74{degrees}C. These loadings are below the individual infinitely safe limits for plutonium and uranium. Additional confirmatory experiments are planned to verify the effects of temperature and multiple contacts of the MST with fresh salt solution on the fissile loadings.

  16. Fissile solubility and monosodium titanate loading tests

    SciTech Connect

    Hobbs, D.T.; Fleischman, S.D.

    1993-02-12

    The solubilities of plutonium and uranium have been determined for alkaline salt solutions having compositions which bound those which will be processed in the In-Tank Precipitation (ITP) process. Loadings of plutonium and uranium onto monosodium titanate (MST) have been determined at temperatures bounding those expected to occur during ITP and using a salt solution which was determined to have the maximum solubility for uranium and plutonium. Fissile loadings increase with decreasing amounts of MST in contact with the salt solutions saturated in plutonium and uranium. At MST concentrations bounding those which are planned for the ITP process, expressions for the maximum loadings (wt %) are determined to be 0.29 - 0.20x[MST] for plutonium and 1.8 - 0.29x[MST] for uranium, where [MST] is the concentration of MST in grams/liter. These expressions are valid over the range of MST concentrations from 0.05 to 0.51 g/L and temperatures of 17[degrees]--74[degrees]C. These loadings are below the individual infinitely safe limits for plutonium and uranium. Additional confirmatory experiments are planned to verify the effects of temperature and multiple contacts of the MST with fresh salt solution on the fissile loadings.

  17. 40 CFR 721.3848 - Glycine, N-(carboxymethyl)-N-dodecyl-, monosodium salt.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...-, monosodium salt. 721.3848 Section 721.3848 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... Specific Chemical Substances § 721.3848 Glycine, N-(carboxymethyl)-N-dodecyl-, monosodium salt. (a... glycine, N-(carboxymethyl)-N-dodecyl-, monosodium salt (PMN P-00-469; CAS No. 141321-68-8) is subject...

  18. 40 CFR 721.3848 - Glycine, N-(carboxymethyl)-N-dodecyl-, monosodium salt.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...-, monosodium salt. 721.3848 Section 721.3848 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... Specific Chemical Substances § 721.3848 Glycine, N-(carboxymethyl)-N-dodecyl-, monosodium salt. (a... glycine, N-(carboxymethyl)-N-dodecyl-, monosodium salt (PMN P-00-469; CAS No. 141321-68-8) is subject...

  19. 40 CFR 721.3848 - Glycine, N-(carboxymethyl)-N-dodecyl-, monosodium salt.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...-, monosodium salt. 721.3848 Section 721.3848 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... Specific Chemical Substances § 721.3848 Glycine, N-(carboxymethyl)-N-dodecyl-, monosodium salt. (a... glycine, N-(carboxymethyl)-N-dodecyl-, monosodium salt (PMN P-00-469; CAS No. 141321-68-8) is subject...

  20. 40 CFR 721.3848 - Glycine, N-(carboxymethyl)-N-dodecyl-, monosodium salt.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...-, monosodium salt. 721.3848 Section 721.3848 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... Specific Chemical Substances § 721.3848 Glycine, N-(carboxymethyl)-N-dodecyl-, monosodium salt. (a... glycine, N-(carboxymethyl)-N-dodecyl-, monosodium salt (PMN P-00-469; CAS No. 141321-68-8) is subject...

  1. 40 CFR 721.3848 - Glycine, N-(carboxymethyl)-N-dodecyl-, monosodium salt.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...-, monosodium salt. 721.3848 Section 721.3848 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... Specific Chemical Substances § 721.3848 Glycine, N-(carboxymethyl)-N-dodecyl-, monosodium salt. (a... glycine, N-(carboxymethyl)-N-dodecyl-, monosodium salt (PMN P-00-469; CAS No. 141321-68-8) is subject...

  2. Effect of free dietary glutamate on gastric secretion in dogs.

    PubMed

    Zolotarev, Vasiliy; Khropycheva, Raisa; Uneyama, Hisayuki; Torii, Kunio

    2009-07-01

    The amino acid, L-glutamate, which is abundant in many foodstuffs, is a potent stimulator of gastric vagal afferents. The aim of the study was to evaluate a role of dietary glutamate in neuroendocrine control of gastric secretion of acid, pepsinogen, and fluid. In mongrel dogs with small gastric pouches surgically prepared according to Pavlov (vagally innervated) or Heidenhain (vagally decentralized), secretion in a pouch was induced by infusion into the main stomach of an amino acid-rich diet lacking glutamate (Elental) or the same diet supplemented with monosodium glutamate (MSG). Having no effect alone, MSG (100 mM) potentiated secretion induced by Elental both in Pavlov and Heidenhain models. In the Pavlov pouch, the effect of MSG was markedly reduced after i.v. injection of granisetron, an antagonist of 5-HT(3) receptors. In the Heidenhain model, MSG enhanced the stimulatory effect of pentagastrin (1 microg/kg, s.c.). In conclusion, dietary glutamate at doses not exceeding its common concentrations in foods substantially potentiates gastric phase secretion induced by stimulation of gastric mucosa with an amino acid-rich diet or by administration of pentagastrin. The effect of glutamate is partially mediated via serotonin secretion and stimulation of 5-HT(3) receptors. PMID:19686114

  3. Possible significance of adverse reactions to glutamate in humans.

    PubMed

    Reif-Lehrer, L

    1976-09-01

    Of those exposed to Chinese restaurant food, our studies indicate that 25% report adverse reactions (Chinese restaurant syndrome (CRS)), presumably to the mono-sodium glutamate (MSG) content. The possible significance of the symptoms is discussed in the light of the known neuroexcitatory activity of MSG. It is suggested that CRS may result from a "benign" inborn "error" of metabolism that is deserving of further study, particularly in individuals with certain other metabolic abnormalities or who are on certain types of drug therapy. PMID:782921

  4. 78 FR 74115 - Monosodium Glutamate From the People's Republic of China and the Republic of Indonesia...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-10

    ... China and the Republic of Indonesia: Initiation of Countervailing Duty Investigations, 78 FR 65269... Administrative Determination Deadlines Pursuant to the Tariff Act of 1930, as Amended, 70 FR 24533 (May 10,...

  5. 78 FR 57881 - Monosodium Glutamate from China and Indonesia; Institution of Antidumping and Countervailing Duty...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-20

    ... took effect on November 7, 2011. See 76 FR 61937 (Oct. 6, 2011) and the newly revised Commission's... investigations and Scheduling of Preliminary Phase Investigations AGENCY: United States International Trade... and commencement of preliminary phase antidumping and countervailing duty investigations Nos....

  6. 78 FR 65278 - Monosodium Glutamate From the People's Republic of China, and the Republic of Indonesia...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-31

    ... Antidumping Duties; Countervailing Duties; Final Rule, 62 FR 27296, 27323 (May 19, 1997). \\8\\ See Antidumping... Procedures, 76 FR 39263 (July 6, 2011) for details of the Department's electronic filing requirements, which... Submission of Factual Information: Final Rule, 78 FR 21246 (April 10, 2013), which modified two...

  7. 78 FR 65269 - Monosodium Glutamate From the People's Republic of China and the Republic of Indonesia...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-31

    ... Duties; Final Rule, 62 FR 27296, 27323 (May 19, 1997). \\7\\ See Antidumping and Countervailing Duty Proceedings: Electronic Filing Procedures; Administrative Protective Order Procedures, 76 FR 39263 (July 6... Information and Time Limits for Submission of Factual Information: Final Rule, 78 FR 21246 (April 10,...

  8. Disorders of glutamate metabolism.

    PubMed

    Kelly, A; Stanley, C A

    2001-01-01

    The significant role the amino acid glutamate assumes in a number of fundamental metabolic pathways is becoming better understood. As a central junction for interchange of amino nitrogen, glutamate facilitates both amino acid synthesis and degradation. In the liver, glutamate is the terminus for release of ammonia from amino acids, and the intrahepatic concentration of glutamate modulates the rate of ammonia detoxification into urea. In pancreatic beta-cells, oxidation of glutamate mediates amino acid-stimulated insulin secretion. In the central nervous system, glutamate serves as an excitatory neurotransmittor. Glutamate is also the precursor of the inhibitory neurotransmittor GABA, as well as glutamine, a potential mediator of hyperammonemic neurotoxicity. The recent identification of a novel form of congenital hyperinsulinism associated with asymptomatic hyperammonemia assigns glutamate oxidation by glutamate dehydrogenase a more important role than previously recognized in beta-cell insulin secretion and hepatic and CNS ammonia detoxification. Disruptions of glutamate metabolism have been implicated in other clinical disorders, such as pyridoxine-dependent seizures, confirming the importance of intact glutamate metabolism. This article will review glutamate metabolism and clinical disorders associated with disrupted glutamate metabolism. PMID:11754524

  9. 21 CFR 184.1521 - Monosodium phosphate derivatives of mono- and diglycerides.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Monosodium phosphate derivatives of mono- and diglycerides. 184.1521 Section 184.1521 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... GENERALLY RECOGNIZED AS SAFE Listing of Specific Substances Affirmed as GRAS § 184.1521 Monosodium...

  10. 21 CFR 184.1521 - Monosodium phosphate derivatives of mono- and diglycerides.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Monosodium phosphate derivatives of mono- and diglycerides. 184.1521 Section 184.1521 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... GENERALLY RECOGNIZED AS SAFE Listing of Specific Substances Affirmed as GRAS § 184.1521 Monosodium...

  11. Metabotropic glutamate receptors inhibit microglial glutamate release

    PubMed Central

    McMullan, Stephen M; Phanavanh, Bounleut; Guo Li, Gary; Barger, Steven W

    2012-01-01

    Pro-inflammatory stimuli evoke an export of glutamate from microglia that is sufficient to contribute to excitotoxicity in neighbouring neurons. Since microglia also express various glutamate receptors themselves, we were interested in the potential feedback of glutamate on this system. Several agonists of mGluRs (metabotropic glutamate receptors) were applied to primary rat microglia, and the export of glutamate into their culture medium was evoked by LPS (lipopolysaccharide). Agonists of group-II and -III mGluR ACPD [(1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid] and L-AP4 [L-(+)-2-amino-4-phosphonobutyric acid] were both capable of completely blocking the glutamate export without interfering with the production of NO (nitric oxide); the group-I agonist tADA (trans-azetidine-2,4-dicarboxylic acid) was ineffective. Consistent with the possibility of feedback, inhibition of mGluR by MSPG [(R,S)-α-2-methyl-4sulfonophenylglycine] potentiated glutamate export. As the group-II and -III mGluR are coupled to Gαi-containing G-proteins and the inhibition of adenylate cyclase, we explored the role of cAMP in this effect. Inhibition of cAMP-dependent protein kinase [also known as protein kinase A (PKA)] by H89 mimicked the effect of ACPD, and the mGluR agonist had its actions reversed by artificially sustaining cAMP through the PDE (phosphodiesterase) inhibitor IBMX (isobutylmethylxanthine) or the cAMP mimetic dbcAMP (dibutyryl cAMP). These data indicate that mGluR activation attenuates a potentially neurotoxic export of glutamate from activated microglia and implicate cAMP as a contributor to this aspect of microglial action. PMID:22770428

  12. SLC1 Glutamate Transporters

    PubMed Central

    Grewer, Christof; Gameiro, Armanda; Rauen, Thomas

    2014-01-01

    The plasma membrane transporters for the neurotransmitter glutamate belong to the solute carrier 1 (SLC1) family. They are secondary active transporters, taking up glutamate into the cell against a substantial concentration gradient. The driving force for concentrative uptake is provided by the cotransport of Na+ ions and the countertransport of one K+ in a step independent of the glutamate translocation step. Due to eletrogenicity of transport, the transmembrane potential can also act as a driving force. Glutamate transporters are expressed in many tissues, but are of particular importance in the brain, where they contribute to the termination of excitatory neurotransmission. Glutamate transporters can also run in reverse, resulting in glutamate release from cells. Due to these important physiological functions, glutamate transporter expression and, therefore, the transport rate, are tightly regulated. This review summarizes recent literature on the functional and biophysical properties, structure-function relationships, regulation, physiological significance, and pharmacology of glutamate transporters. Particular emphasis is on the insight from rapid kinetic and electrophysiological studies, transcriptional regulation of transporter expression, and reverse transport and its importance for pathophysiological glutamate release under ischemic conditions. PMID:24240778

  13. Synthesis and Reaction Chemistry of Nanosize Monosodium Titanate.

    PubMed

    Elvington, Mark C; Taylor-Pashow, Kathryn M L; Tosten, Michael H; Hobbs, David T

    2016-01-01

    This paper describes the synthesis and peroxide-modification of nanosize monosodium titanate (nMST), along with an ion-exchange reaction to load the material with Au(III) ions. The synthesis method was derived from a sol-gel process used to produce micron-sized monosodium titanate (MST), with several key modifications, including altering reagent concentrations, omitting a particle seed step, and introducing a non-ionic surfactant to facilitate control of particle formation and growth. The resultant nMST material exhibits spherical-shaped particle morphology with a monodisperse distribution of particle diameters in the range from 100 to 150 nm. The nMST material was found to have a Brunauer-Emmett-Teller (BET) surface area of 285 m(2)g(-1), which is more than an order of magnitude higher than the micron-sized MST. The isoelectric point of the nMST measured 3.34 pH units, which is a pH unit lower than that measured for the micron-size MST. The nMST material was found to serve as an effective ion exchanger under weakly acidic conditions for the preparation of an Au(III)-exchange nanotitanate. In addition, the formation of the corresponding peroxotitanate was demonstrated by reaction of the nMST with hydrogen peroxide. PMID:26967828

  14. Glutamate and Neurodegenerative Disease

    NASA Astrophysics Data System (ADS)

    Schaeffer, Eric; Duplantier, Allen

    As the main excitatory neurotransmitter in the mammalian central nervous system, glutamate is critically involved in most aspects of CNS function. Given this critical role, it is not surprising that glutamatergic dysfunction is associated with many CNS disorders. In this chapter, we review the literature that links aberrant glutamate neurotransmission with CNS pathology, with a focus on neurodegenerative diseases. The biology and pharmacology of the various glutamate receptor families are discussed, along with data which links these receptors with neurodegenerative conditions. In addition, we review progress that has been made in developing small molecule modulators of glutamate receptors and transporters, and describe how these compounds have helped us understand the complex pharmacology of glutamate in normal CNS function, as well as their potential for the treatment of neurodegenerative diseases.

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

    PubMed

    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

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

    SciTech Connect

    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.

  17. Evaluation of genotoxic effects of five flavour enhancers (glutamates) on the root meristem cells of Allium cepa.

    PubMed

    Türkoğlu, Şifa

    2015-09-01

    The effects of different treatments with flavour enhancers monosodium glutamate, monopotassium glutamate, calcium diglutamate, monoammonium glutamate, and magnesium diglutamate on the cytology, DNA content, and interphase nuclear volume (INV) of A. cepa were investigated. Three concentrations of these additives - 20, 40, and 60 ppm - were applied for 6, 12, and 24 h. All the concentrations of these chemicals showed an inhibitory effect on cell division in root tips of A. cepa and caused a decrease in mitotic index values. Additionally, all the treatments changed the frequency of mitotic phases when compared with the control groups. These compounds increased chromosome abnormalities, among them are micronuclei, c-mitosis, anaphase bridges, stickiness, binucleus, laggards, and breaks. The nuclear DNA content and INV decreased when compared with control groups. PMID:23377115

  18. LEACHING OF TITANIUM FROM MONOSODIUM TITANATE AND MODIFIED MST

    SciTech Connect

    Taylor-Pashow, K.; Fondeur, F.; Fink, S.

    2012-08-01

    Analysis of a fouled coalescer and pre-filters from Actinide Removal Process/Modular Caustic Side Solvent Extraction Unit (ARP/MCU) operations showed evidence of Ti containing solids. Based on these results a series of tests were planned to examine the extent of Ti leaching from monosodium titanate (MST) and modified monosodium titanate (mMST) in various solutions. The solutions tested included a series of salt solutions with varying free hydroxide concentrations, two sodium hydroxide concentrations, 9 wt % and 15 wt %, nitric and oxalic acid solutions. Overall, the amount of Ti leached from the MST and mMST was much greater in the acid solutions compared to the sodium hydroxide or salt solutions, which is consistent with the expected trend. The leaching data also showed that increasing hydroxide concentration, whether pure NaOH solution used for filter cleaning in ARP or the waste salt solution, increased the amount of Ti leached from both the MST and mMST. For the respective nominal contact times with the MST solids - for filter cleaning or the normal filter operation, the dissolved Ti concentrations are comparable suggesting either cause may contribute to the increased Ti fouling on the MCU coalescers. Tests showed that Ti containing solids could be precipitated from solution after the addition of scrub acid and a decrease in temperature similar to expected in MCU operations. FTIR analysis of these solids showed some similarity to the solids observed on the fouled coalescer and pre-filters. Although only a cursory study, this information suggests that the practice of increasing free hydroxide in feed solutions to MCU as a mitigation to aluminosilicate formation may be offset by the impact of formation of Ti solids in the overall process. Additional consideration of this finding from MCU and SWPF operation is warranted.

  19. Non-sterilized fermentative co-production of poly(γ-glutamic acid) and fibrinolytic enzyme by a thermophilic Bacillus subtilis GXA-28.

    PubMed

    Zeng, Wei; Li, Wei; Shu, Lin; Yi, Juyang; Chen, Guiguang; Liang, Zhiqun

    2013-08-01

    Poly(γ-glutamic acid), as a naturally occurring homopolymer, is widely used in industry, agriculture, food and medicine. Fibrinolytic enzyme has a great potential for the prevention and/or treatment of vascular diseases caused by fibrin clots. Co-production of γ-PGA and fibrinolytic enzyme by Bacillus subtilis GXA-28 (CCTCC M 2012347) from soybean residue using cane molasses and monosodium glutamate waste liquor under sterilized and non-sterilized condition were investigated. It was observed that total sugar from cane molasses of 3% (w/w) and glutamate from monosodium glutamate waste liquor of 2% (w/w) were favorable for γ-PGA and fibrinolytic enzyme co-production at pH 7.0 and 45°C. Based on the optimal medium, the γ-PGA and fibrinolytic activity reached 103.5 g/kg-substrates at 22 h and 986 U/g-substrates at 24h under non-sterilized condition, respectively. To our knowledge, the yield of γ-PGA was highest in all reported literatures. PMID:23725975

  20. Adsorption of biometals to monosodium titanate in biological environments

    SciTech Connect

    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.

  1. Adsorption of biometals to monosodium titanate in biological environments.

    PubMed

    Hobbs, D T; Messer, R L W; Lewis, J B; Click, D R; Lockwood, P E; Wataha, J C

    2006-08-01

    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), Au(III), or the Au-organic compound auranofin 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 TNFalpha secretion (ELISA) with or without lipopolysaccharide (LPS) activation. MST adsorbed Cd(II), Hg(II), and Au(III) under conditions similar to those 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 TNFalpha secretion nor modulate LPS-induced TNFalpha 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 or metal compounds for therapeutic applications. PMID:16362965

  2. Synthesis and characterization of monosodium urate (MSU) nano particles

    NASA Astrophysics Data System (ADS)

    Tank, Nirali S.; Rathod, K. R.; Parekh, B. B.; Parikh, K. D.; Joshi, M. J.

    2016-05-01

    In Gout the deposition of crystals of Monosodium Urate (MSU) in various connective tissues and joints occurs, which is very painful with immflamation. The deposition likely to begin with nano particles form and expected to grow in to micro-paricles and hence it is important to synthesize and characrterize MSU nano-particles. The MSU nano particles were synthesized by wet chemical method using NaOH and uric acid (C5H4N4O3) and then characterized by powder XRD, TEM, FT-IR and thermal analysis. From the powder XRD the triclinic structure was found and 40 nm average particle size was estimated by using Scherrer's formula. From TEM the particle size was found to be in the range of 20 to 60 nm. The FT-IR spectrum for the MSU nano particles confirmed the presence of O-H stretching, N-H stretching, N-H rocking, C = O, C = C Enol or Keto and C = N vibrations. The thermal analysis was carried out from room temperature to 900°C. With comparison to the bulk MSU the thermal stability of MSU nano particles was slightly higher and 1.5 water molecules were found to be associated with MSU nano particles. Present results are compared with the bulk MSU.

  3. Monosodium Urate Crystal-Induced Chondrocyte Death via Autophagic Process

    PubMed Central

    Hwang, Hyun Sook; Yang, Chung Mi; Park, Su Jin; Kim, Hyun Ah

    2015-01-01

    Monosodium urate (MSU) crystals, which are highly precipitated in the joint cartilage, increase the production of cartilage-degrading enzymes and pro-inflammatory mediators in cartilage, thereby leading to gouty inflammation and joint damage. In this study, we investigated the effect of MSU crystals on the viability of human articular chondrocytes and the mechanism of MSU crystal-induced chondrocyte death. MSU crystals significantly decreased the viability of primary chondrocytes in a time- and dose-dependent manner. DNA fragmentation was observed in a culture medium of MSU crystal-treated chondrocytes, but not in cell lysates. MSU crystals did not activate caspase-3, a marker of apoptosis, compared with actinomycin D and TNF-α-treated cells. MSU crystals did not directly affect the expression of endoplasmic reticulum (ER) stress markers at the mRNA and protein levels. However, MSU crystals significantly increased the LC3-II level in a time-dependent manner, indicating autophagy activation. Moreover, MSU crystal-induced autophagy and subsequent chondrocyte death were significantly inhibited by 3-methyladenine, a blocker of autophagosomes formation. MSU crystals activated autophagy via inhibition of phosporylation of the Akt/mTOR signaling pathway. These results demonstrate that MSU crystals may cause the death of chondrocytes through the activation of the autophagic process rather than apoptosis or ER stress. PMID:26670233

  4. 21 CFR 582.4521 - Monosodium phosphate derivatives of mono- and diglycerides of edible fats or oils, or edible fat...

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... diglycerides of edible fats or oils, or edible fat-forming fatty acids. 582.4521 Section 582.4521 Food 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...

  5. 21 CFR 582.4521 - Monosodium phosphate derivatives of mono- and diglycerides of edible fats or oils, or edible fat...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... diglycerides of edible fats or oils, or edible fat-forming fatty acids. 582.4521 Section 582.4521 Food 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...

  6. 21 CFR 582.4521 - Monosodium phosphate derivatives of mono- and diglycerides of edible fats or oils, or edible fat...

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... diglycerides of edible fats or oils, or edible fat-forming fatty acids. 582.4521 Section 582.4521 Food 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...

  7. 21 CFR 582.4521 - Monosodium phosphate derivatives of mono- and diglycerides of edible fats or oils, or edible fat...

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... diglycerides of edible fats or oils, or edible fat-forming fatty acids. 582.4521 Section 582.4521 Food 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...

  8. 21 CFR 582.4521 - Monosodium phosphate derivatives of mono- and diglycerides of edible fats or oils, or edible fat...

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... diglycerides of edible fats or oils, or edible fat-forming fatty acids. 582.4521 Section 582.4521 Food 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...

  9. New insights into the bonding arrangements of L- and D-glutamates from solid state 17O NMR

    NASA Astrophysics Data System (ADS)

    Lemaitre, V.; Pike, K. J.; Watts, A.; Anupold, T.; Samoson, A.; Smith, M. E.; Dupree, R.

    2003-03-01

    Magic angle spinning (MAS) from L- and D-glutamic acid-HCl at 14.1 T produces highly structured and very similar NMR spectra. Lines from all 4 oxygen sites are readily distinguished and assigned. These 17O NMR spectra are very different from the previously reported 17O spectrum of the D, L-form presumably because that was a racemic crystal. 17O NMR from L-monosodium glutamate-HCl is very different again requiring the application of double angle rotation and 3 quantum MAS NMR to provide resolution of 5 different sites. Hence high resolution 17O solid state NMR techniques offer possible new insight into biochemical bonding processes.

  10. Gamma-aminobutyric acid production using immobilized glutamate decarboxylase followed by downstream processing with cation exchange chromatography.

    PubMed

    Lee, Seungwoon; Ahn, Jungoh; Kim, Yeon-Gu; Jung, Joon-Ki; Lee, Hongweon; Lee, Eun Gyo

    2013-01-01

    We have developed a gamma-aminobutyric acid (GABA) production technique using his-tag mediated immobilization of Escherichia coli-derived glutamate decarboxylase (GAD), an enzyme that catalyzes the conversion of glutamate to GABA. The GAD was obtained at 1.43 g/L from GAD-overexpressed E. coli fermentation and consisted of 59.7% monomer, 29.2% dimer and 2.3% tetramer with a 97.6% soluble form of the total GAD. The harvested GAD was immobilized to metal affinity gel with an immobilization yield of 92%. Based on an investigation of specific enzyme activity and reaction characteristics, glutamic acid (GA) was chosen over monosodium glutamate (MSG) as a substrate for immobilized GAD, resulting in conversion of 2.17 M GABA in a 1 L reactor within 100 min. The immobilized enzymes retained 58.1% of their initial activities after ten consecutive uses. By using cation exchange chromatography followed by enzymatic conversion, GABA was separated from the residual substrate and leached GAD. As a consequence, the glutamic acid was mostly removed with no detectable GAD, while 91.2% of GABA was yielded in the purification step. PMID:23322022

  11. 21 CFR 184.1521 - Monosodium phosphate derivatives of mono- and diglycerides.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Monosodium phosphate derivatives of mono- and diglycerides. 184.1521 Section 184.1521 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DIRECT FOOD SUBSTANCES AFFIRMED AS GENERALLY RECOGNIZED AS SAFE Listing of Specific Substances Affirmed as GRAS §...

  12. 21 CFR 184.1521 - Monosodium phosphate derivatives of mono- and diglycerides.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Monosodium phosphate derivatives of mono- and diglycerides. 184.1521 Section 184.1521 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION (CONTINUED) DIRECT FOOD SUBSTANCES AFFIRMED AS GENERALLY RECOGNIZED AS SAFE Listing...

  13. 75 FR 40824 - Monosodium methanearsonate (MSMA); Cancellation Order for Certain Pesticide Registrations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-14

    ... Federal Register notice (75 FR 17733; FRL-8819-2)announcing the Agency's receipt of the requests for... April 7, 2010 (75 FR 17733) (FRL-8819-2). The comment period closed on May 7, 2010. VI. Provisions for... AGENCY Monosodium methanearsonate (MSMA); Cancellation Order for Certain Pesticide Registrations...

  14. Growth and adhesion properties of monosodium urate monohydrate (MSU) crystals

    NASA Astrophysics Data System (ADS)

    Perrin, Clare M.

    The presence of monosodium urate monohydrate (MSU) crystals in the synovial fluid has long been associated with the joint disease gout. To elucidate the molecular level growth mechanism and adhesive properties of MSU crystals, atomic force microscopy (AFM), scanning electron microscopy, and dynamic light scattering (DLS) techniques were employed in the characterization of the (010) and (1-10) faces of MSU, as well as physiologically relevant solutions supersaturated with urate. Topographical AFM imaging of both MSU (010) and (1-10) revealed the presence of crystalline layers of urate arranged into v-shaped features of varying height. Growth rates were measured for both monolayers (elementary steps) and multiple layers (macrosteps) on both crystal faces under a wide range of urate supersaturation in physiologically relevant solutions. Step velocities for monolayers and multiple layers displayed a second order polynomial dependence on urate supersaturation on MSU (010) and (1-10), with step velocities on (1-10) generally half of those measured on MSU (010) in corresponding growth conditions. Perpendicular step velocities on MSU (010) were obtained and also showed a second order polynomial dependence of step velocity with respect to urate supersaturation, which implies a 2D-island nucleation growth mechanism for MSU (010). Extensive topographical imaging of MSU (010) showed island adsorption from urate growth solutions under all urate solution concentrations investigated, lending further support for the determined growth mechanism. Island sizes derived from DLS experiments on growth solutions were in agreement with those measured on MSU (010) topographical images. Chemical force microscopy (CFM) was utilized to characterize the adhesive properties of MSU (010) and (1-10). AFM probes functionalized with amino acid derivatives and bio-macromolecules found in the synovial fluid were brought into contact with both crystal faces and adhesion forces were tabulated into

  15. Metabotropic Glutamate Receptors

    PubMed Central

    Dillon, James; Franks, Christopher J.; Murray, Caitriona; Edwards, Richard J.; Calahorro, Fernando; Ishihara, Takeshi; Katsura, Isao; Holden-Dye, Lindy; O'Connor, Vincent

    2015-01-01

    Glutamatergic neurotransmission is evolutionarily conserved across animal phyla. A major class of glutamate receptors consists of the metabotropic glutamate receptors (mGluRs). In C. elegans, three mGluR genes, mgl-1, mgl-2, and mgl-3, are organized into three subgroups, similar to their mammalian counterparts. Cellular reporters identified expression of the mgls in the nervous system of C. elegans and overlapping expression in the pharyngeal microcircuit that controls pharyngeal muscle activity and feeding behavior. The overlapping expression of mgls within this circuit allowed the investigation of receptor signaling per se and in the context of receptor interactions within a neural network that regulates feeding. We utilized the pharmacological manipulation of neuronally regulated pumping of the pharyngeal muscle in the wild-type and mutants to investigate MGL function. This defined a net mgl-1-dependent inhibition of pharyngeal pumping that is modulated by mgl-3 excitation. Optogenetic activation of the pharyngeal glutamatergic inputs combined with electrophysiological recordings from the isolated pharyngeal preparations provided further evidence for a presynaptic mgl-1-dependent regulation of pharyngeal activity. Analysis of mgl-1, mgl-2, and mgl-3 mutant feeding behavior in the intact organism after acute food removal identified a significant role for mgl-1 in the regulation of an adaptive feeding response. Our data describe the molecular and cellular organization of mgl-1, mgl-2, and mgl-3. Pharmacological analysis identified that, in these paradigms, mgl-1 and mgl-3, but not mgl-2, can modulate the pharyngeal microcircuit. Behavioral analysis identified mgl-1 as a significant determinant of the glutamate-dependent modulation of feeding, further highlighting the significance of mGluRs in complex C. elegans behavior. PMID:25869139

  16. Pivotal Enzyme in Glutamate Metabolism of Poly-γ-Glutamate-Producing Microbes

    PubMed Central

    Ashiuchi, Makoto; Yamamoto, Takashi; Kamei, Tohru

    2013-01-01

    The extremely halophilic archaeon Natrialba aegyptiaca secretes the L-homo type of poly-γ-glutamate (PGA) as an extremolyte. We examined the enzymes involved in glutamate metabolism and verified the presence of L-glutamate dehydrogenases, L-aspartate aminotransferase, and L-glutamate synthase. However, neither glutamate racemase nor D-amino acid aminotransferase activity was detected, suggesting the absence of sources of D-glutamate. In contrast, D-glutamate-rich PGA producers mostly possess such intracellular sources of D-glutamate. The results of our present study indicate that the D-glutamate-anabolic enzyme “glutamate racemase” is pivotal in the biosynthesis of PGA. PMID:25371338

  17. Glutamic acid as anticancer agent: An overview

    PubMed Central

    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. 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. PMID:24227952

  18. Computational Studies of Glutamate Transporters

    PubMed Central

    Setiadi, Jeffry; Heinzelmann, Germano; Kuyucak, Serdar

    2015-01-01

    Glutamate is the major excitatory neurotransmitter in the human brain whose binding to receptors on neurons excites them while excess glutamate are removed from synapses via transporter proteins. Determination of the crystal structures of bacterial aspartate transporters has paved the way for computational investigation of their function and dynamics at the molecular level. Here, we review molecular dynamics and free energy calculation methods used in these computational studies and discuss the recent applications to glutamate transporters. The focus of the review is on the insights gained on the transport mechanism through computational methods, which otherwise is not directly accessible by experimental probes. Recent efforts to model the mammalian glutamate and other amino acid transporters, whose crystal structures have not been solved yet, are included in the review. PMID:26569328

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

    PubMed

    Huang, Yan; Su, Lingqia; Wu, Jing

    2016-01-01

    Glutamate decarboxylase (GAD) catalyzes the irreversible decarboxylation of L-glutamate to the valuable food supplement γ-aminobutyric acid (GABA). In this study, GAD from Escherichia coli K12, a pyridoxal phosphate (PLP)-dependent enzyme, was overexpressed in E. coli. The GAD produced in media supplemented with 0.05 mM soluble vitamin B6 analog pyridoxine hydrochloride (GAD-V) activity was 154.8 U mL-1, 1.8-fold higher than that of GAD obtained without supplementation (GAD-C). Purified GAD-V exhibited increased activity (193.4 U mg-1, 1.5-fold higher than that of GAD-C), superior thermostability (2.8-fold greater than that of GAD-C), and higher kcat/Km (1.6-fold higher than that of GAD-C). Under optimal conditions in reactions mixtures lacking added PLP, crude GAD-V converted 500 g L-1 monosodium glutamate (MSG) to GABA with a yield of 100%, and 750 g L-1 MSG with a yield of 88.7%. These results establish the utility of pyridoxine supplementation and lay the foundation for large-scale enzymatic production of GABA. PMID:27438707

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

    PubMed Central

    Huang, Yan; Su, Lingqia; Wu, Jing

    2016-01-01

    Glutamate decarboxylase (GAD) catalyzes the irreversible decarboxylation of L-glutamate to the valuable food supplement γ-aminobutyric acid (GABA). In this study, GAD from Escherichia coli K12, a pyridoxal phosphate (PLP)-dependent enzyme, was overexpressed in E. coli. The GAD produced in media supplemented with 0.05 mM soluble vitamin B6 analog pyridoxine hydrochloride (GAD-V) activity was 154.8 U mL-1, 1.8-fold higher than that of GAD obtained without supplementation (GAD-C). Purified GAD-V exhibited increased activity (193.4 U mg-1, 1.5-fold higher than that of GAD-C), superior thermostability (2.8-fold greater than that of GAD-C), and higher kcat/Km (1.6-fold higher than that of GAD-C). Under optimal conditions in reactions mixtures lacking added PLP, crude GAD-V converted 500 g L-1 monosodium glutamate (MSG) to GABA with a yield of 100%, and 750 g L-1 MSG with a yield of 88.7%. These results establish the utility of pyridoxine supplementation and lay the foundation for large-scale enzymatic production of GABA. PMID:27438707

  1. ANALYSIS OF HARRELL MONOSODIUM TITANATE LOT #s 46000606120, 46000722120, AND 46000808120

    SciTech Connect

    Taylor-Pashow, K.

    2012-10-08

    Monosodium titanate (MST) for use in the Actinide Removal Process (ARP) must be qualified and verified in advance. A single qualification sample for each batch of material is sent to SRNL for analysis, as well as a statistical sampling of verification samples. The Harrell Industries Lot #s 46000706120, 46000722120, and 460008081120 qualification and verification samples met each of the selected specification requirements that were tested with the exception of a few pails being marginally below the lower weight percent solids limit. These deviations from the specifications are viewed as negligible since the corresponding density of the slurries indicates no appreciable shortage of MST solids. Therefore, SRNL recommends acceptance and use of these pails.

  2. SORPTION BEHAVIOR OF MONOSODIUM TITANATE AND AMORPHOUS PEROXOTITANATE MATERIALS UNDER WEAKLY ACIDIC CONDITIONS

    SciTech Connect

    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.

  3. Glutamate receptors at atomic resolution

    SciTech Connect

    Mayer, Mark L.

    2010-12-03

    At synapses throughout the brain and spinal cord, the amino-acid glutamate is the major excitatory neurotransmitter. During evolution, a family of glutamate-receptor ion channels seems to have been assembled from a kit consisting of discrete ligand-binding, ion-channel, modulatory and cytoplasmic domains. Crystallographic studies that exploit this unique architecture have greatly aided structural analysis of the ligand-binding core, but the results also pose a formidable challenge, namely that of resolving the allosteric mechanisms by which individual domains communicate and function in an intact receptor.

  4. Glutamate in peripheral organs: Biology and pharmacology.

    PubMed

    Du, Jie; Li, Xiao-Hui; Li, Yuan-Jian

    2016-08-01

    Glutamate is a versatile molecule existing in both the central nervous system and peripheral organs. Previous studies have mainly focussed on the biological effect of glutamate in the brain. Recently, abundant evidence has demonstrated that glutamate also participates in the regulation of physiopathological functions in peripheral tissues, including the lung, kidney, liver, heart, stomach and immune system, where the glutamate/glutamate receptor/glutamate transporter system plays an important role in the pathogenesis of certain diseases, such as myocardial ischaemia/reperfusion injury and acute gastric mucosa injury. All these findings provide new insight into the biology and pharmacology of glutamate and suggest a potential therapeutic role of glutamate in non-neurological diseases. PMID:27164423

  5. 21 CFR 182.1045 - Glutamic acid.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 3 2013-04-01 2013-04-01 false 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) (c) Limitations, restrictions, or explanation....

  6. 21 CFR 182.1045 - Glutamic acid.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 3 2011-04-01 2011-04-01 false 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) (c) Limitations, restrictions, or explanation....

  7. 21 CFR 182.1045 - Glutamic acid.

    Code of Federal Regulations, 2010 CFR

    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) (c) Limitations, restrictions, or explanation....

  8. 21 CFR 182.1045 - Glutamic acid.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 3 2012-04-01 2012-04-01 false 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) (c) Limitations, restrictions, or explanation....

  9. 21 CFR 182.1045 - Glutamic acid.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Glutamic acid. 182.1045 Section 182.1045 Food and... GENERALLY RECOGNIZED AS SAFE Multiple Purpose GRAS Food Substances § 182.1045 Glutamic acid. (a) Product. Glutamic acid. (b) (c) Limitations, restrictions, or explanation. This substance is generally recognized...

  10. Modes of glutamate receptor gating

    PubMed Central

    Popescu, Gabriela K

    2012-01-01

    Abstract The time course of excitatory synaptic currents, the major means of fast communication between neurons of the central nervous system, is encoded in the dynamic behaviour of post-synaptic glutamate-activated channels. First-pass attempts to explain the glutamate-elicited currents with mathematical models produced reaction mechanisms that included only the most basic functionally defined states: resting vs. liganded, closed vs. open, responsive vs. desensitized. In contrast, single-molecule observations afforded by the patch-clamp technique revealed an unanticipated kinetic multiplicity of transitions: from microseconds-lasting flickers to minutes-long modes. How these kinetically defined events impact the shape of the synaptic response, how they relate to rearrangements in receptor structure, and whether and how they are physiologically controlled represent currently active research directions. Modal gating, which refers to the slowest, least frequently observed ion-channel transitions, has been demonstrated for representatives of all ion channel families. However, reaction schemes have been largely confined to the short- and medium-range time scales. For glutamate receptors as well, modal gating has only recently come under rigorous scrutiny. This article reviews the evidence for modal gating of glutamate receptors and the still developing hypotheses about the mechanism(s) by which modal shifts occur and the ways in which they may impact the time course of synaptic transmission. PMID:22106181

  11. Fluorescence imaging of glutamate release in neurons

    SciTech Connect

    Wang, Ziqiang; Yeung, Edward S.

    1999-12-01

    A noninvasive detection scheme based on glutamate dehydrogenase (GDH) enzymatic assay combined with microscopy was developed to measure the glutamate release in cultured cells from the central nervous system (CNS). The enzyme reaction is very specific and sensitive. The detection limit with charge-coupled device (CCD) imaging is down to {mu}M levels of glutamate with reasonable response time ({approx}30 s). The standard glutamate test shows a linear response over 3 orders of magnitude, from {mu}M to 0.1 mM range. The in vitro monitoring of glutamate release from cultured neuron cells demonstrated excellent spatial and temporal resolution. (c) 1999 Society for Applied Spectroscopy.

  12. Nonvesicular Release of Glutamate by Glial xCT Transporters Suppresses Glutamate Receptor Clustering In Vivo

    PubMed Central

    Augustin, Hrvoje; Grosjean, Yael; Chen, Kaiyun; Sheng, Qi; Featherstone, David E.

    2008-01-01

    We hypothesized that cystine/glutamate transporters (xCTs) might be critical regulators of ambient extracellular glutamate levels in the nervous system and that misregulation of this glutamate pool might have important neurophysiological and/or behavioral consequences. To test this idea, we identified and functionally characterized a novel Drosophila xCT gene, which we subsequently named “genderblind” (gb). Genderblind is expressed in a previously overlooked subset of peripheral and central glia. Genetic elimination of gb causes a 50% reduction in extracellular glutamate concentration, demonstrating that xCT transporters are important regulators of extracellular glutamate. Consistent with previous studies showing that extracellular glutamate regulates postsynaptic glutamate receptor clustering, gb mutants show a large (200–300%) increase in the number of postsynaptic glutamate receptors. This increase in postsynaptic receptor abundance is not accompanied by other obvious synaptic changes and is completely rescued when synapses are cultured in wild-type levels of glutamate. Additional in situ pharmacology suggests that glutamate-mediated suppression of glutamate receptor clustering depends on receptor desensitization. Together, our results suggest that (1) xCT transporters are critical for regulation of ambient extracellular glutamate in vivo; (2) ambient extracellular glutamate maintains some receptors constitutively desensitized in vivo; and (3) constitutive desensitization of ionotropic glutamate receptors suppresses their ability to cluster at synapses. PMID:17202478

  13. Ligands for Ionotropic Glutamate Receptors

    NASA Astrophysics Data System (ADS)

    Swanson, Geoffrey T.; Sakai, Ryuichi

    Marine-derived small molecules and peptides have played a central role in elaborating pharmacological specificities and neuronal functions of mammalian ionotropic glutamate receptors (iGluRs), the primary mediators of excitatory syn-aptic transmission in the central nervous system (CNS). As well, the pathological sequelae elicited by one class of compounds (the kainoids) constitute a widely-used animal model for human mesial temporal lobe epilepsy (mTLE). New and existing molecules could prove useful as lead compounds for the development of therapeutics for neuropathologies that have aberrant glutamatergic signaling as a central component. In this chapter we discuss natural source origins and pharmacological activities of those marine compounds that target ionotropic glutamate receptors.

  14. Physiological roles of dietary glutamate signaling via gut-brain axis due to efficient digestion and absorption.

    PubMed

    Torii, Kunio; Uneyama, Hisayuki; Nakamura, Eiji

    2013-04-01

    Dietary glutamate (Glu) stimulates to evoke the umami taste, one of the five basic tastes, enhancing food palatability. But it is also the main gut energy source for the absorption and metabolism for each nutrient, thus, only a trace amount of Glu reaches the general circulation. Recently, we demonstrated a unique gut sensing system for free Glu (glutamate signaling). Glu is the only nutrient among amino acids, sugars and electrolytes that activates rat gastric vagal afferents from the luminal side specifically via metabotropic Glu receptors type 1 on mucosal cells releasing mucin and nitrite mono-oxide (NO), then NO stimulates serotonin (5HT) release at the enterochromaffin cell. Finally released 5HT stimulates 5HT3 receptor at the nerve end of the vagal afferent fiber. Functional magnetic resonance imaging (f-MRI, 4.7 T) analysis revealed that luminal sensing with 1 % (w/v) monosodium L-glutamate (MSG) in rat stomach activates both the medial preoptic area (body temperature controller) and the dorsomedial hypothalamus (basic metabolic regulator), resulting in diet-induced thermogenesis during mealing without changes of appetite for food. Interestingly, rats were forced to eat a high fat and high sugar diet with free access to 1 % (w/w) MSG and water in a choice paradigm and showed the strong preference for the MSG solution and subsequently, they displayed lower fat deposition, weight gain and blood leptin. On the other hand, these brain functional changes by the f-MRI signal after 60 mM MSG intubation into the stomach was abolished in the case of total vagotomized rats, suggesting that luminal glutamate signaling contributes to control digestion and thermogenesis without obesity. PMID:23463402

  15. Strontium and Actinide Separations from High Level Nuclear Waste Solutions using Monosodium Titanate - Actual Waste Testing

    SciTech Connect

    Peters, T.B.; Barnes, M.J.; Hobbs,D.T.; Walker, D.D.; Fondeur, F.F.; Norato, M.A.; Pulmano, R.L.; Fink, S.D.

    2005-11-01

    Pretreatment processes at the Savannah River Site will separate {sup 90}Sr, alpha-emitting and radionuclides (i.e., actinides) and {sup 137}Cs prior to disposal of the high-level nuclear waste. Separation of {sup 90}Sr and alpha-emitting radionuclides occurs by ion exchange/adsorption using an inorganic material, monosodium titanate (MST). Previously reported testing with simulants indicates that the MST exhibits high selectivity for strontium and actinides in high ionic strength and strongly alkaline salt solutions. This paper provides a summary of data acquired to measure the performance of MST to remove strontium and actinides from actual waste solutions. These tests evaluated the effects of ionic strength, mixing, elevated alpha activities, and multiple contacts of the waste with MST. Tests also provided confirmation that MST performs well at much larger laboratory scales (300-700 times larger) and exhibits little affinity for desorption of strontium and plutonium during washing.

  16. Arsenic levels in blood, urine, and hair of workers applying monosodium methanearsonate (MSMA)

    SciTech Connect

    Abdelghani, A.A.; Anderson, A.C.; Jaghabir, M.; Mather, F.

    1986-05-01

    Uptake and excretion of total arsenic from monosodium methanearsonate (MSMA) in workers who applied the herbicide was followed during the spraying season. Urine, blood, and hair samples were collected and air samples were taken from the workers' breathing zone. Arsenic concentrations in air samples ranged from 0.001-1.086 micrograms/m3. Blood and urine arsenic values ranged from 0.0-0.2 mg/L and 0.002-1.725 mg/L, respectively. The geometric mean arsenic concentration in urine increased during the week but returned to base levels on weekends. Hair arsenic concentrations ranged from 0.02-358.0 mg/kg, increased during the spraying season, and returned to pre-season levels once herbicide application ceased. Three workers had higher than normal pre-exposure hair values. However, only one of the three workers had consistently above normal values throughout the study period.

  17. Chronic effects of arsenic on American red crayfish, Procambarus clarkii, exposed to monosodium methanearsonate (MSMA) herbicide

    SciTech Connect

    Naqvi, S.M. ); Flagge, C.T. )

    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.

  18. CHARACTERIZATION OF MODIFIED MONOSODIUM TITANATE - AN IMPROVED SORBENT FOR STRONTIUM AND ACTINIDE SEPARATIONS

    SciTech Connect

    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.

  19. The glutamate homeostasis hypothesis of addiction.

    PubMed

    Kalivas, Peter W

    2009-08-01

    Addiction is associated with neuroplasticity in the corticostriatal brain circuitry that is important for guiding adaptive behaviour. The hierarchy of corticostriatal information processing that normally permits the prefrontal cortex to regulate reinforcement-seeking behaviours is impaired by chronic drug use. A failure of the prefrontal cortex to control drug-seeking behaviours can be linked to an enduring imbalance between synaptic and non-synaptic glutamate, termed glutamate homeostasis. The imbalance in glutamate homeostasis engenders changes in neuroplasticity that impair communication between the prefrontal cortex and the nucleus accumbens. Some of these pathological changes are amenable to new glutamate- and neuroplasticity-based pharmacotherapies for treating addiction. PMID:19571793

  20. Novel flavours paired with glutamate condition increased intake in older adults in the absence of changes in liking.

    PubMed

    Dermiki, Maria; Prescott, John; Sargent, Laura J; Willway, Joanne; Gosney, Margot A; Methven, Lisa

    2015-07-01

    Previous research on the repeat exposure to a novel flavour combined with monosodium glutamate (MSG) has shown an increase in liking and consumption for the particular flavour. The aim of the current work was to investigate whether this could also be observed in the case of older people, since they are most affected by undernutrition in the developed world and ways to increase consumption of food are of significant importance for this particular age group. For this study, 40 older adults (age 65-88) repeatedly consumed potato soup with two novel flavours (lemongrass and cumin) which were either with or without a high level of MSG (5% w/w). A randomized single blind within-subject design was implemented, where each participant was exposed to both soup flavours three times over 6 days, with one of the soup flavours containing MSG. After three repeat exposures, consumption increased significantly for the soups where the flavours had contained MSG during the repeated exposure (mean weight consumed increased from 123 to 164 g, p = 0.017), implying that glutamate conditioned for increased wanting and consumption, despite the fact that the liking for the soup had not increased. PMID:25754148

  1. Insulin-regulated aminopeptidase in adipocyte is Cys-specific and affected by obesity.

    PubMed

    Alponti, Rafaela Fadoni; Viana, Luciana Godoy; Yamanouye, Norma; Silveira, Paulo Flavio

    2015-08-01

    Insulin-regulated aminopeptidase (IRAP, EC 3.4.11.3) in adipocytes is well known to traffic between high (HDM) and low (LDM) density microsomal fractions toward the plasma membrane (MF) under stimulation by insulin. However, its catalytic preference for aminoacyl substrates with N-terminal Leu or Cys is controversial. Furthermore, possible changes in its traffic under metabolic challenges are unknown. The present study investigated the catalytic activity attributable to EC 3.4.11.3 in HDM, LDM and MF from isolated adipocytes of healthy (C), food deprived (FD) and monosodium glutamate (MSG) obese rats on aminoacyl substrates with N-terminal Cys or Leu, in absence or presence of insulin. Efficacy and reproducibility of subcellular adipocyte fractionation procedure were demonstrated. Comparison among HDM vs LDM vs MF intragroup revealed that hydrolytic activity trafficking from LDM to MF under influence of insulin in C, MSG and FD is only on N-terminal Cys. In MSG the same pattern of anterograde traffic and aminoacyl preference occurred independently of insulin stimulation. The pathophysiological significance of IRAP in adipocytes seems to be linked to comprehensive energy metabolism related roles of endogenous substrates with N-terminal cysteine pair such as vasopressin and oxytocin. PMID:25999180

  2. Synaptic Glutamate Spillover Due to Impaired Glutamate Uptake Mediates Heroin Relapse

    PubMed Central

    Scofield, Michael D.; Boger, Heather; Hensley, Megan; Kalivas, Peter W.

    2014-01-01

    Reducing the enduring vulnerability to relapse is a therapeutic goal in treating drug addiction. Studies with animal models of drug addiction show a marked increase in extrasynaptic glutamate in the core subcompartment of the nucleus accumbens (NAcore) during reinstated drug seeking. However, the synaptic mechanisms linking drug-induced changes in extrasynaptic glutamate to relapse are poorly understood. Here, we discovered impaired glutamate elimination in rats extinguished from heroin self-administration that leads to spillover of synaptically released glutamate into the nonsynaptic extracellular space in NAcore and investigated whether restoration of glutamate transport prevented reinstated heroin seeking. Through multiple functional assays of glutamate uptake and analyzing NMDA receptor-mediated currents, we show that heroin self-administration produced long-lasting downregulation of glutamate uptake and surface expression of the transporter GLT-1. This downregulation was associated with spillover of synaptic glutamate to extrasynaptic NMDA receptors within the NAcore. Ceftriaxone restored glutamate uptake and prevented synaptic glutamate spillover and cue-induced heroin seeking. Ceftriaxone-induced inhibition of reinstated heroin seeking was blocked by morpholino-antisense targeting GLT-1 synthesis. These data reveal that the synaptic glutamate spillover in the NAcore results from reduced glutamate transport and is a critical pathophysiological mechanism underling reinstated drug seeking in rats extinguished from heroin self-administration. PMID:24741055

  3. Regional brain glutamate transport in rats at normal and raised concentrations of circulating glutamate.

    PubMed

    Hawkins, R A; DeJoseph, M R; Hawkins, P A

    1995-08-01

    The permeability of the blood-brain barrier to glutamate was measured by quantitative autoradiography in brains of control rats (average plasma glutamate concentration of 95 microns) and rats infused with glutamate (average plasma glutamate concentration of 837 microns). Measurements of glutamate permeability were initiated by the injection of [14C]glutamate and stopped at 1 min to avoid the accumulation of [14C]glutamate metabolites. Glutamate entered the brain at a slow rate, with an average permeability-surface area product of 7 microliters.min-g-1, except in those areas known to have fenestrated capillaries. Glutamate accumulated in the choroid plexus of ventricles, but did not seem to enter the cerebrospinal fluid in detectable amounts regardless of the circulating concentration. Glutamate accumulated in circumventricular organs, such as the median eminence, where the radioactivity was localized without detectable spread. Infusion of glutamate to create high plasma concentrations did not result in greater spread of [14C]glutamate beyond the immediate vicinity of the circumventricular organs. PMID:7648616

  4. Conversion of agroindustrial residues for high poly(γ-glutamic acid) production by Bacillus subtilis NX-2 via solid-state fermentation.

    PubMed

    Tang, Bao; Xu, Hong; Xu, Zongqi; Xu, Cen; Xu, Zheng; Lei, Peng; Qiu, Yibin; Liang, Jinfeng; Feng, Xiaohai

    2015-04-01

    Poly(γ-glutamic acid) (γ-PGA) production by Bacillus subtilis NX-2 was carried out through solid-state fermentation with dry mushroom residues (DMR) and monosodium glutamate production residues (MGPR; a substitute of glutamate) for the first time. Dry shiitake mushroom residue (DSMR) was found to be the most suitable solid substrate among these DMRs; the optimal DSMR-to-MGPR ratio was optimized as 12:8. To increase γ-PGA production, industrial waste glycerol was added as a carbon source supplement to the solid-state medium. As a result, γ-PGA production increased by 34.8%. The batch fermentation obtained an outcome of 115.6 g kg(-1) γ-PGA and 39.5×10(8) colony forming units g(-1) cells. Furthermore, a satisfactory yield of 107.7 g kg(-1) γ-PGA was achieved by compost experiment on a scale of 50 kg in open air, indicating that economically large-scale γ-PGA production was feasible. Therefore, this study provided a novel method to produce γ-PGA from abundant and low-cost agroindustrial residues. PMID:25670398

  5. Glutamate: Tastant and Neuromodulator in Taste Buds.

    PubMed

    Vandenbeuch, Aurelie; Kinnamon, Sue C

    2016-07-01

    In taste buds, glutamate plays a double role as a gustatory stimulus and neuromodulator. The detection of glutamate as a tastant involves several G protein-coupled receptors, including the heterodimer taste receptor type 1, member 1 and 3 as well as metabotropic glutamate receptors (mGluR1 and mGluR4). Both receptor types participate in the detection of glutamate as shown with knockout animals and selective antagonists. At the basal part of taste buds, ionotropic glutamate receptors [N-methyl-d-aspartate (NMDA) and non-NMDA] are expressed and participate in the modulation of the taste signal before its transmission to the brain. Evidence suggests that glutamate has an efferent function on taste cells and modulates the release of other neurotransmitters such as serotonin and ATP. This short article reviews the recent developments in the field with regard to glutamate receptors involved in both functions as well as the influence of glutamate on the taste signal. PMID:27422519

  6. Glutamate Transporter-Mediated Glutamate Secretion in the Mammalian Pineal Gland

    PubMed Central

    Kim, Mean-Hwan; Uehara, Shunsuke; Muroyama, Akiko; Hille, Bertil; Moriyama, Yoshinori; Koh, Duk-Su

    2008-01-01

    Glutamate transporters are expressed throughout the central nervous system where their major role is to clear released glutamate from presynaptic terminals. Here we report a novel function of the transporter in rat pinealocytes. This electrogenic transporter conducted inward current in response to L-glutamate and L- or D-aspartate and depolarized the membrane in patch clamp experiments. Ca2+ imaging demonstrated that the transporter-mediated depolarization induced a significant Ca2+ influx through voltage-gated Ca2+ channels. The Ca2+ rise finally evoked glutamate exocytosis as detected by carbon-fiber amperometry and by high-performance liquid chromatography. In pineal slices with densely packed pinealocytes, glutamate released from the cells effectively activated glutamate transporters in neighboring cells. The Ca2+ signal generated by KCl depolarization or acetylcholine propagated through several cell layers by virtue of the regenerative ‘glutamate-induced glutamate release’. Therefore we suggest that glutamate transporters mediate synchronized elevation of L-glutamate and thereby efficiently down-regulate melatonin secretion via previously identified inhibitory metabotropic glutamate receptors in the pineal gland. PMID:18945893

  7. Glutamate Racemase Mutants of Bacillus anthracis

    PubMed Central

    Oh, So-Young; Richter, Stefan G.; Missiakas, Dominique M.

    2015-01-01

    ABSTRACT d-Glutamate is an essential component of bacterial peptidoglycan and a building block of the poly-γ-d-glutamic acid (PDGA) capsule of Bacillus anthracis, the causative agent of anthrax. Earlier work suggested that two glutamate racemases, encoded by racE1 and racE2, are each essential for growth of B. anthracis, supplying d-glutamic acid for the synthesis of peptidoglycan and PDGA capsule. Earlier work could not explain, however, why two enzymes that catalyze the same reaction may be needed for bacterial growth. Here, we report that deletion of racE1 or racE2 did not prevent growth of B. anthracis Sterne (pXO1+ pXO2−), the noncapsulating vaccine strain, or of B. anthracis Ames (pXO1+ pXO2+), a fully virulent, capsulating isolate. While mutants with deletions in racE1 and racE2 were not viable, racE2 deletion delayed vegetative growth of B. anthracis following spore germination and caused aberrant cell shapes, phenotypes that were partially restored by exogenous d-glutamate. Deletion of racE1 or racE2 from B. anthracis Ames did not affect the production or stereochemical composition of the PDGA capsule. A model is presented whereby B. anthracis, similar to Bacillus subtilis, utilizes two functionally redundant racemase enzymes to synthesize d-glutamic acid for peptidoglycan synthesis. IMPORTANCE Glutamate racemases, enzymes that convert l-glutamate to d-glutamate, are targeted for antibiotic development. Glutamate racemase inhibitors may be useful for the treatment of bacterial infections such as anthrax, where the causative agent, B. anthracis, requires d-glutamate for the synthesis of peptidoglycan and poly-γ-d-glutamic acid (PDGA) capsule. Here we show that B. anthracis possesses two glutamate racemase genes that can be deleted without abolishing either bacterial growth or PDGA synthesis. These data indicate that drug candidates must inhibit both glutamate racemases, RacE1 and RacE2, in order to block B. anthracis growth and achieve therapeutic

  8. Glutamate-gated Chloride Channels*

    PubMed Central

    Wolstenholme, Adrian J.

    2012-01-01

    Glutamate-gated chloride channels (GluCls) are found only in protostome invertebrate phyla but are closely related to mammalian glycine receptors. They have a number of roles in these animals, controlling locomotion and feeding and mediating sensory inputs into behavior. In nematodes and arthropods, they are targeted by the macrocyclic lactone family of anthelmintics and pesticides, making the GluCls of considerable medical and economic importance. Recently, the three-dimensional structure of a GluCl was solved, the first for any eukaryotic ligand-gated anion channel, revealing a macrocyclic lactone-binding site between the channel domains of adjacent subunits. This minireview will highlight some unique features of the GluCls and illustrate their contribution to our knowledge of the entire Cys loop ligand-gated ion channel superfamily. PMID:23038250

  9. Different pools of glutamate receptors mediate sensitivity to ambient glutamate in the cochlear nucleus

    PubMed Central

    Yang, Yang

    2015-01-01

    Ambient glutamate plays an important role in pathological conditions, such as stroke, but its role during normal activity is not clear. In addition, it is not clear how ambient glutamate acts on glutamate receptors with varying affinities or subcellular localizations. To address this, we studied “endbulb of Held” synapses, which are formed by auditory nerve fibers onto bushy cells (BCs) in the anteroventral cochlear nucleus. When ambient glutamate was increased by applying the glutamate reuptake inhibitor TFB-TBOA, BCs depolarized as a result of activation of N-methyl-d-aspartate receptors (NMDARs) and group I metabotropic glutamate receptors (mGluRs). Application of antagonists against NMDARs (in 0 Mg2+) or mGluRs caused hyperpolarization, indicating that these receptors were bound by a tonic source of glutamate. AMPA receptors did not show these effects, consistent with their lower glutamate affinity. We also evaluated the subcellular localization of the receptors activated by ambient glutamate. The mGluRs were not activated by synaptic stimulation and thus appear to be exclusively extrasynaptic. By contrast, NMDARs in both synaptic and extrasynaptic compartments were activated by ambient glutamate, as shown using the use-dependent antagonist MK-801. Levels of ambient glutamate appeared to be regulated in a spike-independent manner, and glia likely play a major role. These low levels of ambient glutamate likely have functional consequences, as even low concentrations of TBOA caused significant increases in BC spiking following synaptic stimulation. These results indicate that normal resting potential appears to be poised in the region of maximal sensitivity to small changes in ambient glutamate. PMID:25855696

  10. Different pools of glutamate receptors mediate sensitivity to ambient glutamate in the cochlear nucleus.

    PubMed

    Yang, Yang; Xu-Friedman, Matthew A

    2015-06-01

    Ambient glutamate plays an important role in pathological conditions, such as stroke, but its role during normal activity is not clear. In addition, it is not clear how ambient glutamate acts on glutamate receptors with varying affinities or subcellular localizations. To address this, we studied "endbulb of Held" synapses, which are formed by auditory nerve fibers onto bushy cells (BCs) in the anteroventral cochlear nucleus. When ambient glutamate was increased by applying the glutamate reuptake inhibitor TFB-TBOA, BCs depolarized as a result of activation of N-methyl-D-aspartate receptors (NMDARs) and group I metabotropic glutamate receptors (mGluRs). Application of antagonists against NMDARs (in 0 Mg(2+)) or mGluRs caused hyperpolarization, indicating that these receptors were bound by a tonic source of glutamate. AMPA receptors did not show these effects, consistent with their lower glutamate affinity. We also evaluated the subcellular localization of the receptors activated by ambient glutamate. The mGluRs were not activated by synaptic stimulation and thus appear to be exclusively extrasynaptic. By contrast, NMDARs in both synaptic and extrasynaptic compartments were activated by ambient glutamate, as shown using the use-dependent antagonist MK-801. Levels of ambient glutamate appeared to be regulated in a spike-independent manner, and glia likely play a major role. These low levels of ambient glutamate likely have functional consequences, as even low concentrations of TBOA caused significant increases in BC spiking following synaptic stimulation. These results indicate that normal resting potential appears to be poised in the region of maximal sensitivity to small changes in ambient glutamate. PMID:25855696

  11. The effects of intra-articular resiniferatoxin on monosodium iodoacetate-induced osteoarthritic pain in rats

    PubMed Central

    Kim, Youngkyung; Kim, Eun-hye; Lee, Kyu Sang; Lee, Koeun; Park, Sung Ho; Na, Sook Hyun; Ko, Cheolwoong; Yooon, Young Wook

    2016-01-01

    This study was performed to investigate whether an intra-articular injection of transient receptor potential vanilloid 1 (TRPV1) receptor agonist, resiniferatoxin (RTX) would alleviate behavioral signs of arthritic pain in a rat model of osteoarthritis (OA). We also sought to determine the effect of RTX treatment on calcitonin gene-related peptide (CGRP) expression in the spinal cord. Knee joint inflammation was induced by intra-articular injection of monosodium iodoacetate (MIA, 8 mg/50 µl) and weight bearing percentage on right and left hindpaws during walking, paw withdrawal threshold to mechanical stimulation, and paw withdrawal latency to heat were measured to evaluate pain behavior. Intra-articular administration of RTX (0.03, 0.003 and 0.0003%) at 2 weeks after the induction of knee joint inflammation significantly improved reduction of weight bearing on the ipsilateral hindlimb and increased paw withdrawal sensitivity to mechanical and heat stimuli. The reduction of pain behavior persisted for 3~10 days according to each behavioral test. The MIA-induced increase in CGRP immunoreactivity in the spinal cord was decreased by RTX treatment in a dose-dependent manner. The present study demonstrated that a single intra-articular administration of RTX reduced pain behaviors for a relatively long time in an experimental model of OA and could normalize OA-associated changes in peptide expression in the spinal cord. PMID:26807032

  12. REVIEW OF EXPERIMENTAL STUDIES INVESTIGATING THE RATE OF STRONTIUM AND ACTINIDE ADSORPTION BY MONOSODIUM TITANATE

    SciTech Connect

    Hobbs, D.

    2010-10-01

    A number of laboratory studies have been conducted to determine the influence of mixing and mixing intensity, solution ionic strength, initial sorbate concentrations, temperature, and monosodium titanate (MST) concentration on the rates of sorbate removal by MST in high-level nuclear waste solutions. Of these parameters, initial sorbate concentrations, ionic strength, and MST concentration have the greater impact on sorbate removal rates. The lack of a significant influence of mixing and mixing intensity on sorbate removal rates indicates that bulk solution transport is not the rate controlling step in the removal of strontium and actinides over the range of conditions and laboratory-scales investigated. However, bulk solution transport may be a significant parameter upon use of MST in a 1.3 million-gallon waste tank such as that planned for the Small Column Ion Exchange (SCIX) program. Thus, Savannah River National Laboratory (SRNL) recommends completing the experiments in progress to determine if mixing intensity influences sorption rates under conditions appropriate for this program. Adsorption models have been developed from these experimental studies that allow prediction of strontium (Sr), plutonium (Pu), neptunium (Np) and uranium (U) concentrations as a function of contact time with MST. Fairly good agreement has been observed between the predicted and measured sorbate concentrations in the laboratory-scale experiments.

  13. Effect of monosodium methanarsonate application on cuticle wax content of cocklebur and cotton plants.

    PubMed

    Keese, Renee J; Camper, N Dwight

    2006-01-01

    Leaf cuticle waxes were extracted from monosodium methanearsonate (MSMA)-resistant (R) and -susceptible (S) common cocklebur (Xanthium strumarium L.) and cotton (Gossypium hirsutum L.) plants at 0, 3, 5, and 7 days after treatment (DAT) following 1x and 2x MSMA applications. Wax constituents were analyzed by gas chromatography (GC) with flame ionization detection and compared to alkane and alcohol standards of carbon lengths varying from C21 to C30. Differences in waxes were calculated and reported as change per ng mm2-1. Tricosane (C23) was found to increase following MSMA applications. All other alkanes decreased by 7 DAT, with some showing a linear effect over time in the R-cocklebur. Alcohol constituents were also observed to decrease by 7 DAT. Total arsenic in the extracted wax fraction was determined, with greatest quantities detected in the R-cocklebur. Wax changes are not believed to play a role in cotton tolerance, since changes in cuticle concentrations were minimal. Cocklebur resistance to MSMA is not due to cuticle constituents; the wax changes are a secondary effect in response to herbicide application. PMID:16893783

  14. The effects of intra-articular resiniferatoxin on monosodium iodoacetate-induced osteoarthritic pain in rats.

    PubMed

    Kim, Youngkyung; Kim, Eun-Hye; Lee, Kyu Sang; Lee, Koeun; Park, Sung Ho; Na, Sook Hyun; Ko, Cheolwoong; Kim, Junesun; Yooon, Young Wook

    2016-01-01

    This study was performed to investigate whether an intra-articular injection of transient receptor potential vanilloid 1 (TRPV1) receptor agonist, resiniferatoxin (RTX) would alleviate behavioral signs of arthritic pain in a rat model of osteoarthritis (OA). We also sought to determine the effect of RTX treatment on calcitonin gene-related peptide (CGRP) expression in the spinal cord. Knee joint inflammation was induced by intra-articular injection of monosodium iodoacetate (MIA, 8 mg/50 µl) and weight bearing percentage on right and left hindpaws during walking, paw withdrawal threshold to mechanical stimulation, and paw withdrawal latency to heat were measured to evaluate pain behavior. Intra-articular administration of RTX (0.03, 0.003 and 0.0003%) at 2 weeks after the induction of knee joint inflammation significantly improved reduction of weight bearing on the ipsilateral hindlimb and increased paw withdrawal sensitivity to mechanical and heat stimuli. The reduction of pain behavior persisted for 3~10 days according to each behavioral test. The MIA-induced increase in CGRP immunoreactivity in the spinal cord was decreased by RTX treatment in a dose-dependent manner. The present study demonstrated that a single intra-articular administration of RTX reduced pain behaviors for a relatively long time in an experimental model of OA and could normalize OA-associated changes in peptide expression in the spinal cord. PMID:26807032

  15. Vesicular Glutamate Transport Promotes Dopamine Storage and Glutamate Corelease In Vivo

    PubMed Central

    Hnasko, Thomas S.; Chuhma, Nao; Zhang, Hui; Goh, Germaine Y.; Sulzer, David; Palmiter, Richard D.; Rayport, Stephen; Edwards, Robert H.

    2010-01-01

    SUMMARY Dopamine neurons in the ventral tegmental area (VTA) play an important role in the motivational systems underlying drug addiction, and recent work has suggested that they also release the excitatory neurotransmitter glutamate. To assess a physiological role for glutamate corelease, we disrupted the expression of vesicular glutamate transporter 2 selectively in dopamine neurons. The conditional knockout abolishes glutamate release from midbrain dopamine neurons in culture and severely reduces their excitatory synaptic output in mesoaccumbens slices. Baseline motor behavior is not affected, but stimulation of locomotor activity by cocaine is impaired, apparently through a selective reduction of dopamine stores in the projection of VTA neurons to ventral striatum. Glutamate co-entry promotes monoamine storage by increasing the pH gradient that drives vesicular monoamine transport. Remarkably, low concentrations of glutamate acidify synaptic vesicles more slowly but to a greater extent than equimolar Cl−, indicating a distinct, presynaptic mechanism to regulate quantal size. PMID:20223200

  16. Glutamate Receptor Stimulation Up-Regulates Glutamate Uptake in Human Müller Glia Cells.

    PubMed

    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. PMID:27017513

  17. Glutamate Receptor Dynamics in Dendritic Microdomains

    PubMed Central

    Newpher, Thomas M.; Ehlers, Michael D.

    2008-01-01

    Among diverse factors regulating excitatory synaptic transmission, the abundance of postsynaptic glutamate receptors figures prominently in molecular memory and learning-related synaptic plasticity. To allow for both long-term maintenance of synaptic transmission and acute changes in synaptic strength, the relative rates of glutamate receptor insertion and removal must be tightly regulated. Interactions with scaffolding proteins control the targeting and signaling properties of glutamate receptors within the postsynaptic membrane. In addition, extrasynaptic receptor populations control the equilibrium of receptor exchange at synapses and activate distinct signaling pathways involved in plasticity. Here, we review recent findings that have shaped our current understanding of receptor mobility between synaptic and extrasynaptic compartments at glutamatergic synapses, focusing on AMPA and NMDA receptors. We also examine the cooperative relationship between intracellular trafficking and surface diffusion of glutamate receptors that underlies the expression of learning-related synaptic plasticity. PMID:18498731

  18. Mechanism for the activation of glutamate receptors

    Cancer.gov

    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

  19. [Glutamate transporter dysfunction and major mental illnesses].

    PubMed

    Tanaka, Kohichi

    2016-01-01

    Glutamate is the main excitatory neurotransmitter in the central nervous system and plays an important role in most aspects of normal brain function. In spite of its importance as a neurotransmitter, excess glutamate is toxic to neurons. Clearance of extracellular glutamate is critical for maintenance of low extracellular glutamate concentration, and occurs in large part through the activity of GLT1 (EAAT2) and GLAST (EAAT1), which are primarily expressed by astrocytes. Rare variants and down-regulation of GLT1 and GLAST, in psychiatric disorders have been reported. In this review, we demonstrate that various kinds of GLT1 and/or GLAST knockout mice replicate many aspects of the behavioral abnormalities seen in major mental illnesses including schizophrenia, depression, obsessive -compulsive disorders, autism, epilepsy and addiction. PMID:26793898

  20. DNA nanopore translocation in glutamate solutions

    NASA Astrophysics Data System (ADS)

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

    2015-08-01

    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 solutions. We show that it has a linear response at typical voltages and can be used to detect DNA translocations through a nanopore. The glutamate anion also acts as a redox-capable thickening agent, with high-viscosity solutions capable of slowing down the DNA translocation process by up to 11 times, with a corresponding 7 time reduction in signal. These results demonstrate that glutamate can replace chloride as the primary anion in nanopore resistive pulse sensing.

  1. Glutamic Acid Decarboxylation in Chlorella12

    PubMed Central

    Lane, T. R.; Stiller, Mary

    1970-01-01

    The decarboxylation of endogenous free glutamic acid by Chlorella pyrenoidosa, Marburg strain, was induced by a variety of metabolic poisons, by anaerobic conditions, and by freezing and thawing the cells. The rate of decarboxylation was proportional to the concentration of inhibitor present. Possible mechanisms which relate the effects of the various conditions on glutamate decarboxylation and oxygen consumption by Chlorella are discussed. Images PMID:5429350

  2. [Glutamate neurotransmission, stress and hormone secretion].

    PubMed

    Jezová, D; Juránková, E; Vigas, M

    1995-11-01

    Glutamate neurotransmission has been investigated in relation to several physiological processes (learning, memory) as well as to neurodegenerative and other disorders. Little attention has been paid to its involvement in neuroendocrine response during stress. Penetration of excitatory amino acids from blood to the brain is limited by the blood-brain barrier. As a consequence, several toxic effects but also bioavailability for therapeutic purposes are reduced. A free access to circulating glutamate is possible only in brain structures lacking the blood-brain barrier or under conditions of its increased permeability. Excitatory amino acids were shown to stimulate the pituitary hormone release, though the mechanism of their action is still not fully understood. Stress exposure in experimental animals induced specific changes in mRNA levels coding the glutamate receptor subunits in the hippocampus and hypothalamus. The results obtained with the use of glutamate receptor antagonists indicate that a number of specific receptor subtypes contribute to the stimulation of ACTH release during stress. The authors provided also data on the role of NMDA receptors in the control of catecholamine release, particularly in stress-induced secretion of epinephrine. These results were the first piece of evidence on the involvement of endogenous excitatory amino acids in neuroendocrine activation during stress. Neurotoxic effects of glutamate in animals are well described, especially after its administration in the neonatal period. In men, glutamate toxicity and its use as a food additive are a continuous subject of discussions. The authors found an increase in plasma cortisol and norepinephrine, but not epinephrine and prolactin, in response to the administration of a high dose of glutamate. It cannot be excluded that these effects might be induced even by lower doses in situations with increased vulnerability to glutamate action (age, individual variability). (Tab. 1, Fig. 6, Ref. 44

  3. Ionotropic Glutamate Receptors & CNS Disorders

    PubMed Central

    Bowie, Derek

    2008-01-01

    Disorders of the central nervous system (CNS) are complex disease states that represent a major challenge for modern medicine. Although etiology is often unknown, it is established that multiple factors such as defects in genetics and/or epigenetics, the environment as well as imbalance in neurotransmitter receptor systems are all at play in determining an individual’s susceptibility to disease. Gene therapy is currently not available and therefore, most conditions are treated with pharmacological agents that modify neurotransmitter receptor signaling. Here, I provide a review of ionotropic glutamate receptors (iGluRs) and the roles they fulfill in numerous CNS disorders. Specifically, I argue that our understanding of iGluRs has reached a critical turning point to permit, for the first time, a comprehensive re-evaluation of their role in the cause of disease. I illustrate this by highlighting how defects in AMPA receptor trafficking are important to Fragile X mental retardation and ectopic expression of kainate (KA) receptor synapses contributes to the pathology of temporal lobe epilepsy. Finally, I discuss how parallel advances in studies of other neurotransmitter systems may allow pharmacologists to work towards a cure for many CNS disorders rather than developing drugs to treat their symptoms. PMID:18537642

  4. Therapeutic Potential of Metabotropic Glutamate Receptor Modulators

    PubMed Central

    Hovelsø, N; Sotty, F; Montezinho, L.P; Pinheiro, P.S; Herrik, K.F; Mørk, A

    2012-01-01

    Glutamate is the main excitatory neurotransmitter in the central nervous system (CNS) and is a major player in complex brain functions. Glutamatergic transmission is primarily mediated by ionotropic glutamate receptors, which include NMDA, AMPA and kainate receptors. However, glutamate exerts modulatory actions through a family of metabotropic G-protein-coupled glutamate receptors (mGluRs). Dysfunctions of glutamatergic neurotransmission have been implicated in the etiology of several diseases. Therefore, pharmacological modulation of ionotropic glutamate receptors has been widely investigated as a potential therapeutic strategy for the treatment of several disorders associated with glutamatergic dysfunction. However, blockade of ionotropic glutamate receptors might be accompanied by severe side effects due to their vital role in many important physiological functions. A different strategy aimed at pharmacologically interfering with mGluR function has recently gained interest. Many subtype selective agonists and antagonists have been identified and widely used in preclinical studies as an attempt to elucidate the role of specific mGluRs subtypes in glutamatergic transmission. These studies have allowed linkage between specific subtypes and various physiological functions and more importantly to pathological states. This article reviews the currently available knowledge regarding the therapeutic potential of targeting mGluRs in the treatment of several CNS disorders, including schizophrenia, addiction, major depressive disorder and anxiety, Fragile X Syndrome, Parkinson’s disease, Alzheimer’s disease and pain. PMID:22942876

  5. RADIUM AND THORIUM SORPTION BY MONOSODIUM TITANATE (MST) AND MODIFIED MST (mMST)

    SciTech Connect

    Taylor-Pashow, K.; Hobbs, D.

    2012-02-15

    A series of tests were planned to examine the removal of Ra and Th by monosodium titanate (MST) and modified monosodium titanate (mMST). Simulated waste solutions were prepared containing Ra and Th, along with Sr, Np, Pu, and U. Following simulant preparation the simulants were filtered through 0.45-m filters. Analysis of the simulants indicated no Th in the filtered solution. This is due to the very low solubility of Th in alkaline solutions. Based on the reported detection limits for {sup 228}Th by gamma analyses, the solubility of Th in the simulant solutions is < 3.0E-10 g/L or < 1.3E-12 M. Therefore, data could not be obtained regarding the removal of Th by MST and mMST; however, testing proceeded to examine the removal of Ra. Sorption testing indicated that Ra, like Sr, is very rapidly removed from solution by both MST and mMST. The Ra concentration in solution fell below the method detection limit (MDL) within 30 minutes of contact with MST, and within 2 hours of contact with mMST, when tested at 25 C using a 5.6 M Na simulant. Additional testing examined the effects of ionic strength and temperature on the MST and mMST performance. Results from these tests showed that the majority of samples still reached a Ra concentration below the MDL, indicating excellent removal. For the highest ionic strength solution (6.6 M Na), there did appear to be a slight decrease in the Ra removal by mMST, as indicated by a larger number of samples just above the MDL. The effect of temperature on {sup 226}Ra removal is indeterminate for either MST or mMST in the temperature range (25-60 C) and concentrations studied since the final soluble concentration of Ra remained at or below the detection limits for all tests. Desorption testing was also performed using decontaminated salt solution (DSS) diluted to sodium concentrations of 2 M and 0.5 M, to represent the intermediate and final stages of washing. Results from these tests indicated no desorption of any sorbents, with the

  6. Arsenic Retention in Foliage and Soil after Monosodium Methyl Arsenate (MSMA) Application to Turfgrass.

    PubMed

    Matteson, Audrey R; Gannon, Travis W; Jeffries, Matthew D; Haines, Stephanie; Lewis, Dustin F; Polizzotto, Matthew L

    2014-01-01

    Monosodium methyl arsenate (MSMA) is a commonly used herbicide for weed control in turfgrass systems. There is concern that arsenic from applied MSMA could leach to groundwater or run off into surface water, thereby threatening human and ecosystem health. The USEPA has proposed a phase-out of the herbicide but is seeking additional research about the toxicity and environmental impacts of MSMA before establishing a final ruling. Little research has systematically investigated MSMA in field-based settings; instead, risks have been inferred from isolated field measurements or model-system studies. Accordingly, the overall goal of this study was to quantify the fate of arsenic after MSMA application to a managed turfgrass system. After MSMA application to turfgrass-covered and bareground lysimeters, the majority of arsenic was retained in turfgrass foliage and soils throughout year-long experiments, with 50 to 101% of the applied arsenic recovered in turfgrass systems and 55 to 66% recovered in bareground systems. Dissolved arsenic concentrations from 76.2-cm-depth pore water in the MSMA-treated soils were consistently <2 μg L, indistinguishable from background concentrations. As measured by adsorption isotherm experiments, MSMA retention by the sandy soil from our field site was markedly less than retention by a washed sand and a clay loam. Collectively, these results suggest that under aerobic conditions, minimal arsenic leaching to groundwater would occur after a typical application of MSMA to turfgrass. However, repeated MSMA application may pose environmental risks. Additional work is needed to examine arsenic cycling near the soil surface and to define arsenic speciation changes under different soil conditions. PMID:25602572

  7. Management considerations to minimize environmental impacts of arsenic following monosodium methylarsenate (MSMA) applications to turfgrass.

    PubMed

    Mahoney, Denis J; Gannon, Travis W; Jeffries, Matthew D; Matteson, Audrey R; Polizzotto, Matthew L

    2015-03-01

    Monosodium methylarsenate (MSMA) is an organic arsenical herbicide currently utilized in turfgrass and cotton systems. In recent years, concerns over adverse impacts of arsenic (As) from MSMA applications have emerged; however, little research has been conducted in controlled field experiments using typical management practices. To address this knowledge gap, a field lysimeter experiment was conducted during 2012-2013 to determine the fate of As following MSMA applications to a bareground and an established turfgrass system. Arsenic concentrations in soil, porewater, and aboveground vegetation, were measured through one yr after treatment. Aboveground vegetation As concentration was increased compared to nontreated through 120 d after initial treatment (DAIT). In both systems, increased soil As concentrations were observed at 0-4 cm at 30 and 120 DAIT and 0-8 cm at 60 and 365 DAIT, suggesting that As was bound in shallow soil depths. Porewater As concentrations in MSMA-treated lysimeters from a 30-cm depth (22.0-83.8 μg L(-1)) were greater than those at 76-cm depth (0.4-5.1 μg L(-1)). These results were combined with previous research to devise management considerations in systems where MSMA is utilized. MSMA should not be applied if rainfall is forecasted within 7 DAIT and/or in areas with shallow water tables. Further, disposing of MSMA-treated turfgrass aboveground vegetation in a confined area - a common management practice for turfgrass clippings - may be of concern due to As release to surface water or groundwater as the vegetation decomposes. Finally, long-term MSMA use may cause soil As accumulation and thus downward migration of As over time; therefore, MSMA should be used in rotation with other herbicides. PMID:25556868

  8. The Degradation of 14C-Glutamic Acid by L-Glutamic Acid Decarboxylase.

    ERIC Educational Resources Information Center

    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)

  9. Glutamate receptor ligands as anxiolytics.

    PubMed

    Chojnacka-Wójcik, E; Kłodzinska, A; Pilc, A

    2001-08-01

    The glutamatergic system has received considerable attention over recent years as a potential target for anxiolytic drugs. In spite of the pronounced anxiolytic-like effects of competitive and non-competitive antagonists of NMDA receptors in animal models of anxiety, these substances can not be regarded as potential anxiolytic drugs, mainly due to their side-effect profiles (eg, ataxia, myorelaxation, impairment of learning and memory processes and psychotomimetic effects). Antagonists and partial agonists of the glycine, receptor inhibit function of the NMDA receptor complex and evoke in animals an anxiolytic-like response. Although data concerning anti-anxiety-like effects of glycine, receptor antagonists are not very promising, studies are underway to develop new, brain-penetrating agents devoid of side effects. Further developments are necessary to more fully elucidate the possible involvement of AMPA/kainate receptors in anxiety. The recent discovery of metabotropic glutamate receptors, which modulate the function of the glutamatergic system, offers new hope for discovery of a new generation of anxiolytics. MPEP, a highly selective, brain penetrable, noncompetitive mGlu5 receptor antagonist, evokes anxiolytic-like effects in several animal models of anxiety, remaining remarkably free of side effects. LY-354740, a selective brain-penetrable group II mGlu receptor agonist, evokes marked anxiolytic-like effects in animal models of anxiety. LY-354740 causes mild sedation in mice, does not disturb motor coordination and has no potential to cause dependence. Therefore mGlu receptor ligands may become the anxiolytics of the future, free from the side effects characteristic of benzodiazepines. PMID:11892923

  10. Glutamate Metabolism in Major Depressive Disorder

    PubMed Central

    Abdallah, Chadi G.; Jiang, Lihong; De Feyter, Henk M.; Fasula, Madonna; Krystal, John H.; Rothman, Douglas L.; Mason, Graeme F.; Sanacora, Gerard

    2015-01-01

    Objective Emerging evidence suggests abnormalities in amino acid neurotransmitter function and impaired energy metabolism contribute to the underlying pathophysiology of Major Depressive Disorder (MDD). To test whether impairments in energetics and glutamate neurotransmitter cycling are present in MDD we used in vivo 13C magnetic resonance spectroscopy (13C MRS) to measure these fluxes in individuals diagnosed with MDD relative to non-depressed subjects. Method 1H MRS and 13C MRS data were collected on 23 medication-free MDD and 17 healthy subjects. 1H MRS provided total glutamate and GABA concentrations, and 13C MRS, coupled with intravenous infusion of [1-13C]-glucose, provided measures of the neuronal tricarboxylic acid cycle (VTCAN) for mitochondrial energy production, GABA synthesis, and glutamate/glutamine cycling, from voxels placed in the occipital cortex. Results Our main finding was that mitochondrial energy production of glutamatergic neurons was reduced by 26% in MDD subjects (t = 2.57, p = 0.01). Paradoxically we found no difference in the rate of glutamate/glutamine cycle (Vcycle). We also found a significant correlation between glutamate concentrations and Vcycle considering the total sample. Conclusions We interpret the reduction in mitochondrial energy production as being due to either mitochondrial dysfunction or a reduction in proper neuronal input or synaptic strength. Future MRS studies could help distinguish these possibilities. PMID:25073688

  11. Exposure to enriched environment decreases neurobehavioral deficits induced by neonatal glutamate toxicity.

    PubMed

    Horvath, Gabor; Reglodi, Dora; Vadasz, Gyongyver; Farkas, Jozsef; Kiss, Peter

    2013-01-01

    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 some signs and

  12. Permanent Uncoupling of Male-specific CYP2C11 Transcription / Translation by Perinatal Glutamate

    PubMed Central

    Banerjee, Sarmistha; Das, Rajat Kumar; Giffear, Kelly A.; Shapiro, Bernard H.

    2015-01-01

    Perinatal exposure of rats and mice to the typically reported 4mg/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, 2mg/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. PMID:25697375

  13. Permanent uncoupling of male-specific CYP2C11 transcription/translation by perinatal glutamate.

    PubMed

    Banerjee, Sarmistha; Das, Rajat Kumar; Giffear, Kelly A; Shapiro, Bernard H

    2015-04-01

    Perinatal exposure of rats and mice to the typically reported 4mg/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, 2mg/g bd wt on alternate days for the first 9days 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. PMID:25697375

  14. Single channel kinetics of a glutamate receptor.

    PubMed Central

    Kerry, C J; Kits, K S; Ramsey, R L; Sansom, M S; Usherwood, P N

    1987-01-01

    The glutamate receptor-channel of locust muscle membrane was studied using the patch-clamp technique. Muscles were pretreated with concanavalin A to block receptor-channel desensitization, thus facilitating analysis of receptor-channel gating kinetics. Single channel kinetics were analyzed to aid in identification of the molecular basis of channel gating. Channel dwell-time distributions and dwell-time autocorrelation functions were calculated from single channel data recorded in the precence of 10-4M glutamate. Analysis of the dwell time distributions in terms of mixtures of exponential functions revealed there to be at least three open states of the receptor-channel and at least four closed states. Autocorrelation function analysis showed there to be at least three pathways linking the open states with the closed. This results in a minimal scheme for gating of the glutamate receptor-channel, which is suggestive of allosteric models of receptor-channel gating. PMID:2436676

  15. Single Channel Kinetics of a Glutamate Receptor

    PubMed Central

    Kerry, Cathryn J.; Kits, Karel S.; Ramsey, Robert L.; Sansom, Mark S. P.; Usherwood, Peter N. R.

    1986-01-01

    The glutamate receptor-channel of locust muscle membrane was studied using the patch-clamp technique. Muscles were pretreated with concanavalin A to block receptor-channel desensitization, thus facilitating analysis of receptor-channel gating kinetics. Single channel kinetics were analyzed to aid in identification of the molecular basis of channel gating. Channel dwell-time distributions and dwell-time autocorrelation functions were calculated from single channel data recorded in the presence of 10-4 M glutamate. Analysis of the dwell time distributions in terms of mixtures of exponential functions revealed there to be at least three open states of the receptor-channel and at least four closed states. Autocorrelation function analysis showed there to be at least three pathways linking the open states with the closed. This results in a minimal scheme for gating of the glutamate receptor-channel, which is suggestive of allosteric models of receptor-channel gating. PMID:19431683

  16. IN VITRO PERCUTANEOUS ABSORPTION OF MONOSODIUM METHANERARSONATE (MSMA) AND DISODIUM METHANE-ARSONATE (DSMA) IN FEMALE B6C3F1 MICE

    EPA Science Inventory

    Percutaneous absorption of (14C] monosodium methanearsonate (MSMA) and disodium methanearsonate (DSMA) was investigated in female B6C3F1 mice from a variety of exposure conditions, including aqueous solution, solid compound, and soil. hese chemicals are the sodium salts of methan...

  17. PILOT SCALE TESTING OF MONOSODIUM TITANATE MIXING FOR THE SRS SMALL COLUMN ION EXCHANGE PROCESS - 11224

    SciTech Connect

    Poirier, M.; Restivo, M.; Williams, M.; Herman, D.; Steeper, T.

    2011-01-25

    The Small Column Ion Exchange (SCIX) process is being developed to remove cesium, strontium, and select actinides from Savannah River Site (SRS) Liquid Waste using an existing waste tank (i.e., Tank 41H) to house the process. Savannah River National Laboratory (SRNL) is conducting pilot-scale mixing tests to determine the pump requirements for suspending monosodium titanate (MST), crystalline silicotitanate (CST), and simulated sludge. The purpose of this pilot scale testing is to determine the requirements for the pumps to suspend the MST particles so that they can contact the strontium and actinides in the liquid and be removed from the tank. The pilot-scale tank is a 1/10.85 linear scaled model of SRS Tank 41H. The tank diameter, tank liquid level, pump nozzle diameter, pump elevation, and cooling coil diameter are all 1/10.85 of their dimensions in Tank 41H. The pump locations correspond to the proposed locations in Tank 41H by the SCIX program (Risers B5 and B2 for two pump configurations and Risers B5, B3, and B1 for three pump configurations). The conclusions from this work follow: (i) Neither two standard slurry pumps nor two quad volute slurry pumps will provide sufficient power to initially suspend MST in an SRS waste tank. (ii) Two Submersible Mixer Pumps (SMPs) will provide sufficient power to initially suspend MST in an SRS waste tank. However, the testing shows the required pump discharge velocity is close to the maximum discharge velocity of the pump (within 12%). (iii) Three SMPs will provide sufficient power to initially suspend MST in an SRS waste tank. The testing shows the required pump discharge velocity is 66% of the maximum discharge velocity of the pump. (iv) Three SMPs are needed to resuspend MST that has settled in a waste tank at nominal 45 C for four weeks. The testing shows the required pump discharge velocity is 77% of the maximum discharge velocity of the pump. Two SMPs are not sufficient to resuspend MST that settled under these

  18. Neural correlates of hyperalgesia in the monosodium iodoacetate model of osteoarthritis pain

    PubMed Central

    Abaei, Maryam; Sagar, Devi R; Stockley, Elizabeth G; Spicer, Clare H; Prior, Malcolm; Auer, Dorothee P

    2016-01-01

    Background The mechanisms driving osteoarthritic pain remain poorly understood, but there is increasing evidence for a role of the central nervous system in the chronification of pain. We used functional magnetic resonance imaging to investigate the influence of a model of unilateral knee osteoarthritis on nociceptive processing. Results Four to five weeks post intra-articular injection of monosodium iodoacetate (MIA, 1 mg) into the left knee, Sprague Dawley rats were anesthetized for functional magnetic resonance imaging studies to characterize the neural response to a noxious stimulus (intra-articular capsaicin injection). In a two-arm cross-over design, 5 µM/50 µl capsaicin was injected into either the left knee (n = 8, CAPS-MIA) or right control knee (n = 8, CAPS-CON), preceded by contralateral vehicle (SAL) injection. To assess neural correlates of mechanical hyperalgesia, hindpaws were stimulated with von Frey hairs (8 g: MIA; 15 g: control knee, based on behavioral withdrawal responses). The CAPS-MIA group exhibited significant activation of the periaqueductal gray, unilateral thalamus and bilateral mensencephalon, superior-colliculus, and hippocampus, with no significant activation in the other groups/conditions. Capsaicin injection increased functional connectivity in the mid-brain network and mediodorsal thalamic nucleus, hippocampus, and globus pallidus, which was significantly stronger in CAPS-MIA compared to CAPS-CON groups. Mechanical stimulation of the hyperalgesic (ipsilateral to MIA knee) and normalgesic (contralateral) hindpaws evoked qualitatively different brain activation with more widespread brainstem and anterior cingulate (ACC) activation when stimulating the hyperalgesic paw, and clearer frontal sensory activation from the normalgesic paw. Conclusions We provide evidence for modulation of nociceptive processing in a chronic knee osteoarthritis pain model with stronger brain activation and alteration of brain networks

  19. GLT-1: The elusive presynaptic glutamate transporter.

    PubMed

    Rimmele, Theresa S; Rosenberg, Paul A

    2016-09-01

    Historically, glutamate uptake in the CNS was mainly attributed to glial cells for three reasons: 1) none of the glutamate transporters were found to be located in presynaptic terminals of excitatory synapses; 2) the putative glial transporters, GLT-1 and GLAST are expressed at high levels in astrocytes; 3) studies of the constitutive GLT-1 knockout as well as pharmacological studies demonstrated that >90% of glutamate uptake into forebrain synaptosomes is mediated by the operation of GLT-1. Here we summarize the history leading up to the recognition of GLT-1a as a presynaptic glutamate transporter. A major issue now is understanding the physiological and pathophysiological significance of the expression of GLT-1 in presynaptic terminals. To elucidate the cell-type specific functions of GLT-1, a conditional knockout was generated with which to inactivate the GLT-1 gene in different cell types using Cre/lox technology. Astrocytic knockout led to an 80% reduction of GLT-1 expression, resulting in intractable seizures and early mortality as seen also in the constitutive knockout. Neuronal knockout was associated with no obvious phenotype. Surprisingly, synaptosomal uptake capacity (Vmax) was found to be significantly reduced, by 40%, in the neuronal knockout, indicating that the contribution of neuronal GLT-1 to synaptosomal uptake is disproportionate to its protein expression (5-10%). Conversely, the contribution of astrocytic GLT-1 to synaptosomal uptake was much lower than expected. In contrast, the loss of uptake into liposomes prepared from brain protein from astrocyte and neuronal knockouts was proportionate with the loss of GLT-1 protein, suggesting that a large portion of GLT-1 in astrocytic membranes in synaptosomal preparations is not functional, possibly because of a failure to reseal. These results suggest the need to reinterpret many previous studies using synaptosomal uptake to investigate glutamate transport itself as well as changes in glutamate

  20. Mood disorders: regulation by metabotropic glutamate receptors.

    PubMed

    Pilc, Andrzej; Chaki, Shigeyuki; Nowak, Gabriel; Witkin, Jeffrey M

    2008-03-01

    Medicinal therapies for mood disorders neither fully serve the efficacy needs of patients nor are they free of side-effect issues. Although monoamine-based therapies are the primary current treatment approaches, both preclinical and clinical findings have implicated the excitatory neurotransmitter glutamate in the pathogenesis of major depressive disorders. The present commentary focuses on the metabotropic glutamate receptors and their relationship to mood disorders. Metabotropic glutamate (mGlu) receptors regulate glutamate transmission by altering the release of neurotransmitter and/or modulating the post-synaptic responses to glutamate. Convergent biochemical, pharmacological, behavioral, and clinical data will be reviewed that establish glutamatergic neurotransmission via mGlu receptors as a biologically relevant process in the regulation of mood and that these receptors may serve as novel targets for the discovery of small molecule modulators with unique antidepressant properties. Specifically, compounds that antagonize mGlu2, mGlu3, and/or mGlu5 receptors (e.g. LY341495, MGS0039, MPEP, MTEP) exhibit biochemical effects indicative of antidepressant effects as well as in vivo activity in animal models predictive of antidepressant efficacy. Both preclinical and clinical data have previously been presented to define NMDA and AMPA receptors as important targets for the modulation of major depression. In the present review, we present a model suggesting how the interplay of glutamate at the mGlu and at the ionotropic AMPA and NMDA receptors might account for the antidepressant-like effects of glutamatergic- and monoaminergic-based drugs affecting mood in patients. The current data lead to the hypothesis that mGlu-based compounds and conventional antidepressants impact a network of interactive effects that converge upon a down regulation of NMDA receptor function and an enhancement in AMPA receptor signaling. PMID:18164691

  1. Circuit Mapping by UV Uncaging of Glutamate

    PubMed Central

    Shepherd, Gordon M. G.

    2014-01-01

    In laser photostimulation, small clusters of neurons in brain slices are induced to fire action potentials by focal glutamate uncaging, and synaptic connectivity between photoexcited presynaptic neurons and individual postsynaptic neurons is assessed by intracellular recording of synaptic events. With a scanner, this process can be repeated sequentially across a patterned array of stimulus locations, generating maps of neurons’ local sources of synaptic inputs. Laser scanning photostimulation (LSPS) based on patterned glutamate uncaging offers an efficient, quantitative, optical-electrophysiological way to map synaptic circuits in brain slices. PMID:22949715

  2. Molecular physiology of vesicular glutamate transporters in the digestive system

    PubMed Central

    Li, Tao; Ghishan, Fayez K.; Bai, Liqun

    2005-01-01

    Glutamate is the major excitatory neurotransmitter in the mammalian central nervous system (CNS). Packaging and storage of glutamate into glutamatergic neuronal vesicles require ATP-dependent vesicular glutamate uptake systems, which utilize the electrochemical proton gradient as a driving force. Three vesicular glutamate transporters (VGLUT1-3) have been recently identified from neuronal tissue where they play a key role to maintain the vesicular glutamate level. Recently, it has been demonstrated that glutamate signaling is also functional in peripheral neuronal and non-neuronal tissues, and occurs in sites of pituitary, adrenal, pineal glands, bone, GI tract, pancreas, skin, and testis. The glutamate receptors and VGLUTs in digestive system have been found in both neuronal and endocrinal cells. The glutamate signaling in the digestive system may have significant relevance to diabetes and GI tract motility disorders. This review will focus on the most recent update of molecular physiology of digestive VGLUTs. PMID:15793854

  3. 21 CFR 182.1047 - Glutamic acid hydrochloride.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 3 2012-04-01 2012-04-01 false 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....

  4. 21 CFR 182.1047 - Glutamic acid hydrochloride.

    Code of Federal Regulations, 2010 CFR

    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....

  5. 21 CFR 182.1047 - Glutamic acid hydrochloride.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 3 2011-04-01 2011-04-01 false 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....

  6. 21 CFR 182.1047 - Glutamic acid hydrochloride.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Glutamic acid hydrochloride. 182.1047 Section 182...) SUBSTANCES GENERALLY RECOGNIZED AS SAFE Multiple Purpose GRAS Food Substances § 182.1047 Glutamic acid hydrochloride. (a) Product. Glutamic acid hydrochloride. (b) (c) Limitations, restrictions, or explanation....

  7. 21 CFR 182.1047 - Glutamic acid hydrochloride.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 3 2013-04-01 2013-04-01 false 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....

  8. GLUTAMATE NEUROTOXICITY IN RAT AUDITORY SYSTEM: COCHLEAR NUCLEAR COMPLEX

    EPA Science Inventory

    In other systems such as the hypothalamus and hippocampus, it has been shown that cells postsynaptic with respect to glutamatergic inputs degenerate when exposed to large doses of glutamate ("glutamate neurotoxicity"). e have shown that large doses of glutamate administered intra...

  9. 21 CFR 582.1500 - Monoammonium glutamate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Monoammonium glutamate. 582.1500 Section 582.1500 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE General Purpose...

  10. 21 CFR 582.1516 - Monopotassium glutamate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Monopotassium glutamate. 582.1516 Section 582.1516 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE General Purpose...

  11. 21 CFR 582.1516 - Monopotassium glutamate.

    Code of Federal Regulations, 2010 CFR

    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 DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE General Purpose...

  12. 21 CFR 582.1500 - Monoammonium glutamate.

    Code of Federal Regulations, 2010 CFR

    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 DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE General Purpose...

  13. Circuit mapping by ultraviolet uncaging of glutamate.

    PubMed

    Shepherd, Gordon M G

    2012-09-01

    In laser photostimulation, small clusters of neurons in brain slices are induced to fire action potentials by focal glutamate uncaging, and synaptic connectivity between photoexcited presynaptic neurons and individual postsynaptic neurons is assessed by intracellular recording of synaptic events. With a scanner, this process can be repeated sequentially across a patterned array of stimulus locations, generating maps of neurons' local sources of synaptic inputs. Laser scanning photostimulation (LSPS) based on patterned glutamate uncaging offers an efficient, quantitative, optical-electrophysiological way to map synaptic circuits in brain slices. The efficacy of glutamate-based photostimulation for circuit mapping (in contrast to electrical stimulation) derives from the ability to stimulate neurons with high precision and speed, and without stimulating axons of passage. This protocol describes the components, assembly, and operation of a laser scanning microscope for ultraviolet (UV) uncaging, along with experimental methods for circuit mapping in brain slices. It presents a general approach and a set of guidelines for quantitative circuit mapping using "standard" LSPS methods based on single-photon glutamate uncaging using a UV laser, a pair of scanning mirror galvanometers, a patch-clamp setup, and open-source data acquisition software. PMID:22949715

  14. L-glutamate Receptor In Paramecium

    NASA Astrophysics Data System (ADS)

    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.

  15. Glutamate Mediated Astrocytic Filtering of Neuronal Activity

    PubMed Central

    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

  16. Miniaturized thin film glutamate and glutamine biosensors.

    PubMed

    Moser, I; Jobst, G; Aschauer, E; Svasek, P; Varahram, M; Urban, G; Zanin, V A; Tjoutrina, G Y; Zharikova, A V; Berezov, T T

    1995-01-01

    Integrated thin film biosensors were developed for the simultaneous measurement of L-glutamine and L-glutamate in a mu-flow cell. Due to a novel glutaminase with an activity optimum in the neutral pH range, direct monitoring of glutamine in a mammalian cell culture medium could be performed. The glutamine bienzyme sensor was prepared by co-immobilization of glutaminase with glutamate oxidase within a photopatterned poly(2-hydroxyethyl methacrylate) (pHEMA) hydrogel membrane. The sensor response was linear in the concentration range of 50 mumol to 10 mmol glutamine/l. Additionally, a glutamate biosensor was integrated on the sensor chip for difference measurement of possible glutamate interferences. The sensor-chip could be used for at least 300 measurements without any alteration in the performance of its sensors. A new sensor-chip with an integrated flow cell provided the possibility of simultaneous measurement of four different parameters at a cell volume of 1 microliter. In order to complete the microsystem, and in order to obtain a "lab on chip", a battery operated surface mounted device (SMD) potentiostat was developed. PMID:7612205

  17. Amphetamine stimulates movement through thalamocortical glutamate release

    PubMed Central

    Mabrouk, Omar S; Semaan, Daniel Z; Mikelman, Sarah; Gnegy, Margaret E; Kennedy, Robert T

    2014-01-01

    The ventrolateral thalamus (VL) is a primary relay point between the basal ganglia and the primary motor cortex (M1). Using dual probe microdialysis and locomotor behavior monitoring, we investigated the contribution of VL input into M1 during amphetamine (AMPH)-stimulated monoamine release and hyperlocomotion in rats. Tetrodotoxin (TTX) (10 uM) perfusion into the VL significantly lowered hyperactivity induced by AMPH (1 mg/kg i.p.). This behavioral response corresponded to reduced cortical glutamate and monoamine release. To determine which glutamate receptors the thalamocortical projections acted upon, we perfused either the AMPA/kainate receptor antagonist NBQX (10 μM) or the NMDA receptor antagonist (MK-801) intracortically followed by systemic AMPH. The results show that AMPA/kainate, and to a lesser extent NMDA receptors, mediated the observed effects. Since glutamate-monoamine interactions could possibly occur through local or circuit-based mechanisms, we isolated and perfused M1 tissue ex vivo to determine the extent of local glutamate-dopamine interactions. Taken together, these results demonstrate that AMPH generates hyperlocomotive states via thalamocortical signaling and that cortical AMPA receptors are an important mediator of these effects. PMID:23889359

  18. Structural Features of the Glutamate Transporter Family

    PubMed Central

    Slotboom, Dirk Jan; Konings, Wil N.; Lolkema, Juke S.

    1999-01-01

    Neuronal and glial glutamate transporters remove the excitatory neurotransmitter glutamate from the synaptic cleft and thus prevent neurotoxicity. The proteins belong to a large and widespread family of secondary transporters, including bacterial glutamate, serine, and C4-dicarboxylate transporters; mammalian neutral-amino-acid transporters; and an increasing number of bacterial, archaeal, and eukaryotic proteins that have not yet been functionally characterized. Sixty members of the glutamate transporter family were found in the databases on the basis of sequence homology. The amino acid sequences of the carriers have diverged enormously. Homology between the members of the family is most apparent in a stretch of approximately 150 residues in the C-terminal part of the proteins. This region contains four reasonably well-conserved sequence motifs, all of which have been suggested to be part of the translocation pore or substrate binding site. Phylogenetic analysis of the C-terminal stretch revealed the presence of five subfamilies with characterized members: (i) the eukaryotic glutamate transporters, (ii) the bacterial glutamate transporters, (iii) the eukaryotic neutral-amino-acid transporters, (iv) the bacterial C4-dicarboxylate transporters, and (v) the bacterial serine transporters. A number of other subfamilies that do not contain characterized members have been defined. In contrast to their amino acid sequences, the hydropathy profiles of the members of the family are extremely well conserved. Analysis of the hydropathy profiles has suggested that the glutamate transporters have a global structure that is unique among secondary transporters. Experimentally, the unique structure of the transporters was recently confirmed by membrane topology studies. Although there is still controversy about part of the topology, the most likely model predicts the presence of eight membrane-spanning α-helices and a loop-pore structure which is unique among secondary

  19. Glutamate Receptor Agonists and Glutamate Transporter Antagonists Regulate Differentiation of Osteoblast Lineage Cells.

    PubMed

    Xie, Wenjie; Dolder, Silvia; Siegrist, Mark; Wetterwald, Antoinette; Hofstetter, Willy

    2016-08-01

    Development and function of osteoblast lineage cells are regulated by a complex microenvironment consisting of the bone extracellular matrix, cells, systemic hormones and cytokines, autocrine and paracrine factors, and mechanical load. Apart from receptors that transduce extracellular signals into the cell, molecular transporters play a crucial role in the cellular response to the microenvironment. Transporter molecules are responsible for cellular uptake of nutritional components, elimination of metabolites, ion transport, and cell-cell communication. In this report, the expression of molecular transporters in osteoblast lineage cells was investigated to assess their roles in cell development and activity. Low-density arrays, covering membrane and vesicular transport molecules, were used to assess gene expression in osteoblasts representing early and late differentiation states. Receptors and transporters for the amino acid glutamate were found to be differentially expressed during osteoblast development. Glutamate is a neurotransmitter in the central nervous system, and the mechanisms of its release, signal transduction, and cellular reabsorption in the synaptic cleft are well understood. Less clear, however, is the control of equivalent processes in peripheral tissues. In primary osteoblasts, inhibition of glutamate transporters with nonselective inhibitors leads to an increase in the concentration of extracellular glutamate. This change was accompanied by a decrease in osteoblast proliferation, stimulation of alkaline phosphatase, and the expression of transcripts encoding osteocalcin. Enzymatic removal of extracellular glutamate abolished these pro-differentiation effects, as did the inhibition of PKC- and Erk1/2-signaling pathways. These findings demonstrate that glutamate signaling promotes differentiation and activation of osteoblast lineage cells. Consequently, the glutamate system may represent a putative therapeutic target to induce an anabolic response

  20. Optical measurement of synaptic glutamate spillover and reuptake by linker optimized glutamate-sensitive fluorescent reporters

    PubMed Central

    Hires, Samuel Andrew; Zhu, Yongling; Tsien, Roger Y.

    2008-01-01

    Genetically encoded sensors of glutamate concentration are based on FRET between cyan and yellow fluorescent proteins bracketing a bacterial glutamate-binding protein. Such sensors have yet to find quantitative applications in neurons, because of poor response amplitude in physiological buffers or when expressed on the neuronal cell surface. We have improved our glutamate-sensing fluorescent reporter (GluSnFR) by systematic optimization of linker sequences and glutamate affinities. Using SuperGluSnFR, which exhibits a 6.2-fold increase in response magnitude over the original GluSnFR, we demonstrate quantitative optical measurements of the time course of synaptic glutamate release, spillover, and reuptake in cultured hippocampal neurons with centisecond temporal and spine-sized spatial resolution. During burst firing, functionally significant spillover persists for hundreds of milliseconds. These glutamate levels appear sufficient to prime NMDA receptors, potentially affecting dendritic spike initiation and computation. Stimulation frequency-dependent modulation of spillover suggests a mechanism for nonsynaptic neuronal communication. PMID:18332427

  1. Amperometric L-glutamate biosensor based on bacterial cell-surface displayed glutamate dehydrogenase.

    PubMed

    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. PMID:26073813

  2. Monosodium Urate Crystals Promote Innate Anti-Mycobacterial Immunity and Improve BCG Efficacy as a Vaccine against Tuberculosis.

    PubMed

    Taus, Francesco; Santucci, Marilina B; Greco, Emanuela; Morandi, Matteo; Palucci, Ivana; Mariotti, Sabrina; Poerio, Noemi; Nisini, Roberto; Delogu, Giovanni; Fraziano, Maurizio

    2015-01-01

    A safer and more effective anti-Tuberculosis vaccine is still an urgent need. We probed the effects of monosodium urate crystals (MSU) on innate immunity to improve the Bacille Calmette-Guerin (BCG) vaccination. Results showed that in vitro MSU cause an enduring macrophage stimulation of the anti-mycobacterial response, measured as intracellular killing, ROS production and phagolysosome maturation. The contribution of MSU to anti-mycobacterial activity was also shown in vivo. Mice vaccinated in the presence of MSU showed a lower number of BCG in lymph nodes draining the vaccine inoculation site, in comparison to mice vaccinated without MSU. Lastly, we showed that MSU improved the efficacy of BCG vaccination in mice infected with Mycobacterium tuberculosis (MTB), measured in terms of lung and spleen MTB burden. These results demonstrate that the use of MSU as adjuvant may represent a novel strategy to enhance the efficacy of BCG vaccination. PMID:26023779

  3. Monosodium Urate Crystals Promote Innate Anti-Mycobacterial Immunity and Improve BCG Efficacy as a Vaccine against Tuberculosis

    PubMed Central

    Taus, Francesco; Santucci, Marilina B.; Greco, Emanuela; Morandi, Matteo; Palucci, Ivana; Mariotti, Sabrina; Poerio, Noemi; Nisini, Roberto; Delogu, Giovanni; Fraziano, Maurizio

    2015-01-01

    A safer and more effective anti-Tuberculosis vaccine is still an urgent need. We probed the effects of monosodium urate crystals (MSU) on innate immunity to improve the Bacille Calmette-Guerin (BCG) vaccination. Results showed that in vitro MSU cause an enduring macrophage stimulation of the anti-mycobacterial response, measured as intracellular killing, ROS production and phagolysosome maturation. The contribution of MSU to anti-mycobacterial activity was also shown in vivo. Mice vaccinated in the presence of MSU showed a lower number of BCG in lymph nodes draining the vaccine inoculation site, in comparison to mice vaccinated without MSU. Lastly, we showed that MSU improved the efficacy of BCG vaccination in mice infected with Mycobacterium tuberculosis (MTB), measured in terms of lung and spleen MTB burden. These results demonstrate that the use of MSU as adjuvant may represent a novel strategy to enhance the efficacy of BCG vaccination. PMID:26023779

  4. TAILORING INORGANIC SORBENTS FOR SRS STRONTIUM AND ACTINIDE SEPARATIONS: OPTIMIZED MONOSODIUM TITANATE PHASE II FINAL REPORT

    SciTech Connect

    Hobbs, D; Thomas Peters, T; Michael Poirier, M; Mark Barnes, M; Major Thompson, M; Samuel Fink, S

    2007-06-29

    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

  5. Glutamate Neurocircuitry: Theoretical Underpinnings in Schizophrenia

    PubMed Central

    Schwartz, Thomas L.; Sachdeva, Shilpa; Stahl, Stephen M.

    2012-01-01

    The Dopamine Hypothesis of Schizophrenia is actively being challenged by the NMDA Receptor Hypofunctioning Hypothesis of Schizophrenia. The latter hypothesis may actually be the starting point in neuronal pathways that ultimately modifies dopamine pathways involved in generating both positive and negative symptoms of schizophrenia postulated by the former hypothesis. The authors suggest that even this latter, NMDA receptor-based, hypothesis is likely too narrow and offer a review of typical glutamate and dopamine-based neurocircuitry, propose genetic vulnerabilities impacting glutamate neurocircuitry, and provide a broad interpretation of a possible etiology of schizophrenia. In conclusion, there is a brief review of potential schizophrenia treatments that rely on the etiologic theory provided in the body of the paper. PMID:23189055

  6. Glutamate neurotoxicity, oxidative stress and mitochondria.

    PubMed

    Atlante, A; Calissano, P; Bobba, A; Giannattasio, S; Marra, E; Passarella, S

    2001-05-18

    The excitatory neurotransmitter glutamate plays a major role in determining certain neurological disorders. This situation, referred to as 'glutamate neurotoxicity' (GNT), is characterized by an increasing damage of cell components, including mitochondria, leading to cell death. In the death process, reactive oxygen species (ROS) are generated. The present study describes the state of art in the field of GNT with a special emphasis on the oxidative stress and mitochondria. In particular, we report how ROS are generated and how they affect mitochondrial function in GNT. The relationship between ROS generation and cytochrome c release is described in detail, with the released cytochrome c playing a role in the cell defense mechanism against neurotoxicity. PMID:11376653

  7. Three Distinct Glutamate Decarboxylase Genes in Vertebrates

    PubMed Central

    Grone, Brian P.; Maruska, Karen P.

    2016-01-01

    Gamma-aminobutyric acid (GABA) is a widely conserved signaling molecule that in animals has been adapted as a neurotransmitter. GABA is synthesized from the amino acid glutamate by the action of glutamate decarboxylases (GADs). Two vertebrate genes, GAD1 and GAD2, encode distinct GAD proteins: GAD67 and GAD65, respectively. We have identified a third vertebrate GAD gene, GAD3. This gene is conserved in fishes as well as tetrapods. We analyzed protein sequence, gene structure, synteny, and phylogenetics to identify GAD3 as a homolog of GAD1 and GAD2. Interestingly, we found that GAD3 was lost in the hominid lineage. Because of the importance of GABA as a neurotransmitter, GAD3 may play important roles in vertebrate nervous systems. PMID:27461130

  8. Metabotropic Glutamate Receptors for Parkinson's Disease Therapy

    PubMed Central

    Gasparini, Fabrizio; Di Paolo, Thérèse; Gomez-Mancilla, Baltazar

    2013-01-01

    Excessive glutamatergic signalling within the basal ganglia is implicated in the progression of Parkinson's disease (PD) and inthe emergence of dyskinesia associated with long-term treatment with L-DOPA. There is considerable research focus on the discovery and development of compounds that modulate glutamatergic signalling via glutamate receptors, as treatments for PD and L-DOPA-induced dyskinesia (LID). Although initial preclinical studies with ionotropic glutamate receptor antagonists showed antiparkinsonian and antidyskinetic activity, their clinical use was limited due to psychiatric adverse effects, with the exception of amantadine, a weak N-methyl-d-aspartate (NMDA) antagonist, currently used to reduce dyskinesia in PD patients. Metabotropic receptor (mGlu receptor) modulators were considered to have a more favourable side-effect profile, and several agents have been studied in preclinical models of PD. The most promising results have been seen clinically with selective antagonists of mGlu5 receptor and preclinically with selective positive allosteric modulators of mGlu4 receptor. The growing understanding of glutamate receptor crosstalk also raises the possibility of more precise modulation of glutamatergic transmission, which may lead to the development of more effective agents for PD. PMID:23853735

  9. Transport dynamics in a glutamate transporter homologue

    PubMed Central

    Akyuz, Nurunisa; Altman, Roger B.; Blanchard, Scott C.; Boudker, Olga

    2013-01-01

    Summary Glutamate transporters are integral membrane proteins that catalyze neurotransmitter uptake from the synaptic cleft into the cytoplasm of glial cells and neurons1. Their mechanism involves transitions between extracellular- (outward-) and intracellular- (inward-) facing conformations, whereby substrate binding sites become accessible to the opposite sides of the membrane2. This process has been proposed to entail trans-membrane movements of three discrete transport domains within a trimeric scaffold3. Using single-molecule fluorescence resonance energy transfer (smFRET) imaging4, we have directly observed large-scale transport domain movements in a bacterial homologue of glutamate transporters for the first time. We find that individual transport domains alternate between periods of quiescence and periods of rapid transitions, reminiscent of bursting patterns first recorded in single ion channels using patch-clamp methods5,6. We suggest that the switch to the dynamic mode in glutamate transporters is due to separation of the transport domain from the trimeric scaffold, which precedes domain movements across the bilayer. This spontaneous dislodging of the substrate-loaded transport domain is approximately 100-fold slower than subsequent trans-membrane movements and may be rate determining in the transport cycle. PMID:23792560

  10. TAILORING INORGANIC SORBENTS FOR SRS STRONTIUM AND ACTINIDE SEPARATIONS: MODIFIED MONOSODIUM TITANATE PHASE III FINAL REPORT

    SciTech Connect

    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

  11. Bioanalysis of N-acetyl-aspartyl-glutamate as a marker of glutamate carboxypeptidase II inhibition.

    PubMed

    Thomas, Ajit G; Rojas, Camilo J; Hill, Jeanette R; Shaw, Michael; Slusher, Barbara S

    2010-09-01

    We report the characterization of two methods for the analysis of N-acetyl-aspartyl-glutamate (NAAG) in biological fluids. In the first method, NAAG concentrations were calculated based on differences between glutamate concentrations before and after NAAG hydrolysis with exogenous glutamate carboxypeptidase II (GCP II) using high-performance liquid chromatography (HPLC) followed by fluorescence detection. In the second method, NAAG levels were quantified directly using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Analyses of NAAG levels in human cerebrospinal fluid samples using either method gave similar results within experimental error, confirming the validity of the two independent measurements. These methods will be useful in future clinical trials to assess drug-induced GCP II inhibition in biological matrices. PMID:20434427

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

    PubMed

    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. PMID:21437781

  13. The mechanism of proline/glutamate antiport in rat kidney mitochondria. Energy dependence and glutamate-carrier involvement.

    PubMed

    Atlante, A; Passarella, S; Pierro, P; Di Martino, C; Quagliariello, E

    1996-10-01

    Proline/glutamate antiport in rat kidney mitochondria has been studied in terms of two different features: energy dependence and glutamate-carrier contribution to accomplish proline movement across the mitochondrial membrane. Energy dependence of the proline/glutamate antiporter in rat kidney mitochondria has been investigated by means of both spectroscopic measurements and isotopic techniques, using either normal or [14C]glutamate-loaded mitochondria. The sensitivity of the proline/glutamate antiport to the ionophores valinomycin and nigericin, under conditions in which delta psi and delta pH are selectively affected, shows that the exchange is energy dependent. Measurements of both membrane potential and proton movement across the mitochondrial membrane suggest that proline/glutamate antiport is driven by the electrochemical proton gradient via the delta psi dependent proline/glutamate translocator and delta pH-dependent glutamate/OH- carrier. Such a carrier provides for re-uptake of glutamate that has already passed out of the mitochondria in exchange with incoming proline, made possible by the existence of a separate pool of glutamate in the intermembrane space, directly shown by means of HPLC measurements. PMID:8898903

  14. Quantum-mechanical calculations and spectroscopic characteristics of magnesium glutamate glycine and magnesium glutamate arginine

    NASA Astrophysics Data System (ADS)

    Marcoin, W.; Pasterny, K.; Pasterna, G.; Wrzalik, R.

    2006-07-01

    Theoretical calculations of magnesium glutamate-glycine ([Mg(glu-gly)]) and magnesium glutamate-arginine ([Mg(glu-arg)]) structures and their spectroscopic characteristics have been performed in the gas phase with the GAUSSIAN 98 software package using density functional theory (DFT) at the B3PW91 level. The 6-31+G* basis set was selected due to their reasonable quality and size. NMR and IR measurements were carried out and obtained experimental 1H and 13C chemical shifts and IR spectra are compared with calculated spectral parameters.

  15. Topiramate antagonism of L-glutamate-induced paroxysms in planarians

    PubMed Central

    Raffa, Robert B.; Finno, Kristin E.; Tallarida, Christopher S.; Rawls, Scott M.

    2010-01-01

    We recently reported that NMDA (N-Methyl-D-aspartate) and AMPA (α-Amino-3-hydroxy-5-methylisoxazole-4-propionic acid) induce concentration-dependent paroxysms in planarians (Dugesia dorotocephala). Since the postulated mechanisms of action of the sulfamate-substituted monosaccharide antiepileptic drug topiramate include inhibition of glutamate-activated ion channels, we tested the hypothesis that topiramate would inhibit glutamate-induced paroxysms in our model. We demonstrate that: (1) L-glutamate (1–10 mM), but not D-glutamate, induced dose-related paroxysms, and that (2) topiramate dose-relatedly (0.3–3 mM) inhibited L-glutamate-induced paroxysms. These results provide further evidence of a topiramate-sensitive glutamate receptor-mediated activity in this model. PMID:20863783

  16. Exciting Times for Pancreatic Islets: Glutamate Signaling in Endocrine Cells.

    PubMed

    Otter, Silke; Lammert, Eckhard

    2016-03-01

    Glutamate represents a key excitatory neurotransmitter in the central nervous system, and also modulates the function and viability of endocrine cells in pancreatic islets. In insulin-secreting beta cells, glutamate acts as an intracellular messenger, and its transport into secretory granules promotes glucose- and incretin-stimulated insulin secretion. Mitochondrial degradation of glutamate also contributes to insulin release when glutamate dehydrogenase is allosterically activated. It also signals extracellularly via glutamate receptors (AMPA and NMDA receptors) to modulate glucagon, insulin and somatostatin secretion, and islet cell survival. Its degradation products, GABA and γ-hydroxybutyrate, are released and also influence islet cell behavior. Thus, islet glutamate receptors, such as the NMDA receptors, might serve as possible drug targets to develop new medications for adjunct treatment of diabetes. PMID:26740469

  17. From the Cover: Glutamate antagonists limit tumor growth

    NASA Astrophysics Data System (ADS)

    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.

  18. Exercise increases mitochondrial glutamate oxidation in the mouse cerebral cortex.

    PubMed

    Herbst, Eric A F; Holloway, Graham P

    2016-07-01

    The present study investigated the impact of acute exercise on stimulating mitochondrial respiratory function in mouse cerebral cortex. Where pyruvate-stimulated respiration was not affected by acute exercise, glutamate respiration was enhanced following the exercise bout. Additional assessment revealed that this affect was dependent on the presence of malate and did not occur when substituting glutamine for glutamate. As such, our results suggest that glutamate oxidation is enhanced with acute exercise through activation of the malate-aspartate shuttle. PMID:27184881

  19. Astroglial glutamate transporters coordinate excitatory signaling and brain energetics.

    PubMed

    Robinson, Michael B; Jackson, Joshua G

    2016-09-01

    In the mammalian brain, a family of sodium-dependent transporters maintains low extracellular glutamate and shapes excitatory signaling. The bulk of this activity is mediated by the astroglial glutamate transporters GLT-1 and GLAST (also called EAAT2 and EAAT1). In this review, we will discuss evidence that these transporters co-localize with, form physical (co-immunoprecipitable) interactions with, and functionally couple to various 'energy-generating' systems, including the Na(+)/K(+)-ATPase, the Na(+)/Ca(2+) exchanger, glycogen metabolizing enzymes, glycolytic enzymes, and mitochondria/mitochondrial proteins. This functional coupling is bi-directional with many of these systems both being regulated by glutamate transport and providing the 'fuel' to support glutamate uptake. Given the importance of glutamate uptake to maintaining synaptic signaling and preventing excitotoxicity, it should not be surprising that some of these systems appear to 'redundantly' support the energetic costs of glutamate uptake. Although the glutamate-glutamine cycle contributes to recycling of neurotransmitter pools of glutamate, this is an over-simplification. The ramifications of co-compartmentalization of glutamate transporters with mitochondria for glutamate metabolism are discussed. Energy consumption in the brain accounts for ∼20% of the basal metabolic rate and relies almost exclusively on glucose for the production of ATP. However, the brain does not possess substantial reserves of glucose or other fuels. To ensure adequate energetic supply, increases in neuronal activity are matched by increases in cerebral blood flow via a process known as 'neurovascular coupling'. While the mechanisms for this coupling are not completely resolved, it is generally agreed that astrocytes, with processes that extend to synapses and endfeet that surround blood vessels, mediate at least some of the signal that causes vasodilation. Several studies have shown that either genetic deletion or

  20. [Autoantibodies to glutamate and GABA in opiate addiction].

    PubMed

    Vetrile, L A; Fomina, V G; Nevidimova, T I; Vetlugina, T P; Batukhtina, E I; Savochkina, D N; Zakharova, I A; Davydova, T V

    2015-01-01

    Blood serum from 129 patients with opium addiction at different stages of the disease and 63 donors (control group) was examined for the presence of autoantibodies to the exciting and inhibitory amino acids glutamate and GABA. It was shown enhanced production of autoantibodies to glutamate and GABA. Dependence of the level and frequency of detec- tion of autoantibodies to glutamate and GABA on the stage of the disease was revealed. PMID:26852594

  1. Relationship between Increase in Astrocytic GLT-1 Glutamate Transport and Late-LTP

    ERIC Educational Resources Information Center

    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…

  2. Glutamate-induced sensitization of rat masseter muscle fibers.

    PubMed

    Cairns, B E; Gambarota, G; Svensson, P; Arendt-Nielsen, L; Berde, C B

    2002-01-01

    In rats, intradermal or intraarticular injection of glutamate or selective excitatory amino acid receptor agonists acting at peripheral excitatory amino acid receptors can decrease the intensity of mechanical stimulation required to evoke nocifensive behaviors, an indication of hyperalgesia. Since excitatory amino acid receptors have been found on the terminal ends of cutaneous primary afferent fibers, it has been suggested that increased tissue glutamate levels may have a direct sensitizing effect on primary afferent fibers, in particular skin nociceptors. However, less is known about the effects of glutamate on deep tissue afferent fibers. In the present study, a series of experiments were undertaken to investigate the effect of intramuscular injection of glutamate on the excitability and mechanical threshold of masseter muscle afferent fibers in anesthetized rats of both sexes. Injection of 1.0 M, but not 0.1 M glutamate evoked masseter muscle afferent activity that was significantly greater than that evoked by isotonic saline. The mechanical threshold of masseter muscle afferent fibers, which was assessed with a Von Frey hair, was reduced by approximately 50% for a period of 30 min after injection of 1.0 M glutamate, but was unaffected by injections of 0.1 M glutamate or isotonic saline. Injection of 25% dextrose, which has the same osmotic strength as 1.0 M glutamate, did not evoke significant activity in or decrease the mechanical threshold of masseter muscle afferent fibers. Magnetic resonance imaging experiments confirmed that injection of 25% dextrose and 1.0 M glutamate produced similar edema volumes in the masseter muscle tissue. Co-injection of 0.1 M kynurenate, an excitatory amino acid receptor antagonist, and 1.0 M glutamate attenuated glutamate-evoked afferent activity and prevented glutamate-induced mechanical sensitization. When male and female rats were compared, no difference in the baseline mechanical threshold or in the magnitude of glutamate

  3. Drug solubilization effect of lauroyl-L-glutamate.

    PubMed

    Ariki, Ryosuke; Hirano, Atsushi; Arakawa, Tsutomu; Shiraki, Kentaro

    2012-01-01

    This article proposes a new technique for the solubilization of poorly soluble drugs using lauroyl-L-glutamate, which is one of the amino acid detergents, with additional small additives. Lauroyl-L-glutamate was highly effective in solubilizing long-chain alkyl gallates, e.g. dodecyl gallate. Furthermore, lauroyl-L-glutamate and small additives, particularly arginine, acted to increase the solubility of alkyl gallates. The synergistic effect was not observed by sodium dodecyl sulphate with arginine. The solubilizing system can be applied to other drugs because of the low toxicity of both lauroyl-L-glutamate and arginine. PMID:21949409

  4. Glutathione is a Physiologic Reservoir of Neuronal Glutamate

    PubMed Central

    Koga, Minori; Serritella, Anthony V.; Messmer, Marcus M.; Hayashi-Takagi, Akiko; Hester, Lynda D.; Snyder, Solomon H.; Sawa, Akira; Sedlak, Thomas W.

    2013-01-01

    Glutamate, the principal excitatory neurotransmitter of the brain, participates in a multitude of physiologic and pathologic processes, including learning and memory. Glutathione, a tripeptide composed of the amino acids glutamate, cysteine, and glycine, serves important cofactor roles in antioxidant defense and drug detoxification, but glutathione deficits occur in multiple neuropsychiatric disorders. Glutathione synthesis and metabolism are governed by a cycle of enzymes, the γ-glutamyl cycle, which can achieve intracellular glutathione concentrations of 1-10 millimolar. Because of the considerable quantity of brain glutathione and its rapid turnover, we hypothesized that glutathione may serve as a reservoir of neural glutamate. We quantified glutamate in HT22 hippocampal neurons, PC12 cells and primary cortical neurons after treatment with molecular inhibitors targeting three different enzymes of the glutathione metabolic cycle. Inhibiting 5-oxoprolinase and γ-glutamyl transferase, enzymes that liberate glutamate from glutathione, leads to decreases in glutamate. In contrast, inhibition of γ-glutamyl cysteine ligase, which uses glutamate to synthesize glutathione, results in substantial glutamate accumulation. Increased glutamate levels following inhibition of glutathione synthesis temporally precede later effects upon oxidative stress. PMID:21539809

  5. Decreased endothelial nitric oxide, systemic oxidative stress, and increased sympathetic modulation contribute to hypertension in obese rats.

    PubMed

    da Cunha, Natalia Veronez; Pinge-Filho, Phileno; Panis, Carolina; Silva, Bruno Rodrigues; Pernomian, Laena; Grando, Marcella Daruge; Cecchini, Rubens; Bendhack, Lusiane Maria; Martins-Pinge, Marli Cardoso

    2014-05-15

    We investigated the involvement of nitric oxide (NO) and reactive oxygen species (ROS) on autonomic cardiovascular parameters, vascular reactivity, and endothelial cells isolated from aorta of monosodium glutamate (MSG) obese rats. Obesity was induced by administration of 4 mg/g body wt of MSG or equimolar saline [control (CTR)] to newborn rats. At the 60th day, the treatment was started with N(G)-nitro-L-arginine methyl ester (L-NAME, 20 mg/kg) or 0.9% saline. At the 90th day, after artery catheterization, mean arterial pressure (MAP) and heart rate were recorded. Plasma was collected to assess lipid peroxidation. Endothelial cells isolated from aorta were evaluated by flow cytometry and fluorescence intensity (FI) emitted by NO-sensitive dye [4,5-diaminofluoresceindiacetate (DAF-2DA)] and by ROS-sensitive dye [dihydroethidium (DHE)]. Vascular reactivity was made by concentration-response curves of acetylcholine. MSG showed hypertension compared with CTR. Treatment with L-NAME increased MAP only in CTR. The MSG induced an increase in the low-frequency (LF) band and a decrease in the high-frequency band of pulse interval. L-NAME treatment increased the LF band of systolic arterial pressure only in CTR without changes in MSG. Lipid peroxidation levels were higher in MSG and were attenuated after L-NAME. In endothelial cells, basal FI to DAF was higher in CTR than in MSG. In both groups, acetylcholine increased FI for DAF from basal. The FI baseline to DHE was higher in MSG than in CTR. Acetylcholine increased FI to DHE in the CTR group, but decreased in MSG animals. We suggest that reduced NO production and increased production of ROS may contribute to hypertension in obese MSG animals. PMID:24633548

  6. Gut glutamate metabolism is extensive in piglets supplemented with dietary glutamate

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Glutamate (GLU) is a key intestinal oxidative fuel and neurotransmitter. GLU may be a therapeutic nutrient in enhancing intestinal growth and function in premature neonates; however, increased systemic GLU levels may be neurotoxic. We hypothesized that the rates of intestinal GLU absorption are rela...

  7. Cystine/glutamate antiporter blockage induces myelin degeneration.

    PubMed

    Soria, Federico N; Zabala, Alazne; Pampliega, Olatz; Palomino, Aitor; Miguelez, Cristina; Ugedo, Luisa; Sato, Hideyo; Matute, Carlos; Domercq, María

    2016-08-01

    The cystine/glutamate antiporter is a membrane transport system responsible for the uptake of extracellular cystine and release of intracellular glutamate. It is the major source of cystine in most cells, and a key regulator of extrasynaptic glutamate in the CNS. Because cystine is the limiting factor in the biosynthesis of glutathione, and glutamate is the most abundant neurotransmitter, the cystine/glutamate antiporter is a central player both in antioxidant defense and glutamatergic signaling, two events critical to brain function. However, distribution of cystine/glutamate antiporter in CNS has not been well characterized. Here, we analyzed expression of the catalytic subunit of the cystine/glutamate antiporter, xCT, by immunohistochemistry in histological sections of the forebrain and spinal cord. We detected labeling in neurons, oligodendrocytes, microglia, and oligodendrocyte precursor cells, but not in GFAP(+) astrocytes. In addition, we examined xCT expression and function by qPCR and cystine uptake in primary rat cultures of CNS, detecting higher levels of antiporter expression in neurons and oligodendrocytes. Chronic inhibition of cystine/glutamate antiporter caused high toxicity to cultured oligodendrocytes. In accordance, chronic blockage of cystine/glutamate antiporter as well as glutathione depletion caused myelin disruption in organotypic cerebellar slices. Finally, mice chronically treated with sulfasalazine, a cystine/glutamate antiporter inhibitor, showed a reduction in the levels of myelin and an increase in the myelinated fiber g-ratio. Together, these results reveal that cystine/glutamate antiporter is expressed in oligodendrocytes, where it is a key factor to the maintenance of cell homeostasis. GLIA 2016. GLIA 2016;64:1381-1395. PMID:27247047

  8. THE HYDROTHERMAL REACTIONS OF MONOSODIUM TITANATE, CRYSTALLINE SILICOTITANATE AND SLUDGE IN THE MODULAR SALT PROCESS: A LITERATURE SURVEY

    SciTech Connect

    Fondeur, F.; Pennebaker, F.; Fink, S.

    2010-11-11

    The use of crystalline silicotitanate (CST) is proposed for an at-tank process to treat High Level Waste at the Savannah River Site. The proposed configuration includes deployment of ion exchange columns suspended in the risers of existing tanks to process salt waste without building a new facility. The CST is available in an engineered form, designated as IE-911-CW, from UOP. Prior data indicates CST has a proclivity to agglomerate from deposits of silica rich compounds present in the alkaline waste solutions. This report documents the prior literature and provides guidance for the design and operations that include CST to mitigate that risk. The proposed operation will also add monosodium titanate (MST) to the supernate of the tank prior to the ion exchange operation to remove strontium and select alpha-emitting actinides. The cesium loaded CST is ground and then passed forward to the sludge washing tank as feed to the Defense Waste Processing Facility (DWPF). Similarly, the MST will be transferred to the sludge washing tank. Sludge processing includes the potential to leach aluminum from the solids at elevated temperature (e.g., 65 C) using concentrated (3M) sodium hydroxide solutions. Prior literature indicates that both CST and MST will agglomerate and form higher yield stress slurries with exposure to elevated temperatures. This report assessed that data and provides guidance on minimizing the impact of CST and MST on sludge transfer and aluminum leaching sludge.

  9. Effects of RuPeng15 Powder (RPP15) on Monosodium Urate Crystal-Induced Gouty Arthritis in Rats

    PubMed Central

    Kou, Y.-Y.; Li, Y.-F.; Xu, M.; Li, W.-Y.; Yang, M.; Li, R.-L.

    2015-01-01

    RuPeng15 Powder (RPP15) is a herbal multicompound remedy that originates from traditional Tibetan medicine and possesses antigout, anti-inflammatory, and antihyperuricemic properties based on the traditional conceptions. The present study was undertaken to evaluate the therapeutic effect of PRP15 in rat gouty arthritis induced by monosodium urate (MSU) crystals. In the present study, we found that treatment with RPP15 (0.4, 0.8, and 1.2 g/kg) in rats with gouty arthritis induced by MSU crystals significantly attenuated the knee swelling. Histomorphometric and immunohistochemistry analyses revealed that MSU-induced inflammatory cell infiltration and the elevated expressions of nuclear transcription factor-κB p65 (NF-κB p65) in synovial tissues were significantly inhibited, and enzyme-linked immunosorbent assay (ELISA) result showed that MSU-induced high levels of tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-8 (IL-8) in synovial fluid were reduced by treatment with RPP15 (0.4, 0.8, and 1.2 g/kg). We conclude that RPP15 may be a promising candidate for the development of a new treatment for gout and its activity of antigout may be partially related to inhibiting TNF-α, IL-1β, IL-8, and NF-κB p65 expression in the synovial tissues. PMID:26221174

  10. Monosodium Urate in the Presence of RANKL Promotes Osteoclast Formation through Activation of c-Jun N-Terminal Kinase

    PubMed Central

    Choe, Jung-Yoon; Park, Ki-Yeun; Kim, Seong-Kyu

    2015-01-01

    The aim of this study was to clarify the role of monosodium urate (MSU) crystals in receptor activator of nuclear factor kB ligand- (RANKL-) RANK-induced osteoclast formation. RAW 264.7 murine macrophage cells were incubated with MSU crystals or RANKL and differentiated into osteoclast-like cells as confirmed by staining for tartrate-resistant acid phosphatase (TRAP) and actin ring, pit formation assay, and TRAP activity assay. MSU crystals in the presence of RANKL augmented osteoclast differentiation, with enhanced mRNA expression of NFATc1, cathepsin K, carbonic anhydrase II, and matrix metalloproteinase-9 (MMP-9), in comparison to RAW 264.7 macrophages incubated in the presence of RANKL alone. Treatment with both MSU crystals and RANKL induced osteoclast differentiation by activating downstream molecules in the RANKL-RANK pathway including tumor necrosis factor receptor-associated factor 6 (TRAF-6), JNK, c-Jun, and NFATc1. IL-1b produced in response to treatment with both MSU and RANKL is involved in osteoclast differentiation in part through the induction of TRAF-6 downstream of the IL-1b pathway. This study revealed that MSU crystals contribute to enhanced osteoclast formation through activation of RANKL-mediated pathways and recruitment of IL-1b. These findings suggest that MSU crystals might be a pathologic causative agent of bone destruction in gout. PMID:26347587

  11. Permanent uncoupling of male-specific CYP2C11 transcription/translation by perinatal glutamate

    SciTech Connect

    Banerjee, Sarmistha; Das, Rajat Kumar; Giffear, Kelly A.; Shapiro, Bernard H.

    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

  12. Activation Requirements for Metabotropic Glutamate Receptors

    PubMed Central

    Viaene, Angela N.; Petrof, Iraklis; Sherman, S. Murray

    2013-01-01

    It has been common experimentally to use high frequency, tetanic, stimulation to activate metabotropic glutamate receptors (mGluRs) in cortex and thalamus. To determine what type of stimulation is actually necessary to activate mGluRs we examined the effects of varying stimulation duration and intensity on activating mGluR responses. We used a thalamocortical and an intracortical slice preparation from mice and performed whole cell recordings from neurons in the ventral posterior medial nucleus or in layer 4 of primary somatosensory cortex (S1) while electrically stimulating in layer 6 of S1. Extracellular ionotropic glutamate receptor antagonists and GABAA receptor antagonists were used to isolate Group I or Group II mGluR responses. We observed that high frequency stimulation is not necessary for the activation of either Group I or Group II mGluRs. Either could be activated with as few as 2-3 pulses at stimulation frequencies around 15-20Hz. Additionally, increasing the number of pulses, intensity of stimulation, or stimulation frequency increased amplitude and duration of the mGluR response. PMID:23416319

  13. Glutamate-1-semialdehyde aminotransferase from Sulfolobus solfataricus.

    PubMed

    Palmieri, G; Di Palo, M; Scaloni, A; Orru, S; Marino, G; Sannia, G

    1996-12-01

    Glutamate-1-semialdehyde aminotransferase (GSA-AT) from the extremely thermophilic bacterium Sulfolobus solfataricus has been purified to homogeneity and characterized. GSA-AT is the last enzyme in the C5 pathway for the conversion of glutamate into the tetrapyrrole precursor delta-aminolaevulinate (ALA) in plants, algae and several bacteria. The active form of GSA-AT from S. solfataricus seems to be a homodimer with a molecular mass of 87 kDa. The absorption spectrum of the purified aminotransferase is indicative of the presence of pyridoxamine 5'-phosphate (PMP) cofactor, and the catalytic activity of the enzyme is further stimulated by addition of PMP. 3-Amino-2,3-dihydrobenzoic acid is an inhibitor of the aminotransferase activity. The N-terminal amino acid sequence of GSA-AT from S. solfataricus was found to share significant similarity with the eukaryotic and eubacterial enzymes. Evidence is provided that ALA synthesis in S. solfataricus follows the C5 pathway characteristic of plants, algae, cyanobacteria and many other bacteria. PMID:8973563

  14. Effect of biotin on transcription levels of key enzymes and glutamate efflux in glutamate fermentation by Corynebacterium glutamicum.

    PubMed

    Cao, Yan; Duan, Zuoying; Shi, Zhongping

    2014-02-01

    Biotin is an important factor affecting the performance of glutamate fermentation by biotin auxotrophic Corynebacterium glutamicum and glutamate is over-produced only when initial biotin content is controlled at suitable levels or initial biotin is excessive but with Tween 40 addition during fermentation. The transcription levels of key enzymes at pyruvate, isocitrate and α-ketoglutarate metabolic nodes, as well as transport protein (TP) of glutamate were investigated under the conditions of varied biotin contents and Tween 40 supplementation. When biotin was insufficient, the genes encoding key enzymes and TP were down-regulated in the early production phase, in particular, the transcription level of isocitrate dehydrogenase (ICDH) which was only 2% of that of control. Although the cells' morphology transformation and TP level were not affected, low transcription level of ICDH led to lower final glutamate concentration (64 g/L). When biotin was excessive, the transcription levels of key enzymes were at comparable levels as those of control with ICDH as an exception, which was only 3-22% of control level throughout production phase. In this case, little intracellular glutamate accumulation (1.5 mg/g DCW) and impermeable membrane resulted in non glutamate secretion into broth, even though the quantity of TP was more than 10-folds of control level. Addition of Tween 40 when biotin was excessive stimulated the expression of all key enzymes and TP, intracellular glutamate content was much higher (10-12 mg/g DCW), and final glutamate concentration reached control level (75-80 g/L). Hence, the membrane alteration and TP were indispensable in glutamate secretion. Biotin and Tween 40 influenced the expression level of ICDH and glutamate efflux, thereby influencing glutamate production. PMID:23990041

  15. On the regulative role of the glutamate receptor in mitochondria.

    PubMed

    Selin, Alexey A; Lobysheva, Natalia V; Nesterov, Semen V; Skorobogatova, Yulia A; Byvshev, Ivan M; Pavlik, Lyubov L; Mikheeva, Irina B; Moshkov, Dmitry A; Yaguzhinsky, Lev S; Nartsissov, Yaroslav R

    2016-05-01

    The purpose of this work was to study the regulative role of the glutamate receptor found earlier in the brain mitochondria. In the present work a glutamate-dependent signaling system with similar features was detected in mitochondria of the heart. The glutamate-dependent signaling system in the heart mitochondria was shown to be suppressed by γ-aminobutyric acid (GABA). The GABA receptor presence in the heart mitochondria was shown by golding with the use of antibodies to α- and β-subunits of the receptor. The activity of glutamate receptor was assessed according to the rate of synthesis of hydrogen peroxide. The glutamate receptor in mitochondria could be activated only under conditions of hypoxic stress, which in model experiments was imitated by blocking Complex I by rotenone or fatty acids. The glutamate signal in mitochondria was shown to be calcium- and potential-dependent and the activation of the glutamate cascade was shown to be accompanied by production of hydrogen peroxide. It was discovered that H2O2 synthesis involves two complexes of the mitochondrial electron transfer system - succinate dehydrogenase (SDH) and fatty acid dehydrogenase (ETF:QO). Thus, functions of the glutamate signaling system are associated with the system of respiration-glycolysis switching (the Pasteur-Crabtree) under conditions of hypoxia. PMID:26812870

  16. 21 CFR 522.1125 - Hemoglobin glutamer-200 (bovine).

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Hemoglobin glutamer-200 (bovine). 522.1125 Section... § 522.1125 Hemoglobin glutamer-200 (bovine). (a) Specifications. Each 125 milliliter bag contains 13 grams per deciliter of polymerized hemoglobin of bovine origin in modified Lactated Ringer's...

  17. 21 CFR 522.1125 - Hemoglobin glutamer-200 (bovine).

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Hemoglobin glutamer-200 (bovine). 522.1125 Section... § 522.1125 Hemoglobin glutamer-200 (bovine). (a) Specifications. Each 125 milliliter bag contains 13 grams per deciliter of polymerized hemoglobin of bovine origin in modified Lactated Ringer's...

  18. 21 CFR 522.1125 - Hemoglobin glutamer-200 (bovine).

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Hemoglobin glutamer-200 (bovine). 522.1125 Section... § 522.1125 Hemoglobin glutamer-200 (bovine). (a) Specifications. Each 125 milliliter bag contains 13 grams per deciliter of polymerized hemoglobin of bovine origin in modified Lactated Ringer's...

  19. 21 CFR 522.1125 - Hemoglobin glutamer-200 (bovine).

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Hemoglobin glutamer-200 (bovine). 522.1125 Section... § 522.1125 Hemoglobin glutamer-200 (bovine). (a) Specifications. Each 125 milliliter bag contains 13 grams per deciliter of polymerized hemoglobin of bovine origin in modified Lactated Ringer's...

  20. Modulation of intestinal L-glutamate transport by luminal leptin.

    PubMed

    Fanjul, Carmen; Barrenetxe, Jaione; Lostao, María Pilar; Ducroc, Robert

    2015-06-01

    Leptin is secreted into the digestive tract and contributes to the absorption of dietary molecules by regulating transporters activity. Here, we studied the effect of luminal leptin on the intestinal transport of L-glutamate, an important component of human diet. We examined the effect of leptin on L-glutamate uptake in rat intestine in vitro measuring glutamate-induced short-circuit current (Isc) in Ussing chambers and L-[(3)H (U)]-glutamate uptake in jejunal everted rings. Glutamate-induced Isc was only observed in Na(+)-free conditions. This Isc was concentration (1-60 mmol L(-1)) and pH dependent. Luminal leptin increased glutamate Isc (∼100 %). Dose-response curve showed a biphasic pattern, with maximal stimulations observed at 10(-13) and 10(-10) mmol L(-1), that were sensitive to leptin receptor antagonist. In everted rings, two glutamate transport mechanisms were distinguished: a Na(+)-dependent, H(+)-independent, that was inhibited by leptin (∼20 %), and a Na(+)-independent but H(+)-dependent, that was enhanced by leptin (∼20 %), in line with data obtained in Ussing chambers. Altogether, these data reveal original non-monotonic effect of luminal leptin in the intestine and demonstrate a new role for this hormone in the modulation of L-glutamate transport, showing that luminal active gut peptides can influence absorption of amino acids. PMID:25935421

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

    NASA Astrophysics Data System (ADS)

    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.

  2. Neuronal vs glial glutamate uptake: Resolving the conundrum.

    PubMed

    Danbolt, N C; Furness, D N; Zhou, Y

    2016-09-01

    Neither normal brain function nor the pathological processes involved in neurological diseases can be adequately understood without knowledge of the release, uptake and metabolism of glutamate. The reason for this is that glutamate (a) is the most abundant amino acid in the brain, (b) is at the cross-roads between several metabolic pathways, and (c) serves as the major excitatory neurotransmitter. In fact most brain cells express glutamate receptors and are thereby influenced by extracellular glutamate. In agreement, brain cells have powerful uptake systems that constantly remove glutamate from the extracellular fluid and thereby limit receptor activation. It has been clear since the 1970s that both astrocytes and neurons express glutamate transporters. However the relative contribution of neuronal and glial transporters to the total glutamate uptake activity, however, as well as their functional importance, has been hotly debated ever since. The present short review provides (a) an overview of what we know about neuronal glutamate uptake as well as an historical description of how we got there, and (b) a hypothesis reconciling apparently contradicting observations thereby possibly resolving the paradox. PMID:27235987

  3. Cortical neurons exposed to glutamate rapidly leak preloaded chromium 51

    SciTech Connect

    Maulucci-Gedde, M.; Choi, D.W.

    1987-05-01

    The acute toxic effects of excess glutamate exposure on cortical neurons in culture was followed using a novel adaptation of the /sup 51/Cr efflux assay. Although the acute, sodium-dependent phase of glutamate neurotoxicity may contribute to several acute disease settings, including sustained seizures and stroke, functional aspects of the phenomenon have not been previously studied. We report here that the earliest morphologic sign of glutamate neurotoxicity, neuronal swelling, is accompanied by a large efflux of complexed /sup 51/Cr from preloaded neurons in the first hour after exposure, and that this efflux is detectable as early as 15 min after the onset of glutamate exposure. We suggest that this pathological burst of /sup 51/Cr may result from glutamate-induced leakiness of neuronal cell membranes.

  4. Polysaccharides from wolfberry antagonizes glutamate excitotoxicity in rat cortical neurons.

    PubMed

    Ho, Yuen-Shan; Yu, Man-Shan; Yik, Suet-Yi; So, Kwok-Fai; Yuen, Wai-Hung; Chang, Raymond Chuen-Chung

    2009-12-01

    Glutamate excitotoxicity is involved in many neurodegenerative diseases including Alzheimer's disease (AD). Attenuation of glutamate toxicity is one of the therapeutic strategies for AD. Wolfberry (Lycium barbarum) is a common ingredient in oriental cuisines. A number of studies suggest that wolfberry has anti-aging properties. In recent years, there is a trend of using dried Wolfberry as food supplement and health product in UK and North America. Previously, we have demonstrated that a fraction of polysaccharide from Wolfberry (LBA) provided remarkable neuroprotective effects against beta-amyloid peptide-induced cytotoxicity in primary cultures of rat cortical neurons. To investigate whether LBA can protect neurons from other pathological factors such as glutamate found in Alzheimer brain, we examined whether it can prevent neurotoxicity elicited by glutamate in primary cultured neurons. The glutamate-induced cell death as detected by lactate dehydrogenase assay and caspase-3-like activity assay was significantly reduced by LBA at concentrations ranging from 10 to 500 microg/ml. Protective effects of LBA were comparable to memantine, a non-competitive NMDA receptor antagonist. LBA provided neuroprotection even 1 h after exposure to glutamate. In addition to glutamate, LBA attenuated N-methyl-D-aspartate (NMDA)-induced neuronal damage. To further explore whether LBA might function as antioxidant, we used hydrogen peroxide (H(2)O(2)) as oxidative stress inducer in this study. LBA could not attenuate the toxicity of H(2)O(2). Furthermore, LBA did not attenuate glutamate-induced oxidation by using NBT assay. Western blot analysis indicated that glutamate-induced phosphorylation of c-jun N-terminal kinase (JNK) was reduced by treatment with LBA. Taken together, LBA exerted significant neuroprotective effects on cultured cortical neurons exposed to glutamate. PMID:19499323

  5. Glutamate release from astrocytic gliosomes under physiological and pathological conditions.

    PubMed

    Milanese, Marco; Bonifacino, Tiziana; Zappettini, Simona; Usai, Cesare; Tacchetti, Carlo; Nobile, Mario; Bonanno, Giambattista

    2009-01-01

    Glial subcellular particles (gliosomes) have been purified from rat cerebral cortex or mouse spinal cord and investigated for their ability to release glutamate. Confocal microscopy showed that gliosomes are enriched with glia-specific proteins, such as GFAP and S-100 but not neuronal proteins, such as PSD-95, MAP-2, and beta-tubulin III. Furthermore, gliosomes exhibit labeling neither for integrin-alphaM nor for myelin basic protein, specific for microglia and oligodendrocytes, respectively. The gliosomal fraction contains proteins of the exocytotic machinery coexisting with GFAP. Consistent with ultrastructural analysis, several nonclustered vesicles are present in the gliosome cytoplasm. Finally, gliosomes represent functional organelles that actively export glutamate when subjected to releasing stimuli, such as ionomycin, high KCl, veratrine, 4-aminopyridine, AMPA, or ATP by mechanisms involving extracellular Ca2+, Ca2+ release from intracellular stores as well as reversal of glutamate transporters. In addition, gliosomes can release glutamate also by a mechanism involving heterologous transporter activation (heterotransporters) located on glutamate-releasing and glutamate transporter-expressing (homotransporters) gliosomes. This glutamate release involves reversal of glutamate transporters and anion channel opening, but not exocytosis. Both the exocytotic and the heterotransporter-mediated glutamate release were more abundant in gliosomes prepared from the spinal cord of transgenic mice, model of amyotrophic lateral sclerosis, than in controls; suggesting the involvement of astrocytic glutamate release in the excitotoxicity proposed as a cause of motor neuron degeneration. The results support the view that gliosomes may represent a viable preparation that allows to study mechanisms of astrocytic transmitter release and its regulation in healthy animals and in animal models of brain diseases. PMID:19607977

  6. Prefrontal glutamate correlates of methamphetamine sensitization and preference.

    PubMed

    Lominac, Kevin D; Quadir, Sema G; Barrett, Hannah M; McKenna, Courtney L; Schwartz, Lisa M; Ruiz, Paige N; Wroten, Melissa G; Campbell, Rianne R; Miller, Bailey W; Holloway, John J; Travis, Katherine O; Rajasekar, Ganesh; Maliniak, Dan; Thompson, Andrew B; Urman, Lawrence E; Kippin, Tod E; Phillips, Tamara J; Szumlinski, Karen K

    2016-03-01

    Methamphetamine (MA) is a widely misused, highly addictive psychostimulant that elicits pronounced deficits in neurocognitive function related to hypo-functioning of the prefrontal cortex (PFC). Our understanding of how repeated MA impacts excitatory glutamatergic transmission within the PFC is limited, as is information about the relationship between PFC glutamate and addiction vulnerability/resiliency. In vivo microdialysis and immunoblotting studies characterized the effects of MA (ten injections of 2 mg/kg, i.p.) upon extracellular glutamate in C57BL/6J mice and upon glutamate receptor and transporter expression, within the medial PFC. Glutamatergic correlates of both genetic and idiopathic variance in MA preference/intake were determined through studies of high vs. low MA-drinking selectively bred mouse lines (MAHDR vs. MALDR, respectively) and inbred C57BL/6J mice exhibiting spontaneously divergent place-conditioning phenotypes. Repeated MA sensitized drug-induced glutamate release and lowered indices of N-methyl-d-aspartate receptor expression in C57BL/6J mice, but did not alter basal extracellular glutamate content or total protein expression of Homer proteins, or metabotropic or α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid glutamate receptors. Elevated basal glutamate, blunted MA-induced glutamate release and ERK activation, as well as reduced protein expression of mGlu2/3 and Homer2a/b were all correlated biochemical traits of selection for high vs. low MA drinking, and Homer2a/b levels were inversely correlated with the motivational valence of MA in C57BL/6J mice. These data provide novel evidence that repeated, low-dose MA is sufficient to perturb pre- and post-synaptic aspects of glutamate transmission within the medial PFC and that glutamate anomalies within this region may contribute to both genetic and idiopathic variance in MA addiction vulnerability/resiliency. PMID:26742098

  7. Serum Glutamic-Oxaloacetic Transaminase (GOT) and Glutamic-Pyruvic Transaminase (GPT) Levels in Children and Adolescents with Intellectual Disabilities

    ERIC Educational Resources Information Center

    Lin, Jin-Ding; Lin, Pei-Ying; Chen, Li-Mei; Fang, Wen-Hui; Lin, Lan-Ping; Loh, Ching-Hui

    2010-01-01

    The elevated serum glutamic-oxaloacetic transaminase (GOT) and glutamic-pyruvic transaminase (GPT) rate among people with intellectual disabilities (ID) is unknown and have not been sufficiently studies. The present paper aims to provide the profile of GOT and GPT, and their associated relationship with other biochemical levels of children or…

  8. Glutamate-induced glutamate release: A proposed mechanism for calcium bursting in astrocytes

    NASA Astrophysics Data System (ADS)

    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.

  9. Rheology Of MonoSodium Titanate (MST) And Modified Mst (mMST) Mixtures Relevant To The Salt Waste Processing Facility

    SciTech Connect

    Koopman, D. C.; Martino, C. J.; Shehee, T. C.; Poirier, M. R.

    2013-07-31

    The Savannah River National Laboratory performed measurements of the rheology of suspensions and settled layers of treated material applicable to the Savannah River Site Salt Waste Processing Facility. Suspended solids mixtures included monosodium titanate (MST) or modified MST (mMST) at various solid concentrations and soluble ion concentrations with and without the inclusion of kaolin clay or simulated sludge. Layers of settled solids were MST/sludge or mMST/sludge mixtures, either with or without sorbed strontium, over a range of initial solids concentrations, soluble ion concentrations, and settling times.

  10. MyD88-dependent IL-1 receptor signaling is essential for gouty inflammation stimulated by monosodium urate crystals

    PubMed Central

    Chen, Chun-Jen; Shi, Yan; Hearn, Arron; Fitzgerald, Kate; Golenbock, Douglas; Reed, George; Akira, Shizuo; Rock, Kenneth L.

    2006-01-01

    While it is known that monosodium urate (MSU) crystals cause the disease gout, the mechanism by which these crystals stimulate this inflammatory condition has not been clear. Here we find that the Toll/IL-1R (TIR) signal transduction adaptor myeloid differentiation primary response protein 88 (MyD88) is required for acute gouty inflammation. In contrast, other TIR adaptor molecules, TIRAP/Mal, TRIF, and TRAM, are not required for this process. The MyD88-dependent TLR1, -2, -4, -6, -7, -9, and -11 and IL-18 receptor (IL-18R) are not essential for MSU-induced inflammation. Moreover, MSU does not stimulate HEK cells expressing TLR1–11 to activate NF-κB. In contrast, mice deficient in the MyD88-dependent IL-1R showed reduced inflammatory responses, similar to those observed in MyD88-deficient mice. Similarly, mice treated with IL-1 neutralizing antibodies also showed reduced MSU-induced inflammation, demonstrating that IL-1 production and IL-1R activation play essential roles in MSU-triggered inflammation. IL-1R deficiency in bone marrow–derived cells did not affect the inflammatory response; however, it was required in non–bone marrow–derived cells. These results indicate that IL-1 is essential for the MSU-induced inflammatory response and that the requirement of MyD88 in this process is primarily through its function as an adaptor molecule in the IL-1R signaling pathway. PMID:16886064

  11. Enteral administration of monosodium phosphate, monopotassium phosphate and monocalcium phosphate for the treatment of hypophosphataemia in lactating dairy cattle.

    PubMed

    Idink, M J; Grünberg, W

    2015-05-01

    Hypohosphataemia is a frequent finding in early lactating and anorectic dairy cows. Sodium phosphate is commonly used for oral phosphorus (P) supplementation, although other phosphate salts may present useful treatment alternatives. Objectives of this study were to compare the efficacy of monopotassium phosphate (KH2PO4) and monocalcium phosphate (Ca(H2PO4)2) to monosodium phosphate (NaH2PO4) in P-depleted cows. Furthermore, the effect of concentrated NaH2PO4 on the reticular groove reflex was studied. Six healthy but P-depleted dairy cows underwent four treatments in randomised order. Treatments consisted of intraruminal administration of NaH2PO4, KH2PO4 and Ca(H2PO4)2 providing the equivalent of 60 g P. A fourth treatment consisting of concentrated NaH2PO4 combined with acetaminophen as a marker substance was administered orally to determine whether the reticular groove reflex could be induced. Intraruminal administration of NaH2PO4 and KH2PO4 resulted in similar increases in plasma Pi concentrations ([Pi]) while intraruminal Ca(H2PO4)2 resulted in lower increases in plasma [Pi]. Oral and intraruminal administration of NaH2PO4 resulted in similar times to peak plasma [Pi] and acetaminophen concentration, indicating that concentrated NaH2PO4 administered orally did not trigger the reticular groove reflex. These results suggest that oral administration of KH2PO4 is equally effective as NaH2PO4. Oral administration of Ca(H2PO4)2 in contrast has a less pronounced effect on the plasma [Pi]. PMID:25721509

  12. Determination of Fissile Loadings onto Monosodium Titanate (MST) under Conditions Relevant to the Actinide Removal Process Facility

    SciTech Connect

    Peters, T

    2005-11-15

    This report describes the results of an experimental study to measure the sorption of fissile actinides on monosodium titanate (MST) at conditions relevant to operation of the Actinide Removal Process (ARP). The study examined the effect of a single contact of a large volume of radionuclide-spiked simulant solution with a small mass of MST. The volume of simulant to MST (8.5 L to 0.2 g of MST solids) was designed to mimic the maximum phase ratio that occurs between the multiple contacts of MST and waste solution and washing of the accumulated solids cycle of ARP. This work provides the following results. (1) After a contact time of {approx}2 weeks, we measured the following actinide loadings on the MST (average of solution and solids data), Pu: 2.79 {+-} 0.197 wt %, U: 14.0 {+-} 1.04 wt %, and Np: 0.839 {+-} 0.0178 wt %. (2) The plutonium and uranium loadings reported above are considerably higher than previously reported values. The higher loading result from the very high phase ratio and the high initial mass concentrations of uranium and plutonium. A separate upcoming document details the predicted values for this system versus the results. (3) The strontium DF values measured in these tests proved much lower than those reported previously with simulants having the same bulk chemical composition. The low strontium DF values reflect the very low initial mass concentration of strontium in this simulant (<100 {micro}g/L) compared to that in previous testing (> 600 {micro}g/L).

  13. Effect of alcoholic extract of Entada pursaetha DC on monosodium iodoacetate-induced osteoarthritis pain in rats

    PubMed Central

    Kumari, Rashmi R.; More, Amar S.; Gupta, Gaurav; Lingaraju, Madhu C.; Balaganur, Venkanna; Kumar, Pankaj; Kumar, Dinesh; Sharma, Anil K.; Mishra, Santosh K.; Tandan, Surendra Kumar

    2015-01-01

    Background & objectives: Osteoarthritis (OA) is a degenerative disease characterized by joint pain and progressive loss of articular cartilage. Entada pursaetha has been traditionally used in the treatment of inflammatory disease, liver ailment, etc. In this study we investigated suppressive effect of ethanolic extract of E. pursaetha (EPE) on monosodium iodoacetate (MIA)-induced osteoarthritis pain and disease progression by histopathological changes in joints in a rat model. Methods: OA was induced in right knee of rat by intra-articular injection of 3 mg of MIA and characterized by pathological progression of disease and pain of affected joint. Spontaneous movements, mechanical, thermal and cold sensitivity were monitored at days 0 (before drug and MIA injection), 7, 14 and 21 of MIA administration. EPE (30, 100 and 300 mg/kg), vehicle or etoricoxib (10 mg/kg; reference drug) were administered daily for 21 days by oral route. Results: EPE at various doses significantly reduced mechanical, heat, cold hyperalgesia and increased the horizontal and vertical movements in intra-articular MIA injected rats. EPE prevented the damage to cartilage structure and reduced the cellular abnormalities. Articular cartilage of rats treated with EPE at 300 mg/kg group was almost normal with well-developed smooth surface and chondrocytes were distributed individually or arranged in column. Interpretation & conclusions: The present findings showed that the EPE was not only able to mitigate pain and hyperalgesia but also inhibited MIA-induced cartilage degeneration in vivo. EPE may have the potential to become therapeutic modality in the treatment of osteoarthritis. However, further studies need to be done to confirm these findings in other models and clinical trials. PMID:26112847

  14. Monosodium Urate Activates Src/Pyk2/PI3 Kinase and Cathepsin Dependent Unconventional Protein Secretion From Human Primary Macrophages*

    PubMed Central

    Välimäki, Elina; Miettinen, Juho J.; Lietzén, Niina; Matikainen, Sampsa; Nyman, Tuula A.

    2013-01-01

    Monosodium urate (MSU) is an endogenous danger signal that is crystallized from uric acid released from injured cells. MSU is known to activate inflammatory response in macrophages but the molecular mechanisms involved have remained uncharacterized. Activated macrophages start to secrete proteins to activate immune response and to recruit other immune cells to the site of infection and/or tissue damage. Secretome characterization after activation of innate immune system is essential to unravel the details of early phases of defense responses. Here, we have analyzed the secretome of human primary macrophages stimulated with MSU using quantitative two-dimensional gel electrophoresis based proteomics as well as high-throughput qualitative GeLC-MS/MS approach combining protein separation by SDS-PAGE and protein identification by liquid chromatography-MS/MS. Both methods showed that MSU stimulation induced robust protein secretion from lipopolysaccharide-primed human macrophages. Bioinformatic analysis of the secretome data showed that MSU stimulation strongly activates unconventional, vesicle mediated protein secretion. The unconventionally secreted proteins included pro-inflammatory cytokines like IL-1β and IL-18, interferon-induced proteins, and danger signal proteins. Also active forms of lysosomal proteases cathepsins were secreted on MSU stimulation, and cathepsin activity was essential for MSU-induced unconventional protein secretion. Additionally, proteins associated to phosphorylation events including Src family tyrosine kinases were increased in the secretome of MSU-stimulated cells. Our functional studies demonstrated that Src, Pyk2, and PI3 kinases act upstream of cathepsins to activate the overall protein secretion from macrophages. In conclusion, we provide the first comprehensive characterization of protein secretion pathways activated by MSU in human macrophages, and reveal a novel role for cathepsins and Src, Pyk2, PI3 kinases in the activation of

  15. Small molecule glutaminase inhibitors block glutamate release from stimulated microglia.

    PubMed

    Thomas, Ajit G; O'Driscoll, Cliona M; Bressler, Joseph; Kaufmann, Walter; Rojas, Camilo J; Slusher, Barbara S

    2014-01-01

    Glutaminase plays a critical role in the generation of glutamate, a key excitatory neurotransmitter in the CNS. Excess glutamate release from activated macrophages and microglia correlates with upregulated glutaminase suggesting a pathogenic role for glutaminase. Both glutaminase siRNA and small molecule inhibitors have been shown to decrease excess glutamate and provide neuroprotection in multiple models of disease, including HIV-associated dementia (HAD), multiple sclerosis and ischemia. Consequently, inhibition of glutaminase could be of interest for treatment of these diseases. Bis-2-(5-phenylacetimido-1,2,4-thiadiazol-2-yl)ethyl sulfide (BPTES) and 6-diazo-5-oxo-l-norleucine (DON), two most commonly used glutaminase inhibitors, are either poorly soluble or non-specific. Recently, several new BPTES analogs with improved physicochemical properties were reported. To evaluate these new inhibitors, we established a cell-based microglial activation assay measuring glutamate release. Microglia-mediated glutamate levels were significantly augmented by tumor necrosis factor (TNF)-α, phorbol 12-myristate 13-acetate (PMA) and Toll-like receptor (TLR) ligands coincident with increased glutaminase activity. While several potent glutaminase inhibitors abrogated the increase in glutamate, a structurally related analog devoid of glutaminase activity was unable to block the increase. In the absence of glutamine, glutamate levels were significantly attenuated. These data suggest that the in vitro microglia assay may be a useful tool in developing glutaminase inhibitors of therapeutic interest. PMID:24269238

  16. Dietary Glutamate: Interactions With the Enteric Nervous System

    PubMed Central

    Wang, Guo-Du; Wang, Xi-Yu; Xia, Yun

    2014-01-01

    Background/Aims Digestion of dietary protein elevates intraluminal concentrations of glutamate in the small intestine, some of which gain access to the enteric nervous system (ENS). Glutamate, in the central nervous system (CNS), is an excitatory neurotransmitter. A dogma that glutamatergic neurophysiology in the ENS recapitulates CNS glutamatergic function persists. We reassessed the premise that glutamatergic signaling in the ENS recapitulates its neurotransmitter role in the CNS. Methods Pharmacological analysis of actions of receptor agonists and antagonists in concert with immunohistochemical localization of glutamate transporters and receptors was used. Analysis focused on intracellularly-recorded electrical and synaptic behavior of ENS neurons, on stimulation of mucosal secretion by secretomotor neurons in the submucosal plexus and on muscle contractile behavior mediated by musculomotor neurons in the myenteric plexus. Results Immunoreactivity for glutamate was expressed in ENS neurons. ENS neurons expressed immunoreactivity for the EAAC-1 glutamate transporter. Neither L-glutamate nor glutamatergic receptor agonists had excitatory actions on ENS neurons. Metabotropic glutamatergic receptor agonists did not directly stimulate neurogenic mucosal chloride secretion. Neither L-glutamate nor the metabotropic glutamatergic receptor agonist, aminocyclopentane-1,3-dicarboxylic acid (ACPD), changed the mean amplitude of spontaneously occurring contractions in circular or longitudinal strips of intestinal wall from either guinea pig or human small intestinal preparations. Conclusions Early discoveries, for excitatory glutamatergic neurotransmission in the CNS, inspired enthusiasm that investigation in the ENS would yield discoveries recapitulating the CNS glutamatergic story. We found this not to be the case. PMID:24466444

  17. Glutamate carboxypeptidase II (NAALADase) inhibition as a novel therapeutic strategy.

    PubMed

    Thomas, Ajit G; Wozniak, Krystyna M; Tsukamoto, Takashi; Calvin, David; Wu, Ying; Rojas, Camilo; Vornov, James; Slusher, Barbara S

    2006-01-01

    GCP II inhibition decreases extracellular excitotoxic glutamate and increases extracellular NAAG, both of which provide neuroprotection. We have demonstrated with our potent and selective GCP II inhibitors efficacy in models of stroke, ALS and neuropathic pain. GCP II inhibition may have significant potential benefits over existing glutamate-based neuroprotection strategies. The upstream mechanism seems selective for excitotoxic induced glutamate release, as GCP II inhibitors in normal animals induced no change in basal glutamate. This suggestion has recently been corroborated by Lieberman and coworkers24 who found that both NAAG release and increase in GCP II activity appear to be induced by electrical stimulation in crayfish nerve fibers and that subsequent NAAG hydrolysis to glutamate contributes, at least in part, to subsequent NMDA receptor activation. Interestingly, even at relatively high doses of compounds, GCP II inhibition did not appear to be associated with learning/memory deficits in animals. Additionally, quantitative neurophysiological testing data and visual analog scales for 'psychedelic effects' in Phase I single dose and repeat dose studies showed GCP II inhibition to be safe and well tolerated by both healthy volunteers and diabetic patients. GCP II inhibition may represent a novel glutamate regulating strategy devoid of the side effects that have hampered the development of postsynaptic glutamate receptor antagonists. PMID:16802724

  18. Group II metabotropic glutamate receptors inhibit glutamate release at thalamocortical synapses in the developing somatosensory cortex.

    PubMed

    Mateo, Z; Porter, J T

    2007-05-25

    Thalamocortical synapses provide a strong glutamatergic excitation to cortical neurons that is critical for processing sensory information. Unit recordings in vivo indicate that metabotropic glutamate receptors (mGluRs) reduce the effect of thalamocortical input on cortical circuits. However, it is not known whether this reduction is due to a reduction in glutamate release from thalamocortical terminals or from a decrease in cortical neuron excitability. To directly determine whether mGluRs act as autoreceptors on thalamocortical terminals, we examined the effect of mGluR agonists on thalamocortical synapses in slices. Thalamocortical excitatory postsynaptic currents (EPSCs) were recorded in layer IV cortical neurons in developing mouse brain slices. The activation of group II mGluRs with (2S,2'R,3'R)-2-(2',3'-dicarboxycyclopropyl)glycine (DCG IV) reduced thalamocortical EPSCs in both excitatory and inhibitory neurons, while the stimulation of group I or group III mGluRs had no effect on thalamocortical EPSCs. Consistent with a reduction in glutamate release, DCG IV increased the paired pulse ratio and the coefficient of variation of the EPSCs. The reduction induced by DCG IV was reversed by the group II mGluR antagonist, LY341495, and mimicked by another selective group II agonist, (2R,4R)-4-aminopyrrolidine-2,4-dicarboxylic acid (APDC). The mGluR2 subtype appears to mediate the reduction of thalamocortical EPSCs, since the selective mGluR3 agonist, N-acetylaspartylglutamate (NAAG), had no effect on the EPSCs. Consistent with this, we showed that mGluR2 is expressed in the barrels. Furthermore, blocking group II mGluRs with LY341495 reduced the synaptic depression induced by a short stimulus train, indicating that synaptically released glutamate activates these receptors. These results indicate that group II mGluRs modulate thalamocortical processing by inhibiting glutamate release from thalamocortical synapses. This inhibition provides a feedback mechanism for

  19. Dysfunctional TCA-Cycle Metabolism in Glutamate Dehydrogenase Deficient Astrocytes.

    PubMed

    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. PMID:26221781

  20. Revisiting the essentiality of glutamate racemase in Mycobacterium tuberculosis.

    PubMed

    Morayya, Sapna; Awasthy, Disha; Yadav, Reena; Ambady, Anisha; Sharma, Umender

    2015-01-25

    Glutamate racemase (MurI) converts l-glutamate into d-glutamate which is an essential component of peptidoglycan in bacteria. The gene encoding glutamate racemase, murI has been shown to be essential for the growth of a number of bacterial species including Escherichia coli. However, in some Gram-positive species d-amino acid transaminase (Dat) can also convert l-glutamate into d-glutamate thus rendering MurI non-essential for growth. In a recent study the murI gene of Mycobacterium tuberculosis was shown to be non-essential. As d-glutamate is an essential component of peptidoglycan of M. tuberculosis, either Dat or MurI has to be essential for its survival. Since, a Dat encoding gene has not been reported in M. tuberculosis genome sequence, the reported non-essentiality of murI was unexplainable. In order to resolve this dilemma we tried to knockout murI in the presence of single and two copies of murI, in wild type and merodiploid strains respectively. It was found that murI could not be inactivated in the wild type background indicating that it could be an essential gene. Also, inactivation of murI could not be achieved in the presence of externally supplied d-glutamate in 7H9 medium suggesting that M. tuberculosis is unable to take up d-glutamate under the conditions tested. However we could generate murI knockout strains at high frequency when two copies of the gene were present indicating that at least one murI gene is required for cellular viability. The essential nature of MurI in M. tuberculosis H37Rv suggests that it could be a potential drug target. PMID:25447907

  1. Opioid-glutamate interactions in rat locus coeruleus neurons.

    PubMed

    Oleskevich, S; Clements, J D; Williams, J T

    1993-09-01

    1. The effect of mu-opioids on the glutamate response was investigated in rat locus coeruleus (LC) neurons by intracellular recording in the brain slice preparation. Glutamate responses were evoked by bath application of selective glutamate agonists, glutamate iontophoresis, and stimulation of excitatory afferents. 2. The mu-opioid agonist D-Ala2-MePhe4-Gly-ol5-enkephalin (DAMGO; 1 microM) potentiated the response to bath application of N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazole proprionic acid by 91 and 142%, respectively, in slices cut in the horizontal plane. The mechanism of action of this effect was investigated under conditions that limited the DAMGO-induced hyperpolarization and improved the space clamp of the neuron through 1) addition of barium, 2) increase in extracellular potassium concentration, 3) sectioning of the LC in the coronal plane, and 4) addition of carbenoxolone. Each experimental manipulation decreased the DAMGO outward current and reduced the mu-opioid potentiation of the glutamate response. The results suggest that the mu-opioid-mediated potentiation of the glutamate response is dependent on membrane hyperpolarization. 3. Neither forskolin nor the phorbol ester 4b-phorbol 12,13-dibutyrate (PDBu) altered the glutamate-mediated inward currents. The potentiation of the glutamate response by DAMGO was not affected by PDBu. 4. The mu-opioids DAMGO and [met]5enkephalin (10 microM) did not significantly affect the NMDA receptor-mediated depolarization (mean 14%) evoked by local application of glutamate but inhibited the NMDA receptor-mediated synaptic potential (mean 25%).(ABSTRACT TRUNCATED AT 400 WORDS) PMID:7693886

  2. Transport Mechanism of a Bacterial Homologue of Glutamate Transporters

    SciTech Connect

    Reyes, N.; Ginter, C; Boudker, O

    2009-01-01

    Glutamate transporters are integral membrane proteins that catalyse a thermodynamically uphill uptake of the neurotransmitter glutamate from the synaptic cleft into the cytoplasm of glia and neuronal cells by harnessing the energy of pre-existing electrochemical gradients of ions. Crucial to the reaction is the conformational transition of the transporters between outward and inward facing states, in which the substrate binding sites are accessible from the extracellular space and the cytoplasm, respectively. Here we describe the crystal structure of a double cysteine mutant of a glutamate transporter homologue from Pyrococcus horikoshii, GltPh, which is trapped in the inward facing state by cysteine crosslinking. Together with the previously determined crystal structures of Glt{sub Ph} in the outward facing state, the structure of the crosslinked mutant allows us to propose a molecular mechanism by which Glt{sub Ph} and, by analogy, mammalian glutamate transporters mediate sodium-coupled substrate uptake.

  3. Differential Glutamate Metabolism in Proliferating and Quiescent Mammary Epithelial Cells.

    PubMed

    Coloff, Jonathan L; Murphy, J Patrick; Braun, Craig R; Harris, Isaac S; Shelton, Laura M; Kami, Kenjiro; Gygi, Steven P; Selfors, Laura M; Brugge, Joan S

    2016-05-10

    Mammary epithelial cells transition between periods of proliferation and quiescence during development, menstrual cycles, and pregnancy, and as a result of oncogenic transformation. Utilizing an organotypic 3D tissue culture model coupled with quantitative metabolomics and proteomics, we identified significant differences in glutamate utilization between proliferating and quiescent cells. Relative to quiescent cells, proliferating cells catabolized more glutamate via transaminases to couple non-essential amino acid (NEAA) synthesis to α-ketoglutarate generation and tricarboxylic acid (TCA) cycle anaplerosis. As cells transitioned to quiescence, glutamine consumption and transaminase expression were reduced, while glutamate dehydrogenase (GLUD) was induced, leading to decreased NEAA synthesis. Highly proliferative human tumors display high transaminase and low GLUD expression, suggesting that proliferating cancer cells couple glutamine consumption to NEAA synthesis to promote biosynthesis. These findings describe a competitive and partially redundant relationship between transaminases and GLUD, and they reveal how coupling of glutamate-derived carbon and nitrogen metabolism can be regulated to support cell proliferation. PMID:27133130

  4. Transport mechanism of a glutamate transporter homologue GltPh.

    PubMed

    Ji, Yurui; Postis, Vincent L G; Wang, Yingying; Bartlam, Mark; Goldman, Adrian

    2016-06-15

    Glutamate transporters are responsible for uptake of the neurotransmitter glutamate in mammalian central nervous systems. Their archaeal homologue GltPh, an aspartate transporter isolated from Pyrococcus horikoshii, has been the focus of extensive studies through crystallography, MD simulations and single-molecule FRET (smFRET). Here, we summarize the recent research progress on GltPh, in the hope of gaining some insights into the transport mechanism of this aspartate transporter. PMID:27284058

  5. Molecular pharmacology of glutamate transporters, EAATs and VGLUTs.

    PubMed

    Shigeri, Yasushi; Seal, Rebecca P; Shimamoto, Keiko

    2004-07-01

    L-Glutamate serves as a major excitatory neurotransmitter in the mammalian central nervous system (CNS) and is stored in synaptic vesicles by an uptake system that is dependent on the proton electrochemical gradient (VGLUTs). Following its exocytotic release, glutamate activates fast-acting, excitatory ionotropic receptors and slower-acting metabotropic receptors to mediate neurotransmission. Na+-dependent glutamate transporters (EAATs) located on the plasma membrane of neurons and glial cells rapidly terminate the action of glutamate and maintain its extracellular concentration below excitotoxic levels. Thus far, five Na+-dependent glutamate transporters (EAATs 1-5) and three vesicular glutamate transporters (VGLUTs 1-3) have been identified. Examination of EAATs and VGLUTs in brain preparations and by heterologous expression of the various cloned subtypes shows these two transporter families differ in many of their functional properties including substrate specificity and ion requirements. Alterations in the function and/or expression of these carriers have been implicated in a range of psychiatric and neurological disorders. EAATs have been implicated in cerebral stroke, epilepsy, Alzheimer's disease, HIV-associated dementia, Huntington's disease, amyotrophic lateral sclerosis (ALS) and malignant glioma, while VGLUTs have been implicated in schizophrenia. To examine the physiological role of glutamate transporters in more detail, several classes of transportable and non-transportable inhibitors have been developed, many of which are derivatives of the natural amino acids, aspartate and glutamate. This review summarizes the development of these indispensable pharmacological tools, which have been critical to our understanding of normal and abnormal synaptic transmission. PMID:15210307

  6. Transport mechanism of a glutamate transporter homologue GltPh

    PubMed Central

    Ji, Yurui; Postis, Vincent L.G.; Wang, Yingying; Bartlam, Mark; Goldman, Adrian

    2016-01-01

    Glutamate transporters are responsible for uptake of the neurotransmitter glutamate in mammalian central nervous systems. Their archaeal homologue GltPh, an aspartate transporter isolated from Pyrococcus horikoshii, has been the focus of extensive studies through crystallography, MD simulations and single-molecule FRET (smFRET). Here, we summarize the recent research progress on GltPh, in the hope of gaining some insights into the transport mechanism of this aspartate transporter. PMID:27284058

  7. Ammonia Mediates Methamphetamine-Induced Increases in Glutamate and Excitotoxicity

    PubMed Central

    Halpin, Laura E; Northrop, Nicole A; Yamamoto, Bryan K

    2014-01-01

    Ammonia has been identified to have a significant role in the long-term damage to dopamine and serotonin terminals produced by methamphetamine (METH), but how ammonia contributes to this damage is unknown. Experiments were conducted to identify whether increases in brain ammonia affect METH-induced increases in glutamate and subsequent excitotoxicity. Increases in striatal glutamate were measured using in vivo microdialysis. To examine the role of ammonia in mediating changes in extracellular glutamate after METH exposure, lactulose was used to decrease plasma and brain ammonia. Lactulose is a non-absorbable disaccharide, which alters the intestinal lumen through multiple mechanisms that lead to the increased peripheral excretion of ammonia. METH caused a significant increase in extracellular glutamate that was prevented by lactulose. Lactulose had no effect on METH-induced hyperthermia. To determine if ammonia contributed to excitotoxicity, the effect of METH and lactulose treatment on calpain-mediated spectrin proteolysis was measured. METH significantly increased calpain-specific spectrin breakdown products, and this increase was prevented with lactulose treatment. To examine if ammonia-induced increases in extracellular glutamate were mediated by excitatory amino-acid transporters, the reverse dialysis of ammonia, the glutamate transporter inhibitor, DL-threo-β-benzyloxyaspartic acid (TBOA), or the combination of the two directly into the striatum of awake, freely moving rats was conducted. TBOA blocked the increases in extracellular glutamate produced by the reverse dialysis of ammonia. These findings demonstrate that ammonia mediates METH-induced increases in extracellular glutamate through an excitatory amino-acid transporter to cause excitotoxicity. PMID:24165886

  8. Glutamate: the new frontier in pharmacotherapy for cocaine addiction.

    PubMed

    Uys, Joachim D; LaLumiere, Ryan T

    2008-11-01

    Considerable research into the neurobiology of cocaine addiction has shed light on the role of glutamate. Findings from models of relapse to cocaine-seeking indicate that the glutamatergic system is critically involved, as glutamate levels in the nucleus accumbens increase during reinstatement and glutamate receptor activation is necessary for reinstatement to drug-seeking. Thus, it would seem beneficial to block the increased glutamate release, but full antagonists of ionotropic glutamate receptors produce undesirable side effects. Therefore, modulation of glutamatergic transmission would be advantageous and provide novel pharmacotherapeutic avenues. Pharmacotherapies have been developed that have the potential to modulate excessive glutamatergic transmission through ionotropic and metabotropic (mGluR) glutamate receptors. Compounds that modulate glutamatergic transmission through ionotropic glutamate receptors include the non-competitive N-methyl-D-aspartic acid antagonists, amantadine and memantine, and the partial N-methyl-D-aspartic acid agonist d-cycloserine. They have shown promise in preclinical models of cocaine addiction. The mGluR2/3 agonist LY379268 is effective in inhibiting cocaine seeking in preclinical animal models and could decrease stress-induced relapse due to its anxiolytic effects. Similarly, the mGluR1/5 antagonists, 2-methyl-6-(phenylethynyl)pyridine and 3-[2-methyl-4-thiazolyl)ethynyl]pyridine, have shown to be effective in preclinical models of cocaine addiction. The cysteine pro-drug, N-acetylcysteine, restores the inhibitory tone on presynaptic glutamate receptors and has been effective in reducing cue-induced craving and cocaine use in humans. Furthermore, anticonvulsants, such as topiramate or lamotrigine, have shown efficacy in treating cocaine dependence or reducing relapse in humans. Future pharmacotherapy may focus on manipulating signal transduction proteins and pathways, which include Homer/N-methyl-D-aspartic acid complexes, to

  9. P301L tau expression affects glutamate release and clearance in the hippocampal trisynaptic pathway.

    PubMed

    Hunsberger, Holly C; Rudy, Carolyn C; Batten, Seth R; Gerhardt, Greg A; Reed, Miranda N

    2015-01-01

    Individuals at risk of developing Alzheimer's disease (AD) often exhibit hippocampal hyperexcitability. A growing body of evidence suggests that perturbations in the glutamatergic tripartite synapse may underlie this hyperexcitability. Here, we used a tau mouse model of AD (rTg(TauP301L)4510) to examine the effects of tau pathology on hippocampal glutamate regulation. We found a 40% increase in hippocampal vesicular glutamate transporter, which packages glutamate into vesicles, and has previously been shown to influence glutamate release, and a 40% decrease in hippocampal glutamate transporter 1, the major glutamate transporter responsible for removing glutamate from the extracellular space. To determine whether these alterations affected glutamate regulation in vivo, we measured tonic glutamate levels, potassium-evoked glutamate release, and glutamate uptake/clearance in the dentate gyrus, cornu ammonis 3(CA3), and cornu ammonis 1(CA1) regions of the hippocampus. P301L tau expression resulted in a 4- and 7-fold increase in potassium-evoked glutamate release in the dentate gyrus and CA3, respectively, and significantly decreased glutamate clearance in all three regions. Both release and clearance correlated with memory performance in the hippocampal-dependent Barnes maze task. Alterations in mice expressing P301L were observed at a time when tau pathology was subtle and before readily detectable neuron loss. These data suggest novel mechanisms by which tau may mediate hyperexcitability. Pre-synaptic vesicular glutamate transporters (vGLUTs) package glutamate into vesicles before exocytosis into the synaptic cleft. Once in the extracellular space, glutamate acts on glutamate receptors. Glutamate is removed from the extracellular space by excitatory amino acid transporters, including GLT-1, predominantly localized to glia. P301L tau expression increases vGLUT expression and glutamate release, while also decreasing GLT-1 expression and glutamate clearance. PMID

  10. Glutamate Delta-1 Receptor Regulates Metabotropic Glutamate Receptor 5 Signaling in the Hippocampus.

    PubMed

    Suryavanshi, Pratyush S; Gupta, Subhash C; Yadav, Roopali; Kesherwani, Varun; Liu, Jinxu; Dravid, Shashank M

    2016-08-01

    The delta family of ionotropic glutamate receptors consists of glutamate delta-1 (GluD1) and glutamate delta-2 receptors. We have previously shown that GluD1 knockout mice exhibit features of developmental delay, including impaired spine pruning and switch in the N-methyl-D-aspartate receptor subunit, which are relevant to autism and other neurodevelopmental disorders. Here, we identified a novel role of GluD1 in regulating metabotropic glutamate receptor 5 (mGlu5) signaling in the hippocampus. Immunohistochemical analysis demonstrated colocalization of mGlu5 with GluD1 punctas in the hippocampus. Additionally, GluD1 protein coimmunoprecipitated with mGlu5 in the hippocampal membrane fraction, as well as when overexpressed in human embryonic kidney 293 cells, demonstrating that GluD1 and mGlu5 may cooperate in a signaling complex. The interaction of mGlu5 with scaffold protein effector Homer, which regulates mechanistic target of rapamycin (mTOR) signaling, was abnormal both under basal conditions and in response to mGlu1/5 agonist (RS)-3,5-dihydroxyphenylglycine (DHPG) in GluD1 knockout mice. The basal levels of phosphorylated mTOR and protein kinase B, the signaling proteins downstream of mGlu5 activation, were higher in GluD1 knockout mice, and no further increase was induced by DHPG. We also observed higher basal protein translation and an absence of DHPG-induced increase in GluD1 knockout mice. In accordance with a role of mGlu5-mediated mTOR signaling in synaptic plasticity, DHPG-induced internalization of surface α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor subunits was impaired in the GluD1 knockout mice. These results demonstrate that GluD1 interacts with mGlu5, and loss of GluD1 impairs normal mGlu5 signaling potentially by dysregulating coupling to its effector. These studies identify a novel role of the enigmatic GluD1 subunit in hippocampal function. PMID:27231330

  11. Stimulation of peripheral cholinergic nerves by glutamate indicates a new peripheral glutamate receptor.

    PubMed

    Aas, P; Tansø, R; Fonnum, F

    1989-05-01

    The bronchial smooth muscle of the rat was examined for contractile responses to excitatory amino acids. The nerve-mediated contraction induced by electrical field stimulation was enhanced by exogenous L-glutamate (L-Glu). The apparent affinity (ED50) of L-Glu was 3.5 +/- 0.1 mM. Both tetrodotoxin and hemicholinium-3 completely abolished the electrical field-induced contraction and therefore the potentiation by L-Glu, which indicates that L-Glu has a prejunctional effect. Concentrations of L-Glu higher than 22 mM inhibited the electrical field-induced contractions and enhanced the tonus of the smooth muscle by postjunctional stimulation. The ED50 of exogenous ACh was not altered by L-Glu. High concentrations (62 mM) of L-Glu increased the intrinsic activity (alpha) of ACh, indicating a postjunctional potentiation of ACh-induced contractions. L-Glu did not inhibit the activity of acetylcholinesterase, therefore the postjunctional potentiation was not due to ACh accumulation. Inhibition of the electrical field-induced contraction was seen with high concentrations of D-Glu, L-aspartate (L-Asp), L-alpha-amino adipate and ibotenate. Neither glutamate diethyl ester nor 2-amino-5-phosphonovalerate had any inhibitory effects on the L-Glu- and L-Asp-induced alterations of the electrical field-stimulated contraction or on the L-Glu-enhanced tonus of the bronchial smooth muscle. Kainate, N-methyl-D-aspartate, quisqualate and N-acetyl-aspartyl-glutamate had only minor transient potentiating effects on the electrical field-induced contraction. The results provide evidence for a L-Glu receptor in rat bronchi that has a different specificity for glutamate agonists and antagonists than the L-Glu receptor described in the CNS. The receptor seems to be located prejunctionally and enhances nerve-mediated responses and thereby stimulates the bronchial smooth muscle to contract. The possible involvement of this type of receptor in the 'Chinese restaurant syndrome' is discussed. PMID

  12. [Glutamate Metabotropic Receptors: Structure, Localisation, Functions].

    PubMed

    Perfilova, V N; Tyurenkov, I N

    2016-01-01

    The data on the structure, location and functions of the metabotropic glutamate receptor is shown. The family consists of 8 mGluRs subtypes and is divided into three groups: I group--mGluRs1/mGluRs5, II group--mGluRs2/mGluRs3, III group--mGluRs4/mGluRs6/mGluRs7/mGluRs8. They are associated with G-protein; signaling in the cells is carried out by IP3 or adenylate cyclase signaling pathways, in the result of which, mGluRs modify glial and neuronal excitability. Receptors are localized in the CNS and periphery in non-neuronal tissues: bone, heart, kidney, pancreas pod and platelets, the gastrointestinal tract, immune system. Their participation in the mechanisms of neurodegenerative diseases, mental and cognitive disorders, autoimmune processes, etc. is displayed. Agonists, antagonists, allosteric modulators of mGluRs are considered as potential medicines for treatment of mental diseases, including depression, fragile X syndrome, anxiety, obsessive-compulsive disorders, Parkinson's disease, etc. PMID:27530046

  13. Striatal interaction among dopamine, glutamate and ascorbate.

    PubMed

    Morales, Ingrid; Fuentes, Angel; Ballaz, Santiago; Obeso, Jose A; Rodriguez, Manuel

    2012-12-01

    Despite evidence suggesting the interaction among glutamate (GLU), dopamine (DA) and ascorbic acid (AA) in the striatum, their actions are often studied separately. Microdialysis was used here to quantify the extracellular interaction among GLU-DA-AA in the striatum of rats, an interaction which was compared with those studied in the substantia nigra (SN). Perfusion of GLU by reverse microdialysis increased DA and decreased 3,4-dihydroxyphenylacetic acid (DOPAC) in the extracellular medium of the striatum, but increased both DA and DOPAC in the SN. The increase of extracellular DA-concentration induced by the local DA-perfusion decreased the extracellular level of GLU and glutamine, an effect that, as suggested by the GLU and glutamine increase observed after the haloperidol administration, probably involves the D2 dopamine receptor. Local administration of AA increased the extracellular DA, decreased DOPAC and had no effect on GLU and glutamine. Present data suggest that, in the striatum, GLU-release inhibits DA-uptake, DA-release inhibits GLU-release, and AA-release prevents DA-oxidation increasing its extracellular diffusion. These effects were different in the SN where GLU probably promoted the DA-release instead of inhibiting the DA-uptake as presumably occurred in the striatum. Present data denote a marked GLU-DA-AA interaction in the striatum, which might be relevant for the pharmacological control of basal ganglia disorders. PMID:22959966

  14. Reduced hippocampal glutamate in Alzheimer disease.

    PubMed

    Rupsingh, R; Borrie, M; Smith, M; Wells, J L; Bartha, R

    2011-05-01

    Altered neurometabolic profiles have been detected in Alzheimer disease (AD) using (1)H magnetic resonance spectroscopy (MRS), but no definitive biomarker of mild cognitive impairment (MCI) or AD has been established. This study used MRS to compare hippocampal metabolite levels between normal elderly controls (NEC) and subjects with MCI and AD. Short echo-time (TE=46 ms) (1)H spectra were acquired at 4T from the right hippocampus of 23 subjects with AD, 12 subjects with MCI and 15 NEC. Absolute metabolite levels and metabolite ratios were compared between groups using a multivariate analysis of covariance (covariates: age, sex) followed by post hoc Tukey's test (p<0.05 significant). Subjects with AD had decreased glutamate (Glu) as well as decreased Glu/creatine (Cr), Glu/myo-inositol (mI), Glu/N-acetylaspartate (NAA), and NAA/Cr ratios compared to NEC. Subjects with AD also had decreased Glu/mI ratio compared to MCI. There were no differences between subjects with MCI and NEC. Therefore, in addition to NAA/Cr, decreased hippocampal Glu may be an indicator of AD. PMID:19501936

  15. Glutamate Receptor Ion Channels: Structure, Regulation, and Function

    PubMed Central

    Wollmuth, Lonnie P.; McBain, Chris J.; Menniti, Frank S.; Vance, Katie M.; Ogden, Kevin K.; Hansen, Kasper B.; Yuan, Hongjie; Myers, Scott J.; Dingledine, Ray

    2010-01-01

    The mammalian ionotropic glutamate receptor family encodes 18 gene products that coassemble to form ligand-gated ion channels containing an agonist recognition site, a transmembrane ion permeation pathway, and gating elements that couple agonist-induced conformational changes to the opening or closing of the permeation pore. Glutamate receptors mediate fast excitatory synaptic transmission in the central nervous system and are localized on neuronal and non-neuronal cells. These receptors regulate a broad spectrum of processes in the brain, spinal cord, retina, and peripheral nervous system. Glutamate receptors are postulated to play important roles in numerous neurological diseases and have attracted intense scrutiny. The description of glutamate receptor structure, including its transmembrane elements, reveals a complex assembly of multiple semiautonomous extracellular domains linked to a pore-forming element with striking resemblance to an inverted potassium channel. In this review we discuss International Union of Basic and Clinical Pharmacology glutamate receptor nomenclature, structure, assembly, accessory subunits, interacting proteins, gene expression and translation, post-translational modifications, agonist and antagonist pharmacology, allosteric modulation, mechanisms of gating and permeation, roles in normal physiological function, as well as the potential therapeutic use of pharmacological agents acting at glutamate receptors. PMID:20716669

  16. Effect of dexamethasone on fetal hepatic glutamine-glutamate exchange.

    PubMed

    Timmerman, M; Teng, C; Wilkening, R B; Fennessey, P; Battaglia, F C; Meschia, G

    2000-05-01

    Intravenous infusion of dexamethasone (Dex) in the fetal lamb causes a two- to threefold increase in plasma glutamine and other glucogenic amino acids and a decrease of plasma glutamate to approximately one-third of normal. To explore the underlying mechanisms, hepatic amino acid uptake and conversion of L-[1-(13)C]glutamine to L-[1-(13)C]glutamate and (13)CO(2) were measured in six sheep fetuses before and in the last 2 h of a 26-h Dex infusion. Dex decreased hepatic glutamine and alanine uptakes (P < 0.01) and hepatic glutamate output (P < 0.001). Hepatic outputs of the glutamate (R(Glu,Gln)) and CO(2) formed from plasma glutamine decreased to 21 (P < 0.001) and 53% (P = 0.009) of control, respectively. R(Glu,Gln), expressed as a fraction of both outputs, decreased (P < 0.001) from 0.36 +/- 0.02 to 0.18 +/- 0.04. Hepatic glucose output remained virtually zero throughout the experiment. We conclude that Dex decreases fetal hepatic glutamate output by increasing the routing of glutamate carbon into the citric acid cycle and by decreasing the hepatic uptake of glucogenic amino acids. PMID:10780940

  17. NEURONAL ACTIVITY REGULATES GLUTAMATE TRANSPORTER DYNAMICS IN DEVELOPING ASTROCYTES

    PubMed Central

    Benediktsson, A.M.; Marrs, G.S.; Tu, J.C.; Worley, P.F.; Rothstein, J.D.; Bergles, D.E.; Dailey, M.E.

    2011-01-01

    Glutamate transporters maintain a low ambient level of glutamate in the CNS and shape the activation of glutamate receptors at synapses. Nevertheless, the mechanisms that regulate the trafficking and localization of transporters near sites of glutamate release are poorly understood. Here we examined the subcellular distribution and dynamic remodeling of the predominant glutamate transporter GLT-1 (EAAT2) in developing hippocampal astrocytes. Immunolabeling revealed that endogenous GLT-1 is concentrated into discrete clusters along branches of developing astrocytes that were apposed preferentially to synapsin-1 positive synapses. GFP-GLT-1 fusion proteins expressed in astrocytes also formed distinct clusters that lined the edges of astrocyte processes, as well as the tips of filopodia and spine-like structures. Time-lapse 3D confocal imaging in tissue slices revealed that GFP-GLT-1 clusters were dynamically remodeled on a timescale of minutes. Some transporter clusters moved within developing astrocyte branches as filopodia extended and retracted, while others maintained stable positions at the tips of spine-like structures. Blockade of neuronal activity with tetrodotoxin reduced both the density and perisynaptic localization of GLT-1 clusters. Conversely, enhancement of neuronal activity increased the size of GLT-1 clusters and their proximity to synapses. Together, these findings indicate that neuronal activity influences both the organization of glutamate transporters in developing astrocyte membranes and their position relative to synapses. PMID:22052455

  18. Diff Quik staining method for detection and identification of monosodium urate and calcium pyrophosphate crystals in synovial fluids

    PubMed Central

    Selvi, E; Manganelli, S; Catenaccio, M; De Stefano, R; Frati, E; Cucini, S; Marcolongo, R

    2001-01-01

    OBJECTIVE—To evaluate whether the Diff Quik (DQ) staining method might prove useful in identifying monosodium urate (MSU) and calcium pyrophosphate dihydrate (CPPD) crystals on permanent mounted stained slides.
METHODS—27 synovial fluid (SF) samples obtained from the knees of 21 patients with acute CPPD disease and 6 with acute gout were studied. Wet analysis for crystal detection and identification was performed within one hour of joint aspiration. In addition, 16 inflammatory synovial effusions obtained from patients with knee arthritis induced by non-crystalline inflammatory diseases were studied. For each SF, a DQ stained slide was analysed by two of the authors trained in SF analysis. The observers were blinded to the type of crystals present in the SF. Each slide was analysed by compensated polarised as well as transmitted light microscopy. An SF was considered positive if intracellular and/or extracellular crystals were clearly identified. In addition, the observer was asked to identify the type of the crystals using compensated polarised light microscopy. Sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) of the DQ staining method were determined.
RESULTS—51 true positive and 28 true negative cases were correctly classified (39 CPPD samples, 12 MSU samples, 28 samples of crystal unrelated arthropathies). Overall, four false positive and three false negative cases were reported. In all the false positive cases, extracellular CPPD crystals were erroneously identified, whereas CPPD crystals present in the SF were not identified in the three false negative cases. All MSU specimens were correctly diagnosed. The overall specificity, sensitivity, and accuracy using DQ stained slides for crystal confirmation were respectively 87.5%, 94.4%, and 91.9%. The PPV was 92.7% and the NPV 90.3%. In particular, the specificity, sensitivity, and accuracy for CPPD detection were 90.9%, 92.9%, and 91

  19. Impairment of Neuronal Glutamate Uptake and Modulation of the Glutamate Transporter GLT-1 Induced by Retinal Ischemia

    PubMed Central

    Varano, Giuseppe Pasquale; Milanese, Marco; Adornetto, Annagrazia; Nucci, Carlo; Bonanno, Giambattista; Morrone, Luigi Antonio; Corasaniti, Maria Tiziana; Bagetta, Giacinto

    2013-01-01

    Excitotoxicity has been implicated in the retinal neuronal loss in several ocular pathologies including glaucoma. Dysfunction of Excitatory Amino Acid Transporters is often a key component of the cascade leading to excitotoxic cell death. In the retina, glutamate transport is mainly operated by the glial glutamate transporter GLAST and the neuronal transporter GLT-1. In this study we evaluated the expression of GLAST and GLT-1 in a rat model of acute glaucoma based on the transient increase of intraocular pressure (IOP) and characterized by high glutamate levels during the reperfusion that follows the ischemic event associated with raised IOP. No changes were reported in GLAST expression while, at neuronal level, a reduction of glutamate uptake and of transporter reversal-mediated glutamate release was observed in isolated retinal synaptosomes. This was accompanied by modulation of GLT-1 expression leading to the reduction of the canonical 65 kDa form and upregulation of a GLT-1-related 38 kDa protein. These results support a role for neuronal transporters in glutamate accumulation observed in the retina following an ischemic event and suggest the presence of a GLT-1 neuronal new alternative splice variant, induced in response to the detrimental stimulus. PMID:23936321

  20. Therapeutic Effects of Glutamic Acid in Piglets Challenged with Deoxynivalenol

    PubMed Central

    Ren, Wenkai; Yin, Jie; Tan, Bie; Liu, Gang; Li, Lili; Nyachoti, Charles Martin; Xiong, Xia; Wu, Guoyao

    2014-01-01

    The mycotoxin deoxynivalenol (DON), one of the most common food contaminants, primarily targets the gastrointestinal tract to affect animal and human health. This study was conducted to examine the protective function of glutamic acid on intestinal injury and oxidative stress caused by DON in piglets. Twenty-eight piglets were assigned randomly into 4 dietary treatments (7 pigs/treatment): 1) uncontaminated control diet (NC), 2) NC+DON at 4 mg/kg (DON), 3) NC+2% glutamic acid (GLU), and 4) NC+2% glutamic acid + DON at 4 mg/kg (DG). At day 15, 30 and 37, blood samples were collected to determine serum concentrations of CAT (catalase), T-AOC (total antioxidant capacity), H2O2 (hydrogen peroxide), NO (nitric oxide), MDA (maleic dialdehyde), DAO (diamine oxidase) and D-lactate. Intestinal morphology, and the activation of Akt/mTOR/4EBP1 signal pathway, as well as the concentrations of H2O2, MDA, and DAO in kidney, liver and small intestine, were analyzed at day 37. Results showed that DON significantly (P<0.05) induced oxidative stress in piglets, while this stress was remarkably reduced with glutamic acid supplementation according to the change of oxidative parameters in blood and tissues. Meanwhile, DON caused obvious intestinal injury from microscopic observations and permeability indicators, which was alleviated by glutamic acid supplementation. Moreover, the inhibition of DON on Akt/mTOR/4EBP1 signal pathway was reduced by glutamic acid supplementation. Collectively, these data suggest that glutamic acid may be a useful nutritional regulator for DON-induced damage manifested as oxidative stress, intestinal injury and signaling inhibition. PMID:24984001

  1. Phosphorylation and Assembly of Glutamate Receptors after Brain Ischemia

    PubMed Central

    Zhang, Fan; Guo, Ailan; Liu, Chunli; Comb, Micheal; Hu, Bingren

    2012-01-01

    Background and Purpose Over-assembly of synaptic glutamate receptors leads to excitotoxicity. The goal of this study is to investigate phosphorylation and assembly of AMPA and NMDA receptors after brain ischemia with reperfusion (I/R). Methods Rats were subjected to 15 min of global ischemia followed by 0.5, 4, and 24 h of reperfusion. Phosphotyrosine (Ptyr) peptides of glutamate receptors in synaptosomal fraction after I/R were identified and quantified by state-of-the-art immuno-affinity purification of Ptyr peptides followed by LC-MS/MS analysis (IAP-LC/MS/MS). Glutamate receptor phosphorylation and synaptic assembly after I/R were studied by biochemical methods. Results Numerous Ptyr sites of AMPA and NMDA were upregulated by about 2- to 37-fold after I/R. A core glutamate receptor kinase, Src kinase, was significantly activated. GluR2/3 and NR2A/B were rapidly clustered from extrasynaptic to synaptic membrane fractions after I/R. GluR2/3 was then translocated into the intracellular pool, whereas NR2A/B remained in the synaptic fraction for as long as 24 h. Consistently, trafficking-related phosphorylation of GluR2/3-S880 was significantly but transiently upregulated, whereas NR2A/B-Y1246 and -Y1472 were significantly and persistently upregulated after I/R. Conclusions Phosphorylation of glutamate receptors at synapses may lead to over-assembly of glutamate receptors, probably via activation of Src family kinases, after I/R. This study provides “global” proteomic information about glutamate receptor tyrosine phosphorylation after brain ischemia. PMID:23212166

  2. Metabotropic glutamate receptor ligands as potential therapeutics for addiction

    PubMed Central

    Olive, M. F.

    2009-01-01

    There is now compelling evidence that the excitatory amino acid neurotransmitter glutamate plays a pivotal role in drug addiction and alcoholism. As a result, there has been increasing interest in developing glutamate-based therapies for the treatment of addictive disorders. Receptors for glutamate are primarily divided into two classes: ionotropic glutamate receptors (iGluRs) that mediate fast excitatory glutamate transmission, and metabotropic glutamate receptors (mGluRs), which are G-protein coupled receptors that mediate slower, modulatory glutamate transmission. Most iGluR antagonists, while showing some efficacy in animal models of addiction, exhibit serious side effects when tested in humans. mGluR ligands, on the other hand, which have been advanced to testing in clinical trials for various medical conditions, have demonstrated the ability to reduce drug reward, reinforcement, and relapse-like behaviors in animal studies. mGluR ligands that have been shown to be primarily effective are Group I (mGluR1 and mGluR5) negative allosteric modulators and Group II (mGluR2 and mGluR3) orthosteric presynaptic autoreceptor agonists. In this review, we will summarize findings from animal studies suggesting that these mGluR ligands may be of potential benefit in reducing on-going drug self-administration and may aid in the prevention of relapse. The neuroanatomical distribution of mGluR1, mGluR2/3, and mGluR5 receptors and the pharmacological properties of Group I negative allosteric modulators and Group II agonists will also be overviewed. Finally, we will discuss the current status of mGluR ligands in human clinical trials. PMID:19630739

  3. Brain to blood glutamate scavenging as a novel therapeutic modality: a review.

    PubMed

    Boyko, Matthew; Gruenbaum, Shaun E; Gruenbaum, Benjamin F; Shapira, Yoram; Zlotnik, Alexander

    2014-08-01

    It is well known that abnormally elevated glutamate levels in the brain are associated with secondary brain injury following acute and chronic brain insults. As such, a tight regulation of brain glutamate concentrations is of utmost importance in preventing the neurodegenerative effects of excess glutamate. There has been much effort in recent years to better understand the mechanisms by which glutamate is reduced in the brain to non-toxic concentrations, and in how to safely accelerate these mechanisms. Blood glutamate scavengers such as oxaloacetate, pyruvate, glutamate-oxaloacetate transaminase, and glutamate-pyruvate transaminase have been shown to reduce blood glutamate concentrations, thereby increasing the driving force of the brain to blood glutamate efflux and subsequently reducing brain glutamate levels. In the past decade, blood glutamate scavengers have gained increasing international interest, and its uses have been applied to a wide range of experimental contexts in animal models of traumatic brain injury, ischemic stroke, subarachnoid hemorrhage, epilepsy, migraine, and malignant gliomas. Although glutamate scavengers have not yet been used in humans, there is increasing evidence that their use may provide effective and exciting new therapeutic modalities. Here, we review the laboratory evidence for the use of blood glutamate scavengers. Other experimental neuroprotective treatments thought to scavenge blood glutamate, including estrogen and progesterone, beta-adrenergic activation, hypothermia, insulin and glucagon, and hemodialysis and peritoneal dialysis are also discussed. The evidence reviewed here will hopefully pave the way for future clinical trials. PMID:24623040

  4. HIV-1, Methamphetamine and Astrocyte Glutamate Regulation: Combined Excitotoxic Implications for Neuro-AIDS

    PubMed Central

    Cisneros, Irma E; Ghorpade, Anuja

    2012-01-01

    Glutamate, the most abundant excitatory transmitter in the brain can lead to neurotoxicity when not properly regulated. Excitotoxicity is a direct result of abnormal regulation of glutamate concentrations in the synapse, and is a common neurotoxic mediator associated with neurodegenerative disorders. It is well accepted that methamphetamine (METH), a potent central nervous stimulant with high abuse potential, and human immunodeficiency virus (HIV)-1 are implicated in the progression of neurocognitive malfunction. Both have been shown to induce common neurodegenerative effects such as astrogliosis, compromised blood brain barrier integrity, and excitotoxicity in the brain. Reduced glutamate uptake from neuronal synapses likely leads to the accumulation of glutamate in the extracellular spaces. Astrocytes express the glutamate transporters responsible for majority of the glutamate uptake from the synapse, as well as for vesicular glutamate release. However, the cellular and molecular mechanisms of astrocyte-mediated excitotoxicity in the context of METH and HIV-1 are undefined. Topics reviewed include dysregulation of the glutamate transporters, specifically excitatory amino acid transporter-2, metabotropic glutamate receptor(s) expression and the release of glutamate by vesicular exocytosis. We also discuss glutamate concentration dysregulation through astrocytic expression of enzymes for glutamate synthesis and metabolism. Lastly, we discuss recent evidence of various astrocyte and neuron crosstalk mechanisms implicated in glutamate regulation. Astrocytes play an essential role in the neuropathologies associated with METH/HIV-1-induced excitotoxicity. We hope to shed light on common cellular and molecular pathways astrocytes share in glutamate regulation during drug abuse and HIV-1 infection. PMID:22591363

  5. Electrogenic Steps Associated with Substrate Binding to the Neuronal Glutamate Transporter EAAC1.

    PubMed

    Tanui, Rose; Tao, Zhen; Silverstein, Nechama; Kanner, Baruch; Grewer, Christof

    2016-05-27

    Glutamate transporters actively take up glutamate into the cell, driven by the co-transport of sodium ions down their transmembrane concentration gradient. It was proposed that glutamate binds to its binding site and is subsequently transported across the membrane in the negatively charged form. With the glutamate binding site being located partially within the membrane domain, the possibility has to be considered that glutamate binding is dependent on the transmembrane potential and, thus, is electrogenic. Experiments presented in this report test this possibility. Rapid application of glutamate to the wild-type glutamate transporter subtype EAAC1 (excitatory amino acid carrier 1) through photo-release from caged glutamate generated a transient inward current, as expected for the electrogenic inward movement of co-transported Na(+) In contrast, glutamate application to a transporter with the mutation A334E induced transient outward current, consistent with movement of negatively charged glutamate into its binding site within the dielectric of the membrane. These results are in agreement with electrostatic calculations, predicting a valence for glutamate binding of -0.27. Control experiments further validate and rule out other possible explanations for the transient outward current. Electrogenic glutamate binding can be isolated in the mutant glutamate transporter because reactions, such as glutamate translocation and/or Na(+) binding to the glutamate-bound state, are inhibited by the A334E substitution. Electrogenic glutamate binding has to be considered together with other voltage-dependent partial reactions to cooperatively determine the voltage dependence of steady-state glutamate uptake and glutamate buffering at the synapse. PMID:27044739

  6. Metabotropic glutamate receptors depress glutamate-mediated synaptic input to rat midbrain dopamine neurones in vitro.

    PubMed

    Wigmore, M A; Lacey, M G

    1998-02-01

    1. Glutamate (AMPA receptor-mediated) excitatory postsynaptic potentials (e.p.s.ps.), evoked by electrical stimulation rostral to the recording site, were examined by intracellular microelectrode recording from dopamine neurones in parasagittal slices of rat ventral midbrain. 2. The e.p.s.p. was depressed by the group III metabotropic glutamate (mGlu) receptor agonist L-2-amino-4-phosphonobutyric acid (L-AP4; 0.01-30 microM) by up to 60% with an EC50 of 0.82 microM. The depression induced by L-AP4 (3 microM) was reversed by the group III preferring mGlu receptor antagonist, alpha-methyl-4-phosphonophenylglycine (MPPG; 250 microM). 3. The group I and II mGlu agonist, 1S,3R-aminocyclopentanedicarboxylic acid (ACPD; 3-30 microM) also depressed the e.p.s.p. in a concentration-dependent manner. The effect of ACPD (10 microM) was reversed by (+)-alpha-methyl-4-carboxyphenylglycine (MCPG; 1 mM; 4 cells). This effect of ACPD was also partially antagonized (by 50.3+/-15.7%, 4 cells) by MPPG (250 microM). 4. The selective agonist at group I mGlu receptors, dihydroxyphenylglycine (DHPG; 100 microM), decreased e.p.s.p. amplitude by 27.1+/-8.2% (7 cells), as did the group II mGlu receptor-selective agonist (1S,1R,2'R,3'R)-2-(2,3-dicarboxycyclopropyl)glycine (DCG-IV; 1 microM) by 26.7+/-4.3% (5 cells). 5. DHPG (10-100 microM) caused a depolarization of the recorded cell, as did ACPD (3-30 microM), whereas no such postsynaptic effect of either L-AP4 or DCG-IV was observed. 6. These results provide evidence for the presence of presynaptic inhibitory metabotropic glutamate autoreceptors from the mGlu receptor groups II and III on descending glutamatergic inputs to midbrain dopamine neurones. Group I mGlu receptors mediate a postsynaptic depolarization, and can also depress glutamatergic transmission, but may not necessarily be localized presynaptically. These sites represent novel drug targets for treatment of schizophrenia and movement disorders of basal ganglia origin. PMID

  7. Metabotropic glutamate receptors depress glutamate-mediated synaptic input to rat midbrain dopamine neurones in vitro

    PubMed Central

    Wigmore, Mark A; Lacey, Michael G

    1998-01-01

    Glutamate (AMPA receptor-mediated) excitatory postsynaptic potentials (e.p.s.ps.), evoked by electrical stimulation rostral to the recording site, were examined by intracellular microelectrode recording from dopamine neurones in parasagittal slices of rat ventral midbrain. The e.p.s.p. was depressed by the group III metabotropic glutamate (mGlu) receptor agonist L-2-amino-4-phosphonobutyric acid (L-AP4; 0.01–30 μM) by up to 60% with an EC50 of 0.82 μM. The depression induced by L-AP4 (3 μM) was reversed by the group III preferring mGlu receptor antagonist, α-methyl-4-phosphonophenylglycine (MPPG; 250 μM). The group I and II mGlu agonist, 1S,3R-aminocyclopentanedicarboxylic acid (ACPD; 3–30 μM) also depressed the e.p.s.p. in a concentration-dependent manner. The effect of ACPD (10 μM) was reversed by (+)-α-methyl-4-carboxyphenylglycine (MCPG; 1 mM; 4 cells). This effect of ACPD was also partially antagonized (by 50.3±15.7%, 4 cells) by MPPG (250 μM). The selective agonist at group I mGlu receptors, dihydroxyphenylglycine (DHPG; 100 μM), decreased e.p.s.p. amplitude by 27.1±8.2% (7 cells), as did the group II mGlu receptor-selective agonist (1S,1′R,2′R,3′R)-2-(2,3-dicarboxycyclopropyl)glycine (DCG-IV; 1 μM) by 26.7±4.3% (5 cells). DHPG (10–100 μM) caused a depolarization of the recorded cell, as did ACPD (3–30 μM), whereas no such postsynaptic effect of either L-AP4 or DCG-IV was observed. These results provide evidence for the presence of presynaptic inhibitory metabotropic glutamate autoreceptors from the mGlu receptor groups II and III on descending glutamatergic inputs to midbrain dopamine neurones. Group I mGlu receptors mediate a postsynaptic depolarization, and can also depress glutamatergic transmission, but may not necessarily be localized presynaptically. These sites represent novel drug targets for treatment of schizophrenia and movement disorders of basal ganglia origin. PMID:9517386

  8. Mediator-less highly sensitive voltammetric detection of glutamate using glutamate dehydrogenase/vertically aligned CNTs grown on silicon substrate.

    PubMed

    Gholizadeh, Azam; Shahrokhian, Saeed; zad, Azam Iraji; Mohajerzadeh, Shamsoddin; Vosoughi, Manouchehr; Darbari, Sara; Sanaee, Zeinab

    2012-01-15

    A sensitive glutamate biosensor is prepared based on glutamate dehydrogenase/vertically aligned carbon nanotubes (GLDH, VACNTs). Vertically aligned carbon nanotubes were grown on a silicon substrate by direct current plasma enhanced chemical vapor deposition (DC-PECVD) method. The electrochemical behavior of the synthesized VACNTs was investigated by cyclic voltammetry and electrochemical impedance spectroscopic methods. Glutamate dehydrogenase covalently attached on tip of VACNTs. The electrochemical performance of the electrode for detection of glutamate was investigated by cyclic and differential pulse voltammetry. Differential pulse voltammetric determinations of glutamate are performed in mediator-less condition and also, in the presence of 1 and 5 μM thionine as electron mediator. The linear calibration curve of the concentration of glutamate versus peak current is investigated in a wide range of 0.1-500 μM. The mediator-less biosensor has a low detection limit of 57 nM and two linear ranges of 0.1-20 μM with a sensitivity of 0.976 mA mM(-1) cm(-2) and 20-300 μM with a sensitivity of 0.182 mA mM(-1) cm(-2). In the presence of 1 μM thionine as an electron mediator, the prepared biosensor shows a low detection limit of 68 nM and two linear ranges of 0.1-20 with a calibration sensitivity of 1.17 mA mM(-1) cm(-2) and 20-500 μM with a sensitivity of 0.153 mA mM(-1) cm(-2). The effects of the other biological compounds on the voltammetric behavior of the prepared biosensor and its response stability are investigated. The results are demonstrated that the GLDH/VACNTs electrode even without electron mediator is a suitable basic electrode for detection of glutamate. PMID:22040749

  9. Ghrelin Regulates Glucose and Glutamate Transporters in Hypothalamic Astrocytes.

    PubMed

    Fuente-Martín, Esther; García-Cáceres, Cristina; Argente-Arizón, Pilar; Díaz, Francisca; Granado, Miriam; Freire-Regatillo, Alejandra; Castro-González, David; Ceballos, María L; Frago, Laura M; Dickson, Suzanne L; Argente, Jesús; Chowen, Julie A

    2016-01-01

    Hypothalamic astrocytes can respond to metabolic signals, such as leptin and insulin, to modulate adjacent neuronal circuits and systemic metabolism. Ghrelin regulates appetite, adiposity and glucose metabolism, but little is known regarding the response of astrocytes to this orexigenic hormone. We have used both in vivo and in vitro approaches to demonstrate that acylated ghrelin (acyl-ghrelin) rapidly stimulates glutamate transporter expression and glutamate uptake by astrocytes. Moreover, acyl-ghrelin rapidly reduces glucose transporter (GLUT) 2 levels and glucose uptake by these glial cells. Glutamine synthetase and lactate dehydrogenase decrease, while glycogen phosphorylase and lactate transporters increase in response to acyl-ghrelin, suggesting a change in glutamate and glucose metabolism, as well as glycogen storage by astrocytes. These effects are partially mediated through ghrelin receptor 1A (GHSR-1A) as astrocytes do not respond equally to desacyl-ghrelin, an isoform that does not activate GHSR-1A. Moreover, primary astrocyte cultures from GHSR-1A knock-out mice do not change glutamate transporter or GLUT2 levels in response to acyl-ghrelin. Our results indicate that acyl-ghrelin may mediate part of its metabolic actions through modulation of hypothalamic astrocytes and that this effect could involve astrocyte mediated changes in local glucose and glutamate metabolism that alter the signals/nutrients reaching neighboring neurons. PMID:27026049

  10. A novel mechanism of neuroprotection: Blood glutamate grabber.

    PubMed

    Castillo, José; Loza, María Isabel; Mirelman, David; Brea, José; Blanco, Miguel; Sobrino, Tomás; Campos, Francisco

    2016-02-01

    Glutamate excitotoxicity is a primary contributor of ischemic neuronal death and other cellular components of the neurovascular unit. Several strategies have been developed against glutamate excitotoxicity, however none of them have not shown positive results in the clinical practice so far. Nowadays, the concept of blood/brain glutamate grabbing or scavenging is well recognized as a novel and attractive protective strategy to reduce the excitotoxic effect of excess extracellular glutamate that accumulates in the brain following an ischemic stroke. The main advantage of this novel therapeutic strategy is that it occurs in the blood circulation and therefore does not affect the normal brain neurophysiology, as it has been described for other drug treatments used against glutamate excitotoxicity. In this work we report all experimental data from the beginning of our studies, focused on stroke pathology, and we describe new findings about the potential application of this therapy. Future clinical trials will allow to know the real efficacy of this novel therapeutic strategy in stroke patients. PMID:26661174

  11. Neuronal pyruvate carboxylation supports formation of transmitter glutamate.

    PubMed

    Hassel, B; Brâthe, A

    2000-02-15

    Release of transmitter glutamate implies a drain of alpha-ketoglutarate from neurons, because glutamate, which is formed from alpha-ketoglutarate, is taken up by astrocytes. It is generally believed that this drain is compensated by uptake of glutamine from astrocytes, because neurons are considered incapable of de novo synthesis of tricarboxylic acid cycle intermediates, which requires pyruvate carboxylation. Here we show that cultured cerebellar granule neurons form releasable [(14)C]glutamate from H(14)CO(3)(-) and [1-(14)C]pyruvate via pyruvate carboxylation, probably mediated by malic enzyme. The activity of pyruvate carboxylation was calculated to be approximately one-third of the pyruvate dehydrogenase activity in neurons. Furthermore, intrastriatal injection of NaH(14)CO(3) or [1-(14)C]pyruvate labeled glutamate better than glutamine, showing that pyruvate carboxylation occurs in neurons in vivo. This means that neurons themselves to a large extent may support their release of glutamate, and thus entails a revision of the current view of glial-neuronal interactions and the importance of the glutamine cycle. PMID:10662824

  12. Glutamate Excitotoxicity Inflicts Paranodal Myelin Splitting and Retraction

    PubMed Central

    Fu, Yan; Sun, Wenjing; Shi, Yunzhou; Shi, Riyi; Cheng, Ji-Xin

    2009-01-01

    Paranodal myelin damage is observed in white matter injury. However the culprit for such damage remains unknown. By coherent anti-Stokes Raman scattering imaging of myelin sheath in fresh tissues with sub-micron resolution, we observed significant paranodal myelin splitting and retraction following glutamate application both ex vivo and in vivo. Multimodal multiphoton imaging further showed that glutamate application broke axo-glial junctions and exposed juxtaparanodal K+ channels, resulting in axonal conduction deficit that was demonstrated by compound action potential measurements. The use of 4-aminopyridine, a broad-spectrum K+ channel blocker, effectively recovered both the amplitude and width of compound action potentials. Using CARS imaging as a quantitative readout of nodal length to diameter ratio, the same kind of paranodal myelin retraction was observed with applications of Ca2+ ionophore A23187. Moreover, exclusion of Ca2+ from the medium or application of calpain inhibitor abolished paranodal myelin retraction during glutamate exposure. Examinations of glutamate receptor agonists and antagonists further showed that the paranodal myelin damage was mediated by NMDA and kainate receptors. These results suggest that an increased level of glutamate in diseased white matter could impair paranodal myelin through receptor-mediated Ca2+ overloading and subsequent calpain activation. PMID:19693274

  13. Ionotropic glutamate receptor expression in human white matter.

    PubMed

    Christensen, Pia Crone; Samadi-Bahrami, Zahra; Pavlov, Vlady; Stys, Peter K; Moore, G R Wayne

    2016-09-01

    Glutamate is the key excitatory neurotransmitter of the central nervous system (CNS). Its role in human grey matter transmission is well understood, but this is less clear in white matter (WM). Ionotropic glutamate receptors (iGluR) are found on both neuronal cell bodies and glia as well as on myelinated axons in rodents, and rodent WM tissue is capable of glutamate release. Thus, rodent WM expresses many of the components of the traditional grey matter neuron-to-neuron synapse, but to date this has not been shown for human WM. We demonstrate the presence of iGluRs in human WM by immunofluorescence employing high-resolution spectral confocal imaging. We found that the obligatory N-methyl-d-aspartic acid (NMDA) receptor subunit GluN1 and the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunit GluA4 co-localized with myelin, oligodendroglial cell bodies and processes. Additionally, GluA4 colocalized with axons, often in distinct clusters. These findings may explain why human WM is vulnerable to excitotoxic events following acute insults such as stroke and traumatic brain injury and in more chronic inflammatory conditions such as multiple sclerosis (MS). Further exploration of human WM glutamate signalling could pave the way for developing future therapies modulating the glutamate-mediated damage in these and other CNS disorders. PMID:27443784

  14. Ghrelin Regulates Glucose and Glutamate Transporters in Hypothalamic Astrocytes

    PubMed Central

    Fuente-Martín, Esther; García-Cáceres, Cristina; Argente-Arizón, Pilar; Díaz, Francisca; Granado, Miriam; Freire-Regatillo, Alejandra; Castro-González, David; Ceballos, María L.; Frago, Laura M.; Dickson, Suzanne L.; Argente, Jesús; Chowen, Julie A.

    2016-01-01

    Hypothalamic astrocytes can respond to metabolic signals, such as leptin and insulin, to modulate adjacent neuronal circuits and systemic metabolism. Ghrelin regulates appetite, adiposity and glucose metabolism, but little is known regarding the response of astrocytes to this orexigenic hormone. We have used both in vivo and in vitro approaches to demonstrate that acylated ghrelin (acyl-ghrelin) rapidly stimulates glutamate transporter expression and glutamate uptake by astrocytes. Moreover, acyl-ghrelin rapidly reduces glucose transporter (GLUT) 2 levels and glucose uptake by these glial cells. Glutamine synthetase and lactate dehydrogenase decrease, while glycogen phosphorylase and lactate transporters increase in response to acyl-ghrelin, suggesting a change in glutamate and glucose metabolism, as well as glycogen storage by astrocytes. These effects are partially mediated through ghrelin receptor 1A (GHSR-1A) as astrocytes do not respond equally to desacyl-ghrelin, an isoform that does not activate GHSR-1A. Moreover, primary astrocyte cultures from GHSR-1A knock-out mice do not change glutamate transporter or GLUT2 levels in response to acyl-ghrelin. Our results indicate that acyl-ghrelin may mediate part of its metabolic actions through modulation of hypothalamic astrocytes and that this effect could involve astrocyte mediated changes in local glucose and glutamate metabolism that alter the signals/nutrients reaching neighboring neurons. PMID:27026049

  15. Distribution of vesicular glutamate transporters in the human brain

    PubMed Central

    Vigneault, Érika; Poirel, Odile; Riad, Mustapha; Prud'homme, Josée; Dumas, Sylvie; Turecki, Gustavo; Fasano, Caroline; Mechawar, Naguib; El Mestikawy, Salah

    2015-01-01

    Glutamate is the major excitatory transmitter in the brain. Vesicular glutamate transporters (VGLUT1-3) are responsible for uploading glutamate into synaptic vesicles. VGLUT1 and VGLUT2 are considered as specific markers of canonical glutamatergic neurons, while VGLUT3 is found in neurons previously shown to use other neurotransmitters than glutamate. Although there exists a rich literature on the localization of these glutamatergic markers in the rodent brain, little is currently known about the distribution of VGLUT1-3 in the human brain. In the present study, using subtype specific probes and antisera, we examined the localization of the three vesicular glutamate transporters in the human brain by in situ hybridization, immunoautoradiography and immunohistochemistry. We found that the VGLUT1 transcript was highly expressed in the cerebral cortex, hippocampus and cerebellum, whereas VGLUT2 mRNA was mainly found in the thalamus and brainstem. VGLUT3 mRNA was localized in scarce neurons within the cerebral cortex, hippocampus, striatum and raphe nuclei. Following immunoautoradiographic labeling, intense VGLUT1- and VGLUT2-immunoreactivities were observed in all regions investigated (cerebral cortex, hippocampus, caudate-putamen, cerebellum, thalamus, amygdala, substantia nigra, raphe) while VGLUT3 was absent from the thalamus and cerebellum. This extensive mapping of VGLUT1-3 in human brain reveals distributions that correspond for the most part to those previously described in rodent brains. PMID:25798091

  16. Single rodent mesohabenular axons release glutamate and GABA

    PubMed Central

    Root, David H.; Mejias-Aponte, Carlos; Zhang, Shiliang; Wang, Huiling; Hoffman, Alexander F.; Lupica, Carl R.; Morales, Marisela

    2016-01-01

    The lateral habenula (LHb) is involved in reward, aversion, addiction, and depression, through descending interactions with several brain structures, including the ventral tegmental area (VTA). VTA provides reciprocal inputs to LHb, but their actions are unclear. Here we show that the majority of rat and mouse VTA neurons innervating LHb co-express markers for both glutamate-signaling (vesicular glutamate transporter 2, VGluT2) and GABA-signaling (glutamate decarboxylase, GAD; and vesicular GABA transporter, VGaT). A single axon from these mesohabenular neurons co-expresses VGluT2-protein and VGaT-protein, and surprisingly establishes symmetric and asymmetric synapses on LHb neurons. In LHb slices, light activation of mesohabenular fibers expressing channelrhodopsin-2 (ChR2) driven by VGluT2 or VGaT promoters elicits release of both glutamate and GABA onto single LHb neurons. In vivo light-activation of mesohabenular terminals inhibits or excites LHb neurons. Our findings reveal an unanticipated type of VTA neuron that co-transmits glutamate and GABA, and provides the majority of mesohabenular inputs. PMID:25242304

  17. [Glutamate receptor-mediated retinal neuronal injury in experimental glaucoma].

    PubMed

    Wang, Zhong-Feng; Yang, Xiong-Li

    2016-08-25

    Glaucoma, the second leading cause of blindness, is a neurodegenerative disease characterized by optic nerve degeneration related to apoptotic death of retinal ganglion cells (RGCs). In the pathogenesis of RGC death following the onset of glaucoma, functional changes of glutamate receptors are commonly regarded as important risk factors. During the past several years, we have explored the mechanisms underlying RGC apoptosis and retinal Müller cell reactivation (gliosis) in a rat chronic ocular hypertension (COH) model. We demonstrated that elevated intraocular pressure in COH rats may induce changes of various signaling pathways, which are involved in RGC apoptosis by modulating glutamate NMDA and AMPA receptors. Moreover, we also demonstrated that over-activation of group I metabotropic glutamate receptors (mGluR I) by excessive extracellular glutamate in COH rats could contribute to Müller cell gliosis by suppressing Kir4.1 channels. In this review, incorporating our results, we discuss glutamate receptor- mediated RGC apoptosis and Müller cell gliosis in experimental glaucoma. PMID:27546508

  18. Glutamate detection by amino functionalized tetrahedral amorphous carbon surfaces.

    PubMed

    Kaivosoja, Emilia; Tujunen, Noora; Jokinen, Ville; Protopopova, Vera; Heinilehto, Santtu; Koskinen, Jari; Laurila, Tomi

    2015-08-15

    In this paper, a novel amperometric glutamate biosensor with glutamate oxidase (GlOx) immobilized directly on NH2 functionalized, platinum doped tetrahedral amorphous carbon (ta-C) film, has been successfully developed. First, we demonstrate that direct GlOx immobilization is more effective on amino-groups than on carboxyl- or hydroxyl-groups. Second, we show that anodizing and plasma treatments increase the amount of nitrogen and the proportion of protonated amino groups relative to amino groups on the aminosilane coating, which subsequently results in an increased amount of active GlOx on the surface. This effect, however, is found to be unstable due to unstable electrostatic interactions between GlOx and NH3(+). We demonstrate the detection of glutamate in the concentration range of 10µM-1mM using the NH2 functionalized Pt doped ta-C surface. The biosensor showed high sensitivity (2.9nA μM(-1)cm(-2)), low detection limit (10μM) and good storage stability. The electrode response to glutamate was linear in the concentrations ranging from 10µM to 500µM. In conclusion, the study shows that GlOx immobilization is most effective on aminosilane treated ta-C surface without any pre-treatments and the fabricated sensor structure is able to detect glutamate in the micromolar range. PMID:25966399

  19. System xc- regulates microglia and macrophage glutamate excitotoxicity in vivo

    PubMed Central

    Kigerl, Kristina A.; Ankeny, Daniel P.; Garg, Sanjay K.; Wei, Ping; Guan, Zhen; Lai, Wenmin; McTigue, Dana M.; Banerjee, Ruma; Popovich, Phillip G.

    2011-01-01

    It is widely believed that microglia and monocyte-derived macrophages (collectively referred to as central nervous system (CNS) macrophages) cause excitotoxicity in the diseased or injured CNS. This view has evolved mostly from in vitro studies showing that neurotoxic concentrations of glutamate are released from CNS macrophages stimulated with lipopolysaccharide (LPS), a potent inflammogen. We hypothesized that excitotoxic killing by CNS macrophages is more rigorously controlled in vivo, requiring both the activation of the glutamate/cystine antiporter (system xc-) and an increase in extracellular cystine, the substrate that drives glutamate release. Here, we show that non-traumatic microinjection of low-dose LPS into spinal cord gray matter activates CNS macrophages but without causing overt neuropathology. In contrast, neurotoxic inflammation occurs when LPS and cystine are co-injected. Simultaneous injection of NBQX, an antagonist of AMPA glutamate receptors, reduces the neurotoxic effects of LPS+cystine, implicating glutamate as a mediator of neuronal cell death in this model. Surprisingly, neither LPS nor LPS+cystine adversely affects survival of oligodendrocytes or oligodendrocyte progenitor cells. Ex vivo analyses show that redox balance in microglia and macrophages is controlled by induction of system xc- and that high GSH:GSSG ratios predict the neurotoxic potential of these cells. Together, these data indicate that modulation of redox balance in CNS macrophages, perhaps through regulating system xc-, could be a novel approach for attenuating injurious neuroinflammatory cascades. PMID:22079587

  20. Frontal glutamate and reward processing in adolescence and adulthood.

    PubMed

    Gleich, Tobias; Lorenz, Robert C; Pöhland, Lydia; Raufelder, Diana; Deserno, Lorenz; Beck, Anne; Heinz, Andreas; Kühn, Simone; Gallinat, Jürgen

    2015-11-01

    The fronto-limbic network interaction, driven by glutamatergic and dopaminergic neurotransmission, represents a core mechanism of motivated behavior and personality traits. Reward seeking behavior undergoes tremendous changes in adolescence paralleled by neurobiological changes of this network including the prefrontal cortex, striatum and amygdala. Since fronto-limbic dysfunctions also underlie major psychiatric diseases beginning in adolescence, this investigation focuses on network characteristics separating adolescents from adults. To investigate differences in network interactions, the brain reward system activity (slot machine task) together with frontal glutamate concentration (anterior cingulate cortex, ACC) was measured in 28 adolescents and 26 adults employing functional magnetic resonance imaging and magnetic resonance spectroscopy, respectively. An inverse coupling of glutamate concentrations in the ACC and activation of the ventral striatum was observed in adolescents. Further, amygdala response in adolescents was negatively correlated with the personality trait impulsivity. For adults, no significant associations of network components or correlations with impulsivity were found. The inverse association between frontal glutamate concentration and striatal activation in adolescents is in line with the triadic model of motivated behavior stressing the important role of frontal top-down inhibition on limbic structures. Our data identified glutamate as the mediating neurotransmitter of this inhibitory process and demonstrates the relevance of glutamate on the reward system and related behavioral traits like impulsivity. This fronto-limbic coupling may represent a vulnerability factor for psychiatric disorders starting in adolescence but not in adulthood. PMID:25009315

  1. Central Role of Glutamate Metabolism in the Maintenance of Nitrogen Homeostasis in Normal and Hyperammonemic Brain.

    PubMed

    Cooper, Arthur J L; Jeitner, Thomas M

    2016-01-01

    Glutamate is present in the brain at an average concentration-typically 10-12 mM-far in excess of those of other amino acids. In glutamate-containing vesicles in the brain, the concentration of glutamate may even exceed 100 mM. Yet because glutamate is a major excitatory neurotransmitter, the concentration of this amino acid in the cerebral extracellular fluid must be kept low-typically µM. The remarkable gradient of glutamate in the different cerebral compartments: vesicles > cytosol/mitochondria > extracellular fluid attests to the extraordinary effectiveness of glutamate transporters and the strict control of enzymes of glutamate catabolism and synthesis in well-defined cellular and subcellular compartments in the brain. A major route for glutamate and ammonia removal is via the glutamine synthetase (glutamate ammonia ligase) reaction. Glutamate is also removed by conversion to the inhibitory neurotransmitter γ-aminobutyrate (GABA) via the action of glutamate decarboxylase. On the other hand, cerebral glutamate levels are maintained by the action of glutaminase and by various α-ketoglutarate-linked aminotransferases (especially aspartate aminotransferase and the mitochondrial and cytosolic forms of the branched-chain aminotransferases). Although the glutamate dehydrogenase reaction is freely reversible, owing to rapid removal of ammonia as glutamine amide, the direction of the glutamate dehydrogenase reaction in the brain in vivo is mainly toward glutamate catabolism rather than toward the net synthesis of glutamate, even under hyperammonemia conditions. During hyperammonemia, there is a large increase in cerebral glutamine content, but only small changes in the levels of glutamate and α-ketoglutarate. Thus, the channeling of glutamate toward glutamine during hyperammonemia results in the net synthesis of 5-carbon units. This increase in 5-carbon units is accomplished in part by the ammonia-induced stimulation of the anaplerotic enzyme pyruvate carboxylase

  2. Central Role of Glutamate Metabolism in the Maintenance of Nitrogen Homeostasis in Normal and Hyperammonemic Brain

    PubMed Central

    Cooper, Arthur J. L.; Jeitner, Thomas M.

    2016-01-01

    Glutamate is present in the brain at an average concentration—typically 10–12 mM—far in excess of those of other amino acids. In glutamate-containing vesicles in the brain, the concentration of glutamate may even exceed 100 mM. Yet because glutamate is a major excitatory neurotransmitter, the concentration of this amino acid in the cerebral extracellular fluid must be kept low—typically µM. The remarkable gradient of glutamate in the different cerebral compartments: vesicles > cytosol/mitochondria > extracellular fluid attests to the extraordinary effectiveness of glutamate transporters and the strict control of enzymes of glutamate catabolism and synthesis in well-defined cellular and subcellular compartments in the brain. A major route for glutamate and ammonia removal is via the glutamine synthetase (glutamate ammonia ligase) reaction. Glutamate is also removed by conversion to the inhibitory neurotransmitter γ-aminobutyrate (GABA) via the action of glutamate decarboxylase. On the other hand, cerebral glutamate levels are maintained by the action of glutaminase and by various α-ketoglutarate-linked aminotransferases (especially aspartate aminotransferase and the mitochondrial and cytosolic forms of the branched-chain aminotransferases). Although the glutamate dehydrogenase reaction is freely reversible, owing to rapid removal of ammonia as glutamine amide, the direction of the glutamate dehydrogenase reaction in the brain in vivo is mainly toward glutamate catabolism rather than toward the net synthesis of glutamate, even under hyperammonemia conditions. During hyperammonemia, there is a large increase in cerebral glutamine content, but only small changes in the levels of glutamate and α-ketoglutarate. Thus, the channeling of glutamate toward glutamine during hyperammonemia results in the net synthesis of 5-carbon units. This increase in 5-carbon units is accomplished in part by the ammonia-induced stimulation of the anaplerotic enzyme pyruvate

  3. FURTHER DEVELOPMENT OF MODIFIED MONOSODIUM TITANATE, AN IMPROVED SORBENT FOR PRETREATMENT OF HIGH LEVEL NUCLEAR WASTE AT THE SAVANNAH RIVER SITE

    SciTech Connect

    Taylor-Pashow, K.; Hobbs, D.; Fondeur, F.; Fink, S.

    2011-01-12

    High-level nuclear waste produced from fuel reprocessing operations at the Savannah River Site (SRS) requires pretreatment to remove Cs-137, Sr-90, and alpha-emitting radionuclides (i.e., actinides) prior to disposal onsite as low level waste. Separation processes planned at SRS include caustic side solvent extraction, for Cs-137 removal, and sorption of Sr-90 and alpha-emitting radionuclides onto monosodium titanate (MST). The predominant alpha-emitting radionuclides in the highly alkaline waste solutions include plutonium isotopes Pu-238, Pu-239, and Pu-240. This paper describes recent results from the development of an improved titanate material that exhibits increased removal kinetics and effective capacity for Sr-90 and alpha-emitting radionuclides compared to the baseline MST material.

  4. N-acetyl-aspartyl-glutamate and inhibition of glutamate carboxypeptidases protects against soman-induced neuropathology.

    PubMed

    Guo, Huifu; Liu, Jiong; Van Shura, Kerry; Chen, HuaZhen; Flora, Michael N; Myers, Todd M; McDonough, John H; McCabe, Joseph T

    2015-05-01

    N-acetyl-aspartyl-glutamate (NAAG) is the most abundant neuropeptide in the mammalian brain. In a variety of animal models of brain injury, the administration of NAAG-related compounds, or inhibitors of glutamate carboxypeptidases (GCPs; the enzymes that hydrolyze NAAG), were shown to be neuroprotective. This study determined the impact of the administration of three NAAG-related compounds, NAAG, β-NAAG (a NAAG homologue resistant to degradation), and 2-phosphonomethyl pentanedioic acid (2-PMPA; an inhibitor of GCP enzymes), on the neuropathology that develops following exposure to the nerve agent, soman. When given 1 min after soman exposure, NAAG-related drug treatments did not alter the survival rate or body weight loss seen 24 h after rats were exposed to soman. Likewise, brain levels of both NAAG and its metabolite, N-acetyl-aspartate (NAA), were substantially decreased 24 h after soman, and in particularly vulnerable brain regions the drug treatments were unable to attenuate the reduction in NAA and NAAG levels. Histochemical study indicated there was a dramatic increase in Fluoro-Jade C (FJC) staining, indicative of neuron cell death, 24 h after soman exposure. However, in the amygdala and in the entorhinal and piriform limbic cortex, which sustained severe neuropathology following soman intoxication, single or combined injections of NAAG compounds and 2-PMPA significantly reduced the number of FJC-positive cells, and effect size estimates suggest that in some brain regions the treatments were effective. The findings suggest that NAAG neurotransmission in the central nervous system is significantly altered by soman exposure, and that the administration of NAAG-related compounds and 2-PMPA reduces neuron cell death in brain regions that sustain severe damage. PMID:25825357

  5. FATE OF FISSILE MATERIAL BOUND TO MONOSODIUM TITANATE DURING COOPER CATALYZED PEROXIDE OXIDATION OF TANK 48H WASTE

    SciTech Connect

    Taylor-Pashow, K.

    2012-08-09

    At the Savannah River Site (SRS), Tank 48H currently holds approximately 240,000 gallons of slurry which contains potassium and cesium tetraphenylborate (TPB). A copper catalyzed peroxide oxidation (CCPO) reaction is currently being examined as a method for destroying the TPB present in Tank 48H. Part of the development of that process includes an examination of the fate of the Tank 48H fissile material which is adsorbed onto monosodium titanate (MST) particles. This report details results from experiments designed to examine the potential degradation of MST during CCPO processing and the subsequent fate of the adsorbed fissile material. Experiments were conducted to simulate the CCPO process on MST solids loaded with sorbates in a simplified Tank 48H simulant. Loaded MST solids were placed into the Tank 48H simplified simulant without TPB, and the experiments were then carried through acid addition (pH adjustment to 11), peroxide addition, holding at temperature (50 C) for one week, and finally NaOH addition to bring the free hydroxide concentration to a target concentration of 1 M. Testing was conducted without TPB to show the maximum possible impact on MST since the competing oxidation of TPB with peroxide was absent. In addition, the Cu catalyst was also omitted, which will maximize the interaction of H{sub 2}O{sub 2} with the MST; however, the results may be non-conservative assuming the Cu-peroxide active intermediate is more reactive than the peroxide radical itself. The study found that both U and Pu desorb from the MST when the peroxide addition begins, although to different extents. Virtually all of the U goes into solution at the beginning of the peroxide addition, whereas Pu reaches a maximum of {approx}34% leached during the peroxide addition. Ti from the MST was also found to come into solution during the peroxide addition. Therefore, Ti is present with the fissile in solution. After the peroxide addition is complete, the Pu and Ti are found to

  6. TAILORING INORGANIC SORBENTS FOR SRS STRONTIUM AND ACTINIDE SEPARATIONS: OPTIMIZED MONOSODIUM TITANATEPHASE II INTERIM REPORT FOR EXTERNAL RELEASE

    SciTech Connect

    Hobbs, D; Michael Poirier, M; Mark Barnes, M; Mary Thompson, M

    2006-08-31

    This document provides an interim summary 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 materials. The activities included determining the key synthesis conditions for preparation of the modified MST, preparation of the modified MST at a larger laboratory scale, demonstration of the strontium and actinide removal characteristics with actual tank waste supernate and characterization of the modified MST. Key findings and conclusions include the following: (1) Samples of the modified MST prepared by Method 2 and Method 3 exhibited the best combination of strontium and actinide removal. (2) We selected Method 3 to scale up and test performance with actual waste solution. (3) We successfully prepared three batches of the modified MST using the Method 3 procedure at a 25-gram scale. (4) Performance tests indicated successful scale-up to the 25-gram scale with excellent performance and reproducibility among each of the three batches. For example, the plutonium decontamination factors (6-hour contact time) for the modified MST samples averaged 13 times higher than that of the baseline MST sample at half the sorbent concentration (0.2 g L{sup -1} for modified MST versus 0.4 g L{sup -1} for baseline MST). (5) Performance tests with actual waste supernate demonstrated that the modified MST exhibited better strontium and plutonium removal performance than that of the baseline MST. For example, the decontamination factors for the modified MST measured 2.6 times higher for strontium and between 5.2 to 11 times higher for plutonium compared to the baseline MST sample. The modified MST did not exhibit improved neptunium removal performance over that of the baseline MST. (6) Two strikes of the modified MST provided increased removal of strontium and actinides from actual waste compared to a single strike. The improved performance

  7. Aminotransferase and glutamate dehydrogenase activities in lactobacilli and streptococci.

    PubMed

    Peralta, Guillermo Hugo; Bergamini, Carina Viviana; Hynes, Erica Rut

    2016-01-01

    Aminotransferases and glutamate dehydrogenase are two main types of enzymes involved in the initial steps of amino acid catabolism, which plays a key role in the cheese flavor development. In the present work, glutamate dehydrogenase and aminotransferase activities were screened in twenty one strains of lactic acid bacteria of dairy interest, either cheese-isolated or commercial starters, including fifteen mesophilic lactobacilli, four thermophilic lactobacilli, and two streptococci. The strains of Streptococcus thermophilus showed the highest glutamate dehydrogenase activity, which was significantly elevated compared with the lactobacilli. Aspartate aminotransferase prevailed in most strains tested, while the levels and specificity of other aminotransferases were highly strain- and species-dependent. The knowledge of enzymatic profiles of these starter and cheese-isolated cultures is helpful in proposing appropriate combinations of strains for improved or increased cheese flavor. PMID:27266631

  8. Mapping Auditory Synaptic Circuits with Photostimulation of Caged Glutamate.

    PubMed

    Sturm, Joshua J; Nguyen, Tuan; Kandler, Karl

    2016-01-01

    Photostimulation of neurons with caged glutamate is a viable tool for mapping the strength and spatial distribution of synaptic networks in living brain slices. In photostimulation experiments, synaptic connectivity is assessed by eliciting action potentials in putative presynaptic neurons via focal photolysis of caged glutamate, while measuring postsynaptic responses via intracellular recordings. Two approaches are commonly used for delivering light to small, defined areas in the slice preparation; an optical fiber-based method and a laser-scanning-based method. In this chapter, we outline the technical bases for using photostimulation of caged glutamate to map synaptic circuits, and discuss the advantages and disadvantages of using fiber-based vs. laser-based systems. PMID:27259947

  9. Astrocytic Dysfunction and Addiction: Consequences of Impaired Glutamate Homeostasis

    PubMed Central

    Scofield, Michael D.; Kalivas, Peter W.

    2016-01-01

    Addiction is characterized as a chronic relapsing disorder whereby addicted individuals persistently engage in drug seeking and use despite profound negative consequences. The results of studies using animal models of addiction and relapse indicate that drug seeking is mediated by alterations in cortico-accumbal plasticity induced by chronic drug exposure. Among the maladaptive responses to drug exposure are long-lasting alterations in the expression of proteins localized to accumbal astrocytes, which are responsible for maintaining glutamate homeostasis. These alterations engender an aberrant potentiation of glutamate transmission in the cortico-accumbens circuit that is linked to the reinstatement of drug seeking. Accordingly, pharmacological restoration of glutamate homeostasis functions as an efficient method of reversing drug-induced plasticity and inhibiting drug seeking in both rodents and humans. PMID:24496610

  10. Ubiquitin-dependent trafficking and turnover of ionotropic glutamate receptors

    PubMed Central

    Goo, Marisa S.; Scudder, Samantha L.; Patrick, Gentry N.

    2015-01-01

    Changes in synaptic strength underlie the basis of learning and memory and are controlled, in part, by the insertion or removal of AMPA-type glutamate receptors at the postsynaptic membrane of excitatory synapses. Once internalized, these receptors may be recycled back to the plasma membrane by subunit-specific interactions with other proteins or by post-translational modifications such as phosphorylation. Alternatively, these receptors may be targeted for destruction by multiple degradation pathways in the cell. Ubiquitination, another post-translational modification, has recently emerged as a key signal that regulates the recycling and trafficking of glutamate receptors. In this review, we will discuss recent findings on the role of ubiquitination in the trafficking and turnover of ionotropic glutamate receptors and plasticity of excitatory synapses. PMID:26528125

  11. Chronic Glutamate Toxicity in Neurodegenerative Diseases—What is the Evidence?

    PubMed Central

    Lewerenz, Jan; Maher, Pamela

    2015-01-01

    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. PMID:26733784

  12. WAY208466 inhibits glutamate release at hippocampal nerve terminals.

    PubMed

    Wang, Hue Yu; Lu, Cheng Wei; Lin, Tzu Yu; Kuo, Jinn Rung; Wang, Su Jane

    2016-06-15

    Evidence suggests that the glutamatergic system plays a crucial role in the pathophysiology and treatment of depression. This study investigates the effect of WAY208466, a 5-HT6 receptor agonist exhibiting an antidepressant effect, on glutamate release from rat hippocampal nerve terminals (synaptosomes). WAY208466 inhibited the Ca(2+)-dependent release of glutamate that was evoked by exposing the synaptosomes to the potassium channel blocker 4-aminopyridine, and the selective 5-HT6 receptor antagonist SB258585 blocked this phenomenon. The WAY208466-mediated inhibition of glutamate release was associated with a reduction of 4-aminopyridine-induced increase in the cytosolic free Ca(2+) concentration ([Ca(2+)]C) mediated via Cav2.2 (N-type) and Cav2.1 (P/Q-type) channels. WAY208466 did not alter the resting synaptosomal membrane potential or 4-aminopyridine-mediated depolarization; thus, the inhibition of the Ca(2+) influx could not be attributed to the decrease in synaptosomal excitability caused by 5-HT6 receptor activation. Furthermore, the effect of WAY208466 on 4-aminopyridine-evoked glutamate release was prevented by a Gi/Go-protein inhibitor pertussis toxin, adenylate cyclase inhibitor SQ22536, and a protein kinase A inhibitor H89. These results suggest that WAY208466 acts at the 5-HT6 receptors present in the hippocampal nerve terminals to suppress the Gi/Go-protein-coupled adenylate cyclase/protein kinase A cascade, which subsequently reduces the Ca(2+) influx via N- and P/Q-type Ca(2+) channels to inhibit the evoked glutamate release. This finding implicated a potential therapeutic role of 5-HT6 receptor agonist in the treatment of depression and other neurological diseases associated with glutamate excitotoxicity. PMID:27068148

  13. Two Pathways of Glutamate Fermentation by Anaerobic Bacteria

    PubMed Central

    Buckel, Wolfgang; Barker, H. A.

    1974-01-01

    Two pathways are involved in the fermentation of glutamate to acetate, butyrate, carbon dioxide, and ammonia—the methylaspartate and the hydroxyglutarate pathways which are used by Clostridium tetanomorphum and Peptococcus aerogenes, respectively. Although these pathways give rise to the same products, they are easily distinguished by different labeling patterns of the butyrate when [4-14C]glutamate is used as substrate. Schmidt degradation of the radioactive butyrate from C. tetanomorphum yielded equally labeled propionate and carbon dioxide, whereas nearly all the radioactivity of the butyrate from P. aerogenes was recovered in the corresponding propionate. This procedure was used as a test for the pathway of glutamate fermentation by 15 strains (9 species) of anaerobic bacteria. The labeling patterns of the butyrate indicate that glutamate is fermented via the methylaspartate pathway by C. tetani, C. cochlearium, and C. saccarobutyricum, and via the hydroxyglutarate pathway by Acidaminococcus fermentans, C. microsporum, Fusobacterium nucleatum, and F. fusiformis. Enzymes specific for each pathway were assayed in crude extracts of the above organisms. 3-Methylaspartase was found only in clostridia which use the methylaspartate pathway, including Clostridium SB4 and C. sticklandii, which probably degrade glutamate to acetate and carbon dioxide by using a second amino acid as hydrogen acceptor. High levels of 2-hydroxyglutarate dehydrogenase were found exclusively in organisms that use the hydroxyglutarate pathway. The data indicate that only two pathways are involved in the fermentation of glutamate by the bacteria analyzed. The methylaspartate pathway appears to be used only by species of Clostridium, whereas the hydroxyglutarate pathway is used by representatives of several genera. PMID:4813895

  14. Rapid glutamate release in the mediobasal hypothalamus accompanies feeding and is exaggerated by an obesogenic food

    PubMed Central

    Guyenet, Stephan J.; Matsen, Miles E.; Morton, Gregory J.; Kaiyala, Karl J.; Schwartz, Michael W.

    2013-01-01

    The mediobasal hypothalamus (MBH) plays a central role in the regulation of food intake and energy balance. Although the excitatory neurotransmitter glutamate is implicated in energy balance regulation by the MBH, the hypothesis that feeding elicits local glutamate release remains untested. To test this hypothesis, we employed a glutamate biosensor that measures glutamate concentrations at 1-s intervals in conscious, freely behaving rats. Results indicate that feeding is associated with an increase of MBH glutamate concentration that occurs within 1–2 s of oral contact with a food pellet, and the glutamate response to a palatable high-fat pellet is greatly exaggerated relative to chow. In contrast, glutamate responses were not observed during water ingestion or other observed behaviors. These findings indicate that feeding is associated with rapid release of glutamate in the MBH, that this release is exaggerated with an obesogenic food, and that this response is likely stimulated by orosensory factors. PMID:24199157

  15. [Glutamate and malignant gliomas, from epilepsia to biological aggressiveness: therapeutic implications].

    PubMed

    Blecic, Serge; Rynkowski, Michal; De Witte, Olivier; Lefranc, Florence

    2013-09-01

    In this review article, we describe the unrecognized roles of glutamate and glutamate receptors in malignant glioma biology. The neurotransmitter glutamate released from malignant glioma cells in the extracellular matrix is responsible for seizure induction and at higher concentration neuronal cell death. This neuronal cell death will create vacated place for tumor growth. Glutamate also stimulates the growth and the migration of glial tumor cells by means of the activation of glutamate receptors on glioma cells in a paracrine and autocrine manner. The multitude of effects of glutamate in glioma biology supports the rationale for pharmacological targeting of glutamate receptors and transporters in the adjuvant treatment of malignant gliomas in neurology and neuro-oncology. Using the website www.clinicaltrials.gov/ as a reference - a service developed by the National Library of Medicine for the National Health Institute in USA - we have evoked the few clinical trials completed and currently ongoing with therapies targeting the glutamate receptors. PMID:23883552

  16. Glutamate transporters and presynaptic metabotropic glutamate receptors protect neocortical Cajal-Retzius cells against over-excitation.

    PubMed

    Dvorzhak, Anton; Unichenko, Petr; Kirischuk, Sergei

    2012-08-01

    Cajal-Retzius (CR) cells, early generated neurons in the marginal zone of developing neocortex, are reported to be highly vulnerable to excitotoxic damage. Because extracellular glutamate concentration in the central nervous system is mainly controlled by glutamate transporters (EAATs), we studied the effects of EAAT blockade on CR cells. DL: -TBOA, a specific EAAT antagonist, induced NMDA receptor-dependent bursting discharges in layer 2/3 pyramidal neurons, indicating that EAATs operate in the uptake mode and their blockade leads to elevation of extracellular glutamate concentration. In CR cells, however, DL: -TBOA failed to change either the membrane resistance or holding current, and moreover, it reduced the frequency of spontaneous GABAergic postsynaptic currents. DL: -TBOA decreased the mean amplitude and increased paired-pulse ratio of evoked GABAergic postsynaptic currents, indicating the presynaptic locus of its action. Indeed, LY379268, a specific agonist of group II metabotropic glutamate receptors (mGluR-II), mimicked the DL: -TBOA-mediated effects, and LY341495, an unspecific mGluR antagonist, eliminated the DL: -TBOA-induced effects. As dihydrokainic acid, a specific EAAT2 blocker, failed to affect evoked GABAergic postsynaptic currents, whereas TFB-TBOA, a selective blocker of EAAT1 and EAAT2, produced effects similar to that of DL: -TBOA, extracellular glutamate concentration in the marginal zone is mainly controlled by EAAT1 (GLAST). Thus, even though CR cells are highly vulnerable to excitotoxic damage, a number of mechanisms serve to protect them against excessive extracellular glutamate concentration including a lack of functional glutamatergic synapses, Mg(2+) blockade of NMDA receptors, and presynaptic mGluRs that inhibit transmission at GABAergic synapses. PMID:22665047

  17. Temperature Differentially Facilitates Spontaneous but Not Evoked Glutamate Release from Cranial Visceral Primary Afferents

    PubMed Central

    Fawley, Jessica A.; Hofmann, Mackenzie E.; Largent-Milnes, Tally M.; Andresen, Michael C.

    2015-01-01

    Temperature is fundamentally important to all biological functions including synaptic glutamate release. Vagal afferents from the solitary tract (ST) synapse on second order neurons in the nucleus of the solitary tract, and glutamate release at this first central synapse controls autonomic reflex function. Expression of the temperature-sensitive Transient Receptor Potential Vanilloid Type 1 receptor separates ST afferents into C-fibers (TRPV1+) and A-fibers (TRPV1-). Action potential-evoked glutamate release is similar between C- and A-fiber afferents, but TRPV1 expression facilitates a second form of synaptic glutamate release in C-fibers by promoting substantially more spontaneous glutamate release. The influence of temperature on different forms of glutamate release is not well understood. Here we tested how temperature impacts the generation of evoked and spontaneous release of glutamate and its relation to TRPV1 expression. In horizontal brainstem slices of rats, activation of ST primary afferents generated synchronous evoked glutamate release (ST-eEPSCs) at constant latency whose amplitude reflects the probability of evoked glutamate release. The frequency of spontaneous EPSCs in these same neurons measured the probability of spontaneous glutamate release. We measured both forms of glutamate from each neuron during ramp changes in bath temperature of 4–5°C. Spontaneous glutamate release from TRPV1+ closely tracked with these thermal changes indicating changes in the probability of spontaneous glutamate release. In the same neurons, temperature changed axon conduction registered as latency shifts but ST-eEPSC amplitudes were constant and independent of TRPV1 expression. These data indicate that TRPV1-operated glutamate release is independent of action potential-evoked glutamate release in the same neurons. Together, these support the hypothesis that evoked and spontaneous glutamate release originate from two pools of vesicles that are independently

  18. Rapid Microelectrode Measurements and the Origin and Regulation of Extracellular Glutamate in Rat Prefrontal Cortex

    PubMed Central

    Hascup, E.R.; Hascup, K.N.; Stephens, M.; Pomerleau, F.; Huettl, P.; Gratton, A.; Gerhardt, G.A.

    2010-01-01

    Glutamate in the prefrontal cortex (PFC) plays a significant role in several mental illnesses, including schizophrenia, addiction and anxiety. Previous studies on PFC glutamate-mediated function have used techniques that raise questions on the neuronal vs. astrocytic origin of glutamate. The present studies used enzyme-based microelectrode arrays (MEAs) to monitor second-by-second resting glutamate levels in the PFC of awake rats. Locally-applied drugs were employed in an attempt to discriminate between the neuronal or glial components of the resting glutamate signal. Local application of tetrodotoxin (TTX; sodium channel blocker), produced a significant (~40%) decline in resting glutamate levels. In addition significant reductions in extracellular glutamate were seen with locally-applied ω-conotoxin (MVIIC; ~50%; calcium channel blocker), and the mGluR⅔ agonist, LY379268 (~20%), and a significant increase with the mGluR⅔ antagonist LY341495 (~40%), effects all consistent with a large neuronal contribution to the resting glutamate levels. Local administration of D,L-threo-β-benzyloxyaspartate (TBOA; glutamate transporter inhibitor) produced an ~120% increase in extracellular glutamate levels, supporting that excitatory amino acid transporters, which are largely located on glia, modulate clearance of extracellular glutamate. Interestingly, local application of (S)-4-carboxyphenylglycine (CPG; cystine/glutamate antiporter inhibitor), produced small, non-significant bi-phasic changes in extracellular glutamate versus vehicle control. Finally, pre-administration of TTX completely blocked the glutamate response to tail pinch stress. Taken together, these results support that PFC resting glutamate levels in rats as measured by the MEA technology are at least 40-50% derived from neurons. Furthermore, these data support that the impulse flow-dependent glutamate release from a physiologically-evoked event is entirely neuronally derived. PMID:20969570

  19. Cocaine-induced neuroadaptations in the dorsal striatum: glutamate dynamics and behavioral sensitization.

    PubMed

    Parikh, Vinay; Naughton, Sean X; Shi, Xiangdang; Kelley, Leslie K; Yegla, Brittney; Tallarida, Christopher S; Rawls, Scott M; Unterwald, Ellen M

    2014-09-01

    Recent evidence suggests that diminished ability to control cocaine seeking arises from perturbations in glutamate homeostasis in the nucleus accumbens. However, the neurochemical substrates underlying cocaine-induced neuroadaptations in the dorsal striatum and how these mechanisms link to behavioral plasticity is not clear. We employed glutamate-sensitive microelectrodes and amperometry to study the impact of repeated cocaine administration on glutamate dynamics in the dorsolateral striatum of awake freely-moving rats. Depolarization-evoked glutamate release was robustly increased in cocaine-pretreated rats challenged with cocaine. Moreover, the clearance of glutamate signals elicited either by terminal depolarization or blockade of non-neuronal glutamate transporters slowed down dramatically in cocaine-sensitized rats. Repeated cocaine exposure also reduced the neuronal tone of striatal glutamate. Ceftriaxone, a β-lactam antibiotic that activates the astrocytic glutamate transporter, attenuated the effects of repeated cocaine exposure on synaptic glutamate release and glutamate clearance kinetics. Finally, the antagonism of AMPA glutamate receptors in the dorsolateral striatum blocked the development of behavioral sensitization to repeated cocaine administration. Collectively, these data suggest that repeated cocaine exposure disrupts presynaptic glutamate transmission and transporter-mediated clearance mechanisms in the dorsal striatum. Moreover, such alterations produce an over activation of AMPA receptors in this brain region leading to the sensitized behavioral response to repeated cocaine. PMID:24911954

  20. 40 CFR 721.3821 - L-Glutamic acid, N-(1-oxododecyl)-.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false L-Glutamic acid, N-(1-oxododecyl... Substances § 721.3821 L-Glutamic acid, N-(1-oxododecyl)-. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as L-Glutamic acid, N-(1-oxododecyl)- (PMN...

  1. 40 CFR 721.3821 - L-Glutamic acid, N-(1-oxododecyl)-.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false L-Glutamic acid, N-(1-oxododecyl... Substances § 721.3821 L-Glutamic acid, N-(1-oxododecyl)-. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as L-Glutamic acid, N-(1-oxododecyl)- (PMN...

  2. 40 CFR 721.3821 - L-Glutamic acid, N-(1-oxododecyl)-.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false L-Glutamic acid, N-(1-oxododecyl... Substances § 721.3821 L-Glutamic acid, N-(1-oxododecyl)-. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as L-Glutamic acid, N-(1-oxododecyl)- (PMN...

  3. 40 CFR 721.3821 - L-Glutamic acid, N-(1-oxododecyl)-.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false L-Glutamic acid, N-(1-oxododecyl... Substances § 721.3821 L-Glutamic acid, N-(1-oxododecyl)-. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as L-Glutamic acid, N-(1-oxododecyl)- (PMN...

  4. 40 CFR 721.3821 - L-Glutamic acid, N-(1-oxododecyl)-.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false L-Glutamic acid, N-(1-oxododecyl... Substances § 721.3821 L-Glutamic acid, N-(1-oxododecyl)-. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as L-Glutamic acid, N-(1-oxododecyl)- (PMN...

  5. Astrocyte/neuron ratio and its importance on glutamate toxicity: an in vitro voltammetric study.

    PubMed

    Hacimuftuoglu, Ahmet; Tatar, Abdulgani; Cetin, Damla; Taspinar, Numan; Saruhan, Fatih; Okkay, Ufuk; Turkez, Hasan; Unal, Deniz; Stephens, Robert Louis; Suleyman, Halis

    2016-08-01

    The purpose of this study was to clarify the relationship between neuron cells and astrocyte cells in regulating glutamate toxicity on the 10th and 20th day in vitro. A mixed primary culture system from newborn rats that contain cerebral cortex neurons cells was employed to investigate the glutamate toxicity. All cultures were incubated with various glutamate concentrations, then viability tests and histological analyses were performed. The activities of glutamate transporters were determined by using in vitro voltammetry technique. Viable cell number was decreased significantly on the 10th day at 10(-7) M and at 10(-6) M glutamate applications, however, viable cell number was not decreased at 20th day. Astrocyte number was increased nearly six times on the 20th day as compared to the 10th day. The peak point of glutamate reuptake capacity was about 2 × 10(-4) M on the 10th day and 10(-3) M on the 20th day. According to our results, we suggested that astrocyte age was important to maintain neuronal survival against glutamate toxicity. Thus, we revealed activation or a trigger point of glutamate transporters on astrocytes due to time since more glutamate was taken up by astrocytes when glutamate transporters on the astrocyte were triggered with high exogenous glutamate concentrations. In conclusion, the present investigation is the first voltammetric study on the reuptake parameters of glutamate in vitro. PMID:26438331

  6. [Effectiveness of glutamate in the treatment of early manifestations of occupational fluorosis].

    PubMed

    Grekhova, T D; Katsnelśon, B A; Kolmogortseva, V M; Konysheva, L K; Babakova, O M

    1994-01-01

    Efficiency of glutamic acid for therapy of early signs of occupational fluorosis was studied in workers engaged into cryolite production. The study proved that use of glutamic acid in occupational conditions prevents progressing of metabolic disorders. The results encourage recommendations to include glutamate into therapeutic and prophylactic nutrition of workers exposed to fluor compounds, into nutritive additions according to special recipe. PMID:7987560

  7. Triple threat treatment: Exploiting the dependence receptor properties of metabotropic glutamate receptor 1 against melanoma

    PubMed Central

    Gelb, Tara; Hathaway, Hannah A; Wroblewski, Jarda T

    2014-01-01

    Melanoma cells that express metabotropic glutamate 1 (mGlu1) receptors depend on glutamate for their survival and proliferation. The dependence receptor properties of mGlu1 allow us to propose and justify three promising approaches for melanoma treatment: glutamate depletion, mGlu1 receptor antagonism, and targeting of mGlu1 receptor signaling.

  8. Continuous glutamate production using an immobilized whole-cell system

    SciTech Connect

    Kim, H.S.; Ryu, D.D.Y.

    1982-10-01

    For the purpose of saving the energy and raw materials required in a glutamate fermentation, an immobilized whole-cell system was prepared and its performance in a continuous reactor system was evaluated. Corynebacterium glutamicum (a mutant strain of ATCC 13058) whole cell was immobilized in k-carrageenan matrix and the gel structure was strengthened by treatment with a hardening agent. The effective diffusivities of carrageenan gel for glucose and oxygen were formed to decrease significantly with an increase in carrageenan concentration, while the gel strength showed an increasing trend. Based on the physical and chemical properties of carrageenan gel, the immobilized method was improved and the operation of the continuous reactor system was partially optimized. In an air-stirred fermentor, the continuous production of glutamate was carried out. The effect of the dilution rate of glutamate production and operation stability was investigated. The performance of the continuous wbole-cell reactor system was evaluated by measuring glutamate productivity for a period of 30 days; it was found to be far superior to the performance of convention batch reactor systems using free cells.

  9. Blood and Brain Glutamate Levels in Children with Autistic Disorder

    ERIC Educational Resources Information Center

    Hassan, Tamer H.; Abdelrahman, Hadeel M.; Fattah, Nelly R. Abdel; El-Masry, Nagda M.; Hashim, Haitham M.; El-Gerby, Khaled M.; Fattah, Nermin R. Abdel

    2013-01-01

    Despite of the great efforts that move forward to clarify the pathophysiologic mechanisms in autism, the cause of this disorder, however, remains largely unknown. There is an increasing body of literature concerning neurochemical contributions to the pathophysiology of autism. We aimed to determine blood and brain levels of glutamate in children…

  10. Microbial production and chemical transformation of poly-γ-glutamate

    PubMed Central

    Ashiuchi, Makoto

    2013-01-01

    Poly-γ-glutamate (PGA), a novel polyamide material with industrial applications, possesses a nylon-like backbone, is structurally similar to polyacrylic acid, is biodegradable and is safe for human consumption. PGA is frequently found in the mucilage of natto, a Japanese traditional fermented food. To date, three different types of PGA, namely a homo polymer of d-glutamate (D-PGA), a homo polymer of l-glutamate (L-PGA), and a random copolymer consisting of d- and l-glutamate (DL-PGA), are known. This review will detail the occurrence and physiology of PGA. The proposed reaction mechanism of PGA synthesis including its localization and the structure of the involved enzyme, PGA synthetase, are described. The occurrence of multiple carboxyl residues in PGA likely plays a role in its relative unsuitability for the development of bio-nylon plastics and thus, establishment of an efficient PGA-reforming strategy is of great importance. Aside from the potential applications of PGA proposed to date, a new technique for chemical transformation of PGA is also discussed. Finally, some techniques for PGA and its derivatives in advanced material technology are presented. PMID:23855427

  11. Neonatal hyperammonemia: the N-carbamoyl-L-glutamic acid test.

    PubMed

    Guffon, Nathalie; Schiff, Manuel; Cheillan, David; Wermuth, Bendicht; Häberle, Johannes; Vianey-Saban, Christine

    2005-08-01

    In a prospective study, patients with a suspected urea cycle defect underwent oral N-carbamoyl-L-glutamic acid loading testing. In patients with subsequently confirmed N-acetylglutamate synthase deficiency, hyperammonemia normalized within 8 hours. This test may be useful in the early diagnosis of patients with suspected urea cycle disorders. PMID:16126063

  12. Does formate reduce alpha-ketoglutarate and ammonia to glutamate?

    NASA Technical Reports Server (NTRS)

    Maughan, Q.; Miller, S. L.; Bada, J. L. (Principal Investigator)

    1999-01-01

    The reported reduction of alpha-ketoglutarate and ammonia by formate is much slower than described (Morowitz et al., 1995). The formate reduction if any is small under these conditions. Glutamate is produced from a reduction by a second molecule of alpha-ketoglutarate involving an oxidative decarboxylation.

  13. Control of cortical neuronal migration by glutamate and GABA.

    PubMed

    Luhmann, Heiko J; Fukuda, A; Kilb, W

    2015-01-01

    Neuronal migration in the cortex is controlled by the paracrine action of the classical neurotransmitters glutamate and GABA. Glutamate controls radial migration of pyramidal neurons by acting primarily on NMDA receptors and regulates tangential migration of inhibitory interneurons by activating non-NMDA and NMDA receptors. GABA, acting on ionotropic GABAA-rho and GABAA receptors, has a dichotomic action on radially migrating neurons by acting as a GO signal in lower layers and as a STOP signal in upper cortical plate (CP), respectively. Metabotropic GABAB receptors promote radial migration into the CP and tangential migration of interneurons. Besides GABA, the endogenous GABAergic agonist taurine is a relevant agonist controlling radial migration. To a smaller extent glycine receptor activation can also influence radial and tangential migration. Activation of glutamate and GABA receptors causes increases in intracellular Ca(2+) transients, which promote neuronal migration by acting on the cytoskeleton. Pharmacological or genetic manipulation of glutamate or GABA receptors during early corticogenesis induce heterotopic cell clusters in upper layers and loss of cortical lamination, i.e., neuronal migration disorders which can be associated with neurological or neuropsychiatric diseases. The pivotal role of NMDA and ionotropic GABA receptors in cortical neuronal migration is of major clinical relevance, since a number of drugs acting on these receptors (e.g., anti-epileptics, anesthetics, alcohol) may disturb the normal migration pattern when present during early corticogenesis. PMID:25688185

  14. Caffeine promotes glutamate and histamine release in the posterior hypothalamus

    PubMed Central

    Kodama, Tohru; Siegel, Jerome M.

    2014-01-01

    Histamine neurons are active during waking and largely inactive during sleep, with minimal activity during rapid-eye movement (REM) sleep. Caffeine, the most widely used stimulant, causes a significant increase of sleep onset latency in rats and humans. We hypothesized that caffeine increases glutamate release in the posterior hypothalamus (PH) and produces increased activity of wake-active histamine neurons. Using in vivo microdialysis, we collected samples from the PH after caffeine administration in freely behaving rats. HPLC analysis and biosensor measurements showed a significant increase in glutamate levels beginning 30 min after caffeine administration. Glutamate levels remained elevated for at least 140 min. GABA levels did not significantly change over the same time period. Histamine level significantly increased beginning 30 min after caffeine administration and remained elevated for at least 140 min. Immunostaining showed a significantly elevated number of c-Fos-labeled histamine neurons in caffeine-treated rats compared with saline-treated animals. We conclude that increased glutamate levels in the PH activate histamine neurons and contribute to caffeine-induced waking and alertness. PMID:25031227

  15. Control of cortical neuronal migration by glutamate and GABA

    PubMed Central

    Luhmann, Heiko J.; Fukuda, A.; Kilb, W.

    2015-01-01

    Neuronal migration in the cortex is controlled by the paracrine action of the classical neurotransmitters glutamate and GABA. Glutamate controls radial migration of pyramidal neurons by acting primarily on NMDA receptors and regulates tangential migration of inhibitory interneurons by activating non-NMDA and NMDA receptors. GABA, acting on ionotropic GABAA-rho and GABAA receptors, has a dichotomic action on radially migrating neurons by acting as a GO signal in lower layers and as a STOP signal in upper cortical plate (CP), respectively. Metabotropic GABAB receptors promote radial migration into the CP and tangential migration of interneurons. Besides GABA, the endogenous GABAergic agonist taurine is a relevant agonist controlling radial migration. To a smaller extent glycine receptor activation can also influence radial and tangential migration. Activation of glutamate and GABA receptors causes increases in intracellular Ca2+ transients, which promote neuronal migration by acting on the cytoskeleton. Pharmacological or genetic manipulation of glutamate or GABA receptors during early corticogenesis induce heterotopic cell clusters in upper layers and loss of cortical lamination, i.e., neuronal migration disorders which can be associated with neurological or neuropsychiatric diseases. The pivotal role of NMDA and ionotropic GABA receptors in cortical neuronal migration is of major clinical relevance, since a number of drugs acting on these receptors (e.g., anti-epileptics, anesthetics, alcohol) may disturb the normal migration pattern when present during early corticogenesis. PMID:25688185

  16. Antipsychotic treatment modulates glutamate transport and NMDA receptor expression.

    PubMed

    Zink, Mathias; Englisch, Susanne; Schmitt, Andrea

    2014-11-01

    Schizophrenia patients often suffer from treatment-resistant cognitive and negative symptoms, both of which are influenced by glutamate neurotransmission. Innovative therapeutic strategies such as agonists at metabotropic glutamate receptors or glycin reuptake inhibitors try to modulate the brain's glutamate network. Interactions of amino acids with monoamines have been described on several levels, and first- and second-generation antipsychotic agents (FGAs, SGAs) are known to exert modulatory effects on the glutamatergic system. This review summarizes the current knowledge on effects of FGAs and SGAs on glutamate transport and receptor expression derived from pharmacological studies. Such studies serve as a control for molecular findings in schizophrenia brain tissue and are clinically relevant. Moreover, they may validate animal models for psychosis, foster basic research on antipsychotic substances and finally lead to a better understanding of how monoaminergic and amino acid neurotransmissions are intertwined. In the light of these results, important differences dependent on antipsychotic substances, dosage and duration of treatment became obvious. While some post-mortem findings might be confounded with multifold drug effects, others are unlikely to be influenced by antipsychotic treatment and could represent important markers of schizophrenia pathophysiology. In similarity to the convergence of toxic and psychotomimetic effects of dopaminergic, serotonergic and anti-glutamatergic substances, the therapeutic mechanisms of SGAs might merge on a yet to be defined molecular level. In particular, serotonergic effects of SGAs, such as an agonism at 5HT1A receptors, represent important targets for further clinical research. PMID:25214389

  17. Structure-activity relationships of glutamate carboxypeptidase II (GCPII) inhibitors.

    PubMed

    Ferraris, D V; Shukla, K; Tsukamoto, T

    2012-01-01

    Glutamate carboxypeptidase II (GCPII, EC 3.4.17.21) is a zinc metallopeptidase that hydrolyzes N-acetylaspartylglutamate (NAAG) into N-acetylaspartate (NAA) and glutamate in the nervous system. Inhibition of GCPII has the potential to reduce extracellular glutamate and represents an opportune target for treating neurological disorders in which excess glutamate is considered pathogenic. Furthermore, GCPII was found to be identical to a tumor marker, prostate-specific membrane antigen (PSMA), and has drawn significant interest as a diagnostic and/or therapeutic target in oncology. Over the past 15 years, tremendous efforts have been made in the discovery of potent GCPII inhibitors, particularly those with phosphorus-, urea- and thiol-based zinc binding groups. In addition, significant progress has been made in understanding the three-dimensional structural characteristics of GCPII in complex with various ligands. The purpose of this review article is to analyze the structure-activity relationships (SAR) of GCPII inhibitors reported to date, which are classified on the basis of their zinc-binding group. SAR and crystallographic data are evaluated in detail for each of these series to highlight the future challenges and opportunities to identify clinically viable GCPII inhibitors. PMID:22304717

  18. Paraventricular Stimulation with Glutamate Elicits Bradycardia and Pituitary Responses

    NASA Technical Reports Server (NTRS)

    Darlington, Daniel N.; Miyamoto, Michael; Keil, Lanny C.; Dallman, Mary F.

    1989-01-01

    The excitatory neurotransmitter, L-glutamate (0.5 M, pH 7.4), or the organic acid, acetate (0.5 M, pH 7.4), was microinjected (50 nl over 2 min) directly into the paraventricular nuclei (PVN) of pentobarbital sodium-anesthetized rats while arterial blood pressure and heart rate and plasma adrenocorticotropic hormone (ACTH), vasopressin, and oxytocin were measured. Activation of PVN neurons with L-glutamate led to increases in plasma ACTH, vasopressin, and oxytocin and a profound bradycardia (-80 beats/min) with little change in arterial blood pressure. Microinjection of acetate had no effect on the above variables. The decrease in heart rate was shown to be dependent on the concentration of glutamate injected and the volume of injectate. The bradycardia was mediated through the autonomic nervous system because ganglionic blockade (pentolinium tartrate) eliminated the response; atropine and propranolol severely attenuated the bradycardia. The bradycardia was greatest when L-glutamate was microinjected into the caudal PVN. Injections into the rostral PVN or into nuclei surrounding the PVN led to small or nonsignificant decreases in heart rate. Focal electric stimulation (2-50 pA) of the PVN also led to decreases in heart rate and arterial blood pressure. These data suggest that activation of PVN neurons leads to the release of ACTH, vasopressin, and oxytocin from the pituitary and a bradycardia that is mediated by the autonomic nervous system.

  19. [Glutamic acid group poisoning. So-called Chinese restaurant syndrome].

    PubMed

    Rudin, O; Stauffer, E; Cramer, Y; Krämer, M

    1989-01-01

    After eating a soup 10 persons (out of 100) fell sick; within 10 minutes they suffered from nervous muscle convulsions, trembling, mouth desiccation and dilatation of the pupils. The soup contained glutamate as flavour enhancer in an unusually high concentration of 31 grams per litre. PMID:2573344

  20. Vasorelaxation induced by L-glutamate in porcine coronary arteries.

    PubMed

    Nguyen-Duong, H

    2001-04-20

    Isolated porcine coronary arteries (PCA) contracted by depolarization with high K0 or by histamine (10 microM) were relaxed concentration-dependently by glutamic acid, aspartic acid, N-methyl-D-aspartate (NMDA) and, gamma-aminobutyric acid (GABA). In the PCA preparations contracted by high K0 or histamine the effects were monophasic, but the histamine-induced effects were more sustained and of larger amplitude. The ED50 values of cumulative concentration-response (CCR) curves obtained for the relaxation induced by L-glutamate in histamine-stimulated PCA preparations were shifted from 0.8 mM to 0.25 microM in presence of 1 mM glycine, a co-agonist required for the activation of NMDA receptors. The relaxations resulting from low-affinity binding of L-glutamic were dependent on Ca0 as evidenced by the shift of CCR curves to the right in the presence of 5-100 mM K0. In contrast, CCR curves obtained for contractions induced by NaF (1.5-12 mM), were significantly shifted to the left (from 6.3 to 3.1 mM). A depression of the maximum effect observed at higher F- concentrations was reversed by addition of 5 mM Mg0. Data show that glutamate induces a vasorelaxation that may be associated with symptoms seen in Chinese restaurant syndrome. PMID:11339334

  1. Regulation of glutamate metabolism by protein kinases in mycobacteria.

    PubMed

    O'Hare, Helen M; Durán, Rosario; Cerveñansky, Carlos; Bellinzoni, Marco; Wehenkel, Anne Marie; Pritsch, Otto; Obal, Gonzalo; Baumgartner, Jens; Vialaret, Jérome; Johnsson, Kai; Alzari, Pedro M

    2008-12-01

    Protein kinase G of Mycobacterium tuberculosis has been implicated in virulence and in regulation of glutamate metabolism. Here we show that this kinase undergoes a pattern of autophosphorylation that is distinct from that of other M. tuberculosis protein kinases characterized to date and we identify GarA as a substrate for phosphorylation by PknG. Autophosphorylation of PknG has little effect on kinase activity but promotes binding to GarA, an interaction that is also detected in living mycobacteria. PknG phosphorylates GarA at threonine 21, adjacent to the residue phosphorylated by PknB (T22), and these two phosphorylation events are mutually exclusive. Like the homologue OdhI from Corynebacterium glutamicum, the unphosphorylated form of GarA is shown to inhibit alpha-ketoglutarate decarboxylase in the TCA cycle. Additionally GarA is found to bind and modulate the activity of a large NAD(+)-specific glutamate dehydrogenase with an unusually low affinity for glutamate. Previous reports of a defect in glutamate metabolism caused by pknG deletion may thus be explained by the effect of unphosphorylated GarA on these two enzyme activities, which may also contribute to the attenuation of virulence. PMID:19019160

  2. PRRT2 Mutant Leads to Dysfunction of Glutamate Signaling.

    PubMed

    Li, Ming; Niu, Fenghe; Zhu, Xilin; Wu, Xiaopan; Shen, Ning; Peng, Xiaozhong; Liu, Ying

    2015-01-01

    Paroxysmal kinesigenic choreoathetosis (PKC) is an inherited disease of the nervous system. We previously identified PRRT2 as the causative gene of PKC. However, as little is known about the function of PRRT2, elucidating its function will benefit not only PKC studies, but also many other related disorders. Here, we reveal higher levels of glutamate in the plasma of PKC patients and the culture medium of neurons following knock-out Prrt2 expression. Using double immunostaining assays we confirm Prrt2 is located at the glutamatergic neurons in accordance with its function. Our co-immunoprecipitation assays reveal mutant PRRT2 interferes with SNAP25 and GRIA1 interactions, respectively. Furthermore, using live-labeling techniques, we confirmed co-transfection with mutant PRRT2 caused an increase in GRIA1 distribution on the cell surface. Therefore, our results suggest that mutant PRRT2, probably through its weakened interaction with SNAP25, affects glutamate signaling and glutamate receptor activity, resulting in the increase of glutamate release and subsequent neuronal hyperexcitability. PMID:25915028

  3. PRRT2 Mutant Leads to Dysfunction of Glutamate Signaling

    PubMed Central

    Li, Ming; Niu, Fenghe; Zhu, Xilin; Wu, Xiaopan; Shen, Ning; Peng, Xiaozhong; Liu, Ying

    2015-01-01

    Paroxysmal kinesigenic choreoathetosis (PKC) is an inherited disease of the nervous system. We previously identified PRRT2 as the causative gene of PKC. However, as little is known about the function of PRRT2, elucidating its function will benefit not only PKC studies, but also many other related disorders. Here, we reveal higher levels of glutamate in the plasma of PKC patients and the culture medium of neurons following knock-out Prrt2 expression. Using double immunostaining assays we confirm Prrt2 is located at the glutamatergic neurons in accordance with its function. Our co-immunoprecipitation assays reveal mutant PRRT2 interferes with SNAP25 and GRIA1 interactions, respectively. Furthermore, using live-labeling techniques, we confirmed co-transfection with mutant PRRT2 caused an increase in GRIA1 distribution on the cell surface. Therefore, our results suggest that mutant PRRT2, probably through its weakened interaction with SNAP25, affects glutamate signaling and glutamate receptor activity, resulting in the increase of glutamate release and subsequent neuronal hyperexcitability. PMID:25915028

  4. Synthesis and characterization of higher amino acid Schiff bases, as monosodium salts and neutral forms. Investigation of the intramolecular hydrogen bonding in all Schiff bases, antibacterial and antifungal activities of neutral forms

    NASA Astrophysics Data System (ADS)

    Güngör, Özlem; Gürkan, Perihan

    2014-09-01

    Schiff bases derived from 5-nitro-salicylaldehyde and 4-aminobutyric acid, 5-aminopentanoic acid and 6-aminohexanoic acid were synthesized both as monosodium salts (1a-3a) and neutral forms (1b-3b). The monosodium-Schiff bases were characterized by elemental analysis, 1H/13C NMR, IR, powder XRD, UV-vis spectra and conductivity measurements. The neutral-Schiff bases were characterized by elemental analysis, 1H/13C NMR, 2D NMR (HMQC), mass, IR, powder XRD, UV-vis spectra and conductivity measurements. The intramolecular hydrogen bonding and related tautomeric equilibria in all the Schiff bases were studied by UV-vis and 1H NMR spectra in solution. Additionally, the neutral-Schiff bases were screened against Staphylococcus aureus-EB18, S. aureus-ATCC 25923, Escherichia coli-ATCC 11230, Candida albicans-M3 and C. albicans-ATCC 16231.

  5. On the potential role of glutamate transport in mental fatigue.

    PubMed

    Rönnbäck, Lars; Hansson, Elisabeth

    2004-11-01

    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

  6. Prefrontal Cortex Glutamate Correlates with Mental Perspective-Taking

    PubMed Central

    Montag, Christiane; Schubert, Florian; Heinz, Andreas; Gallinat, Jürgen

    2008-01-01

    Background Dysfunctions in theory of mind and empathic abilities have been suggested as core symptoms in major psychiatric disorders including schizophrenia and autism. Since self monitoring, perspective taking and empathy have been linked to prefrontal (PFC) and anterior cingulate cortex (ACC) function, neurotransmitter variations in these areas may account for normal and pathological variations of these functions. Converging evidence indicates an essential role of glutamatergic neurotransmission in psychiatric diseases with pronounced deficits in empathy. However, the role of the glutamate system for different dimensions of empathy has not been investigated so far. Methodology/Principal Findings Absolute concentrations of cerebral glutamate in the ACC, left dorsolateral PFC and left hippocampus were determined by 3-tesla proton magnetic resonance spectroscopy (1H-MRS) in 17 healthy individuals. Three dimensions of empathy were estimated by a self-rating questionnaire, the Interpersonal Reactivity Index (IRI). Linear regression analysis showed that dorsolateral PFC glutamate concentration was predicted by IRI factor “perspective taking” (T = −2.710, p = 0.018; adjusted alpha-level of 0.017, Bonferroni) but not by “empathic concern” or “personal distress”. No significant relationship between IRI subscores and the glutamate levels in the ACC or left hippocampus was detected. Conclusions/Significance This is the first study to investigate the role of the glutamate system for dimensions of theory of mind and empathy. Results are in line with recent concepts that executive top-down control of behavior is mediated by prefrontal glutamatergic projections. This is a preliminary finding that needs a replication in an independent sample. PMID:19060949

  7. Glutamate and GABA in Vestibulo-Sympathetic Pathway Neurons

    PubMed Central

    Holstein, Gay R.; Friedrich, Victor L. Jr.; Martinelli, Giorgio P.

    2016-01-01

    The vestibulo-sympathetic reflex (VSR) actively modulates blood pressure during changes in posture. This reflex allows humans to stand up and quadrupeds to rear or climb without a precipitous decline in cerebral perfusion. The VSR pathway conveys signals from the vestibular end organs to the caudal vestibular nuclei. These cells, in turn, project to pre-sympathetic neurons in the rostral and caudal ventrolateral medulla (RVLM and CVLM, respectively). The present study assessed glutamate- and GABA-related immunofluorescence associated with central vestibular neurons of the VSR pathway in rats. Retrograde FluoroGold tract tracing was used to label vestibular neurons with projections to RVLM or CVLM, and sinusoidal galvanic vestibular stimulation (GVS) was employed to activate these pathways. Central vestibular neurons of the VSR were identified by co-localization of FluoroGold and cFos protein, which accumulates in some vestibular neurons following galvanic stimulation. Triple-label immunofluorescence was used to co-localize glutamate- or GABA- labeling in the identified VSR pathway neurons. Most activated projection neurons displayed intense glutamate immunofluorescence, suggestive of glutamatergic neurotransmission. To support this, anterograde tracer was injected into the caudal vestibular nuclei. Vestibular axons and terminals in RVLM and CVLM co-localized the anterograde tracer and vesicular glutamate transporter-2 signals. Other retrogradely-labeled cFos-positive neurons displayed intense GABA immunofluorescence. VSR pathway neurons of both phenotypes were present in the caudal medial and spinal vestibular nuclei, and projected to both RVLM and CVLM. As a group, however, triple-labeled vestibular cells with intense glutamate immunofluorescence were located more rostrally in the vestibular nuclei than the GABAergic neurons. Only the GABAergic VSR pathway neurons showed a target preference, projecting predominantly to CVLM. These data provide the first

  8. Glutamate and GABA in Vestibulo-Sympathetic Pathway Neurons.

    PubMed

    Holstein, Gay R; Friedrich, Victor L; Martinelli, Giorgio P

    2016-01-01

    The vestibulo-sympathetic reflex (VSR) actively modulates blood pressure during changes in posture. This reflex allows humans to stand up and quadrupeds to rear or climb without a precipitous decline in cerebral perfusion. The VSR pathway conveys signals from the vestibular end organs to the caudal vestibular nuclei. These cells, in turn, project to pre-sympathetic neurons in the rostral and caudal ventrolateral medulla (RVLM and CVLM, respectively). The present study assessed glutamate- and GABA-related immunofluorescence associated with central vestibular neurons of the VSR pathway in rats. Retrograde FluoroGold tract tracing was used to label vestibular neurons with projections to RVLM or CVLM, and sinusoidal galvanic vestibular stimulation (GVS) was employed to activate these pathways. Central vestibular neurons of the VSR were identified by co-localization of FluoroGold and cFos protein, which accumulates in some vestibular neurons following galvanic stimulation. Triple-label immunofluorescence was used to co-localize glutamate- or GABA- labeling in the identified VSR pathway neurons. Most activated projection neurons displayed intense glutamate immunofluorescence, suggestive of glutamatergic neurotransmission. To support this, anterograde tracer was injected into the caudal vestibular nuclei. Vestibular axons and terminals in RVLM and CVLM co-localized the anterograde tracer and vesicular glutamate transporter-2 signals. Other retrogradely-labeled cFos-positive neurons displayed intense GABA immunofluorescence. VSR pathway neurons of both phenotypes were present in the caudal medial and spinal vestibular nuclei, and projected to both RVLM and CVLM. As a group, however, triple-labeled vestibular cells with intense glutamate immunofluorescence were located more rostrally in the vestibular nuclei than the GABAergic neurons. Only the GABAergic VSR pathway neurons showed a target preference, projecting predominantly to CVLM. These data provide the first

  9. Transport-mediated release of endogenous glutamate in the vertebrate retina.

    PubMed

    Maguire, G; Simko, H; Weinreb, R N; Ayoub, G

    1998-08-01

    In the present study we measured calcium-dependent, vesicular glutamate release, and calcium-independent, transport-mediated glutamate release patterns in the vertebrate retina to better understand the sources of elevated glutamate in neural tissue under ischemic conditions. A potassium concentration of 40 mM, which mimics the extracellular potassium concentration in the central nervous system during ischemia, was applied to the bathing medium of a retinal slice prepared from zebrafish. High external potassium evoked release of endogenous glutamate that was measured using a glutamate-specific fluorometric assay applied to the bath. The slice was visualized under 668 nm light using Normarski optics and fluorescent images were captured using a cooled charge-coupled device (CCD) camera. Following the elevation of external potassium to 40 mM several bands of glutamate fluorescence, reflecting the spatial distribution of glutamate release, were observed. A calcium-dependent cloud of glutamate was observed in the inner plexiform layer, that was antagonized by bath-applied nifedipine. A relatively dense glutamate cloud (1-10 microM) was observed over the ganglion cell layer, which was blocked by dihydrokainate, a glutamate transport antagonist. In contrast, nifedipine, an inhibitor of calcium-dependent neurotransmitter release in the retina, failed to block the cloud of released glutamate in the ganglion cell layer. These data suggest that under pathological conditions in the eye where glutamate levels are elevated surrounding retinal ganglion cells, such as observed in some forms of glaucoma, a possible source of the elevated glutamate is through a glutamate transporter operating in a reversed direction. A likely candidate for mediating this reversed transport of glutamate is the retinal Muller cell. PMID:9644233

  10. Laser-scanning astrocyte mapping reveals increased glutamate-responsive domain size and disrupted maturation of glutamate uptake following neonatal cortical freeze-lesion

    PubMed Central

    Armbruster, Moritz; Hampton, David; Yang, Yongjie; Dulla, Chris G.

    2014-01-01

    Astrocytic uptake of glutamate shapes extracellular neurotransmitter dynamics, receptor activation, and synaptogenesis. During development, glutamate transport becomes more robust. How neonatal brain insult affects the functional maturation of glutamate transport remains unanswered. Neonatal brain insult can lead to developmental delays, cognitive losses, and epilepsy; the disruption of glutamate transport is known to cause changes in synaptogenesis, receptor activation, and seizure. Using the neonatal freeze-lesion (FL) model, we have investigated how insult affects the maturation of astrocytic glutamate transport. As lesioning occurs on the day of birth, a time when astrocytes are still functionally immature, this model is ideal for identifying changes in astrocyte maturation following insult. Reactive astrocytosis, astrocyte proliferation, and in vitro hyperexcitability are known to occur in this model. To probe astrocyte glutamate transport with better spatial precision we have developed a novel technique, Laser Scanning Astrocyte Mapping (LSAM), which combines glutamate transport current (TC) recording from astrocytes with laser scanning glutamate photolysis. LSAM allows us to identify the area from which a single astrocyte can transport glutamate and to quantify spatial heterogeneity in the rate of glutamate clearance kinetics within that domain. Using LSAM, we report that cortical astrocytes have an increased glutamate-responsive area following FL and that TCs have faster decay times in distal, as compared to proximal processes. Furthermore, the developmental shift from GLAST- to GLT-1-dominated clearance is disrupted following FL. These findings introduce a novel method to probe astrocyte glutamate uptake and show that neonatal cortical FL disrupts the functional maturation of cortical astrocytes. PMID:25249939

  11. Construction of glutamate biosensor based on covalent immobilization of glutamate oxidase on polypyrrole nanoparticles/polyaniline modified gold electrode.

    PubMed

    Batra, Bhawna; Kumari, Seema; Pundir, Chandra Shekhar

    2014-04-10

    A method is described for construction of a highly sensitive electrochemical biosensor for detection of glutamate. The biosensor is based on covalent immobilization of glutamate oxidase (GluOx) onto polypyrrole nanoparticles and polyaniline composite film (PPyNPs/PANI) electrodeposited onto Au electrode. The enzyme electrode was characterized by cyclic voltammetry (CV), scanning electron microscopy (SEM), X-ray diffraction (XRD), transmission electron microscopy (TEM), Fourier transform infra-red spectroscopy (FTIR) and electrochemical impedance spectroscopy (EIS). The biosensor showed optimum response within 3s at pH 7.5 (0.1 M sodium phosphate) and 35 °C, when operated at 50 mV s⁻¹. It exhibited excellent sensitivity (detection limit as 0.1 nM), fast response time and wider linear range (from 0.02 to 400 μM). Analytical recovery of added glutamate (5 mM and 10 mM) was 95.56 and 97%, while within batch and between batch coefficients of variation were 3.2% and 3.35% respectively. The enzyme electrode was used 100 times over a period of 60 days, when stored at 4 °C. The biosensor measured glutamate level in food stuff, which correlated well with a standard colorimetric method (r=0.99). PMID:24629270

  12. Simultaneous and selective production of levan and poly(gamma-glutamic acid) by Bacillus subtilis.

    PubMed

    Shih, Ing-Lung; Yu, Yun-Ti

    2005-01-01

    Bacillus subtilis(natto) Takahashi, used to prepare the fermented soybean product natto, was grown in a basal medium containing 5% (w/w) sucrose and 1.5% (w/w) L-glutamate and produced 58% (w/w) poly(gamma-glutamic acid) and 42% (w/w) levan simultaneously. After 21 h, 40-50 mg levan ml-1 had been produced in medium containing 20% (w/w) sucrose but without L-glutamate. In medium containing L-glutamic acid but without sucrose, mainly poly(gamma-glutamic acid) was produced. PMID:15703872

  13. Glial and light-dependent glutamate metabolism in the suprachiasmatic nuclei.

    PubMed

    Leone, M J; Beaule, C; Marpegan, L; Simon, T; Herzog, E D; Golombek, D A

    2015-05-01

    The suprachiasmatic nuclei, the main circadian clock in mammals, are entrained by light through glutamate released from retinal cells. Astrocytes are key players in glutamate metabolism but their role in the entrainment process is unknown. We studied the time dependence of glutamate uptake and glutamine synthetase (GS) activity finding diurnal oscillations in glutamate uptake (high levels during the light phase) and daily and circadian fluctuations in GS activity (higher during the light phase and the subjective day). These results show that glutamate-related astroglial processes exhibit diurnal and circadian variations, which could affect photic entrainment of the circadian system. PMID:25798929

  14. Detection of the Messenger RNA Encoding for the Ferredoxin-Dependent Glutamate Synthase in Maize Leaf

    PubMed Central

    Commere, Bernard; Vidal, Jean; Suzuki, Akira; Gadal, Pierre; Caboche, Michel

    1986-01-01

    Ferredoxin-dependent glutamate synthase (EC 1.4.7.1), glutamate oxoglutarate aminotransferase (glutamate synthase) (GOGAT) messenger RNA was extracted from maize (Zea mays L.) leaves and partially purified through oligo(dT)-cellulose chromatography and ultracentrifugation in a sucrose gradient. mRNA were translated in vitro using a reticulocyte system. The glutamate synthase subunit was characterized by immunoprecipitation with antibodies raised against the rice (Oryza sativa L.) ferredoxin-glutamate synthase. The in vitro synthesized protein and the 145 kilodaltons genuine maize leaf subunit of GOGAT were found to comigrate in sodium dodecyl sulfate-polyacrylamide gel electrophoresis experiments. Images Fig. 1 Fig. 2 Fig. 3 PMID:16664732

  15. Electrogenic glutamate uptake is a major current carrier in the membrane of axolotl retinal glial cells

    NASA Astrophysics Data System (ADS)

    Brew, Helen; Attwell, David

    1987-06-01

    Glutamate is taken up avidly by glial cells in the central nervous system1. Glutamate uptake may terminate the transmitter action of glutamate released from neurons1, and keep extracellular glutamate at concentrations below those which are neurotoxic. We report here that glutamate evokes a large inward current in retinal glial cells which have their membrane potential and intracellular ion concentrations controlled by the whole-cell patch-clamp technique2. This current seems to be due to an electrogenic glutamate uptake carrier, which transports at least two sodium ions with every glutamate anion carried into the cell. Glutamate uptake is strongly voltage-dependent, decreasing at depolarized potentials: when fully activated, it contributes almost half of the conductance in the part of the glial cell membrane facing the retinal neurons. The spatial localization, glutamate affinity and magnitude of the uptake are appropriate for terminating the synaptic action of glutamate released from photoreceptors and bipolar cells. These data challenge present explanations of how the b-wave of the electroretinogram is generated, and suggest a mechanism for non-vesicular voltage-dependent release of glutamate from neurons.

  16. Ammonia triggers exocytotic release of L-glutamate from cultured rat astrocytes.

    PubMed

    Görg, Boris; Morwinsky, Anke; Keitel, Verena; Qvartskhava, Natalia; Schrör, Karsten; Häussinger, Dieter

    2010-04-15

    Ammonia toxicity to the brain involves NMDA receptor overactivation and glutamate excitotoxicity. The mechanisms underlying glutamate release from astrocytes in response to ammonia were addressed in this study. In cultured rat astrocytes, glutamate immunoreactivity (IR) was punctate and partly colocalized with transfected VAMP2-YFP. NH(4)Cl (5 mmol/L) and hypoosmotic exposure (205 mosmol/L) induced a rapid colchicine-sensitive loss of cellular glutamate and glutamate appearance in the extracellular space. The NH(4)Cl-induced glutamate loss from astrocytes was strongly blunted after transfection of the cells with VAMP2 siRNA. Ammonia-induced exocytosis of VAMP2-YFP expressing vesicles was shown by total internal reflection fluorescence microscopy (TIRF-M). Glutamate exocytosis in response to ammonia was sensitive to chelation of Ca(2+), cyclooxygenase inhibition by indomethacin and colchicine. Ammonia triggered the rapid formation of prostanoids, which were identified as upstream events in ammonia-induced glutamate exocytosis. Also, addition of prostaglandin E(2) or of tumor necrosis factor (TNF)-alpha triggered glutamate exocytosis. Inhibition of ammonia-induced glutamate exocytosis after transfection of VAMP2 siRNA inhibited ammonia-induced RNA oxidation. It is concluded that ammonia triggers a prostanoid- and Ca(2+)-dependent glutamate exocytosis, which is essential for induction of ammonia-induced RNA oxidation. PMID:20014275

  17. Hypoxia regulates glutamate metabolism and membrane transport in rat PC12 cells.

    PubMed

    Kobayashi, S; Millhorn, D E

    2001-03-01

    We investigated the effect of hypoxia on glutamate metabolism and uptake in rat pheochromocytoma (PC12) cells. Various key enzymes relevant to glutamate production, metabolism and transport were coordinately regulated by hypoxia. PC12 cells express two glutamate-metabolizing enzymes, glutamine synthetase (GS) and glutamate decarboxylase (GAD), as well as the glutamate-producing enzyme, phosphate-activated glutaminase (PAG). Exposure to hypoxia (1% O(2)) for 6 h or longer increased expression of GS mRNA and protein and enhanced GS enzymatic activity. In contrast, hypoxia caused a significant decrease in expression of PAG mRNA and protein, and also decreased PAG activity. In addition, hypoxia led to an increase in GAD65 and GAD67 protein levels and GAD enzymatic activity. PC12 cells express three Na(+)-dependent glutamate transporters; EAAC1, GLT-1 and GLAST. Hypoxia increased EAAC1 and GLT-1 protein levels, but had no effect on GLAST. Chronic hypoxia significantly enhanced the Na(+)-dependent component of glutamate transport. Furthermore, chronic hypoxia decreased cellular content of glutamate, but increased that of glutamine. Taken together, the hypoxia-induced changes in enzymes related to glutamate metabolism and transport are consistent with a decrease in the extracellular concentration of glutamate. This may have a role in protecting PC12 cells from the cytotoxic effects of glutamate during chronic hypoxia. PMID:11259512

  18. Enzyme-Doped Thin Films and Optical Fiber Sensors for Glutamate

    NASA Astrophysics Data System (ADS)

    Rickus, Jenna L.; Tobin, Allan J.; Zink, Jeffrey I.; Dunn, Bruce S.

    2002-10-01

    Biomolecules encapsulated in porous silicate glass using the sol-gel process form optically transparent materials capable of biorecognition. We are working to design biosensors from these materials for the detection of glutamate, the major excitatory neurotransmitter in the central nervous system. Previously we demonstrated the ability of glutamate dehydrogenase (GDH)-doped sol-gel bulk materials to measure glutamate at varying concentrations. Here we show that GDH can be encapsulated in a thin film while retaining its enzymatic activity. The films are likely to be reaction limited rather than diffusion limited, as the reaction rate at saturating glutamate concentrations varies linearly with enzyme loading. At a given enzyme loading, the film reaction rate increases with increasing glutamate concentration, demonstrating its potential as a glutamate sensor material. In addition we have shown that the enzyme-doped sol-gel glass can be deposited onto the tip of an optical fiber. The fiber is active and responds to the presence of glutamate.

  19. Glutamate release from satellite glial cells of the murine trigeminal ganglion.

    PubMed

    Wagner, Lysann; Warwick, Rebekah A; Pannicke, Thomas; Reichenbach, Andreas; Grosche, Antje; Hanani, Menachem

    2014-08-22

    It has been proposed that glutamate serves as a mediator between neurons and satellite glial cells (SGCs) in sensory ganglia and that SGCs release glutamate. Using a novel method, we studied glutamate release from SGCs from murine trigeminal ganglia. Sensory neurons with adhering SGCs were enzymatically isolated from wild type and transgenic mice in which vesicular exocytosis was suppressed in glial cells. Extracellular glutamate was detected by microfluorimetry. After loading the cells with a photolabile Ca(2+) chelator, the intracellular Ca(2+) concentration was raised in SGCs by a UV pulse, which resulted in glutamate release. The amount of released glutamate was decreased in cells with suppressed exocytosis and after pharmacological block of hemichannels. The data demonstrate that SGCs of the trigeminal ganglion release glutamate in a Ca(2+)-dependent manner. PMID:24993296

  20. Effect of insulin on the compartmentation of glutamate for protein synthesis

    SciTech Connect

    Brown, A.B.; Mohan, C.; Bessman, S.P.

    1986-03-05

    The effect of insulin on the formation of CO/sub 2/ and incorporation of 1-/sup 14/C glutamine and U-/sup 14/C acetate into protein was studied in isolated rat hepatocytes. Insulin caused an 18% increase in /sup 14/CO/sub 2/ production from U-/sup 14/C acetate in comparison to a 10% increase from 1-/sup 14/C glutamate. Insulin caused a greater increase in the incorporation of tracer acetate carbons into hepatocyte protein. Hydrolysis of labeled protein and subsequent determination of glutamate specific activity revealed that incorporation of acetate carbons into protein as glutamate was about 52% greater in the presence of insulin. These results demonstrate the existence of two compartments of glutamate for protein synthesis: (i) glutamate generated in the Krebs cycle through transamination of a-ketoglutarate; (ii) cytosolic glutamate. Insulin had a greater stimulatory effect on the incorporation of glutamate generated in the Krebs cycle.

  1. Vitamin C neuroprotection against dose-dependent glutamate-induced neurodegeneration in the postnatal brain.

    PubMed

    Shah, Shahid Ali; Yoon, Gwang Ho; Kim, Hyun-Ok; Kim, Myeong Ok

    2015-05-01

    Glutamate-induced excitotoxicity due to over-activation of glutamate receptors and associated energy depletion (phosphorylation and activation of AMPK) results in neuronal cell death in various neurological disorders. Restoration of energy balance during an excitotoxic insult is critical for neuronal survival. Ascorbic acid (vitamin C), an essential nutrient with well-known antioxidant potential, protects the brain from oxidative damage in various models of neurodegeneration. In this study, we reported the therapeutic efficacy of vitamin C in response to glutamate-induced excitation, resulting in energy depletion and apoptosis in the hippocampus of the developing rat brain. A single subcutaneous injection of glutamate at two different concentrations (5 and 10 mg/kg) in postnatal day 7 rat pups increased brain glutamate levels and increased the protein expression of neuronal apoptotic markers. Both doses of glutamate upregulated the ratio of pro-apoptotic Bax to anti-apoptotic Bcl-2, cytochrome-c release, caspase-3 activation and the expression of PARP-1. However, co-treatment of vitamin C (250 mg/kg) with glutamate decreased brain glutamate levels and reversed the changes induced by glutamate in the developing hippocampus. Interestingly, only a high dose of glutamate caused the phosphorylation and activation of AMPK and induced neuronal cell death, whereas a low dose of glutamate failed to mediate these effects. Vitamin C supplementation reduced the glutamate-induced phosphorylation of AMPK and attenuated neuronal cell death, as assessed morphologically by Fluoro Jade B in the hippocampal CA1 region of the developing brain. Taken together, our results indicated that glutamate in both concentrations is toxic to the immature rat brain, whereas vitamin C is pharmacologically effective against glutamate-induced neurodegeneration. PMID:25701025

  2. Sodium-Dependent Glutamate Uptake by an Alkaliphilic, Thermophilic Bacillus Strain, TA2.A1

    PubMed Central

    Peddie, Catherine J.; Cook, Gregory M.; Morgan, Hugh W.

    1999-01-01

    A strain of Bacillus designated TA2.A1, isolated from a thermal spring in Te Aroha, New Zealand, grew optimally at pH 9.2 and 70°C. Bacillus strain TA2.A1 utilized glutamate as a sole carbon and energy source for growth, and sodium chloride (>5 mM) was an obligate requirement for growth. Growth on glutamate was inhibited by monensin and amiloride, both inhibitors that collapse the sodium gradient (ΔpNa) across the cell membrane. N,N-Dicyclohexylcarbodiimide inhibited the growth of Bacillus strain TA2.A1, suggesting that an F1F0-ATPase (H type) was being used to generate cellular ATP needed for anabolic reactions. Vanadate, an inhibitor of V-type ATPases, did not affect the growth of Bacillus strain TA2.A1. Glutamate transport by Bacillus strain TA2.A1 could be driven by an artificial membrane potential (ΔΨ), but only when sodium was present. In the absence of sodium, the rate of ΔΨ-driven glutamate uptake was fourfold lower. No glutamate transport was observed in the presence of ΔpNa alone (i.e., no ΔΨ). Glutamate uptake was specifically inhibited by monensin, and the Km for sodium was 5.6 mM. The Hill plot had a slope of approximately 1, suggesting that sodium binding was noncooperative and that the glutamate transporter had a single binding site for sodium. Glutamate transport was not affected by the protonophore carbonyl cyanide m-chlorophenylhydrazone, suggesting that the transmembrane pH gradient was not required for glutamate transport. The rate of glutamate transport increased with increasing glutamate concentration; the Km for glutamate was 2.90 μM, and the Vmax was 0.7 nmol · min−1 mg of protein. Glutamate transport was specifically inhibited by glutamate analogues. PMID:10322019

  3. 1,25-Dihydroxyvitamin D induces the glutamate transporter SLC1A1 and alters glutamate handling in non-transformed mammary cells.

    PubMed

    Beaudin, Sarah; Welsh, JoEllen

    2016-03-15

    Genomic profiling of immortalized human mammary epithelial (hTERT-HME1) cells identified several metabolic genes, including the membrane glutamate transporter, SLC1A1, as 1,25-dihydroxyvitamin D3 (1,25D) regulated. In these studies we have surveyed the effects of 1,25D on known glutamate transporters and evaluated its impact on cellular glutamate handling. We confirm that expression of SLC1A1 and all of its known transcript variants are significantly upregulated in hTERT-HME1 cells following 1,25D treatment. Expression of the full-length cognate protein, EAAT3, is correspondingly increased in 1,25D treated hTERT-HME1 cells. Under the same conditions, the expression of two other glutamate transporters--SLC1A6 (EAAT4) and SLC1A2 (EAAT2 or GLT-1)--is enhanced by 1,25D while that of SLC1A3 (EAAT1 or GLAST) and SLC7A11 (xCT) is decreased. Glutamate is not essential for growth of hTERT-HME1 cells, and supplemental glutamate (up to 0.5 mM) does not abrogate the growth inhibitory effects of 1,25D. These data suggest that extracellular glutamate is not a major contributor to cellular energy metabolism in hTERT-HME1 cells under basal conditions and that the growth inhibitory effects of 1,25D are not secondary to its effects on glutamate handling. Instead, the effects of 1,25D on glutamate transporters translated to a decrease in cellular glutamate concentration and an increase in media glutamate concentration, suggesting that one or more of these transporters functions to export glutamate in response to 1,25D exposure. The reduced cellular glutamate concentration may also reflect its incorporation into the cellular glutathione (GSH) pool, which is increased upon 1,25D treatment. In support of this concept, the expression of GCLC (which codes for the rate-limiting enzyme in GSH synthesis) and genes which generate reducing equivalents in the form of NADPH (ie, G6PD, PGD, IDH2) are elevated in 1,25D-treated cells. Taken together, these data identify 1,25D as a physiological

  4. High-Throughput Assay Development for Cystine-Glutamate Antiporter (xc-) Highlights Faster Cystine Uptake than Glutamate Release in Glioma Cells

    PubMed Central

    Thomas, Ajit G.; Sattler, Rita; Tendyke, Karen; Loiacono, Kara A.; Hansen, Hans; Sahni, Vishal; Hashizume, Yutaka; Rojas, Camilo; Slusher, Barbara S.

    2015-01-01

    The cystine-glutamate antiporter (system xc-) is a Na+-independent amino acid transporter that exchanges extracellular cystine for intracellular glutamate. It is thought to play a critical role in cellular redox processes through regulation of intracellular glutathione synthesis via cystine uptake. In gliomas, system xc- expression is universally up-regulated while that of glutamate transporters down-regulated, leading to a progressive accumulation of extracellular glutamate and excitotoxic cell death of the surrounding non-tumorous tissue. Additionally, up-regulation of system xc- in activated microglia has been implicated in the pathogenesis of several neurodegenerative disorders mediated by excess glutamate. Consequently, system xc- is a new drug target for brain cancer and neuroinflammatory diseases associated with excess extracellular glutamate. Unfortunately no potent and selective small molecule system xc- inhibitors exist and to our knowledge, no high throughput screening (HTS) assay has been developed to identify new scaffolds for inhibitor design. To develop such an assay, various neuronal and non-neuronal human cells were evaluated as sources of system xc-. Human glioma cells were chosen based on their high system xc- activity. Using these cells, [14C]-cystine uptake and cystine-induced glutamate release assays were characterized and optimized with respect to cystine and protein concentrations and time of incubation. A pilot screen of the LOPAC/NINDS libraries using glutamate release demonstrated that the logistics of the assay were in place but unfortunately, did not yield meaningful pharmacophores. A larger, HTS campaign using the 384-well cystine-induced glutamate release as primary assay and the 96-well 14C-cystine uptake as confirmatory assay is currently underway. Unexpectedly, we observed that the rate of cystine uptake was significantly faster than the rate of glutamate release in human glioma cells. This was in contrast to the same rates of

  5. Leptin regulates glutamate and glucose transporters in hypothalamic astrocytes

    PubMed Central

    Fuente-Martín, Esther; García-Cáceres, Cristina; Granado, Miriam; de Ceballos, María L.; Sánchez-Garrido, Miguel Ángel; Sarman, Beatrix; Liu, Zhong-Wu; Dietrich, Marcelo O.; Tena-Sempere, Manuel; Argente-Arizón, Pilar; Díaz, Francisca; Argente, Jesús; Horvath, Tamas L.; Chowen, Julie A.

    2012-01-01

    Glial cells perform critical functions that alter the metabolism and activity of neurons, and there is increasing interest in their role in appetite and energy balance. Leptin, a key regulator of appetite and metabolism, has previously been reported to influence glial structural proteins and morphology. Here, we demonstrate that metabolic status and leptin also modify astrocyte-specific glutamate and glucose transporters, indicating that metabolic signals influence synaptic efficacy and glucose uptake and, ultimately, neuronal function. We found that basal and glucose-stimulated electrical activity of hypothalamic proopiomelanocortin (POMC) neurons in mice were altered in the offspring of mothers fed a high-fat diet. In adulthood, increased body weight and fasting also altered the expression of glucose and glutamate transporters. These results demonstrate that whole-organism metabolism alters hypothalamic glial cell activity and suggest that these cells play an important role in the pathology of obesity. PMID:23064363

  6. Functional Insights from Glutamate Receptor Ion Channel Structures

    PubMed Central

    Kumar, Janesh; Mayer, Mark L.

    2014-01-01

    X-ray crystal structures for the soluble amino terminal and ligand binding domains of glutamate receptor ion channels, combined with a 3.6 Å resolution structure of the full length AMPA receptor GluA2 homotetramer, provide unique insights into the mechanisms of iGluR assembly and function. Increasingly sophisticated biochemical, computational and electrophysiological experiments are beginning to reveal the mechanism of action of partial agonists, and yield new models for the mechanism of action of allosteric modulators. Newly identified NMDA receptor ligands acting at novel sites offer hope for development of subtype selective modulators. Many issues remain unsolved, including the role of the ATD in AMPA receptor signaling, and the mechanisms by which auxiliary proteins regulate receptor activity. The structural basis for ion permeation and ion channel block also remain areas of uncertainty, and despite substantial progress, molecular dynamics simulations have yet to reveal how binding of glutamate opens the ion channel pore. PMID:22974439

  7. Synthesis of biobased succinonitrile from glutamic acid and glutamine.

    PubMed

    Lammens, Tijs M; Le Nôtre, Jérôme; Franssen, Maurice C R; Scott, Elinor L; Sanders, Johan P M

    2011-06-20

    Succinonitrile is the precursor of 1,4-diaminobutane, which is used for the industrial production of polyamides. This paper describes the synthesis of biobased succinonitrile from glutamic acid and glutamine, amino acids that are abundantly present in many plant proteins. Synthesis of the intermediate 3-cyanopropanoic amide was achieved from glutamic acid 5-methyl ester in an 86 mol% yield and from glutamine in a 56 mol % yield. 3-Cyanopropanoic acid can be converted into succinonitrile, with a selectivity close to 100% and a 62% conversion, by making use of a palladium(II)-catalyzed equilibrium reaction with acetonitrile. Thus, a new route to produce biobased 1,4-diaminobutane has been discovered. PMID:21557494

  8. [Cardioprotective properties of new glutamic acid derivative under stress conditions].

    PubMed

    Perfilova, V N; Sadikova, N V; Berestovitskaia, V M; Vasil'eva, O S

    2014-01-01

    The effect of new glutamic acid derivative on the cardiac ino- and chronotropic functions has been studied in experiments on rats exposed to 24-hour immobilization-and-pain stress. It is established that glutamic acid derivative RGPU-238 (glufimet) at a dose of 28.7 mg/kg increases the increment of myocardial contractility and relaxation rates and left ventricular pressure in stress-tested animals by 13 1,1, 72.4, and 118.6%, respectively, as compared to the control group during the test for adrenoreactivity. Compound RGPU-238 increases the increment of the maximum intensity of myocardium functioning by 196.5 % at 30 sec of isometric workload as compared to the control group. The cardioprotective effect of compound RGPU-238 is 1.5 - 2 times higher than that of the reference drug phenibut. PMID:25365864

  9. The Role of Metabotropic Glutamate Receptor Genes in Schizophrenia.

    PubMed

    Maj, Carlo; Minelli, Alessandra; Giacopuzzi, Edoardo; Sacchetti, Emilio; Gennarelli, Massimo

    2016-01-01

    Genomic studies revealed two main components in the genetic architecture of schizophrenia, one constituted by common variants determining a distributed polygenic effect and one represented by a large number of heterogeneous rare and highly disruptive mutations. These gene modifications often affect neural transmission and different studies proved an involvement of metabotropic glutamate receptors in schizophrenia phenotype. Through the combination of literature information with genomic data from public repositories, we analyzed the current knowledge on the involvement of genetic variations of the human metabotropic glutamate receptors in schizophrenia and related endophenotypes. Despite the analysis did not reveal a definitive connection, different suggestive associations have been identified and in particular a relevant role has emerged for GRM3 in affecting specific schizophrenia endophenotypes. This supports the hypothesis that these receptors are directly involved in schizophrenia disorder. PMID:27296644

  10. Glutamate modulators in the treatment of obsessive-compulsive disorder

    PubMed Central

    Pittenger, Christopher

    2015-01-01

    Established treatments for obsessive-compulsive disorder (OCD) are of benefit in approximately 3 of every 4 patients, but refractory disease remains distressingly common, and many treatment responders continue to experience considerable morbidity. This motivates a search for new insights into pathophysiology that may inform novel treatment strategies. Much recent work has focused on the neurotransmitter glutamate. Several lines of neurochemical and genetic evidence suggests that glutamate dysregulation may contribute to OCD, although much remains unclear. The off-label use of a number of pharmacological agents approved for other indications has been investigated in refractory OCD. We summarize investigations of memantine, riluzole, ketamine, D-cycloserine, glycine, N-acetylserine, topiramate, and lamotrigine. Evidence exists for benefit from each of these in some patients; though none has been proven effective with sufficient clarity to be considered part of standard care, these agents are options in individuals whose symptoms are refractory to better-established therapeutic strategies. PMID:26236057

  11. Dorsal Raphe Neurons Signal Reward through 5-HT and Glutamate

    PubMed Central

    Liu, Zhixiang; Zhou, Jingfeng; Li, Yi; Hu, Fei; Lu, Yao; Ma, Ming; Feng, Qiru; Zhang, Ju-en; Wang, Daqing; Zeng, Jiawei; Bao, Junhong; Kim, Ji-Young; Chen, Zhou-Feng; Mestikawy, Salah El; Luo, Minmin

    2015-01-01

    Summary The dorsal raphe nucleus (DRN) in the midbrain is a key center for serotonin (5-hydroxytryptamine; 5-HT) expressing neurons. Serotonergic neurons in the DRN have been theorized to encode punishment by opposing the reward signaling of dopamine neurons. Here, we show that DRN neurons encode reward, but not punishment, through 5-HT and glutamate. Optogenetic stimulation of DRN Pet-1 neurons reinforces mice to explore the stimulation-coupled spatial region, shifts sucrose preference, drives optical self-stimulation, and directs sensory discrimination learning. DRN Pet-1 neurons increase their firing activity during reward tasks and this activation can be used to rapidly change neuronal activity patterns in the cortnassociated with 5-HT, they also release glutamate, and both neurotransmitters contribute to reward signaling. These experiments demonstrate the ability of DRN neurons to organize reward behaviors and might provide insights into the underlying mechanisms of learning facilitation and anhedonia treatment. PMID:24656254

  12. Relevance of exocytotic glutamate release from retinal glia.

    PubMed

    Slezak, Michal; Grosche, Antje; Niemiec, Aurore; Tanimoto, Naoyuki; Pannicke, Thomas; Münch, Thomas A; Crocker, Britni; Isope, Philippe; Härtig, Wolfgang; Beck, Susanne C; Huber, Gesine; Ferracci, Geraldine; Perraut, Martine; Reber, Michael; Miehe, Monique; Demais, Valérie; Lévêque, Christian; Metzger, Daniel; Szklarczyk, Klaudia; Przewlocki, Ryszard; Seeliger, Mathias W; Sage-Ciocca, Dominique; Hirrlinger, Johannes; Reichenbach, Andreas; Reibel, Sophie; Pfrieger, Frank W

    2012-05-10

    Glial cells release molecules that influence brain development, function, and disease. Calcium-dependent exocytosis has been proposed as potential release mechanism in astroglia, but the physiological relevance of "gliotransmission" in vivo remains controversial. We focused on the impact of glial exocytosis on sensory transduction in the retina. To this end, we generated transgenic mice to block exocytosis by Cre recombinase-dependent expression of the clostridial botulinum neurotoxin serotype B light chain, which cleaves vesicle-associated membrane protein 1-3. Ubiquitous and neuronal toxin expression caused perinatal lethality and a reduction of synaptic transmission thus validating transgene function. Toxin expression in Müller cells inhibited vesicular glutamate release and impaired glial volume regulation but left retinal histology and visual processing unaffected. Our model to study gliotransmission in vivo reveals specific functions of exocytotic glutamate release in retinal glia. PMID:22578502

  13. Role of astrocytic glutamate transporter in alcohol use disorder

    PubMed Central

    Ayers-Ringler, Jennifer R; Jia, Yun-Fang; Qiu, Yan-Yan; Choi, Doo-Sup

    2016-01-01

    Alcohol use disorder (AUD) is one of the most widespread neuropsychiatric conditions, having a significant health and socioeconomic impact. According to the 2014 World Health Organization global status report on alcohol and health, the harmful use of alcohol is responsible for 5.9% of all deaths worldwide. Additionally, 5.1% of the global burden of disease and injury is ascribed to alcohol (measured in disability adjusted life years, or disability adjusted life years). Although the neurobiological basis of AUD is highly complex, the corticostriatal circuit contributes significantly to the development of addictive behaviors. In-depth investigation into the changes of the neurotransmitters in this circuit, dopamine, gamma-aminobutyricacid, and glutamate, and their corresponding neuronal receptors in AUD and other addictions enable us to understand the molecular basis of AUD. However, these discoveries have also revealed a dearth of knowledge regarding contributions from non-neuronal sources. Astrocytes, though intimately involved in synaptic function, had until recently been noticeably overlooked in their potential role in AUD. One major function of the astrocyte is protecting neurons from excitotoxicity by removing glutamate from the synapse via excitatory amino acid transporter type 2. The importance of this key transporter in addiction, as well as ethanol withdrawal, has recently become evident, though its regulation is still under investigation. Historically, pharmacotherapy for AUD has been focused on altering the activity of neuronal glutamate receptors. However, recent clinical evidence has supported the animal-based findings, showing that regulating glutamate homeostasis contributes to successful management of recovery from AUD. PMID:27014596

  14. Role of astrocytic glutamate transporter in alcohol use disorder.

    PubMed

    Ayers-Ringler, Jennifer R; Jia, Yun-Fang; Qiu, Yan-Yan; Choi, Doo-Sup

    2016-03-22

    Alcohol use disorder (AUD) is one of the most widespread neuropsychiatric conditions, having a significant health and socioeconomic impact. According to the 2014 World Health Organization global status report on alcohol and health, the harmful use of alcohol is responsible for 5.9% of all deaths worldwide. Additionally, 5.1% of the global burden of disease and injury is ascribed to alcohol (measured in disability adjusted life years, or disability adjusted life years). Although the neurobiological basis of AUD is highly complex, the corticostriatal circuit contributes significantly to the development of addictive behaviors. In-depth investigation into the changes of the neurotransmitters in this circuit, dopamine, gamma-aminobutyricacid, and glutamate, and their corresponding neuronal receptors in AUD and other addictions enable us to understand the molecular basis of AUD. However, these discoveries have also revealed a dearth of knowledge regarding contributions from non-neuronal sources. Astrocytes, though intimately involved in synaptic function, had until recently been noticeably overlooked in their potential role in AUD. One major function of the astrocyte is protecting neurons from excitotoxicity by removing glutamate from the synapse via excitatory amino acid transporter type 2. The importance of this key transporter in addiction, as well as ethanol withdrawal, has recently become evident, though its regulation is still under investigation. Historically, pharmacotherapy for AUD has been focused on altering the activity of neuronal glutamate receptors. However, recent clinical evidence has supported the animal-based findings, showing that regulating glutamate homeostasis contributes to successful management of recovery from AUD. PMID:27014596

  15. Metabotropic glutamate receptor regulation of neuronal cell death.

    PubMed

    Spillson, Alison Berent; Russell, James W

    2003-11-01

    The metabotropic glutamate receptors (mGluRs) are a family of glutamate-sensitive receptors that regulate neuronal function separately from the ionotropic glutamate receptors. By coupling to guanosine nucleotide-binding proteins (G proteins), mGluRs are able to regulate neuronal injury and survival, likely through a series of downstream protein kinase and cysteine protease signaling pathways that affect mitochondrial regulated programmed cell death (PCD). The physiological relevance of this system is supported by evidence that mGluRs are associated with cell survival in several central nervous system neurodegenerative diseases. Evidence is presented that mGluRs are also able to prevent PCD in the peripheral nervous system, and that this may provide a novel mechanism for treatment of diabetic neuropathy. In dorsal root ganglion (DRG) neurons, a high glucose load increases generation of reactive oxygen species (ROS), destabilizes the inner mitochondrial membrane potential (Deltapsi(M)), induces cytochrome c release from the mitochondrial intermembrane space, and induces downstream activation of caspases. In high-glucose conditions, the group II metabotropic glutamate agonist N-acetylaspartylglutamate (NAAG) blocks caspase activation and is completely reversed by the mGluR3 antagonist (S)-alpha-ethylglutamic acid (EGLU). Furthermore, the direct mGluR3 agonist (2R,4R)-4-aminopyrrolidine-2, 4-dicarboxylate (APDC) prevents induction of ROS. Together these findings are consistent with an emerging concept that mGluRs may protect against cellular injury by regulating oxidative stress in the neuron. More complete understanding of the complex PCD regulatory pathways mediated by mGluRs will provide new therapeutic approaches for the treatment of a wide variety of neurodegenerative diseases. PMID:14597332

  16. Expression of glutamate carboxypeptidase II in human brain.

    PubMed

    Sácha, P; Zámecník, J; Barinka, C; Hlouchová, K; Vícha, A; Mlcochová, P; Hilgert, I; Eckschlager, T; Konvalinka, J

    2007-02-23

    Glutamate carboxypeptidase II (GCPII) is a transmembrane glycoprotein expressed in various tissues. When expressed in the brain it cleaves the neurotransmitter N-acetylaspartylglutamate (NAAG), yielding free glutamate. In jejunum it hydrolyzes folylpoly-gamma-glutamate, thus facilitating folate absorption. The prostate form of GCPII, known as prostate specific membrane antigen (PSMA), is an established cancer marker. The NAAG-hydrolyzing activity of GCPII has been implicated in a number of pathological conditions in which glutamate is neurotoxic (e.g. amyotrophic lateral sclerosis, Huntington's disease, Alzheimer's disease, epilepsy, schizophrenia, and stroke). Inhibition of GCPII was shown to be neuroprotective in tissue culture and in animal models. GCPII is therefore an interesting putative therapeutic target. However, only very limited and controversial data on the expression and localization of GCPII in human brain are available. Therefore, we set out to analyze the activity and expression of GCPII in various compartments of the human brain using a radiolabeled substrate of the enzyme and the novel monoclonal antibody GCP-04, which recognizes an epitope on the extracellular portion of the enzyme and is more sensitive to GCPII than to the homologous GCPIII. We show that this antibody is more sensitive in immunoblots than the widely used antibody 7E11. By Western blot, we show that there are approximately 50-300 ng of GCPII/mg of total protein in human brain, depending on the specific area. Immunohistochemical analysis revealed that astrocytes specifically express GCPII in all parts of the brain. GCPII is enzymatically active and the level of activity follows the expression pattern. Using pure recombinant GCPII and homologous GCPIII, we conclude that GCPII is responsible for the majority of overall NAAG-hydrolyzing activity in the human brain. PMID:17150306

  17. Beyond Dopamine: Glutamate as a Target for Future Antipsychotics

    PubMed Central

    Sendt, Kyra-Verena; Giaroli, Giovanni; Tracy, Derek K.

    2012-01-01

    The dopamine hypothesis of schizophrenia remains the primary theoretical framework for the pharmacological treatment of the disorder. Despite various lines of evidence of dopaminergic abnormalities and reasonable efficacy of current antipsychotic medication, a significant proportion of patients show suboptimal treatment responses, poor tolerability, and a subsequent lack of treatment concordance. In recent decades, intriguing evidence for the critical involvement of other neurotransmitter systems in the pathophysiology of schizophrenia has emerged, most notably of dysfunctions within the glutamate pathways. Consequently, the glutamate synapse has arisen as a promising target for urgently needed novel antipsychotic compounds—particularly in regards to debilitating negative and cognitive symptoms poorly controlled by currently available drugs. In this paper, recent findings integrating glutamatergic and dopaminergic abnormalities in schizophrenia and their implications for novel pharmacological targets are discussed. An overview of compounds in various stages of development is given: drugs enhancing NMDA receptor function as well as metabotropic glutamate receptor (mGluR) agonist and positive allosteric modulators (PAMs) are emphasised. Together with other agents more indirectly affecting glutamatergic neurotransmission, their potential future role in the pharmacotherapy of schizophrenia is critically evaluated. PMID:22830044

  18. Glutamate Receptor Homologs in Plants: Functions and Evolutionary Origins

    PubMed Central

    Price, Michelle Beth; Jelesko, John; Okumoto, Sakiko

    2012-01-01

    The plant glutamate-like receptor homologs (GLRs) are homologs of mammalian ionotropic glutamate receptors (iGluRs) which were discovered more than 10 years ago, and are hypothesized to be potential amino acid sensors in plants. Although initial progress on this gene family has been hampered by gene redundancy and technical issues such as gene toxicity; genetic, pharmacological, and electrophysiological approaches are starting to uncover the functions of this protein family. In parallel, there has been tremendous progress in elucidating the structure of animal glutamate receptors (iGluRs), which in turn will help understanding of the molecular mechanisms of plant GLR functions. In this review, we will summarize recent progress on the plant GLRs. Emerging evidence implicates plant GLRs in various biological processes in and beyond N sensing, and implies that there is some overlap in the signaling mechanisms of amino acids between plants and animals. Phylogenetic analysis using iGluRs from metazoans, plants, and bacteria showed that the plant GLRs are no more closely related to metazoan iGluRs as they are to bacterial iGluRs, indicating the separation of plant, other eukaryotic, and bacterial GLRs might have happened as early on as the last universal common ancestor. Structural similarities and differences with animal iGluRs, and the implication thereof, are also discussed. PMID:23115559

  19. Dysfunction of Glutamate Receptors in Microglia May Cause Neurodegeneration.

    PubMed

    Noda, Mami

    2016-01-01

    Dysregulation of glutamate signalling is important in Alzheimer's disease and other pathologies. There has been a focus on changes in neuronal glutamate signalling, but microglia also express glutamate receptors (GluRs), which are known to modulate their responses to neuropathology. Microglia express both metabotropic and ionotropic GluRs. Among ionotropic GluRs, microglial AMPA (α-amino-hydroxy-5-methyl-isoxazole-4-propionate)-type of GluRs (AMPA-Rs) are Ca2+ impermeable due to the expression of subunit GluA2. Upon activation of microglia, expression level of surface GluA2 subunits significantly increase, while expression of GluA1, A3 and A4 subunits on membrane surface significantly decrease. Owing to the GluA2 subunits-dominant composition, AMPA-Rs in activated microglia show little response to Glu. On the other hand, microglia lacking GluA2 show higher Ca(2+)-permeability, consequently inducing a significant increase in the release of the pro-inflammatory cytokine, such as TNF-α. It is suggested that membrane translocation of GluA2-containing AMPA-Rs in activated microglia has functional importance. Thus, dysfunction or decreased expression of GluA2 reported in patients with neurodegenerative diseases such as Alzheimer's and Creutzfeldt-Jakob disease may accelerate Glu neurotoxicity via excess release of proinflammatory cytokines from microglia, causing more neuronal death. PMID:26567741

  20. [PECULIARITIES OF THE CEREBROVASCULAR EFFECTS OF GLUTAMIC ACID].

    PubMed

    Gan'shina, T S; Kurza, E V; Kurdyumov, I N; Maslennikov, D V; Mirzoyan, R S

    2016-01-01

    Experiments on nonlinear rats subjected to global transient cerebral ischemia revealed the ability of glutamic acid to improve cerebral circulation. Consequently, the excitatory amino acid can produce adverse (neurotoxic) and positive (anti-ischemic) effects in cerebral ischemia. The cerebrovascular effect of glutamic acid in cerebral ischemia is attenuated on the background action of the MNDA receptor blocker MK-801 (0.5 mg/kg intravenously) and eliminated by bicuculline. When glutamic acid is combined with the non-competitive MNDA receptor antagonist MK-801, neither one nor another drug shows its vasodilator effect. The results are indicative of the interaction between excitatory and inhibitory systems on the level of cerebral vessels and once again confirm our previous conclusion about the decisive role of GABA(A) receptors in brain vessels in the implementation of anti-ischemic activity of endogenous compounds (melatonin) and well-known pharmacological substances (mexidol, afobazole), and new chemical compounds based on GABA-containing lipid derivatives. PMID:27455572

  1. Targeting glutamate uptake to treat alcohol use disorders

    PubMed Central

    Rao, P.S.S.; Bell, Richard L.; Engleman, Eric A.; Sari, Youssef

    2015-01-01

    Alcoholism is a serious public health concern that is characterized by the development of tolerance to alcohol's effects, increased consumption, loss of control over drinking and the development of physical dependence. This cycle is often times punctuated by periods of abstinence, craving and relapse. The development of tolerance and the expression of withdrawal effects, which manifest as dependence, have been to a great extent attributed to neuroadaptations within the mesocorticolimbic and extended amygdala systems. Alcohol affects various neurotransmitter systems in the brain including the adrenergic, cholinergic, dopaminergic, GABAergic, glutamatergic, peptidergic, and serotonergic systems. Due to the myriad of neurotransmitter and neuromodulator systems affected by alcohol, the efficacies of current pharmacotherapies targeting alcohol dependence are limited. Importantly, research findings of changes in glutamatergic neurotransmission induced by alcohol self- or experimenter-administration have resulted in a focus on therapies targeting glutamatergic receptors and normalization of glutamatergic neurotransmission. Glutamatergic receptors implicated in the effects of ethanol include the ionotropic glutamate receptors (AMPA, Kainate, and NMDA) and some metabotropic glutamate receptors. Regarding glutamatergic homeostasis, ceftriaxone, MS-153, and GPI-1046, which upregulate glutamate transporter 1 (GLT1) expression in mesocorticolimbic brain regions, reduce alcohol intake in genetic animal models of alcoholism. Given the hyperglutamatergic/hyperexcitable state of the central nervous system induced by chronic alcohol abuse and withdrawal, the evidence thus far indicates that a restoration of glutamatergic concentrations and activity within the mesocorticolimbic system and extended amygdala as well as multiple memory systems holds great promise for the treatment of alcohol dependence. PMID:25954150

  2. Crystal structure of a chimaeric bacterial glutamate dehydrogenase.

    PubMed

    Oliveira, Tânia; Sharkey, Michael A; Engel, Paul C; Khan, Amir R

    2016-06-01

    Glutamate dehydrogenases (EC 1.4.1.2-4) catalyse the oxidative deamination of L-glutamate to α-ketoglutarate using NAD(P)(+) as a cofactor. The bacterial enzymes are hexameric, arranged with 32 symmetry, and each polypeptide consists of an N-terminal substrate-binding segment (domain I) followed by a C-terminal cofactor-binding segment (domain II). The catalytic reaction takes place in the cleft formed at the junction of the two domains. Distinct signature sequences in the nucleotide-binding domain have been linked to the binding of NAD(+) versus NADP(+), but they are not unambiguous predictors of cofactor preference. In the absence of substrate, the two domains move apart as rigid bodies, as shown by the apo structure of glutamate dehydrogenase from Clostridium symbiosum. Here, the crystal structure of a chimaeric clostridial/Escherichia coli enzyme has been determined in the apo state. The enzyme is fully functional and reveals possible determinants of interdomain flexibility at a hinge region following the pivot helix. The enzyme retains the preference for NADP(+) cofactor from the parent E. coli domain II, although there are subtle differences in catalytic activity. PMID:27303899

  3. Isocitrate Dehydrogenase and Glutamate Synthesis in Acetobacter suboxydans1

    PubMed Central

    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

  4. Group III metabotropic glutamate receptors and drug addiction

    PubMed Central

    Mao, Limin; Guo, Minglei; Jin, Daozhong; Xue, Bing; Wang, John Q.

    2014-01-01

    Neuroadaptations of glutamatergic transmission in the limbic reward circuitry are linked to persistent drug addiction. Accumulating data have demonstrated roles of ionotropic glutamate receptors and group I and II metabotropic glutamate receptors (mGluRs) in this event. Emerging evidence also identifies Gαi/o-coupled group III mGluRs (mGluR4/7/8 subtypes enriched in the limbic system) as direct substrates of drugs of abuse and active regulators of drug action. Auto- and heteroreceptors of mGluR4/7/8 reside predominantly on nerve terminals of glutamatergic corticostriatal and GABAergic striatopallidal pathways, respectively. These presynaptic receptors regulate basal and/or phasic release of respective transmitters to maintain basal ganglia homeostasis. In response to operant administration of common addictive drugs, such as psychostimulants (cocaine and amphetamine), alcohol and opiates, limbic group III mGluRs undergo drastic adaptations to contribute to the enduring remodeling of excitatory synapses and to usually suppress drug seeking behavior. As a result, a loss-of-function mutation (knockout) of individual group III receptor subtypes often promotes drug seeking. This review summarizes the data from recent studies on three group III receptor subtypes (mGluR4/7/8) expressed in the basal ganglia and analyzes their roles in the regulation of dopamine and glutamate signaling in the striatum and their participation in the addictive properties of three major classes of drugs (psychostimulants, alcohol, and opiates). PMID:24078068

  5. Group III metabotropic glutamate receptors and drug addiction.

    PubMed

    Mao, Limin; Guo, Minglei; Jin, Daozhong; Xue, Bing; Wang, John Q

    2013-12-01

    Neuroadaptations of glutamatergic transmission in the limbic reward circuitry are linked to persistent drug addiction. Accumulating data have demonstrated roles of ionotropic glutamate receptors and group I and II metabotropic glutamate receptors (mGluRs) in this event. Emerging evidence also identifies Gαi/o-coupled group III mGluRs (mGluR4/7/8 subtypes enriched in the limbic system) as direct substrates of drugs of abuse and active regulators of drug action. Auto- and heteroreceptors of mGluR4/7/8 reside predominantly on nerve terminals of glutamatergic corticostriatal and GABAergic striatopallidal pathways, respectively. These presynaptic receptors regulate basal and/or phasic release of respective transmitters to maintain basal ganglia homeostasis. In response to operant administration of common addictive drugs, such as psychostimulants (cocaine and amphetamine), alcohol and opiates, limbic group III mGluRs undergo drastic adaptations to contribute to the enduring remodeling of excitatory synapses and to usually suppress drug seeking behavior. As a result, a loss-of-function mutation (knockout) of individual group III receptor subtypes often promotes drug seeking. This review summarizes the data from recent studies on three group III receptor subtypes (mGluR4/7/8) expressed in the basal ganglia and analyzes their roles in the regulation of dopamine and glutamate signaling in the striatum and their participation in the addictive properties of three major classes of drugs (psychostimulants, alcohol, and opiates). PMID:24078068

  6. An Optimized Glutamate Receptor Photoswitch with Sensitized Azobenzene Isomerization.

    PubMed

    Gascón-Moya, Marta; Pejoan, Arnau; Izquierdo-Serra, Mercè; Pittolo, Silvia; Cabré, Gisela; Hernando, Jordi; Alibés, Ramon; Gorostiza, Pau; Busqué, Félix

    2015-10-16

    A new azobenzene-based photoswitch, 2, has been designed to enable optical control of ionotropic glutamate receptors in neurons via sensitized two-photon excitation with NIR light. In order to develop an efficient and versatile synthetic route for this molecule, a modular strategy is described which relies on the use of a new linear fully protected glutamate derivative stable in basic media. The resulting compound undergoes one-photon trans-cis photoisomerization via two different mechanisms: direct excitation of its azoaromatic unit and irradiation of the pyrene sensitizer, a well-known two-photon sensitive chromophore. Moreover, 2 presents large thermal stability of its cis isomer, in contrast to other two-photon responsive switches relying on the intrinsic nonlinear optical properties of push-pull substituted azobenzenes. As a result, the molecular system developed herein is a very promising candidate for evoking large photoinduced biological responses during the multiphoton operation of neuronal glutamate receptors with NIR light, which require accumulation of the protein-bound cis state of the switch upon repeated illumination. PMID:26414427

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

    NASA Astrophysics Data System (ADS)

    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.

  8. Zisheng Shenqi decoction ameliorates monosodium urate crystal-induced gouty arthritis in rats through anti-inflammatory and anti-oxidative effects.

    PubMed

    Han, Jieru; Xie, Ying; Sui, Fangyu; Liu, Chunhong; Du, Xiaowei; Liu, Chenggang; Feng, Xiaoling; Jiang, Deyou

    2016-09-01

    Based on traditional Chinese medicinal theories on gouty arthritis, Zisheng Shenqi decoction (ZSD), a novel Chinese medicinal formula, was developed due to its multiple functions, including reinforcing renal function, promoting blood circulation and relieving pain. In the present study, the effect of ZSD on monosodium urate (MSU) crystal-induced gouty arthritis in rats was investigated and the underlying mechanisms were examined. The data from these investigations showed that the injection of MSU crystals into the ankle joint cavity caused significant elevations in ankle swelling and inflammatory cell infiltration into the synovium, whereas these abnormal changes were markedly suppressed by oral administration of ZSD (40 mg/kg) for 7 days. Mechanically, ZSD treatment prevented MSU crystal‑induced inflammatory responses, as evidenced by downregulation in the expression levels of NACHT domain, leucine‑rich repeat and pyrin domain containing protein (NALP) 1 and NALP6 inflammasomes, decreased serum levels of tumor necrosis factor‑α and interleukin‑1β, and inhibited activation of nuclear factor‑κB. In addition, ZSD administration markedly enhanced the anti-oxidant status in MSU crystal‑induced rats by the increase in the activities of superoxide dismutase and glutathione peroxidase, and the levels of reduced glutathione. These results indicated that ZSD effectively prevented MSU crystal-induced gouty arthritis via modulating multiple anti‑oxidative and anti‑inflammatory pathways, suggesting a promising herbal formula for the prevention and treatment of gouty arthritis. PMID:27432278

  9. Therapeutic effect of the saponin fraction from Clematis chinensis Osbeck roots on osteoarthritis induced by monosodium iodoacetate through protecting articular cartilage.

    PubMed

    Wu, Wenjun; Xu, Xianxiang; Dai, Yue; Xia, Lunzhu

    2010-04-01

    The objective of the present study was to investigate the effect of the saponin fraction from Clematis chinensis Osbeck roots (SFC) on an osteoarthritis model in rats and to explore its underlying mechanisms. Osteoarthritis was induced by intraarticular injection of monosodium iodoacetate (MIA) into knee joints of rats, and SFC and diclofenac were orally administered once a day for 28 consecutive days. Joint swelling, macroscopic observation, histological assessment and proteoglycan (PG) degradation were examined. In vitro, cultured rabbit chondrocytes were stimulated with MIA and sodium nitroprusside (SNP), respectively. The effects of SFC on MIA- and SNP-induced chondrocyte injury were examined by MTT assay. It was shown that SFC (50, 100, 200 mg/kg) dose-dependently reduced cartilage injury and PG degradation induced by MIA. Diclofenac (4 mg/kg) only slightly alleviated cartilage injury and PG degradation. SFC also prevented SNP- or MIA-induced rabbit chondrocyte impairment. These results indicate that SFC is effective in ameliorating joint destruction and cartilage erosion in MIA-induced osteoarthritic in rats, and the mechanisms of action for protecting articular cartilage are through preventing extracellular matrix degradation and chondrocyte injury. PMID:19655297

  10. Anti-inflammatory effect of egg white-chalcanthite and purple bamboo salts mixture on arthritis induced by monosodium iodoacetate in Sprague-Dawley rats

    PubMed Central

    Lee, Tae-Hee; Song, Hyun-kyung; Jang, Ja-Young; Kim, Dong-Yoon; Park, Hyun-Kyung; Choi, Eun-A

    2016-01-01

    The aim of this study is to investigate the potential of anti-osteoarthritis effects on egg white-chalcanthite (EC), purple bamboo salts (PBS), and a mixture of EC and PBS (EC+PBS). EC is a mixture of egg white and pulverized chalcanthite. PBS has been widely used as one of functional foods in Korea and shows unique features compared with common salt. Osteoarthritis was induced by intra-articular injection of monosodium iodoacetate (MIA, 4mg/kg bw) in Sprague-Dawley (SD) rats. Test substances were administered once daily for 6 weeks at doses of 10 mg EC, EC+100 mg PBS, EC+200 mg PBS before and after MIA injection. Each substance was assessed by blood chemistry parameters, and by serum cytokines including IL-1β and IL-6, and nitric oxide (NO) and prostaglandin-E2 (PGE2). Structural changes of articular cartilage were also evaluated by histopathological examination. As a result, body weight and blood chemistry parameter were not different in all experimental groups. EC+PBS mixture reduced the production of PGE2, NO, IL-1β, and IL-6. In histological grade of osteoarthritis, EC+PBS mixture had a tendency to ameliorate damage of articular cartilage induced by MIA in a dose-dependent manner. In conclusion, EC+PBS mixture was demonstrated to have a potential for anti-inflammatory effect against osteoarthritis induced by MIA in a dose-dependent manner. PMID:27382377

  11. Effects of deer bone extract on the expression of pro-inflammatory cytokine and cartilage-related genes in monosodium iodoacetate-induced osteoarthritic rats.

    PubMed

    Lee, Hyunji; Choi, Hyeon-Son; Park, Yooheon; Ahn, Chang Won; Jung, Sung Ug; Park, Soo Hyun; Suh, Hyung Joo

    2014-01-01

    Deer bone extract has the potential to relieve the discomfort or the articular cartilaginous damage associated with osteoarthritic (OA) and may be useful as a natural supplement for OA treatment without serious side effects. We analyzed the expression of pro-inflammatory cytokine and cartilage-related genes in monosodium iodoacetate-induced OA rats. Increases in the levels of serum pro-inflammatory cytokines, such as interleukin-1β, interleukin-6, and tumor necrosis factor-α were significantly inhibited by the administration of deer bone extract (p<0.05). Decreases in the expression of collagen type II (COL2) and tissue inhibitors of metalloproteinases (TIMPs) mRNAs in the cartilage were significantly inhibited by deer bone extract treatment (p<0.05). The deer bone extract significantly suppressed the expression of matrix metalloproteinases (MMPs) mRNAs in the cartilage. The deer bone extract induced the up-regulation of COL2 and TIMP mRNAs and the down-regulation of MMP mRNAs by suppressing the expression of pro-inflammatory cytokine mRNAs. PMID:25273135

  12. Zisheng Shenqi decoction ameliorates monosodium urate crystal-induced gouty arthritis in rats through anti-inflammatory and anti-oxidative effects

    PubMed Central

    Han, Jieru; Xie, Ying; Sui, Fangyu; Liu, Chunhong; Du, Xiaowei; Liu, Chenggang; Feng, Xiaoling; Jiang, Deyou

    2016-01-01

    Based on traditional Chinese medicinal theories on gouty arthritis, Zisheng Shenqi decoction (ZSD), a novel Chinese medicinal formula, was developed due to its multiple functions, including reinforcing renal function, promoting blood circulation and relieving pain. In the present study, the effect of ZSD on monosodium urate (MSU) crystal-induced gouty arthritis in rats was investigated and the underlying mechanisms were examined. The data from these investigations showed that the injection of MSU crystals into the ankle joint cavity caused significant elevations in ankle swelling and inflammatory cell infiltration into the synovium, whereas these abnormal changes were markedly suppressed by oral administration of ZSD (40 mg/kg) for 7 days. Mechanically, ZSD treatment prevented MSU crystal-induced inflammatory responses, as evidenced by downregulation in the expression levels of NACHT domain, leucine-rich repeat and pyrin domain containing protein (NALP) 1 and NALP6 inflammasomes, decreased serum levels of tumor necrosis factor-α and interleukin-1β, and inhibited activation of nuclear factor-κB. In addition, ZSD administration markedly enhanced the anti-oxidant status in MSU crystal-induced rats by the increase in the activities of superoxide dismutase and glutathione peroxidase, and the levels of reduced glutathione. These results indicated that ZSD effectively prevented MSU crystal-induced gouty arthritis via modulating multiple anti-oxidative and anti-inflammatory pathways, suggesting a promising herbal formula for the prevention and treatment of gouty arthritis. PMID:27432278

  13. Effects of Modified Simiao Decoction on IL-1β and TNFα Secretion in Monocytic THP-1 Cells with Monosodium Urate Crystals-Induced Inflammation

    PubMed Central

    Liu, Ya-Fei; Tu, Sheng-Hao; Chen, Zhe; Wang, Yu; Hu, Yong-Hong; Dong, Hui

    2014-01-01

    Simiao pill, a Chinese herbal formula containing four herbs, has been used in the treatment of gouty arthritis for many years. The aim of this study was to explore the effects of modified Simiao decoction (MSD) on IL-1β and TNFα secretion in monocytic THP-1 cells with monosodium urate (MSU) crystals-induced inflammation. The MSU crystals-induced inflammation model in THP-1 cells was successfully established by the stimulation of phorbol 12-myristate 13-acetate (PMA) and MSU crystals. Then, the MSD-derived serum or control serum extracted from rat was administered to different treatment groups. The morphology of MSU crystals and THP-1 cells was observed. IL-1β and TNFα protein expression in supernatant of THP-1 cells were determined by ELISA. Our data demonstrated that MSU crystals induced time-dependent increase of IL-1β and TNFα. Moreover, MSD significantly decreased IL-1β release in THP-1 cells with MSU crystals-induced inflammation. These results suggest that MSD is promising in the treatment of MSU crystals-induced inflammation in THP-1 cells. MSD may act as an anti-IL-1 agent in treating gout. The underlying mechanism may be related to NALP3 inflammasome which needs to be validated in future studies. PMID:24999366

  14. Involvement of glutamate in the respiratory metabolism of Bradyrhizobium japonicum bacteroids.

    PubMed

    Salminen, S O; Streeter, J G

    1987-02-01

    Bradyrhizobium japonicum bacteroids were isolated anaerobically and supplied with 14C-labeled succinate, malate, aspartate, or glutamate for periods of up to 60 min in the presence of myoglobin to control the O2 concentration. Succinate and malate were absorbed about twice as rapidly as glutamate and aspartate. Conversion of substrate to CO2 was most rapid for malate, followed by succinate, glutamate, and aspartate. When CO2 production was expressed as a proportion of total carbon taken up, malate was still the most rapidly respired substrate, with 68% of the label absorbed converted to CO2. The comparable values for succinate, glutamate, and aspartate were 37, 50, and 38%, respectively. Considering the fate of labeled substrate not respired, greater than 95% of absorbed glutamate remained as glutamate in the bacteroids. In contrast, from 39 to 66% of the absorbed succinate, malate, or aspartate was converted to glutamate. An increase in the rate of CO2 formation from labeled substrates after 20 min appeared to coincide with a maximum accumulation of label in glutamate. The results indicate the presence of a substantial glutamate pool in bacteroids and the involvement of glutamate in the respiratory metabolism of bacteroids. PMID:2879829

  15. Glutamate-mediated protection of crayfish glial cells from PDT-induced apoptosis

    NASA Astrophysics Data System (ADS)

    Rudkovskii, M. V.; Romanenko, N. P.; Berezhnaya, E. V.; Kovaleva, V. D.; Uzdensky, A. B.

    2011-03-01

    Photodynamic treatment that causes intense oxidative stress and kills cells is currently used in neurooncology. However, along with tumor it damages surrounding healthy neurons and glial cells. In order to study the possible role of glutamate-related signaling pathways in photodynamic injury of neurons and glia, we investigated photodynamic effect of alumophthalocyanine Photosens on isolated crayfish stretch receptor that consists of a single neuron surrounded by glial cells. The laser diode (670 nm, 0.4 W/cm2) was used for dye photoexcitation. Application of glutamate increased photodynamically induced necrosis of neurons and glial cells but significantly decreased glial apoptosis. The natural neuroglial mediator N-acetylaspartylglutamate, which releases glutamate after cleavage in the extracellular space by glutamate carboxypeptidase II, also inhibited photoinduced apoptosis. Inhibition of glutamate carboxypeptidase II, oppositely, enhanced apoptosis of glial cells. These data confirm the anti-apoptotic activity of glutamate. Application of NMDA or inhibition of NMDA receptors by MK801 did not influence photodynamic death of neurons and glial cells that indicated nonparticipation of NMDA receptors in these processes. Inhibition of metabotropic glutamate receptors by AP-3 decreased PDT-induced apoptosis. One can suggest that crayfish neurons naturally secrete NAAG, which being cleaved by GCOP produces glutamate. Glutamate prevents photoinduced apoptosis of glial cells possibly through metabotropic but not ionotropic glutamate receptors.

  16. Glutamate-mediated protection of crayfish glial cells from PDT-induced apoptosis

    NASA Astrophysics Data System (ADS)

    Rudkovskii, M. V.; Romanenko, N. P.; Berezhnaya, E. V.; Kovaleva, V. D.; Uzdensky, A. B.

    2010-10-01

    Photodynamic treatment that causes intense oxidative stress and kills cells is currently used in neurooncology. However, along with tumor it damages surrounding healthy neurons and glial cells. In order to study the possible role of glutamate-related signaling pathways in photodynamic injury of neurons and glia, we investigated photodynamic effect of alumophthalocyanine Photosens on isolated crayfish stretch receptor that consists of a single neuron surrounded by glial cells. The laser diode (670 nm, 0.4 W/cm2) was used for dye photoexcitation. Application of glutamate increased photodynamically induced necrosis of neurons and glial cells but significantly decreased glial apoptosis. The natural neuroglial mediator N-acetylaspartylglutamate, which releases glutamate after cleavage in the extracellular space by glutamate carboxypeptidase II, also inhibited photoinduced apoptosis. Inhibition of glutamate carboxypeptidase II, oppositely, enhanced apoptosis of glial cells. These data confirm the anti-apoptotic activity of glutamate. Application of NMDA or inhibition of NMDA receptors by MK801 did not influence photodynamic death of neurons and glial cells that indicated nonparticipation of NMDA receptors in these processes. Inhibition of metabotropic glutamate receptors by AP-3 decreased PDT-induced apoptosis. One can suggest that crayfish neurons naturally secrete NAAG, which being cleaved by GCOP produces glutamate. Glutamate prevents photoinduced apoptosis of glial cells possibly through metabotropic but not ionotropic glutamate receptors.

  17. Magnetic Resonance Spectroscopy Studies of Glutamate-Related Abnormalities in Mood Disorders

    PubMed Central

    Yüksel, Cagri; Öngür, Dost

    2010-01-01

    In mood disorders there is growing evidence for glutamatergic abnormalities derived from peripheral measures of glutamatergic metabolites in patients, postmortem studies on glutamate related markers, and animal studies on the mechanism of action of available treatments. Magnetic resonance spectroscopy (MRS) has the potential to corroborate and extend these findings with the advantage of in vivo assessment of glutamate-related metabolites in different disease states, in response to treatment, and in relation with functional imaging data. In this article we first review the biological significance of glutamate, glutamine, and Glx (composed mainly of glutamate and glutamine). Next we review the MRS literature in mood disorders examining these glutamate-related metabolites. Here, we find a highly consistent pattern of Glx level reductions in major depressive disorder and elevations in bipolar disorder. In addition, studies of depression regardless of diagnosis provide suggestive evidence for reduced glutamine/glutamate ratio, and in mania for elevated glutamine/glutamate ratio. These patterns suggest that the glutamate-related metabolite pool (not all of it necessarily relevant to neurotransmission) is constricted in major depressive disorder and expanded in bipolar disorder. Depressive and manic episodes may be characterized by modulation of the glutamine/glutamate ratio in opposite directions, possibly suggesting reduced vs. elevated glutamate conversion to glutamine by glial cells, respectively. We discuss the implications of these results for the pathophysiology of mood disorders, and suggest future directions for MRS studies. PMID:20728076

  18. A Glutamic Acid-Producing Lactic Acid Bacteria Isolated from Malaysian Fermented Foods

    PubMed Central

    Zareian, Mohsen; Ebrahimpour, Afshin; Bakar, Fatimah Abu; Mohamed, Abdul Karim Sabo; Forghani, Bita; Ab-Kadir, Mohd Safuan B.; Saari, Nazamid

    2012-01-01

    l-glutamaic acid is the principal excitatory neurotransmitter in the brain and an important intermediate in metabolism. In the present study, lactic acid bacteria (218) were isolated from six different fermented foods as potent sources of glutamic acid producers. The presumptive bacteria were tested for their ability to synthesize glutamic acid. Out of the 35 strains showing this capability, strain MNZ was determined as the highest glutamic-acid producer. Identification tests including 16S rRNA gene sequencing and sugar assimilation ability identified the strain MNZ as Lactobacillus plantarum. The characteristics of this microorganism related to its glutamic acid-producing ability, growth rate, glucose consumption and pH profile were studied. Results revealed that glutamic acid was formed inside the cell and excreted into the extracellular medium. Glutamic acid production was found to be growth-associated and glucose significantly enhanced glutamic acid production (1.032 mmol/L) compared to other carbon sources. A concentration of 0.7% ammonium nitrate as a nitrogen source effectively enhanced glutamic acid production. To the best of our knowledge this is the first report of glutamic acid production by lactic acid bacteria. The results of this study can be further applied for developing functional foods enriched in glutamic acid and subsequently γ-amino butyric acid (GABA) as a bioactive compound. PMID:22754309

  19. Effect of carnitine on muscular glutamate uptake and intramuscular glutathione in malignant diseases

    PubMed Central

    Breitkreutz, R; Babylon, A; Hack, V; Schuster, K; Tokus, M; Böhles, H; Hagmüller, E; Edler, L; Holm, E; Dröge, W

    2000-01-01

    Abnormally low intramuscular glutamate and glutathione (GSH) levels and/or a decreased muscular uptake of glutamate by the skeletal muscle tissue have previously been found in malignant diseases and simian immunodeficiency virus (SIV) infection and may contribute to the development of cachexia. We tested the hypothesis that an impaired mitochondrial energy metabolism may compromise the Na+-dependent glutamate transport. A randomized double-blind clinical trial was designed to study the effects of L -carnitine, i.e. an agent known to enhance mitochondrial integrity and function, on the glutamate transport and plasma glutamate level of cancer patients. The effect of carnitine on the intramuscular glutamate and GSH levels was examined in complementary experiments with tumour-bearing mice. In the mice, L -carnitine treatment ameliorated indeed the tumour-induced decrease in muscular glutamate and GSH levels and the increase in plasma glutamate levels. The carnitine-treated group in the randomized clinical study showed also a significant decrease in the plasma glutamate levels but only a moderate and statistically not significant increase in the relative glutamate uptake in the lower extremities. Further studies may be warranted to determine the effect of L -carnitine on the intramuscular GSH levels in cancer patients. © 2000 Cancer Research Campaign PMID:10646895

  20. The role of glutamate signaling in pain processes and its regulation by GCP II inhibition.

    PubMed

    Wozniak, K M; Rojas, C; Wu, Y; Slusher, B S

    2012-01-01

    Glutamate is the predominant excitatory neurotransmitter used by primary afferent synapses and neurons in the spinal cord dorsal horn. Glutamate and glutamate receptors are also located in areas of the brain, spinal cord and periphery that are involved in pain sensation and transmission. Not surprisingly, glutamate receptors have been an attractive target for new pain therapies. However, their widespread distribution and array of function has often resulted in drugs targeting these sites having undesirable side-effects. This chapter will review, in general terms, the current knowledge of glutamate and its effects at various glutamate receptors with regards to nociception. In addition, we will briefly review the glutamatergic drugs currently in use as treatments for pain, as well as known novel candidates in various stages of clinical trial. Lastly, we will summarize the data supporting a novel target for pain intervention by way of GCPII inhibition, which appears devoid of the side-effects associated with direct glutamate receptor antagonists and thus holds major promise for future therapy. GCPII (glutamate carboxypeptidase II) cleaves the prevalent neuropeptide NAAG into NAA and glutamate and there is widespread evidence and belief that targeting the glutamate derived from this enzymatic action may be a promising therapeutic route. PMID:22304711

  1. Protein kinase C -dependent regulation of synaptosomal glutamate uptake under conditions of hypergravity

    NASA Astrophysics Data System (ADS)

    Borisova, Tatiana; Krisanova, Natalia; Borisov, Arseniy; Sivko, Roman

    Glutamate is not only the main excitatory neurotransmitter in the mammalian CNS, but also a potent neurotoxin. Excessive concentration of ambient glutamate over activates glutamate receptors and causes neurotoxicity. Uptake of glutamate from the extracellular space into nerve cells was mediated by sodium-dependent glutamate transporters located in the plasma membrane. It was shown that the activity of glutamate transporters in rat brain nerve terminals was decreased after hypergravity (centrifugation of rats in special containers at 10 G for 1 hour). This decrease may result from the reduction in the number of glutamate transporters expressed in the plasma membrane of nerve terminals after hypergravity that was regulated by protein kinase C. The possibility of the involvement of protein kinase C in the regulation of the activity of glutamate transporters was assessed under conditions of hypergravity. The effect of protein kinase C inhibitor GF 109 203X on synaptosomal L-[14C]glutamate uptake was analysed. It was shown that the inhibitor decreased L-[14C]glutamate uptake by 15 % in control but did not influence it after hypergravity. In control, the initial velocity of L-[14C]glutamate uptake in the presence of the inhibitor decreased from 2.5 ± 0.2 nmol x min-1 x mg-1 of proteins to 2.17 ± 0.1 nmol x min-1 x mg-1 of proteins, whereas after hypergravity this value lowered from 2.05 ± 0.1 nmol x min-1 x mg-1 of proteins to 2.04 ± 0.1 nmol x min-1 x mg-1 of proteins. Thus, protein kinase C -dependent alteration in the cell surface expression of glutamate transporters may be one of the causes of a decrease in the activity of glutamate transporters after hypergravity.

  2. The glutamate and neutral amino acid transporter family: physiological and pharmacological implications.

    PubMed

    Kanai, Yoshikatsu; Hediger, Matthias A

    2003-10-31

    The solute carrier family 1 (SLC1) is composed of five high affinity glutamate transporters, which exhibit the properties of the previously described system XAG-, as well as two Na+-dependent neutral amino acid transporters with characteristics of the so-called "ASC" (alanine, serine and cysteine). The SLC1 family members are structurally similar, with almost identical hydropathy profiles and predicted membrane topologies. The transporters have eight transmembrane domains and a structure reminiscent of a pore loop between the seventh and eighth domains [Neuron 21 (1998) 623]. However, each of these transporters exhibits distinct functional properties. Glutamate transporters mediate transport of L-Glu, L-Asp and D-Asp, accompanied by the cotransport of 3 Na+ and one 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. Given the high concentrating capacity provided by the unique ion coupling pattern of glutamate transporters, they play crucial roles in protecting neurons against glutamate excitotoxicity in the central nervous system (CNS). The regulation and manipulation of their function is a critical issue in the pathogenesis and treatment of CNS disorders involving glutamate excitotoxicity. Loss of function of the glial glutamate transporter GLT1 (SLC1A2) has been implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS), resulting in damage of adjacent motor neurons. The importance of glial glutamate transporters in protecting neurons from extracellular glutamate was further demonstrated in studies of the slc1A2 glutamate transporter knockout mouse. The findings suggest that therapeutic upregulation of GLT1 may be beneficial in a variety of pathological conditions. Selective inhibition of the neuronal glutamate transporter EAAC1 (SLC1A1) but not the glial glutamate transporters may be of therapeutic interest, allowing blockage of glutamate exit from

  3. Evidence for Astrocytes as a Potential Source of the Glutamate Excess in Temporal Lobe Epilepsy

    PubMed Central

    Perez, Edgar L; Lauritzen, Fredrik; Wang, Yue; Lee, Tih-Shih W; Kang, Dewey; Zaveri, Hitten P; Chaudhry, Farrukh A; Ottersen, Ole P; Bergersen, Linda H; Eid, Tore

    2012-01-01

    Increased extracellular brain glutamate has been implicated in the pathophysiology of human refractory temporal lobe epilepsy (TLE), but the cause of the excessive glutamate is unknown. Prior studies by us and others have shown that the glutamate degrading enzyme glutamine synthetase (GS) is deficient in astrocytes in the epileptogenic hippocampal formation in a subset of patients with TLE. We have postulated that the loss of GS in TLE leads to increased glutamate in astrocytes with elevated concentrations of extracellular glutamate and recurrent seizures as the ultimate end-points. Here we test the hypothesis that the deficiency in GS leads to increased glutamate in astrocytes. Rats were chronically infused with methionine sulfoximine (MSO, n=4) into the hippocampal formation to induce GS-deficiency and recurrent seizures. A separate group of rats was infused with 0.9% NaCl (saline) as a control (n=6). At least 10 days after the start of infusion, once recurrent seizures were established in the MSO-treated rats, the concentration of glutamate was assessed in CA1 of the hippocampal formation by immunogold electron microscopy. The concentration of glutamate was 47% higher in astrocytes in the MSO-treated vs. saline-treated rats (p=0.02), and the ratio of glutamate in astrocytes relative to axon terminals was increased by 74% in the MSO-treated rats (p=0.003). These data support our hypothesis that a deficiency in GS leads to increased glutamate in astrocytes. We additionally propose that the GS-deficient astrocytes in the hippocampal formation in TLE lead to elevated extracellular brain glutamate either through decreased clearance of extracellular glutamate or excessive release of glutamate into the extracellular space from these cells, or a combination of the two. PMID:22659305

  4. Serum Glutamate Levels Correlate with Gleason Score and Glutamate Blockade Decreases Proliferation, Migration, and Invasion and Induces Apoptosis in Prostate Cancer Cells

    PubMed Central

    Koochekpour, Shahriar; Majumdar, Sunipa; Azabdaftari, Gissou; Attwood, Kristopher; Scioneaux, Ray; Subramani, Dhatchayini; Manhardt, Charles; Lorusso, Giovanni D.; Willard, Stacey S.; Thompson, Hillary; Shourideh, Mojgan; Rezaei, Katayoon; Sartor, Oliver; Mohler, James L.; Vessella, Robert L.

    2012-01-01

    Purpose During glutaminolysis, glutamine is catabolized to glutamate and incorporated into citric acid cycle and lipogenesis. Serum glutamate levels were measured in patients with primary prostate cancer (PCa) or metastatic castrate-resistant PCa (mCRPCa) to establish clinical relevance. The effect of glutamate-deprivation or blockade by metabotropic glutamate receptor 1 (GRM1)-antagonists was investigated on PCa cells’ growth, migration, and invasion to establish biological relevance. Experimental Design Serum glutamate levels were measured in normal men (n = 60) and patients with primary PCa (n = 197) or mCRPCa (n = 109). GRM1 expression in prostatic tissues was examined using immunohistochemistry (IHC). Cell growth, migration, and invasion were determined using cell cytotoxicity and modified Boyden chamber assays, respectively. Apoptosis was detected using immunoblotting against cleaved caspases, PARP and γ-H2AX. Results Univariate and multivariate analyses demonstrated significantly higher serum glutamate levels in Gleason score ≥ 8 than in the Gleason sscore ≤ 7 and in African Americans than in the Caucasian Americans. African Americans with mCRPCa significantly higher serum glutamate levels than those with primary PCa or benign prostate. However, in Caucasian Americans, serum glutamate levels were similar in normal research subjects and patients with mCRPC. IHC demonstrated weak or no expression of GRM1 in luminal acinar epithelial cells of normal or hyperplastic glands, but high expression in primary or metastatic PCa tissues. Glutamate deprivation or blockade decreased PCa cells’ proliferation, migration, and invasion and led to apoptotic cell death. Conclusions Glutamate expression is mechanistically associated with and may provide a biomarker of PCa aggressiveness. PMID:23072969

  5. Glutamate Synthase: Properties of the Reduced Nicotinamide Adenine Dinucleotide-Dependent Enzyme from Saccharomyces cerevisiae

    PubMed Central

    Roon, Robert J.; Even, Harvey L.; Larimore, Fred

    1974-01-01

    A reduced nicotinamide adenine dinucleotide (NADH)-dependent glutamate synthase has been detected and partially purified from crude extracts of Saccharomyces cerevisiae. The enzyme is specific for NADH, glutamine, and α-ketoglutarate (Km values of 2.6 μM, 1.0 mM, and 140 μM, respectively) and has a pH optimum between 7.1 and 7.7. The stoichiometry of the reaction has been determined as 2 mol of glutamate synthesized per mol of glutamine consumed. Glutamate synthase can be distinguished from either of the glutamate dehydrogenases of yeast on the basis of its substrate requirements and behavior during agarose gel and ion exchange chromatography. Variations in the specific activity of glutamate synthase, which occur in response to changes in the growth medium, are similar in character to those observed with the nicotinamide adenine dinucleotide phosphate-dependent (anabolic) glutamate dehydrogenase. PMID:4362465

  6. Sensorineural deafness and seizures in mice lacking vesicular glutamate transporter 3.

    PubMed

    Seal, Rebecca P; Akil, Omar; Yi, Eunyoung; Weber, Christopher M; Grant, Lisa; Yoo, Jong; Clause, Amanda; Kandler, Karl; Noebels, Jeffrey L; Glowatzki, Elisabeth; Lustig, Lawrence R; Edwards, Robert H

    2008-01-24

    The expression of unconventional vesicular glutamate transporter VGLUT3 by neurons known to release a different classical transmitter has suggested novel roles for signaling by glutamate, but this distribution has raised questions about whether the protein actually contributes to glutamate release. We now report that mice lacking VGLUT3 are profoundly deaf due to the absence of glutamate release from hair cells at the first synapse in the auditory pathway. The early degeneration of some cochlear ganglion neurons in knockout mice also indicates an important developmental role for the glutamate released by hair cells before the onset of hearing. In addition, the mice exhibit primary, generalized epilepsy that is accompanied by remarkably little change in ongoing motor behavior. The glutamate release conferred by expression of VGLUT3 thus has an essential role in both function and development of the auditory pathway, as well as in the control of cortical excitability. PMID:18215623

  7. Serotonin impairs copulation and attenuates ejaculation-induced glutamate activity in the medial preoptic area.

    PubMed

    Dominguez, Juan M; Hull, Elaine M

    2010-08-01

    The medial preoptic area (MPOA) is critical for male sexual behavior. Glutamate is released in the MPOA of male rats during copulation, and increasing glutamate levels by reverse dialysis of glutamate uptake inhibitors facilitates mating. Conversely, increased release of serotonin (5-HT) inhibits sexual behavior. In both rats and men, selective serotonin reuptake inhibitors (SSRIs) impair erection, ejaculation, and libido. Here we reverse-dialyzed 5-HT through concentric microdialysis probes in the MPOA of male rats; concurrently we collected 2-min samples for analysis of glutamate and measured sexual behavior. Sexual activity, and especially ejaculation, increased levels of glutamate in the MPOA. However, reverse dialysis of 5-HT into the MPOA impaired ejaculatory ability and attenuated glutamate release. Implications of these results for impairment of sexual behavior that results from administration of SSRIs are discussed. PMID:20695654

  8. Riluzole rescues glutamate alterations, cognitive deficits, and tau pathology associated with P301L tau expression.

    PubMed

    Hunsberger, Holly C; Weitzner, Daniel S; Rudy, Carolyn C; Hickman, James E; Libell, Eric M; Speer, Rebecca R; Gerhardt, Greg A; Reed, Miranda N

    2015-10-01

    Hyperexcitability of the hippocampus is a commonly observed phenomenon in the years preceding a diagnosis of Alzheimer's disease (AD). Our previous work suggests a dysregulation in glutamate neurotransmission may mediate this hyperexcitability, and glutamate dysregulation correlates with cognitive deficits in the rTg(TauP301L)4510 mouse model of AD. To determine whether improving glutamate regulation would attenuate cognitive deficits and AD-related pathology, TauP301L mice were treated with riluzole (~ 12.5 mg/kg/day p.o.), an FDA-approved drug for amyotrophic lateral sclerosis that lowers extracellular glutamate levels. Riluzole-treated TauP301L mice exhibited improved performance in the water radial arm maze and the Morris water maze, associated with a decrease in glutamate release and an increase in glutamate uptake in the dentate gyrus, cornu ammonis 3 (CA3), and cornu ammonis 1 (CA1) regions of the hippocampus. Riluzole also attenuated the TauP301L-mediated increase in hippocampal vesicular glutamate transporter 1, which packages glutamate into vesicles and influences glutamate release; and the TauP301L-mediated decrease in hippocampal glutamate transporter 1, the major transporter responsible for removing glutamate from the extracellular space. The TauP301L-mediated reduction in PSD-95 expression, a marker of excitatory synapses in the hippocampus, was also rescued by riluzole. Riluzole treatment reduced total levels of tau, as well as the pathological phosphorylation and conformational changes in tau associated with the P301L mutation. These findings open new opportunities for the development of clinically applicable therapeutic approaches to regulate glutamate in vulnerable circuits for those at risk for the development of AD. PMID:26146790

  9. Detection of glutamate release from neurons by genetically encoded surface-displayed FRET nanosensors

    NASA Astrophysics Data System (ADS)

    Okumoto, Sakiko; Looger, Loren L.; Micheva, Kristina D.; Reimer, Richard J.; Smith, Stephen J.; Frommer, Wolf B.

    2005-06-01

    Glutamate is the predominant excitatory neurotransmitter in the mammalian brain. Once released, its rapid removal from the synaptic cleft is critical for preventing excitotoxicity and spillover to neighboring synapses. Despite consensus on the role of glutamate in normal and disease physiology, technical issues limit our understanding of its metabolism in intact cells. To monitor glutamate levels inside and at the surface of living cells, genetically encoded nanosensors were developed. The fluorescent indicator protein for glutamate (FLIPE) consists of the glutamate/aspartate binding protein ybeJ from Escherichia coli fused to two variants of the green fluorescent protein. Three sensors with lower affinities for glutamate were created by mutation of residues peristeric to the ybeJ binding pocket. In the presence of ligands, FLIPEs show a concentration-dependent decrease in FRET efficiency. When expressed on the surface of rat hippocampal neurons or PC12 cells, the sensors respond to extracellular glutamate with a reversible concentration-dependent decrease in FRET efficiency. Depolarization of neurons leads to a reduction in FRET efficiency corresponding to 300 nM glutamate at the cell surface. No change in FRET was observed when cells expressing sensors in the cytosol were superfused with up to 20 mM glutamate, consistent with a minimal contribution of glutamate uptake to cytosolic glutamate levels. The results demonstrate that FLIPE sensors can be used for real-time monitoring of glutamate metabolism in living cells, in tissues, or in intact organisms, providing tools for studying metabolism or for drug discovery. aspartate | hippocampal neuron | neurotransmitter | secretion | transport

  10. Magnesium Sulfate Protects Against the Bioenergetic Consequences of Chronic Glutamate Receptor Stimulation

    PubMed Central

    Clerc, Pascaline; Young, Christina A.; Bordt, Evan A.; Grigore, Alina M.; Fiskum, Gary; Polster, Brian M.

    2013-01-01

    Extracellular glutamate is elevated following brain ischemia or trauma and contributes to neuronal injury. We tested the hypothesis that magnesium sulfate (MgSO4, 3 mM) protects against metabolic failure caused by excitotoxic glutamate exposure. Rat cortical neuron preparations treated in medium already containing a physiological concentration of Mg2+ (1 mM) could be segregated based on their response to glutamate (100 µM). Type I preparations responded with a decrease or small transient increase in oxygen consumption rate (OCR). Type II neurons responded with >50% stimulation in OCR, indicating a robust response to increased energy demand without immediate toxicity. Pre-treatment with MgSO4 improved the initial bioenergetic response to glutamate and ameliorated subsequent loss of spare respiratory capacity, measured following addition of the uncoupler FCCP, in Type I but not Type II neurons. Spare respiratory capacity in Type I neurons was also improved by incubation with MgSO4 or NMDA receptor antagonist MK801 in the absence of glutamate treatment. This finding indicates that the major difference between Type I and Type II preparations is the amount of endogenous glutamate receptor activity. Incubation of Type II neurons with 5 µM glutamate prior to excitotoxic (100 µM) glutamate exposure recapitulated a Type I phenotype. MgSO4 protected against an excitotoxic glutamate-induced drop in neuronal ATP both with and without prior 5 µM glutamate exposure. Results indicate that MgSO4 protects against chronic moderate glutamate receptor stimulation and preserves cellular ATP following treatment with excitotoxic glutamate. PMID:24236167

  11. Role of nitric oxide and cyclic GMP in glutamate-induced neuronal death.

    PubMed

    Montoliu, C; Llansola, M; Monfort, P; Corbalan, R; Fernandez-Marticorena, I; Hernandez-Viadel, M L; Felipo, V

    2001-04-01

    Glutamate is the main excitatory neurotransmitter in mammals. However, excessive activation of glutamate receptors is neurotoxic, leading to neuronal degeneration and death. In many systems, including primary cultures of cerebellar neurons, glutamate neurotoxicity is mainly mediated by excessive activation of NMDA receptors, leading to increased intracellular calcium which binds to calmodulin and activates neuronal nitric oxide synthase (NOS), increasing nitric oxide (NO) which in turn activates guanylate cyclase and increases cGMP. Inhibition of NOS prevents glutamate neurotoxicity, indicating that NO mediates glutamate-induced neuronal death in this system. NO generating agents such as SNAP also induce neuronal death. Compounds that can act as "scavengers" of NO such as Croman 6 (CR-6) prevent glutamate neurotoxicity. The role of cGMP in the mediation of glutamate neurotoxicity remains controversial. Some reports indicate that cGMP mediates glutamate neurotoxicity while others indicate that cGMP is neuroprotective. We have studied the role of cGMP in the mediation of glutamate and NO neurotoxicity in cerebellar neurons. Inhibition of soluble guanylate cyclase prevents glutamate and NO neurotoxicity. There is a good correlation between inhibition of cGMP formation and neuroprotection. Moreover 8-Br-cGMP, a cell permeable analog of cGMP, induced neuronal death. These results indicate that increased intracellular cGMP is involved in the mechanism of neurotoxicity. Inhibitors of phosphodiesterase increased extracellular but not intracellular cGMP and prevented glutamate neurotoxicity. Addition of cGMP to the medium also prevented glutamate neurotoxicity. These results are compatible with a neurotoxic effect of increased intracellular cGMP and a neuroprotective effect of increased extracellular cGMP. PMID:14715472

  12. Mechanisms for maintaining extracellular glutamate levels in the anoxic turtle striatum.

    PubMed

    Milton, Sarah L; Thompson, John W; Lutz, Peter L

    2002-05-01

    The turtle Trachemys scripta is one of a limited group of vertebrates that can withstand hours to days without oxygen. One facet of anoxic survival is the turtle's ability to maintain basal extracellular glutamate levels, whereas in most vertebrates, anoxia triggers massive excitotoxic glutamate release. We investigated glutamate release and reuptake in the anoxic turtle and the effects of adenosine and ATP-sensitive potassium (K(ATP)) channels on glutamate homeostasis. Striatal extracellular glutamate was measured in anesthetized T. scripta by microdialysis in normoxia and over 2-h anoxia. Glutamate release is decreased by 44% in the early anoxic turtle; this anoxia-induced decrease in glutamate release was prevented when K(ATP) channels and adenosine receptors were blocked simultaneously but not when either mechanism was blocked individually. We hypothesize that the continued release and reuptake of glutamate during anoxia help maintain neuronal tone and aid in the recovery of a functional neuronal network after long periods of anoxia, whereas activation of adenosine and/or K(ATP) conserves energy by reducing glutamate release and lowering transport costs. PMID:11959671

  13. On the defensive action of glutamate against the cytotoxicity and fibrogenicity of quartz dust.

    PubMed Central

    Morosova, K I; Aronova, G V; Katsnelson, B A; Velichkovski, B T; Genkin, A M; Elnichnykh, L N; Privalova, L I

    1982-01-01

    The cytotoxic action of quartz (DQ12) particles on cultures of rat peritoneal macrophages, as estimated by the inhibition of the TTC-reductase activity, is considerably reduced by preincubation with glutamic acid and by adding sodium glutamate (15 mg/ml) to the drinking water of the rats donating the macrophages. This increase in macrophage resistance under the influence of glutamate is the most probable cause of the delay in the development of silicotic fibrosis shown in several experiments on rats intratracheally injected with quartz and then treated by prolonged administration of glutamate. This effect is probably connected with the influence of glutamate on the stability of the macrophage membranes, which can in its turn be explained by different mechanisms, including the influence on the synthesis and phosphorylation of adenosine nucleotides. Such an influence was shown in rats receiving glutamate by the change of the ATP/ADP ratio in macrophages, but not in erythrocytes. The resistance of rat erythrocytes to the haemolytic action of quartz is also not influenced by the action of glutamate neither in vitro nor in vivo. Such differences in the influences of glutamate on two types of cells, equally susceptible to quartz cytotoxicity but considerably differing in the character of energy metabolism, is an indirect proof of the role of the latter in the realisation of the anticytotoxic, and thereby antifibrogenic, effect of glutamate. PMID:6124270

  14. Relationship between Zinc (Zn2+) and Glutamate Receptors in the Processes Underlying Neurodegeneration

    PubMed Central

    Pochwat, Bartłomiej; Nowak, Gabriel; Szewczyk, Bernadeta

    2015-01-01

    The results from numerous studies have shown that an imbalance between particular neurotransmitters may lead to brain circuit dysfunction and development of many pathological states. The significance of glutamate pathways for the functioning of the nervous system is equivocal. On the one hand, glutamate transmission is necessary for neuroplasticity, synaptogenesis, or cell survival, but on the other hand an excessive and long-lasting increased level of glutamate in the synapse may lead to cell death. Under clinical conditions, hyperactivity of the glutamate system is associated with ischemia, epilepsy, and neurodegenerative diseases such as Alzheimer's, Huntington's, and many others. The achievement of glutamate activity in the physiological range requires efficient control by endogenous regulatory factors. Due to the fact that the free pool of ion Zn2+ is a cotransmitter in some glutamate neurons; the role of this element in the pathophysiology of a neurodegenerative diseases has been intensively studied. There is a lot of evidence for Zn2+ dyshomeostasis and glutamate system abnormalities in ischemic and neurodegenerative disorders. However, the precise interaction between Zn2+ regulative function and the glutamate system is still not fully understood. This review describes the relationship between Zn2+ and glutamate dependent signaling pathways under selected pathological central nervous system (CNS) conditions. PMID:26106488

  15. Importance of glutamate-generating metabolic pathways for memory consolidation in chicks.

    PubMed

    Gibbs, Marie E; Hertz, Leif

    2005-07-15

    Glutamatergic and noradrenergic stimulation is essential for formation of memory of single-trial discriminative avoidance of colored beads in the 1-day-old chick. Transmitter glutamate is released soon after training and again before memory consolidation 30 min after training. Memory consolidation is abolished by posttraining injection of iodoacetate, which inhibits glycolysis and thus not only energy metabolism but also pyruvate carboxylase-dependent glucose conversion to glutamate, needed for consolidation; a similar effect is evoked by the antagonists propranolol acting at beta(2)-adrenoceptors or SR59230A acting at beta(3)-adrenoceptors. This paper shows that the effect of these inhibitors can be overcome by central injection of glutamine, providing an alternate source of transmitter glutamate and compensating for the inhibition of glycolysis by iodoacetate or the blockade of adrenergic stimulation of glycogenolysis by propranolol or of glucose uptake by SR59230A. Conversely, inhibition of memory consolidation by methionine sulfoximine (MSO), an inhibitor of glutamine synthetase and thus of the glutamate-glutamine cycle, essential for neuronal reaccumulation of previously released transmitter glutamate, could be challenged by noradrenaline, stimulating glucose uptake and glycogenolysis and providing glutamate synthesis from glucose to compensate for the lack of return of previously released glutamate. Also, administration of either glutamine or noradrenaline could prevent the spontaneous decay of labile memory 30 min after training on a weakened stimulus, suggesting that direct supply of glutamate from glucose may secure sufficient supplies of transmitter glutamate for release prior to memory consolidation at 30 min. PMID:15929064

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

    PubMed

    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. PMID:27184733

  17. Local glutamate release in the rat ventral lateral thalamus evoked by high-frequency stimulation

    NASA Astrophysics Data System (ADS)

    Agnesi, Filippo; Blaha, Charles D.; Lin, Jessica; Lee, Kendall H.

    2010-04-01

    Thalamic deep brain stimulation (DBS) is proven therapy for essential tremor, Parkinson's disease and Tourette's syndrome. We tested the hypothesis that high-frequency electrical stimulation results in local thalamic glutamate release. Enzyme-linked glutamate amperometric biosensors were implanted in anesthetized rat thalamus adjacent to the stimulating electrode. Electrical stimulation was delivered to investigate the effect of frequency, pulse width, voltage-controlled or current-controlled stimulation, and charge balancing. Monophasic electrical stimulation-induced glutamate release was linearly dependent on stimulation frequency, intensity and pulse width. Prolonged stimulation evoked glutamate release to a plateau that subsequently decayed back to baseline after stimulation. Glutamate release was less pronounced with voltage-controlled stimulation and not present with charge balanced current-controlled stimulation. Using fixed potential amperometry in combination with a glutamate bioprobe and adjacent microstimulating electrode, the present study has shown that monophasic current-controlled stimulation of the thalamus in the anesthetized rat evoked linear increases in local extracellular glutamate concentrations that were dependent on stimulation duration, frequency, intensity and pulse width. However, the efficacy of monophasic voltage-controlled stimulation, in terms of evoking glutamate release in the thalamus, was substantially lower compared to monophasic current-controlled stimulation and entirely absent with biphasic (charge balanced) current-controlled stimulation. It remains to be determined whether similar glutamate release occurs with human DBS electrodes and similar charge balanced stimulation. As such, the present results indicate the importance of evaluating local neurotransmitter dynamics in studying the mechanism of action of DBS.

  18. Glutamate carboxypeptidase inhibition reduces the severity of chemotherapy-induced peripheral neurotoxicity in rat.

    PubMed

    Carozzi, Valentina A; Chiorazzi, Alessia; Canta, Annalisa; Lapidus, Rena G; Slusher, Barbara S; Wozniak, Krystyna M; Cavaletti, Guido

    2010-05-01

    Chemotherapy is the most common method to treat cancer. The use of certain antineoplastic drugs, however, is associated with the development of peripheral neuropathy that can be dose-limiting. Excitotoxic glutamate release, leading to excessive glutamatergic neurotransmission and activation of N-methyl-D-aspartate (NMDA) receptors, is associated with neuronal damage and death in several nervous system disorders. N-Acetyl-aspartyl-glutamate (NAAG) is an abundant neuropeptide widely distributed in the central and peripheral nervous system which is physiologically hydrolyzed by the enzyme glutamate carboxypeptidase into N-Acetyl-aspartyl (NAA) and glutamate. Pharmacological inhibition of glutamate carboxypeptidase results in decreased glutamate and increased endogenous NAAG and has been shown to provide neuroprotection in several preclinical models. Here, we report the neuroprotective effect of an orally available glutamate carboxypeptidase inhibitor on three well-established animal models of chemotherapy (cisplatin, paclitaxel, bortezomib)-induced peripheral neuropathy. In all cases, glutamate carboxypeptidase inhibition significantly improved the chemotherapy-induced nerve conduction velocity deficits. In addition, morphological and morphometrical alterations induced by cisplatin and bortezomib in dorsal root ganglia (DRG) were improved by glutamate carboxypeptidase inhibition. Our data support a novel approach for the treatment of chemotherapy-induced peripheral neuropathy. PMID:19763734

  19. Molecular basis for convergent evolution of glutamate recognition by pentameric ligand-gated ion channels

    PubMed Central

    Lynagh, Timothy; Beech, Robin N.; Lalande, Maryline J.; Keller, Kevin; Cromer, Brett A.; Wolstenholme, Adrian J.; Laube, Bodo

    2015-01-01

    Glutamate is an indispensable neurotransmitter, triggering postsynaptic signals upon recognition by postsynaptic receptors. We questioned the phylogenetic position and the molecular details of when and where glutamate recognition arose in the glutamate-gated chloride channels. Experiments revealed that glutamate recognition requires an arginine residue in the base of the binding site, which originated at least three distinct times according to phylogenetic analysis. Most remarkably, the arginine emerged on the principal face of the binding site in the Lophotrochozoan lineage, but 65 amino acids upstream, on the complementary face, in the Ecdysozoan lineage. This combined experimental and computational approach throws new light on the evolution of synaptic signalling. PMID:25708000

  20. Resting Glutamate Levels and Rapid Glutamate Transients in the Prefrontal Cortex of the Flinders Sensitive Line Rat: A Genetic Rodent Model of Depression

    PubMed Central

    Hascup, Kevin N; Hascup, Erin R; Stephens, Michelle L; Glaser, Paul EA; Yoshitake, Takashi; Mathé, Aleksander A; Gerhardt, Greg A; Kehr, Jan

    2011-01-01

    Despite the numerous drugs targeting biogenic amines for major depressive disorder (depression), the search for novel therapeutics continues because of their poor response rates (∼30%) and slow onset of action (2–4 weeks). To better understand role of glutamate in depression, we used an enzyme-based microelectrode array (MEA) that was selective for glutamate measures with fast temporal (2 Hz) and high spatial (15 × 333 μm) resolution. These MEAs were chronically implanted into the prefrontal cortex of 3- to 6-month-old and 12- to 15-month-old Flinders Sensitive Line (FSL) and control Flinders Resistant Line (FRL) rats, a validated genetic rodent model of depression. Although no changes in glutamate dynamics were observed between 3 and 6 months FRL and FSL rats, a significant increase in resting glutamate levels was observed in the 12- to 15-month-old FSL rats compared with the 3- to 6-month-old FSL and age-matched FRL rats on days 3–5 post-implantation. Our MEA also recorded, for the first time, a unique phenomenon in all the four rat groups of fluctuations in resting glutamate, which we have termed glutamate transients. Although these events lasted only for seconds, they did occur throughout the testing paradigm. The average concentration of these glutamate-burst events was significantly increased in the 12- to 15-month-old FSL rats compared with 3- to 6-month-old FSL and age-matched FRL rats. These studies lay the foundation for future studies of both tonic and phasic glutamate signaling in rat models of depression to better understand the potential role of glutamate signaling in depression. PMID:21525860

  1. The dissolution of natural and artificial dusts in glutamic acid

    NASA Astrophysics Data System (ADS)

    Ling, Zhang; Faqin, Dong; Xiaochun, He

    2015-06-01

    This article describes the characteristics of natural dusts, industrial dusts, and artificial dusts, such as mineral phases, chemical components, morphological observation and size. Quartz and calcite are the main phases of natural dusts and industrial dusts with high SiO2 and CaO and low K2O and Na2O in the chemical composition. The dissolution and electrochemical action of dusts in glutamic acid liquor at the simulated human body temperature (37 °C) in 32 h was investigated. The potential harm that the dust could lead to in body glutamic acid acidic environment, namely biological activity, is of great importance for revealing the human toxicological mechanism. The changes of pH values and electric conductivity of suspension of those dusts were similar, increased slowly in the first 8 h, and then the pH values increased rapidly. The total amount of dissolved ions of K, Ca, Na, and Mg was 35.4 to 429 mg/kg, particularly Ca was maximal of 20 to 334 mg/kg. The total amount of dissolved ions of Fe, Zn, Mn, Pb, and Ba was 0.18 to 5.59 mg/kg and in Al and Si was 3.0 to 21.7 mg/kg. The relative solubility order of dusts in glutamic acid is wollastonite > serpentine > sepiolite, the cement plant industrial dusts > natural dusts > power plant industrial dusts. The wollastonite and cement plant industrial dusts have the highest solubility, which also have high content of CaO; this shows that there are a poorer corrosion-resisting ability and lower bio-resistibility. Sepiolite and power plant industrial dusts have lowest solubility, which also have high content of SiO2; this shows that there are a higher corrosion-resisting ability and stronger bio-resistibility.

  2. SYNAPTIC VESICLE PROTEIN TRAFFICKING AT THE GLUTAMATE SYNAPSE

    PubMed Central

    Santos, Magda S.; Li, Haiyan; Voglmaier, Susan M.

    2009-01-01

    Expression of the integral and associated proteins of synaptic vesicles is subject to regulation over time, by region, and in response to activity. The process by which changes in protein levels and isoforms result in different properties of neurotransmitter release involves protein trafficking to the synaptic vesicle. How newly synthesized proteins are incorporated into synaptic vesicles at the presynaptic bouton is poorly understood. During synaptogenesis, synaptic vesicle proteins sort through the secretory pathway and are transported down the axon in precursor vesicles that undergo maturation to form synaptic vesicles. Changes in protein content of synaptic vesicles could involve the formation of new vesicles that either mix with the previous complement of vesicles or replace them, presumably by their degradation or inactivation. Alternatively, new proteins could individually incorporate into existing synaptic vesicles, changing their functional properties. Glutamatergic vesicles likely express many of the same integral membrane proteins and share certain common mechanisms of biogenesis, recycling, and degradation with other synaptic vesicles. However, glutamatergic vesicles are defined by their ability to package glutamate for release, a property conferred by the expression of a vesicular glutamate transporter (VGLUT). VGLUTs are subject to regional, developmental, and activity-dependent changes in expression. In addition, VGLUT isoforms differ in their trafficking, which may target them to different pathways during biogenesis or after recycling, which may in turn sort them to different vesicle pools. Emerging data indicate that differences in the association of VGLUTs and other synaptic vesicle proteins with endocytic adaptors may influence their trafficking. These observations indicate that independent regulation of synaptic vesicle protein trafficking has the potential to influence synaptic vesicle protein composition, the maintenance of synaptic vesicle

  3. AGC1/2, the mitochondrial aspartate-glutamate carriers.

    PubMed

    Amoedo, N D; Punzi, G; Obre, E; Lacombe, D; De Grassi, A; Pierri, C L; Rossignol, R

    2016-10-01

    In this review we discuss the structure and functions of the aspartate/glutamate carriers (AGC1-aralar and AGC2-citrin). Those proteins supply the aspartate synthesized within mitochondrial matrix to the cytosol in exchange for glutamate and a proton. A structure of an AGC carrier is not available yet but comparative 3D models were proposed. Moreover, transport assays performed by using the recombinant AGC1 and AGC2, reconstituted into liposome vesicles, allowed to explore the kinetics of those carriers and to reveal their specific transport properties. AGCs participate to a wide range of cellular functions, as the control of mitochondrial respiration, calcium signaling and antioxydant defenses. AGC1 might also play peculiar tissue-specific functions, as it was found to participate to cell-to-cell metabolic symbiosis in the retina. On the other hand, AGC1 is involved in the glutamate-mediated excitotoxicity in neurons and AGC gene or protein alterations were discovered in rare human diseases. Accordingly, a mice model of AGC1 gene knock-out presented with growth delay and generalized tremor, with myelinisation defects. More recently, AGC was proposed to play a crucial role in tumor metabolism as observed from metabolomic studies showing that the asparate exported from the mitochondrion by AGC1 is employed in the regeneration of cytosolic glutathione. Therefore, given the central role of AGCs in cell metabolism and human pathology, drug screening are now being developed to identify pharmacological modulators of those carriers. This article is part of a Special Issue entitled: Mitochondrial Channels edited by Pierre Sonveaux, Pierre Maechler and Jean-Claude Martinou. PMID:27132995

  4. Arsenic and lead residues in carrots from foliar applications of monosodium methanearsonate (MSMA): A comparison between mineral and organic soils, or from soil residues.

    PubMed

    Zandstra, B H; De Kryger, T A

    2007-01-01

    Carrot roots may absorb arsenic residues when grown in soil that has been treated previously with arsenical pesticides. Arsenic residues in crops also may result from the inappropriate application of post-emergence arsenical herbicides. To compare potential sources of arsenic residues, carrots were planted in mineral or organic soil and treated post-emergence with the herbicide monosodium methanearsonate (MSMA) at 0, 0.56, 1.12, 2.24, 4.48, or 8.96 kg ha(-1). Arsenic concentration in all plant parts declined between 30 days before harvest and harvest. Arsenic concentration in peeled carrot roots ranged from less than the limit of detection (LOD) for untreated carrots to 0.963 mg kg(-1) (fresh weight) at harvest for carrots treated with 8.96 kg ha(-1) MSMA. In another study, carrots were grown in a greenhouse in soil collected from an old orchard site that had been sprayed with lead arsenate for many years. The old orchard site soil had an arsenic level of 110 mg kg(-1), and similar non-orchard soil had an arsenic level of 1.97 mg kg(-1). All carrot plant segments from plants grown in old orchard soil had higher arsenic concentrations than those from non-orchard soil. Peeled carrot roots from non-orchard soil contained 0.034 mg kg(-1) arsenic, while the peeled roots from old orchard soil had 0.135 mg kg(-1). Old orchard soil had a lead level of 496 mg kg(-1), compared with 6.52 mg kg(-1) for non-orchard soil. Peeled carrot roots from old orchard soil contained 0.885 mg kg(-1) lead, and peeled roots from non-orchard soil contained 0.147 mg kg(-1) lead. PMID:17164215

  5. Deer bone extract suppresses articular cartilage damage induced by monosodium iodoacetate in osteoarthritic rats: an in vivo micro-computed tomography study.

    PubMed

    Lee, Hyunji; Park, Yooheon; Ahn, Chang Won; Park, Soo Hyun; Jung, Eun Young; Suh, Hyung Joo

    2014-06-01

    We evaluated the anti-osteoarthritic effects of deer bone extract on articular cartilage damage by using micro-computed tomography (micro-CT) in monosodium iodoacetate (MIA)-induced osteoarthritis (OA) in rats. Male Wistar rats (6 weeks of age) were randomly divided into 5 groups (10 rats/group): sham control (SC; PBS injection+PBS 1 mL treatment); negative control (NC; MIA injection+PBS 1 mL treatment); positive control (PC; MIA injection+250 mg/kg glucosamine sulfate/chondroitin sulfate mixture treatment); low dose (LDB; MIA injection+250 mg/kg deer bone extract treatment); and high dose (HDB; MIA injection+500 mg/kg deer bone extract treatment). After 50 days of treatment, we observed that the administration of deer bone extract protected against bone destruction and reduced the number of erosion lacunae. When deer bone extract was administered, the trabecular thickness distribution (Tb.Th) (LDB: 75.9 μm, HDB: 80.7 μm vs. NC: 48.0 μm) and the trabecular bone volume fraction ratio (BV/TV) (LDB: 43.8%, HDB: 48.2% vs. NC: 39.1%) were significantly restored. Additionally, the trabecular separation (Tb.Sp) increase caused by MIA was decreased significantly with the administration of deer bone extract (LDB: 73.4 μm, HDB: 81.2 μm vs. NC: 112.0 μm). We concluded that the oral administration of deer bone extract effectively relieved the morphological changes induced by MIA injection in an animal model. PMID:24797662

  6. Genetic insights into migraine and glutamate: a protagonist driving the headache.

    PubMed

    Gasparini, Claudia F; Smith, Robert A; Griffiths, Lyn R

    2016-08-15

    Migraine is a complex polygenic disorder that continues to be a great source of morbidity in the developed world with a prevalence of 12% in the Caucasian population. Genetic and pharmacological studies have implicated the glutamate pathway in migraine pathophysiology. Glutamate profoundly impacts brain circuits that regulate core symptom domains in a range of neuropsychiatric conditions and thus remains a "hot" target for drug discovery. Glutamate has been implicated in cortical spreading depression (CSD), the phenomenon responsible for migraine with aura and in animal models carrying FHM mutations. Genotyping case-control studies have shown an association between glutamate receptor genes, namely, GRIA1 and GRIA3 with migraine with indirect supporting evidence from GWAS. New evidence localizes PRRT2 at glutamatergic synapses and shows it affects glutamate signalling and glutamate receptor activity via interactions with GRIA1. Glutamate-system defects have also been recently implicated in a novel FHM2 ATP1A2 disease-mutation mouse model. Adding to the growing evidence neurophysiological findings support a role for glutamate in cortical excitability. In addition to the existence of multiple genes to choreograph the functions of fast-signalling glutamatergic neurons, glutamate receptor diversity and regulation is further increased by the post-translational mechanisms of RNA editing and miRNAs. Ongoing genetic studies, GWAS and meta-analysis implicate neurogenic mechanisms in migraine pathology and the first genome-wide associated locus for migraine on chromosome X. Finally, in addition to glutamate modulating therapies, the kynurenine pathway has emerged as a candidate for involvement in migraine pathophysiology. In this review we discuss recent genetic evidence and glutamate modulating therapies that bear on the hypothesis that a glutamatergic mechanism may be involved in migraine susceptibility. PMID:27423601

  7. Researching glutamate - induced cytotoxicity in different cell lines: a comparative/collective analysis/study.

    PubMed

    Kritis, Aristeidis A; Stamoula, Eleni G; Paniskaki, Krystallenia A; Vavilis, Theofanis D

    2015-01-01

    Although glutamate is one of the most important excitatory neurotransmitters of the central nervous system, its excessive extracellular concentration leads to uncontrolled continuous depolarization of neurons, a toxic process called, excitotoxicity. In excitotoxicity glutamate triggers the rise of intracellular Ca(2+) levels, followed by up regulation of nNOS, dysfunction of mitochondria, ROS production, ER stress, and release of lysosomal enzymes. Excessive calcium concentration is the key mediator of glutamate toxicity through over activation of ionotropic and metabotropic receptors. In addition, glutamate accumulation can also inhibit cystine (CySS) uptake by reversing the action of the CySS/glutamate antiporter. Reversal of the antiporter action reinforces the aforementioned events by depleting neurons of cysteine and eventually glutathione's reducing potential. Various cell lines have been employed in the pursuit to understand the mechanism(s) by which excitotoxicity affects the cells leading them ultimately to their demise. In some cell lines glutamate toxicity is exerted mainly through over activation of NMDA, AMPA, or kainate receptors whereas in other cell lines lacking such receptors, the toxicity is due to glutamate induced oxidative stress. However, in the greatest majority of the cell lines ionotropic glutamate receptors are present, co-existing to CySS/glutamate antiporters and metabotropic glutamate receptors, supporting the assumption that excitotoxicity effect in these cells is accumulative. Different cell lines differ in their responses when exposed to glutamate. In this review article the responses of PC12, SH-SY5Y, HT-22, NT-2, OLCs, C6, primary rat cortical neurons, RGC-5, and SCN2.2 cell systems are systematically collected and analyzed. PMID:25852482

  8. Peripherally restricted viral challenge elevates extracellular glutamate and enhances synaptic transmission in the hippocampus.

    PubMed

    Hunsberger, Holly C; Wang, Desheng; Petrisko, Tiffany J; Alhowail, Ahmad; Setti, Sharay E; Suppiramaniam, Vishnu; Konat, Gregory W; Reed, Miranda N

    2016-07-01

    Peripheral infections increase the propensity and severity of seizures in susceptible populations. We have previously shown that intraperitoneal injection of a viral mimic, polyinosinic-polycytidylic acid (PIC), elicits hypersusceptibility of mice to kainic acid (KA)-induced seizures. This study was undertaken to determine whether this seizure hypersusceptibility entails alterations in glutamate signaling. Female C57BL/6 mice were intraperitoneally injected with PIC, and after 24 h, glutamate homeostasis in the hippocampus was monitored using the enzyme-based microelectrode arrays. PIC challenge robustly increased the level of resting extracellular glutamate. While pre-synaptic potassium-evoked glutamate release was not affected, glutamate uptake was profoundly impaired and non-vesicular glutamate release was augmented, indicating functional alterations of astrocytes. Electrophysiological examination of hippocampal slices from PIC-challenged mice revealed a several fold increase in the basal synaptic transmission as compared to control slices. PIC challenge also increased the probability of pre-synaptic glutamate release as seen from a reduction of paired-pulse facilitation and synaptic plasticity as seen from an enhancement of long-term potentiation. Altogether, our results implicate a dysregulation of astrocytic glutamate metabolism and an alteration of excitatory synaptic transmission as the underlying mechanism for the development of hippocampal hyperexcitability, and consequently seizure hypersusceptibility following peripheral PIC challenge. Peripheral infections/inflammations enhance seizure susceptibility. Here, we explored the effect of peritoneal inflammation induced by a viral mimic on glutamate homeostasis and glutamatergic neurotransmission in the mouse hippocampus. We found that peritoneal inflammation elevated extracellular glutamate concentration and enhanced the probability of pre-synaptic glutamate release resulting in hyperexcitability of

  9. Researching glutamate – induced cytotoxicity in different cell lines: a comparative/collective analysis/study

    PubMed Central

    Kritis, Aristeidis A.; Stamoula, Eleni G.; Paniskaki, Krystallenia A.; Vavilis, Theofanis D.

    2015-01-01

    Although glutamate is one of the most important excitatory neurotransmitters of the central nervous system, its excessive extracellular concentration leads to uncontrolled continuous depolarization of neurons, a toxic process called, excitotoxicity. In excitotoxicity glutamate triggers the rise of intracellular Ca2+ levels, followed by up regulation of nNOS, dysfunction of mitochondria, ROS production, ER stress, and release of lysosomal enzymes. Excessive calcium concentration is the key mediator of glutamate toxicity through over activation of ionotropic and metabotropic receptors. In addition, glutamate accumulation can also inhibit cystine (CySS) uptake by reversing the action of the CySS/glutamate antiporter. Reversal of the antiporter action reinforces the aforementioned events by depleting neurons of cysteine and eventually glutathione’s reducing potential. Various cell lines have been employed in the pursuit to understand the mechanism(s) by which excitotoxicity affects the cells leading them ultimately to their demise. In some cell lines glutamate toxicity is exerted mainly through over activation of NMDA, AMPA, or kainate receptors whereas in other cell lines lacking such receptors, the toxicity is due to glutamate induced oxidative stress. However, in the greatest majority of the cell lines ionotropic glutamate receptors are present, co-existing to CySS/glutamate antiporters and metabotropic glutamate receptors, supporting the assumption that excitotoxicity effect in these cells is accumulative. Different cell lines differ in their responses when exposed to glutamate. In this review article the responses of PC12, SH-SY5Y, HT-22, NT-2, OLCs, C6, primary rat cortical neurons, RGC-5, and SCN2.2 cell systems are systematically collected and analyzed. PMID:25852482

  10. Imaging extracellular waves of glutamate during calcium signaling in cultured astrocytes.

    PubMed

    Innocenti, B; Parpura, V; Haydon, P G

    2000-03-01

    A growing body of evidence proposes that glial cells have the potential to play a role as modulators of neuronal activity and synaptic transmission by releasing the neurotransmitter glutamate (Arague et al., 1999). We explore the spatial nature of glutamate release from astrocytes with an enzyme-linked assay system and CCD imaging technology. In the presence of glutamate, L-glutamic dehydrogenase (GDH) reduces NAD(+) to NADH, a product that fluoresces when excited with UV light. Theoretically, provided that GDH and NAD(+) are present in the bathing saline, the release of glutamate from stimulated astrocytes can be optically detected by monitoring the accumulation of NADH. Indeed, stimuli that induce a wave of elevated calcium among astrocytes produced a corresponding spread of extracellular NADH fluorescence. Treatment of cultures either with thapsigargin, to deplete internal calcium stores, or with the membrane-permeant calcium chelator BAPTA AM significantly decreased the accumulation of NADH, demonstrating that this fluorometric assay effectively monitors calcium-dependent glutamate release. With a temporal resolution of 500 msec and spatial resolution of approximately 20 micrometer, discrete regions of glutamate release were not reliably resolved. The wave of glutamate release that underlies the NADH fluorescence propagated at an average speed of approximately 26 micrometer/sec, correlating with the rate of calcium wave progression (10-30 micrometer/sec), and caused a localized accumulation of glutamate in the range of 1-100 microM. Further analysis of the fluorescence accumulation clearly demonstrated that glutamate is released in a regenerative manner, with subsequent cells that are involved in the calcium wave releasing additional glutamate. PMID:10684881

  11. Biochemical and spectroscopic properties of Brucella microti glutamate decarboxylase, a key component of the glutamate-dependent acid resistance system

    PubMed Central

    Grassini, Gaia; Pennacchietti, Eugenia; Cappadocio, Francesca; Occhialini, Alessandra; De Biase, Daniela

    2015-01-01

    In orally acquired bacteria, the ability to counteract extreme acid stress (pH ⩽ 2.5) ensures survival during transit through the animal host stomach. In several neutralophilic bacteria, the glutamate-dependent acid resistance system (GDAR) is the most efficient molecular system in conferring protection from acid stress. In Escherichia coli its structural components are either of the two glutamate decarboxylase isoforms (GadA, GadB) and the antiporter, GadC, which imports glutamate and exports γ-aminobutyrate, the decarboxylation product. The system works by consuming protons intracellularly, as part of the decarboxylation reaction, and exporting positive charges via the antiporter. Herein, biochemical and spectroscopic properties of GadB from Brucella microti (BmGadB), a Brucella species which possesses GDAR, are described. B. microti belongs to a group of lately described and atypical brucellae that possess functional gadB and gadC genes, unlike the most well-known “classical” Brucella species, which include important human pathogens. BmGadB is hexameric at acidic pH. The pH-dependent spectroscopic properties and activity profile, combined with in silico sequence comparison with E. coli GadB (EcGadB), suggest that BmGadB has the necessary structural requirements for the binding of activating chloride ions at acidic pH and for the closure of its active site at neutral pH. On the contrary, cellular localization analysis, corroborated by sequence inspection, suggests that BmGadB does not undergo membrane recruitment at acidic pH, which was observed in EcGadB. The comparison of GadB from evolutionary distant microorganisms suggests that for this enzyme to be functional in GDAR some structural features must be preserved. PMID:25853037

  12. Glutamate Oxaloacetate Transaminase in Pea Root Nodules 1

    PubMed Central

    Appels, Michiel A.; Haaker, Huub

    1991-01-01

    Glutamate oxaloacetate transaminase (l-glutamate: oxaloacetate aminotransferase, EC 2.6.1.1 [GOT]), a key enzyme in the flow of carbon between the organic acid and amino acid pools in pea (Pisum sativum L.) root nodules, was studied. By ion exchange chromatography, the presence of two forms of GOT in the cytoplasm of pea root nodule cells was established. The major root nodule form was present in only a small quantity in the cytoplasm of root cells. Fractionation of root nodule cell extracts demonstrated that the increase in the GOT activity during nodule development was due to the increase of the activity in the cytoplasm of the plant cells, and not to an increase in activity in the plastids or in the mitochondria. The kinetic properties of the different cytoplasmic forms of GOT were studied. Some of the Km values differed, but calculations indicated that not the kinetic properties but a high concentration of the major root nodule form caused the observed increase in GOT activity in the pea root nodules. It was found that the reactions of the malate/aspartate shuttle are catalyzed by intact bacteroids, and that these reactions can support nitrogen fixation. It is proposed that the main function of the nodule-stimulated cytoplasmic form of GOT is participation in this shuttle. PMID:16668048

  13. Conformation of poly(γ-glutamic acid) in aqueous solution.

    PubMed

    Muroga, Yoshio; Nakaya, Asami; Inoue, Atsuki; Itoh, Daiki; Abiru, Masaya; Wada, Kaori; Takada, Masako; Ikake, Hiroki; Shimizu, Shigeru

    2016-04-01

    Local conformation and overall conformation of poly(γ-DL-glutamic acid) (PγDLGA) and poly(γ-L-glutamic acid) (PγLGA) in aqueous solution was studied as a function of degree of ionization ε by (1) H-NMR, circular dichroism, and potentiometric titration. It was clarified that their local conformation is represented by random coil over an entire ε range and their overall conformation is represented by expanded random-coil in a range of ε > ε(*) , where ε(*) is about 0.3, 0.35, 0.45, and 0.5 for added-salt concentration of 0.02M, 0.05M, 0.1M, and 0.2M, respectively. In a range of ε < ε(*) , however, ε dependence of their overall conformation is significantly differentiated from each other. PγDLGA tends to aggregate intramolecularly and/or intermolecularly with decreasing ε, but PγLGA still behaves as expanded random-coil. It is speculated that spatial arrangement of adjacent carboxyl groups along the backbone chain essentially affects the overall conformation of PγGA in acidic media. PMID:26574908

  14. Structural mechanism of glutamate receptor activation and desensitization.

    PubMed

    Meyerson, Joel R; Kumar, Janesh; Chittori, Sagar; Rao, Prashant; Pierson, Jason; Bartesaghi, Alberto; Mayer, Mark L; Subramaniam, Sriram

    2014-10-16

    Ionotropic glutamate receptors are ligand-gated ion channels that mediate excitatory synaptic transmission in the vertebrate brain. To gain a better understanding of how structural changes gate ion flux across the membrane, we trapped rat AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) and kainate receptor subtypes in their major functional states and analysed the resulting structures using cryo-electron microscopy. We show that transition to the active state involves a 'corkscrew' motion of the receptor assembly, driven by closure of the ligand-binding domain. Desensitization is accompanied by disruption of the amino-terminal domain tetramer in AMPA, but not kainate, receptors with a two-fold to four-fold symmetry transition in the ligand-binding domains in both subtypes. The 7.6 Å structure of a desensitized kainate receptor shows how these changes accommodate channel closing. These findings integrate previous physiological, biochemical and structural analyses of glutamate receptors and provide a molecular explanation for key steps in receptor gating. PMID:25119039

  15. Abnormal glutamate release in aged BTBR mouse model of autism

    PubMed Central

    Wei, Hongen; Ding, Caiyun; Jin, Guorong; Yin, Haizhen; Liu, Jianrong; Hu, Fengyun

    2015-01-01

    Autism is a neurodevelopmental disorder characterized by abnormal reciprocal social interactions, communication deficits, and repetitive behaviors with restricted interests. Most of the available research on autism is focused on children and young adults and little is known about the pathological alternation of autism in older adults. In order to investigate the neurobiological alternation of autism in old age stage, we compared the morphology and synaptic function of excitatory synapses between the BTBR mice with low level sociability and B6 mice with high level sociability. The results revealed that the number of excitatory synapse colocalized with pre- and post-synaptic marker was not different between aged BTBR and B6 mice. The aged BTBR mice had a normal structure of dendritic spine and the expression of Shank3 protein in the brain as well as that in B6 mice. The baseline and KCl-evoked glutamate release from the cortical synaptoneurosome in aged BTBR mice was lower than that in aged B6 mice. Overall, the data indicate that there is a link between disturbances of the glutamate transmission and autism. These findings provide new evidences for the hypothesis of excitation/inhibition imbalance in autism. Further work is required to determine the cause of this putative abnormality. PMID:26617779

  16. Metabotropic Glutamate Receptor Dependent Cortical Plasticity in Chronic Pain.

    PubMed

    Koga, Kohei; Li, Shermaine; Zhuo, Min

    2016-01-01

    Many cortical areas play crucial roles in higher order brain functions such as pain and emotion-processing, decision-making, and cognition. Among them, anterior cingulate cortex (ACC) and insular cortex (IC) are two key areas. Glutamate mediates major excitatory transmission during long-term plasticity in both physiological and pathological conditions. Specifically related to nociceptive or pain behaviors, metabotropic glutamate subtype receptors (mGluRs) have been involved in different types of synaptic modulation and plasticity from periphery to the spinal cord. However, less is known about their functional roles in plasticity related to pain and its related behaviors within cortical regions. In this review, we first summarized previous studies of synaptic plasticity in both the ACC and IC, and discussed how mGluRs may be involved in both cortical long-term potentiation (LTP) and long-term depression (LTD)-especially in LTD. The activation of mGluRs contributes to the induction of LTD in both ACC and IC areas. The loss of LTD caused by peripheral amputation or nerve injury can be rescued by priming ACC or IC with activations of mGluR1 receptors. We also discussed the potential functional roles of mGluRs for pain-related behaviors. We propose that targeting mGluRs in the cortical areas including the ACC and IC may provide a new therapeutic strategy for the treatment of chronic pain, phantom pain or anxiety. PMID:27296638

  17. Variant ionotropic glutamate receptors as chemosensory receptors in Drosophila

    PubMed Central

    Benton, Richard; Vannice, Kirsten S.; Gomez-Diaz, Carolina; Vosshall, Leslie B.

    2009-01-01

    Summary Ionotropic glutamate receptors (iGluRs) mediate neuronal communication at synapses throughout vertebrate and invertebrate nervous systems. We have characterized a novel family of iGluR-related genes in Drosophila, which we name Ionotropic Receptors (IRs). These receptors do not belong to the well-described Kainate, AMPA, or NMDA classes of iGluRs, and have divergent ligand-binding domains that lack their characteristic glutamate-interacting residues. IRs are expressed in a combinatorial fashion in sensory neurons that respond to many distinct odors but do not express either insect odorant receptors (ORs) or gustatory receptors (GRs). IR proteins accumulate in sensory dendrites and not at synapses. Mis-expression of IRs induces novel odor responses in ectopic neurons. Together, these results lead us to propose that the IRs comprise a novel family of chemosensory receptors. Conservation of IR/iGluR-related proteins in bacteria, plants, and animals suggests that this receptor family represents an evolutionarily ancient mechanism for sensing both internal and external chemical cues. PMID:19135896

  18. Activity-Dependent Plasticity of Astroglial Potassium and Glutamate Clearance

    PubMed Central

    Cheung, Giselle; Sibille, Jérémie; Zapata, Jonathan; Rouach, Nathalie

    2015-01-01

    Recent evidence has shown that astrocytes play essential roles in synaptic transmission and plasticity. Nevertheless, how neuronal activity alters astroglial functional properties and whether such properties also display specific forms of plasticity still remain elusive. Here, we review research findings supporting this aspect of astrocytes, focusing on their roles in the clearance of extracellular potassium and glutamate, two neuroactive substances promptly released during excitatory synaptic transmission. Their subsequent removal, which is primarily carried out by glial potassium channels and glutamate transporters, is essential for proper functioning of the brain. Similar to neurons, different forms of short- and long-term plasticity in astroglial uptake have been reported. In addition, we also present novel findings showing robust potentiation of astrocytic inward currents in response to repetitive stimulations at mild frequencies, as low as 0.75 Hz, in acute hippocampal slices. Interestingly, neurotransmission was hardly affected at this frequency range, suggesting that astrocytes may be more sensitive to low frequency stimulation and may exhibit stronger plasticity than neurons to prevent hyperexcitability. Taken together, these important findings strongly indicate that astrocytes display both short- and long-term plasticity in their clearance of excess neuroactive substances from the extracellular space, thereby regulating neuronal activity and brain homeostasis. PMID:26346563

  19. Stability of Poly(α-L Glutamic Acid).

    NASA Astrophysics Data System (ADS)

    Choi, Peter; Chen, Y. Z.; Prohofsky, E. W.

    1996-03-01

    For the protein to go to their folded biologically active state, it must first undergo formation of the stabilizing α-helix structure. Taking the repeating unit cells of Glutamic acid in an α-helix structure, the analysis can be made of the vibrational dynamics of the Poly(α-L Glutamic acid). The method used was mean field, modified, self-consistent phonon theory (MSPA) developed by Prohofsky et al. The modes contributing to the fluctuations of the α-helix hydrogen bonds were analyzed yielding the break down probability from the room temperature to the critical temperature Tc where the hydrogen bond probability is over 0.5. The inverse proportionality of the opening bond probability to the relaxation time τ * was then used to compare our results to ultra sonic and electric-field jump experiments. These experiments were done at temperatures ranging from 295 K to 310 K. The data obtained from these experiments agrees well with the temperature dependent MSPA open bond probabilities with correlation constant of (1.6 ± 0.1)x10e-8. Our calculation also yielded critical melting temperature of Tc=332 K.

  20. Dopamine-glutamate interactions in the basal ganglia.

    PubMed

    Schmidt, W J

    1998-01-01

    In an attempt to formulate a working hypothesis of basal-ganglia functions, arguments are considered suggesting that the basal ganglia are involved in a process of response selection i.e. in the facilitation of "wanted" and in the suppression of "unwanted" behaviour. The meso-accumbal dopamine-system is considered to mediate natural and drug-induced reward and sensitization. The meso-striatal dopamine-system seems to fulfill similar functions: It may mediate reinforcement which strengthens a given behaviour when elicited subsequently, but which is not experienced as reward or hedonia. Glutamate as the transmitter of the corticofugal projections to the basal ganglia nuclei and of the subthalamic neurons is critically involved in basal ganglia functions and dysfunctions; for example Parkinson's disease can be considered to be a secondary hyperglutamatergic disease. Additionally, glutamate is an essential factor in the plasticity response of the basal-ganglia. However, opposite to previous suggestions, the NMDA-receptor blocker MK-801 does not prevent psychostimulant- nor morphine-induced day to day increase (sensitization) of locomotion. Also the day to day increase of haloperidol-induced catalepsy was not prevented by MK-801. PMID:9871434