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Sample records for elevated insular glutamate

  1. Memory Trace Reactivation and Behavioral Response during Retrieval Are Differentially Modulated by Amygdalar Glutamate Receptors Activity: Interaction between Amygdala and Insular Cortex

    ERIC Educational Resources Information Center

    Osorio-Gómez, Daniel; Guzmán-Ramos, Kioko; Bermúdez-Rattoni, Federico

    2017-01-01

    The insular cortex (IC) is required for conditioned taste aversion (CTA) retrieval. However, it remains unknown which cortical neurotransmitters levels are modified upon CTA retrieval. Using in vivo microdialysis, we observed that there were clear elevations in extracellular glutamate, norepinephrine, and dopamine in and around the center of the…

  2. Memory Trace Reactivation and Behavioral Response during Retrieval Are Differentially Modulated by Amygdalar Glutamate Receptors Activity: Interaction between Amygdala and Insular Cortex

    ERIC Educational Resources Information Center

    Osorio-Gómez, Daniel; Guzmán-Ramos, Kioko; Bermúdez-Rattoni, Federico

    2017-01-01

    The insular cortex (IC) is required for conditioned taste aversion (CTA) retrieval. However, it remains unknown which cortical neurotransmitters levels are modified upon CTA retrieval. Using in vivo microdialysis, we observed that there were clear elevations in extracellular glutamate, norepinephrine, and dopamine in and around the center of the…

  3. Cardiovascular and single-unit responses to L-glutamate injection into the posterior insular cortex in rat.

    PubMed

    Ranjbar, A; Hatam, M; Nasimi, A

    2015-10-15

    The insular cortex in rat is a longitudinal strip that runs along the rostral half of the rhinal fissure. The previous studies showed connections between the posterior insular cortex (PIC) and some major cardiovascular centers. Based on the stimulation site, electrical or chemical stimulation of the PIC induced an increase or a decrease in blood pressure (BP) and heart rate (HR). There is no report of simultaneous cardiovascular and single-unit recording microinjection of Glut in the PIC. In this study, L-glutamate was microinjected into the PIC of urethane anesthetized rats and arterial pressure, HR and single-unit responses were recorded simultaneously. Also the response of the neurons to baroreceptor activation was explored. Glut produced five types of long oscillatory, pressor, depressor, bradycardic and tachycardic cardiovascular responses, with no association between pressure and HR responses. We also observed five single-unit responses, consisting of short excitatory, long oscillatory, excitatory, inhibitory and mixed responses. There was an association between oscillation in BP and in single-unit response. There were some differences between the two sides especially for single-unit responses. In conclusion, there were five types of cardiovascular and five types of single-unit responses, to Glut microinjection into PIC, from which three types were correlated. The left side of the PIC is involved more in the cardiovascular functions. These data along with the fact that most recorded neurons responded to baroreceptor activation, might imply the presence of feedback systems in the PIC, producing irregularity in BP and HR. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  4. Disruptions in Serotonergic Regulation of Cortical Glutamate Release in Primate Insular Cortex in Response to Chronic Ethanol and Nursery Rearing

    PubMed Central

    Alexander, Georgia M.; Graef, John D.; Hammarback, James A.; Nordskog, Brian K.; Burnett, Elizabeth J.; Daunais, James B.; Bennett, Allyson J.; Friedman, David P.; Suomi, Stephen J.; Godwin, Dwayne W.

    2015-01-01

    Early-life stress has been shown to increase susceptibility to anxiety and substance abuse. Disrupted activity within the anterior insular cortex (AIC) has been shown to play a role in both of these disorders. Altered serotonergic processing is implicated in controlling the activity levels of the associated cognitive networks. We therefore investigated changes in both serotonin receptor expression and glutamatergic synaptic activity in the AIC of alcohol-drinking rhesus monkeys. We studied tissues from male rhesus monkeys raised under two conditions: Male rhesus monkeys 1) “Mother reared” (MR) by adult females (n=9), or; 2) “Nursery reared” (NR), i.e., separated from their mothers and reared as a separate group under surrogate/peer-reared conditions (n=9). The NR condition represents a long-standing and well-validated nonhuman primate model of early life stress. All monkeys were trained to self-administer ethanol (4% w/v) or an isocaloric maltose-dextrin control solution. Subsets from each rearing condition were then given daily access to either ethanol, water or maltose dextrin for 12 months. Tissues were collected at necropsy and were further analyzed. Using real time RT-PCR we found that ethanol-naïve, NR monkeys had lower AIC levels of 5-HT1A and 5-HT2A receptor mRNA compared to ethanol-naïve, MR animals. While NR monkeys consumed more ethanol over the 12-month period compared to MR animals, both MR and NR animals expressed greater 5-HT1A and 5-HT2A receptor mRNA levels following chronic alcohol self-administration. The interaction between nursery-rearing conditions and alcohol consumption resulted in a significant enhancement of both 5-HT1A and 5-HT2A receptor mRNA levels such that lower expression levels observed in nursery rearing conditions were not found in the alcohol self-administration group. Using voltage clamp recordings in the whole cell configuration we recorded excitatory postsynaptic currents in both ethanol-naïve and chronic self

  5. Peripheral viral challenge elevates extracellular glutamate in the hippocampus leading to seizure hypersusceptibility.

    PubMed

    Hunsberger, Holly C; Konat, Gregory W; Reed, Miranda N

    2017-02-28

    Peripheral viral infections increase seizure propensity and intensity in susceptible individuals. We have modeled this comorbidity by demonstrating that the acute phase response instigated by an intraperitoneal (i.p.) injection of a viral mimetic, polyinosinic-polycytidylic acid (PIC), induces protracted hypersusceptibility to kainic acid-induced seizures. We have further demonstrated that PIC challenge robustly increases the level of tonic extracellular glutamate and neuronal excitability in the hippocampus. This study was undertaken to determine a relationship between tonic glutamate and seizure susceptibility following PIC challenge. Briefly, glutamate-sensing microelectrodes were permanently implanted into the CA1 of 8-week-old female C57BL/6 mice. Following a 3-day recovery, acute phase response was induced by i.p. injection of 12 mg/kg of PIC, while saline-injected mice served as controls. Tonic glutamate was measured at 1, 2, 3 and 4 days after PIC challenge. PIC challenge induced an approximately fourfold increase in tonic glutamate levels measured after 24 h. The levels gradually declined to the baseline values within 4 days. Twenty-four hours after PIC challenge, the mice featured an approximately threefold increase in cumulative seizure scores and twofold increase in the duration of status epilepticus induced by subcutaneous injection of 12 mg/kg of kainic acid. Seizure scores positively correlated with pre-seizure tonic glutamate. Moreover, seizures resulted in a profound (76%) elevation of extracellular glutamate in the CA1 of PIC-challenged but not saline-injected mice. Our results implicate the increase in extracellular glutamate as a mediator of seizure hypersusceptibility induced by peripheral viral challenge.

  6. Elevated baseline serum glutamate as a pharmacometabolomic biomarker for acamprosate treatment outcome in alcohol-dependent subjects

    PubMed Central

    Nam, H W; Karpyak, V M; Hinton, D J; Geske, J R; Ho, A M C; Prieto, M L; Biernacka, J M; Frye, M A; Weinshilboum, R M; Choi, D-S

    2015-01-01

    Acamprosate has been widely used since the Food and Drug Administration approved the medication for treatment of alcohol use disorders (AUDs) in 2004. Although the detailed molecular mechanism of acamprosate remains unclear, it has been largely known that acamprosate inhibits glutamate action in the brain. However, AUD is a complex and heterogeneous disorder. Thus, biomarkers are required to prescribe this medication to patients who will have the highest likelihood of responding positively. To identify pharmacometabolomic biomarkers of acamprosate response, we utilized serum samples from 120 alcohol-dependent subjects, including 71 responders (maintained continuous abstinence) and 49 non-responders (any alcohol use) during 12 weeks of acamprosate treatment. Notably, baseline serum glutamate levels were significantly higher in responders compared with non-responders. Importantly, serum glutamate levels of responders are normalized after acamprosate treatment, whereas there was no significant glutamate change in non-responders. Subsequent functional studies in animal models revealed that, in the absence of alcohol, acamprosate activates glutamine synthetase, which synthesizes glutamine from glutamate and ammonia. These results suggest that acamprosate reduces serum glutamate levels for those who have elevated baseline serum glutamate levels among responders. Taken together, our findings demonstrate that elevated baseline serum glutamate levels are a potential biomarker associated with positive acamprosate response, which is an important step towards development of a personalized approach to treatment for AUD. PMID:26285131

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

    PubMed

    Banday, Viqar Showkat; Lejon, Kristina

    2017-02-01

    Although type 1 diabetes (T1D) is a T-cell-mediated disease in the effector stage, the mechanism behind the initial beta cell assault is less understood. Metabolomic differences, including elevated levels of glutamic acid, have been observed in patients with T1D before disease onset, as well as in pre-diabetic non-obese diabetic (NOD) mice. Increased levels of glutamic acid damage both neurons and beta cells, implying that this could contribute to the initial events of T1D pathogenesis. We investigated the underlying genetic factors and consequences of the increased levels of glutamic acid in NOD mice. Serum glutamic acid levels from a (NOD×B6)F2 cohort (n = 182) were measured. By genome-wide and Idd region targeted microsatellite mapping, genetic association was detected for six regions including Idd2, Idd4 and Idd22. In silico analysis of potential enzymes and transporters located in and around the mapped regions that are involved in glutamic acid metabolism consisted of alanine aminotransferase, glutamic-oxaloacetic transaminase, aldehyde dehydrogenase 18 family, alutamyl-prolyl-tRNA synthetase, glutamic acid transporters GLAST and EAAC1. Increased EAAC1 protein expression was observed in lysates from livers of NOD mice compared with B6 mice. Functional consequence of the elevated glutamic acid level in NOD mice was tested by culturing NOD. Rag2(-/-) Langerhans' islets with glutamic acid. Induction of apoptosis of the islets was detected upon glutamic acid challenge using TUNEL assay. Our results support the notion that a dysregulated metabolome could contribute to the initiation of T1D. We suggest that targeting of the increased glutamic acid in pre-diabetic patients could be used as a potential therapy. © 2016 John Wiley & Sons Ltd.

  8. Malignant infarction in cats after prolonged middle cerebral artery occlusion: glutamate elevation related to decrease of cerebral perfusion pressure.

    PubMed

    Toyota, Shingo; Graf, Rudolf; Valentino, Mario; Yoshimine, Toshiki; Heiss, Wolf-Dieter

    2002-05-01

    To study the putative role and predictive significance of glutamate elevation in space-occupying ischemic stroke, we investigated the correlation between perfusional disturbances and glutamate alterations in a transient ischemia model in cats that is susceptible to secondary deterioration after reperfusion. In 10 halothane-anesthetized cats, the left middle cerebral artery was occluded for 3 hours, followed by 6 hours of reperfusion. Laser-Doppler flowmetry (LDF) probes, microdialysis/high-performance liquid chromatography, and pressure sensors measured simultaneously regional cerebral blood flow (CBF), extracellular amino acids, mean arterial blood pressure, and intracranial pressure, respectively. Cerebral perfusion pressure (CPP) was calculated. In complementary experiments (n=2), regional CBF was assessed by sequential positron emission tomography. Middle cerebral artery occlusion reduced LDF-measured CBF in all animals to <25% of control. In 5 of 10 cats, glutamate rose approximately 30-fold during ischemia. LDF-measured CBF and glutamate primarily recovered after reperfusion. Glutamate rose again in the late reperfusion phase, when CPP decreased to <60 mm Hg, and symptoms of transtentorial herniation were recognized. Positron emission tomography revealed ischemic thresholds of 15 to 20 mL/100 g per minute for secondary deterioration. In the other 5 cats, ischemic elevation of glutamate was significantly smaller, and signs of secondary deterioration were not recognized. Glutamate determinations during ischemia predict fatal outcome, as do intracranial pressure and CPP measurements during early reperfusion. Secondary amino acid elevation during reperfusion is presumably caused by a drastic decrease of CPP to <50 mm Hg in the final stage of space-occupying, malignant focal ischemia. At this stage, a further progression of injury due to increased glutamate may be irrelevant with respect to fatal outcome.

  9. Depletion of serotonin in the basolateral amygdala elevates glutamate receptors and facilitates fear-potentiated startle

    PubMed Central

    Tran, L; Lasher, B K; Young, K A; Keele, N B

    2013-01-01

    Our previous experiments demonstrated that systemic depletion of serotonin (5-hydroxytryptamine, 5-HT), similar to levels reported in patients with emotional disorders, enhanced glutamateric activity in the lateral nucleus of the amygdala (LA) and potentiated fear behaviors. However, the effects of isolated depletion of 5-HT in the LA, and the molecular mechanisms underlying enhanced glutamatergic activity are unknown. In the present study, we tested the hypothesis that depletion of 5-HT in the LA induces increased fear behavior, and concomitantly enhances glutamate receptor (GluR) expression. Bilateral infusions of 5,7-dihydroxytryptamine (4 μg per side) into the LA produced a regional reduction of serotonergic fibers, resulting in decreased 5-HT concentrations. The induction of low 5-HT in the LA elevated fear-potentiated startle, with a parallel increase in GluR1 mRNA and GluR1 protein expression. These findings suggest that low 5-HT concentrations in the LA may facilitate fear behavior through enhanced GluR-mediated mechanisms. Moreover, our data support a relationship between 5-HT and glutamate in psychopathologies. PMID:24002084

  10. Elevation of 2-AG by monoacylglycerol lipase inhibition in the visceral insular cortex interferes with anticipatory nausea in a rat model.

    PubMed

    Limebeer, Cheryl L; Rock, Erin M; Puvanenthirarajah, Nirushan; Niphakis, Micah J; Cravatt, Benjamin F; Parker, Linda A

    2016-04-01

    Anticipatory nausea (AN) is a conditioned nausea reaction experienced by chemotherapy patients upon returning to the clinic. Currently, there are no specific treatments for this phenomenon, with the classic antiemetic treatments (e.g., ondansetron) providing no relief. The rat model of AN, contextually elicited conditioned gaping reactions in rats, provides a tool for assessing potential treatments for this difficult to treat disorder. Systemically administered drugs which elevate the endocannabinoids, anandamide (AEA) and 2-arachidonoyl glycerol (2-AG), by interfering with their respective degrading enzymes, fatty acid amide hydrolase (FAAH) and monoacyl glycerol lipase (MAGL) interfere with AN in the rat model. We have shown that MAGL inhibition within the visceral insular cortex (VIC) interferes with acute nausea in the gaping model (Sticht et al., 2015). Here we report that bilateral infusion of the MAGL inhibitor, MJN110 (but neither the FAAH inhibitor, PF3845, nor ondansetron) into the VIC suppressed contextually elicited conditioned gaping, and this effect was reversed by coadministration of the CB1 antagonist, AM251. These findings suggest that 2-AG within the VIC plays a critical role in the regulation of both acute nausea and AN. Because there are currently no specific therapeutics for chemotherapy patients that develop anticipatory nausea, MAGL inhibition by MJN110 may be a candidate treatment. (PsycINFO Database Record

  11. Selective effects of potassium elevations on glutamate signaling and action potential conduction in hippocampus.

    PubMed

    Meeks, Julian P; Mennerick, Steven

    2004-01-07

    High-frequency synaptic transmission is depressed by moderate rises in the extracellular potassium concentration ([K+]o). Previous reports have indicated that depression of action potential signaling may underlie the synaptic depression. Here, we investigated the specific contribution of K+-induced action potential changes to synaptic depression. We found that glutamatergic transmission in the hippocampal area CA1 was significantly depressed by 8-10 mM [K+]o, but that GABAergic transmission remained intact. Riluzole, a drug that slows recovery from inactivation of voltage-gated sodium channels (NaChs), interacts with subthreshold [K+]o to depress afferent volleys and EPSCs strongly. Thus, elevated [K+]o likely depresses synapses by slowing NaCh recovery from inactivation. It is unclear from previous studies whether [K+]o-induced action potential depression is caused by changes in initiation, reliability, or waveform. We investigated these possibilities explicitly. [K+]o-induced afferent volley depression was independent of stimulus strength, suggesting that changes in action potential initiation do not explain [K+]o-induced depression. Measurements of action potentials from single axons revealed that 8 mM [K+]o increased conduction failures in a subpopulation of fibers and depressed action potential amplitude in all fibers. Together, these changes quantitatively account for the afferent volley depression. We estimate that conduction failure explains more than half of the synaptic depression observed at 8 mM [K+]o, with the remaining depression likely explained by waveform changes. These mechanisms of selective sensitivity of glutamate release to [K+]o accumulation represent a unique neuromodulatory mechanism and a brake on runaway excitation.

  12. Insular cortex lesions, cardiac troponin, and detection of previously unknown atrial fibrillation in acute ischemic stroke: insights from the troponin elevation in acute ischemic stroke study.

    PubMed

    Scheitz, Jan F; Erdur, Hebun; Haeusler, Karl Georg; Audebert, Heinrich J; Roser, Mattias; Laufs, Ulrich; Endres, Matthias; Nolte, Christian H

    2015-05-01

    Detection rates of paroxysmal atrial fibrillation (AF) after acute ischemic stroke increase with duration of ECG monitoring. To date, it is unknown which patient group may benefit most from intensive monitoring strategies. Therefore, we aimed to identify predictors of previously unknown AF during in-hospital ECG monitoring. All consecutive patients with imaging-confirmed ischemic stroke admitted to our tertiary care hospital from February 2011 to December 2013 were registered prospectively. Patients received continuous bedside ECG monitoring for at least 24 hours. Detection of previously unknown AF during in-hospital ECG monitoring was obtained from medical records. Patients with AF on admission ECG or known history of AF were excluded from analysis. Among 1228 patients (median age, 73 years; median National Institutes of Health Stroke Scale, 4; 43.4% women), previously unknown AF was detected in 114 (9.3%) during a median time of continuous ECG monitoring of 3 days (interquartile range, 2-4 days). Duration of monitoring (P<0.01), older age (P<0.01), history of hypertension (P=0.03), insular cortex involvement (P<0.01), and higher high-sensitivity cardiac troponin T (P=0.04) on admission were independently associated with subsequent detection of AF in a multiple regression analysis. Addition of high-sensitivity cardiac troponin T, insular cortex stroke, or both to the CHADS2 score (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, stroke [2P]) significantly improved c-statistics from 0.63 to 0.68 (P=0.01), 0.70 (P<0.01), and 0.72 (P<0.001), respectively. Insular cortex involvement, higher admission high-sensitivity cardiac troponin T, older age, hypertension, and longer monitoring are associated with new detection of AF during in-hospital ECG monitoring. Patients with higher high-sensitivity cardiac troponin T or insular cortex involvement may be candidates for prolonged ECG monitoring. © 2015 American Heart Association, Inc.

  13. Elevated ammonium levels: differential acute effects on three glutamate transporter isoforms.

    PubMed

    Søgaard, Rikke; Novak, Ivana; MacAulay, Nanna

    2012-03-15

    Increased ammonium (NH(4)(+)/NH(3)) in the brain is a significant factor in the pathophysiology of hepatic encephalopathy, which involves altered glutamatergic neurotransmission. In glial cell cultures and brain slices, glutamate uptake either decreases or increases following acute ammonium exposure but the factors responsible for the opposing effects are unknown. Excitatory amino acid transporter isoforms EAAT1, EAAT2, and EAAT3 were expressed in Xenopus oocytes to study effects of ammonium exposure on their individual function. Ammonium increased EAAT1- and EAAT3-mediated [(3)H]glutamate uptake and glutamate transport currents but had no effect on EAAT2. The maximal EAAT3-mediated glutamate transport current was increased but the apparent affinities for glutamate and Na(+) were unaltered. Ammonium did not affect EAAT3-mediated transient currents, indicating that EAAT3 surface expression was not enhanced. The ammonium-induced stimulation of EAAT3 increased with increasing extracellular pH, suggesting that the gaseous form NH(3) mediates the effect. An ammonium-induced intracellular alkalinization was excluded as the cause of the enhanced EAAT3 activity because 1) ammonium acidified the oocyte cytoplasm, 2) intracellular pH buffering with MOPS did not reduce the stimulation, and 3) ammonium enhanced pH-independent cysteine transport. Our data suggest that the ammonium-elicited uptake stimulation is not caused by intracellular alkalinization or changes in the concentrations of cotransported ions but may be due to a direct effect on EAAT1/EAAT3. We predict that EAAT isoform-specific effects of ammonium combined with cell-specific differences in EAAT isoform expression may explain the conflicting reports on ammonium-induced changes in glial glutamate uptake.

  14. Insular epilepsy surgery.

    PubMed

    Laoprasert, Pramote; Ojemann, Jeffrey G; Handler, Michael H

    2017-04-01

    Since it was originally described nearly 70 years ago, insular epilepsy has been increasingly recognized and may explain failures after apparently well-planned operations. We review the history of awareness of the phenomenon, techniques for its assessment, and its surgical management. Insular epilepsy can mimic features of frontal, parietal, or temporal seizures. It should be considered when a combination of somatosensory, visceral, and motor symptoms is observed early in a seizure. Extraoperative intracranial recordings are required to accurately diagnose insular seizures. Stereo-electroencephalography (EEG) or craniotomy with implantation of surface and depth electrodes have been used successfully to identify insular onset of seizures. Surgical resection of an insular focus may be performed with good success and acceptable risk. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

  15. Treatment-Resistant Schizophrenia Patients Show Elevated Anterior Cingulate Cortex Glutamate Compared to Treatment-Responsive.

    PubMed

    Mouchlianitis, Elias; Bloomfield, Michael A P; Law, Vincent; Beck, Katherine; Selvaraj, Sudhakar; Rasquinha, Naresh; Waldman, Adam; Turkheimer, Federico E; Egerton, Alice; Stone, James; Howes, Oliver D

    2016-05-01

    Resistance to antipsychotic treatment is a significant clinical problem in patients with schizophrenia with approximately 1 in 3 showing limited or no response to repeated treatments with antipsychotic medication. The neurobiological basis for treatment resistance is unknown but recent evidence implicates glutamatergic function in the anterior cingulate cortex. We examined glutamate levels of chronically ill treatment-resistant patients directly compared to treatment-responsive patients. We acquired proton magnetic resonance spectroscopy (1H-MRS) at 3 Tesla from 21 treatment-resistant and 20 treatment-responsive patients. All participants had a DSM-IV diagnosis of schizophrenia. Treatment-resistant patients were classified using the modified Kane criteria. The groups were matched for age, sex, smoking status, and illness duration. Glutamate to creatine ratio levels were higher in treatment-resistant patients (Mean [SD] = 1.57 [0.24]) than in treatment-responsive patients (Mean[SD] = 1.38 [0.23]), (T[35] = 2.34, P = .025, 2-tailed), with a large effect size of d = 0.76. A model assuming 2 populations showed a 25% improvement in the fit of the Akaike weights (0.55) over a model assuming 1 population (0.44), producing group values almost identical to actual group means. Increased anterior cingulate glutamate level is associated with treatment-resistant schizophrenia. This appears to be a stable neurobiological trait of treatment-resistant patients. We discuss possible explanations for glutamatergic dysfunction playing a significant role in resistance to conventional antipsychotic treatments, which are all dopamine-2 receptor blockers. Our findings suggest that glutamatergic treatments may be particularly effective in resistant patients and that 1H-MRS glutamate indices can potentially have clinical use. © The Author 2015. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email

  16. Glutamate receptor antagonism in inferior colliculus attenuates elevated startle response of high anxiety diazepam-withdrawn rats.

    PubMed

    Cabral, A; De Ross, J; Castilho, V M; Brandão, M L; Nobre, M J

    2009-07-07

    Rats segregated according to low (LA) or high (HA) anxiety levels have been used as an important tool in the study of fear and anxiety. Since the efficacy of an anxiolytic compound is a function of the animal's basal anxiety level, it is possible that chronic treatment with a benzodiazepine (Bzp) affects LA and HA animals differently. Based on these assumptions, this study aimed to provide some additional information on the influence of acute, chronic (18 days) and withdrawal effects (48 h) from diazepam (10 mg/kg), in rats with LA or HA levels, on startle response amplitude. For this purpose, the elevated plus-maze (EPM) test was used. In addition, the role of glutamate receptors of the central nucleus of the inferior colliculus (cIC), the most important mesencephalic tectum integrative structure of the auditory pathways and a brain region that is linked to the processing of auditory information of aversive nature, was also evaluated. Our results showed that, contrary to the results obtained in LA rats, long-term treatment with diazepam promoted anxiolytic and aversive effects in HA animals that were tested under chronic effects or withdrawal from this drug, respectively. In addition, since Bzp withdrawal may function as an unconditioned stressor, the negative affective states observed in HA rats could be a by-product of GABA-glutamate imbalance in brain systems that modulate unconditioned fear and anxiety behaviors, since the blockade of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) and N-methyl-D-aspartate (NMDA) glutamate receptors in the cIC clearly reduced the aversion promoted by diazepam withdrawal.

  17. Postmortem elevation in extracellular glutamate in the rat hippocampus when brain temperature is maintained at physiological levels: implications for the use of human brain autopsy tissues.

    PubMed

    Geddes, J W; Chang, N G; Ackley, D C; Soultanian, N S; McGillis, J P; Yokel, R A

    1999-06-12

    Postmortem alterations in the neuronal cytoskeleton resemble some aspects of the cytoskeletal disruption associated with neurodegenerative disorders, and are also similar to those observed following ischemia and produced by excitotoxins in vivo and in vitro. This suggests the involvement of excitotoxic mechanisms during the postmortem interval. The purpose of this study was to determine if extracellular levels of glutamate are elevated postmortem. Extracellular levels of GABA and taurine were also monitored using in vivo microdialysis. These three amino acids were analyzed using high-performance liquid chromatography. When postmortem rat brain temperature cooled rapidly to near room temperature, dialysate concentrations of glutamate were not increased in the hippocampal CA1 region during a 2-h postmortem interval, although increased extracellular levels of GABA and taurine were observed. In contrast, maintenance of brain temperature at 37 degrees C resulted in a 12-to-40 fold elevation in extracellular glutamate levels 20-120 min postmortem. In addition, the elevation in dialysate taurine concentration was greater than that observed in rats in which postmortem brain temperature was not maintained. Excitatory amino acid antagonists, NBQX (2, 3-dihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxaline) and MK-801 (dizocilpine, (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cylohepten-5, 10-imine hydrogen maleate blocked the additional elevation in taurine associated with maintaining brain at 37 degrees C, but had less robust effects against glutamate and GABA release. The results indicate that extracellular concentrations of glutamate, taurine and GABA increase in postmortem rat brain when physiologic temperatures are maintained, but that these increases are blunted when brain temperature decreases. After death, the human brain cools much more slowly than does the rat brain. Therefore, extracellular glutamate levels are likely to increase in the postmortem human brain and may

  18. Elevated basal glutamate and unchanged glutamine and GABA in refractory epilepsy: Microdialysis study of 79 patients at the yale epilepsy surgery program.

    PubMed

    Çavuş, Idil; Romanyshyn, Jonathan C; Kennard, Jeremy T; Farooque, Pue; Williamson, Anne; Eid, Tore; Spencer, Susan S; Duckrow, Robert; Dziura, James; Spencer, Dennis D

    2016-07-01

    Aberrant glutamate and γ-aminobutyric acid (GABA) neurotransmission contribute to seizure generation and the epileptic state. However, whether levels of these neurochemicals are abnormal in epileptic patients is unknown. Here, we report on interictal levels of glutamate, glutamine, and GABA in epilepsy patients at seizure onset and nonepileptic sites, cortical lesions, and from patients with poorly localized neocortical epilepsies. Subjects (n = 79) were medically refractory epilepsy patients undergoing intracranial electroencephalogram evaluation. Microdialysis probes (n = 125) coupled to depth electrodes were implanted within suspected seizure onset sites and microdialysis samples were obtained during interictal periods. Glutamate, glutamine, and GABA were measured using high-performance liquid chromatography. Probe locations were subsequently classified by consensus of expert epileptologists. Glutamate levels were elevated in epileptogenic (p = 0.03; n = 7), nonlocalized (p < 0.001), and lesional cortical sites (p < 0.001) when compared to nonepileptogenic cortex. Glutamate was also elevated in epileptogenic (p < 0.001) compared to nonepileptogenic hippocampus. There were no statistical differences in GABA or glutamine, although GABA levels showed high variability across patients and groups. Our findings indicate that chronically elevated extracellular glutamate is a common pathological feature among epilepsies with different etiology. Contrary to our predictions, GABA and glutamine levels were not decreased in any of the measured areas. Whereas variability in GABA levels may in part be attributed to the use of GABAergic antiepileptic drugs, the stability in glutamine across patient groups indicate that extracellular glutamine levels are under tighter metabolic regulation than previously thought. Ann Neurol 2016;80:35-45. © 2016 American Neurological Association.

  19. [Insular epilepsy: The Montreal experience].

    PubMed

    Nguyen, D K; Surbeck, W; Weil, A G; Villemure, J-G; Bouthillier, A

    2009-10-01

    In this article, we review recently published data on the role of the insula in refractory partial epilepsy and summarize our own experience in the investigation and treatment of this entity. Case studies and evoked responses obtained from insular cortical stimulation reveal a wide array of clinical manifestations which may mimic temporal, frontal or parietal lobe seizures. Clinicians should hence lower their threshold to sample the insula with intracerebral electrodes. Lack of recognition of insular seizures may explain part of epilepsy surgery failures. Advances in microneurosurgery open the way to safer insular resection.

  20. Glutamate-induced elevations in intracellular chloride concentration in hippocampal cell cultures derived from EYFP-expressing mice.

    PubMed

    Slemmer, Jennifer E; Matsushita, Shinichi; De Zeeuw, Chris I; Weber, John T; Knöpfel, Thomas

    2004-06-01

    The homeostasis of intracellular Cl(-) concentration ([Cl(-)](i)) is critical for neuronal function, including gamma-aminobutyric acid (GABA)ergic synaptic transmission. Here, we investigated activity-dependent changes in [Cl(-)](i) using a transgenetically expressed Cl(-)-sensitive enhanced yellow-fluorescent protein (EYFP) in cultures of mouse hippocampal neurons. Application of glutamate (100 microm for 3 min) in a bath perfusion to cell cultures of various days in vitro (DIV) revealed a decrease in EYFP fluorescence. The EYFP signal increased in amplitude with increasing DIV, reaching a maximal response after 7 DIV. Glutamate application resulted in a slight neuronal acidification. Although EYFP fluorescence is sensitive to pH, EYFP signals were virtually abolished in Cl(-)-free solution, demonstrating that the EYFP signal represented an increase in [Cl(-)](i). Similar to glutamate, a rise in [Cl(-)](i) was also induced by specific ionotropic glutamate receptor agonists and by increasing extracellular [K(+)], indicating that an increase in driving force for Cl(-) suffices to increase [Cl(-)](i). To elucidate the membrane mechanisms mediating the Cl(-) influx, a series of blockers of ion channels and transporters were tested. The glutamate-induced increase in [Cl(-)](i) was resistant to furosemide, bumetanide and 4,4'-diisothiocyanato-stilbene-2,2'-disulphonic acid (DIDS), was reduced by bicuculline to about 80% of control responses, and was antagonized by niflumic acid (NFA) and 5-nitro-2-(3-phenylpropylamino)benzoic acid (NPPB). We conclude that membrane depolarization increases [Cl(-)](i) via several pathways involving NFA- and NPPB-sensitive anion channels and GABA(A) receptors, but not through furosemide-, bumetanide- or DIDS-sensitive Cl(-) transporters. The present study highlights the vulnerability of [Cl(-)](i) homeostasis after membrane depolarization in neurons.

  1. Initial elevations in glutamate and dopamine neurotransmission decline with age, as does exploratory behavior, in LRRK2 G2019S knock-in mice.

    PubMed

    Volta, Mattia; Beccano-Kelly, Dayne A; Paschall, Sarah A; Cataldi, Stefano; MacIsaac, Sarah E; Kuhlmann, Naila; Kadgien, Chelsie A; Tatarnikov, Igor; Fox, Jesse; Khinda, Jaskaran; Mitchell, Emma; Bergeron, Sabrina; Melrose, Heather; Farrer, Matthew J; Milnerwood, Austen J

    2017-09-20

    LRRK2 mutations produce end-stage Parkinson's disease (PD) with reduced nigrostriatal dopamine, whereas, asymptomatic carriers have increased dopamine turnover and altered brain connectivity. LRRK2 pathophysiology remains unclear, but reduced dopamine and mitochondrial abnormalities occur in aged G2019S mutant knock-in (GKI) mice. Conversely, cultured GKI neurons exhibit increased synaptic transmission. We assessed behavior and synaptic glutamate and dopamine function across a range of ages. Young GKI mice exhibit more vertical exploration, elevated glutamate and dopamine transmission, and aberrant D2-receptor responses. These phenomena decline with age, but are stable in littermates. In young GKI mice, dopamine transients are slower, independent of dopamine transporter (DAT), increasing the lifetime of extracellular dopamine. Slowing of dopamine transients is observed with age in littermates, suggesting premature ageing of dopamine synapses in GKI mice. Thus, GKI mice exhibit early, but declining, synaptic and behavioral phenotypes, making them amenable to investigation of early pathophysiological, and later parkinsonian-like, alterations. This model will prove valuable in efforts to develop neuroprotection for PD.

  2. Diffuse Brain Injury Elevates Tonic Glutamate Levels and Potassium-Evoked Glutamate Release in Discrete Brain Regions at Two Days Post-Injury: An Enzyme-Based Microelectrode Array Study

    PubMed Central

    Hinzman, Jason M.; Currier Thomas, Theresa; Burmeister, Jason J.; Quintero, Jorge E.; Huettl, Peter; Pomerleau, Francois; Gerhardt, Greg A.

    2010-01-01

    Abstract Traumatic brain injury (TBI) survivors often suffer from a wide range of post-traumatic deficits, including impairments in behavioral, cognitive, and motor function. Regulation of glutamate signaling is vital for proper neuronal excitation in the central nervous system. Without proper regulation, increases in extracellular glutamate can contribute to the pathophysiology and neurological dysfunction seen in TBI. In the present studies, enzyme-based microelectrode arrays (MEAs) that selectively measure extracellular glutamate at 2 Hz enabled the examination of tonic glutamate levels and potassium chloride (KCl)-evoked glutamate release in the prefrontal cortex, dentate gyrus, and striatum of adult male rats 2 days after mild or moderate midline fluid percussion brain injury. Moderate brain injury significantly increased tonic extracellular glutamate levels by 256% in the dentate gyrus and 178% in the dorsal striatum. In the dorsal striatum, mild brain injury significantly increased tonic glutamate levels by 200%. Tonic glutamate levels were significantly correlated with injury severity in the dentate gyrus and striatum. The amplitudes of KCl-evoked glutamate release were increased significantly only in the striatum after moderate injury, with a 249% increase seen in the dorsal striatum. Thus, with the MEAs, we measured discrete regional changes in both tonic and KCl-evoked glutamate signaling, which were dependent on injury severity. Future studies may reveal the specific mechanisms responsible for glutamate dysregulation in the post-traumatic period, and may provide novel therapeutic means to improve outcomes after TBI. PMID:20233041

  3. Newly-diagnosed pediatric epilepsy is associated with elevated autoantibodies to glutamic acid decarboxylase but not cardiolipin.

    PubMed

    Veri, Kadi; Uibo, Oivi; Talvik, Tiina; Talvik, Inga; Metsküla, Kaja; Napa, Aita; Vaher, Ulvi; Õiglane-Šlik, Eve; Rein, Reet; Kolk, Anneli; Traat, Aili; Uibo, Raivo

    2013-07-01

    Glutamic acid decarboxylase autoantibodies (GADA) and anti-cardiolipin autoantibodies (ACA) have been detected in adult subjects with epilepsy, though the functional implications of these findings are a matter of debate. This study aimed to determine the prevalence of GADA and ACA and to investigate their clinical significance in pediatric subjects with newly-diagnosed epilepsy. For this purpose GADA and ACA were assessed by enzyme-linked immunosorbent assays in 208 pediatric patients with newly-diagnosed epilepsy and 128 controls. The clinical data (results of electroencephalography, magnetic resonance imaging, 6-month outcome etc.) was compared to antibody test results. Our study revealed GADA in 14 (6.7%) patients with epilepsy and in 1 (0.8%) control, which was a statistically significant difference (P=0.010; Chi-square test). The GADA-positive and -negative patients had similar clinical characteristics. The prevalence of ACA in patients with epilepsy (6.3%) was not significantly different than controls (2.6%). These results suggest that GADA is associated with epilepsy in a subgroup of newly-diagnosed pediatric patients. Further studies are required to determine the prognostic significance and pathogenic role of GADA among pediatric subjects with epilepsy.

  4. Effects of glutamate and its metabotropic receptors class 1 antagonist in appetitive taste memory formation.

    PubMed

    Ramírez-Lugo, Leticia; Zavala-Vega, Sergio; Pedroza-Llinas, Rodrigo; Núñez-Jaramillo, Luis; Bermúdez-Rattoni, Federico

    2015-05-01

    Cortical glutamatergic activity is known to be important for memory formation in different learning tasks. For example, glutamate activity in the insular cortex plays an important role in aversive taste memory formation by signaling the unconditioned stimulus. However, the role of glutamate in the insular cortex in appetitive taste learning has remained poorly studied. Therefore, we considered the function of glutamate in attenuation of neophobia, a model of appetitive taste recognition memory. For this purpose, we performed infusions of vehicle, glutamate, a specific mGluR1 antagonist (AIDA) or a combination of glutamate and AIDA at 0 or 30 min, and glutamate or vehicle at 60 min after novel saccharin consumption. Glutamate infusion impaired appetitive taste recognition memory when infused at 0 or 30 min, whereas, AIDA infusions produced enhanced appetitive memory at the same infusion times. Furthermore, when glutamate and AIDA were infused together no effect on attenuation of neophobia was observed. As opposed to shorter infusion times, the administration of glutamate 60 min after the presentation of the saccharin consumption was ineffective in the impairment of the appetitive taste memory. These results are discussed in view of the effect of glutamate and its mGluR1 during the appetitive taste recognition memory formation in the insular cortex. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Food related processes in the insular cortex

    PubMed Central

    Frank, Sabine; Kullmann, Stephanie; Veit, Ralf

    2013-01-01

    The insular cortex is a multimodal brain region with regional cytoarchitectonic differences indicating various functional specializations. As a multisensory neural node, the insular cortex integrates perception, emotion, interoceptive awareness, cognition, and gustation. Regarding the latter, predominantly the anterior part of the insular cortex is regarded as the primary taste cortex. In this review, we will specifically focus on the involvement of the insula in food processing and on multimodal integration of food-related items. Influencing factors of insular activation elicited by various foods range from calorie-content to the internal physiologic state, body mass index or eating behavior. Sensory perception of food-related stimuli including seeing, smelling, and tasting elicits increased activation in the anterior and mid-dorsal part of the insular cortex. Apart from the pure sensory gustatory processing, there is also a strong association with the rewarding/hedonic aspects of food items, which is reflected in higher insular activity and stronger connections to other reward-related areas. Interestingly, the processing of food items has been found to elicit different insular activation in lean compared to obese subjects and in patients suffering from an eating disorder (anorexia nervosa (AN), bulimia nervosa (BN)). The knowledge of functional differences in the insular cortex opens up the opportunity for possible noninvasive treatment approaches for obesity and eating disorders. To target brain functions directly, real-time functional magnetic resonance imaging neurofeedback offers a state-of-the-art tool to learn to control the anterior insular cortex activity voluntarily. First evidence indicates that obese adults have an enhanced ability to regulate the anterior insular cortex. PMID:23986683

  6. 24 CFR 570.441 - Citizen participation-insular areas.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 24 Housing and Urban Development 3 2010-04-01 2010-04-01 false Citizen participation-insular areas...-Entitlement CDBG Grants in Hawaii and Insular Areas Programs § 570.441 Citizen participation—insular areas. (a... shall comply with the citizen participation requirements described in this section. An insular area...

  7. Pure dysarthria due to an insular infarction.

    PubMed

    Hiraga, Akiyuki; Tanaka, Saiko; Kamitsukasa, Ikuo

    2010-06-01

    Cortical infarction presenting with pure dysarthria is rarely reported. Previous studies have reported pure dysarthria due to cortical stroke at the precentral gyrus or middle frontal gyrus. We report a 72-year-old man who developed pure dysarthria caused by an acute cortical infarction in the insular cortex. The role of the insula in language has been difficult to assess clinically because of the rarity of pure insular strokes. Our patient showed pure dysarthria without aphasia, indicating that pure dysarthria can be the sole manifestation of insular infarctions.

  8. Effects of insular stimulation on thermal nociception.

    PubMed

    Denis, D J; Marouf, R; Rainville, P; Bouthillier, A; Nguyen, D K

    2016-05-01

    Electrical stimulation used for brain mapping in the postero-superior insula can evoke pain. The effects of prolonged high frequency insular stimulation on pain thresholds are unknown. Prolonged high frequency insular stimulation, by virtue of its inhibitory properties on networks, could decrease thermal nociception. Epileptic subjects had electrodes implanted in the insular cortex for the purpose of epileptic focus resection. Thermal and pressure nociceptive thresholds were tested bilaterally on the forearm on two consecutive days. Randomly assigned double-blind high frequency (150 Hz) insular stimulation took place for 10 min before pain testing either on the first day or on the second day. Six subjects (three females; mean age of 35 years) were included. Insular stimulation increased heat pain threshold on the ipsilateral (p = 0.003; n = 6) and contralateral sides (p = 0.047; n = 6). Differences in cold pain threshold did not reach statistical significance (ipsilateral: p = 0.341, contralateral: p = 0.143; n = 6), but one subject had a profound decrease in both heat and cold pain responses. Pressure pain threshold was not modified by insular stimulation (ipsilateral: p = 0.1123; contralateral: p = 0.1192; n = 6). Two of the three subjects who had a postero-superior operculo-insulectomy developed central pain with contralateral thermal nociceptive deficit. High frequency inhibitory postero-superior insular stimulation may have the potential to decrease thermal nociception. Together with previous studies, our data support the notion that the integrity of this brain region is necessary for thermal but not pressure nociceptive processing. © 2015 European Pain Federation - EFIC®

  9. Insular Epilepsy: Semiology and Noninvasive Investigations.

    PubMed

    Obaid, Sami; Zerouali, Younes; Nguyen, Dang Khoa

    2017-07-01

    In this review, authors discuss the semiology and noninvasive investigations of insular epilepsy, an underrecognized type of epilepsy, which may mimic other focal epilepsies. In line with the various functions of the insula and its widespread network of connections, insular epilepsy may feature a variety of early ictal manifestations from somatosensory, visceral, olfactory, gustatory, or vestibular manifestations. Depending on propagation pathways, insular seizures may also include altered consciousness, dystonic posturing, complex motor behaviors, and even autonomic features. Considering the variability in seizure semiology, recognition of insular epilepsy may be challenging and confirmation by noninvasive tests is warranted although few studies have assessed their value. Detection of an insular lesion on MRI greatly facilitates the diagnosis. Scalp EEG findings in frontocentral and/or temporal derivations will generally allow lateralization of the seizure focus. Ictal single-photon computed tomography has moderate sensitivity, whereas positron emission tomography has lower sensitivity. Among newer techniques, magnetoencephalography is highly beneficial, whereas proton magnetic resonance spectroscopy currently has limited value.

  10. Prolonged continuous intravenous infusion of the dipeptide L-alanine- L-glutamine significantly increases plasma glutamine and alanine without elevating brain glutamate in patients with severe traumatic brain injury

    PubMed Central

    2014-01-01

    .75 g/ kg/ d up to 5 days) increased plasma and brain glutamine and alanine levels. This was not associated with elevated glutamate or signs of potential glutamate-mediated cerebral injury. The increased nitrogen load should be considered in patients with renal and hepatic dysfunction. Trial registration Clinicaltrials.gov NCT02130674. Registered 5 April 2014 PMID:24992948

  11. 27 CFR 479.121 - Insular possessions.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 3 2014-04-01 2014-04-01 false Insular possessions. 479.121 Section 479.121 Alcohol, Tobacco Products, and Firearms BUREAU OF ALCOHOL, TOBACCO, FIREARMS, AND EXPLOSIVES, DEPARTMENT OF JUSTICE FIREARMS AND AMMUNITION MACHINE GUNS, DESTRUCTIVE DEVICES, AND CERTAIN...

  12. 27 CFR 479.121 - Insular possessions.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 3 2012-04-01 2010-04-01 true Insular possessions. 479.121 Section 479.121 Alcohol, Tobacco Products, and Firearms BUREAU OF ALCOHOL, TOBACCO, FIREARMS, AND EXPLOSIVES, DEPARTMENT OF JUSTICE FIREARMS AND AMMUNITION MACHINE GUNS, DESTRUCTIVE DEVICES, AND CERTAIN...

  13. 27 CFR 479.121 - Insular possessions.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 3 2013-04-01 2013-04-01 false Insular possessions. 479.121 Section 479.121 Alcohol, Tobacco Products, and Firearms BUREAU OF ALCOHOL, TOBACCO, FIREARMS, AND EXPLOSIVES, DEPARTMENT OF JUSTICE FIREARMS AND AMMUNITION MACHINE GUNS, DESTRUCTIVE DEVICES, AND CERTAIN...

  14. 27 CFR 479.121 - Insular possessions.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 3 2011-04-01 2010-04-01 true Insular possessions. 479.121 Section 479.121 Alcohol, Tobacco Products, and Firearms BUREAU OF ALCOHOL, TOBACCO, FIREARMS, AND EXPLOSIVES, DEPARTMENT OF JUSTICE FIREARMS AND AMMUNITION MACHINE GUNS, DESTRUCTIVE DEVICES, AND CERTAIN...

  15. 27 CFR 479.121 - Insular possessions.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 3 2010-04-01 2010-04-01 false Insular possessions. 479.121 Section 479.121 Alcohol, Tobacco Products, and Firearms BUREAU OF ALCOHOL, TOBACCO, FIREARMS, AND EXPLOSIVES, DEPARTMENT OF JUSTICE FIREARMS AND AMMUNITION MACHINE GUNS, DESTRUCTIVE DEVICES, AND CERTAIN...

  16. Extreme insular dwarfism evolved in a mammoth

    PubMed Central

    Herridge, Victoria L.; Lister, Adrian M.

    2012-01-01

    The insular dwarfism seen in Pleistocene elephants has come to epitomize the island rule; yet our understanding of this phenomenon is hampered by poor taxonomy. For Mediterranean dwarf elephants, where the most extreme cases of insular dwarfism are observed, a key systematic question remains unresolved: are all taxa phyletic dwarfs of a single mainland species Palaeoloxodon antiquus (straight-tusked elephant), or are some referable to Mammuthus (mammoths)? Ancient DNA and geochronological evidence have been used to support a Mammuthus origin for the Cretan ‘Palaeoloxodon’ creticus, but these studies have been shown to be flawed. On the basis of existing collections and recent field discoveries, we present new, morphological evidence for the taxonomic status of ‘P’. creticus, and show that it is indeed a mammoth, most probably derived from Early Pleistocene Mammuthus meridionalis or possibly Late Pliocene Mammuthus rumanus. We also show that Mammuthus creticus is smaller than other known insular dwarf mammoths, and is similar in size to the smallest dwarf Palaeoloxodon species from Sicily and Malta, making it the smallest mammoth species known to have existed. These findings indicate that extreme insular dwarfism has evolved to a similar degree independently in two elephant lineages. PMID:22572206

  17. Extreme insular dwarfism evolved in a mammoth.

    PubMed

    Herridge, Victoria L; Lister, Adrian M

    2012-08-22

    The insular dwarfism seen in Pleistocene elephants has come to epitomize the island rule; yet our understanding of this phenomenon is hampered by poor taxonomy. For Mediterranean dwarf elephants, where the most extreme cases of insular dwarfism are observed, a key systematic question remains unresolved: are all taxa phyletic dwarfs of a single mainland species Palaeoloxodon antiquus (straight-tusked elephant), or are some referable to Mammuthus (mammoths)? Ancient DNA and geochronological evidence have been used to support a Mammuthus origin for the Cretan 'Palaeoloxodon' creticus, but these studies have been shown to be flawed. On the basis of existing collections and recent field discoveries, we present new, morphological evidence for the taxonomic status of 'P'. creticus, and show that it is indeed a mammoth, most probably derived from Early Pleistocene Mammuthus meridionalis or possibly Late Pliocene Mammuthus rumanus. We also show that Mammuthus creticus is smaller than other known insular dwarf mammoths, and is similar in size to the smallest dwarf Palaeoloxodon species from Sicily and Malta, making it the smallest mammoth species known to have existed. These findings indicate that extreme insular dwarfism has evolved to a similar degree independently in two elephant lineages.

  18. Forest fires in the insular Caribbean

    Treesearch

    A.M.J. Robbins; C.M. Eckelmann; M. Quinones

    2008-01-01

    This paper presents a summary of the forest fire reports in the insular Caribbean derived from both management reports and an analysis of publicly available Moderate Resolution Imaging Spectrodiometer (MODIS) satellite active fire products from the region. A vast difference between the amount of fires reported by land managers and fire points in the MODIS Fire...

  19. Extrasynaptic glutamate release through cystine/glutamate antiporter contributes to ischemic damage

    PubMed Central

    Soria, Federico N.; Pérez-Samartín, Alberto; Martin, Abraham; Gona, Kiran Babu; Llop, Jordi; Szczupak, Boguslaw; Chara, Juan Carlos; Matute, Carlos; Domercq, María

    2014-01-01

    During brain ischemia, an excessive release of glutamate triggers neuronal death through the overactivation of NMDA receptors (NMDARs); however, the underlying pathways that alter glutamate homeostasis and whether synaptic or extrasynaptic sites are responsible for excess glutamate remain controversial. Here, we monitored ischemia-gated currents in pyramidal cortical neurons in brain slices from rodents in response to oxygen and glucose deprivation (OGD) as a real-time glutamate sensor to identify the source of glutamate release and determined the extent of neuronal damage. Blockade of excitatory amino acid transporters or vesicular glutamate release did not inhibit ischemia-gated currents or neuronal damage after OGD. In contrast, pharmacological inhibition of the cystine/glutamate antiporter dramatically attenuated ischemia-gated currents and cell death after OGD. Compared with control animals, mice lacking a functional cystine/glutamate antiporter exhibited reduced anoxic depolarization and neuronal death in response to OGD. Furthermore, glutamate released by the cystine/glutamate antiporter activated extrasynaptic, but not synaptic, NMDARs, and blockade of extrasynaptic NMDARs reduced ischemia-gated currents and cell damage after OGD. Finally, PET imaging showed increased cystine/glutamate antiporter function in ischemic rats. Altogether, these data suggest that cystine/glutamate antiporter function is increased in ischemia, contributing to elevated extracellular glutamate concentration, overactivation of extrasynaptic NMDARs, and ischemic neuronal death. PMID:25036707

  20. Metabotropic glutamate receptor 1 and glutamate signaling in human melanoma.

    PubMed

    Namkoong, Jin; Shin, Seung-Shick; Lee, Hwa Jin; Marín, Yarí E; Wall, Brian A; Goydos, James S; Chen, Suzie

    2007-03-01

    Recently, several laboratories have started to investigate the involvement of glutamate signaling in cancer. In previous studies, we reported on a transgenic mouse model that develops melanoma spontaneously. Subsequent studies in these mice identified that the aberrant expression of metabotropic glutamate receptor 1 (GRM1) in melanocytes played a critical role in the onset of melanoma. Confirmation of the etiologic role of GRM1 in melanoma development was shown in a second transgenic line with GRM1 expression under the regulation of a melanocyte-specific dopachrome tautomerase promoter. Ectopic expression of GRM1 was also detected in a subset of human melanoma cell lines and biopsies, suggesting that aberrant expression of GRM1 in melanocytes may contribute to the development of human melanoma. GRM1, a seven-transmembrane domain G protein-coupled receptor, is normally expressed and functional in neuronal cells, and its ligand, glutamate, is the major excitatory neurotransmitter. Human melanoma cells are shown here to release elevated levels of glutamate, implying a possible autocrine loop. Treatment of GRM1-expressing human melanoma cells with a GRM1 antagonist (LY367385 or BAY36-7620) or a glutamate release inhibitor (riluzole) leads to a suppression of cell proliferation as well as a decrease in levels of extracellular glutamate. Treatment of human melanoma cell xenografts with riluzole for 18 days via p.o. gavage or i.v. injection leads to inhibition of tumor growth by 50% in comparison with controls. These data suggest the importance of glutamate signaling in human melanoma and imply that the suppression of glutamate signaling may be a new target for melanoma therapy.

  1. Insular volume reduction in fragile X syndrome.

    PubMed

    Cohen, Jeremy D; Nichols, Taylor; Brignone, Laura; Hall, Scott S; Reiss, Allan L

    2011-06-01

    Fragile X syndrome (FraX) is the most common form of inherited mental deficit and is caused by mutations of the Fragile X Mental Retardation 1 (FMR1) gene on the X chromosome. While males and females with the full FMR1 mutation are affected differently because the disorder is X-linked, both suffer from varying degrees of cognitive impairment, attention deficits and social anxiety. The insula is a sensory integrative region that has been increasingly suggested as a critical area involved in anxiety manifestation. The current study was designed to examine possible changes in insular volume in FraX compared to age- and gender-matched typically developing healthy controls (HC) as well as age-, gender-, and intelligence-matched developmentally delayed controls (DD). An established native-space, manual morphometry method was utilized to quantify total and regional insular volumes using structural magnetic resonance imaging. Total, anterior and posterior insular volumes were found to be reduced in FraX compared to both HC and DD. The current data add to a growing literature concerning brain abnormalities in FraX and suggests that significant volume reduction of the insula is a component of the FraX neuroanatomical phenotype. This finding also provides an intriguing potential neural correlate for hyperarousal and gaze aversion, which are prominent behavioral symptoms of FraX.

  2. Insular Volume Reduction in Fragile X Syndrome

    PubMed Central

    Cohen, Jeremy D.; Nichols, Taylor; Brignone, Laura; Hall, Scott S.; Reiss, Allan L.

    2011-01-01

    Fragile X Syndrome (FraX) is the most common form of inherited mental deficit and is caused by mutations of the Fragile X Mental Retardation 1 (FMR1) gene on the X chromosome. While males and females with the full FMR1 mutation are affected differently because the disorder is X-linked, both suffer from varying degrees of cognitive impairment, attention deficits and social anxiety. The insula is a sensory integrative region that has been increasingly suggested as a critical area involved in anxiety manifestation. The current study was designed to examine possible changes in insular volume in FraX compared to age- and gender-matched typically developing healthy controls (HC) as well as age, gender-, and intelligence-matched developmentally delayed controls (DD). An established native-space, manual morphometry method was utilized to quantify total and regional insular volumes using structural magnetic resonance imaging. Total, anterior and posterior insular volumes were found to be reduced in FraX compared to both HC and DD. The current data add to a growing literature concerning brain abnormalities in FraX and suggests that significant volume reduction of the insula is a component of the FraX neuroanatomical phenotype. This finding also provides an intriguing potential neural correlate for hyperarousal and gaze aversion, which are prominent behavioral symptoms of FraX. PMID:21291994

  3. Multidimensional assessment of empathic abilities in patients with insular glioma.

    PubMed

    Chen, Peng; Wang, Guangming; Ma, Ru; Jing, Fang; Zhang, Yongjun; Wang, Ying; Zhang, Peng; Niu, Chaoshi; Zhang, Xiaochu

    2016-10-01

    Recent studies have provided evidence that there are two possible systems for empathy: affective empathy (AE) and cognitive empathy (CE). Neuroimaging paradigms have proven that the insular cortex is involved in empathy processing, particularly in AE. However, these observations do not provide causal evidence for the role of the insula in empathy. Although impairments in empathy have been described following insular damage in a few case studies, it is not clear whether insular cortex is involved in CE and whether these two systems are impaired independently or laterally in patients with insular gliomas. In this study, we assessed 17 patients with an insular glioma, 17 patients with a noninsular glioma, and 30 healthy controls using a method that combined a self-report empathy questionnaire with the emotion recognition task, assessment of empathy for others' pain, and the emotional perspective-taking paradigm. We found that patients with an insular glioma had lower scores for empathic concern and perspective taking than did either healthy controls or lesion controls. The patients' abilities to recognize facial emotions, perceive others' pain, and understand the emotional perspectives of others were also significantly impaired. Furthermore, we did not observe a laterality effect on either AE or CE among those with insular lesions. These findings revealed that both AE and CE are impaired in patients with an insular glioma and that the insular cortex may be a central neuroanatomical structure in both the AE and CE systems.

  4. 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

  5. Deciphering arboviral emergence within insular ecosystems.

    PubMed

    Tortosa, Pablo; Pascalis, Hervé; Guernier, Vanina; Cardinale, Eric; Le Corre, Matthieu; Goodman, Steven M; Dellagi, Koussay

    2012-08-01

    The spatial dynamics of zoonotic arthropod-borne viruses is a fashionable though challenging topic. Inter-human local transmission of a given arbovirus during an outbreak and its spread over large distances are considered as key parameters of emergence. Here, we suggest that insular ecosystems provide ideal natural "laboratory" conditions to uncouple local transmission from long distance spread, and differentiate these two processes. Due to geographic isolation, often-limited land surface area and relatively homogenous ecosystems, oceanic islands display low species richness and often-high levels of endemism. These aspects provide the means for comprehensive entomological surveys and investigations of original host/pathogen interactions. In addition, islands are interconnected through discrete anthropogenic and non-anthropogenic exchanges: whilst islands maintain a substantial level of human and domestic animal exchange with other neighbouring or distant territories, they also comprise dispersal and migratory pathways of volant organisms (insects, birds and bats). Hence, both anthropogenic and non-anthropogenic exchanges in island systems are easier to identify and investigate than in continuous, continental systems. Finally, island ecosystems tend to be notably simpler, more prone to invasive taxa and, therefore, easier to document the colonization or displacement of vector species. These different aspects are presented and overlaid upon the spread of arboviruses within two distinct insular systems: islands of Polynesia and the south-western Indian Ocean. The former have been repeatedly affected by Dengue fever epidemics, while the latter recently suffered four successive epidemics, probably of east African origin, three of which involved the emerging viruses Chikungunya, Rift Valley and Dengue fever. Here, we review some new insights into arboviral spread and evolution associated with investigations that followed these epidemics, as well as several aspects that

  6. Glutamate ameliorates experimental vincristine neuropathy.

    PubMed

    Boyle, F M; Wheeler, H R; Shenfield, G M

    1996-10-01

    The dose-limiting toxicity of the chemotherapeutic agent vincristine is peripheral neuropathy, for which there is no established therapy. The amino acid glutamate has been proposed as a neuroprotectant for vincristine, but a full preclinical evaluation of its efficacy, safety and mechanism of action has been hampered by a lack of suitable animal models. We report the development of a Dark Agouti rat model of sensorimotor peripheral neuropathy, to investigate the neurotoxicity of cytotoxic drugs. Neuropathy was manifested as gait disturbance in 100% of vincristine-treated animals (n = 12), significant elevation of the tail-flick threshold (5.1 +/- 2 sec) and significantly impaired mean Rotarod times (55 +/- 41 sec) developing after administration of 1.5 mg/kg vincristine over 2 weeks. Among vincristine-treated animals supplemented p.o. with sodium glutamate (500 mg/kg/day in drinking water) from 24 hr before vincristine treatment, only one (8%, P = .01) developed gait disturbance, the tall-flick threshold was not significantly different from controls and the mean Rotarod score was 188 +/- 18 sec (P = .004). Glutamate thus significantly protected against both sensory and motor neuropathy. We observed no intrinsic neurotoxicity with glutamate and no interference with the cytotoxic efficacy of vincristine against a transplantable rat mammary adenocarcinoma grown s.c. in Dark Agouti rats. Our findings suggest that glutamate is likely to be a safe and effective neuroprotectant for patients receiving vincristine, and it warrants further clinical evaluation. The mechanism of this selective neuroprotection by glutamate remains to be elucidated. Our rat model may be of use in determining whether glutamate offers protection from other neurotoxic drugs.

  7. Morphometry of Human Insular Cortex and Insular Volume Reduction in Williams syndrome

    PubMed Central

    Cohen, Jeremy D.; Mock, Jeffrey R.; Nichols, Taylor; Zadina, Janet; Corey, David M.; Lemen, Lisa; Bellugi, Ursula; Galaburda, Albert; Reiss, Allan; Foundas, Anne L.

    2009-01-01

    Functional imaging in humans and anatomical data in monkeys have implicated the insula as a multimodal sensory integrative brain region. The topography of insular connections is organized by its cytoarchitectonic regions. Previous attempts to measure the insula have utilized either indirect or automated methods. This study was designed to develop a reliable method for obtaining volumetric magnetic resonance imaging (MRI) measurements of the human insular cortex, and to validate that method by examining the anatomy of insular cortex in adults with Williams syndrome (WS) and healthy age-matched controls. Statistical reliability was obtained among three raters for this method, supporting its reproducibility not only across raters, but within different software packages. The procedure described here utilizes native-space morphometry as well as a method for dividing the insula into connectivity-based sub-regions estimated from cytoarchitectonics. Reliability was calculated in both ANALYZE (n=3) and BrainImageJava (N=10) where brain scans were measured once in each hemisphere by each rater. This highly reliable method revealed total, anterior, and posterior insular volume reduction bilaterally (all p’s < .002) in WS, after accounting for reduced total brain volumes in these participants. Although speculative, the reduced insular volumes in WS may represent a neural risk for the development of hyperaffiliative social behavior with increased specific phobias, and implicate the insula as a critical limbic integrative region. Native-space quantification of the insula may be valuable in the study of neurodevelopmental or neuropsychiatric disorders related to anxiety and social behavior. PMID:19660766

  8. 38 CFR 3.40 - Philippine and Insular Forces.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Forces. 3.40 Section 3.40 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS... Insular Forces. (a) Regular Philippine Scouts. Service in the Philippine Scouts (except that described in paragraph (b) of this section), the Insular Force of the Navy, Samoan Native Guard, and Samoan Native Band...

  9. 38 CFR 3.40 - Philippine and Insular Forces.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Forces. 3.40 Section 3.40 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS... Insular Forces. (a) Regular Philippine Scouts. Service in the Philippine Scouts (except that described in paragraph (b) of this section), the Insular Force of the Navy, Samoan Native Guard, and Samoan Native Band...

  10. 38 CFR 3.40 - Philippine and Insular Forces.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Forces. 3.40 Section 3.40 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS... Insular Forces. (a) Regular Philippine Scouts. Service in the Philippine Scouts (except that described in paragraph (b) of this section), the Insular Force of the Navy, Samoan Native Guard, and Samoan Native Band...

  11. Are there differences in immune function between continental and insular birds?

    PubMed Central

    Matson, Kevin D

    2006-01-01

    Generally, immune system architecture varies with different environments, which presumably reflect different pathogen pressures. Specifically, populations from relatively disease-free, oceanic islands are expected to exhibit reorganized immune systems, which might be characterized by attenuated responses, given the costs of immune function. Some insular animals exhibit an ‘island syndrome,’ including increased susceptibility to disease, and some insular populations have declined when they failed to resist infection by introduced pathogens. I measured eight indices of immune function (haemolysis, haemagglutination, concentration of haptoglobin and concentration of five leukocyte types) in 15 phylogenetically matched pairs of bird populations from North America and from the islands of Hawaii, Bermuda and the Galápagos. Immune responses were not attenuated in insular birds, and several indices, including the concentration of plasma haptoglobin, were elevated. Thus, I find no support for the specific hypothesis that depauperate parasite communities and the costs of immune defences select for reduced immune function. Instead, I suggest that life on islands leads to an apparent reorganization of immune function, which is defined by increases in defences that are innate and inducible. These increases might signal that systems of acquired humoral immunity and immunological memory are less important or dysfunctional in island populations. PMID:16928627

  12. Anterior insular cortex is necessary for empathetic pain perception

    PubMed Central

    Gu, Xiaosi; Gao, Zhixian; Wang, Xingchao; Liu, Xun; Knight, Robert T.; Hof, Patrick R.

    2012-01-01

    Empathy refers to the ability to perceive and share another person’s affective state. Much neuroimaging evidence suggests that observing others’ suffering and pain elicits activations of the anterior insular and the anterior cingulate cortices associated with subjective empathetic responses in the observer. However, these observations do not provide causal evidence for the respective roles of anterior insular and anterior cingulate cortices in empathetic pain. Therefore, whether these regions are ‘necessary’ for empathetic pain remains unknown. Herein, we examined the perception of others’ pain in patients with anterior insular cortex or anterior cingulate cortex lesions whose locations matched with the anterior insular cortex or anterior cingulate cortex clusters identified by a meta-analysis on neuroimaging studies of empathetic pain perception. Patients with focal anterior insular cortex lesions displayed decreased discrimination accuracy and prolonged reaction time when processing others’ pain explicitly and lacked a typical interference effect of empathetic pain on the performance of a pain-irrelevant task. In contrast, these deficits were not observed in patients with anterior cingulate cortex lesions. These findings reveal that only discrete anterior insular cortex lesions, but not anterior cingulate cortex lesions, result in deficits in explicit and implicit pain perception, supporting a critical role of anterior insular cortex in empathetic pain processing. Our findings have implications for a wide range of neuropsychiatric illnesses characterized by prominent deficits in higher-level social functioning. PMID:22961548

  13. Extensive Clonality and Strong Differentiation in the Insular Pacific Tree Santalum insulare: Implications for its Conservation

    PubMed Central

    LHUILLIER, EMELINE; BUTAUD, JEAN-FRANÇOIS; BOUVET, JEAN-MARC

    2006-01-01

    • Background and Aims The impact of evolutionary forces on insular systems is particularly exacerbated by the remoteness of islands, strong founder effects, small population size and the influence of biotic and abiotic factors. Patterns of molecular diversity were analysed in an island system with Santalum insulare, a sandalwood species endemic to eastern Polynesia. The aims were to evaluate clonality and to study the genetic diversity and structure of this species, in order to understand the evolutionary process and to define a conservation strategy. • Methods Eight nuclear microsatellites were used to investigate clonality, genetic variation and structure of the French Polynesian sandalwood populations found on ten islands distributed over three archipelagos. • Key Results It was found that 58 % of the 384 trees analysed were clones. The real size of the populations is thus dramatically reduced, with sometimes only one genet producing ramets by root suckering. The diversity parameters were low for islands (nA = 1·5–5·0; HE = 0·28–0·49). No departure from Hardy–Weinberg proportion was observed except within Tahiti island, where a significant excess of homozygotes was noted in the highland population. Genetic structure was characterized by high levels of differentiation between archipelagos (27 % of the total variation) and islands (FST = 0·50). The neighbour-joining tree did not discriminate the three archipelagos but separated the Society archipelago from the other two. • Conclusions This study shows that clonality is a frequent phenomenon in S. insulare. The genetic diversity within populations is lower than the values assessed in species distributed on the mainland, as a consequence of insularity. But this can also be explained by the overexploitation of sandalwood. The differentiation between archipelagos and islands within archipelagos is very high because of the limited gene flow due to oceanic barriers. Delineation of evolutionary

  14. Anterior Insular Cortex and Emotional Awareness

    PubMed Central

    Gu, Xiaosi; Hof, Patrick R.; Friston, Karl J.; Fan, Jin

    2014-01-01

    This paper reviews the foundation for a role of the human anterior insular cortex (AIC) in emotional awareness, defined as the conscious experience of emotions. We first introduce the neuroanatomical features of AIC and existing findings on emotional awareness. Using empathy, the awareness and understanding of other people’s emotional states, as a test case, we then present evidence to demonstrate: 1) AIC and anterior cingulate cortex (ACC) are commonly coactivated as revealed by a meta-analysis, 2) AIC is functionally dissociable from ACC, 3) AIC integrates stimulus-driven and top-down information, and 4) AIC is necessary for emotional awareness. We propose a model in which AIC serves two major functions: integrating bottom-up interoceptive signals with top-down predictions to generate a current awareness state and providing descending predictions to visceral systems that provide a point of reference for autonomic reflexes. We argue that AIC is critical and necessary for emotional awareness. PMID:23749500

  15. Non-Targeted Metabolomics Analysis of Golden Retriever Muscular Dystrophy-Affected Muscles Reveals Alterations in Arginine and Proline Metabolism, and Elevations in Glutamic and Oleic Acid In Vivo

    PubMed Central

    Abdullah, Muhammad; Kornegay, Joe N.; Honcoop, Aubree; Parry, Traci L.; Balog-Alvarez, Cynthia J.; Muehlbauer, Michael J.; Newgard, Christopher B.; Patterson, Cam

    2017-01-01

    Background: Like Duchenne muscular dystrophy (DMD), the Golden Retriever Muscular Dystrophy (GRMD) dog model of DMD is characterized by muscle necrosis, progressive paralysis, and pseudohypertrophy in specific skeletal muscles. This severe GRMD phenotype includes moderate atrophy of the biceps femoris (BF) as compared to unaffected normal dogs, while the long digital extensor (LDE), which functions to flex the tibiotarsal joint and serves as a digital extensor, undergoes the most pronounced atrophy. A recent microarray analysis of GRMD identified alterations in genes associated with lipid metabolism and energy production. Methods: We, therefore, undertook a non-targeted metabolomics analysis of the milder/earlier stage disease GRMD BF muscle versus the more severe/chronic LDE using GC-MS to identify underlying metabolic defects specific for affected GRMD skeletal muscle. Results: Untargeted metabolomics analysis of moderately-affected GRMD muscle (BF) identified eight significantly altered metabolites, including significantly decreased stearamide (0.23-fold of controls, p = 2.89 × 10−3), carnosine (0.40-fold of controls, p = 1.88 × 10−2), fumaric acid (0.40-fold of controls, p = 7.40 × 10−4), lactamide (0.33-fold of controls, p = 4.84 × 10−2), myoinositol-2-phosphate (0.45-fold of controls, p = 3.66 × 10−2), and significantly increased oleic acid (1.77-fold of controls, p = 9.27 × 10−2), glutamic acid (2.48-fold of controls, p = 2.63 × 10−2), and proline (1.73-fold of controls, p = 3.01 × 10−2). Pathway enrichment analysis identified significant enrichment for arginine/proline metabolism (p = 5.88 × 10−4, FDR 4.7 × 10−2), where alterations in L-glutamic acid, proline, and carnosine were found. Additionally, multiple Krebs cycle intermediates were significantly decreased (e.g., malic acid, fumaric acid, citric/isocitric acid, and succinic acid), suggesting that altered energy metabolism may be underlying the observed GRMD BF muscle

  16. Non-Targeted Metabolomics Analysis of Golden Retriever Muscular Dystrophy-Affected Muscles Reveals Alterations in Arginine and Proline Metabolism, and Elevations in Glutamic and Oleic Acid In Vivo.

    PubMed

    Abdullah, Muhammad; Kornegay, Joe N; Honcoop, Aubree; Parry, Traci L; Balog-Alvarez, Cynthia J; O'Neal, Sara K; Bain, James R; Muehlbauer, Michael J; Newgard, Christopher B; Patterson, Cam; Willis, Monte S

    2017-07-29

    Like Duchenne muscular dystrophy (DMD), the Golden Retriever Muscular Dystrophy (GRMD) dog model of DMD is characterized by muscle necrosis, progressive paralysis, and pseudohypertrophy in specific skeletal muscles. This severe GRMD phenotype includes moderate atrophy of the biceps femoris (BF) as compared to unaffected normal dogs, while the long digital extensor (LDE), which functions to flex the tibiotarsal joint and serves as a digital extensor, undergoes the most pronounced atrophy. A recent microarray analysis of GRMD identified alterations in genes associated with lipid metabolism and energy production. We, therefore, undertook a non-targeted metabolomics analysis of the milder/earlier stage disease GRMD BF muscle versus the more severe/chronic LDE using GC-MS to identify underlying metabolic defects specific for affected GRMD skeletal muscle. Untargeted metabolomics analysis of moderately-affected GRMD muscle (BF) identified eight significantly altered metabolites, including significantly decreased stearamide (0.23-fold of controls, p = 2.89 × 10(-3)), carnosine (0.40-fold of controls, p = 1.88 × 10(-2)), fumaric acid (0.40-fold of controls, p = 7.40 × 10(-4)), lactamide (0.33-fold of controls, p = 4.84 × 10(-2)), myoinositol-2-phosphate (0.45-fold of controls, p = 3.66 × 10(-2)), and significantly increased oleic acid (1.77-fold of controls, p = 9.27 × 10(-2)), glutamic acid (2.48-fold of controls, p = 2.63 × 10(-2)), and proline (1.73-fold of controls, p = 3.01 × 10(-2)). Pathway enrichment analysis identified significant enrichment for arginine/proline metabolism (p = 5.88 × 10(-4), FDR 4.7 × 10(-2)), where alterations in L-glutamic acid, proline, and carnosine were found. Additionally, multiple Krebs cycle intermediates were significantly decreased (e.g., malic acid, fumaric acid, citric/isocitric acid, and succinic acid), suggesting that altered energy metabolism may be underlying the observed GRMD BF muscle dysfunction. In contrast, two

  17. The Role of the Insular Cortex in Retaliation

    PubMed Central

    Lobbestael, Jill; Arntz, Arnoud; Brugman, Suzanne; Sack, Alexander Thomas

    2016-01-01

    The insular cortex has consistently been associated with various aspects of emotion regulation and social interaction, including anger processing and overt aggression. Aggression research distinguishes proactive or instrumental aggression from retaliation, i.e. aggression in response to provocation. Here, we investigated the specific role of the insular cortex during retaliation, employing a controlled behavioral aggression paradigm implementing different levels of provocation. Fifteen healthy male volunteers underwent whole brain functional magnetic resonance imaging (fMRI) to identify brain regions involved in interaction with either a provoking or a non-provoking opponent. FMRI group analyses were complemented by examining the parametric modulations of brain activity related to the individual level of displayed aggression. These analyses identified a hemispheric lateralization as well as an anatomical segregation of insular cortex with specifically the left posterior part being involved in retaliation. The left-lateralization of insular activity during retaliation is in accordance with evidence from electro-physiological studies, suggesting left-lateralized fronto-cortical dominance during anger processing and aggressive acts. The posterior localization of insular activity, on the other hand, suggests a spatial segregation within insular cortex with particularly the posterior part being involved in the processing of emotions that trigger intense bodily sensations and immediate action tendencies. PMID:27096431

  18. Orosensory and Homeostatic Functions of the Insular Taste Cortex.

    PubMed

    de Araujo, Ivan E; Geha, Paul; Small, Dana M

    2012-03-01

    The gustatory aspect of the insular cortex is part of the brain circuit that controls ingestive behaviors based on chemosensory inputs. However, the sensory properties of foods are not restricted to taste and should also include salient features such as odor, texture, temperature, and appearance. Therefore, it is reasonable to hypothesize that specialized circuits within the central taste pathways must be involved in representing several other oral sensory modalities in addition to taste. In this review, we evaluate current evidence indicating that the insular gustatory cortex functions as an integrative circuit, with taste-responsive regions also showing heightened sensitivity to olfactory, somatosensory, and even visual stimulation. We also review evidence for modulation of taste-responsive insular areas by changes in physiological state, with taste-elicited neuronal responses varying according to the nutritional state of the organism. We then examine experimental support for a functional map within the insular cortex that might reflect the various sensory and homeostatic roles associated with this region. Finally, we evaluate the potential role of the taste insular cortex in weight-gain susceptibility. Taken together, the current experimental evidence favors the view that the insular gustatory cortex functions as an orosensory integrative system that not only enables the formation of complex flavor representations but also mediates their modulation by the internal state of the body, playing therefore a central role in food intake regulation.

  19. Insular cortex mediates increased pain tolerance in yoga practitioners.

    PubMed

    Villemure, Chantal; Ceko, Marta; Cotton, Valerie A; Bushnell, M Catherine

    2014-10-01

    Yoga, an increasingly popular discipline among Westerners, is frequently used to improve painful conditions. We investigated possible neuroanatomical underpinnings of the beneficial effects of yoga using sensory testing and magnetic resonance imaging techniques. North American yogis tolerated pain more than twice as long as individually matched controls and had more gray matter (GM) in multiple brain regions. Across subjects, insular GM uniquely correlated with pain tolerance. Insular GM volume in yogis positively correlated with yoga experience, suggesting a causal relationship between yoga and insular size. Yogis also had increased left intrainsular white matter integrity, consistent with a strengthened insular integration of nociceptive input and parasympathetic autonomic regulation. Yogis, as opposed to controls, used cognitive strategies involving parasympathetic activation and interoceptive awareness to tolerate pain, which could have led to use-dependent hypertrophy of insular cortex. Together, these findings suggest that regular and long-term yoga practice improves pain tolerance in typical North Americans by teaching different ways to deal with sensory inputs and the potential emotional reactions attached to those inputs leading to a change in insular brain anatomy and connectivity.

  20. Insular Cortex Mediates Increased Pain Tolerance in Yoga Practitioners

    PubMed Central

    Villemure, Chantal; Čeko, Marta; Cotton, Valerie A.; Bushnell, M. Catherine

    2014-01-01

    Yoga, an increasingly popular discipline among Westerners, is frequently used to improve painful conditions. We investigated possible neuroanatomical underpinnings of the beneficial effects of yoga using sensory testing and magnetic resonance imaging techniques. North American yogis tolerated pain more than twice as long as individually matched controls and had more gray matter (GM) in multiple brain regions. Across subjects, insular GM uniquely correlated with pain tolerance. Insular GM volume in yogis positively correlated with yoga experience, suggesting a causal relationship between yoga and insular size. Yogis also had increased left intrainsular white matter integrity, consistent with a strengthened insular integration of nociceptive input and parasympathetic autonomic regulation. Yogis, as opposed to controls, used cognitive strategies involving parasympathetic activation and interoceptive awareness to tolerate pain, which could have led to use-dependent hypertrophy of insular cortex. Together, these findings suggest that regular and long-term yoga practice improves pain tolerance in typical North Americans by teaching different ways to deal with sensory inputs and the potential emotional reactions attached to those inputs leading to a change in insular brain anatomy and connectivity. PMID:23696275

  1. Orosensory and Homeostatic Functions of the Insular Taste Cortex

    PubMed Central

    de Araujo, Ivan E.; Geha, Paul

    2014-01-01

    The gustatory aspect of the insular cortex is part of the brain circuit that controls ingestive behaviors based on chemosensory inputs. However, the sensory properties of foods are not restricted to taste and should also include salient features such as odor, texture, temperature, and appearance. Therefore, it is reasonable to hypothesize that specialized circuits within the central taste pathways must be involved in representing several other oral sensory modalities in addition to taste. In this review, we evaluate current evidence indicating that the insular gustatory cortex functions as an integrative circuit, with taste-responsive regions also showing heightened sensitivity to olfactory, somatosensory, and even visual stimulation. We also review evidence for modulation of taste-responsive insular areas by changes in physiological state, with taste-elicited neuronal responses varying according to the nutritional state of the organism. We then examine experimental support for a functional map within the insular cortex that might reflect the various sensory and homeostatic roles associated with this region. Finally, we evaluate the potential role of the taste insular cortex in weight-gain susceptibility. Taken together, the current experimental evidence favors the view that the insular gustatory cortex functions as an orosensory integrative system that not only enables the formation of complex flavor representations but also mediates their modulation by the internal state of the body, playing therefore a central role in food intake regulation. PMID:25485032

  2. Insular ecosystems of the southeastern United States—A regional synthesis to support biodiversity conservation in a changing climate

    USGS Publications Warehouse

    Cartwright, Jennifer M.; Wolfe, William J.

    2016-08-11

    In the southeastern United States, insular ecosystems—such as rock outcrops, depression wetlands, high-elevation balds, flood-scoured riparian corridors, and insular prairies and barrens—occupy a small fraction of land area but constitute an important source of regional and global biodiversity, including concentrations of rare and endemic plant taxa. Maintenance of this biodiversity depends upon regimes of abiotic stress and disturbance, incorporating factors such as soil surface temperature, widely fluctuating hydrologic conditions, fires, flood scouring, and episodic droughts that may be subject to alteration by climate change. Over several decades, numerous localized, site-level investigations have yielded important information about the floristics, physical environments, and ecological dynamics of these insular ecosystems; however, the literature from these investigations has generally remained fragmented. This report consists of literature syntheses for eight categories of insular ecosystems of the southeastern United States, concerning (1) physical geography, (2) ecological determinants of community structures including vegetation dynamics and regimes of abiotic stress and disturbance, (3) contributions to regional and global biodiversity, (4) historical and current anthropogenic threats and conservation approaches, and (5) key knowledge gaps relevant to conservation, particularly in terms of climate-change effects on biodiversity. This regional synthesis was undertaken to discern patterns across ecosystems, identify knowledge gaps, and lay the groundwork for future analyses of climate-change vulnerability. Findings from this synthesis indicate that, despite their importance to regional and global biodiversity, insular ecosystems of the southeastern United States have been subjected to a variety of direct and indirect human alterations. In many cases, important questions remain concerning key determinants of ecosystem function. In particular, few

  3. The hybrid operculo-insular electrode: a new electrode for intracranial investigation of perisylvian/insular refractory epilepsy.

    PubMed

    Bouthillier, Alain; Surbeck, Werner; Weil, Alexander G; Tayah, Tania; Nguyen, Dang K

    2012-06-01

    Precise localization of an epileptic focus in the perisylvian/insular area is a major challenge. The difficult access and the high density of blood vessels within the sylvian fissure have lead to poor coverage of intrasylvian (opercular and insular) cortex by available electrodes. To report the creation of a novel electrode designed to record epileptic activity from both the insular cortex and the hidden surfaces of the opercula. The hybrid operculo-insular electrode was fabricated by Ad-Tech Medical Instrument Corporation (Racine, Wisconsin). It was used in combination with regular subdural and depth electrodes for long-term intracranial recordings. The hybrid electrode, which contains both a depth and a strip (opercular) component, is inserted after microsurgical opening of the sylvian fissure. The depth component is implanted directly into the insular cortex. The opercular component has 1 or 2 double-sided recording contacts that face the hidden surfaces of the opercula. The hybrid operculo-insular electrode was used in 5 patients. This method of invasive investigation allowed including (2 patients) or excluding (3 patients) the insula as part of the epileptic focus and the surgical resection. It also allowed extending the epileptogenic zone to include the hidden surface of the frontal operculum in 1 patient. There were no complications related to the insertion of this new electrode. The new hybrid operculo-insular electrode can be used for intracranial investigation of perisylvian/insular refractory epilepsy. It can contribute to increasing cortical coverage of this complex region and may allow better definition of the epileptic focus.

  4. Mechanisms of glutamate transport.

    PubMed

    Vandenberg, Robert J; Ryan, Renae M

    2013-10-01

    L-Glutamate is the predominant excitatory neurotransmitter in the mammalian central nervous system and plays important roles in a wide variety of brain functions, but it is also a key player in the pathogenesis of many neurological disorders. The control of glutamate concentrations is critical to the normal functioning of the central nervous system, and in this review we discuss how glutamate transporters regulate glutamate concentrations to maintain dynamic signaling mechanisms between neurons. In 2004, the crystal structure of a prokaryotic homolog of the mammalian glutamate transporter family of proteins was crystallized and its structure determined. This has paved the way for a better understanding of the structural basis for glutamate transporter function. In this review we provide a broad perspective of this field of research, but focus primarily on the more recent studies with a particular emphasis on how our understanding of the structure of glutamate transporters has generated new insights.

  5. [Risk taking and the insular cortex].

    PubMed

    Ishii, Hironori; Tsutsui, Ken-Ichiro; Iijima, Toshio

    2013-08-01

    Risk taking can lead to ruin, but sometimes, it can also provide great success. How does our brain make a decision on whether to take a risk or to play it safe? Recent studies have revealed the neural basis of risky decision making. In this review, we focus on the role of the anterior insular cortex (AIC) in risky decision making. Although human imaging studies have shown activations of the AIC in various gambling tasks, the causal involvement of the AIC in risky decision making was still unclear. Recently, we demonstrated a causality of the AIC in risky decision making by using a pharmacological approach in behaving rats-temporary inactivation of the AIC decreased the risk preference in gambling tasks, whereas temporary inactivation of the adjacent orbitofrontal cortex (OFC) increased the risk preference. The latter finding is consistent with a previous finding that patients with damage to the OFC take abnormally risky decisions in the Iowa gambling task. On the basis of these observations, we hypothesize that the intact AIC promotes risk-seeking behavior, and that the AIC and OFC are crucial for balancing the opposing motives of whether to take a risk or avoid it. However, the functional relationship between the AIC and OFC remains unclear. Future combinations of inactivation and electrophysiological studies may promote further understanding of risky decision making.

  6. Anterior insular cortex and emotional awareness.

    PubMed

    Gu, Xiaosi; Hof, Patrick R; Friston, Karl J; Fan, Jin

    2013-10-15

    This paper reviews the foundation for a role of the human anterior insular cortex (AIC) in emotional awareness, defined as the conscious experience of emotions. We first introduce the neuroanatomical features of AIC and existing findings on emotional awareness. Using empathy, the awareness and understanding of other people's emotional states, as a test case, we then present evidence to demonstrate: 1) AIC and anterior cingulate cortex (ACC) are commonly coactivated as revealed by a meta-analysis, 2) AIC is functionally dissociable from ACC, 3) AIC integrates stimulus-driven and top-down information, and 4) AIC is necessary for emotional awareness. We propose a model in which AIC serves two major functions: integrating bottom-up interoceptive signals with top-down predictions to generate a current awareness state and providing descending predictions to visceral systems that provide a point of reference for autonomic reflexes. We argue that AIC is critical and necessary for emotional awareness. Copyright © 2013 Wiley Periodicals, Inc.

  7. The Insular Cortex and Takotsubo Cardiomyopathy.

    PubMed

    Nagai, Michiaki; Dote, Keigo; Kato, Masaya; Sasaki, Shota; Oda, Noboru; Kagawa, Eisuke; Nakano, Yoshinori; Yamane, Aya; Higashihara, Tasuku; Miyauchi, Shunsuke; Tsuchiya, Akane; Harada, Wakako; Kario, Kazuomi

    2017-01-01

    Transient left ventricular dysfunction in patients under emotional stress, also known as Takotsubo cardiomyopathy, has been recognized as a distinct clinical entity. Recent studies have supported the concept notion that the cardiovascular system is regulated by cortical modulation. A network consisting of the insular cortex (Ic), anterior cingulate gyrus, and amygdala plays a crucial role in the regulation of the central autonomic nervous system in relation to emotional stress such as anxiety, fear and sadness. Because the Ic is located in the region of the middle cerebral arteries, its structure tends to be exposed to a higher risk of cerebrovascular disease. Ic damage has been associated with myocardial injury, increased brain natriuretic peptide, and the incidence of Takotsubo cardiomyopathy. Because Ic damage has been associated with increased sympathetic nervous system activity, Ic damage is suggested to have a pivotal role in the pathophysiology of Takotsubo cardiomyopathy. In this review, we focus on the role of the Ic as a mediator for the cardiovascular system in relation to emotional stress, and we summarizes the current knowledge on the relationships between the Ic and Takotsubo cardiomyopathy. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  8. 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…

  9. 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…

  10. Repeated Binge Drinking Increases Perineuronal Nets in the Insular Cortex

    PubMed Central

    Chen, Hu; He, Donghong; Lasek, Amy W.

    2015-01-01

    Background Alcohol exposure leads to changes in the extracellular matrix (ECM) in the brain, which profoundly impacts neuronal plasticity. Perineuronal nets (PNs) are specialized ECM structures that enclose subpopulations of neurons in the cortex. Adolescent exposure to alcohol induces long-lasting increases in the expression of PN components in the cortex in adult mice. However, it has not been determined whether binge alcohol exposure in young adults alters PNs. Here, we examined PNs and their core components in the insula and primary motor cortex after repeated binge-like ethanol consumption in adult mice. Methods The 4 day drinking in the dark (DID) procedure was performed in mice for 1 or 6 weeks to model binge alcohol consumption. The impact of ethanol drinking on PNs was examined by fluorescent staining of brain sections using a marker for PNs, Wisteria floribunda agglutinin (WFA). In another set of experiments, cortex was dissected and Western blots and quantitative real-time PCR (qPCR) were performed to evaluate the expression of the PN proteins aggrecan, brevican, and phosphacan. Results Binge-like ethanol drinking for 6 weeks caused a significant increase in PNs in the insula, as measured by WFA binding. Aggrecan, brevican and phosphacan protein expression, and aggrecan mRNA expression, were also elevated in the insula after 6 weeks of ethanol drinking. In contrast, expression of PN components did not change after 1 week of DID. The increase in PNs appears to be specific to the insula, since alterations were not observed in the primary motor cortex. Conclusions Our results provide the first evidence that insular PNs increase after long-term binge drinking. The insula mediates compulsive alcohol use. Since PNs influence neuronal firing and plasticity, increased PNs in the insula after multiple binge cycles may contribute to restricted neuronal plasticity and lead to the development of compulsive alcohol use. PMID:26332441

  11. Lights and shadows in the evolutionary patterns of insular bovids.

    PubMed

    Rozzi, Roberto; Palombo, Maria Rita

    2014-03-01

    Endemic bovids are intriguing elements of insular faunas. The living species include the Japanese serow (Capricornis crispus) and the Formosan serow (C. swinhoei), the tamaraw from Mindoro, Philippines, (Bubalus mindorensis) and the anoas (B. depressicornis and B. quarlesi), 2 species of dwarf buffalos endemic to Sulawesi, Indonesia. Fossil endemic bovids are only recorded in some Asian, North American and Western Mediterranean islands. Here we present a comprehensive overview of the changes in body size and evolutionary patterns exhibited by both extant and extinct insular bovids. Our appraisal indicates that each insular representative of Bovidae shows its own peculiar evolutionary model, albeit some parallel trends exist (e.g. reduction in body size, allometric changes in limb bones, alteration of the life history traits). Some changes in morphology (e.g. the simplification of horn cores, the increase in hypsodonty, the acquisition of a 'low-gear' locomotion), for instance, appear as common, albeit not general, patterns triggered by a combination of selective forces. Body size patterns support the 'generality of the island rule' and suggest that biotic interaction had/have a major role in influencing body size evolution in these species, although in different ways on different islands. All things considered, available evidence suggest that a major role in the evolution of insular bovids is played by the structure of the insular community, the nature of available niches and by the dynamics of ecological interactions.

  12. Image-guided transsylvian, transinsular approach for insular cavernous angiomas.

    PubMed

    Tirakotai, Wuttipong; Sure, Ulrich; Benes, Ludwig; Krischek, Boris; Bien, Siegfried; Bertalanffy, Helmut

    2007-07-01

    Surgical treatment of cavernomas arising in the insula is especially challenging because of the proximity to the internal capsule and lenticulostriate arteries. We present our technique of image guidance for operations on insular cavernomas and assess its clinical usefulness. Between 1997 and 2003, with the guidance of a frameless stereotactic system (BrainLab AG, Munich, Germany), we operated on eight patients who harbored an insular cavernoma. Neuronavigation was used for 1) accurate planning of the craniotomy, 2) identification of the distal sylvian fissure, and, finally, 3) finding the exact site for insular corticotomy. Postoperative clinical and neuroradiological evaluations were performed in each patient. The navigation system worked properly in all eight neurosurgical patients. Exact planning of the approach and determination of the ideal trajectory of dissection toward the cavernoma was possible in every patient. All cavernomas were readily identified and completely removed by use of microsurgical techniques. No surgical complications occurred, and the postoperative course was uneventful in all patients. Image guidance during surgery for insular cavernomas provides high accuracy for lesion targeting and permits excellent anatomic orientation. Accordingly, safe exposure can be obtained because of a tailored dissection of the sylvian fissure and minimal insular corticotomy.

  13. Image-guided transsylvian, transinsular approach for insular cavernous angiomas.

    PubMed

    Tirakotai, Wuttipong; Sure, Ulrich; Benes, Ludwig; Krischek, Boris; Bien, Sigfried; Bertalanffy, Helmut

    2003-12-01

    Surgical treatment of cavernomas arising in the insula is especially challenging because of the proximity to the internal capsule and lenticulostriate arteries. We present our technique of image guidance for operations on insular cavernomas and assess its clinical usefulness. Between 1997 and 2003, with the guidance of a frameless stereotactic system (BrainLab AG, Munich, Germany), we operated on eight patients who harbored an insular cavernoma. Neuronavigation was used for 1) accurate planning of the craniotomy, 2) identification of the distal sylvian fissure, and, finally, 3) finding the exact site for insular corticotomy. Postoperative clinical and neuroradiological evaluations were performed in each patient. The navigation system worked properly in all eight neurosurgical patients. Exact planning of the approach and determination of the ideal trajectory of dissection toward the cavernoma was possible in every patient. All cavernomas were readily identified and completely removed by use of microsurgical techniques. No surgical complications occurred, and the postoperative course was uneventful in all patients. Image guidance during surgery for insular cavernomas provides high accuracy for lesion targeting and permits excellent anatomic orientation. Accordingly, safe exposure can be obtained because of a tailored dissection of the sylvian fissure and minimal insular corticotomy.

  14. Report to Congress on Insular Area energy vulnerability

    SciTech Connect

    Not Available

    1994-05-01

    This report was prepared in response to Section 1406 of the Energy Policy Act of 1992 (Public Law 102-486), which directed the Department of Energy (DOE) to ``conduct a study of the implications of the unique vulnerabilities of the insular areas to an oil supply disruption,`` and to ``outline how the insular areas shall gain access to vital oil supplies during times of national emergency.`` The Act defines the insular areas to be the US Virgin Islands and Puerto Rico in the Caribbean, and Guam, American Samoa, the Commonwealth of the Northern Mariana Islands (CNMI), and Palau in the Pacific. In the study, ``unique vulnerabilities`` were defined as susceptibility to: (1) more frequent or more likely interruptions of oil supplies compared to the US Mainland, and/or (2) disproportionately larger or more likely economic losses in the event of an oil supply disruption. In order to assess unique vulnerabilities, the study examined the insular areas` experience during past global disruptions of oil supplies and during local emergencies caused by natural disasters. The effects of several possible future global disruptions and local emergencies were also analyzed. Analyses were based on historical data, simulations using energy and economic models, and interviews with officials in the insular governments and the energy industry.

  15. Forest fires in the insular Caribbean.

    PubMed

    Robbins, A Marcus J; Eckelmann, Claus-Martin; Quiñones, Maya

    2008-12-01

    This paper presents a summary of the forest fire reports in the insular Caribbean derived from both management reports and an analysis of publicly available Moderate Resolution Imaging Spectrodiometer (MODIS) satellite active fire products from the region. A vast difference between the amount of fires reported by land managers and fire points in the MODIS Fire Information for Resource Management System data can be observed. Future research is recommended to better understand the nature of these differences. While there is a general lack of available statistical data on forest fires in the Caribbean, a few general observations can be made: Forest fires occur mainly in dry forest types (500 to 1000 mm of mean annual rainfall). These are also the areas where most human settlements are located. Lowland high forests and montane forests with higher rainfall (1000 and more mm y(-1)) are less susceptible to forest fire, but they can burn in exceptionally dry years. Most of the dry forest ecosystems in the Caribbean can be considered to be fire-sensitive ecosystems, while the pine forests in the Caribbean (Cuba, Dominican Republic, and the Bahamas) are maintained by wildfires. In fire-sensitive ecosystems, uncontrolled burning often encourages the spread of alien invasive species. A Caribbean Fire Management Cooperation Strategy was developed between 2005 and 2006 under auspices of the Food and Agriculture Organization of the United Nations. This regional strategy aims to strengthen Caribbean fire management networking by encouraging closer collaboration among countries with similar ecological conditions. The strategy for the Caribbean identifies a number of research, training, and management activities to improve wildfire management capacity in the Caribbean.

  16. 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

  17. Insular cortex activity and the evocation of laughter.

    PubMed

    Wattendorf, Elise; Westermann, Birgit; Lotze, Martin; Fiedler, Klaus; Celio, Marco R

    2016-06-01

    The insular cortex is fundamentally involved in the processing of interoceptive information. It has been postulated that the integrative monitoring of the bodily responses to environmental stimuli is crucial for the recognition and experience of emotions. Because emotional arousal is known to be closely coupled to functions of the anterior insula, we suspected laughter to be associated primarily with neuronal activity in this region. An anatomically constrained re-analysis of our imaging data pertaining to ticklish laughter, to inhibited ticklish laughter, and to voluntary laughter revealed regional differences in the levels of neuronal activity in the posterior and mid-/anterior portions of the insula. Ticklish laughter was associated specifically with right ventral anterior insular activity, which was not detected under the other two conditions. Hence, apparently, only laughter that is evoked as an emotional response bears the signature of autonomic arousal in the insular cortex.

  18. 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.

  19. The role of hypothermia in the regulation of blood glutamate levels in naive rats.

    PubMed

    Boyko, Matthew; Kuts, Ruslan; Gruenbaum, Benjamin F; Melamed, Israel; Gruenbaum, Shaun E; Klein, Moti; Shapira, Yoram; Zlotnik, Alexander

    2013-04-01

    The exact mechanism of hypothermia-induced neuroprotection has not been determined yet; however, we hypothesized that it may be mediated by a blood glutamate-scavenging effect. Here, we examine the effect of hypothermic conditions (mild, moderate, and deep) on blood glutamate levels in naive rats. To identify the mechanism of hypothermia-induced glutamate reduction, we also measured concentrations of glutamate oxaloacetate transaminase (GOT) and glutamate pyruvate transaminase (GPT), the primary regulators of glutamate concentration in blood. Rats were anesthetized with isoflurane, and their rectal temperature was maintained for 6 hours at 36 to 37°C, 33 to 36°C, 30 to 32°C, 18 to 22°C, or was not maintained artificially. At 6 hours, active cooling was discontinued and rats were allowed to rewarm. There were 12 rats in each group for a total of 60 rats. Blood samples were drawn at 0, 3, 6, 12, 24, and 48 hours for the determination of blood glutamate, GOT, and GPT levels. A strong correlation between body temperature and blood glutamate levels was observed (P<0.001). Mild (33 to 36°C) and moderate (30 to 32°C) hypothermia led to reduced blood glutamate levels (P<0.001). Deep hypothermia (18 to 22°C) was associated with significant elevations in blood glutamate levels (P<0.001). Hypothermia, irrespective of the degree, led to elevations in GOT in plasma (P<0.001). Mild and moderate hypothermia led to a reduction in blood glutamate levels in rats, whereas deep hypothermia was associated with a significant elevation in blood glutamate levels. We further demonstrated an elevation of GOT and GPT levels, supporting their involvement in reducing blood glutamate by the conversion of glutamate to 2-ketoglutarate. We suggest that the neuroprotective properties of hypothermia may be partially because of a blood glutamate-scavenging mechanism.

  20. Nerve Growth Factor with Insular Cortical Grafts Induces Recovery of Learning and Reestablishes Graft Choline Acetyltransferase Activity

    PubMed Central

    Escobar, M. L.; Jiménez, N.; López-García, J. C.; Tapia, R.; Bermúdez-Rattoni, F.

    1993-01-01

    Rats showing disrupted taste aversion due to insular cortex (IC)-lesions received either IC-grafts with NGF, grafts without NGF, or NGF alone. An additional group served as lesioned controls. Only those animals that received IC-grafts with NGF recovered the ability to learn the conditioned taste aversion task, at 15 days post-graft. Choline acetyltransferase (ChAT) activity in the IC-grafts with, but not without NGF, was similar to the IC activity of unoperated controls. In contrast, glutamate decarboxylase activity was similar in all the groups. These findings suggest that IC-grafts associated with NGF induce recovery of learning abilities in IC-lesioned rats, which correlates with reestablishment of ChAT activity in the grafts at 15 days post-implantation. PMID:8110867

  1. 24 CFR 570.405 - The insular areas.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 24 Housing and Urban Development 3 2011-04-01 2010-04-01 true The insular areas. 570.405 Section 570.405 Housing and Urban Development Regulations Relating to Housing and Urban Development (Continued) OFFICE OF ASSISTANT SECRETARY FOR COMMUNITY PLANNING AND DEVELOPMENT, DEPARTMENT OF HOUSING AND...

  2. 24 CFR 35.940 - Special requirements for insular areas.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 24 Housing and Urban Development 1 2011-04-01 2011-04-01 false Special requirements for insular areas. 35.940 Section 35.940 Housing and Urban Development Office of the Secretary, Department of Housing and Urban Development LEAD-BASED PAINT POISONING PREVENTION IN CERTAIN RESIDENTIAL...

  3. 24 CFR 35.940 - Special requirements for insular areas.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 24 Housing and Urban Development 1 2012-04-01 2012-04-01 false Special requirements for insular areas. 35.940 Section 35.940 Housing and Urban Development Office of the Secretary, Department of Housing and Urban Development LEAD-BASED PAINT POISONING PREVENTION IN CERTAIN RESIDENTIAL...

  4. 24 CFR 35.940 - Special requirements for insular areas.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 24 Housing and Urban Development 1 2013-04-01 2013-04-01 false Special requirements for insular areas. 35.940 Section 35.940 Housing and Urban Development Office of the Secretary, Department of Housing and Urban Development LEAD-BASED PAINT POISONING PREVENTION IN CERTAIN RESIDENTIAL...

  5. 24 CFR 35.940 - Special requirements for insular areas.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 24 Housing and Urban Development 1 2014-04-01 2014-04-01 false Special requirements for insular areas. 35.940 Section 35.940 Housing and Urban Development Office of the Secretary, Department of Housing and Urban Development LEAD-BASED PAINT POISONING PREVENTION IN CERTAIN RESIDENTIAL...

  6. 24 CFR 35.940 - Special requirements for insular areas.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 24 Housing and Urban Development 1 2010-04-01 2010-04-01 false Special requirements for insular areas. 35.940 Section 35.940 Housing and Urban Development Office of the Secretary, Department of Housing and Urban Development LEAD-BASED PAINT POISONING PREVENTION IN CERTAIN RESIDENTIAL...

  7. 24 CFR 570.442 - Reallocations-Insular Areas.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... Section 570.442 Housing and Urban Development Regulations Relating to Housing and Urban Development... according to population. (b) Any Insular Area grant funds for a fiscal year reserved for an applicant that... according to population. (c) No amounts shall be reallocated under this section in any fiscal year to any...

  8. 24 CFR 570.405 - The insular areas.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 24 Housing and Urban Development 3 2010-04-01 2010-04-01 false The insular areas. 570.405 Section 570.405 Housing and Urban Development Regulations Relating to Housing and Urban Development (Continued) OFFICE OF ASSISTANT SECRETARY FOR COMMUNITY PLANNING AND DEVELOPMENT, DEPARTMENT OF HOUSING AND...

  9. 24 CFR 570.442 - Reallocations-Insular Areas.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... HOUSING AND URBAN DEVELOPMENT COMMUNITY FACILITIES COMMUNITY DEVELOPMENT BLOCK GRANTS Small Cities, Non... according to population. (b) Any Insular Area grant funds for a fiscal year reserved for an applicant that... according to population. (c) No amounts shall be reallocated under this section in any fiscal year to...

  10. Ideas on the Margins: Professional Counseling and Ideological Insularity

    ERIC Educational Resources Information Center

    Hansen, James

    2010-01-01

    Efforts to professionalize counseling practice have yielded extraordinary benefits to counselors. However, professionalization has also caused counselors to adopt strict definitions of their education, practices, and ethics. In order to combat the ideological insularity brought on by professionalization, several marginalized ideas are considered.…

  11. Insular Cortex Is Involved in Consolidation of Object Recognition Memory

    ERIC Educational Resources Information Center

    Bermudez-Rattoni, Federico; Okuda, Shoki; Roozendaal, Benno; McGaugh, James L.

    2005-01-01

    Extensive evidence indicates that the insular cortex (IC), also termed gustatory cortex, is critically involved in conditioned taste aversion and taste recognition memory. Although most studies of the involvement of the IC in memory have investigated taste, there is some evidence that the IC is involved in memory that is not based on taste. In…

  12. Freshwater resources in the insular Caribbean: an environmental perspective

    Treesearch

    T. Heartsill Scalley

    2012-01-01

    From islands with no permanent flowing streams to those with navigable inland waters, the insular Caribbean contains a great range of conditions regarding the access to freshwater resources. Because of the variation in topography and size, the ability of islands to retain freshwater also varies widely. The usage of freshwater in this region is being led by two major...

  13. The cystine/glutamate antiporter system xc− drives breast tumor cell glutamate release and cancer-induced bone pain

    PubMed Central

    Slosky, Lauren M.; BassiriRad, Neemah M.; Symons, Ashley M.; Thompson, Michelle; Doyle, Timothy; Forte, Brittany L.; Staatz, William D.; Bui, Lynn; Neumann, William L.; Mantyh, Patrick W.; Salvemini, Daniela; Largent-Milnes, Tally M.; Vanderah, Todd W.

    2016-01-01

    Abstract Bone is one of the leading sites of metastasis for frequently diagnosed malignancies, including those arising in the breast, prostate and lung. Although these cancers develop unnoticed and are painless in their primary sites, bone metastases result in debilitating pain. Deeper investigation of this pain may reveal etiology and lead to early cancer detection. Cancer-induced bone pain (CIBP) is inadequately managed with current standard-of-care analgesics and dramatically diminishes patient quality of life. While CIBP etiology is multifaceted, elevated levels of glutamate, an excitatory neurotransmitter, in the bone-tumor microenvironment may drive maladaptive nociceptive signaling. Here, we establish a relationship between the reactive nitrogen species peroxynitrite, tumor-derived glutamate, and CIBP. In vitro and in a syngeneic in vivo model of breast CIBP, murine mammary adenocarcinoma cells significantly elevated glutamate via the cystine/glutamate antiporter system xc−. The well-known system xc− inhibitor sulfasalazine significantly reduced levels of glutamate and attenuated CIBP-associated flinching and guarding behaviors. Peroxynitrite, a highly reactive species produced in tumors, significantly increased system xc− functional expression and tumor cell glutamate release. Scavenging peroxynitrite with the iron and mangano-based porphyrins, FeTMPyP and SRI10, significantly diminished tumor cell system xc− functional expression, reduced femur glutamate levels and mitigated CIBP. In sum, we demonstrate how breast cancer bone metastases upregulate a cystine/glutamate co-transporter to elevate extracellular glutamate. Pharmacological manipulation of peroxynitrite or system xc− attenuates CIBP, supporting a role for tumor-derived glutamate in CIBP and validating the targeting of system xc− as a novel therapeutic strategy for the management of metastatic bone pain. PMID:27482630

  14. Insular projections to the parahippocampal region in the rat.

    PubMed

    Mathiasen, Mathias L; Hansen, Lilliane; Witter, Menno P

    2015-06-15

    The insular cortex is involved in the perception of interoceptive signals, coding of emotional and affective states, and processing information from gustatory, olfactory, auditory, somatosensory, and nociceptive modalities. This information represents an important component of episodic memory, mediated by the parahippocampal-hippocampal region. A comprehensive description of insular projections to the latter region is lacking. Previous studies reported that insular projections do not target any of the subdivisions in the hippocampal formation (the dentate gyus, the cornu ammonis [CA] fields 1, 2, and 3 and the subiculum), but, in contrast, target the parahippocampal region (perirhinal, postrhinal, lateral and medial entorhinal cortices, and pre- and parasubiculum). The present study examined the topographical and laminar organization of insular projections to the parahippocampal region in the rat with the use of anterograde tracing. Notably, our results corroborated the absence of hippocampal projections. We further showed that the perirhinal and the lateral entorhinal cortices received extensive projections from the insular cortex, primarily from its agranular areas. With the exception of a weak projection to the postrhinal cortex, projections to the remaining parahippocampal areas were either absent or very sparse. The projections to the lateral entorhinal cortex displayed a preference for the deep layers of its most lateral subdivisions, known also to receive hippocampal inputs. Projections to the perirhinal cortex primarily targeted the superficial layers with a preference for its ventral subdivision, referred to as area 35. Our findings indicate that only processed information, reflecting emotional and affective states, but not primary gustatory and viscerosensory information, has direct access to the parahippocampal-hippocampal system.

  15. Repeated cycles of chronic intermittent ethanol exposure increases basal glutamate in the nucleus accumbens of mice without affecting glutamate transport.

    PubMed

    Griffin, William C; Ramachandra, Vorani S; Knackstedt, Lori A; Becker, Howard C

    2015-01-01

    Repeated cycles of chronic intermittent ethanol (CIE) exposure increase voluntary consumption of ethanol in mice. Previous work has shown that extracellular glutamate in the nucleus accumbens (NAc) is significantly elevated in ethanol-dependent mice and that pharmacologically manipulating glutamate concentrations in the NAc will alter ethanol drinking, indicating that glutamate homeostasis plays a crucial role in ethanol drinking in this model. The present studies were designed to measure extracellular glutamate at a time point in which mice would ordinarily be allowed voluntary access to ethanol in the CIE model and, additionally, to measure glutamate transport capacity in the NAc at the same time point. Extracellular glutamate was measured using quantitative microdialysis procedures. Glutamate transport capacity was measured under Na(+)-dependent and Na(+)-independent conditions to determine whether the function of excitatory amino acid transporters (also known as system XAG) or of system Xc (-) (glial cysteine-glutamate exchanger) was influenced by CIE exposure. The results of the quantitative microdialysis experiment confirm increased extracellular glutamate (approximately twofold) in the NAc of CIE exposed mice (i.e., ethanol-dependent) compared to non-dependent mice in the NAc, consistent with earlier work. However, the increase in extracellular glutamate was not due to altered transporter function in the NAc of ethanol-dependent mice, because neither Na(+)-dependent nor Na(+)-independent glutamate transport was significantly altered by CIE exposure. These findings point to the possibility that hyperexcitability of cortical-striatal pathways underlies the increases in extracellular glutamate found in the ethanol-dependent mice.

  16. Insula and sensory insular cortex and somatosensory control in patients with insular stroke.

    PubMed

    Baier, B; zu Eulenburg, P; Geber, C; Rohde, F; Rolke, R; Maihöfner, C; Birklein, F; Dieterich, M

    2014-11-01

    In functional imaging studies, the insular cortex (IC) has been identified as an essential part of the processing of a whole spectrum of multimodal sensory input. However, there are no lesion studies including a sufficient number of patients, which would reinforce the functional imaging data obtained from healthy subjects. Such lesion studies should examine how damage to the IC affects sensory perception. We chose acute stroke patients with lesions affecting the IC in order to fill this gap. A comprehensive sensory profiling by applying a quantitative sensory testing protocol was performed and a voxel-lesion behaviour mapping analysis in 24 patients with acute unilateral cortical damage was applied. Our data demonstrate that patients with lesions of the posterior IC have deficits in temperature perception, but did not show other sensory deficits such as hot or cold pain perception associated with specific lesion locations. Our data allow the conclusion that the posterior IC may represent the major region responsible for encoding warm and cold perception in the brain. To what extent focal IC lesions may also impair pain processing or induce post-stroke pain has to be addressed in future studies including more patients. © 2014 European Pain Federation - EFIC®

  17. Montane Forest Management in the Insular Caribbean.

    Treesearch

    F. H. Wadsworth

    1999-01-01

    Two Elevations-above 800m and above 300m- define the montane forests of the caribbean islands. Of the 36 islands considered, 27 have mountains above 300m and 14, above 800m. of the 233,000 km2 of the island, at least 118,000 km2 are above 300m m, and 60,000 km2 are above 800 m.

  18. Body Size Evolution in Insular Speckled Rattlesnakes (Viperidae: Crotalus mitchellii)

    PubMed Central

    Meik, Jesse M.; Lawing, A. Michelle; Pires-daSilva, André

    2010-01-01

    Background Speckled rattlesnakes (Crotalus mitchellii) inhabit multiple islands off the coast of Baja California, Mexico. Two of the 14 known insular populations have been recognized as subspecies based primarily on body size divergence from putative mainland ancestral populations; however, a survey of body size variation from other islands occupied by these snakes has not been previously reported. We examined body size variation between island and mainland speckled rattlesnakes, and the relationship between body size and various island physical variables among 12 island populations. We also examined relative head size among giant, dwarfed, and mainland speckled rattlesnakes to determine whether allometric differences conformed to predictions of gape size (and indirectly body size) evolving in response to shifts in prey size. Methodology/Principal Findings Insular speckled rattlesnakes show considerable variation in body size when compared to mainland source subspecies. In addition to previously known instances of gigantism on Ángel de la Guarda and dwarfism on El Muerto, various degrees of body size decrease have occurred frequently in this taxon, with dwarfed rattlesnakes occurring mostly on small, recently isolated, land-bridge islands. Regression models using the Akaike information criterion (AIC) showed that mean SVL of insular populations was most strongly correlated with island area, suggesting the influence of selection for different body size optima for islands of different size. Allometric differences in head size of giant and dwarf rattlesnakes revealed patterns consistent with shifts to larger and smaller prey, respectively. Conclusions/Significance Our data provide the first example of a clear relationship between body size and island area in a squamate reptile species; among vertebrates this pattern has been previously documented in few insular mammals. This finding suggests that selection for body size is influenced by changes in community dynamics

  19. Body size evolution in insular speckled rattlesnakes (Viperidae: Crotalus mitchellii).

    PubMed

    Meik, Jesse M; Lawing, A Michelle; Pires-daSilva, André

    2010-03-04

    Speckled rattlesnakes (Crotalus mitchellii) inhabit multiple islands off the coast of Baja California, Mexico. Two of the 14 known insular populations have been recognized as subspecies based primarily on body size divergence from putative mainland ancestral populations; however, a survey of body size variation from other islands occupied by these snakes has not been previously reported. We examined body size variation between island and mainland speckled rattlesnakes, and the relationship between body size and various island physical variables among 12 island populations. We also examined relative head size among giant, dwarfed, and mainland speckled rattlesnakes to determine whether allometric differences conformed to predictions of gape size (and indirectly body size) evolving in response to shifts in prey size. Insular speckled rattlesnakes show considerable variation in body size when compared to mainland source subspecies. In addition to previously known instances of gigantism on Angel de la Guarda and dwarfism on El Muerto, various degrees of body size decrease have occurred frequently in this taxon, with dwarfed rattlesnakes occurring mostly on small, recently isolated, land-bridge islands. Regression models using the Akaike information criterion (AIC) showed that mean SVL of insular populations was most strongly correlated with island area, suggesting the influence of selection for different body size optima for islands of different size. Allometric differences in head size of giant and dwarf rattlesnakes revealed patterns consistent with shifts to larger and smaller prey, respectively. Our data provide the first example of a clear relationship between body size and island area in a squamate reptile species; among vertebrates this pattern has been previously documented in few insular mammals. This finding suggests that selection for body size is influenced by changes in community dynamics that are related to graded differences in area over what are

  20. 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.

  1. Activation of right insular cortex during imaginary speech articulation.

    PubMed

    Kato, Yutaka; Muramatsu, Taro; Kato, Motoichiro; Shintani, Masuro; Kashima, Haruo

    2007-03-26

    Human speech articulation is a complex process controlled by a form of 'programming' implemented in the brain. Analysis of speech articulation using neuroimaging techniques is difficult, however, because motor noise is time-locked to the articulatory events. The current magnetoencephalography study, in which 12 participants were required to imagine vocalizing a phonogram after a visual cue, was designed to visualize the prearticulatory 'automatic' processes corresponding to the motor initiation. Magnetic activity correlating with the preparation for articulation occurred in the insular cortices at about 160 ms after the visual cue, and had a relative dominance in the right hemisphere. This suggests that motor control of speech proceeds from the insular regions, although the 'automatic' nature of our task might have led to the observed right-sided dominance.

  2. History of glutamate production.

    PubMed

    Sano, Chiaki

    2009-09-01

    In 1907 Kikunae Ikeda, a professor at the Tokyo Imperial University, began his research to identify the umami component in kelp. Within a year, he had succeeded in isolating, purifying, and identifying the principal component of umami and quickly obtained a production patent. In 1909 Saburosuke Suzuki, an entrepreneur, and Ikeda began the industrial production of monosodium l-glutamate (MSG). The first industrial production process was an extraction method in which vegetable proteins were treated with hydrochloric acid to disrupt peptide bonds. l-Glutamic acid hydrochloride was then isolated from this material and purified as MSG. Initial production of MSG was limited because of the technical drawbacks of this method. Better methods did not emerge until the 1950s. One of these was direct chemical synthesis, which was used from 1962 to 1973. In this procedure, acrylonitrile was the starting material, and optical resolution of dl-glutamic acid was achieved by preferential crystallization. In 1956 a direct fermentation method to produce glutamate was introduced. The advantages of the fermentation method (eg, reduction of production costs and environmental load) were large enough to cause all glutamate manufacturers to shift to fermentation. Today, total world production of MSG by fermentation is estimated to be 2 million tons/y (2 billion kg/y). However, future production growth will likely require further innovation.

  3. Glutamate and Parkinson's disease.

    PubMed

    Blandini, F; Porter, R H; Greenamyre, J T

    1996-02-01

    Altered glutamatergic neurotransmission and neuronal metabolic dysfunction appear to be central to the pathophysiology of Parkinson's disease (PD). The substantia nigra pars compacta--the area where the primary pathological lesion is located--is particularly exposed to oxidative stress and toxic and metabolic insults. A reduced capacity to cope with metabolic demands, possibly related to impaired mitochondrial function, may render nigral highly vulnerable to the effects of glutamate, which acts as a neurotoxin in the presence of impaired cellular energy metabolism. In this way, glutamate may participate in the pathogenesis of PD. Degeneration of dopamine nigral neurons is followed by striatal dopaminergic denervation, which causes a cascade of functional modifications in the activity of basal ganglia nuclei. As an excitatory neurotransmitter, glutamate plays a pivotal role in normal basal ganglia circuitry. With nigrostriatal dopaminergic depletion, the glutamatergic projections from subthalamic nucleus to the basal ganglia output nuclei become overactive and there are regulatory changes in glutamate receptors in these regions. There is also evidence of increased glutamatergic activity in the striatum. In animal models, blockade of glutamate receptors ameliorates the motor manifestations of PD. Therefore, it appears that abnormal patterns of glutamatergic neurotransmission are important in the symptoms of PD. The involvement of the glutamatergic system in the pathogenesis and symptomatology of PD provides potential new targets for therapeutic intervention in this neurodegenerative disorder.

  4. The Insular Taste Cortex Contributes to Odor Quality Coding

    PubMed Central

    Veldhuizen, Maria G.; Nachtigal, Danielle; Teulings, Lynsey; Gitelman, Darren R.; Small, Dana M.

    2010-01-01

    Despite distinct peripheral and central pathways, stimulation of both the olfactory and the gustatory systems may give rise to the sensation of sweetness. Whether there is a common central mechanism producing sweet quality sensations or two discrete mechanisms associated independently with gustatory and olfactory stimuli is currently unknown. Here we used fMRI to determine whether odor sweetness is represented in the piriform olfactory cortex, which is thought to code odor quality, or in the insular taste cortex, which is thought to code taste quality. Fifteen participants sampled two concentrations of a pure sweet taste (sucrose), two sweet food odors (chocolate and strawberry), and two sweet floral odors (lilac and rose). Replicating prior work we found that olfactory stimulation activated the piriform, orbitofrontal and insular cortices. Of these regions, only the insula also responded to sweet taste. More importantly, the magnitude of the response to the food odors, but not to the non-food odors, in this region of insula was positively correlated with odor sweetness rating. These findings demonstrate that insular taste cortex contributes to odor quality coding by representing the taste-like aspects of food odors. Since the effect was specific to the food odors, and only food odors are experienced with taste, we suggest this common central mechanism develops as a function of experiencing flavors. PMID:20700500

  5. Insular Volume Reduction in Patients with Social Anxiety Disorder.

    PubMed

    Kawaguchi, Akiko; Nemoto, Kiyotaka; Nakaaki, Shutaro; Kawaguchi, Takatsune; Kan, Hirohito; Arai, Nobuyuki; Shiraishi, Nao; Hashimoto, Nobuhiko; Akechi, Tatsuo

    2016-01-01

    Despite the fact that social anxiety disorder (SAD) is highly prevalent, there have been only a few structural imaging studies. Moreover, most of them reported about a volume reduction in amygdale, which plays a key role in the neural function of SAD. Insula is another region of interest. Its hyperactivity in regard to processing negative emotional information or interoceptive awareness has been detected in patients with SAD. Referring to these studies, we hypothesized that insular volumes might reduce in patients with SAD and made a comparison of insular volumes between 13 patients with SAD and 18 healthy controls with matched age and gender using voxel-based morphometry. As a result, we found a significant volume reduction in insula in the SAD group. Our results suggest that the patients with SAD might have an insular volume reduction apart from amygdala. Since insula plays a critical role in the pathology of SAD, more attention should be paid not only to functional study but also morphometrical study of insula.

  6. Anterior insular cortex mediates bodily sensibility and social anxiety

    PubMed Central

    Shibata, Midori; Moriguchi, Yoshiya; Umeda, Satoshi

    2013-01-01

    Studies in psychiatry and cognitive neuroscience have reported an important relationship between individual interoceptive accuracy and anxiety level. This indicates that greater attention to one’s bodily state may contribute to the development of intense negative emotions and anxiety disorders. We hypothesized that reactivity in the anterior insular cortex underlies the intensity of interoceptive awareness and anxiety. To elucidate this triadic mechanism, we conducted functional magnetic resonance imaging (fMRI) and mediation analyses to examine the relationship between emotional disposition and activation in the anterior insular cortex while participants evaluated their own emotional and bodily states. Our results indicated that right anterior insular activation was positively correlated with individual levels of social anxiety and neuroticism and negatively correlated with agreeableness and extraversion. The results of the mediation analyses revealed that activity in the right anterior insula mediated the activity of neural correlates of interoceptive sensibility and social fear. Our findings suggest that attention to interoceptive sensation affects personality traits through how we feel emotion subjectively in various situations. PMID:22977199

  7. Relation of the insular claustrum to the neocortex in Insectivora.

    PubMed

    Narkiewicz, O; Mamos, L

    1990-01-01

    The claustra of 9 species of Insectivora (Sorex araneus, Sorex minutus, Tenrec ecaudatus, Solenodon paradoxus, Neomys fodiens, Erinaceus europaeus, Talpa europaea, Desmana moschata, Potamogale velox) were investigated. In all examined animals we found two parts of the insular claustrum: the main part called by us the pars principalis and more medially situated lamina profunda claustri. In the "basal" Insectivora the main part is in close contact with the layer VIa of the neocortex. In some more developed "basal" and in all "progressive" Insectivora the area capsularis appears. Dorsolaterally it separates the main part of the insular claustrum from the neocortex and possesses, besides neurons, also numerous fibers of the extreme capsule. The above data strongly suggest that in the phylogenesis the insular claustrum originates from the cortex from which it gets separated by the extreme capsule. Lamina profunda claustri is rather a narrow band of neurons situated on the medial side of the pars principalis and mostly separated from it by a thin lamina of white substance. Lamina profunda is continuous with the layer VIb of the neocortex.

  8. Glutamate, GABA, and glutamine are synchronously upregulated in the mouse lateral septum during the postpartum period.

    PubMed

    Zhao, Changjiu; Gammie, Stephen C

    2014-12-03

    Dramatic structural and functional remodeling occurs in the postpartum brain for the establishment of maternal care, which is essential for the growth and development of young offspring. Glutamate and GABA signaling are critically important in modulating multiple behavioral performances. Large scale signaling changes occur in the postpartum brain, but it is still not clear to what extent the neurotransmitters glutamate and GABA change and whether the ratio of glutamate/GABA remains balanced. In this study, we examined the glutamate/GABA-glutamine cycle in the lateral septum (LS) of postpartum female mice. In postpartum females (relative to virgins), tissue levels of glutamate and GABA were elevated in LS and increased mRNA was found for the respective enzymes producing glutamate and GABA, glutaminase (Gls) and glutamate decarboxylase 1 and 2 (Gad1 and Gad2). The common precursor, glutamine, was elevated as was the enzyme that produces it, glutamate-ammonia ligase (Glul). Additionally, glutamate, GABA, and glutamine were positively correlated and the glutamate/GABA ratio was almost identical in the postpartum and virgin females. Collectively, these findings indicate that glutamate and GABA signaling are increased and that the ratio of glutamate/GABA is well balanced in the maternal LS. The postpartum brain may provide a useful model system for understanding how glutamate and GABA are linked despite large signaling changes. Given that some mental health disorders, including depression and schizophrenia display dysregulated glutamate/GABA ratio, and there is increased vulnerability to mental disorders in mothers, it is possible that these postpartum disorders emerge when glutamate and GABA changes are not properly coordinated.

  9. 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.

  10. Elevating your elevator talk

    USDA-ARS?s Scientific Manuscript database

    An important and often overlooked item that every early career researcher needs to do is compose an elevator talk. The elevator talk, named because the talk should not last longer than an average elevator ride (30 to 60 seconds), is an effective method to present your research and yourself in a clea...

  11. 203 Insular Depth Electrode in Pediatric Treatment-Refractory Epilepsy.

    PubMed

    Tomycz, Luke; Haider, Ali; Hamilton, Maura; Clarke, David B; Lee, Mark R

    2016-08-01

    It has been increasingly recognized that the insular cortex plays an important role in frontotemporal epilepsy (FTE) in children. The insula, however, cannot properly by monitored with conventional subdural grids, and open surgical resection of the insula is technically difficult and often associated with significant morbidity. Stereotactically placed insular depth electrodes allow direct and comprehensive monitoring of this region, and can easily be replaced with a laser applicator for minimally invasive treatment via thermo-ablation. We used Current Procedural Terminology (CPT) billing records dating from January 2010 to the present day to identify all the cases of depth electrode insertion performed at Dell Children's Medical Center (Austin, Texas). Electronic medical records were then reviewed to specifically identify insular depth electrodes. Of the 104 depth electrodes placed in 80 patients, 45 of these were inserted into the insular cortex. In more than half of these cases, insular involvement prompted thermoablation or surgical resection of some portion of the insula. There were no serious adverse effects or complications associated with the placement of insular depth electrodes. Insular depth electrodes were used in cases with subtle cortical thickening as well as magnetoencephalography (MEG) dipole clustering within the insular cortex. They were also used in many cases of FTE where seizures recurred after an initial surgical resection. Given the low morbidity and comprehensive coverage attainable with 2 posteriorly placed depth electrodes, it is worth considering whether insular depth electrodes should be part of the standard presurgical evaluation in every pediatric patient with partial, nonlesional, frontotemporal epilepsy.

  12. Blocking glutamate carboxypeptidase II inhibits glutamate excitotoxicity and regulates immune responses in experimental autoimmune encephalomyelitis.

    PubMed

    Ha, Danbee; Bing, So Jin; Ahn, Ginnae; Kim, Jinhee; Cho, Jinhee; Kim, Areum; Herath, Kalahe H I N M; Yu, Hak Sun; Jo, Sangmee Ahn; Cho, Ik-Hyun; Jee, Youngheun

    2016-09-01

    Experimental autoimmune encephalomyelitis (EAE) is an inflammatory disease in the murine central nervous system (CNS) and recapitulates the clinical and pathological features of human multiple sclerosis (MS). Glutamate carboxipeptidase II (GCPII), an enzyme expressed exclusively on astrocytes, is known to affect the disease progression of various neurological disorders by producing glutamate. Despite several findings indicating possible link between glutamate and MS/EAE, however, the involvement of astrocyte or GCPII on glutamate excitotoxicity has not received much attention in MS/EAE. When we examined GCPII expression during EAE progression in this study, we observed significantly elevated GCPII expression in peak stage of disease localized mainly in astrocytes. Intrigued by these results, we tried a potent GCPII inhibitor, 2-phosphonomethyl pentanedioic acid (2-PMPA), on EAE mice and noticed markedly attenuated EAE clinical signs along with significantly inhibited infiltration of inflammatory cells into CNS. Furthermore, 2-PMPA dampened the function of Th1 cell lineage and down-regulated mGluR1 expression in both periphery and CNS contributing to glutamate-mediated immune regulation. Our observations identify a sequence of events triggering EAE through GCPII overexpression, which may offer a novel therapeutic approach to the treatment of MS. © 2016 Federation of European Biochemical Societies.

  13. Modulation of Astrocyte Glutamate Transporters Decreases Seizures in a Mouse Model of Tuberous Sclerosis Complex

    PubMed Central

    Zeng, Ling-Hui; Bero, Adam W.; Zhang, Bo; Holtzman, David M.; Wong, Michael

    2010-01-01

    Astrocyte dysfunction may contribute to epileptogenesis and other neurological deficits in Tuberous Sclerosis Complex (TSC). In particular, decreased expression and function of astrocyte glutamate transporters have been implicated in causing elevated extracellular glutamate levels, neuronal death, and epilepsy in a mouse model of TSC (Tsc1GFAPCKO mice), involving inactivation of the Tsc1 gene primarily in astrocytes. Here, we tested whether pharmacological induction of astrocyte glutamate transporter expression can prevent the neurological phenotype of Tsc1GFAPCKO mice. Early treatment with ceftriaxone prior to the onset of epilepsy increased expression of astrocyte glutamate transporters, decreased extracellular glutamate levels, neuronal death, and seizure frequency, and improved survival in Tsc1GFAPCKO mice. In contrast, late treatment with ceftriaxone after onset of epilepsy increased glutamate transporter expression, but had no effect on seizures. These results indicate that astrocyte glutamate transporters contribute to epileptogenesis in Tsc1GFAPCKO mice and suggest novel therapeutic strategies for epilepsy in TSC directed at astrocytes. PMID:20045054

  14. Prefrontal glutamate correlates of methamphetamine sensitization and preference

    PubMed Central

    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.

    2016-01-01

    Methamphetamine (MA) is a widely abused, highly addictive, psychostimulant that elicits pronounced deficits in neurocognitive function related to hypo-functioning of the prefrontal cortex (PFC). Our understanding of how repeated methamphetamine impacts excitatory glutamatergic transmission within the PFC is limited, as is information about the relation between PFC glutamate and addiction vulnerability/resiliency. In vivo microdialysis and immunoblotting studies characterized the effects of methamphetamine (10 injections of 2 mg/kg, IP) 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 versus low MA-drinking selectively bred mouse lines (MAHDR versus MALDR, respectively) and inbred C57BL/6J mice exhibiting spontaneously divergent place-conditioning phenotypes. Repeated methamphetamine sensitized drug-induced glutamate release and lowered indices of NMDA receptor expression in C57BL/6J mice, but did not alter basal extracellular glutamate content or total protein expression of Homer proteins, or metabotropic or AMPA glutamate receptors. Elevated basal glutamate, blunted methamphetamine-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 versus low methamphetamine drinking, and Homer2a/b levels were inversely correlated with the motivational valence of methamphetamine in C57BL/6J mice. These data provide novel evidence that repeated, low-dose, methamphetamine 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 methamphetamine addiction vulnerability/resiliency. PMID:26742098

  15. 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.

  16. How can we explain the frontal presentation of insular lobe epilepsy? The impact of non-linear analysis of insular seizures.

    PubMed

    Hagiwara, Koichi; Jung, Julien; Bouet, Romain; Abdallah, Chifaou; Guénot, Marc; Garcia-Larrea, Luis; Mauguière, François; Rheims, Sylvain; Isnard, Jean

    2017-05-01

    For a decade it has been known that the insular lobe epilepsy can mimic frontal lobe epilepsy. We aimed to clarify the pattern of functional coupling occurring during the frontal presentation. We analyzed five insular lobe epilepsy patients. Frontal semiology was predominant for three of them, whereas insular semiology was predominant for the two others. We applied the non-linear regression analysis to stereoelectroencephalography-recorded seizures. A directed functional coupling index was calculated during clonic discharge periods that were accompanied either with frontal or insular semiology. We found significant functional coupling between the insula and mesial frontal/cingulate regions, with the former being a leader region for seizures propagation. Extra-insular regions showed significantly less or even no coupling with the mesial hemispheric regions. The three patients with frontal semiology showed strong couplings with the mesial frontal as well as cingulate regions, including the medial orbitofrontal cortex, pre-SMA/SMA, and the anterior to posterior cingulate. The two patients with the insular semiology only showed couplings between the insula and cingulate regions. The frontal semiology was expressed by strong functional couplings between the insula and mesial frontal regions. The insular origin of seizure should be considered in cryptogenic mesial frontal epilepsies. Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

  17. Repeated exposure to moderate doses of ethanol augments hippocampal glutamate neurotransmission by increasing release

    PubMed Central

    Chefer, Vladimir; Meis, Jennifer; Wang, Grace; Kuzmin, Alexander; Bakalkin, Georgy; Shippenberg, Toni

    2013-01-01

    The present study used conventional and quantitative microdialysis to assess glutamatergic and GABAergic neurotransmission in the hippocampal CA3 area of the rat following a moderate-dose ethanol treatment regimen. Male Wistar rats received 3.4 g/kg of ethanol or water for 6 days via gastric gavage. Microdialysis experiments commenced 2 days later. Basal and depolarization-induced glutamate overflow were significantly elevated in ethanol-treated animals. Basal and depolarization-induced gamma-aminobutyric acid (GABA) overflow were unaltered. Quantitative no-net-flux microdialysis was used to determine if changes in dialysate glutamate levels following ethanol administration are due to an increase in release or a decrease in uptake.To confirm the validity of this method for quantifying basal glutamate dynamics, extracellular concentrations of glutamate and the extraction fraction, which reflects changes in analyte clearance, were quantified in response to retro-dialysis of the glutamate uptake blocker trans-pyrrolidine-2,4-dicarboxylic acid (tPDC). tPDC significantly decreased the extraction fraction for glutamate, resulting in augmented extracellular glutamate concentrations. Repeated ethanol administration did not alter the glutamate extraction fraction. However, extracellular glutamate concentrations were significantly elevated, indicating that glutamate release is increased as a consequence of repeated ethanol administration. These data demonstrate that repeated bouts of moderate ethanol consumption alter basal glutamate dynamics in the CA3 region of the dorsal hippocampus. Basal glutamate release is augmented, whereas glutamate uptake is unchanged. Furthermore, they suggest that dysregulation of glutamate transmission in this region may contribute to the previously documented deficits in cognitive function associated with moderate dose ethanol use. PMID:21182572

  18. 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

  19. Insular primary glioblastomas with IDH mutations: Clinical and biological specificities.

    PubMed

    Hata, Nobuhiro; Hatae, Ryusuke; Yoshimoto, Koji; Murata, Hideki; Kuga, Daisuke; Akagi, Yojiro; Sangatsuda, Yuhei; Suzuki, Satoshi O; Iwaki, Toru; Mizoguchi, Masahiro; Iihara, Koji

    2017-01-24

    Isocitrate dehydrogenase (IDH) mutation is a good prognostic marker for glioblastoma (GBM). Although it is infrequent in primary tumors, it is found in most lower-grade gliomas. Thus, it is unclear whether IDH mutation is a marker for a specific phenotype of apparently primary de novo GBMs (pGBMs), or a marker for secondary tumors (sGBMs). We addressed this issue by analyzing clinical, radiographic and molecular findings in our institutional case series. Our cases included 92 pGBMs, with five cases of IDH1 mutations at R132 and no IDH2 mutations. The median overall survival of these five patients was 29 months (range: 4 to >40 months), which is considered good prognoses. Clinical and radiographic characteristics were distinct from IDH-wildtype (IDH-wt) pGBMs. IDH-mutant (IDH-mut) tumors consistently involved insular lesions and were subdivided into: (i) the two cases of elderly patients with long clinical histories and features implying multistep tumor development; and (ii) the three cases of younger patients with diffusely swelling insular tumors, slight contrast enhancement and no necrosis. Genetic and expression analyses of IDH-mut pGBMs were similar to those of sGBMs, suggesting that they are indeed distinct from their IDH-wt counterparts. TERT promoter mutation, a genetic marker of oligodendroglial derivation, was detected in one long-surviving case, but genetic alterations in the astrocyte-sGBM pathway were generally prevalent in IDH-mut pGBMs. Our results present a unique phenotype of IDH-mut pGBMs arising from insular cortex region, the molecular backgrounds of which are similar to sGBMs.

  20. Differential Responses of the Insular Cortex Gyri to Autonomic Challenges

    PubMed Central

    Macey, Paul M.; Wu, Paula; Kumar, Rajesh; Ogren, Jennifer A.; Richardson, Heidi L.; Woo, Mary A.; Harper, Ronald M.

    2014-01-01

    Determining insular functional topography is essential for assessing autonomic consequences of neural injury. We examined that topography in the five major insular cortex gyri to three autonomic challenges, the Valsalva, hand grip, and foot cold pressor, using functional magnetic resonance imaging (fMRI) procedures. Fifty-seven healthy subjects (age±std: 47±9 years) performed four 18 s Valsalva maneuvers (30 mmHg load pressure), four hand grip challenges (16 s at 80% effort), and a foot cold pressor (60 s, 4°C), with fMRI scans recorded every 2 s. Signal trends were compared across gyri using repeated measures ANOVA. Significantly (P<0.05) higher signals in left anterior versus posterior gyri appeared during Valsalva strain, and in the first 4 s of recovery. The right anterior gyri showed sustained higher signals up to 2 s post-challenge, relative to posterior gyri, with sub-gyral differentiation. Left anterior gyri signals were higher than posterior areas during the hand grip challenge. All right anterior gyri showed increased signals over posterior up to 12 s post-challenge, with decline in the most-anterior gyrus from 10–24 s during recovery. The left three anterior gyri showed relatively lower signals only during the 90 s recovery of the cold pressor, while the two most-anterior right gyri signals increased only during the stimulus. More-differentiated representation of autonomic signals appear in the anterior right insula for the Valsalva maneuver, a bilateral, more-posterior signal representation for hand grip, and preferentially right-sided, anterior-posterior representation for the cold pressor. The functional organization of the insular cortex is gyri-specific to unique autonomic challenges. PMID:22342370

  1. Insular avian adaptations on two Neotropical continental islands

    PubMed Central

    Wright, Natalie A.; Steadman, David W.

    2012-01-01

    Aim Most studies of avian insular adaptations have focused on oceanic islands, which may not allow characters that are insular adaptations to be teased apart from those that benefit dispersal and colonization. Using birds on continental islands, we investigated characters that evolved in situ in response to insular environments created by late Pleistocene sea level rise. Location Trinidad and Tobago, nearby Caribbean islands and continental South America. Methods We weighed fresh flight muscles and measured museum skeletal specimens of seven species of birds common to the continental islands of Trinidad and Tobago. Results When corrected for body size, study species exhibited significantly smaller flight muscles, sterna and sternal keels on Tobago than on larger Trinidad and continental South America. Tobago populations were more ‘insular’ in their morphologies than conspecifics on Trinidad or the continent in other ways as well, including having longer bills, longer wings, longer tails and longer legs. Main conclusions We hypothesize that the longer bills enhance foraging diversity, the longer wings and tails compensate for the smaller pectoral assemblage (allowing for retention of volancy, but with a probable reduction in flight power and speed), and the longer legs expand perching ability. Each of these differences is likely to be related to the lower diversity and fewer potential predators and competitors on Tobago compared with Trinidad. These patterns of smaller flight muscles and larger bills, legs, wings and tails in island birds are not the results of selection for island dispersal and colonization, but probably arose from selection pressures acting on populations already inhabiting these islands. PMID:23066173

  2. The conversion of glutamate by glutamine synthase in neocortical astrocytes from juvenile rat is important to limit glutamate spillover and peri/extrasynaptic activation of NMDA receptors.

    PubMed

    Trabelsi, Yosra; Amri, Mohamed; Becq, Hélène; Molinari, Florence; Aniksztejn, Laurent

    2017-02-01

    Glutamate transporters (EAATs) are important to maintain spatial and temporal specificity of synaptic transmission. Their efficiency to uptake and transport glutamate into the intracellular space depends on several parameters including the intracellular concentrations of Na(+) and glutamate, the elevations of which may slow down the cycling rate of EAATs. In astrocytes, glutamate is maintained at low concentration due to the presence of specific enzymes such as glutamine synthase (GS). GS inhibition results in cytosolic accumulation of glutamate suggesting that the conversion of glutamate by GS is important for EAATs operation. Here we recorded astrocytes from juvenile rat neocortical slices and analyzed the consequences of elevated intracellular glutamate concentrations and of GS inhibition on the time course of synaptically evoked transporter current (STC). In slices from rats treated with methionine sulfoximine (MSO), a GS inhibitor, STC evoked by short burst of high frequency stimulation (HFS; 100 Hz for 100 ms) but not by low frequency stimulation (LFS; 0.1 Hz) was twice slower than STC evoked from saline injected rats. Same results were obtained for astrocytes recorded with pipette containing 3-10 mM glutamate and compared with cells recorded with 0 or1 mM glutamate in the patch pipette. We also showed that HFS elicited significantly larger NMDAR-excitatory postsynaptic currents (EPSCs) with a stronger peri/extrasynaptic component in pyramidal cells from MSO-treated compared with saline treated rats. Taken together our data demonstrate that the conversion of glutamate by GS is fundamental to ensure an efficient clearance of glutamate by EAATs and to prevent glutamate spillover. GLIA 2017;65:401-415.

  3. Altered Functional Connectivity of the Insular Cortex across Prefrontal Networks in Cocaine Addiction

    PubMed Central

    Cisler, Josh M.; Elton, Amanda; Kennedy, Ashley P.; Young, Jonathan; Smitherman, Sonet; James, George Andrew; Kilts, Clinton D.

    2013-01-01

    Interoception is theorized to be an important process mediating substance use disorders, and the insular cortex is recognized as a core neural region supporting interoception. The purpose of this study was to compare the integration of the insular cortex into prefrontal-related resting-state networks between individuals with cocaine dependence and healthy controls. 41 participants with cocaine dependence and 19 control participants underwent a resting-state 3T fMRI scan. Individuals with cocaine dependence demonstrated altered functional connectivity of the insular cortex, predominantly the right insular cortex, with all eight prefrontal-related resting-state networks identified through Independent Component Analysis (ICA). A conjunction analysis demonstrated that the right insular cortex was the neural region with the highest number of common group differences across the networks. There was no evidence that insular cortex connectivity commonly differed between groups for non-prefrontal-related networks. Further, seed-based functional connectivity analyses extended the network analyses and indicated that cocaine dependence was associated with greater connectivity of the right insula with the dorsomedial PFC, inferior frontal gyrus, and bilateral dlPFC. These data support the hypothesis that cocaine dependence is related to altered functional interactions of the insular cortex with prefrontal networks. The results suggest possible neural mechanisms by which the insular cortex and interoceptive information influence cognitive control and decision-making processes presumably mediated by prefrontal networks in the cocaine dependence process. PMID:23684980

  4. Isolated left posterior insular infarction and convergent roles in verbal fluency, language, memory, and executive function.

    PubMed

    Julayanont, Parunyou; Ruthirago, Doungporn; DeToledo, John C

    2016-07-01

    The posterior insular cortex-a complex structure interconnecting various brain regions for different functions-is a rare location for ischemic stroke. We report a patient with isolated left posterior insular infarction who presented with multiple cognitive impairment, including impairment in semantic and phonemic verbal fluency.

  5. Electrical stimulation of the insular region attenuates nicotine-taking and nicotine-seeking behaviors.

    PubMed

    Pushparaj, Abhiram; Hamani, Clement; Yu, Wilson; Shin, Damian S; Kang, Bin; Nobrega, José N; Le Foll, Bernard

    2013-03-01

    Pharmacological inactivation of the granular insular cortex is able to block nicotine-taking and -seeking behaviors in rats. In this study, we explored the potential of modulating activity in the insular region using electrical stimulation. Animals were trained to self-administer nicotine (0.03 mg/kg per infusion) under a fixed ratio-5 (FR-5) schedule of reinforcement followed by a progressive ratio (PR) schedule. Evaluation of the effect of stimulation in the insular region was performed on nicotine self-administration under FR-5 and PR schedules, as well on reinstatement of nicotine-seeking behavior induced by nicotine-associated cues or nicotine-priming injections. The effect of stimulation was also examined in brain slices containing insular neurons. Stimulation significantly attenuated nicotine-taking, under both schedules of reinforcement, as well as nicotine-seeking behavior induced by cues and priming. These effects appear to be specific to nicotine-associated behaviors, as stimulation did not have any effect on food-taking behavior. They appear to be anatomically specific, as stimulation surrounding the insular region had no effect on behavior. Stimulation of brain slices containing the insular region was found to inactivate insular neurons. Our results suggest that deep brain stimulation to modulate insular activity should be further explored.

  6. Electrical Stimulation of the Insular Region Attenuates Nicotine-Taking and Nicotine-Seeking Behaviors

    PubMed Central

    Pushparaj, Abhiram; Hamani, Clement; Yu, Wilson; Shin, Damian S; Kang, Bin; Nobrega, José N; Le Foll, Bernard

    2013-01-01

    Pharmacological inactivation of the granular insular cortex is able to block nicotine-taking and -seeking behaviors in rats. In this study, we explored the potential of modulating activity in the insular region using electrical stimulation. Animals were trained to self-administer nicotine (0.03 mg/kg per infusion) under a fixed ratio-5 (FR-5) schedule of reinforcement followed by a progressive ratio (PR) schedule. Evaluation of the effect of stimulation in the insular region was performed on nicotine self-administration under FR-5 and PR schedules, as well on reinstatement of nicotine-seeking behavior induced by nicotine-associated cues or nicotine-priming injections. The effect of stimulation was also examined in brain slices containing insular neurons. Stimulation significantly attenuated nicotine-taking, under both schedules of reinforcement, as well as nicotine-seeking behavior induced by cues and priming. These effects appear to be specific to nicotine-associated behaviors, as stimulation did not have any effect on food-taking behavior. They appear to be anatomically specific, as stimulation surrounding the insular region had no effect on behavior. Stimulation of brain slices containing the insular region was found to inactivate insular neurons. Our results suggest that deep brain stimulation to modulate insular activity should be further explored. PMID:23249816

  7. 19 CFR 7.4 - Watches and watch movements from U.S. insular possessions.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 19 Customs Duties 1 2014-04-01 2014-04-01 false Watches and watch movements from U.S. insular... STATION § 7.4 Watches and watch movements from U.S. insular possessions. (a) The issuance of an... Watches and Watch Movements, by the Department of Commerce, authorizes a producer of watches in the...

  8. 19 CFR 7.4 - Watches and watch movements from U.S. insular possessions.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 19 Customs Duties 1 2011-04-01 2011-04-01 false Watches and watch movements from U.S. insular... STATION § 7.4 Watches and watch movements from U.S. insular possessions. (a) The issuance of an... Watches and Watch Movements, by the Department of Commerce, authorizes a producer of watches in the...

  9. 19 CFR 7.4 - Watches and watch movements from U.S. insular possessions.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 19 Customs Duties 1 2012-04-01 2012-04-01 false Watches and watch movements from U.S. insular... STATION § 7.4 Watches and watch movements from U.S. insular possessions. (a) The issuance of an... Watches and Watch Movements, by the Department of Commerce, authorizes a producer of watches in the...

  10. 19 CFR 7.4 - Watches and watch movements from U.S. insular possessions.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 19 Customs Duties 1 2013-04-01 2013-04-01 false Watches and watch movements from U.S. insular... STATION § 7.4 Watches and watch movements from U.S. insular possessions. (a) The issuance of an... Watches and Watch Movements, by the Department of Commerce, authorizes a producer of watches in the...

  11. 19 CFR 7.4 - Watches and watch movements from U.S. insular possessions.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 19 Customs Duties 1 2010-04-01 2010-04-01 false Watches and watch movements from U.S. insular... STATION § 7.4 Watches and watch movements from U.S. insular possessions. (a) The issuance of an... Watches and Watch Movements, by the Department of Commerce, authorizes a producer of watches in the U.S...

  12. Biological significance of glutamate signaling during digestion of food through the gut-brain axis.

    PubMed

    Kitamura, Akihiko; Tsurugizawa, Tomokazu; Torii, Kunio

    2011-01-01

    Monosodium L-glutamate (MSG) elicits a unique taste termed umami and is widely used as a flavor enhancer in various cuisines. In addition, recent studies suggest the existence of sensors for L-glutamate (Glu) and transduction molecules in the gut mucosa as well as in the oral cavity. The vagal gastric afferent responds specifically to the luminal stimulation of Glu in the stomach and regulates the autonomic reflexes. The intragastric infusion of Glu also activates several brain areas (insular cortex, limbic system, and hypothalamus) and is able to induce flavor-preference learning in rats. These results suggest that umami signaling via gustatory and visceral pathways plays an important role in the processes of digestion, absorption, metabolism, and other physiological functions via activation of the brain. Copyright © 2011 S. Karger AG, Basel.

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

    PubMed

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

    2015-07-01

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

  14. Left-insular damage, autonomic instability, and sudden unexpected death in epilepsy.

    PubMed

    Lacuey, Nuria; Zonjy, Bilal; Theerannaew, Wanchat; Loparo, Kenneth A; Tatsuoka, Curtis; Sahadevan, Jayakumar; Lhatoo, Samden D

    2016-02-01

    We analyzed the only two sudden unexpected death in epilepsy (SUDEP) cases from 320 prospectively recruited patients in the three-year Prevention and Risk Identification of SUDEP Mortality (PRISM) project. Both patients had surgically refractory epilepsy, evidence of left insular damage following previous temporal/temporo-insular resections, and progressive changes in heart rate variability (HRV) in monitored evaluations prior to death. Insular damage is known to cause autonomic dysfunction and increased mortality in acute stroke. This report suggests a possible role for the insula in the pathogenesis of SUDEP. The presence of intrinsic insular lesions or acquired insular damage in patients with refractory epilepsy may be an additional risk factor for SUDEP.

  15. Left-Insular Damage, Autonomic Instability and Sudden Unexpected Death in Epilepsy

    PubMed Central

    Lacuey, Nuria; Zonjy, Bilal; Theerannaew, Wanchat; Loparo, Kenneth A.; Tatsuoka, Curtis; Sahadevan, Jayakumar; Lhatoo, Samden D.

    2015-01-01

    We analyzed the only two sudden unexpected death in epilepsy (SUDEP) cases from 320 prospectively recruited patients in the three-year Prevention and Risk Identification of SUDEP Mortality (PRISM) Project. Both patients had surgically refractory epilepsy, evidence of left insular damage following previous temporal/temporo-insular resections, and progressive changes in Heart Rate Variability (HRV) in monitored evaluations prior to death. Insular damage is known to cause autonomic dysfunction and increased mortality in acute stroke. This report suggests a possible role for the insula in the pathogenesis of SUDEP. The presence of intrinsic insular lesions or acquired insular damage in refractory epilepsy patients may be an additional risk factor for SUDEP. PMID:26797084

  16. Phylogeny and adaptation shape the teeth of insular mice.

    PubMed

    Ledevin, Ronan; Chevret, Pascale; Ganem, Guila; Britton-Davidian, Janice; Hardouin, Emilie A; Chapuis, Jean-Louis; Pisanu, Benoit; da Luz Mathias, Maria; Schlager, Stefan; Auffray, Jean-Christophe; Renaud, Sabrina

    2016-02-10

    By accompanying human travels since prehistorical times, the house mouse dispersed widely throughout the world, and colonized many islands. The origin of the travellers determined the phylogenetic source of the insular mice, which encountered diverse ecological and environmental conditions on the various islands. Insular mice are thus an exceptional model to disentangle the relative role of phylogeny, ecology and climate in evolution. Molar shape is known to vary according to phylogeny and to respond to adaptation. Using for the first time a three-dimensional geometric morphometric approach, compared with a classical two-dimensional quantification, the relative effects of size variation, phylogeny, climate and ecology were investigated on molar shape diversity across a variety of islands. Phylogeny emerged as the factor of prime importance in shaping the molar. Changes in competition level, mostly driven by the presence or absence of the wood mouse on the different islands, appeared as the second most important effect. Climate and size differences accounted for slight shape variation. This evidences a balanced role of random differentiation related to history of colonization, and of adaptation possibly related to resource exploitation. © 2016 The Author(s).

  17. Sensory convergence in the parieto-insular vestibular cortex

    PubMed Central

    Shinder, Michael E.

    2014-01-01

    Vestibular signals are pervasive throughout the central nervous system, including the cortex, where they likely play different roles than they do in the better studied brainstem. Little is known about the parieto-insular vestibular cortex (PIVC), an area of the cortex with prominent vestibular inputs. Neural activity was recorded in the PIVC of rhesus macaques during combinations of head, body, and visual target rotations. Activity of many PIVC neurons was correlated with the motion of the head in space (vestibular), the twist of the neck (proprioceptive), and the motion of a visual target, but was not associated with eye movement. PIVC neurons responded most commonly to more than one stimulus, and responses to combined movements could often be approximated by a combination of the individual sensitivities to head, neck, and target motion. The pattern of visual, vestibular, and somatic sensitivities on PIVC neurons displayed a continuous range, with some cells strongly responding to one or two of the stimulus modalities while other cells responded to any type of motion equivalently. The PIVC contains multisensory convergence of self-motion cues with external visual object motion information, such that neurons do not represent a specific transformation of any one sensory input. Instead, the PIVC neuron population may define the movement of head, body, and external visual objects in space and relative to one another. This comparison of self and external movement is consistent with insular cortex functions related to monitoring and explains many disparate findings of previous studies. PMID:24671533

  18. Phylogeny and adaptation shape the teeth of insular mice

    PubMed Central

    Ledevin, Ronan; Chevret, Pascale; Ganem, Guila; Britton-Davidian, Janice; Hardouin, Emilie A.; Chapuis, Jean-Louis; Pisanu, Benoit; da Luz Mathias, Maria; Schlager, Stefan; Auffray, Jean-Christophe; Renaud, Sabrina

    2016-01-01

    By accompanying human travels since prehistorical times, the house mouse dispersed widely throughout the world, and colonized many islands. The origin of the travellers determined the phylogenetic source of the insular mice, which encountered diverse ecological and environmental conditions on the various islands. Insular mice are thus an exceptional model to disentangle the relative role of phylogeny, ecology and climate in evolution. Molar shape is known to vary according to phylogeny and to respond to adaptation. Using for the first time a three-dimensional geometric morphometric approach, compared with a classical two-dimensional quantification, the relative effects of size variation, phylogeny, climate and ecology were investigated on molar shape diversity across a variety of islands. Phylogeny emerged as the factor of prime importance in shaping the molar. Changes in competition level, mostly driven by the presence or absence of the wood mouse on the different islands, appeared as the second most important effect. Climate and size differences accounted for slight shape variation. This evidences a balanced role of random differentiation related to history of colonization, and of adaptation possibly related to resource exploitation. PMID:26842576

  19. Structural Differences in Insular Cortex Reflect Vicarious Injustice Sensitivity

    PubMed Central

    Baumgartner, Thomas; Saulin, Anne; Hein, Grit; Knoch, Daria

    2016-01-01

    Sensitivity to injustice inflicted on others is a strong motivator of human social behavior. There are, however, enormous individual differences in vicarious injustice sensitivity. Some people are strongly affected when witnessing injustice, while others barely notice it, but the factors behind this heterogeneity are poorly understood. Here we examine the neuroanatomical basis of these differences using voxel-based morphometry and Freesurfer image analysis suite. Whole brain corrected analyses show that a person’s propensity to be vicariously affected by injustice to others is reflected by the gray matter volume and thickness of the bilateral mid insular cortex. The larger a person’s gray matter volume and thickness of the mid insula, the higher that person’s sensitivity to injustice experienced by others. These findings show that the individual neuroanatomy of the mid insular cortex captures a person’s predisposition to be vicariously affected by injustice, and thus adds a novel aspect to previous functional work that has linked this region to the processing of transient vicarious states. PMID:27930678

  20. Visualization of glutamate as a volume transmitter.

    PubMed

    Okubo, Yohei; Iino, Masamitsu

    2011-02-01

    Glutamate is the major excitatory neurotransmitter in the central nervous system. Although glutamate mediates synaptically confined point-to-point transmission, it has been suggested that under certain conditions glutamate may escape from the synaptic cleft (glutamate spillover), accumulate in the extrasynaptic space, and mediate volume transmission to regulate important brain functions. However, the inability to directly measure glutamate dynamics around active synapses has limited our understanding of glutamatergic volume transmission. The recent development of a family of fluorescent glutamate indicators has enabled the visualization of extrasynaptic glutamate dynamics in brain tissues. In this topical review, we examine glutamate as a volume transmitter based on novel results of glutamate imaging in the brain.

  1. Agmatine Prevents Adaptation of the Hippocampal Glutamate System in Chronic Morphine-Treated Rats.

    PubMed

    Wang, Xiao-Fei; Zhao, Tai-Yun; Su, Rui-Bin; Wu, Ning; Li, Jin

    2016-12-01

    Chronic exposure to opioids induces adaptation of glutamate neurotransmission, which plays a crucial role in addiction. Our previous studies revealed that agmatine attenuates opioid addiction and prevents the adaptation of glutamate neurotransmission in the nucleus accumbens of chronic morphine-treated rats. The hippocampus is important for drug addiction; however, whether adaptation of glutamate neurotransmission is modulated by agmatine in the hippocampus remains unknown. Here, we found that continuous pretreatment of rats with ascending doses of morphine for 5 days resulted in an increase in the hippocampal extracellular glutamate level induced by naloxone (2 mg/kg, i.p.) precipitation. Agmatine (20 mg/kg, s.c.) administered concurrently with morphine for 5 days attenuated the elevation of extracellular glutamate levels induced by naloxone precipitation. Furthermore, in the hippocampal synaptosome model, agmatine decreased the release and increased the uptake of glutamate in synaptosomes from chronic morphine-treated rats, which might contribute to the reduced elevation of glutamate levels induced by agmatine. We also found that expression of the hippocampal NR2B subunit, rather than the NR1 subunit, of N-methyl-D-aspartate receptors (NMDARs) was down-regulated after chronic morphine treatment, and agmatine inhibited this reduction. Taken together, agmatine prevented the adaptation of the hippocampal glutamate system caused by chronic exposure to morphine, including modulating extracellular glutamate concentration and NMDAR expression, which might be one of the mechanisms underlying the attenuation of opioid addiction by agmatine.

  2. Insular balance of glutamatergic and GABAergic signaling modulates pain processing.

    PubMed

    Watson, Christopher J

    2016-10-01

    Neuroimaging studies of patients with chronic pain have shown that neurotransmitter abnormalities, including increases in glutamate and decreases in GABA, could be responsible for the cortical hyperactivity and hyperalgesia/allodynia observed in some pain conditions. These finding are particularly evident in the insula, a brain region known to play a role in both the sensory-discriminative and the affective-motivational aspects of pain processing. However, clinical studies are not entirely able to determine the directionality of these findings, nor whether they are causal or epiphenomenon. Thus, a set of animal studies was performed to determine whether alterations in glutamate and GABA are the result of injury, the cause of augmented pain processing, or both. Compared with controls, the excitatory neurotransmitters glutamate and aspartate are significantly higher in the rat insula after chronic constriction injury of the sciatic nerve (CCI). The CCI also produced significant increases in allodynia (mechanical and cold), thermal hyperalgesia, and nociceptive aversiveness. Unilateral microinjection of ionotropic glutamate receptor antagonists restored these nociceptive behaviors to preinjury values. Increasing endogenous levels of GABA or enhancing signaling at inhibitory glycinergic receptors had similar effects as the glutamate receptor antagonists. In naive rats, increasing endogenous levels of glutamate, decreasing endogenous levels of GABA, or blocking strychnine-sensitive glycine receptors in the insula significantly increased thermal hyperalgesia and mechanical allodynia. These data support the hypothesis that an altered balance of excitatory and inhibitory neurotransmitters in brain regions such as the insula occurs in chronic pain states and leads to augmented central pain processing and increased pain sensitivity.

  3. Dwarfism in insular sloths: biogeography, selection, and evolutionary rate.

    PubMed

    Anderson, Robert P; Handley, Charles O

    2002-05-01

    The islands of Bocas del Toro, Panama, were sequentially separated from the adjacent mainland by rising sea levels during the past 10,000 years. Three-toed sloths (Bradypus) from five islands are smaller than their mainland counterparts, and the insular populations themselves vary in mean body size. We first examine relationships between body size and physical characteristics of the islands, testing hypotheses regarding optimal body size, evolutionary equilibria, and the presence of dispersal in this system. To do so, we conduct linear regressions of body size onto island area, distance from the mainland, and island age. Second, we retroactively calculate two measures of the evolutionary rate of change in body size (haldanes and darwins) and the standardized linear selection differential, or selection intensity (i). We also test the observed morphological changes against models of evolution by genetic drift. The results indicate that mean body size decreases linearly with island age, explaining up to 97% of the variation among population means. Neither island area nor distance from the mainland is significant in multiple regressions that include island age. Thus, we find no evidence for differential optimal body size among islands, or for dispersal in the system. In contrast, the dependence of body size on island age suggests uniform directional selection for small body size in the insular populations. Although genetic drift cannot be discounted as the cause for this evolution in body size, the probability is small given the consistent direction of evolution (repeated dwarfism). The insular sloths show a sustained rate of evolution similar to those measured in haldanes over tens of generations, appearing to unite micro- and macroevolutionary time scales. Furthermore, the magnitude and rate of this example of rapid differentiation fall within predictions of theoretical models from population genetics. However, the linearity of the relationship between body size and

  4. Influence of glutamic acid enantiomers on C-mineralization.

    PubMed

    Formánek, Pavel; Vranová, Valerie; Lojková, Lea

    2015-02-01

    Seasonal dynamics in the mineralization of glutamic acid enantiomers in soils from selected ecosystems was determined and subjected to a range of treatments: ambient x elevated CO2 level and meadow x dense x thinned forest environment. Mineralization of glutamic acid was determined by incubation of the soil with 2 mg L- or D-glutamic acid g(-1) of dry soil to induce the maximum respiration rate. Mineralization of glutamic acid enantiomers in soils fluctuates over the course of a vegetation season, following a similar trend across a range of ecosystems. Mineralization is affected by environmental changes and management practices, including elevated CO2 level and thinning intensity. L-glutamic acid metabolism is more dependent on soil type as compared to metabolism of its D-enantiomer. The results support the hypothesis that the slower rate of D- compared to L- amino acid mineralization is due to different roles in anabolism and catabolism of the soil microbial community. © 2014 Wiley Periodicals, Inc.

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

    PubMed

    Zhang, Chao; Wang, Chendan; Ren, Jianbo; Guo, Xiangjie; Yun, Keming

    2016-10-24

    Glutamate is not only a neurotransmitter but also an important neurotoxin in central nervous system (CNS). Chronic elevation of glutamate induces both neuronal and glial cell apoptosis. However, its effect on astrocytes is complex and still remains unclear. In this study, we investigated whether morphine, a common opioid ligand, could affect glutamate-induced apoptosis in astrocytes. Primary cultured astrocytes were incubated with glutamate in the presence/absence of morphine. It was found that morphine could reduce glutamate-induced apoptosis of astrocytes. Furthermore, glutamate activated Ca(2+) release, thereby inducing endoplasmic reticulum (ER) stress in astrocytes, while morphine attenuated this deleterious effect. Using siRNA to reduce the expression of κ-opioid receptor, morphine could not effectively inhibit glutamate-stimulated Ca(2+) release in astrocytes, the protective effect of morphine on glutamate-injured astrocytes was also suppressed. These results suggested that morphine could protect astrocytes from glutamate-induced apoptosis via reducing Ca(2+) overload and ER stress pathways. In conclusion, this study indicated that excitotoxicity participated in the glutamate mediated apoptosis in astrocytes, while morphine attenuated this deleterious effect via regulating Ca(2+) release and ER stress.

  6. 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

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

    PubMed

    Henry-Unaeze, Helen Nonye

    2017-09-18

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

  8. De novo artistic activity following insular-SII ischemia.

    PubMed

    Thomas-Anterion, Catherine; Creac'h, Christelle; Dionet, Elsa; Borg, Céline; Extier, Chantal; Faillenot, Isabelle; Peyron, Roland

    2010-07-01

    We report here the case of a female patient who developed the following behavioural changes after a brain lesion involving the left posterior insula and SII cortices. She discovered de novo artistic capabilities for painting, with an episodic and compulsive need to paint ("hyperpainting"), but also exhibited changes in her ability to feel emotions. In addition, she had a typical neuropathic pain syndrome, including provoked pain and spontaneous pain, whose intensity was worsened when she painted with cold colours. This case-report suggests some kind of synaesthesiae, which has previously been reported for other sensory modalities. These findings suggest that a cross-talk between emotional, thermosensory, pain, and motivational functions may take place during recovery, at the level of the left insular-SII cortices. Copyright 2010. Published by Elsevier B.V.

  9. Auditory, Somatosensory, and Multisensory Insular Cortex in the Rat

    PubMed Central

    Rodgers, Krista M.; Benison, Alexander M.; Klein, Andrea

    2008-01-01

    Compared with other areas of the forebrain, the function of insular cortex is poorly understood. This study examined the unisensory and multisensory function of the rat insula using high-resolution, whole-hemisphere, epipial evoked potential mapping. We found the posterior insula to contain distinct auditory and somatotopically organized somatosensory fields with an interposed and overlapping region capable of integrating these sensory modalities. Unisensory and multisensory responses were uninfluenced by complete lesioning of primary and secondary auditory and somatosensory cortices, suggesting a high degree of parallel afferent input from the thalamus. In light of the established connections of the posterior insula with the amygdala, we propose that integration of auditory and somatosensory modalities reported here may play a role in auditory fear conditioning. PMID:18424777

  10. Gustatory insular cortex, aversive taste memory and taste neophobia.

    PubMed

    Lin, Jian-You; Arthurs, Joe; Reilly, Steve

    2015-03-01

    Prior research indicates a role for the gustatory insular cortex (GC) in taste neophobia. Rats with lesions of the GC show much weaker avoidance to a novel and potentially dangerous taste than do neurologically intact animals. The current study used the retention of conditioned taste aversion (CTA) as a tool to determine whether the GC modulates neophobia by processing taste novelty or taste danger. The results show that GC lesions attenuate CTA retention (Experiment 1) and impair taste neophobia (Experiment 2). Given that normal CTA retention does not involve the processing of taste novelty, the pattern of results suggests that the GC is involved in taste neophobia via its function in processing the danger conveyed by a taste stimulus.

  11. Taste and olfactory intensity perception changes following left insular stroke.

    PubMed

    Mak, Y Erica; Simmons, Katharine B; Gitelman, Darren R; Small, Dana M

    2005-12-01

    The authors tested suprathreshold intensity perception of gustatory and olfactory stimuli in a 70-year-old right-handed man following a left posterior insular stroke and compared his results with those of age-matched controls. Both modalities revealed significant differences between left (ipsilateral to lesion) and right (contralateral) ratings of intensity. In both gustation and olfaction, these differences were driven primarily by trends toward increased contralateral sensitivity relative to controls. Intensity changes were most pronounced for unpleasant odors and for tastes perceived strongly as either pleasant (sweet) or unpleasant (salty, bitter). These results show that a left posterior insula lesion may affect taste and olfactory perception similarly by increasing sensitivity contralateral to the lesion. One possible mechanism is release from inhibition at the cortical level. Copyright (c) 2006 APA, all rights reserved.

  12. ALTERED PREFRONTAL AND INSULAR CORTICAL THICKNESS IN ADOLESCENT MARIJUANA USERS

    PubMed Central

    Lopez-Larson, Melissa P.; Bogorodzki, Piotr; Rogowska, Jadwiga; McGlade, Erin; King, Jace B.; Terry, Janine; Yurgelun-Todd, Deborah

    2011-01-01

    Introduction There are limited data regarding the impact of marijuana (MJ) on cortical development during adolescence. Adolescence is a period of substantial brain maturation and cortical thickness abnormalities may be indicative of disruptions of normal cortical development. This investigation applied cortical-surface based techniques to compare cortical thickness measures in MJ using adolescents compared to non-using controls. Methods Eighteen adolescents with heavy MJ use and 18 non-using controls similar in age received MRI scans using a 3T Siemens scanner. Cortical reconstruction and volumetric segmentation was performed with FreeSurfer. Group differences in cortical thickness were assessed using statistical difference maps covarying for age and gender. Results Compared to non-users, MJ users had decreased cortical thickness in right caudal middle frontal, bilateral insula and bilateral superior frontal corticies. Marijuana users had increased cortical thickness in the bilateral lingual, right superior temporal, right inferior parietal and left paracentral regions. In the MJ users, negative correlations were found between frontal and lingual regions for urinary cannabinoid levels and between age of onset of use and the right superior frontal gyrus. Conclusion This is one of the first studies to evaluate cortical thickness in a group of adolescents with heavy MJ use compared to non-users. Our findings are consistent with prior studies that documented abnormalities in prefrontal and insular regions. Our results suggest that age of regular use may be associated with altered prefrontal cortical gray matter development in adolescents. Furthermore, reduced insular cortical thickness may be a biological marker for increased risk of substance dependence. PMID:21310189

  13. Insular Organization of Gene Space in Grass Genomes

    PubMed Central

    Massa, Alicia N.; Wanjugi, Humphrey; Deal, Karin R.; You, Frank M.; Xu, Xiangyang; Gu, Yong Q.; Luo, Ming-Cheng; Anderson, Olin D.; Chan, Agnes P.; Rabinowicz, Pablo

    2013-01-01

    Wheat and maize genes were hypothesized to be clustered into islands but the hypothesis was not statistically tested. The hypothesis is statistically tested here in four grass species differing in genome size, Brachypodium distachyon, Oryza sativa, Sorghum bicolor, and Aegilops tauschii. Density functions obtained under a model where gene locations follow a homogeneous Poisson process and thus are not clustered are compared with a model-free situation quantified through a non-parametric density estimate. A simple homogeneous Poisson model for gene locations is not rejected for the small O. sativa and B. distachyon genomes, indicating that genes are distributed largely uniformly in those species, but is rejected for the larger S. bicolor and Ae. tauschii genomes, providing evidence for clustering of genes into islands. It is proposed to call the gene islands “gene insulae” to distinguish them from other types of gene clustering that have been proposed. An average S. bicolor and Ae. tauschii insula is estimated to contain 3.7 and 3.9 genes with an average intergenic distance within an insula of 2.1 and 16.5 kb, respectively. Inter-insular distances are greater than 8 and 81 kb and average 15.1 and 205 kb, in S. bicolor and Ae. tauschii, respectively. A greater gene density observed in the distal regions of the Ae. tauschii chromosomes is shown to be primarily caused by shortening of inter-insular distances. The comparison of the four grass genomes suggests that gene locations are largely a function of a homogeneous Poisson process in small genomes. Nonrandom insertions of LTR retroelements during genome expansion creates gene insulae, which become less dense and further apart with the increase in genome size. High concordance in relative lengths of orthologous intergenic distances among the investigated genomes including the maize genome suggests functional constraints on gene distribution in the grass genomes. PMID:23326580

  14. Insular organization of gene space in grass genomes.

    PubMed

    Gottlieb, Andrea; Müller, Hans-Georg; Massa, Alicia N; Wanjugi, Humphrey; Deal, Karin R; You, Frank M; Xu, Xiangyang; Gu, Yong Q; Luo, Ming-Cheng; Anderson, Olin D; Chan, Agnes P; Rabinowicz, Pablo; Devos, Katrien M; Dvorak, Jan

    2013-01-01

    Wheat and maize genes were hypothesized to be clustered into islands but the hypothesis was not statistically tested. The hypothesis is statistically tested here in four grass species differing in genome size, Brachypodium distachyon, Oryza sativa, Sorghum bicolor, and Aegilops tauschii. Density functions obtained under a model where gene locations follow a homogeneous Poisson process and thus are not clustered are compared with a model-free situation quantified through a non-parametric density estimate. A simple homogeneous Poisson model for gene locations is not rejected for the small O. sativa and B. distachyon genomes, indicating that genes are distributed largely uniformly in those species, but is rejected for the larger S. bicolor and Ae. tauschii genomes, providing evidence for clustering of genes into islands. It is proposed to call the gene islands "gene insulae" to distinguish them from other types of gene clustering that have been proposed. An average S. bicolor and Ae. tauschii insula is estimated to contain 3.7 and 3.9 genes with an average intergenic distance within an insula of 2.1 and 16.5 kb, respectively. Inter-insular distances are greater than 8 and 81 kb and average 15.1 and 205 kb, in S. bicolor and Ae. tauschii, respectively. A greater gene density observed in the distal regions of the Ae. tauschii chromosomes is shown to be primarily caused by shortening of inter-insular distances. The comparison of the four grass genomes suggests that gene locations are largely a function of a homogeneous Poisson process in small genomes. Nonrandom insertions of LTR retroelements during genome expansion creates gene insulae, which become less dense and further apart with the increase in genome size. High concordance in relative lengths of orthologous intergenic distances among the investigated genomes including the maize genome suggests functional constraints on gene distribution in the grass genomes.

  15. Modulation of taste-induced Elk-1 activation by identified neurotransmitter systems in the insular cortex of the behaving rat.

    PubMed

    Berman, Diego E

    2003-01-01

    Taste consumption activates the extracellular responsive kinases 1-2 (ERK1-2) and the transcription factor Elk-1 in the insular cortex (IC) of the behaving rat. ERKs activation, an obligatory step for the encoding of long- but not short-term memory, was shown to be regulated by multiple neurotransmitter systems in the IC. Here I show, by the use of local microinfusions of pharmacological agents into the IC of the behaving rat, that a set of similar systems is required for the taste-induced activation of Elk-1. N-Methyl-D-aspartate (NMDA), glutamate metabotropic (mGlu), ionotropic AMPA/kainate (AMPA), muscarinic, and dopaminergic receptors, which all contribute to the acquisition of taste memory, are also responsible for Elk-1 activation. However, blockade of the beta-adrenergic transmission does not affect Elk-1 activation. I also show that the basal level of Elk-1 activation in cortex is mainly maintained by GABAergic transmission. Thus, the formation of taste memory triggers the activation of Elk-1 in the IC of the behaving rat via selected neurotransmitter and neuromodulatory systems.

  16. 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

  17. Caffeine promotes glutamate and histamine release in the posterior hypothalamus.

    PubMed

    John, Joshi; Kodama, Tohru; Siegel, Jerome M

    2014-09-15

    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.

  18. Altered insular activation and increased insular functional connectivity during sad and happy face processing in adolescent major depressive disorder

    PubMed Central

    Blom, Eva Henje; Connolly, Colm G.; Ho, Tiffany C.; LeWinn, Kaja Z.; Mobayed, Nisreen; Han, Laura; Paulus, Martin P.; Wu, Jing; Simmons, Alan N.; Yang, Tony T.

    2015-01-01

    Background Major depressive disorder (MDD) is a leading cause of disability worldwide and occurs commonly first during adolescence. The insular cortex (IC) plays an important role in integrating emotion processing with interoception and has been implicated recently in the pathophysiology of adult and adolescent MDD. However, no studies have yet specifically examined the IC in adolescent MDD during processing of faces in the sad- happy continuum. Thus, the aim of the present study is to investigate the IC during sad and happy face processing in adolescents with MDD compared to healthy controls (HCL). Methods Thirty-one adolescents (22 female) with MDD and 36 (23 female) HCL underwent a well-validated emotional processing fMRI paradigm that included sad and happy face stimuli. Results The MDD group showed significantly less differential activation of the anterior/middle insular cortex (AMIC) in response to sad versus happy faces compared to the HCL group. AMIC also showed greater functional connectivity with right fusiform gyrus, left middle frontal gyrus, and right amygdala/parahippocampal gyrus in the MDD compared to HCL group. Moreover, differential activation to sad and happy faces in AMIC correlated negatively with depression severity within the MDD group. Limitations Small age-range and cross-sectional nature precluded assessment of development of the AMIC in adolescent depression. Conclusions Given the role of the IC in integrating bodily stimuli with conscious cognitive and emotional processes, our findings of aberrant AMIC function in adolescent MDD provide a neuroscientific rationale for targeting the AMIC in the development of new treatment modalities. PMID:25827506

  19. Altered insular activation and increased insular functional connectivity during sad and happy face processing in adolescent major depressive disorder.

    PubMed

    Henje Blom, Eva; Connolly, Colm G; Ho, Tiffany C; LeWinn, Kaja Z; Mobayed, Nisreen; Han, Laura; Paulus, Martin P; Wu, Jing; Simmons, Alan N; Yang, Tony T

    2015-06-01

    Major depressive disorder (MDD) is a leading cause of disability worldwide and occurs commonly first during adolescence. The insular cortex (IC) plays an important role in integrating emotion processing with interoception and has been implicated recently in the pathophysiology of adult and adolescent MDD. However, no studies have yet specifically examined the IC in adolescent MDD during processing of faces in the sad-happy continuum. Thus, the aim of the present study is to investigate the IC during sad and happy face processing in adolescents with MDD compared to healthy controls (HCL). Thirty-one adolescents (22 female) with MDD and 36 (23 female) HCL underwent a well-validated emotional processing fMRI paradigm that included sad and happy face stimuli. The MDD group showed significantly less differential activation of the anterior/middle insular cortex (AMIC) in response to sad versus happy faces compared to the HCL group. AMIC also showed greater functional connectivity with right fusiform gyrus, left middle frontal gyrus, and right amygdala/parahippocampal gyrus in the MDD compared to HCL group. Moreover, differential activation to sad and happy faces in AMIC correlated negatively with depression severity within the MDD group. Small age-range and cross-sectional nature precluded assessment of development of the AMIC in adolescent depression. Given the role of the IC in integrating bodily stimuli with conscious cognitive and emotional processes, our findings of aberrant AMIC function in adolescent MDD provide a neuroscientific rationale for targeting the AMIC in the development of new treatment modalities. Copyright © 2015 Elsevier B.V. All rights reserved.

  20. 24 CFR 570.440 - Application requirements for insular area grants funded under section 106.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Regulations Relating to Housing and Urban Development (Continued) OFFICE OF ASSISTANT SECRETARY FOR COMMUNITY PLANNING AND DEVELOPMENT, DEPARTMENT OF HOUSING AND URBAN DEVELOPMENT COMMUNITY FACILITIES COMMUNITY... statement. The insular area jurisdiction shall submit to HUD a final statement describing its...

  1. 24 CFR 570.440 - Application requirements for insular area grants funded under section 106.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... Regulations Relating to Housing and Urban Development (Continued) OFFICE OF ASSISTANT SECRETARY FOR COMMUNITY PLANNING AND DEVELOPMENT, DEPARTMENT OF HOUSING AND URBAN DEVELOPMENT COMMUNITY FACILITIES COMMUNITY... statement. The insular area jurisdiction shall submit to HUD a final statement describing its...

  2. 24 CFR 570.440 - Application requirements for insular area grants funded under section 106.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... Regulations Relating to Housing and Urban Development (Continued) OFFICE OF ASSISTANT SECRETARY FOR COMMUNITY PLANNING AND DEVELOPMENT, DEPARTMENT OF HOUSING AND URBAN DEVELOPMENT COMMUNITY FACILITIES COMMUNITY... statement. The insular area jurisdiction shall submit to HUD a final statement describing its...

  3. 24 CFR 570.440 - Application requirements for insular area grants funded under section 106.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... Relating to Housing and Urban Development (Continued) OFFICE OF ASSISTANT SECRETARY FOR COMMUNITY PLANNING AND DEVELOPMENT, DEPARTMENT OF HOUSING AND URBAN DEVELOPMENT COMMUNITY FACILITIES COMMUNITY... statement. The insular area jurisdiction shall submit to HUD a final statement describing its...

  4. A quantitative analysis of L-glutamate-regulated Na+ dynamics in mouse cortical astrocytes: implications for cellular bioenergetics.

    PubMed

    Chatton, J Y; Marquet, P; Magistretti, P J

    2000-11-01

    The mode of Na+ entry and the dynamics of intracellular Na+ concentration ([Na+]i) changes consecutive to the application of the neurotransmitter glutamate were investigated in mouse cortical astrocytes in primary culture by video fluorescence microscopy. An elevation of [Na+]i was evoked by glutamate, whose amplitude and initial rate were concentration dependent. The glutamate-evoked Na+ increase was primarily due to Na+-glutamate cotransport, as inhibition of non-NMDA ionotropic receptors by 6-cyano-7-nitroquinoxiline-2,3-dione (CNQX) only weakly diminished the response and D-aspartate, a substrate of the glutamate transporter, produced [Na+]i elevations similar to those evoked by glutamate. Non-NMDA receptor activation could nevertheless be demonstrated by preventing receptor desensitization using cyclothiazide. Thus, in normal conditions non-NMDA receptors do not contribute significantly to the glutamate-evoked Na+ response. The rate of Na+ influx decreased during glutamate application, with kinetics that correlate well with the increase in [Na+]i and which depend on the extracellular concentration of glutamate. A tight coupling between Na+ entry and Na+/K+ ATPase activity was revealed by the massive [Na+]i increase evoked by glutamate when pump activity was inhibited by ouabain. During prolonged glutamate application, [Na+]i remains elevated at a new steady-state where Na+ influx through the transporter matches Na+ extrusion through the Na+/K+ ATPase. A mathematical model of the dynamics of [Na+]i homeostasis is presented which precisely defines the critical role of Na+ influx kinetics in the establishment of the elevated steady state and its consequences on the cellular bioenergetics. Indeed, extracellular glutamate concentrations of 10 microM already markedly increase the energetic demands of the astrocytes.

  5. The action of antidepressants on the glutamate system: regulation of glutamate release and glutamate receptors.

    PubMed

    Musazzi, Laura; Treccani, Giulia; Mallei, Alessandra; Popoli, Maurizio

    2013-06-15

    Recent compelling evidence has suggested that the glutamate system is a primary mediator of psychiatric pathology and also a target for rapid-acting antidepressants. Clinical research in mood and anxiety disorders has shown alterations in levels, clearance, and metabolism of glutamate and consistent volumetric changes in brain areas where glutamate neurons predominate. In parallel, preclinical studies with rodent stress and depression models have found dendritic remodeling and synaptic spines reduction in corresponding areas, suggesting these as major factors in psychopathology. Enhancement of glutamate release/transmission, in turn induced by stress/glucocorticoids, seems crucial for structural/functional changes. Understanding mechanisms of maladaptive plasticity may allow identification of new targets for drugs and therapies. Interestingly, traditional monoaminergic-based antidepressants have been repeatedly shown to interfere with glutamate system function, starting with modulation of N-methyl-D-aspartate (NMDA) receptors. Subsequently, it has been shown that antidepressants reduce glutamate release and synaptic transmission; in particular, it was found antidepressants prevent the acute stress-induced enhancement of glutamate release. Additional studies have shown that antidepressants may partly reverse the maladaptive changes in synapses/circuitry in stress and depression models. Finally, a number of studies over the years have shown that these drugs regulate glutamate receptors, reducing the function of NMDA receptors, potentiating the function of α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptors, and, more recently, exerting variable effects on different subtypes of metabotropic glutamate receptors. The development of NMDA receptor antagonists has opened new avenues for glutamatergic, rapid acting, antidepressants, while additional targets in the glutamate synapse await development of new compounds for better, faster antidepressant action

  6. Glutamate-induced calcium signals stimulate CO production in piglet astrocytes

    PubMed Central

    Xi, Qi; Tcheranova, Dilyara; Basuroy, Shyamali; Parfenova, Helena; Jaggar, Jonathan H.

    2011-01-01

    Glutamate-stimulated, astrocyte-derived carbon monoxide (CO) causes cerebral arteriole dilation by activating smooth muscle cell large-conductance Ca2+-activated K+ channels. Here, we examined the hypothesis that glutamate activates heme oxygenase (HO)-2 and CO production via the intracellular Ca2+ concentration ([Ca2+]i)/Ca2+-calmodulin signaling pathway in newborn pig astrocytes. The major findings are: 1) glutamate stimulated Ca2+ transients and increased steady-state [Ca2+]i in cerebral cortical astrocytes in primary culture, 2) in astrocytes permeabilized with ionomycin, elevation of [Ca2+]i concentration-dependently increased CO production, 3) glutamate did not affect CO production at any [Ca2+]i when the [Ca2+]i was held constant, 4) thapsigargin, a sarco/endoplasmic reticulum Ca2+-ATPase blocker, decreased basal CO production and blocked glutamate-induced increases in CO, and 5) calmidazolium, a calmodulin inhibitor, blocked CO production induced by glutamate and by [Ca2+]i elevation. Taken together, our data are consistent with the hypothesis that glutamate elevates [Ca2+]i in astrocytes, leading to Ca2+- and calmodulin-dependent HO-2 activation, and CO production. PMID:21572018

  7. Glutamate pharmacology and metabolism in peripheral primary afferents: physiological and pathophysiological mechanisms.

    PubMed

    Miller, Kenneth E; Hoffman, E Matthew; Sutharshan, Mathura; Schechter, Ruben

    2011-06-01

    In addition to using glutamate as a neurotransmitter at central synapses, many primary sensory neurons release glutamate from peripheral terminals. Primary sensory neurons with cell bodies in dorsal root or trigeminal ganglia produce glutaminase, the synthetic enzyme for glutamate, and transport the enzyme in mitochondria to peripheral terminals. Vesicular glutamate transporters fill neurotransmitter vesicles with glutamate and they are shipped to peripheral terminals. Intense noxious stimuli or tissue damage causes glutamate to be released from peripheral afferent nerve terminals and augmented release occurs during acute and chronic inflammation. The site of action for glutamate can be at the autologous or nearby nerve terminals. Peripheral nerve terminals contain both ionotropic and metabotropic excitatory amino acid receptors (EAARs) and activation of these receptors can lower the activation threshold and increase the excitability of primary afferents. Antagonism of EAARs can reduce excitability of activated afferents and produce antinociception in many animal models of acute and chronic pain. Glutamate injected into human skin and muscle causes acute pain. Trauma in humans, such as arthritis, myalgia, and tendonitis, elevates glutamate levels in affected tissues. There is evidence that EAAR antagonism at peripheral sites can provide relief in some chronic pain sufferers. Copyright © 2011. Published by Elsevier Inc.

  8. 1,25-Dihydroxyvitamin D induces the glutamate transporter SLC1A1 and alters glutamate handling in non-transformed mammary cells

    PubMed Central

    Beaudin, Sarah; Welsh, JoEllen

    2016-01-01

    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

  9. 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

  10. Glutamic acid as anticancer agent: An overview.

    PubMed

    Dutta, Satyajit; Ray, Supratim; Nagarajan, K

    2013-10-01

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

  11. 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

  12. Distribution and biology of Indo-Pacific insular hypogeal shrimps

    USGS Publications Warehouse

    Maciolek, J.A.

    1983-01-01

    Ten species of caridean shrimps, representing nine genera in five families, have been found in exposures of the marine water table at 28 islands from Hawaii to the western Indian Ocean. Synthesis of literature information and personal observations indicate that, as a group, these shrimps are characterized by red body pigment, reduced but pigmented eyes, euryhalinity, a proclivity for interstitial seawater in limestone or lava rock, generalized food requirements, and probable pre-Pleistocene origins. The shrimps have not been found in waters cooler than about 20°C.Species are often solitary, but as many as five are known to coexist. Six of the species have widely scattered populations, some as far apart as Hawaii and the Red Sea. Passive oceanic dispersal is endorsed as a general explanation for such apparently disjunct distributions. On the basis of an assumed primary habitat requirement of interstitial marine water, which could include that in shallow submerged rock as well as that in emergent (insular) rock, I hypothesize a much more cosmopolitan distribution of these shrimps in the Indo-Pacific Tropical Zone.

  13. The anterior insular cortex represents breaches of taste identity expectation.

    PubMed

    Veldhuizen, Maria G; Douglas, Danielle; Aschenbrenner, Katja; Gitelman, Darren R; Small, Dana M

    2011-10-12

    Despite the importance of breaches of taste identity expectation for survival, its neural correlate is unknown. We used fMRI in 16 women to examine brain response to expected and unexpected receipt of sweet taste and tasteless/odorless solutions. During expected trials (70%), subjects heard "sweet" or "tasteless" and received the liquid indicated by the cue. During unexpected trials (30%), subjects heard sweet but received tasteless or they heard tasteless but received sweet. After delivery, subjects indicated stimulus identity by pressing a button. Reaction time was faster and more accurate after valid cuing, indicating that the cues altered expectancy as intended. Tasting unexpected versus expected stimuli resulted in greater deactivation in fusiform gyri, possibly reflecting greater suppression of visual object regions when orienting to, and identifying, an unexpected taste. Significantly greater activation to unexpected versus expected stimuli occurred in areas related to taste (thalamus, anterior insula), reward [ventral striatum (VS), orbitofrontal cortex], and attention [anterior cingulate cortex, inferior frontal gyrus, intraparietal sulcus (IPS)]. We also observed an interaction between stimulus and expectation in the anterior insula (primary taste cortex). Here response was greater for unexpected versus expected sweet compared with unexpected versus expected tasteless, indicating that this region is preferentially sensitive to breaches of taste expectation. Connectivity analyses confirmed that expectation enhanced network interactions, with IPS and VS influencing insular responses. We conclude that unexpected oral stimulation results in suppression of visual cortex and upregulation of sensory, attention, and reward regions to support orientation, identification, and learning about salient stimuli.

  14. Glutamate pays its own way in astrocytes.

    PubMed

    McKenna, Mary C

    2013-12-16

    In vitro and in vivo studies have shown that glutamate can be oxidized for energy by brain astrocytes. The ability to harvest the energy from glutamate provides astrocytes with a mechanism to offset the high ATP cost of the uptake of glutamate from the synaptic cleft. This brief review focuses on oxidative metabolism of glutamate by astrocytes, the specific pathways involved in the complete oxidation of glutamate and the energy provided by each reaction.

  15. Prefrontal cortex glutamate and extraversion

    PubMed Central

    Schubert, Florian; Jaedke, Maren; Gallinat, Jürgen; Bajbouj, Malek

    2012-01-01

    Extraversion is considered one of the core traits of personality. Low extraversion has been associated with increased vulnerability to affective and anxiety disorders. Brain imaging studies have linked extraversion, approach behaviour and the production of positive emotional states to the dorsolateral prefrontal cortex (DLPFC) and glutamatergic neurotransmission. However, the relationship between extraversion and glutamate in the DLPFC has not been investigated so far. In order to address this issue, absolute glutamate concentrations in the DLPFC and the visual cortex as a control region were measured by 3-Tesla proton magnetic resonance spectroscopy (1H-MRS) in 29 subjects with high and low extraversion. We found increased glutamate levels in the DLPFC of introverts as compared with extraverts. The increased glutamate concentration was specific for the DLPFC and negatively associated with state anxiety. Although preliminary, results indicate altered top-down control of DLPFC due to reduced glutamate concentration as a function of extraversion. Glutamate measurement with 1H-MRS may facilitate the understanding of biological underpinnings of personality traits and psychiatric diseases associated with dysfunctions in approach behaviour and the production of positive emotional states. PMID:22016442

  16. Prefrontal cortex glutamate and extraversion.

    PubMed

    Grimm, Simone; Schubert, Florian; Jaedke, Maren; Gallinat, Jürgen; Bajbouj, Malek

    2012-10-01

    Extraversion is considered one of the core traits of personality. Low extraversion has been associated with increased vulnerability to affective and anxiety disorders. Brain imaging studies have linked extraversion, approach behaviour and the production of positive emotional states to the dorsolateral prefrontal cortex (DLPFC) and glutamatergic neurotransmission. However, the relationship between extraversion and glutamate in the DLPFC has not been investigated so far. In order to address this issue, absolute glutamate concentrations in the DLPFC and the visual cortex as a control region were measured by 3-Tesla proton magnetic resonance spectroscopy (1H-MRS) in 29 subjects with high and low extraversion. We found increased glutamate levels in the DLPFC of introverts as compared with extraverts. The increased glutamate concentration was specific for the DLPFC and negatively associated with state anxiety. Although preliminary, results indicate altered top-down control of DLPFC due to reduced glutamate concentration as a function of extraversion. Glutamate measurement with 1H-MRS may facilitate the understanding of biological underpinnings of personality traits and psychiatric diseases associated with dysfunctions in approach behaviour and the production of positive emotional states.

  17. 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.

  18. Bicyclic glutamic acid derivatives.

    PubMed

    Meyer, Udo; Bisel, Philippe; Weckert, Edgar; Frahm, August Wilhelm

    2006-05-15

    For the second-generation asymmetric synthesis of the trans-tris(homoglutamic) acids via Strecker reaction of chiral ketimines, the cyanide addition as the key stereodifferentiating step produces mixtures of diastereomeric alpha-amino nitrile esters the composition of which is independent of the reaction temperature and the type of the solvent, respectively. The subsequent hydrolysis is exclusively achieved with concentrated H(2)SO(4) yielding diastereomeric mixtures of three secondary alpha-amino alpha-carbamoyl-gamma-esters and two diastereomeric cis-fused angular alpha-carbamoyl gamma-lactams as bicyclic glutamic acid derivatives, gained from in situ stereomer differentiating cyclisation of the secondary cis-alpha-amino alpha-carbamoyl-gamma-esters. Separation was achieved by CC. The pure secondary trans-alpha-amino alpha-carbamoyl-gamma-esters cyclise on heating and treatment with concentrated H(2)SO(4), respectively, to diastereomeric cis-fused angular secondary alpha-amino imides. Their hydrogenolysis led to the enantiomeric cis-fused angular primary alpha-amino imides. The configuration of all compounds was completely established by NMR methods, CD-spectra, and by X-ray analyses of the (alphaR,1R,5R)-1-carbamoyl-2-(1-phenylethyl)-2-azabicyclo[3.3.0]octan-3-one and of the trans-alphaS,1S,2R-2-ethoxycarbonylmethyl-1-(1-phenylethylamino)cyclopentanecarboxamide.

  19. Subgroup characteristics of insular low-grade glioma based on clinical and molecular analysis of 42 cases.

    PubMed

    Tang, Chao; Zhang, Zhen-yu; Chen, Ling-chao; Sun, Zelin; Zhang, Yi; Qin, Zhiyong; Yao, Yu; Zhou, Liang-fu

    2016-02-01

    Although the classification of insular glioma has been established based on the anatomical location in order to facilitate personalized surgical resection, the diagnosis based on anatomical and functional characteristics becomes more complex when insular tumors extend into either the frontobasal brain region and/or the temporal lobe, as part of the limbic system. Moreover, prognosis of insular tumor resection is still controversial. Further analysis of subgroup characteristics of insular grade II gliomas based on clinical and molecular analysis is required to reliably determine patients' survival rates. In this retrospective study 20 purely insular grade II gliomas patients and 22 paralimbic grade II gliomas that involved frontal and/or temporal lobes were compared with regard to epidemiological and clinical characteristics. The molecular profiles including Isocitrate dehydrogenase 1 (IDH1), telomerase reverse transcriptase (TERT) promoter, and P53 mutations, 1p19q co-deletion were analyzed, and microRNA profiles were assessed by microarray and bioinformatics analysis. Purely insular grade II gliomas displayed a high frequency of IDH1 mutations with favorable outcome. IDH1 mutated paralimbic glioma shared many parameters with the purely insular glioma in respect to growth patterns, survival, and microRNA profile, but differed significantly from the IDH1 wild type paralimbic gliomas. Our findings suggest that IDH1 mutations can define subpopulations of insular gliomas with distinct disease entities regardless of tumor extension patterns. These findings could be useful to develop a customized treatment strategy for insular glioma patients.

  20. Electrical Stimulations of the Human Insula: Their Contribution to the Ictal Semiology of Insular Seizures.

    PubMed

    Mazzola, Laure; Mauguière, François; Isnard, Jean

    2017-07-01

    Stereotactic stimulations of the insular cortex through intracranial electrodes aim at characterizing the semiology of insular seizures. These stimulations, carried out in the context of Stereo-Electro-Encephalography (SEEG) during presurgical monitoring of epilepsy, reproduce the ictal symptoms observed during the development of insular seizures. The authors reviewed the results of insular stimulations performed in 222 patients admitted between 1997 and 2015 for presurgical SEEG exploration of atypical temporal or perisylvian epilepsy. Stimulations (50 Hz, trains of 5 seconds, pulses of 0.5 ms, intensity 0.2-3.5 mA) were carried out using transopercular electrodes implanted orthogonal to midsagittal plane. Out of a total of 669 stimulations, 550 were clinically eloquent in the absence of any postdischarge (237 and 313, respectively, in the right and left insulae). Somatosensory responses (61% of evoked sensations) including pain and visceral sensations (14.9%) were the most frequent, followed by auditory sensations (8%), vestibular illusions (7.5%), speech impairment (5%), gustatory, (2.7%), and olfactory (1%) sensations. Although these responses showed some functional segregation (in particular a privileged pain representation in the postero-superior quadrant), there was a clear spatial overlap between representations of the different modalities. Symptoms evoked by insular stimulations are multiple. None of them can be considered as absolutely specific to the insular cortex, but the occurrence in given seizure of a somatosensory symptom such as pain or of a laryngeal spasm associated with vestibular, auditory, aphasic, or olfacto-gustatory symptoms points to a discharge development in the insular cortex, which is the only cortical region where stimulations demonstrate such a multimodal representation.

  1. Negative childhood experiences alter a prefrontal-insular-motor cortical network in healthy adults: A preliminary multimodal rsfMRI-fMRI-MRS-dMRI study

    PubMed Central

    Duncan, Niall W.; Hayes, Dave J.; Wiebking, Christine; Tiret, Brice; Pietruska, Karin; Chen, David Q.; Rainville, Pierre; Marjańska, Malgorzata; Mohammid, Omar; Doyon, Julien; Hodaie, Mojgan; Northoff, Georg

    2016-01-01

    Research in humans and animals has shown that negative childhood experiences (NCE) can have long-term effects on the structure and function of the brain. Alterations have been noted in grey and white matter, in the brain’s resting state, on the glutamatergic system, and on neural and behavioural responses to aversive stimuli. These effects can be linked to psychiatric disorder such as depression and anxiety disorders that are influenced by excessive exposure to early life stressors. The aim of the current study was to investigate the effect of NCEs on these systems. Resting state functional MRI (rsfMRI), aversion task fMRI, glutamate magnetic resonance spectroscopy (MRS), and diffusion magnetic resonance imaging (dMRI) were combined with the Childhood Trauma Questionnaire (CTQ) in healthy subjects to examine the impact of NCEs on the brain. Low CTQ scores, a measure of NCEs, were related to higher resting state glutamate levels and higher resting state entropy in the medial prefrontal cortex (mPFC). CTQ scores, mPFC glutamate and entropy, correlated with neural BOLD responses to the anticipation of aversive stimuli in regions throughout the aversion-related network, with strong correlations between all measures in the motor cortex and left insula. Structural connectivity strength, measured using mean fractional anisotropy, between the mPFC and left insula correlated to aversion-related signal changes in the motor cortex. These findings highlight the impact of NCEs on multiple inter-related brain systems. In particular, they highlight the role of a prefrontal-insular-motor cortical network in the processing and responsivity to aversive stimuli and its potential adaptability by NCEs. PMID:26287448

  2. Glutamate dysregulation in the trigeminal ganglion: a novel mechanism for peripheral sensitization of the craniofacial region.

    PubMed

    Laursen, J C; Cairns, B E; Dong, X D; Kumar, U; Somvanshi, R K; Arendt-Nielsen, L; Gazerani, P

    2014-01-03

    In the trigeminal ganglion (TG), satellite glial cells (SGCs) form a functional unit with neurons. It has been proposed that SGCs participate in regulating extracellular glutamate levels and that dysfunction of this SGC capacity can impact nociceptive transmission in craniofacial pain conditions. This study investigated whether SGCs release glutamate and whether elevation of TG glutamate concentration alters response properties of trigeminal afferent fibers. Immunohistochemistry was used to assess glutamate content and the expression of excitatory amino acid transporter (EAAT)1 and EAAT2 in TG sections. SGCs contained glutamate and expressed EAAT1 and EAAT2. Potassium chloride (10 mM) was used to evoke glutamate release from cultured rat SGCs treated with the EAAT1/2 inhibitor (3S)-3-[[3-[[4-(trifluoromethyl)ben zoyl]amino]phenyl]methoxy]-L-aspartic acid (TFB-TBOA) or control. Treatment with TFB-TBOA (1 and 10 μM) significantly reduced the glutamate concentration from 10.6 ± 1.1 to 5.8 ± 1.4 μM and 3.0 ± 0.8 μM, respectively (p<0.05). Electrophysiology experiments were conducted in anaesthetized rats to determine the effect of intraganglionic injections of glutamate on the response properties of ganglion neurons that innervated either the temporalis or masseter muscle. Intraganglionic injection of glutamate (500 mM, 3 μl) evoked afferent discharge and significantly reduced muscle afferent mechanical threshold. Glutamate-evoked discharge was attenuated bythe N-methyl-D-aspartate receptor antagonist 2-amino-5-phosphonovalerate (APV) and increased by TFB-TBOA, whereas mechanical sensitization was only sensitive to APV. Antidromic invasion of muscle afferent fibers by electrical stimulation of the caudal brainstem (10 Hz) or local anesthesia of the brainstem with lidocaine did not alter glutamate-induced mechanical sensitization. These findings provide a novel mechanism whereby dysfunctional trigeminal SGCs could contribute to cranial muscle tenderness in

  3. Abnormalities in glutamate metabolism and excitotoxicity in the retinal diseases.

    PubMed

    Ishikawa, Makoto

    2013-01-01

    In the physiological condition, glutamate acts as an excitatory neurotransmitter in the retina. However, excessive glutamate can be toxic to retinal neurons by overstimulation of the glutamate receptors. Glutamate excess is primarily attributed to perturbation in the homeostasis of the glutamate metabolism. Major pathway of glutamate metabolism consists of glutamate uptake by glutamate transporters followed by enzymatic conversion of glutamate to nontoxic glutamine by glutamine synthetase. Glutamate metabolism requires energy supply, and the energy loss inhibits the functions of both glutamate transporters and glutamine synthetase. In this review, we describe the present knowledge concerning the retinal glutamate metabolism under the physiological and pathological conditions.

  4. Biochemical and immunological changes on oral glutamate feeding in male albino rats

    NASA Astrophysics Data System (ADS)

    Kumar, D.; Bansal, Anju; Thomas, Pauline; Sairam, M.; Sharma, S. K.; Mongia, S. S.; Singh, R.; Selvamurthy, W.

    High altitude stress leads to lipid peroxidation and free radical formation which results in cell membrane damage in organs and tissues, and associated mountain diseases. This paper discusses the changes in biochemical parameters and antibody response on feeding glutamate to male albino Sprague Dawley rats under hypoxic stress. Exposure of rats to simulated hypoxia at 7576 m, for 6 h daily for 5 consecutive days, in an animal decompression chamber at 32+/-2° C resulted in an increase in plasma malondialdehyde level with a concomitant decrease in blood glutathione (reduced) level. Supplementation of glutamate orally at an optimal dose (27 mg/kg body weight) in male albino rats under hypoxia enhanced glutathione level and decreased malondialdehyde concentration significantly. Glutamate feeding improved total plasma protein and glucose levels under hypoxia. The activities of serum glutamate oxaloacetate transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) and the urea level remained elevated on glutamate supplementation under hypoxia. Glutamate supplementation increased the humoral response against sheep red blood cells (antibody titre). These results indicate a possible utility of glutamate in the amelioration of hypoxia-induced oxidative stress.

  5. Disrupted resting-state insular subregions functional connectivity in post-traumatic stress disorder.

    PubMed

    Zhang, Youxue; Xie, Bing; Chen, Heng; Li, Meiling; Guo, Xiaonan; Chen, Huafu

    2016-07-01

    Post-traumatic stress disorder (PTSD) is suggested to be a structural and functional abnormality in the insula. The insula, which consists of distinct subregions with various patterns of connectivity, displays complex and diverse functions. However, whether these insular subregions have different patterns of connectivity in PTSD remains unclear. Investigating the abnormal functional connectivity of the insular subregions is crucial to reveal its potential effect on diseases specifically PTSD. This study uses a seed-based method to investigate the altered resting-state functional connectivity of insular subregions in PTSD. We found that patients with PTSD showed reduced functional connectivity compared with healthy controls (HCs) between the left ventral anterior insula and the anterior cingulate cortex. The patients with PTSD also exhibited decreased functional connectivity between the right posterior insula and left inferior parietal lobe, and the postcentral gyrus relative to HCs. These results suggest the involvement of altered functional connectivity of insular subregions in the abnormal regulation of emotion and processing of somatosensory information in patients with PTSD. Such impairments in functional connectivity patterns of the insular subregions may advance our understanding of the pathophysiological basis underlying PTSD.

  6. Disrupted resting-state insular subregions functional connectivity in post-traumatic stress disorder

    PubMed Central

    Zhang, Youxue; Xie, Bing; Chen, Heng; Li, Meiling; Guo, Xiaonan; Chen, Huafu

    2016-01-01

    Abstract Post-traumatic stress disorder (PTSD) is suggested to be a structural and functional abnormality in the insula. The insula, which consists of distinct subregions with various patterns of connectivity, displays complex and diverse functions. However, whether these insular subregions have different patterns of connectivity in PTSD remains unclear. Investigating the abnormal functional connectivity of the insular subregions is crucial to reveal its potential effect on diseases specifically PTSD. This study uses a seed-based method to investigate the altered resting-state functional connectivity of insular subregions in PTSD. We found that patients with PTSD showed reduced functional connectivity compared with healthy controls (HCs) between the left ventral anterior insula and the anterior cingulate cortex. The patients with PTSD also exhibited decreased functional connectivity between the right posterior insula and left inferior parietal lobe, and the postcentral gyrus relative to HCs. These results suggest the involvement of altered functional connectivity of insular subregions in the abnormal regulation of emotion and processing of somatosensory information in patients with PTSD. Such impairments in functional connectivity patterns of the insular subregions may advance our understanding of the pathophysiological basis underlying PTSD. PMID:27399097

  7. A review and outlook of terrestrial and insular vegetation classification research in China

    NASA Astrophysics Data System (ADS)

    Cai, Yanhong; Li, Xiaoming; Wei, Yongjie; Ye, Ran

    2017-04-01

    The terrestrial vegetation classification in China has attained significant development on the basis of the field investigation and its related research during the past century. Lacking of the observation data, the research situation of insular vegetation classification is diametrical. This article is aiming to fill the vacancy by the conclusive research. Firstly, the article reviews the research experience of Chinese terrestrial vegetation classification and regionalization. Taking the islands of Zhejiang Province and Fujian Province as example, it comes up with the exploration of the relationship between insular vegetation classification and climatic limitation factors, and the approach of researching insular vegetation types and its distribution. Secondly, according to the theory of terrestrial classification, the article discusses the possible vegetation types of the islands of Zhejiang Province and Fujian Province, and make sure that insular vegetation type should be in the range of terrestrial vegetation. Finally, based on the integrative analysis, a new approach of insular vegetation classification is proposed. Starting from the climatic limitation factors distributions, the vegetation types and their distribution have been being deduced, in consideration of the relationship between vegetation and climatic limitation factors, which differ from method of the land vegetation classification.

  8. Neuronavigated Fiber Dissection with Pial Preservation: Laboratory Model to Simulate Opercular Approaches to Insular Tumors.

    PubMed

    Mandonnet, Emmanuel; Martino, Juan; Sarubbo, Silvio; Corrivetti, Francesco; Bouazza, Schahrazed; Bresson, Damien; Duffau, Hugues; Froelich, Sebastien

    2017-02-01

    Advances in the oncologic and functional results of insular surgery have been reported recently. Such successes have been made possible by the advent of the transopercular approach under awake monitoring and by improved anatomic and functional knowledge of white matter pathways surrounding the insula. Nonetheless, given the rarity of insular tumors, it is difficult to get familiar with the complex 3-dimensional anatomy of the different neuronal and vascular structures encountered during a transopercular insular resection. We thus propose to develop a laboratory model allowing to train transopercular approaches of the insula. Two hemispheres prepared with Klinger's technique were dissected under light microscope, preserving all pial membranes. The different steps of the dissection were video recorded. Preservation of pial membranes enabled us to simulate subpial resection, both during operculum removal and during insular cortex resection. The medial wall of the resection was defined by the inferior-fronto-occipital fasciculus, protecting from the lenticulostriate arteries. In this paper, we show that Klinger dissection with preservation of pial membranes provides a realistic model of insular surgery, allowing surgeons to learn and train on this highly specialized surgery. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Insular Area energy vulnerability, Puerto Rico, US Virgin Islands. Technical Appendix 1

    SciTech Connect

    Stern, M.; Willard, E.E.; Efferding, S.

    1994-05-01

    This report was prepared in response to Section 1406 of the Energy Policy Act of 1992 (P.L. 192-486). The Act directed the Department of Energy (DOE) to ``conduct a study of the implications of the unique vulnerabilities of the insular areas to an oil supply disruption,`` and to ``outline how the insular areas shall gain access to vital oil supplies during times of national emergency.`` The Act defines the insular areas to be the US Virgin Islands and Puerto Rico in the Caribbean, and Guam, American Samoa, the Commonwealth of the Northern Mariana Islands (CNMI), and Palau in the Pacific. This report is the analysis of Puerto Rico and the US Virgin Islands. In the study, ``unique vulnerabilities`` were defined as susceptibility to: (1) more frequent or more likely interruptions of oil supplies compared to the mainland, and/or (2) disproportionately larger or more likely economic losses in the event of an oil supply disruption. In order to asses unique vulnerabilities, the study examined in the insular areas` experience during past global disruptions of oil supplies and during local emergencies caused by natural disasters. The effects of several possible future global disruptions and local emergencies were also analyzed. Analyses were based on historical data, simulations using energy and economic models, and interviews with officials in the insular governments and the energy industry.

  10. Tuberculosis Epidemiology in Islands: Insularity, Hosts and Trade

    PubMed Central

    Acevedo, Pelayo; Romero, Beatriz; Vicente, Joaquin; Caracappa, Santo; Galluzzo, Paola; Marineo, Sandra; Vicari, Domenico; Torina, Alessandra; Casal, Carmen; de la Fuente, Jose; Gortazar, Christian

    2013-01-01

    Because of their relative simplicity and the barriers to gene flow, islands are ideal systems to study the distribution of biodiversity. However, the knowledge that can be extracted from this peculiar ecosystem regarding epidemiology of economically relevant diseases has not been widely addressed. We used information available in the scientific literature for 10 old world islands or archipelagos and original data on Sicily to gain new insights into the epidemiology of the Mycobacterium tuberculosis complex (MTC). We explored three nonexclusive working hypotheses on the processes modulating bovine tuberculosis (bTB) herd prevalence in cattle and MTC strain diversity: insularity, hosts and trade. Results suggest that bTB herd prevalence was positively correlated with island size, the presence of wild hosts, and the number of imported cattle, but neither with isolation nor with cattle density. MTC strain diversity was positively related with cattle bTB prevalence, presence of wild hosts and the number of imported cattle, but not with island size, isolation, and cattle density. The three most common spoligotype patterns coincided between Sicily and mainland Italy. However in Sicily, these common patterns showed a clearer dominance than on the Italian mainland, and seven of 19 patterns (37%) found in Sicily had not been reported from continental Italy. Strain patterns were not spatially clustered in Sicily. We were able to infer several aspects of MTC epidemiology and control in islands and thus in fragmented host and pathogen populations. Our results point out the relevance of the intensity of the cattle commercial networks in the epidemiology of MTC, and suggest that eradication will prove more difficult with increasing size of the island and its environmental complexity, mainly in terms of the diversity of suitable domestic and wild MTC hosts. PMID:23923053

  11. Tuberculosis epidemiology in islands: insularity, hosts and trade.

    PubMed

    Acevedo, Pelayo; Romero, Beatriz; Vicente, Joaquin; Caracappa, Santo; Galluzzo, Paola; Marineo, Sandra; Vicari, Domenico; Torina, Alessandra; Casal, Carmen; de la Fuente, Jose; Gortazar, Christian

    2013-01-01

    Because of their relative simplicity and the barriers to gene flow, islands are ideal systems to study the distribution of biodiversity. However, the knowledge that can be extracted from this peculiar ecosystem regarding epidemiology of economically relevant diseases has not been widely addressed. We used information available in the scientific literature for 10 old world islands or archipelagos and original data on Sicily to gain new insights into the epidemiology of the Mycobacterium tuberculosis complex (MTC). We explored three nonexclusive working hypotheses on the processes modulating bovine tuberculosis (bTB) herd prevalence in cattle and MTC strain diversity: insularity, hosts and trade. Results suggest that bTB herd prevalence was positively correlated with island size, the presence of wild hosts, and the number of imported cattle, but neither with isolation nor with cattle density. MTC strain diversity was positively related with cattle bTB prevalence, presence of wild hosts and the number of imported cattle, but not with island size, isolation, and cattle density. The three most common spoligotype patterns coincided between Sicily and mainland Italy. However in Sicily, these common patterns showed a clearer dominance than on the Italian mainland, and seven of 19 patterns (37%) found in Sicily had not been reported from continental Italy. Strain patterns were not spatially clustered in Sicily. We were able to infer several aspects of MTC epidemiology and control in islands and thus in fragmented host and pathogen populations. Our results point out the relevance of the intensity of the cattle commercial networks in the epidemiology of MTC, and suggest that eradication will prove more difficult with increasing size of the island and its environmental complexity, mainly in terms of the diversity of suitable domestic and wild MTC hosts.

  12. Temporal prediction errors modulate cingulate-insular coupling.

    PubMed

    Limongi, Roberto; Sutherland, Steven C; Zhu, Jian; Young, Michael E; Habib, Reza

    2013-05-01

    Prediction error (i.e., the difference between the expected and the actual event's outcome) mediates adaptive behavior. Activity in the anterior mid-cingulate cortex (aMCC) and in the anterior insula (aINS) is associated with the commission of prediction errors under uncertainty. We propose a dynamic causal model of effective connectivity (i.e., neuronal coupling) between the aMCC, the aINS, and the striatum in which the task context drives activity in the aINS and the temporal prediction errors modulate extrinsic cingulate-insular connections. With functional magnetic resonance imaging, we scanned 15 participants when they performed a temporal prediction task. They observed visual animations and predicted when a stationary ball began moving after being contacted by another moving ball. To induced uncertainty-driven prediction errors, we introduced spatial gaps and temporal delays between the balls. Classical and Bayesian fMRI analyses provided evidence to support that the aMCC-aINS system along with the striatum not only responds when humans predict whether a dynamic event occurs but also when it occurs. Our results reveal that the insula is the entry port of a three-region pathway involved in the processing of temporal predictions. Moreover, prediction errors rather than attentional demands, task difficulty, or task duration exert an influence in the aMCC-aINS system. Prediction errors debilitate the effect of the aMCC on the aINS. Finally, our computational model provides a way forward to characterize the physiological parallel of temporal prediction errors elicited in dynamic tasks.

  13. Downregulation of postsynaptic density-95-interacting regulator of spine morphogenesis reduces glutamate-induced excitotoxicity by differentially regulating glutamate receptors in rat cortical neurons.

    PubMed

    Luo, Peng; Yang, Yuefan; Liu, Wei; Rao, Wei; Bian, Huan; Li, Xin; Chen, Tao; Liu, Mengdong; Zhao, Yongbo; Dai, Shuhui; Yan, Xu; Fei, Zhou

    2013-12-01

    Glutamate-induced excitotoxicity is involved in many neurological diseases. Preso, a novel postsynaptic scaffold protein, mediates excitatory synaptic transmission and various synaptic functions. In this study, we investigated the role of Preso in the regulation of glutamate-induced excitotoxicity in rat cortical neurons. Knockdown of Preso with small interfering RNA improved neuronal viability and attenuated the elevation of lactate dehydrogenase (LDH) release after glutamate treatment. Downregulation of Preso also inhibited an increase in the BAX/Bcl-2 ratio and cleavage of caspase-9 and caspase-3. Although the expression and distribution of metabotropic glutamate receptor (mGluR) 1/5, NR1, NR2A and NR2B were not changed by knockdown of Preso, downregulation of Preso protected neurons from glutamate-induced excitotoxicity by inhibiting mGluR and N-methyl-D-aspartate receptor function. However, downregulation of Preso neither affected the expression of GluR1 and GluR2 nor influenced the function of α-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor after glutamate treatment. Furthermore, intracellular Ca(2+) was an important downstream effector of Preso in the regulation of excitotoxicity. These results suggest that expression of Preso promotes the induction of excitotoxicity by facilitating different glutamate receptor signaling pathways. Therefore, Preso might be a potential pharmacological target for preventing and treating neurological diseases.

  14. Glutamate and ATP signalling in white matter pathology

    PubMed Central

    Matute, Carlos

    2011-01-01

    Excessive signalling by excitatory neurotransmitters like glutamate and ATP can be deleterious to neurons and oligodendroglia, and cause disease. In particular, sustained activation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), kainate and N-methyl-d-aspartate (NMDA) receptors damages oligodendrocytes, a feature that depends entirely on Ca2+ overload of the cytoplasm and that can be initiated by disruption of glutamate homeostasis. Thus, inhibition of glutamate uptake by activated microglia can compromise glutamate homeostasis and induce oligodendrocyte excitotoxicity. Moreover, non-lethal, brief activation of kainate receptors in oligodendrocytes rapidly sensitizes these cells to complement attack as a consequence of oxidative stress. In addition to glutamate, ATP signalling can directly trigger oligodendrocyte excitotoxicity via activation of Ca2+-permeable P2X7 purinergic receptors, which mediates ischaemic damage to white matter (WM) and causes lesions that are reminiscent of multiple sclerosis (MS) plaques. Conversely, blockade of P2X7 receptors attenuates post-ischaemic injury to WM and ameliorates chronic experimental autoimmune encephalomyelitis, a model of MS. Importantly, P2X7 expression is elevated in normal-appearing WM in patients with MS, suggesting that signalling through this receptor in oligodendrocytes may be enhanced in this disease. Altogether, these observations reveal novel mechanisms by which altered glutamate and ATP homeostasis can trigger oligodendrocyte death. This review aims at summarizing current knowledge about the mechanisms leading to WM damage as a consequence of altered neurotransmitter signalling, and their relevance to disease. This knowledge will generate new therapeutic avenues to treat more efficiently acute and chronic WM pathology. PMID:21250988

  15. Role of Glutamate Transporters in Redox Homeostasis of the Brain

    PubMed Central

    Robert, Stephanie M.; Ogunrinu-Babarinde, Toyin; Holt, Kenneth T.; Sontheimer, Harald

    2014-01-01

    Redox homeostasis is especially important in the brain where high oxygen consumption produces an abundance of harmful oxidative by-products. Glutathione (GSH) is a tripeptide non-protein thiol. It is the central nervous system’s most abundant antioxidant, and the master controller of brain redox homeostasis. The glutamate transporters, System xc− (SXC) and the Excitatory Amino Acid Transporters (EAAT), play important, synergistic roles in the synthesis of GSH. In glial cells, SXC mediates the uptake of cystine, which after intracellular reduction to cysteine, reacts with glutamate during the rate-limiting step of GSH synthesis. EAAT3 mediates direct cysteine uptake for neuronal GSH synthesis. SXC and EAAT work in concert in glial cells to provide two intracellular substrates for GSH synthesis, cystine and glutamate. Their cyclical basal function also prevents a buildup of extracellular glutamate, which SXC releases extracellularly in exchange for cystine uptake. Maintaining extracellular glutamate homeostasis is critical to prevent neuronal toxicity, as well as glutamate-mediated SXC inhibition, of which each could lead to a depletion of intracellular GSH and loss of cellular redox control. Many neurological diseases show evidence of GSH dysfunction, and increased GSH has been widely associated with chemotherapy and radiotherapy resistance of gliomas. We present evidence suggesting that gliomas expressing elevated levels of SXC are more reliant on GSH for growth and survival. They have an increased inherent radiation resistance, yet inhibition of SXC can increase tumor sensitivity at low radiation doses. GSH depletion through SXC inhibition may be a viable mechanism to enhance current glioma treatment strategies and make tumors more sensitive to radiation and chemotherapy protocols. PMID:24418113

  16. Metabotropic glutamate receptors in cancer.

    PubMed

    Yu, Lumeng J; Wall, Brian A; Wangari-Talbot, Janet; Chen, Suzie

    2016-02-16

    Metabotropic glutamate receptors (mGluRs) are widely known for their roles in synaptic signaling. However, accumulating evidence suggests roles of mGluRs in human malignancies in addition to synaptic transmission. Somatic cell homeostasis presents intriguing possibilities of mGluRs and glutamate signaling as novel targets for human cancers. More recently, aberrant glutamate signaling has been shown to participate in the transformation and maintenance of various cancer types, including glioma, melanoma skin cancer, breast cancer, and prostate cancer, indicating that genes encoding mGluRs, GRMs, can function as oncogenes. Here, we provide a review on the interactions of mGluRs and their ligand, glutamate, in processes that promote the growth of tumors of neuronal and non-neuronal origins. Further, we discuss the evolution of riluzole, a glutamate release inhibitor approved for amyotrophic lateral sclerosis (ALS), but now fashioned as an mGluR1 inhibitor for melanoma therapy and as a radio-sensitizer for tumors that have metastasized to the brain. With the success of riluzole, it is not far-fetched to believe that other drugs that may act directly or indirectly on other mGluRs can be beneficial for multiple applications.

  17. A giant submarine slope failure on the northern insular slope of Puerto Rico

    USGS Publications Warehouse

    Schwab, W.C.; Danforth, W.W.; Scanlon, K.M.; Masson, D.G.

    1991-01-01

    A large amphitheater-shaped scarp, approximately 55 km across, was imaged on the northern insular slope of Puerto Rico using long-range sidescan sonar and bathymetric data. This scarp results from the removal of more than 1500 km3 of Tertiary strata. A review of seismic-reflection profiles, stratigraphic data, and subsidence models of the northern insular margin of Puerto Rico were used to infer that large-scale slope failure was induced by the tectonic oversteepening of the insular slope and was responsible for the formation of the scarp. The oversteepening probably was caused by the most recent episode of convergence of the Caribbean and North American plates, which began between approximately 4 and 2.5 m.y. ago. The Tertiary strata have been tilted approximately 4.5?? to the north in the last 4 m.y. ?? 1991.

  18. Feelings of warmth correlate with neural activity in right anterior insular cortex.

    PubMed

    Olausson, H; Charron, J; Marchand, S; Villemure, C; Strigo, I A; Bushnell, M C

    2005-11-25

    The neural coding of perception can differ from that for the physical attributes of a stimulus. Recent studies suggest that activity in right anterior insular cortex may underlie thermal perception, particularly that of cold. We now examine whether this region is also important for the perception of warmth. We applied cutaneous warm stimuli on the left leg (warmth) in normal subjects (n = 7) during functional magnetic resonance imaging (fMRI). After each stimulus, subjects rated their subjective intensity of the stimulus using a visual analogue scale (VAS), and correlations were determined between the fMRI signal and the VAS ratings. We found that intensity ratings of warmth correlated with the fMRI signal in the right (contralateral to stimulation) anterior insular cortex. These results, in conjunction with previous reports, suggest that the right anterior insular cortex is important for different types of thermal perception.

  19. Dyscalculia, Dysgraphia, and Left-Right Confusion from a Left Posterior Peri-Insular Infarct

    PubMed Central

    Bhattacharyya, S.; Cai, X.; Klein, J. P.

    2014-01-01

    The Gerstmann syndrome of dyscalculia, dysgraphia, left-right confusion, and finger agnosia is generally attributed to lesions near the angular gyrus of the dominant hemisphere. A 68-year-old right-handed woman presented with sudden difficulty completing a Sudoku grid and was found to have dyscalculia, dysgraphia, and left-right confusion. Magnetic resonance imaging (MRI) showed a focus of abnormal reduced diffusivity in the left posterior insula and temporoparietal operculum consistent with acute infarct. Gerstmann syndrome from an insular or peri-insular lesion has not been described in the literature previously. Pathological and functional imaging studies show connections between left posterior insular region and inferior parietal lobe. We postulate that the insula and operculum lesion disrupted key functional networks resulting in a pseudoparietal presentation. PMID:24817791

  20. Dyscalculia, dysgraphia, and left-right confusion from a left posterior peri-insular infarct.

    PubMed

    Bhattacharyya, S; Cai, X; Klein, J P

    2014-01-01

    The Gerstmann syndrome of dyscalculia, dysgraphia, left-right confusion, and finger agnosia is generally attributed to lesions near the angular gyrus of the dominant hemisphere. A 68-year-old right-handed woman presented with sudden difficulty completing a Sudoku grid and was found to have dyscalculia, dysgraphia, and left-right confusion. Magnetic resonance imaging (MRI) showed a focus of abnormal reduced diffusivity in the left posterior insula and temporoparietal operculum consistent with acute infarct. Gerstmann syndrome from an insular or peri-insular lesion has not been described in the literature previously. Pathological and functional imaging studies show connections between left posterior insular region and inferior parietal lobe. We postulate that the insula and operculum lesion disrupted key functional networks resulting in a pseudoparietal presentation.

  1. Putamen involvement and survival outcomes in patients with insular low-grade gliomas.

    PubMed

    Wang, Yongheng; Wang, Yinyan; Fan, Xing; Li, Shaowu; Liu, Xing; Wang, Jiangfei; Jiang, Tao

    2017-06-01

    OBJECTIVE Insular glioma has a unique origin and biological behavior; however, the associations between its anatomical features and prognosis have not been well established. The object of this study was to propose a classification system of insular low-grade gliomas based on preoperative MRI findings and to assess the system's association with survival outcome. METHODS A total of 211 consecutively collected patients diagnosed with low-grade insular gliomas was analyzed. All patients were classified according to whether tumor involved the putamen on MR images. The prognostic role of this novel putaminal classification, as well as that of Yaşargil's classification, was examined using multivariate analyses. RESULTS Ninety-nine cases (46.9%) of insular gliomas involved the putamen. Those tumors involving the putamen, as compared with nonputaminal tumors, were larger (p < 0.001), less likely to be associated with a history of seizures (p = 0.04), more likely to have wild-type IDH1 (p = 0.003), and less likely to be totally removed (p = 0.02). Significant favorable predictors of overall survival on univariate analysis included a high preoperative Karnofsky Performance Scale score (p = 0.02), a history of seizures (p = 0.04), gross-total resection (p = 0.006), nonputaminal tumors (p < 0.001), and an IDH1 mutation (p < 0.001). On multivariate analysis, extent of resection (p = 0.035), putamen classification (p = 0.014), and IDH1 mutation (p = 0.026) were independent predictors of overall survival. No prognostic role was found for Yaşargil's classification. CONCLUSIONS The current study's findings suggest that the putamen classification is an independent predictor of survival outcome in patients with insular low-grade gliomas. This newly proposed classification allows preoperative survival prediction for patients with insular gliomas.

  2. 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.

  3. A role for the anterior insular cortex in the global neuronal workspace model of consciousness.

    PubMed

    Michel, Matthias

    2017-03-01

    According to the global neuronal workspace model of consciousness, consciousness results from the global broadcast of information throughout the brain. The global neuronal workspace is mainly constituted by a fronto-parietal network. The anterior insular cortex is part of this global neuronal workspace, but the function of this region has not yet been defined within the global neuronal workspace model of consciousness. In this review, I hypothesize that the anterior insular cortex implements a cross-modal priority map, the function of which is to determine priorities for the processing of information and subsequent entrance in the global neuronal workspace.

  4. Impaired executive functioning after left anterior insular stroke: a case report.

    PubMed

    Markostamou, Ioanna; Rudolf, Jobst; Tsiptsios, Iakovos; Kosmidis, Mary H

    2015-01-01

    Given the insular's anatomic complexity and functional interconnectivity, acute lesions may result in varied clinical presentations, including autonomic, somatosensory, perceptual, motor, affective, and cognitive deficits. Although functional neuroimaging studies have demonstrated its role in executive functions, no clinical manifestations have been reported to date. We present the case of a woman with an acute left anterior insular infarction leading to executive (i.e., word and design fluency, mental flexibility, sustained attention, inhibitory control), but not language, visuoperceptual, or memory impairment. This case confirms the left anterior insula's involvement in executive functioning and suggests that an infarction may result in executive impairment.

  5. Glutamate: a truly functional amino acid.

    PubMed

    Brosnan, John T; Brosnan, Margaret E

    2013-09-01

    Glutamate is one of the most abundant of the amino acids. In addition to its role in protein structure, it plays critical roles in nutrition, metabolism and signaling. Post-translational carboxylation of glutamyl residues increases their affinity for calcium and plays a major role in hemostasis. Glutamate is of fundamental importance to amino acid metabolism, yet the great bulk of dietary glutamate is catabolyzed within the intestine. It is necessary for the synthesis of key molecules, such as glutathione and the polyglutamated folate cofactors. It plays a major role in signaling. Within the central nervous system, glutamate is the major excitatory neurotransmitter and its product, GABA, the major inhibitory neurotransmitter. Glutamate interaction with specific taste cells in the tongue is a major component of umami taste. The finding of glutamate receptors throughout the gastrointestinal tract has opened up a new vista in glutamate function. Glutamate is truly a functional amino acid.

  6. 21 CFR 582.1516 - Monopotassium glutamate.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... Additives § 582.1516 Monopotassium glutamate. (a) Product. Monopotassium glutamate. (b) Conditions of use. This substance is generally recognized as safe when used in accordance with good manufacturing or...

  7. 21 CFR 582.1500 - Monoammonium glutamate.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... Additives § 582.1500 Monoammonium glutamate. (a) Product. Monoammonium glutamate. (b) Conditions of use. This substance is generally recognized as safe when used in accordance with good manufacturing or...

  8. Imaging extrasynaptic glutamate dynamics in the brain

    PubMed Central

    Sakamoto, Hirokazu; Iinuma, Sho; Yamasaki, Miwako; Watanabe, Masahiko; Hirose, Kenzo; Iino, Masamitsu

    2010-01-01

    Glutamate is the major neurotransmitter in the brain, mediating point-to-point transmission across the synaptic cleft in excitatory synapses. Using a glutamate imaging method with fluorescent indicators, we show that synaptic activity generates extrasynaptic glutamate dynamics in the vicinity of active synapses. These glutamate dynamics had magnitudes and durations sufficient to activate extrasynaptic glutamate receptors in brain slices. We also observed crosstalk between synapses—i.e., summation of glutamate released from neighboring synapses. Furthermore, we successfully observed that sensory input from the extremities induced extrasynaptic glutamate dynamics within the appropriate sensory area of the cerebral cortex in vivo. Thus, the present study clarifies the spatiotemporal features of extrasynaptic glutamate dynamics, and opens up an avenue to directly visualizing synaptic activity in live animals. PMID:20308566

  9. Increasing Our Insular World View: Interoception and Psychopathology for Psychotherapists.

    PubMed

    Duquette, Patrice

    2017-01-01

    Interoception has been determined to be an elemental aspect of the neural foundations of physiological homeostasis, subjective experience, and motivated behavior. This paper reviews current neuroscience research regarding interoception and forms of interoceptive dysfunction that may result in psychopathology, focusing on depression, and anxiety, in a manner conducive to psychotherapists engaging with it to consider clinical applications. Pertinent aspects of interoceptive system processes in relation to psychopathology are addressed: Functional interoceptive ability and the forms of its expression, the difficulty of accurate measurement of such within an individual or group, interoceptive inference processes and perturbations. Predictive coding, considered in this context as interoceptive inference, a process that integrates bottom-up and top down lines of neural information emerging from the multitude of bidirectional, anatomically hierarchical connections the insular cortex makes with other cortical, and subcortical structures, will be addressed regarding its place in psychopathological formulations. Clinical vignettes will elucidate how interoceptive disturbances might present in the therapeutic relationship, supporting the evaluation and application of scientific theory, and research findings by psychotherapists. The clinical implications of this neuroscientific research have received little attention in the psychotherapeutic setting. Increasing the knowledge base of psychotherapists and furthering awareness of the functional interactions of body and brain toward the creation of healthy and psychopathological experience benefits the patient. There is immediate need for the translational expression of scientific findings into the psychological evaluation of patients, therapeutic process, and treatment. While it may seem distant and unrelated to the affective processes that occur within the psychotherapeutic exchange, neuroscience adds a unique perspective from

  10. Increasing Our Insular World View: Interoception and Psychopathology for Psychotherapists

    PubMed Central

    Duquette, Patrice

    2017-01-01

    Interoception has been determined to be an elemental aspect of the neural foundations of physiological homeostasis, subjective experience, and motivated behavior. This paper reviews current neuroscience research regarding interoception and forms of interoceptive dysfunction that may result in psychopathology, focusing on depression, and anxiety, in a manner conducive to psychotherapists engaging with it to consider clinical applications. Pertinent aspects of interoceptive system processes in relation to psychopathology are addressed: Functional interoceptive ability and the forms of its expression, the difficulty of accurate measurement of such within an individual or group, interoceptive inference processes and perturbations. Predictive coding, considered in this context as interoceptive inference, a process that integrates bottom-up and top down lines of neural information emerging from the multitude of bidirectional, anatomically hierarchical connections the insular cortex makes with other cortical, and subcortical structures, will be addressed regarding its place in psychopathological formulations. Clinical vignettes will elucidate how interoceptive disturbances might present in the therapeutic relationship, supporting the evaluation and application of scientific theory, and research findings by psychotherapists. The clinical implications of this neuroscientific research have received little attention in the psychotherapeutic setting. Increasing the knowledge base of psychotherapists and furthering awareness of the functional interactions of body and brain toward the creation of healthy and psychopathological experience benefits the patient. There is immediate need for the translational expression of scientific findings into the psychological evaluation of patients, therapeutic process, and treatment. While it may seem distant and unrelated to the affective processes that occur within the psychotherapeutic exchange, neuroscience adds a unique perspective from

  11. Amyotrophic lateral sclerosis in Sardinia, insular Italy, 1995-2009.

    PubMed

    Pugliatti, Maura; Parish, Leslie D; Cossu, Paola; Leoni, Stefania; Ticca, Anna; Saddi, M Valeria; Ortu, Enzo; Traccis, Sebastiano; Borghero, Giuseppe; Puddu, Roberta; Chiò, Adriano; Pirina, Pietro

    2013-02-01

    Recent genetic studies suggest a Sardinian type of amyotrophic lateral sclerosis (ALS). Thus, ALS incidence, prevalence and survival were investigated in a large population of Sardinians aimed to disclose population-specific patterns and their temporal changes. This is a population-based incidence and prevalence study in northern and central Sardinia, insular Italy (over 700,000 population). Incidence rates were computed for the time interval 1995-2009 and by quinquennia. Prevalence was computed for prevalence days 31 December 2004 and 2009. Onset-based survival for 1995-2009 is also reported. All ALS patients (El Escorial Criteria) in the study area were retrospectively included. The ALS crude incidence from 2005-2009 was 2.5 (95 % CIs: 0.1, 4.9), 3.4 in men and 1.6 in women. Onset occurred most often between the age of 65-74 years in men and 55-64 years in women. The ALS incidence tended to increase over the period 1995-2009. The mean age at onset was 61.7 years with no difference based on gender, varying significantly from 59.9 years in 1995-1999 to 63.9 years in 2005-2009. On December 31, 2009, the ALS crude prevalence was 10.8 per 100,000 (95 % CIs: 8.6, 13.1), 13.8 in men and 8.0 in women, whereas it was 6.3 per 100,000 (95 % CIs: 4.1, 8.6) on December 31, 2004 (M:F ratio of 0.95). Mean survival from onset was 37.0 months, with no difference based on gender, and a tendency to decrease during the period 1995-2009, in relation to type and age of onset. The population-based incidence and prevalence data of ALS in Sardinians indicate an increase of the disease occurrence over the past 40 years, providing support for a population-specific variant of ALS in Sardinia.

  12. Ciprofloxacin triggered glutamate production by Corynebacterium glutamicum.

    PubMed

    Lubitz, Dorit; Wendisch, Volker F

    2016-10-07

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

  13. 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. This...

  14. 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) [Reserved] (c) Limitations, restrictions, or...

  15. 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 as...

  16. 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. This...

  17. 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. This...

  18. Deletion of genes involved in glutamate metabolism to improve poly-gamma-glutamic acid production in B. amyloliquefaciens LL3.

    PubMed

    Zhang, Wei; He, Yulian; Gao, Weixia; Feng, Jun; Cao, Mingfeng; Yang, Chao; Song, Cunjiang; Wang, Shufang

    2015-02-01

    Here, we attempted to elevate poly-gamma-glutamic acid (γ-PGA) production by modifying genes involved in glutamate metabolism in Bacillus amyloliquefaciens LL3. Products of rocR, rocG and gudB facilitate the conversion from glutamate to 2-oxoglutarate in Bacillus subtillis. The gene odhA is responsible for the synthesis of a component of the 2-oxoglutarate dehydrogenase complex that catalyzes the oxidative decarboxylation of 2-oxoglutarate to succinyl coenzyme A. In-frame deletions of these four genes were performed. In shake flask experiments the gudB/rocG double mutant presented enhanced production of γ-PGA, a 38 % increase compared with wild type. When fermented in a 5-L fermenter with pH control, the γ-PGA yield of the rocR mutant was increased to 5.83 g/L from 4.55 g/L for shake flask experiments. The gudB/rocG double mutant produced 5.68 g/L γ-PGA compared with that of 4.03 g/L for the wild type, a 40 % increase. Those results indicated the possibility of improving γ-PGA production by modifying glutamate metabolism, and identified potential genetic targets to improve γ-PGA production.

  19. 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

  20. Synaptic modulation by astrocytes via Ca2+-dependent glutamate release.

    PubMed

    Santello, M; Volterra, A

    2009-01-12

    In the past 15 years the classical view that astrocytes play a relatively passive role in brain function has been overturned and it has become increasingly clear that signaling between neurons and astrocytes may play a crucial role in the information processing that the brain carries out. This new view stems from two seminal observations made in the early 1990s: 1. astrocytes respond to neurotransmitters released during synaptic activity with elevation of their intracellular Ca2+ concentration ([Ca2+]i); 2. astrocytes release chemical transmitters, including glutamate, in response to [Ca2+]i elevations. The simultaneous recognition that astrocytes sense neuronal activity and release neuroactive agents has been instrumental for understanding previously unknown roles of these cells in the control of synapse formation, function and plasticity. These findings open a conceptual revolution, leading to rethink how brain communication works, as they imply that information travels (and is processed) not just in the neuronal circuitry but in an expanded neuron-glia network. In this review we critically discuss the available information concerning: 1. the characteristics of the astrocytic Ca2+ responses to synaptic activity; 2. the basis of Ca2+-dependent glutamate exocytosis from astrocytes; 3. the modes of action of astrocytic glutamate on synaptic function.

  1. Rapid changes in expression of glutamate transporters after spinal cord injury.

    PubMed

    Vera-Portocarrero, Louis P; Mills, Charles D; Ye, Zaiming; Fullwood, Steven D; McAdoo, David J; Hulsebosch, Claire E; Westlund, Karin N

    2002-02-08

    Glutamate is a major excitatory neurotransmitter in the mammalian CNS. After its release, specific transporter proteins rapidly remove extracellular glutamate from the synaptic cleft. The clearance of excess extracellular glutamate prevents accumulation under normal conditions; however, CNS injury elevates extracellular glutamate concentrations to neurotoxic levels. The purpose of this study was to examine changes in expression and in spatial localization of glial glutamate transporters GLAST (EAAT1) and GLT-1 (EAAT2) and the neuronal glutamate transporter EAAC1 (EAAT3) after spinal cord contusion injury (SCI). The levels of all three transporters significantly increased at the epicenter of injury (T10) and in segments rostral and caudal to the epicenter as determined by Western blot analysis. Quantitative immunohistochemistry demonstrated an increase in GLAST staining in laminae I-V and lamina X both rostral and caudal to the epicenter of injury. Staining for GLT-1 increased significantly in lamina I rostral to the injury site and in the entire gray matter caudal to the injury site. A significant increase in EAAC1 staining was observed in laminae I-IV rostral to the epicenter of injury and throughout the gray matter caudal to the injury site. The results suggest that upregulation of these high affinity transporters occurs rapidly and is important in regulating glutamate homeostasis after SCI.

  2. ELEVATING MECHANISM

    DOEpatents

    Frederick, H.S.; Kinsella, M.A.

    1959-02-24

    An elevator is described, which is arranged for movement both in a horizontal and in a vertical direction so that the elevating mechanism may be employed for servicing equipment at separated points in a plant. In accordance with the present invention, the main elevator chassis is suspended from a monorail. The chassis, in turn supports a vertically moveable carriage, a sub- carriage vertically moveable on the carriage, and a turntable carried by the sub- carriage and moveable through an arc of 90 with the equipment attached thereto. In addition, the chassis supports all the means required to elevate or rotate the equipment.

  3. 47 CFR 54.101 - Supported services for rural, insular and high cost areas.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... extent the local government in an eligible carrier's service area has implemented 911 or enhanced 911... cost areas. 54.101 Section 54.101 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED... services for rural, insular and high cost areas. (a) Services designated for support. The...

  4. 47 CFR 54.101 - Supported services for rural, insular and high cost areas.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ..., to the extent the local government in an eligible carrier's service area has implemented 911 or... cost areas. 54.101 Section 54.101 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED... services for rural, insular and high cost areas. (a) Services designated for support. Voice...

  5. 47 CFR 54.101 - Supported services for rural, insular and high cost areas.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ..., to the extent the local government in an eligible carrier's service area has implemented 911 or... cost areas. 54.101 Section 54.101 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED... services for rural, insular and high cost areas. (a) Services designated for support. Voice...

  6. Differential Effects of Insular and Ventromedial Prefrontal Cortex Lesions on Risky Decision-Making

    ERIC Educational Resources Information Center

    Clark, L.; Bechara, A.; Damasio, H.; Aitken, M. R. F.; Sahakian, B. J.; Robbins, T. W.

    2008-01-01

    The ventromedial prefrontal cortex (vmPFC) and insular cortex are implicated in distributed neural circuitry that supports emotional decision-making. Previous studies of patients with vmPFC lesions have focused primarily on decision-making under uncertainty, when outcome probabilities are ambiguous (e.g. the Iowa Gambling Task). It remains unclear…

  7. The biogeography of threatened insular iguanas and opportunities for invasive vertebrate management

    USGS Publications Warehouse

    Tershy, Bernie R.; Newton, Kelly M.; Spatz, Dena R.; Swinnerton, Kirsty; Iverson, John B.; Fisher, Robert N.; Harlow, Peter S.; Holmes, Nick D.; Croll, Donald A.; Iverson, J.B.; Grant, T. D.; Knapp, C. R.; Pasachnik, S. A.

    2016-01-01

    Iguanas are a particularly threatened group of reptiles, with 61% of species at risk of extinction. Primary threats to iguanas include habitat loss, direct and indirect impacts by invasive vertebrates, overexploitation, and human disturbance. As conspicuous, charismatic vertebrates, iguanas also represent excellent flagships for biodiversity conservation. To assist planning for invasive vertebrate management and thus benefit threatened iguana recovery, we identified all islands with known extant or extirpated populations of Critically Endangered and Endangered insular iguana taxa as recognized by the International Union for Conservation of Nature (IUCN) Red List of Threatened Species. For each island, we determined total area, sovereignty, the presence of invasive alien vertebrates, and human population. For the 23 taxa of threatened insular iguanas we identified 230 populations, of which iguanas were extant on 185 islands and extirpated from 45 islands. Twenty-one iguana taxa (91% of all threatened insular iguana taxa) occurred on at least one island with invasive vertebrates present; 16 taxa had 100% of their population(s) on islands with invasive vertebrates present. Rodents, cats, ungulates, and dogs were the most common invasive vertebrates. We discuss biosecurity, eradication, and control of invasive vertebrates to benefit iguana recovery: (1) on islands already free of invasive vertebrates; (2) on islands with high iguana endemicity; and (3) for species and subspecies with small total populations occurring across multiple small islands. Our analyses provide an important first step toward understanding how invasive vertebrate management can be planned effectively to benefit threatened insular iguanas.

  8. Evidence of correlated evolution of hypsodonty and exceptional longevity in endemic insular mammals.

    PubMed

    Jordana, Xavier; Marín-Moratalla, Nekane; DeMiguel, Daniel; Kaiser, Thomas M; Köhler, Meike

    2012-08-22

    Here, we test whether the increase in tooth height in insular endemics results from the expansion of the dietary niche under resource limitation, as widely considered, or whether it represents an investment in dental durability in response to the selection for extended longevity under low levels of extrinsic mortality. We tested these hypotheses in the extremely hypsodont fossil bovid Myotragus balearicus from the Balearic Islands, an ideal model to study the evolutionary trends on islands. Dental abrasion was significantly lower in the insular bovid than in highly hypsodont continental artiodactyls, suggesting that feeding habits are not the sole driving force behind increased crown height. However, the estimated longevity for M. balearicus based on dental durability was two times that predicted from body mass. Survivorship curves confirm that an extraordinarily large number of individuals approached the longevity of the species. Our results, hence, provide evidence that hypsodonty in insular endemics is the outcome of selection for increased durability of the permanent dentition in association with an extended lifespan. In the context of insularity, our results lend additional support to the disposable soma theory of ageing confirming the dependency of somatic maintenance and repair on lifespan, and its control by resource availability and extrinsic mortality.

  9. Loss of long-term depression in the insular cortex after tail amputation in adult mice

    PubMed Central

    2014-01-01

    The insular cortex (IC) is an important forebrain structure involved in pain perception and taste memory formation. Using a 64-channel multi-electrode array system, we recently identified and characterized two major forms of synaptic plasticity in the adult mouse IC: long-term potentiation (LTP) and long-term depression (LTD). In this study, we investigate injury-related metaplastic changes in insular synaptic plasticity after distal tail amputation. We found that tail amputation in adult mice produced a selective loss of low frequency stimulation-induced LTD in the IC, without affecting (RS)-3,5-dihydroxyphenylglycine (DHPG)-evoked LTD. The impaired insular LTD could be pharmacologically rescued by priming the IC slices with a lower dose of DHPG application, a form of metaplasticity which involves activation of protein kinase C but not protein kinase A or calcium/calmodulin-dependent protein kinase II. These findings provide important insights into the synaptic mechanisms of cortical changes after peripheral amputation and suggest that restoration of insular LTD may represent a novel therapeutic strategy against the synaptic dysfunctions underlying the pathophysiology of phantom pain. PMID:24398034

  10. Surgery of insular and paralimbic diffuse low-grade gliomas: technical considerations.

    PubMed

    Michaud, Karine; Duffau, Hugues

    2016-11-01

    Once considered a "no man's land" especially when invaded by a diffuse low grade glioma (DLGG), the insula remains to this day a surgical challenge. Surgery for insular DLGG involves consideration of its hidden location under the potentially eloquent operculae, the proximity to vascular tree and high density of functions not only in the insular cortex but also in the white fiber pathways passing under the insular lobe. The natural history of DLGG and the potential benefits and consequences of the surgical approach also need a close look. In the last decade, a better knowledge of the functional anatomy and connectivity of this region, as well as an improvement in surgical techniques as direct stimulation mapping, combined with an increasing literature showing a favorable impact of maximal resection for DLGG, were deciding factors in the paradigmatic shift from expectative treatment to early surgical management. Here, our goal is to discuss the structural and functional aspects of the insula, the specificities of insular and paralimbic DLGG by emphasizing the technical considerations of surgery in this region, as well as its oncological and functional outcomes. In summary, this new strategy based upon early maximal safe surgical resection showed both oncological benefit and preservation of quality of life-or even an improvement thanks to epilepsy relief.

  11. Node Detection Using High-Dimensional Fuzzy Parcellation Applied to the Insular Cortex.

    PubMed

    Vercelli, Ugo; Diano, Matteo; Costa, Tommaso; Nani, Andrea; Duca, Sergio; Geminiani, Giuliano; Vercelli, Alessandro; Cauda, Franco

    2016-01-01

    Several functional connectivity approaches require the definition of a set of regions of interest (ROIs) that act as network nodes. Different methods have been developed to define these nodes and to derive their functional and effective connections, most of which are rather complex. Here we aim to propose a relatively simple "one-step" border detection and ROI estimation procedure employing the fuzzy c-mean clustering algorithm. To test this procedure and to explore insular connectivity beyond the two/three-region model currently proposed in the literature, we parcellated the insular cortex of 20 healthy right-handed volunteers scanned in a resting state. By employing a high-dimensional functional connectivity-based clustering process, we confirmed the two patterns of connectivity previously described. This method revealed a complex pattern of functional connectivity where the two previously detected insular clusters are subdivided into several other networks, some of which are not commonly associated with the insular cortex, such as the default mode network and parts of the dorsal attentional network. Furthermore, the detection of nodes was reliable, as demonstrated by the confirmative analysis performed on a replication group of subjects.

  12. Node Detection Using High-Dimensional Fuzzy Parcellation Applied to the Insular Cortex

    PubMed Central

    Vercelli, Ugo; Diano, Matteo; Costa, Tommaso; Nani, Andrea; Duca, Sergio; Geminiani, Giuliano; Vercelli, Alessandro; Cauda, Franco

    2016-01-01

    Several functional connectivity approaches require the definition of a set of regions of interest (ROIs) that act as network nodes. Different methods have been developed to define these nodes and to derive their functional and effective connections, most of which are rather complex. Here we aim to propose a relatively simple “one-step” border detection and ROI estimation procedure employing the fuzzy c-mean clustering algorithm. To test this procedure and to explore insular connectivity beyond the two/three-region model currently proposed in the literature, we parcellated the insular cortex of 20 healthy right-handed volunteers scanned in a resting state. By employing a high-dimensional functional connectivity-based clustering process, we confirmed the two patterns of connectivity previously described. This method revealed a complex pattern of functional connectivity where the two previously detected insular clusters are subdivided into several other networks, some of which are not commonly associated with the insular cortex, such as the default mode network and parts of the dorsal attentional network. Furthermore, the detection of nodes was reliable, as demonstrated by the confirmative analysis performed on a replication group of subjects. PMID:26881093

  13. Differential Effects of Insular and Ventromedial Prefrontal Cortex Lesions on Risky Decision-Making

    ERIC Educational Resources Information Center

    Clark, L.; Bechara, A.; Damasio, H.; Aitken, M. R. F.; Sahakian, B. J.; Robbins, T. W.

    2008-01-01

    The ventromedial prefrontal cortex (vmPFC) and insular cortex are implicated in distributed neural circuitry that supports emotional decision-making. Previous studies of patients with vmPFC lesions have focused primarily on decision-making under uncertainty, when outcome probabilities are ambiguous (e.g. the Iowa Gambling Task). It remains unclear…

  14. Evidence of correlated evolution of hypsodonty and exceptional longevity in endemic insular mammals

    PubMed Central

    Jordana, Xavier; Marín-Moratalla, Nekane; DeMiguel, Daniel; Kaiser, Thomas M.; Köhler, Meike

    2012-01-01

    Here, we test whether the increase in tooth height in insular endemics results from the expansion of the dietary niche under resource limitation, as widely considered, or whether it represents an investment in dental durability in response to the selection for extended longevity under low levels of extrinsic mortality. We tested these hypotheses in the extremely hypsodont fossil bovid Myotragus balearicus from the Balearic Islands, an ideal model to study the evolutionary trends on islands. Dental abrasion was significantly lower in the insular bovid than in highly hypsodont continental artiodactyls, suggesting that feeding habits are not the sole driving force behind increased crown height. However, the estimated longevity for M. balearicus based on dental durability was two times that predicted from body mass. Survivorship curves confirm that an extraordinarily large number of individuals approached the longevity of the species. Our results, hence, provide evidence that hypsodonty in insular endemics is the outcome of selection for increased durability of the permanent dentition in association with an extended lifespan. In the context of insularity, our results lend additional support to the disposable soma theory of ageing confirming the dependency of somatic maintenance and repair on lifespan, and its control by resource availability and extrinsic mortality. PMID:22535784

  15. Effects of Dietary Supplementation with Glutamate and Aspartate on Diquat-Induced Oxidative Stress in Piglets

    PubMed Central

    Ren, Wenkai; Duan, Jielin; Yang, Guan; Zhao, Yurong; Fang, Rejun; Chen, Lixiang; Li, Tiejun; Yin, Yulong

    2015-01-01

    This study aimed to investigate the protective effects of dietary glutamate and aspartate supplementations on diquat-induced oxidative stress in piglets. Diquat injection significantly reduced growth performance, including body weight, average daily weight gain, and feed intake (P<0.05). Meanwhile, diquat administration induced oxidative stress evidenced by the decreased serum nitric oxide (NO) and elevated malondialdeyhde (MDA) concentration (P<0.05). Furthermore, diquat-induced oxidative stress disrupted intestinal absorption system and decreased serum threonine, serine, and glycine levels. Dietary supplementation with glutamate improved final body weight, antioxidant system, and expressions of amino acids transporters and enhanced serum glutamate concentration compared with diquat group (P<0.05). While aspartate failed to alleviate diquat-induced oxidative stress, growth depression, and dysfunction of nutrients absorption except for liver relative weight. In conclusion, dietary supplementation with glutamate confers beneficial effects on diquat-induced oxidative stress in piglets, while aspartate exhibits little effects. PMID:25875335

  16. Glutamate Induces Calcium Waves in Cultured Astrocytes: Long-Range Glial Signaling

    NASA Astrophysics Data System (ADS)

    Cornell-Bell, Ann H.; Finkbeiner, Steven M.; Cooper, Mark S.; Smith, Stephen J.

    1990-01-01

    The finding that astrocytes possess glutamate-sensitive ion channels hinted at a previously unrecognized signaling role for these cells. Now it is reported that cultured hippocampal astrocytes can respond to glutamate with a prompt and oscillatory elevation of cytoplasmic free calcium, visible through use of the fluorescent calcium indicator fluo-3. Two types of glutamate receptor-one preferring quisqualate and releasing calcium from intracellular stores and the other preferring kainate and promoting surface-membrane calcium influx-appear to be involved. Moreover, glutamate-induced increases in cytoplasmic free calcium frequently propagate as waves within the cytoplasm of individual astrocytes and between adjacent astrocytes in confluent cultures. These propagating waves of calcium suggest that networks of astrocytes may constitute a long-range signaling system within the brain.

  17. Effects of dietary supplementation with glutamate and aspartate on diquat-induced oxidative stress in piglets.

    PubMed

    Yin, Jie; Liu, Mingfeng; Ren, Wenkai; Duan, Jielin; Yang, Guan; Zhao, Yurong; Fang, Rejun; Chen, Lixiang; Li, Tiejun; Yin, Yulong

    2015-01-01

    This study aimed to investigate the protective effects of dietary glutamate and aspartate supplementations on diquat-induced oxidative stress in piglets. Diquat injection significantly reduced growth performance, including body weight, average daily weight gain, and feed intake (P<0.05). Meanwhile, diquat administration induced oxidative stress evidenced by the decreased serum nitric oxide (NO) and elevated malondialdeyhde (MDA) concentration (P<0.05). Furthermore, diquat-induced oxidative stress disrupted intestinal absorption system and decreased serum threonine, serine, and glycine levels. Dietary supplementation with glutamate improved final body weight, antioxidant system, and expressions of amino acids transporters and enhanced serum glutamate concentration compared with diquat group (P<0.05). While aspartate failed to alleviate diquat-induced oxidative stress, growth depression, and dysfunction of nutrients absorption except for liver relative weight. In conclusion, dietary supplementation with glutamate confers beneficial effects on diquat-induced oxidative stress in piglets, while aspartate exhibits little effects.

  18. Insular shifts in body size of rice frogs in the Zhoushan Archipelago, China.

    PubMed

    Wu, Zhengjun; Li, Yiming; Murray, Brad R

    2006-09-01

    1. Differences in body size between mainland and island populations have been reported for reptiles, birds and mammals. Despite widespread recognition of insular shifts in body size in these taxa, there have been no reports of such body size shifts in amphibians. 2. We provide the first evidence of an insular shift in body size for an amphibian species, the rice frog Rana limnocharis. We found significant increases in body size of rice frogs on most sampled islands in the Zhoushan archipelago when compared with neighbouring mainland China. 3. Large body size in rice frogs on islands was significantly related to increased population density, in both breeding and non-breeding seasons. Increases in rice frog density were significantly related to higher resource availability on islands. Increased resource availability on islands has led to higher carrying capacities, which has subsequently facilitated higher densities and individual growth rates, resulting in larger body size in rice frogs. We also suggest that large body size has evolved on islands, as larger individuals are competitively superior under conditions of harsh intraspecific competition at high densities. 4. Increases in body size in rice frogs were not related to several factors that have been implicated previously in insular shifts in body size in other taxa. We found no significant relationships between body size of rice frogs and prey size, number of larger or smaller frog species, island area or distance of islands from the mainland. 5. Our findings contribute to the formation of a broad, repeatable ecological generality for insular shifts in body size across a range of terrestrial vertebrate taxa, and provide support for recent theoretical work concerning the importance of resource availability for insular shifts in body size.

  19. Preconditioning induces tolerance by suppressing glutamate release in neuron culture ischemia models.

    PubMed

    Tauskela, Joseph S; Aylsworth, Amy; Hewitt, Melissa; Brunette, Eric; Mealing, Geoffrey A R

    2012-07-01

    This study determined how preconditioned neurons responded to oxygen-glucose deprivation (OGD) to result in neuroprotection instead of neurotoxicity. Neurons preconditioned using chronically elevated synaptic activity displayed suppressed elevations in extracellular glutamate ([glutamateex ]) and intracellular Ca(2+) (Ca(2+) in ) during OGD. The glutamate uptake inhibitor TBOA induced neurotoxicity, but at a longer OGD duration for preconditioned cultures, suggestive of delayed up-regulation of transporter activity relative to non-preconditioned cultures. This delay was attributed to a critically attenuated release of glutamate, based on tolerance observed against insults mimicking key neurotoxic signaling during OGD (OGD-mimetics). Specifically, in the presence of TBOA, preconditioned neurons displayed potent protection to the OGD-mimetics: ouabain (a Na(+) /K(+) ATPase inhibitor), high 55 mM KCl extracellular buffer (plasma membrane depolarization), veratridine (a Na(+) ionophore), and paraquat (intracellular superoxide producer), which correlated with suppressed [glutamateex ] elevations in the former two insults. Tolerance by preconditioning was reversed by manipulations that increased [glutamateex ], such as by exposure to TBOA or GABAA receptor agonists during OGD, or by exposure to exogenous NMDA or glutamate. Pre-synaptic suppression of neuronal glutamate release by preconditioning, possibly via suppressed exocytic release, represents a key convergence point in neuroprotection during exposure to OGD and OGD-mimetics. © 2012 National Research Council Canada. Journal of Neurochemistry © 2012 International Society for Neurochemistry.

  20. Effect of ambient extracellular glutamate on Drosophila glutamate receptor trafficking and function.

    PubMed

    Chen, Kaiyun; Augustin, Hrvoje; Featherstone, David E

    2009-01-01

    Measurements suggest that the hemolymph glutamate concentrations in Drosophila are relatively high. This raises the possibility that extracellular glutamate could be an important regulator of glutamatergic transmission in vivo. Using voltage clamp electrophysiology, we found that synaptic currents in D. melanogaster larval neuromuscular junctions are reduced by extracellular glutamate (EC50: approximately 0.4 mM), such that only 10-30% of receptors were functionally available in 1 mM extracellular glutamate. The kinetics of synaptic currents were also slowed in a dose-dependent fashion (EC50: approximately 1 mM), consistent with the idea that extracellular glutamate preferentially removes the fastest-desensitizing receptors from the functional pool. Prolonged exposure (several hours) to extracellular glutamate also triggers loss of glutamate receptor immunoreactivity from neuromuscular junctions. To determine whether this receptor loss requires that glutamate bind directly to the lost receptors, we examined glutamate-dependent loss of receptor immunoreactivity in larvae with glutamate receptor ligand binding mutations. Our results suggest that glutamate-dependent receptor loss requires binding of glutamate directly to the lost receptors. To determine whether lost receptor protein is degraded or merely redistributed, we used immunoblots. Results suggest that glutamate receptor protein is redistributed, but not degraded, after prolonged exposure to high extracellular glutamate.

  1. Endocannabinoid regulation of nausea is mediated by 2-arachidonoylglycerol (2-AG) in the rat visceral insular cortex.

    PubMed

    Sticht, Martin A; Limebeer, Cheryl L; Rafla, Benjamin R; Abdullah, Rehab A; Poklis, Justin L; Ho, Winnie; Niphakis, Micah J; Cravatt, Benjamin F; Sharkey, Keith A; Lichtman, Aron H; Parker, Linda A

    2016-03-01

    Cannabinoid (CB) agonists suppress nausea in humans and animal models; yet, their underlying neural substrates remain largely unknown. Evidence suggests that the visceral insular cortex (VIC) plays a critical role in nausea. Given the expression of CB1 receptors and the presence of endocannabinoids in this brain region, we hypothesized that the VIC endocannabinoid system regulates nausea. In the present study, we assessed whether inhibiting the primary endocannabinoid hydrolytic enzymes in the VIC reduces acute lithium chloride (LiCl)-induced conditioned gaping, a rat model of nausea. We also quantified endocannabinoid levels during an episode of nausea, and assessed VIC neuronal activation using the marker, c-Fos. Local inhibition of monoacylglycerol lipase (MAGL), the main hydrolytic enzyme of 2-arachidonylglycerol (2-AG), reduced acute nausea through a CB1 receptor mechanism, whereas inhibition of fatty acid amide hydrolase (FAAH), the primary catabolic enzyme of anandamide (AEA), was without effect. Levels of 2-AG were also selectively elevated in the VIC during an episode of nausea. Inhibition of MAGL robustly increased 2-AG in the VIC, while FAAH inhibition had no effect on AEA. Finally, we demonstrated that inhibition of MAGL reduced VIC Fos immunoreactivity in response to LiCl treatment. Taken together, these findings provide compelling evidence that acute nausea selectively increases 2-AG in the VIC, and suggests that 2-AG signaling within the VIC regulates nausea by reducing neuronal activity in this forebrain region. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Endocannabinoid regulation of nausea is mediated by 2-arachidonoylglycerol (2-AG) in the rat visceral insular cortex

    PubMed Central

    Sticht, Martin A.; Limebeer, Cheryl L.; Rafla, Benjamin R.; Abdullah, Rehab A.; Poklis, Justin L.; Ho, Winnie; Niphakis, Micah J.; Cravatt, Benjamin F.; Sharkey, Keith A.; Lichtman, Aron H.; Parker, Linda A.

    2015-01-01

    Cannabinoid (CB) agonists suppress nausea in humans and animal models; yet, their underlying neural substrates remain largely unknown. Evidence suggests that the visceral insular cortex (VIC) plays a critical role in nausea. Given the expression of CB1 receptors and the presence of endocannabinoids in this brain region, we hypothesized that the VIC endocannabinoid system regulates nausea. In the present study, we assessed whether inhibiting the primary endocannabinoid hydrolytic enzymes in the VIC reduces acute lithium chloride (LiCl)-induced conditioned gaping, a rat model of nausea. We also quantified endocannabinoid levels during an episode of nausea, and assessed VIC neuronal activation using the marker, c-Fos. Local inhibition of monoacylglycerol lipase (MAGL), the main hydrolytic enzyme of 2-arachidonylglycerol (2-AG), reduced acute nausea through a CB1 receptor mechanism, whereas inhibition of fatty acid amide hydrolase (FAAH), the primary catabolic enzyme of anandamide (AEA), was without effect. Levels of 2-AG were also selectively elevated in the VIC during an episode of nausea. Inhibition of MAGL robustly increased 2-AG in the VIC, while FAAH inhibition had no effect on AEA. Finally, we demonstrated that inhibition of MAGL reduced VIC Fos immunoreactivity in response to LiCl treatment. Taken together, these findings provide compelling evidence that acute nausea selectively increases 2-AG in the VIC, and suggests that 2-AG signaling within the VIC regulates nausea by reducing neuronal activity in this forebrain region. PMID:26541329

  3. 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.

  4. Ligands for Ionotropic Glutamate Receptors

    PubMed Central

    Swanson, Geoffrey T.; Sakai, Ryuichi

    2010-01-01

    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 synaptic 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. PMID:19184587

  5. Inducible Glutamate Oxaloacetate Transaminase as a Therapeutic Target Against Ischemic Stroke

    PubMed Central

    Khanna, Savita; Briggs, Zachary

    2015-01-01

    Abstract Significance: Glutamate serves multi-faceted (patho)physiological functions in the central nervous system as the most abundant excitatory neurotransmitter and under pathological conditions as a potent neurotoxin. Regarding the latter, elevated extracellular glutamate is known to play a central role in ischemic stroke brain injury. Recent Advances: Glutamate oxaloacetate transaminase (GOT) has emerged as a new therapeutic target in protecting against ischemic stroke injury. Oxygen-sensitive induction of GOT expression and activity during ischemic stroke lowers glutamate levels at the stroke site while sustaining adenosine triphosphate levels in brain. The energy demands of the brain are among the highest of all organs underscoring the need to quickly mobilize alternative carbon skeletons for metabolism in the absence of glucose during ischemic stroke. Recent work builds on the important observation of Hans Krebs that GOT-mediated metabolism of glutamate generates tri-carboxylic acid (TCA) cycle intermediates in brain tissue. Taken together, outcomes suggest GOT may enable the transformative switch of otherwise excitotoxic glutamate into life-sustaining TCA cycle intermediates during ischemic stroke. Critical Issues: Neuroprotective strategies that focus solely on blocking mechanisms of glutamate-mediated excitotoxicity have historically failed in clinical trials. That GOT can enable glutamate to assume the role of a survival factor represents a paradigm shift necessary to develop the overall significance of glutamate in stroke biology. Future Directions: Ongoing efforts are focused to develop the therapeutic significance of GOT in stroke-affected brain. Small molecules that target induction of GOT expression and activity in the ischemic penumbra are the focus of ongoing studies. Antioxid. Redox Signal. 22, 175–186. PMID:25343301

  6. Off-line concomitant release of dopamine and glutamate involvement in taste memory consolidation.

    PubMed

    Guzmán-Ramos, Kioko; Osorio-Gómez, Daniel; Moreno-Castilla, Perla; Bermúdez-Rattoni, Federico

    2010-07-01

    It has been postulated that memory consolidation process requires post-learning molecular changes that will support long-term experiences. In the present study, we assessed with in vivo microdialysis and capillary electrophoresis whether such changes involve the release of neurotransmitters at post-acquisition stages. Using conditioned taste aversion paradigm we observed spontaneous off-line (i.e. in absence of stimulation) dopamine and glutamate reactivation within the insular cortex about 45 min after the stimuli association. These increments did not appear in control groups that were unable to acquire the task, and it seems to be dependent on amygdala activity since its reversible inactivation by tetrodotoxin impaired cortical off-line release of both neurotransmitters and memory consolidation. In addition, blockade of dopaminergic D1 and/or NMDA receptors before the off-line activity impaired long- but not short-term memory. These results suggest that off-line extracellular increments of glutamate and dopamine have a significant functional role in consolidation of taste memory.

  7. c-Fos positive nucleus reveals that contextual specificity of latent inhibition is dependent of insular cortex.

    PubMed

    Quintero, Esperanza; Vargas, Juan Pedro; Diaz, Estrella; Escarabajal, María Dolores; Carrasco, Manuel; López, Juan Carlos

    2014-09-01

    The present study analyzed the functional activity of granular and agranular insular cortices in contextual specificity of latent inhibition using a conditioned taste aversion paradigm. c-Fos immunolabeling was examined in insular cortex in preexposed and no preexposed groups under similar and different context conditions. Result showed that the exposition to a novel taste increased c-fos activity in insular cortex. However, a context shift caused an increase in immunolabeling in animals preexposed to saccharine. These results suggest insular cortex is part of a complex system to evaluate taste-response, and it may read the meaning of taste stimuli depending on the context. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. New perspectives on glutamate receptor antagonists as antidepressants.

    PubMed

    Chung, Chihye

    2012-03-01

    Classical antidepressants elevate the monoamine levels in the brain by preventing re-uptake of monoamines after release. Treatment of depression with monoamine re-uptake inhibitors is associated with low clinical efficacy and remission rate due to the delayed onset of therapeutic responses. Therefore, the development of alternative antidepressants is essential for successful treatment of this disease. Recently, glutamate receptor antagonists including ketamine and 2-methyl-6-(phenylethynyl)-pyridine (MPEP) have received wide attention as fast-acting therapeutic alternatives for treatment of depression.

  9. The Many Roles of Glutamate in Metabolism

    PubMed Central

    Walker, Mark C.

    2015-01-01

    The amino acid glutamate is a major metabolic hub in many organisms and as such is involved in diverse processes in addition to its role in protein synthesis. Nitrogen assimilation, nucleoside, amino acid, and cofactor biosynthesis, as well as secondary natural product formation all utilize glutamate in some manner. Glutamate also plays a role in the catabolism of certain amines. Understanding glutamate's role in these various processes can aid in genome mining for novel metabolic pathways or the engineering of pathways for bioremediation or chemical production of valuable compounds. PMID:26323613

  10. Dehydroepiandrosterone's antiepileptic action in FeCl3-induced epileptogenesis involves upregulation of glutamate transporters.

    PubMed

    Mishra, Monika; Singh, Rameshwar; Mukherjee, Somnath; Sharma, Deepak

    2013-09-01

    Dehydroepiandrosterone (DHEA), a neuroactive androgen steroid, has antiepileptic action in iron-induced experimental epilepsy (which models post-traumatic clinical epilepsy). In iron-induced epilepsy increased extracellular glutamate resulting from its reduced glial uptake due to the down-regulation (decreased expression) of transporters (glial and or neuronal) is active during epileptogenesis. The present study was aimed at determining whether the mechanism of antiepileptic action of DHEA involved upregulation (increased expression) of glutamate transporters. Iron-induced epileptogenesis was performed in rats by FeCl3 injection into the cerebral cortex. DHEA was administered intraperitoneally to the iron-induced epileptic rats for 7, 14 and 21 days. Levels of glutamate transporters mRNAs expression were measured using quantitative PCR in the hippocampus during the chronic phase of iron-induced epileptogenesis. There were significant reductions in the glutamate transporter mRNAs in epileptogenesis. DHEA treatment resulted in a significant elevation of glutamate transporters: GLT-1, GLAST and EACC-1 mRNA indicating that the DHEA treatment induced upregulation of these transporters. The results are of significance in respect of the mechanism of the antiepileptic action of neurosteroids and the glutamate transporters as therapeutic targets in glutamatergic epileptogenesis. Copyright © 2013 Elsevier B.V. All rights reserved.

  11. G-protein coupled receptor-evoked glutamate exocytosis from astrocytes: role of prostaglandins.

    PubMed

    Cali, Corrado; Lopatar, Jan; Petrelli, Francesco; Pucci, Luca; Bezzi, Paola

    2014-01-01

    Astrocytes are highly secretory cells, participating in rapid brain communication by releasing glutamate. Recent evidences have suggested that this process is largely mediated by Ca(2+)-dependent regulated exocytosis of VGLUT-positive vesicles. Here by taking advantage of VGLUT1-pHluorin and TIRF illumination, we characterized mechanisms of glutamate exocytosis evoked by endogenous transmitters (glutamate and ATP), which are known to stimulate Ca(2+) elevations in astrocytes. At first we characterized the VGLUT1-pHluorin expressing vesicles and found that VGLUT1-positive vesicles were a specific population of small synaptic-like microvesicles containing glutamate but which do not express VGLUT2. Endogenous mediators evoked a burst of exocytosis through activation of G-protein coupled receptors. Subsequent glutamate exocytosis was reduced by about 80% upon pharmacological blockade of the prostaglandin-forming enzyme, cyclooxygenase. On the other hand, receptor stimulation was accompanied by extracellular release of prostaglandin E2 (PGE2). Interestingly, administration of exogenous PGE2 produced per se rapid, store-dependent burst exocytosis of glutamatergic vesicles in astrocytes. Finally, when PGE2-neutralizing antibody was added to cell medium, transmitter-evoked exocytosis was again significantly reduced (by about 50%). Overall these data indicate that cyclooxygenase products are responsible for a major component of glutamate exocytosis in astrocytes and that large part of such component is sustained by autocrine/paracrine action of PGE2.

  12. Effects of aluminium exposure on brain glutamate and GABA systems: an experimental study in rats.

    PubMed

    Nayak, P; Chatterjee, A K

    2001-12-01

    It has been postulated that the neurotoxic effects of aluminium could be mediated through glutamate, an excitatory amino acid. Hence the effects of aluminium administration (at a dose of 4.2mg/kg body weight daily as aluminium chloride, hexahydrate, intraperitoneally, for 4 weeks) on glutamate and gamma-amino butyrate (GABA), an inhibitory amino acid, and related enzyme activities in different regions of the brain were studied in albino rats. The glutamate level increased significantly in the cerebrum, thalamic area, midbrain-hippocampal region and cerebellum in response to in vivo aluminium exposure. The aluminium insult also caused significant increases in glutamate alpha-decarboxylase activity in all the brain regions. However, on aluminium insult, the GABA content was not significantly changed except in the thalamic area, where it was elevated. On the contrary, the GABA-T activities of all the regions were reduced significantly in all regions except the midbrain-hippocampal region. However, the succinic semi-aldehyde content of all brain regions increased, often significantly. The aluminium-induced modification of the enzyme activities may be either due to the direct impact of aluminium or due to aluminium-induced changes in the cellular environment. The aluminium-induced differential regional accumulation of glutamate or other alterations in enzymes of the glutamate-GABA system may be one of the causes of aluminium-induced neurotoxicity.

  13. Insulin and glucagon share the same mechanism of neuroprotection in diabetic rats: role of glutamate

    PubMed Central

    Fanne, Rami Abu; Nassar, Taher; Heyman, Samuel N.; Hijazi, Nuha

    2011-01-01

    In patients with acute ischemic stroke, diabetes and hyperglycemia are associated with increased infarct size, more profound neurologic deficits and higher mortality. Notwithstanding extensive clinical and experimental data, treatment of stroke-associated hyperglycemia with insulin is controversial. In addition to hyperglycemia, diabetes and even early prediabetic insulin resistance are associated with increased levels of amino acids, including the neurotoxic glutamate, in the circulation. The pleiotropic metabolic effects of insulin include a reduction in the concentration of amino acids in the circulation. In this article, we show that in diabetic rats exposed to transient middle cerebral artery occlusion, a decrease of plasma glutamate by insulin or glucagon reduces CSF glutamate, improves brain histology, and preserves neurologic function. The neuroprotective effect of insulin and glucagon was similar, notwithstanding their opposite effects on blood glucose. The therapeutic window of both hormones overlapped with the short duration (∼30 min) of elevated brain glutamate following brain trauma in rodents. Similar neuroprotective effects were found after administration of the glutamate scavenger oxaloacetate, which does not affect glucose metabolism. These data indicate that insulin and glucagon exert a neuroprotective effect within a very brief therapeutic window that correlates with their capacity to reduce glutamate, rather than by modifying glucose levels. PMID:21677268

  14. Evidence for involvement of nitric oxide and GABAB receptors in MK-801- stimulated release of glutamate in rat prefrontal cortex

    PubMed Central

    Roenker, Nicole L.; Gudelsky, Gary A.; Ahlbrand, Rebecca; Horn, Paul S.; Richtand, Neil M.

    2012-01-01

    Systemic administration of NMDA receptor antagonists elevates extracellular glutamate within prefrontal cortex. The cognitive and behavioral effects of NMDA receptor blockade have direct relevance to symptoms of schizophrenia, and recent studies demonstrate an important role for nitric oxide and GABAB receptors in mediating the effects of NMDA receptor blockade on these behaviors. We sought to extend those observations by directly measuring the effects of nitric oxide and GABAB receptor mechanisms on MK-801-induced glutamate release in the prefrontal cortex. Systemic MK-801 injection (0.3 mg/kg) to male Sprague-Dawley rats significantly increased extracellular glutamate levels in prefrontal cortex, as determined by microdialysis. This effect was blocked by pretreatment with the nitric oxide synthase inhibitor L-NAME (60 mg/kg). Reverse dialysis of the nitric oxide donor SNAP (0.5 – 5 mM) directly into prefrontal cortex mimicked the effect of systemic MK-801, dose-dependently elevating cortical extracellular glutamate. The effect of MK-801 was also blocked by systemic treatment with the GABAB receptor agonist baclofen (5 mg/kg). In combination, these data suggest increased nitric oxide formation is necessary for NMDA antagonist-induced elevations of extracellular glutamate in the prefrontal cortex. Additionally, the data suggest GABAB receptor activation can modulate the NMDA antagonist-induced increase in cortical glutamate release. PMID:22579658

  15. Impaired anterior insular activation during risky decision making in young adults with internet gaming disorder.

    PubMed

    Lee, Deokjong; Lee, Junghan; Yoon, Kang Joon; Kee, Namkoong; Jung, Young-Chul

    2016-05-25

    Internet gaming disorder is defined as excessive and compulsive use of the internet to engage in games that leads to clinically significant psychosocial impairment. We tested the hypothesis that individuals with internet gaming disorder would be less sensitive to high-risk situations and show aberrant brain activation related to risk prediction processing. Young adults with internet gaming disorder underwent functional MRI while performing a risky decision-making task. The healthy control group showed stronger activations within the dorsal attention network and the anterior insular cortex, which were not found in the internet gaming disorder group. Our findings imply that young adults with internet gaming disorder show impaired anterior insular activation during risky decision making, which might make them vulnerable when they need to adapt new behavioral strategies in high-risk situations.

  16. Mainland size variation informs predictive models of exceptional insular body size change in rodents

    PubMed Central

    Durst, Paul A. P.; Roth, V. Louise

    2015-01-01

    The tendency for island populations of mammalian taxa to diverge in body size from their mainland counterparts consistently in particular directions is both impressive for its regularity and, especially among rodents, troublesome for its exceptions. However, previous studies have largely ignored mainland body size variation, treating size differences of any magnitude as equally noteworthy. Here, we use distributions of mainland population body sizes to identify island populations as ‘extremely’ big or small, and we compare traits of extreme populations and their islands with those of island populations more typical in body size. We find that although insular rodents vary in the directions of body size change, ‘extreme’ populations tend towards gigantism. With classification tree methods, we develop a predictive model, which points to resource limitations as major drivers in the few cases of insular dwarfism. Highly successful in classifying our dataset, our model also successfully predicts change in untested cases. PMID:26085585

  17. Synaptic glutamate spillover due to impaired glutamate uptake mediates heroin relapse.

    PubMed

    Shen, Hao-wei; Scofield, Michael D; Boger, Heather; Hensley, Megan; Kalivas, Peter W

    2014-04-16

    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.

  18. 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

  19. Esophageal Acid Stimulation Alters Insular Cortex Functional Connectivity in Gastroesophageal Reflux Disease

    PubMed Central

    Siwiec, Robert M.; Babaei, Arash; Kern, Mark; Samuel, Erica A.; Li, Shi-Jiang; Shaker, Reza

    2014-01-01

    Background The insula plays a significant role in the interoceptive processing of visceral stimuli. We have previously shown that GERD patients have increased insular cortex activity during esophageal stimulation, suggesting a sensitized esophago-cortical neuraxis. However, information regarding the functional connectivity (FC) of the insula during visceral stimulation is lacking. The primary aim of this study was to investigate the FC of insular subregions during esophageal acid stimulation. Methods Functional imaging data was obtained from 12 GERD patients and 14 healthy subjects during four steady state conditions: (1) presence of transnasal esophageal catheter (pre-infusion); (2) neutral solution; (3) acid infusion; (4) presence of transnasal esophageal catheter following infusions (post-infusion). The insula was parcellated into 6 regions of interest (ROI). FC maps between each insular ROI and interoceptive regions were created. Differences in FC between GERD patients and healthy subjects were determined across the 4 study conditions. Key Results All GERD patients experienced heartburn during and after esophageal acidification. Significant differences between GERD patients and healthy subjects were seen in: (1) insula-thalamic FC (neutral solution infusion, acid infusion, post-infusion); (2) insula-amygdala FC (acid infusion, post-infusion); (3) insula-hippocampus and insula-cingulate FC (post-infusion). Conclusions & Inferences Esophageal stimulation in GERD patients revealed significant insular cortex FC differences with regions involved in viscerosensation and interoception. The results of our study provide further evidence that the insula, located at the transition of afferent physiologic information to human feelings, is essential for both visceral homeostasis and the experience of heartburn in GERD patients. PMID:25367277

  20. Delta and gamma oscillations in operculo-insular cortex underlie innocuous cold thermosensation

    PubMed Central

    Vinding, Mikkel C.; Allen, Micah; Jensen, Troels Staehelin; Finnerup, Nanna Brix

    2017-01-01

    Cold-sensitive and nociceptive neural pathways interact to shape the quality and intensity of thermal and pain perception. Yet the central processing of cold thermosensation in the human brain has not been extensively studied. Here, we used magnetoencephalography and EEG in healthy volunteers to investigate the time course (evoked fields and potentials) and oscillatory activity associated with the perception of cold temperature changes. Nonnoxious cold stimuli consisting of Δ3°C and Δ5°C decrements from an adapting temperature of 35°C were delivered on the dorsum of the left hand via a contact thermode. Cold-evoked fields peaked at around 240 and 500 ms, at peak latencies similar to the N1 and P2 cold-evoked potentials. Importantly, cold-related changes in oscillatory power indicated that innocuous thermosensation is mediated by oscillatory activity in the range of delta (1–4 Hz) and gamma (55–90 Hz) rhythms, originating in operculo-insular cortical regions. We suggest that delta rhythms coordinate functional integration between operculo-insular and frontoparietal regions, while gamma rhythms reflect local sensory processing in operculo-insular areas. NEW & NOTEWORTHY Using magnetoencephalography, we identified spatiotemporal features of central cold processing, with respect to the time course, oscillatory profile, and neural generators of cold-evoked responses in healthy human volunteers. Cold thermosensation was associated with low- and high-frequency oscillatory rhythms, both originating in operculo-insular regions. These results support further investigations of central cold processing using magnetoencephalography or EEG and the clinical utility of cold-evoked potentials for neurophysiological assessment of cold-related small-fiber function and damage. PMID:28250150

  1. Delta and gamma oscillations in operculo-insular cortex underlie innocuous cold thermosensation.

    PubMed

    Fardo, Francesca; Vinding, Mikkel C; Allen, Micah; Jensen, Troels Staehelin; Finnerup, Nanna Brix

    2017-05-01

    Cold-sensitive and nociceptive neural pathways interact to shape the quality and intensity of thermal and pain perception. Yet the central processing of cold thermosensation in the human brain has not been extensively studied. Here, we used magnetoencephalography and EEG in healthy volunteers to investigate the time course (evoked fields and potentials) and oscillatory activity associated with the perception of cold temperature changes. Nonnoxious cold stimuli consisting of Δ3°C and Δ5°C decrements from an adapting temperature of 35°C were delivered on the dorsum of the left hand via a contact thermode. Cold-evoked fields peaked at around 240 and 500 ms, at peak latencies similar to the N1 and P2 cold-evoked potentials. Importantly, cold-related changes in oscillatory power indicated that innocuous thermosensation is mediated by oscillatory activity in the range of delta (1-4 Hz) and gamma (55-90 Hz) rhythms, originating in operculo-insular cortical regions. We suggest that delta rhythms coordinate functional integration between operculo-insular and frontoparietal regions, while gamma rhythms reflect local sensory processing in operculo-insular areas.NEW & NOTEWORTHY Using magnetoencephalography, we identified spatiotemporal features of central cold processing, with respect to the time course, oscillatory profile, and neural generators of cold-evoked responses in healthy human volunteers. Cold thermosensation was associated with low- and high-frequency oscillatory rhythms, both originating in operculo-insular regions. These results support further investigations of central cold processing using magnetoencephalography or EEG and the clinical utility of cold-evoked potentials for neurophysiological assessment of cold-related small-fiber function and damage. Copyright © 2017 the American Physiological Society.

  2. Evidence of Genetic Differentiation for Hawaii Insular False Killer Whales (Pseudorca crassidens)

    DTIC Science & Technology

    2010-05-01

    other delphinids (i.e., 1-2%) but comparable to estimates of nucleotide diversity for sperm whales (Physeter macrocephalus, 0.38%, Lyrholm et al. 1996...and biased substitution patterns in the mitochondrial DNA control region of sperm whales : implications for estimates of time since common ancestry...Schultz, Janet L. Thieleking and Daniel L. Webster EVIDENCE OF GENETIC DIFFERENTIATION FOR HAWAI I INSULAR FALSE KILLER WHALES ` (Pseudorca crassidens

  3. Probabilistic Tractography Recovers a Rostrocaudal Trajectory of Connectivity Variability in the Human Insular Cortex

    PubMed Central

    Cerliani, Leonardo; Thomas, Rajat M; Jbabdi, Saad; Siero, Jeroen CW; Nanetti, Luca; Crippa, Alessandro; Gazzola, Valeria; D'Arceuil, Helen; Keysers, Christian

    2012-01-01

    The insular cortex of macaques has a wide spectrum of anatomical connections whose distribution is related to its heterogeneous cytoarchitecture. Although there is evidence of a similar cytoarchitectural arrangement in humans, the anatomical connectivity of the insula in the human brain has not yet been investigated in vivo. In the present work, we used in vivo probabilistic white-matter tractography and Laplacian eigenmaps (LE) to study the variation of connectivity patterns across insular territories in humans. In each subject and hemisphere, we recovered a rostrocaudal trajectory of connectivity variation ranging from the anterior dorsal and ventral insula to the dorsal caudal part of the long insular gyri. LE suggested that regional transitions among tractography patterns in the insula occur more gradually than in other brain regions. In particular, the change in tractography patterns was more gradual in the insula than in the medial premotor region, where a sharp transition between different tractography patterns was found. The recovered trajectory of connectivity variation in the insula suggests a relation between connectivity and cytoarchitecture in humans resembling that previously found in macaques: tractography seeds from the anterior insula were mainly found in limbic and paralimbic regions and in anterior parts of the inferior frontal gyrus, while seeds from caudal insular territories mostly reached parietal and posterior temporal cortices. Regions in the putative dysgranular insula displayed more heterogeneous connectivity patterns, with regional differences related to the proximity with either putative granular or agranular regions. Hum Brain Mapp 33:2005–2034, 2012. © 2011 Wiley Periodicals, Inc. PMID:21761507

  4. Insular pathology in young people with high-functioning autism and first-episode psychosis.

    PubMed

    Parellada, M; Pina-Camacho, L; Moreno, C; Aleman, Y; Krebs, M-O; Desco, M; Merchán-Naranjo, J; Del Rey-Mejías, A; Boada, L; Llorente, C; Moreno, D; Arango, C; Janssen, J

    2017-10-01

    Autism Spectrum Disorders (ASD) and psychosis share deficits in social cognition. The insular region has been associated with awareness of self and reality, which may be basic for proper social interactions. Total and regional insular volume and thickness measurements were obtained from a sample of 30 children and adolescents with ASD, 29 with early onset first-episode psychosis (FEP), and 26 healthy controls (HC). Total, regional, and voxel-level volume and thickness measurements were compared between groups (with correction for multiple comparisons), and the relationship between these measurements and symptom severity was explored. Compared with HC, a shared volume deficit was observed for the right (but not the left) anterior insula (ASD: p = 0.007, FEP: p = 0.032), and for the bilateral posterior insula: (left, ASD: p = 0.011, FEP: p = 0.033; right, ASD: p = 0.004, FEP: p = 0.028). A voxel-based morphometry (VBM) conjunction analysis showed that ASD and FEP patients shared a gray matter volume and thickness deficit in the left posterior insula. Within patients, right anterior (r = -0.28, p = 0.041) and left posterior (r = -0.29, p = 0.030) insular volumes negatively correlated with the severity of insight deficits, and left posterior insular volume negatively correlated with the severity of 'autistic-like' symptoms (r = -0.30, p = 0.028). The shared reduced volume and thickness in the anterior and posterior regions of the insula in ASD and FEP provides the first tentative evidence that these conditions share structural pathology that may be linked to shared symptomatology.

  5. Population size and time since island isolation determine genetic diversity loss in insular frog populations.

    PubMed

    Wang, Supen; Zhu, Wei; Gao, Xu; Li, Xianping; Yan, Shaofei; Liu, Xuan; Yang, Ji; Gao, Zengxiang; Li, Yiming

    2014-02-01

    Understanding the factors that contribute to loss of genetic diversity in fragmented populations is crucial for conservation measurements. Land-bridge archipelagoes offer ideal model systems for identifying the long-term effects of these factors on genetic variations in wild populations. In this study, we used nine microsatellite markers to quantify genetic diversity and differentiation of 810 pond frogs (Pelophylax nigromaculatus) from 24 islands of the Zhoushan Archipelago and three sites on nearby mainland China and estimated the effects of the island area, population size, time since island isolation, distance to the mainland and distance to the nearest larger island on reduced genetic diversity of insular populations. The mainland populations displayed higher genetic diversity than insular populations. Genetic differentiations and no obvious gene flow were detected among the frog populations on the islands. Hierarchical partitioning analysis showed that only time since island isolation (square-root-transformed) and population size (log-transformed) significantly contributed to insular genetic diversity. These results suggest that decreased genetic diversity and genetic differentiations among insular populations may have been caused by random genetic drift following isolation by rising sea levels during the Holocene. The results provide strong evidence for a relationship between retained genetic diversity and population size and time since island isolation for pond frogs on the islands, consistent with the prediction of the neutral theory for finite populations. Our study highlights the importance of the size and estimated isolation time of populations in understanding the mechanisms of genetic diversity loss and differentiation in fragmented wild populations. © 2013 John Wiley & Sons Ltd.

  6. Decreased insular connectivity in drug-naive major depressive disorder at rest.

    PubMed

    Guo, Wenbin; Liu, Feng; Xiao, Changqing; Zhang, Zhikun; Liu, Jianrong; Yu, Miaoyu; Zhang, Jian; Zhao, Jingping

    2015-07-01

    The insula has extensive links to the fronto-limbic circuit and associated regions, which is involved in the neurobiology of major depressive disorder (MDD). However, few studies are designed to examine the insular connectivity in MDD. This study was performed to examine the insular connectivity in drug-naive MDD directly by using the insular cortices as seeds. Functional magnetic resonance imaging data were obtained from 44 drug-naive MDD patients and 44 healthy controls at rest. The functional connectivity (FC) method was used to analyze the images. Significantly decreased FCs were found between the right insula and the left middle frontal gyrus (MFG, orbital part), left superior temporal gyrus (STG), right putamen, and right middle occipital gyrus (MOG), and between the left insula and the left superior temporal pole and right MOG in the patients compared with the controls. There were significantly negative correlations between the z values of the left insula-left superior temporal pole connectivity and the current episode duration (r=-0.332, p=0.028), between the z values of the right insula-left STG connectivity and the episode number (r=-0.343, p=0.023), and between the z values of the right insula-left MFG (orbital part) connectivity and the Automatic Thoughts Questionnaire scores (r=-0.359, p=0.017) in the patients. The findings reveal that depressed patients have decreased insular connectivity with the fronto-limbic circuit, hate circuit, and visual regions, and suggest that the insula may act as an integration center of emotional processing which is disrupted in the depressed patients. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. Involvement of the glutamate/glutamine cycle and glutamate transporter GLT-1 in antidepressant-like effects of Xiao Yao san on chronically stressed mice.

    PubMed

    Ding, Xiu-Fang; Li, Yue-Hua; Chen, Jia-Xu; Sun, Long-Ji; Jiao, Hai-Yan; Wang, Xin-Xin; Zhou, Yan

    2017-06-19

    Xiao Yao San (XYS) is an herbal prescription which is used in the treatment of depression for thousands of years from Song dynasty in China (960-1127 A.D.), and is the bestselling and most popular herb formula for treating major depression. This study aimed to assess the chronic antidepressant effects of XYS and fluoxetine in depressed mice induced by chronic unpredictable mild stress (CUMS) and its association with  alterations in glutamate/glutamine cycle and glutamate transporters. Mice in the control and model group were given 0.5 ml physiological saline by intragastric administration. Mice in two treatment groups were given XYS (0.25 g/kg/d) and fluoxetine (2.6 mg/kg/d), respectively. The depressive-like behaviors such as forced swim test (FST), sucrose preference test (SPT) and novelty-suppressed feeding (NSF) test were measured after mice exposed to CUMS for 21 days. Body weight, contents of glutamate and glutamine, glutamine/glutamate ratio that is usually thought to reflect glutamate/glutamine cycle, and the protein and mRNA expressions of glutamate transporters (excitatory amino acid transporter 1-2,GLAST/EAAT1 and GLT-1/EAAT2) were measured. The immunoreactivities of GLAST and GLT-1 in the hippocampus were also investigated. After CUMS exposure, mice exhibited depressive-like behaviors, body weight loss, increased glutamate level, decreased glutamine level, elevated glutamine/glutamate ratio, decreased GLT-1 protein expression and mRNA level, and decreased average optical density (AOD) of GLT-1 in the CA1, CA3 and DG in the hippocampus. These abnormalities could be effectively reversed by XYS or fluoxetine treatment. In addition, the study also found that GLAST expression in the hippocampus could not be altered by 21-d CUMS. The studies indicated that XYS may have therapeutic actions on depression -like behavior s induced by CUMS in mice possibly mediated by modulation of glutamate/glutamine cycle and glutamate transporter GLT-1 in the hippocampus.

  8. Clinical considerations and surgical approaches for low-grade gliomas in deep hemispheric locations: insular lesions.

    PubMed

    Hinojosa, J; Gil-Robles, S; Pascual, B

    2016-10-01

    Insula and paralimbic region represent a common location for gliomas in adulthood. However, limbic and paralimbic tumors are rare in children. Reports of pediatric insular tumors are scarce in literature, and most of them are included in adult's series, so their management and outcome can be outlined only after extracting data from these reports. Due to their predominantly low grade, they usually have a benign course for some time, what make them ideal candidates for total resection. However, their intricate location and spread to key areas, including the temporal lobe, make them a surgical challenge. The transsylvian route, with or without resection of the frontal and/or temporal operculae, which requires exposure of part or all of the insula is commonly selected for insular tumor approaches. Intraoperative functional mapping is a standard procedure for resection of central region tumors in adults. In children and young individuals, awake craniotomy is not always possible and surgical planning usually relay on functional and anatomical preoperative studies. The main goal when approaching an insular tumor is to achieve the largest extent of resection to increase overall patient survival while preserving the functional status, minimizing postoperative morbidity and increasing the quality of life. The extent of resection seems to be correlated also with the control of associated (and usually intractable) epilepsy.

  9. Insular neural system controls decision-making in healthy and methamphetamine-treated rats

    PubMed Central

    Mizoguchi, Hiroyuki; Katahira, Kentaro; Inutsuka, Ayumu; Fukumoto, Kazuya; Nakamura, Akihiro; Wang, Tian; Nagai, Taku; Sato, Jun; Sawada, Makoto; Ohira, Hideki; Yamanaka, Akihiro; Yamada, Kiyofumi

    2015-01-01

    Patients suffering from neuropsychiatric disorders such as substance-related and addictive disorders exhibit altered decision-making patterns, which may be associated with their behavioral abnormalities. However, the neuronal mechanisms underlying such impairments are largely unknown. Using a gambling test, we demonstrated that methamphetamine (METH)-treated rats chose a high-risk/high-reward option more frequently and assigned higher value to high returns than control rats, suggestive of changes in decision-making choice strategy. Immunohistochemical analysis following the gambling test revealed aberrant activation of the insular cortex (INS) and nucleus accumbens in METH-treated animals. Pharmacological studies, together with in vivo microdialysis, showed that the insular neural system played a crucial role in decision-making. Moreover, manipulation of INS activation using designer receptor exclusively activated by designer drug technology resulted in alterations to decision-making. Our findings suggest that the INS is a critical region involved in decision-making and that insular neural dysfunction results in risk-taking behaviors associated with altered decision-making. PMID:26150496

  10. A volumetric comparison of the insular cortex and its subregions in primates

    PubMed Central

    Bauernfeind, Amy L.; de Sousa, Alexandra A.; Avasthi, Tanvi; Dobson, Seth D.; Raghanti, Mary Ann; Lewandowski, Albert H.; Zilles, Karl; Semendeferi, Katerina; Allman, John M.; (Bud) Craig, Arthur D.; Hof, Patrick R.; Sherwood, Chet C.

    2013-01-01

    The neuronal composition of the insula in primates displays a gradient, transitioning from granular neocortex in the posterior-dorsal insula to agranular neocortex in the anterior-ventral insula with an intermediate zone of dysgranularity. Additionally, apes and humans exhibit a distinctive subdomain in the agranular insula, the frontoinsular cortex (FI), defined by the presence of clusters of von Economo neurons (VENs). Studies in humans indicate that the ventral anterior insula, including agranular insular cortex and FI, is involved in social awareness, and that the posterodorsal insula, including granular and dysgranular cortices, produces an internal representation of the body’s homeostatic state. We examined the volumes of these cytoarchitectural areas of insular cortex in 30 primate species, including the volume of FI in apes and humans. Results indicate that the whole insula scales hyperallometrically (exponent = 1.13) relative to total brain mass, and the agranular insula (including FI) scales against total brain mass with even greater positive allometry (exponent = 1.23), providing a potential neural basis for enhancement of social cognition in association with increased brain size. The relative volumes of the subdivisions of the insular cortex, after controlling for total brain volume, are not correlated with species typical social group size. Although its size is predicted by primate-wide allometric scaling patterns, we found that the absolute volume of the left and right agranular insula and left FI are among the most differentially expanded of the human cerebral cortex compared to our closest living relative, the chimpanzee. PMID:23466178

  11. Insular neural system controls decision-making in healthy and methamphetamine-treated rats.

    PubMed

    Mizoguchi, Hiroyuki; Katahira, Kentaro; Inutsuka, Ayumu; Fukumoto, Kazuya; Nakamura, Akihiro; Wang, Tian; Nagai, Taku; Sato, Jun; Sawada, Makoto; Ohira, Hideki; Yamanaka, Akihiro; Yamada, Kiyofumi

    2015-07-21

    Patients suffering from neuropsychiatric disorders such as substance-related and addictive disorders exhibit altered decision-making patterns, which may be associated with their behavioral abnormalities. However, the neuronal mechanisms underlying such impairments are largely unknown. Using a gambling test, we demonstrated that methamphetamine (METH)-treated rats chose a high-risk/high-reward option more frequently and assigned higher value to high returns than control rats, suggestive of changes in decision-making choice strategy. Immunohistochemical analysis following the gambling test revealed aberrant activation of the insular cortex (INS) and nucleus accumbens in METH-treated animals. Pharmacological studies, together with in vivo microdialysis, showed that the insular neural system played a crucial role in decision-making. Moreover, manipulation of INS activation using designer receptor exclusively activated by designer drug technology resulted in alterations to decision-making. Our findings suggest that the INS is a critical region involved in decision-making and that insular neural dysfunction results in risk-taking behaviors associated with altered decision-making.

  12. Insular and hippocampal contributions to remembering people with an impression of bad personality

    PubMed Central

    Shigemune, Yayoi; Nouchi, Rui; Kambara, Toshimune; Kawashima, Ryuta

    2013-01-01

    Our impressions of other people are formed mainly from the two possible factors of facial attractiveness and trustworthiness. Previous studies have shown the importance of orbitofrontal–hippocampal interactions in the better remembering of attractive faces, and psychological data have indicated that faces giving an impression of untrustworthiness are remembered more accurately than those giving an impression of trustworthiness. However, the neural mechanisms of the latter effect are largely unknown. To investigate this issue, we investigated neural activities with event-related fMRI while the female participants rated their impressions of the personalities of men in terms of trustworthiness. After the rating, memory for faces was tested to identify successful encoding activity. As expected, faces that gave bad impressions were remembered better than those that gave neutral or good impressions. In fMRI data, right insular activity reflected an increasing function of bad impressions, and bilateral hippocampal activities predicted subsequent memory success. Additionally, correlation between these insular and hippocampal regions was significant only in the encoding of faces associated with a bad impression. Better memory for faces associated with an impression of bad personality could reflect greater interaction between the avoidance-related insular region and the encoding-related hippocampal region. PMID:22349799

  13. Insular and hippocampal contributions to remembering people with an impression of bad personality.

    PubMed

    Tsukiura, Takashi; Shigemune, Yayoi; Nouchi, Rui; Kambara, Toshimune; Kawashima, Ryuta

    2013-06-01

    Our impressions of other people are formed mainly from the two possible factors of facial attractiveness and trustworthiness. Previous studies have shown the importance of orbitofrontal-hippocampal interactions in the better remembering of attractive faces, and psychological data have indicated that faces giving an impression of untrustworthiness are remembered more accurately than those giving an impression of trustworthiness. However, the neural mechanisms of the latter effect are largely unknown. To investigate this issue, we investigated neural activities with event-related fMRI while the female participants rated their impressions of the personalities of men in terms of trustworthiness. After the rating, memory for faces was tested to identify successful encoding activity. As expected, faces that gave bad impressions were remembered better than those that gave neutral or good impressions. In fMRI data, right insular activity reflected an increasing function of bad impressions, and bilateral hippocampal activities predicted subsequent memory success. Additionally, correlation between these insular and hippocampal regions was significant only in the encoding of faces associated with a bad impression. Better memory for faces associated with an impression of bad personality could reflect greater interaction between the avoidance-related insular region and the encoding-related hippocampal region.

  14. Variable temporo-insular cortex neuroanatomy in primates suggests a bottleneck effect in eastern gorillas

    PubMed Central

    Barks, Sarah K.; Bauernfeind, Amy L.; Bonar, Christopher J.; Cranfield, Michael R.; de Sousa, Alexandra A.; Erwin, Joseph M.; Hopkins, William D.; Lewandowski, Albert H.; Mudakikwa, Antoine; Phillips, Kimberley A.; Raghanti, Mary Ann; Stimpson, Cheryl D.; Hof, Patrick R.; Zilles, Karl; Sherwood, Chet C.

    2013-01-01

    In this study, we describe an atypical neuroanatomical feature present in several primate species that involves a fusion between the temporal lobe (often including Heschl’s gyrus in great apes) and the posterior dorsal insula, such that a portion of insular cortex forms an isolated pocket medial to the Sylvian fissure. We assessed the frequency of this fusion in 56 primate species (including apes, Old World monkeys, New World monkeys, and strepsirrhines) using either magnetic resonance images or histological sections. A fusion between temporal cortex and posterior insula was present in 22 species (7 apes, 2 Old World monkeys, 4 New World monkeys, and 9 strepsirrhines). The temporo-insular fusion was observed in most eastern gorilla (Gorilla beringei beringei and G. b. graueri) specimens (62% and 100% of cases, respectively) but less frequently in other great apes and was never found in humans. We further explored the histology of this fusion in eastern gorillas by examining the cyto- and myeloarchitecture within this region, and observed that the degree to which deep cortical layers and white matter are incorporated into the fusion varies among individuals within a species. We suggest that fusion between temporal and insular cortex is an example of a relatively rare neuroanatomical feature that has become more common in eastern gorillas, possibly as the result of a population bottleneck effect. Characterizing the phylogenetic distribution of this morphology highlights a derived feature of these great apes. PMID:23939630

  15. Effects of phosphoenolpyruvate carboxylase desensitization on glutamic acid production in Corynebacterium glutamicum ATCC 13032.

    PubMed

    Wada, Masaru; Sawada, Kazunori; Ogura, Kotaro; Shimono, Yuta; Hagiwara, Takuya; Sugimoto, Masakazu; Onuki, Akiko; Yokota, Atsushi

    2016-02-01

    Phosphoenolpyruvate carboxylase (PEPC) in Corynebacterium glutamicum ATCC13032, a glutamic-acid producing actinobacterium, is subject to feedback inhibition by metabolic intermediates such as aspartic acid and 2-oxoglutaric acid, which implies the importance of PEPC in replenishing oxaloacetic acid into the TCA cycle. Here, we investigated the effects of feedback-insensitive PEPC on glutamic acid production. A single amino-acid substitution in PEPC, D299N, was found to relieve the feedback control by aspartic acid, but not by 2-oxoglutaric acid. A simple mutant, strain R1, having the D299N substitution in PEPC was constructed from ATCC 13032 using the double-crossover chromosome replacement technique. Strain R1 produced glutamic acid at a concentration of 31.0 g/L from 100 g/L glucose in a jar fermentor culture under biotin-limited conditions, which was significantly higher than that of the parent, 26.0 g/L (1.19-fold), indicative of the positive effect of desensitized PEPC on glutamic acid production. Another mutant, strain DR1, having both desensitized PEPC and PYK-gene deleted mutations, was constructed in a similar manner using strain D1 with a PYK-gene deleted mutation as the parent. This mutation had been shown to enhance glutamic acid production in our previous study. Although marginal, strain D1 produced higher glutamic acid, 28.8 g/L, than ATCC13032 (1.11-fold). In contrast, glutamic acid production by strain DR-1 was elevated up to 36.9 g/L, which was 1.42-fold higher than ATCC13032 and significantly higher than the other three strains. The results showed a synergistic effect of these two mutations on glutamic acid production in C. glutamicum. Copyright © 2015 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  16. Using glutamate homeostasis as a target for treating addictive disorders.

    PubMed

    Reissner, Kathryn J; Kalivas, Peter W

    2010-09-01

    Well-developed cellular mechanisms exist to preserve glutamate homeostasis and regulate extrasynaptic glutamate levels. Accumulating evidence indicates that disruptions in glutamate homeostasis are associated with addictive disorders. The disruptions in glutamate concentrations observed after prolonged exposure to drugs of abuse are associated with changes in the function and activity of several key components within the homeostatic control mechanism, including the cystine/glutamate exchanger xc(-) and the glial glutamate transporter, EAAT2/GLT-1. Changes in the balance between synaptic and extrasynaptic glutamate levels in turn influence signaling through presynaptic and postsynaptic glutamate receptors, and thus affect synaptic plasticity and circuit-level activity. In this review, we describe the evidence for impaired glutamate homeostasis as a critical mediator of long-term drug-seeking behaviors, how chronic neuroadaptations in xc(-) and the glutamate transporter, GLT-1, mediate a disruption in glutamate homeostasis, and how targeting these components restores glutamate levels and inhibits drug-seeking behaviors.

  17. Two insular regions are differentially involved in behavioral variant FTD and nonfluent/agrammatic variant PPA.

    PubMed

    Mandelli, Maria Luisa; Vitali, Paolo; Santos, Miguel; Henry, Maya; Gola, Kelly; Rosenberg, Lynne; Dronkers, Nina; Miller, Bruce; Seeley, William W; Gorno-Tempini, Maria Luisa

    2016-01-01

    The non-fluent/agrammatic variant of primary progressive aphasia (nfvPPA) and the behavioral variant frontotemporal dementia (bvFTD) are focal neurodegenerative disorders belonging to the FTD-spectrum clinical syndromes. NfvPPA is characterized by effortful speech and/or agrammatism and left frontal atrophy, while bvFTD is characterized by social-emotional dysfunction often accompanied by right-lateralized frontal damage. Despite their contrasting clinical presentations, both disorders show prominent left anterior insula atrophy. We investigated differential patterns of insular sub-region atrophy in nfvPPA and bvFTD. Based on knowledge of insular connectivity and physiology, we hypothesized that the left superior precentral region of the dorsal anterior insula (SPGI) would be more atrophic in nvfPPA due to its critical role in motor speech, whereas the ventral anterior region would be more atrophied in bvFTD reflecting its known role in social-emotional-autonomic functions. Early stage nfvPPA and bvFTD patients matched for disease severity, age, gender and education and healthy controls participated in the study. Detailed clinical history, neurological examination, neuropsychological screening evaluation, and high-resolution T1-weighted brain magnetic resonance imaging (MRI) were collected. Voxel-based morphometry (VBM) was applied to perform group comparisons across the whole brain and in bilateral insula region of interest (ROI). Correlation analyses between insular sub-region atrophy and relevant clinical features were performed. Whole brain group comparisons between nfvPPA and bvFTD showed the expected predominantly left or right anterior insular atrophy pattern. ROI analysis of bilateral insula showed that the left SPGI was significantly more atrophied in nfvPPA compared to bvFTD, while the bilateral ventral anterior and right dorsal anterior insula sub-regions were more atrophied in bvFTD than nfvPPA. Only left SPGI volume correlated with speech production

  18. Two insular regions are differentially involved in behavioral variant FTD and nonfluent/agrammatic variant PPA

    PubMed Central

    Mandelli, Maria Luisa; Vitali, Paolo; Santos, Miguel; Henry, Maya; Gola, Kelly; Rosenberg, Lynne; Dronkers, Nina; Miller, Bruce; Seeley, William W.; Gorno-Tempini, Maria Luisa

    2016-01-01

    The non-fluent/agrammatic variant of primary progressive aphasia (nfvPPA) and the behavioral variant frontotemporal dementia (bvFTD) are focal neurodegenerative disorders belonging to the FTD-spectrum clinical syndromes. NfvPPA is characterized by effortful speech and/or agrammatism and left frontal atrophy, while bvFTD is characterized by social-emotional dysfunction often accompanied by right-lateralized frontal damage. Despite their contrasting clinical presentations, both disorders show prominent left anterior insula atrophy. We investigated differential patterns of insular subregion atrophy in nfvPPA and bvFTD. Based on knowledge of insular connectivity and physiology, we hypothesized that the left superior precentral region of the dorsal anterior insula (SPGI) would be more atrophic in nvfPPA due to its critical role in motor speech, whereas the ventral anterior region would be more atrophied in bvFTD reflecting its known role in social-emotional-autonomic functions. Early stage nfvPPA and bvFTD patients matched for disease severity, age, gender and education and healthy controls participated in the study. Detailed clinical history, neurological examination, neuropsychological screening evaluation, and high-resolution T1-weighted brain magnetic resonance images (MRI) were collected. Voxel-based morphometry (VBM) was applied to perform group comparisons across the whole brain and in bilateral insula region of interest (ROI). Correlation analyses between insular subregion atrophy and relevant clinical features were performed. Whole brain group comparisons between nfvPPA and bvFTD showed the expected predominantly left or right anterior insular atrophy pattern. ROI analysis of bilateral insula showed that the left SPGI was significantly more atrophied in nfvPPA compared to bvFTD, while the bilateral ventral anterior and right dorsal anterior insula subregions were more atrophied in bvFTD than nfvPPA. Only left SPGI volume correlated with speech production

  19. 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. © 2016 American Society for Nutrition.

  20. Alcohol drinking and deprivation alter basal extracellular glutamate concentrations and clearance in the mesolimbic system of alcohol-preferring (P) rats.

    PubMed

    Ding, Zheng-Ming; Rodd, Zachary A; Engleman, Eric A; Bailey, Jason A; Lahiri, Debomoy K; McBride, William J

    2013-03-01

    The present study determined the effects of voluntary ethanol drinking and deprivation on basal extracellular glutamate concentrations and clearance in the mesolimbic system and tested the hypothesis that chronic ethanol drinking would persistently increase basal glutamate neurotransmission. Three groups of alcohol-preferring (P) rats were used: 'water group (WG),' 'ethanol maintenance group (MG; 24-hour free choice water versus 15% ethanol)' and 'ethanol deprivation group (DG; 2 weeks of deprivation).' Quantitative microdialysis and Western blots were conducted to measure basal extracellular glutamate concentrations, clearance and proteins associated with glutamate clearance. Chronic alcohol drinking produced a 70-100% increase of basal extracellular glutamate concentrations in the posterior ventral tegmental area (4.0 versus 7.0 μM) and nucleus accumbens shell (3.0 versus 6.0 μM). Glutamate clearances were reduced by 30-40% in both regions of MG rats compared with WG rats. In addition, Western blots revealed a 40-45% decrease of excitatory amino transporter 1 (EAAT1) protein, but no significant changes in the levels of EAAT2 or cystine-glutamate antiporter in these regions of MG versus WG rats. The enhanced glutamate concentrations returned to control levels, accompanied by a recovery of glutamate clearance following deprivation. These results indicated that chronic alcohol drinking enhanced extracellular glutamate concentrations in the mesolimbic system, as a result, in part, of reduced clearance, suggesting that enhanced glutamate neurotransmission may contribute to the maintenance of alcohol drinking. However, because the increased glutamate levels returned to normal after deprivation, elevated glutamate neurotransmission may not contribute to the initiation of relapse drinking.

  1. Glutamate Fermentation-2: Mechanism of L-Glutamate Overproduction in Corynebacterium glutamicum.

    PubMed

    Hirasawa, Takashi; Wachi, Masaaki

    The nonpathogenic coryneform bacterium, Corynebacterium glutamicum, was isolated as an L-glutamate-overproducing microorganism by Japanese researchers and is currently utilized in various amino acid fermentation processes. L-Glutamate production by C. glutamicum is induced by limitation of biotin and addition of fatty acid ester surfactants and β-lactam antibiotics. These treatments affect the cell surface structures of C. glutamicum. After the discovery of C. glutamicum, many researchers have investigated the underlying mechanism of L-glutamate overproduction with respect to the cell surface structures of this organism. Furthermore, metabolic regulation during L-glutamate overproduction by C. glutamicum, particularly, the relationship between central carbon metabolism and L-glutamate biosynthesis, has been investigated. Recently, the role of a mechanosensitive channel protein in L-glutamate overproduction has been reported. In this chapter, mechanisms of L-glutamate overproduction by C. glutamicum have been reviewed.

  2. Kanamycin ototoxicity in glutamate transporter knockout mice.

    PubMed

    Shimizu, Yoshitaka; Hakuba, Nobuhiro; Hyodo, Jun; Taniguchi, Masafumi; Gyo, Kiyofumi

    2005-06-03

    Glutamate-aspartate transporter (GLAST), a powerful glutamate uptake system, removes released glutamate from the synaptic cleft and facilitates the re-use of glutamate as a neurotransmitter recycling system. Aminoglycoside-induced hearing loss is mediated via a glutamate excitotoxic process. We investigated the effect of aminoglycoside ototoxicity in GLAST knockout mice using the recorded auditory brainstem response (ABR) and number of hair cells in the cochlea. Kanamycin (100 mg/mL) was injected directly into the posterior semicircular canal of mice. Before the kanamycin treatment, there was no difference in the ABR threshold average between the wild-type and knockout mice. Kanamycin injection aggravated the ABR threshold in the GLAST knockout mice compared with the wild-type mice, and the IHC degeneration was more severe in the GLAST knockout mice. These findings suggest that GLAST plays an important role in preventing the degeneration of inner hair cells in aminoglycoside ototoxicity.

  3. Glutamate-based antidepressants: preclinical psychopharmacology.

    PubMed

    Pilc, Andrzej; Wierońska, Joanna M; Skolnick, Phil

    2013-06-15

    Over the past 20 years, converging lines of evidence have both linked glutamatergic dysfunction to the pathophysiology of depression and demonstrated that the glutamatergic synapse presents multiple targets for developing novel antidepressants. The robust antidepressant effects of the N-methyl-D-aspartate receptor antagonists ketamine and traxoprodil provide target validation for this family of ionotropic glutamate receptors. This article reviews the preclinical evidence that it may be possible to develop glutamate-based antidepressants by not only modulating ionotropic (N-methyl-D-aspartate and alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid) and metabotropic glutamate (mGlu) receptors, including mGlu2/3, mGLu5 and mGlu7 receptors, but also by altering synaptic concentrations of glutamate via specialized transporters such as glial glutamate transporter 1 (excitatory amino-acid transporter 2).

  4. Effects of Prolonged Exposure to Hypobaric Hypoxia on Oxidative Stress, Inflammation and Gluco-Insular Regulation: The Not-So-Sweet Price for Good Regulation

    PubMed Central

    Siervo, Mario; Riley, Heather L.; Fernandez, Bernadette O.; Leckstrom, Carl A.; Martin, Daniel S.; Mitchell, Kay; Levett, Denny Z. H.; Montgomery, Hugh E.; Mythen, Monty G.

    2014-01-01

    Objectives The mechanisms by which low oxygen availability are associated with the development of insulin resistance remain obscure. We thus investigated the relationship between such gluco-insular derangements in response to sustained (hypobaric) hypoxemia, and changes in biomarkers of oxidative stress, inflammation and counter-regulatory hormone responses. Methods After baseline testing in London (75 m), 24 subjects ascended from Kathmandu (1,300 m) to Everest Base Camp (EBC;5,300 m) over 13 days. Of these, 14 ascended higher, with 8 reaching the summit (8,848 m). Assessments were conducted at baseline, during ascent to EBC, and 1, 6 and 8 week(s) thereafter. Changes in body weight and indices of gluco-insular control were measured (glucose, insulin, C-Peptide, homeostasis model assessment of insulin resistance [HOMA-IR]) along with biomarkers of oxidative stress (4-hydroxy-2-nonenal-HNE), inflammation (Interleukin-6 [IL-6]) and counter-regulatory hormones (glucagon, adrenalin, noradrenalin). In addition, peripheral oxygen saturation (SpO2) and venous blood lactate concentrations were determined. Results SpO2 fell significantly from 98.0% at sea level to 82.0% on arrival at 5,300 m. Whilst glucose levels remained stable, insulin and C-Peptide concentrations increased by >200% during the last 2 weeks. Increases in fasting insulin, HOMA-IR and glucagon correlated with increases in markers of oxidative stress (4-HNE) and inflammation (IL-6). Lactate levels progressively increased during ascent and remained significantly elevated until week 8. Subjects lost on average 7.3 kg in body weight. Conclusions Sustained hypoxemia is associated with insulin resistance, whose magnitude correlates with the degree of oxidative stress and inflammation. The role of 4-HNE and IL-6 as key players in modifying the association between sustained hypoxia and insulin resistance merits further investigation. PMID:24733551

  5. Nanomolar vitamin E alpha-tocotrienol inhibits glutamate-induced activation of phospholipase A2 and causes neuroprotection.

    PubMed

    Khanna, Savita; Parinandi, Narasimham L; Kotha, Sainath R; Roy, Sashwati; Rink, Cameron; Bibus, Douglas; Sen, Chandan K

    2010-03-01

    Our previous works have elucidated that the 12-lipoxygenase pathway is directly implicated in glutamate-induced neural cell death, and that such that toxicity is prevented by nM concentrations of the natural vitamin E alpha-tocotrienol (TCT). In the current study we tested the hypothesis that phospholipase A(2) (PLA(2)) activity is sensitive to glutamate and mobilizes arachidonic acid (AA), a substrate for 12-lipoxygenase. Furthermore, we examined whether TCT regulates glutamate-inducible PLA(2) activity in neural cells. Glutamate challenge induced the release of [(3)H]AA from HT4 neural cells. Such response was attenuated by calcium chelators (EGTA and BAPTA), cytosolic PLA(2) (cPLA(2))-specific inhibitor (AACOCF(3)) as well as TCT at 250 nM. Glutamate also caused the elevation of free polyunsaturated fatty acid (AA and docosahexaenoic acid) levels and disappearance of phospholipid-esterified AA in neural cells. Furthermore, glutamate induced a time-dependent translocation and enhanced serine phosphorylation of cPLA(2) in the cells. These effects of glutamate on fatty acid levels and on cPLA(2) were significantly attenuated by nM TCT. The observations that AACOCF(3), transient knock-down of cPLA(2) as well as TCT significantly protected against the glutamate-induced death of neural cells implicate cPLA(2) as a TCT-sensitive mediator of glutamate induced neural cell death. This work presents first evidence recognizing glutamate-induced changes in cPLA(2) as a novel mechanism responsible for neuroprotection observed in response to nanomolar concentrations of TCT.

  6. Cingulo-insular structural alterations associated with psychogenic symptoms, childhood abuse and PTSD in functional neurological disorders.

    PubMed

    Perez, David L; Matin, Nassim; Barsky, Arthur; Costumero-Ramos, Victor; Makaretz, Sara J; Young, Sigrid S; Sepulcre, Jorge; LaFrance, W Curt; Keshavan, Matcheri S; Dickerson, Bradford C

    2017-06-01

    Adverse early-life events are predisposing factors for functional neurological disorder (FND) and post-traumatic stress disorder (PTSD). Cingulo-insular regions are implicated in the biology of both conditions and are sites of stress-mediated neuroplasticity. We hypothesised that functional neurological symptoms and the magnitude of childhood abuse would be associated with overlapping anterior cingulate cortex (ACC) and insular volumetric reductions, and that FND and PTSD symptoms would map onto distinct cingulo-insular areas. This within-group voxel-based morphometry study probes volumetric associations with self-report measures of functional neurological symptoms, adverse life events and PTSD symptoms in 23 mixed-gender FND patients. Separate secondary analyses were also performed in the subset of 18 women with FND to account for gender-specific effects. Across the entire cohort, there were no statistically significant volumetric associations with self-report measures of functional neurological symptom severity or childhood abuse. In women with FND, however, parallel inverse associations were observed between left anterior insular volume and functional neurological symptoms as measured by the Patient Health Questionnaire-15 and the Screening for Somatoform Symptoms Conversion Disorder subscale. Similar inverse relationships were also appreciated between childhood abuse burden and left anterior insular volume. Across all subjects, PTSD symptom severity was inversely associated with dorsal ACC volume, and the magnitude of lifetime adverse events was inversely associated with left hippocampal volume. This study reveals distinct cingulo-insular alterations for FND and PTSD symptoms and may advance our understanding of FND. Potential biological convergence between stress-related neuroplasticity, functional neurological symptoms and reduced insular volume was identified. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017

  7. Using glutamate homeostasis as a target for treating addictive disorders

    PubMed Central

    Reissner, Kathryn J.; Kalivas, Peter W.

    2010-01-01

    Well-developed cellular mechanisms exist to preserve glutamate homeostasis and regulate extrasynaptic glutamate levels. Accumulating evidence indicates that disruptions in glutamate homeostasis are associated with addictive disorders. The disruptions in glutamate concentrations observed following prolonged exposure to drugs of abuse are associated with changes in the function and activity of several key components within the homeostatic control mechanism, including the cystine/glutamate exchanger xc− and the glial glutamate transporter EAAT2/GLT-1. Changes in the balance between synaptic and extrasynaptic glutamate levels in turn influence signaling through pre- and postsynaptic glutamate receptors, and thus affect synaptic plasticity and circuit-level activity. In this review we describe the evidence for impaired glutamate homestasis as a critical mediator of long-term drug-seeking behaviors, how chronic neuroadaptations in xc− and GLT-1 mediate a disruption in glutamate homeostasis, and how targeting these components restores glutamate levels and inhibits drug-seeking behaviors. PMID:20634691

  8. ABNORMAL GLUTAMATE HOMEOSTASIS AND IMPAIRED SYNAPTIC PLASTICITY AND LEARNING IN A MOUSE MODEL OF TUBEROUS SCLEROSIS COMPLEX

    PubMed Central

    Zeng, Ling-Hui; Ouyang, Yannan; Gazit, Vered; Cirrito, John R.; Jansen, Laura A.; Ess, Kevin C.; Yamada, Kelvin A.; Wozniak, David F.; Holtzman, David M.; Gutmann, David H.; Wong, Michael

    2007-01-01

    Mice with inactivation of the Tuberous sclerosis complex-1 (Tsc1) gene in glia (Tsc1GFAPCKO mice) have deficient astrocyte glutamate transporters and develop seizures, suggesting that abnormal glutamate homeostasis contributes to neurological abnormalities in these mice. We examined the hypothesis that Tsc1GFAPCKO mice have elevated extracellular brain glutamate levels that may cause neuronal death, abnormal glutamatergic synaptic function, and associated impairments in behavioral learning. In vivo microdialysis documented elevated glutamate levels in hippocampi of Tsc1GFAPCKO mice and several cell death assays demonstrated neuronal death in hippocampus and neocortex. Impairment of long-term potentiation (LTP) with tetanic stimulation was observed in hippocampal slices from Tsc1GFAPCKO mice and was reversed by low concentrations of NMDA antagonist, indicating that excessive synaptic glutamate directly inhibited LTP. Finally, Tsc1GFAPCKO mice exhibited deficits in two hippocampal-dependent learning paradigms. These results suggest that abnormal glutamate homeostasis predisposes to excitotoxic cell death, impaired synaptic plasticity and learning deficits in Tsc1GFAPCKO mice. PMID:17714952

  9. Status of ammonia, glutamate, lactate and pyruvate during Plasmodium yoelii infection and pyrimethamine treatment in mice.

    PubMed

    Agarwal, A; Tripathi, L M; Pandey, V C

    1997-09-01

    Ammonia, lactate, glutamate and pyruvate levels in blood, liver, brain, spleen and kidney were determined during Plasmodium yoelii infection and pyrimethamine treatment in mice. Ammonia and lactate levels showed significant increase with rise in parasitaemia except in spleen where decrease in the lactate levels was observed. The glutamate level displayed a marked decrease in blood, liver and splenic tissues, whereas, significant increase in glutamate level in kidney was observed, although its level in cerebral tissue remained unaltered. The pyruvate level in blood and liver showed a noticeable decrease but brain, spleen and kidney registered an elevation of the same due to the parasitic infection. Pyrimethamine (oral) treatment (10 mg/kg body weight) to infected mice (5-10%) for four days brought back the altered levels of the above cellular constituents in different tissues to normal, a week after cessation of drug treatment.

  10. Modulation of pineal melatonin synthesis by glutamate involves paracrine interactions between pinealocytes and astrocytes through NF-κB activation.

    PubMed

    Villela, Darine; Atherino, Victoria Fairbanks; Lima, Larissa de Sá; Moutinho, Anderson Augusto; do Amaral, Fernanda Gaspar; Peres, Rafael; Martins de Lima, Thais; Torrão, Andréa da Silva; Cipolla-Neto, José; Scavone, Cristóforo; Afeche, Solange Castro

    2013-01-01

    The glutamatergic modulation of melatonin synthesis is well known, along with the importance of astrocytes in mediating glutamatergic signaling in the central nervous system. Pinealocytes and astrocytes are the main cell types in the pineal gland. The objective of this work was to investigate the interactions between astrocytes and pinealocytes as a part of the glutamate inhibitory effect on melatonin synthesis. Rat pinealocytes isolated or in coculture with astrocytes were incubated with glutamate in the presence of norepinephrine, and the melatonin content, was quantified. The expression of glutamate receptors, the intracellular calcium content and the NF- κ B activation were analyzed in astrocytes and pinealocytes. TNF- α 's possible mediation of the effect of glutamate was also investigated. The results showed that glutamate's inhibitory effect on melatonin synthesis involves interactions between astrocytes and pinealocytes, possibly through the release of TNF- α . Moreover, the activation of the astrocytic NF- κ B seems to be a necessary step. In astrocytes and pinealocytes, AMPA, NMDA, and group I metabotropic glutamate receptors were observed, as well as the intracellular calcium elevation. In conclusion, there is evidence that the modulation of melatonin synthesis by glutamate involves paracrine interactions between pinealocytes and astrocytes through the activation of the astrocytic NF- κ B transcription factor and possibly by subsequent TNF- α release.

  11. Fate of glutamate carbon and nitrogen in isolated guinea-pig kidney-cortex tubules. Evidence for involvement of glutamate dehydrogenase in glutamine sythesis from glutamate.

    PubMed

    Baverel, G; Genoux, C; Forissier, M; Pellet, M

    1980-06-15

    1. The pathways and the fate of glutamate carbon and nitrogen were investigated in isolated guinea-pig kidney-cortex tubules. 2. At low glutamate concentration (1 mM), the glutamate carbon skeleton was either completely oxidized or converted into glutamine. At high glutamate concentration (5 mM), glucose, lactate and alanine were additional products of glutamate metabolism. 3. At neither concentration of glutamate was there accumulation of ammonia. 4. Nitrogen-balance calculations and the release of 14CO2 from L-[1-14C]glutamate (which gives an estimation of the flux of glutamate carbon skeleton through alpha-oxoglutarate dehydrogenase) clearly indicated that, despite the absence of ammonia accumulation, glutamate metabolism was initiated by the action of glutamate dehydrogenase and not by transamination reactions as suggested by Klahr, Schoolwerth & Bourgoignie [(1972) Am. J. Physiol. 222, 813-820] and Preuss [(1972) Am. J. Physiol. 222, 1395-1397]. Additional evidence for this was obtained by the use of (i) amino-oxyacetate, an inhibitor of transaminases, which did not decrease glutamate removal, or (ii) L-methionine DL-sulphoximine, an inhibitor of glutamine synthetase, which caused an accumulation of ammonia from glutamate. 5. Addition of NH4Cl plus glutamate caused an increase in both glutamate removal and glutamine synthesis, demonstrating that the supply of ammonia via glutamate dehydrogenase is the rate-limiting step in glutamine formation from glutamate. NH4Cl also inhibited the flux of glutamate through glutamate dehydrogenase and the formation of glucose, alanine and lactate. 6. The activities of enzymes possibly involved in the glutamate conversion into pyruvate were measured in guinea-pig renal cortex. 7. Renal arteriovenous-difference measurements revealed that in vivo the guinea-pig kidney adds glutamine and alanine to the circulating blood.

  12. Glutamate and Brain Glutaminases in Drug Addiction.

    PubMed

    Márquez, Javier; Campos-Sandoval, José A; Peñalver, Ana; Matés, José M; Segura, Juan A; Blanco, Eduardo; Alonso, Francisco J; de Fonseca, Fernando Rodríguez

    2017-03-01

    Glutamate is the principal excitatory neurotransmitter in the central nervous system and its actions are related to the behavioral effects of psychostimulant drugs. In the last two decades, basic neuroscience research and preclinical studies with animal models are suggesting a critical role for glutamate transmission in drug reward, reinforcement, and relapse. Although most of the interest has been centered in post-synaptic glutamate receptors, the presynaptic synthesis of glutamate through brain glutaminases may also contribute to imbalances in glutamate homeostasis, a key feature of the glutamatergic hypothesis of addiction. Glutaminases are the main glutamate-producing enzymes in brain and dysregulation of their function have been associated with neurodegenerative diseases and neurological disorders; however, the possible implication of these enzymes in drug addiction remains largely unknown. This mini-review focuses on brain glutaminase isozymes and their alterations by in vivo exposure to drugs of abuse, which are discussed in the context of the glutamate homeostasis theory of addiction. Recent findings from mouse models have shown that drugs induce changes in the expression profiles of key glutamatergic transmission genes, although the molecular mechanisms that regulate drug-induced neuronal sensitization and behavioral plasticity are not clear.

  13. ASIC1a regulates insular long-term depression and is required for the extinction of conditioned taste aversion

    PubMed Central

    Li, Wei-Guang; Liu, Ming-Gang; Deng, Shining; Liu, Yan-Mei; Shang, Lin; Ding, Jing; Hsu, Tsan-Ting; Jiang, Qin; Li, Ying; Li, Fei; Zhu, Michael Xi; Xu, Tian-Le

    2016-01-01

    Acid-sensing ion channel 1a (ASIC1a) has been shown to play important roles in synaptic plasticity, learning and memory. Here we identify a crucial role for ASIC1a in long-term depression (LTD) at mouse insular synapses. Genetic ablation and pharmacological inhibition of ASIC1a reduced the induction probability of LTD without affecting that of long-term potentiation in the insular cortex. The disruption of ASIC1a also attenuated the extinction of established taste aversion memory without altering the initial associative taste learning or its long-term retention. Extinction of taste aversive memory led to the reduced insular synaptic efficacy, which precluded further LTD induction. The impaired LTD and extinction learning in ASIC1a null mice were restored by virus-mediated expression of wild-type ASIC1a, but not its ion-impermeable mutant, in the insular cortices. Our data demonstrate the involvement of an ASIC1a-mediated insular synaptic depression mechanism in extinction learning, which raises the possibility of targeting ASIC1a to manage adaptive behaviours. PMID:27924869

  14. Cocaine-induced neuroadaptations in glutamate transmission

    PubMed Central

    Schmidt, Heath D.; Pierce, R. Christopher

    2017-01-01

    A growing body of evidence indicates that repeated exposure to cocaine leads to profound changes in glutamate transmission in limbic nuclei, particularly the nucleus accumbens. This review focuses on preclinical studies of cocaine-induced behavioral plasticity, including behavioral sensitization, self-administration, and the reinstatement of cocaine seeking. Behavioral, pharmacological, neurochemical, electrophysiological, biochemical, and molecular biological changes associated with cocaine-induced plasticity in glutamate systems are reviewed. The ultimate goal of these lines of research is to identify novel targets for the development of therapies for cocaine craving and addiction. Therefore, we also outline the progress and prospects of glutamate modulators for the treatment of cocaine addiction. PMID:20201846

  15. In the grey zone between epilepsy and schizophrenia: alterations in group II metabotropic glutamate receptors.

    PubMed

    Dedeurwaerdere, Stefanie; Boets, Stephanie; Janssens, Pieter; Lavreysen, Hilde; Steckler, Thomas

    2015-09-01

    Glutamate is the major excitatory neurotransmitter in the brain. The glutamate system plays an important role in the formation of synapses during brain development and synaptic plasticity. Dysfunctions in glutamate regulation may lead to hyperexcitatory neuronal networks and neurotoxicity. Glutamate excess is possibly of great importance in the pathophysiology of several neurological and psychiatric disorders such as epilepsy and schizophrenia. Interestingly, cross talk between these disorders has been well documented: psychiatric comorbidities are frequent in epilepsy and temporal lobe epilepsy is one of the highest risk factors for developing psychosis. Therefore, dysfunctions in glutamatergic neurotransmission might constitute a common pathological mechanism. A major negative feedback system is regulated by the presynaptic group II metabotropic glutamate (mGlu) receptors including mGlu2/3 receptors. These receptors are predominantly localised extrasynaptically in basal ganglia and limbic structures. Hence, mGlu2/3 receptors are an interesting target for the treatment of disorders like epilepsy and schizophrenia. A dysfunction in the glutamate system may be associated with alterations in mGlu2/3 receptor expression. In this review, we describe the localization of mGlu2/3 receptors in the healthy brain of mice, rats and humans. Secondly, changes in mGlu2/3 receptor density of the brain regions affected in epilepsy and schizophrenia are summarised. Increased mGlu2/3 receptor density might represent a compensatory mechanism of the brain to regulate elevated glutamate levels, while reduced mGlu2/3 receptor density in some brain regions may further contribute to the aberrant hyperexcitability. Further research considering the mGlu2/3 receptor can contribute significantly to the understanding of the etiological and therapeutic role of group II mGlu receptor in epilepsy, epilepsy with psychosis and schizophrenia.

  16. Effects of Ceftriaxone on Glial Glutamate Transporters in Wistar Rats Administered Sequential Ethanol and Methamphetamine

    PubMed Central

    Althobaiti, Yusuf S.; Alshehri, Fahad S.; Almalki, Atiah H.; Sari, Youssef

    2016-01-01

    Methamphetamine (METH) is one of the psychostimulants that is co-abused with ethanol. Repeated exposure to high dose of METH has been shown to cause increases in extracellular glutamate concentration. We have recently reported that ethanol exposure can also increase the extracellular glutamate concentration and downregulate the expression of glutamate transporter subtype 1 (GLT-1). GLT-1 is a glial transporter that regulates the majority of extracellular glutamate. A Wistar rat model of METH and ethanol co-abuse was used to examine the expression of GLT-1 as well as other glutamate transporters such as cystine/glutamate exchanger (xCT) and glutamate aspartate transporter (GLAST). We also examined the body temperature in rats administered METH, ethanol or both drugs. We further investigated the effects of ceftriaxone (CEF), a β-lactam antibiotic known to upregulate GLT-1, in this METH/ethanol co-abuse rat model. After 7 days of either ethanol (6 g/kg) or water oral gavage, Wistar rats received either saline or METH (10 mg/kg i.p. every 2 h × 4), followed by either saline or CEF (200 mg/kg) posttreatment. METH administered alone decreased GLT-1 expression in the nucleus accumbens (NAc) and prefrontal cortex (PFC) and increased body temperature, but did not reduce either xCT or GLAST expression in ethanol and water-pretreated rats. Interestingly, ethanol and METH were found to have an additive effect on the downregulation of GLT-1 expression in the NAc but not in the PFC. Moreover, ethanol alone caused GLT-1 downregulation in the NAc and elevated body temperature compared to control. Finally, CEF posttreatment significantly reversed METH-induced hyperthermia, restored GLT-1 expression, and increased xCT expression. These findings suggest the potential therapeutic role of CEF against METH- or ethanol/METH-induced hyperglutamatergic state and hyperthermia. PMID:27713684

  17. The effects of feral cats on insular wildlife: the Club-Med syndrome

    USGS Publications Warehouse

    Hess, Steve C.; Danner, Raymond M.; Timm, R.M.

    2012-01-01

    Domestic cats have been introduced to many of the world‘s islands where they have been particularly devastating to insular wildlife which, in most cases, evolved in the absence of terrestrial predatory mammals and feline diseases. We review the effects of predation, feline diseases, and the life history characteristics of feral cats and their prey that have contributed to the extirpation and extinction of many insular vertebrate species. The protozoan Toxoplasma gondii is a persistent land-based zoonotic pathogen hosted by cats that is known to cause mortality in several insular bird species. It also enters marine environments in cat feces where it can cause the mortality of marine mammals. Feral cats remain widespread on islands throughout the world and are frequently subsidized in colonies which caretakers often assert have little negative effect on native wildlife. However, population genetics, home range, and movement studies all suggest that there are no locations on smaller islands where these cats cannot penetrate within two generations. While the details of past vertebrate extinctions were rarely documented during contemporary time, a strong line of evidence is emerging that the removal of feral cats from islands can rapidly facilitate the recolonization of extirpated species, particularly seabirds. Islands offer unique, mostly self-contained ecosystems in which to conduct controlled studies of the effects of feral cats on wildlife, having implications for continental systems. The response of terrestrial wildlife such as passerine birds, small mammals, and herptiles still needs more thorough long-term monitoring and documentation after the removal of feral cats.

  18. Subacute Pain after Traumatic Brain Injury Is Associated with Lower Insular N-Acetylaspartate Concentrations

    PubMed Central

    Govind, Varan; Adcock, James P.; Levin, Bonnie E.; Maudsley, Andrew A.

    2016-01-01

    Abstract Persistent pain is experienced by more than 50% of persons who sustain a traumatic brain injury (TBI), and more than 30% experience significant pain as early as 6 weeks after injury. Although neuropathic pain is a common consequence after CNS injuries, little attention has been given to neuropathic pain symptoms after TBI. Magnetic resonance spectroscopy (MRS) studies in subjects with TBI show decreased brain concentrations of N-acetylaspartate (NAA), a marker of neuronal density and viability. Although decreased brain NAA has been associated with neuropathic pain associated with spinal cord injury (SCI) and diabetes, this relationship has not been examined after TBI. The primary purpose of this study was to test the hypothesis that lower NAA concentrations in brain areas involved in pain perception and modulation would be associated with greater severity of neuropathic pain symptoms. Participants with TBI underwent volumetric MRS, pain and psychosocial interviews. Cluster analysis of the Neuropathic Pain Symptom Inventory subscores resulted in two TBI subgroups: The Moderate Neuropathic Pain (n = 17; 37.8%), with significantly (p = 0.038) lower insular NAA than the Low or no Neuropathic Pain group (n = 28; 62.2%), or age- and sex-matched controls (n = 45; p < 0.001). A hierarchical linear regression analysis controlling for age, sex, and time post-TBI showed that pain severity was significantly (F = 11.0; p < 0.001) predicted by a combination of lower insular NAA/Creatine (p < 0.001), lower right insular gray matter fractional volume (p < 0.001), female sex (p = 0.005), and older age (p = 0.039). These findings suggest that neuronal dysfunction in brain areas involved in pain processing is associated with pain after TBI. PMID:26486760

  19. Subacute Pain after Traumatic Brain Injury Is Associated with Lower Insular N-Acetylaspartate Concentrations.

    PubMed

    Widerström-Noga, Eva; Govind, Varan; Adcock, James P; Levin, Bonnie E; Maudsley, Andrew A

    2016-07-15

    Persistent pain is experienced by more than 50% of persons who sustain a traumatic brain injury (TBI), and more than 30% experience significant pain as early as 6 weeks after injury. Although neuropathic pain is a common consequence after CNS injuries, little attention has been given to neuropathic pain symptoms after TBI. Magnetic resonance spectroscopy (MRS) studies in subjects with TBI show decreased brain concentrations of N-acetylaspartate (NAA), a marker of neuronal density and viability. Although decreased brain NAA has been associated with neuropathic pain associated with spinal cord injury (SCI) and diabetes, this relationship has not been examined after TBI. The primary purpose of this study was to test the hypothesis that lower NAA concentrations in brain areas involved in pain perception and modulation would be associated with greater severity of neuropathic pain symptoms. Participants with TBI underwent volumetric MRS, pain and psychosocial interviews. Cluster analysis of the Neuropathic Pain Symptom Inventory subscores resulted in two TBI subgroups: The Moderate Neuropathic Pain (n = 17; 37.8%), with significantly (p = 0.038) lower insular NAA than the Low or no Neuropathic Pain group (n = 28; 62.2%), or age- and sex-matched controls (n = 45; p < 0.001). A hierarchical linear regression analysis controlling for age, sex, and time post-TBI showed that pain severity was significantly (F = 11.0; p < 0.001) predicted by a combination of lower insular NAA/Creatine (p < 0.001), lower right insular gray matter fractional volume (p < 0.001), female sex (p = 0.005), and older age (p = 0.039). These findings suggest that neuronal dysfunction in brain areas involved in pain processing is associated with pain after TBI.

  20. Apigenin, a natural flavonoid, inhibits glutamate release in the rat hippocampus.

    PubMed

    Chang, Chia Ying; Lin, Tzu Yu; Lu, Cheng Wei; Wang, Chia Chuan; Wang, Ying Chou; Chou, Shang Shing Peter; Wang, Su Jane

    2015-09-05

    The purpose of this study was to examine the effect and mechanism of apigenin, a natural flavonoid, on glutamate release in the rat hippocampus. In rat hippocampal nerve terminals (synaptosomes), apigenin inhibited glutamate release and the elevation of the cytosolic free Ca(2+) concentration evoked by 4-aminopyridine, whereas it had no effect on 4-aminopyridine-mediated depolarization and Na(+) influx. The apigenin-mediated inhibition of evoked glutamate release was prevented by chelating the extracellular Ca(2+) ions and blocking Cav2.2 (N-type) and Cav2.1 (P/Q-type) channel activity. Furthermore, we determined that gamma-aminobutyric acid type A (GABAA) receptors are present in the hippocampal nerve terminals because they are colocalized with the presynaptic marker synaptophysin. However, the effect of apigenin on 4-aminopyridine-evoked glutamate release from synaptosomes was unaffected by the GABAA receptor antagonists SR95531 and bicuculline. Furthermore, in slice preparations, whole-cell patch-clamp experiments showed that apigenin reduced the frequency of spontaneous excitatory postsynaptic currents without affecting their amplitude, suggesting a presynaptic mechanism. On the basis of these results, we suggested that apigenin exerts its presynaptic inhibition probably by reducing Ca(2+) entry mediated by the Cav2.2 (N-type) and Cav2.1 (P/Q-type) channels, thereby inhibiting glutamate release from the rat hippocampal nerve terminals.

  1. Decreased expression of glutamate transporters in astrocytes after human traumatic brain injury.

    PubMed

    van Landeghem, Frank K H; Weiss, Thorsten; Oehmichen, Manfred; von Deimling, Andreas

    2006-10-01

    The primary mechanism for eliminating synaptically released glutamate is uptake by astrocytes. In the present study, we examined whether traumatic brain injury (TBI) affects the cellular expression of glutamate transporters EAAT1 and EAAT2. Morphometrical immunohistochemical analysis demonstrated a predominant expression of EAAT1 and EAAT2 in astrocytes of normal human neocortex (n = 10). Following traumatic injury of human brain (n = 55), the number of EAAT2-positive cells was decreased for a prolonged survival period within the traumatized neocortex and the pericontusional region. GFAP-positive astrocytes decreased in number within the first 24 h. Thereafter, the number of GFAP-positive astrocytes increased again, indicating formation of reactive gliosis. Double immunofluorescence examinations revealed a reduction in absolute numbers of GFAP-positive astrocytes coexpressing EAAT1 or EAAT2 at survival times up to 7 days. In addition, the relative fractions of astrocytes coexpressing glutamate transporters decreased following TBI. We conclude that the posttraumatic reduction in cellular EAAT 1 and EAAT2 expression is predominantly due to degeneration of astrocytes and to downregulation in surviving astrocytes. Our results support the view that reduced glutamate uptake by astrocytes contributes to posttraumatic elevation of extracellular glutamate in humans.

  2. Designing Novel Nanoformulations Targeting Glutamate Transporter Excitatory Amino Acid Transporter 2: Implications in Treating Drug Addiction

    PubMed Central

    Rao, PSS; Yallapu, Murali M.; Sari, Youssef; Fisher, Paul B.; Kumar, Santosh

    2015-01-01

    Chronic drug abuse is associated with elevated extracellular glutamate concentration in the brain reward regions. Deficit of glutamate clearance has been identified as a contributing factor that leads to enhanced glutamate concentration following extended drug abuse. Importantly, normalization of glutamate level through induction of glutamate transporter 1 (GLT1)/ excitatory amino acid transporter 2 (EAAT2) expression has been described in several in vivo studies. GLT1 upregulators including ceftriaxone, a beta-lactam antibiotic, have been effective in attenuating drug-seeking and drug-consumption behavior in rodent models. However, potential obstacles toward clinical translation of GLT1 (EAAT2) upregulators as treatment for drug addiction might include poor gastrointestinal absorption, serious peripheral adverse effects, and/or suboptimal CNS concentrations. Given the growing success of nanotechnology in targeting CNS ailments, nanoformulating known GLT1 (EAAT2) upregulators for selective uptake across the blood brain barrier presents an ideal therapeutic approach for treating drug addiction. In this review, we summarize the results obtained with promising GLT1 (EAAT2) inducing compounds in animal models recapitulating drug addiction. Additionally, the various nanoformulations that can be employed for selectively increasing the CNS bioavailability of GLT1 (EAAT2) upregulators are discussed. Finally, the applicability of GLT1 (EAAT2) induction via central delivery of drug-loaded nanoformulations is described. PMID:26635971

  3. Designing Novel Nanoformulations Targeting Glutamate Transporter Excitatory Amino Acid Transporter 2: Implications in Treating Drug Addiction.

    PubMed

    Rao, Pss; Yallapu, Murali M; Sari, Youssef; Fisher, Paul B; Kumar, Santosh

    Chronic drug abuse is associated with elevated extracellular glutamate concentration in the brain reward regions. Deficit of glutamate clearance has been identified as a contributing factor that leads to enhanced glutamate concentration following extended drug abuse. Importantly, normalization of glutamate level through induction of glutamate transporter 1 (GLT1)/ excitatory amino acid transporter 2 (EAAT2) expression has been described in several in vivo studies. GLT1 upregulators including ceftriaxone, a beta-lactam antibiotic, have been effective in attenuating drug-seeking and drug-consumption behavior in rodent models. However, potential obstacles toward clinical translation of GLT1 (EAAT2) upregulators as treatment for drug addiction might include poor gastrointestinal absorption, serious peripheral adverse effects, and/or suboptimal CNS concentrations. Given the growing success of nanotechnology in targeting CNS ailments, nanoformulating known GLT1 (EAAT2) upregulators for selective uptake across the blood brain barrier presents an ideal therapeutic approach for treating drug addiction. In this review, we summarize the results obtained with promising GLT1 (EAAT2) inducing compounds in animal models recapitulating drug addiction. Additionally, the various nanoformulations that can be employed for selectively increasing the CNS bioavailability of GLT1 (EAAT2) upregulators are discussed. Finally, the applicability of GLT1 (EAAT2) induction via central delivery of drug-loaded nanoformulations is described.

  4. Xanthohumol-induced presynaptic reduction of glutamate release in the rat hippocampus.

    PubMed

    Chang, Yi; Lin, Tzu Yu; Lu, Cheng Wei; Huang, Shu Kuei; Wang, Ying Chou; Wang, Su Jane

    2016-01-01

    This study examined whether xanthohumol, a hop-derived prenylated flavonoid present in beer, affects glutamate release in the rat hippocampus. In the rat hippocampal nerve terminals (synaptosomes), xanthohumol inhibited the release of 4-aminopyridine (4-AP)-evoked glutamate and the elevation of cytosolic Ca(2+) concentration, whereas it had no effect on 4-AP-mediated depolarization. The inhibitory effect of xanthohumol on the evoked glutamate release was prevented by removing extracellular Ca(2+), using the Cav2.2 (N-type) and Cav2.1 (P/Q-type) channel blocker ω-CgTX MVIIC, the calmodulin antagonists W7 and calmidazolium, and the protein kinase A inhibitor H89; however, no such effect was observed when the G-protein inhibitor N-ethylmaleimide was used. In addition, immunocytochemical data demonstrated that GABAA receptors are present in the hippocampal synaptosomes and that the xanthohumol effect on evoked glutamate release was antagonized by the GABAA receptor antagonist SR95531. Furthermore, in slice preparations, xanthohumol reduced the frequency of miniature excitatory postsynaptic currents without affecting their amplitude. We conclude that xanthohumol acts at GABAA receptors present in the hippocampal nerve terminals to decrease the Ca(2+) influx through N- and P/Q-type Ca(2+) channels, which subsequently suppresses the Ca(2+)-calmodulin/PKA cascade to decrease the evoked glutamate release.

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

    USDA-ARS?s Scientific Manuscript database

    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...

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

    USDA-ARS?s Scientific Manuscript database

    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...

  7. The shore fishes of the Trindade-Martin Vaz insular complex: an update.

    PubMed

    Simon, T; Macieira, R M; Joyeux, J-C

    2013-06-01

    A compilation of historical and recent collections and observations of shore fishes yielded 154 recorded species for Trindade and 67 for Martin Vaz. Twelve taxa, mostly small cryptobenthic species with limited dispersal capabilities and low ecological amplitude, are endemic to this insular complex. In several cases, the seamounts of the Vitória-Trindade Chain appear to have acted as stepping stones between the mainland and islands in periods of low sea level. © 2013 The Authors. Journal of Fish Biology © 2013 The Fisheries Society of the British Isles.

  8. Insular species swarm goes underground: two new troglobiont Cylindroiulus millipedes from Madeira (Diplopoda: Julidae).

    PubMed

    Reboleira, Ana Sofia P S; Enghoff, Henrik

    2014-04-04

    Two new species of the genus Cylindroiulus Verhoeff, 1894, C. julesvernei and C. oromii, are described from the subterranean ecosystem of Madeira Island, Portugal. Species are illustrated with photographs and diagrammatic drawings. The new species belong to the Cylindroiulus madeirae-group, an insular species swarm distributed in the archipelagos of Madeira and the Canary Islands. We discuss the differences between the new species and their relatives and present information on the subterranean environment of Madeira. An updated overview of the subterranean biodiversity of millipedes in Macaronesia is also provided.

  9. CB1 receptor antagonism in the granular insular cortex or somatosensory area facilitates consolidation of object recognition memory.

    PubMed

    O'Brien, Lesley D; Sticht, Martin A; Mitchnick, Krista A; Limebeer, Cheryl L; Parker, Linda A; Winters, Boyer D

    2014-08-22

    Cannabinoid agonists typically impair memory, whereas CB1 receptor antagonists enhance memory performance under specific conditions. The insular cortex has been implicated in object memory consolidation. Here we show that infusions of the CB1 receptor antagonist SR141716 enhances long-term object recognition memory in rats in a dose-dependent manner (facilitation with 1.5, but not 0.75 or 3 μg/μL) when administered into the granular insular cortex; the SR141716 facilitation was seen with a memory delay of 72 h, but not when the delay was shorter (1 h), consistent with enhancement of memory consolidation. Moreover, a sub-group of rats with cannulas placed in the somatosensory area were also facilitated. These results highlight the robust potential of cannabinoid antagonists to facilitate object memory consolidation, as well as the capacity for insular and somatosensory cortices to contribute to object processing, perhaps through enhancement of tactile representation.

  10. Mutism and auditory agnosia due to bilateral insular damage--role of the insula in human communication.

    PubMed

    Habib, M; Daquin, G; Milandre, L; Royere, M L; Rey, M; Lanteri, A; Salamon, G; Khalil, R

    1995-03-01

    We report a case of transient mutism and persistent auditory agnosia due to two successive ischemic infarcts mainly involving the insular cortex on both hemispheres. During the 'mutic' period, which lasted about 1 month, the patient did not respond to any auditory stimuli and made no effort to communicate. On follow-up examinations, language competences had re-appeared almost intact, but a massive auditory agnosia for non-verbal sounds was observed. From close inspection of lesion site, as determined with brain resonance imaging, and from a study of auditory evoked potentials, it is concluded that bilateral insular damage was crucial to both expressive and receptive components of the syndrome. The role of the insula in verbal and non-verbal communication is discussed in the light of anatomical descriptions of the pattern of connectivity of the insular cortex.

  11. Population structure and genetic diversity in insular populations of Nasutitermes takasagoensis (Isoptera: Termitidae) analyzed by AFLP markers.

    PubMed

    García, Julio; Maekawa, Kiyoto; Miura, Toru; Matsumoto, Tadao

    2002-10-01

    Dispersal ability and degree of inbreeding in a population can indirectly be assessed using genetic markers. In general, it was suggested that winged termites are not able to fly distances greater than several hundred meters. Here, amplified fragment length polymorphism (AFLP) was used to analyze genetic diversity, population substructure, and gene flow among insular populations of the termite Nasutitermes takasagoensis (Isoptera: Termitidae) in the Yaeyama Islands, Okinawa, Japan. Samples were collected from 77 nests on seven islands of the Yaeyama Group. Using three primer combinations a total of 155 bands were generated with 78 (50%) polymorphic bands. Genetic distance and G(st) values among insular populations were calculated. Relatively high genetic diversity and low values of G (st), suggest there is moderate subpopulation structure. Based on these results, we discussed two possibilities; first, winged termites are able to fly over distances of several kilometers, and second, these results were obtained because insular populations share a recent common origin.

  12. Elevation changes

    USGS Publications Warehouse

    Jayko, A. S.; Marshall, G.A.; Carver, G.A.

    1992-01-01

    Elevation changes, as well as horizontal displacements of the Earth's surface, are an expected consequence of dip-slip displacement on earthquake faults. the rock surrounding and overlying the fault is forced to stretch and bend to accommodate fault slip. Slip in the case of the April 25 mainshock is thought to have occurred on a gently inclined plane dipping to the northeast at a small angle (see article on preliminary seismological results in this issue).The associated fault-plane solution implies that rock overlying the fault plane (the hanging-wall block west and south of the epicenter) rose and shifted to the northeast. The map on the next page shows the location of the epicenter and approximate extent of uplift and subsidence derived from estimates of the geometry, location. and slip on the buried fault plane. 

  13. Construction of a potentiometric glutamate biosensor for determination of glutamate in some real samples.

    PubMed

    Y Lmaz, Demet; Karaku, Emine

    2011-12-01

    The potentiometric glutamate biosensor based on ammonium-selective poly(vinylchloride) (PVC) membrane electrode was constructed by chemically immobilizing glutamate oxidase. Ammonium ions produced after an enzymatic reaction were determined potentiometrically. We determined the optimum working conditions of the biosensor such as buffer concentration, buffer pH, lifetime, response time, linear working range, kinetic constants (K(m) and V(max)) of glutamate oxidase enzyme used for biosensor construction values, and other response characteristics. Additionally, glutamate assay in some real samples such as chicken bullion, healthy human serum, and commercial multipower amino acid mixture were also successfully carried out. The results showed good agreement with previously reported values.

  14. GABA-Mediated Inactivation of Medial Prefrontal and Agranular Insular Cortex in the Rat: Contrasting Effects on Hunger- and Palatability-Driven Feeding.

    PubMed

    Baldo, Brian A; Spencer, Robert C; Sadeghian, Ken; Mena, Jesus D

    2016-03-01

    A microanalysis of hunger-driven and palatability-driven feeding was carried out after muscimol-mediated inactivation of two frontal regions in rats, the agranular/dysgranular insular cortex (AIC) and the ventromedial prefrontal cortex (vmPFC). Food and water intake, feeding microstructure, and general motor activity were measured under two motivational conditions: food-deprived rats given standard chow or ad libitum-fed rats given a palatable chocolate shake. Muscimol infusions into the AIC diminished intake, total feeding duration, and average feeding bout duration for the palatable-food condition only but failed to alter exploratory-like behavior (ambulation or rearing). In contrast, intra-vmPFC muscimol infusions did not alter the overall intake of chow or chocolate shake. However, these infusions markedly increased mean feeding bout duration for both food types and produced a modest but significant reduction of exploratory-like behavior. The lengthening of feeding-bout duration and reduction in rearing were mimicked by intra-vmPFC blockade of AMPA-type but not NMDA-type glutamate receptors. Neither water consumption nor the microstructure of water drinking was affected by inactivation of either site. These results indicate a regional heterogeneity in frontal control of feeding behavior. Neural processing in AIC supports palatability-driven feeding but is not necessary for intake of a standard food under a food-restriction condition, whereas ventromedial prefrontal cortex, and AMPA signaling therein, modulates the duration of individual feeding bouts regardless of motivational context. Results are discussed in the context of regionally heterogeneous frontal modulation of two distinct components of feeding behavior: reward valuation based upon taste perception (AIC) vs switching between ingestive and non-ingestive (eg, exploratory-like) behavioral repertoires (vmPFC).

  15. GABA-Mediated Inactivation of Medial Prefrontal and Agranular Insular Cortex in the Rat: Contrasting Effects on Hunger- and Palatability-Driven Feeding

    PubMed Central

    Baldo, Brian A; Spencer, Robert C; Sadeghian, Ken; Mena, Jesus D

    2016-01-01

    A microanalysis of hunger-driven and palatability-driven feeding was carried out after muscimol-mediated inactivation of two frontal regions in rats, the agranular/dysgranular insular cortex (AIC) and the ventromedial prefrontal cortex (vmPFC). Food and water intake, feeding microstructure, and general motor activity were measured under two motivational conditions: food-deprived rats given standard chow or ad libitum-fed rats given a palatable chocolate shake. Muscimol infusions into the AIC diminished intake, total feeding duration, and average feeding bout duration for the palatable-food condition only but failed to alter exploratory-like behavior (ambulation or rearing). In contrast, intra-vmPFC muscimol infusions did not alter the overall intake of chow or chocolate shake. However, these infusions markedly increased mean feeding bout duration for both food types and produced a modest but significant reduction of exploratory-like behavior. The lengthening of feeding-bout duration and reduction in rearing were mimicked by intra-vmPFC blockade of AMPA-type but not NMDA-type glutamate receptors. Neither water consumption nor the microstructure of water drinking was affected by inactivation of either site. These results indicate a regional heterogeneity in frontal control of feeding behavior. Neural processing in AIC supports palatability-driven feeding but is not necessary for intake of a standard food under a food-restriction condition, whereas ventromedial prefrontal cortex, and AMPA signaling therein, modulates the duration of individual feeding bouts regardless of motivational context. Results are discussed in the context of regionally heterogeneous frontal modulation of two distinct components of feeding behavior: reward valuation based upon taste perception (AIC) vs switching between ingestive and non-ingestive (eg, exploratory-like) behavioral repertoires (vmPFC). PMID:26202102

  16. DNA nanopore translocation in glutamate solutions.

    PubMed

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

    2015-08-28

    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.

  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. Glutamate and dopamine components in schizophrenia

    PubMed Central

    Seeman, Philip

    2009-01-01

    The treatment of schizophrenia for the last half century has been with dopamine (DA) D2 receptor blockers, implicating a hyperdopamine basis for psychosis. However, a 2007 report found that the glutamate agonist LY404039 was effective in schizophrenia, suggesting a hypoglutamate state for the illness. Although phencyclidine psychosis also supports a hypoglutamate cause, assessing the basic and clinical findings shows that phencyclidine has DA D2 agonist actions as well. Accurate Dreiding models of phencyclidine and the LY glutamate agonists precisely fit the known tetrahedral model of the D2 receptor that accommodates all DA agonists. A further view is that metabotropic glutamate agonists also exert D2 agonism, and their antipsychotic doses (about 100 mg/d) are predicted by their dissociation constants (about 20 nM) for D2. Hence, the clinical antipsychotic action of a glutamate agonist may depend on its ability to interfere with DA neurotransmission by its DA partial agonism. PMID:19270765

  19. 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.

  20. 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

  1. Susceptibility to Infection and Immune Response in Insular and Continental Populations of Egyptian Vulture: Implications for Conservation

    PubMed Central

    Gangoso, Laura; Grande, Juan M.; Lemus, Jesús A.; Blanco, Guillermo; Grande, Javier; Donázar, José A.

    2009-01-01

    Background A generalized decline in populations of Old World avian scavengers is occurring on a global scale. The main cause of the observed crisis in continental populations of these birds should be looked for in the interaction between two factors - changes in livestock management, including the increased use of pharmaceutical products, and disease. Insular vertebrates seem to be especially susceptible to diseases induced by the arrival of exotic pathogens, a process often favored by human activities, and sedentary and highly dense insular scavengers populations may be thus especially exposed to infection by such pathogens. Here, we compare pathogen prevalence and immune response in insular and continental populations of the globally endangered Egyptian vulture under similar livestock management scenarios, but with different ecological and evolutionary perspectives. Methods/Principal Findings Adult, immature, and fledgling vultures from the Canary Islands and the Iberian Peninsula were sampled to determine a) the prevalence of seven pathogen taxa and b) their immunocompetence, as measured by monitoring techniques (white blood cells counts and immunoglobulins). In the Canarian population, pathogen prevalence was higher and, in addition, an association among pathogens was apparent, contrary to the situation detected in continental populations. Despite that, insular fledglings showed lower leukocyte profiles than continental birds and Canarian fledglings infected by Chlamydophila psittaci showed poorer cellular immune response. Conclusions/Significance A combination of environmental and ecological factors may contribute to explain the high susceptibility to infection found in insular vultures. The scenario described here may be similar in other insular systems where populations of carrion-eaters are in strong decline and are seriously threatened. Higher susceptibility to infection may be a further factor contributing decisively to the extinction of island scavengers

  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. Activation of Pedunculopontine Glutamate Neurons Is Reinforcing.

    PubMed

    Yoo, Ji Hoon; Zell, Vivien; Wu, Johnathan; Punta, Cindy; Ramajayam, Nivedita; Shen, Xinyi; Faget, Lauren; Lilascharoen, Varoth; Lim, Byung Kook; Hnasko, Thomas S

    2017-01-04

    Dopamine transmission from midbrain ventral tegmental area (VTA) neurons underlies behavioral processes related to motivation and drug addiction. The pedunculopontine tegmental nucleus (PPTg) is a brainstem nucleus containing glutamate-, acetylcholine-, and GABA-releasing neurons with connections to basal ganglia and limbic brain regions. Here we investigated the role of PPTg glutamate neurons in reinforcement, with an emphasis on their projections to VTA dopamine neurons. We used cell-type-specific anterograde tracing and optogenetic methods to selectively label and manipulate glutamate projections from PPTg neurons in mice. We used anatomical, electrophysiological, and behavioral assays to determine their patterns of connectivity and ascribe functional roles in reinforcement. We found that photoactivation of PPTg glutamate cell bodies could serve as a direct positive reinforcer on intracranial self-photostimulation assays. Further, PPTg glutamate neurons directly innervate VTA; photostimulation of this pathway preferentially excites VTA dopamine neurons and is sufficient to induce behavioral reinforcement. These results demonstrate that ascending PPTg glutamate projections can drive motivated behavior, and PPTg to VTA synapses may represent an important target relevant to drug addiction and other mental health disorders.

  4. 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

  5. Intracellular synthesis of glutamic acid in Bacillus methylotrophicus SK19.001, a glutamate-independent poly(γ-glutamic acid)-producing strain.

    PubMed

    Peng, Yingyun; Zhang, Tao; Mu, Wanmeng; Miao, Ming; Jiang, Bo

    2016-01-15

    Bacillus methylotrophicus SK19.001 is a glutamate-independent strain that produces poly(γ-glutamic acid) (γ-PGA), a polymer of D- and L-glutamic acids that possesses applications in food, the environment, agriculture, etc. This study was undertaken to explore the synthetic pathway of intracellular L- and D-glutamic acid in SK19.001 by investigating the effects of tricarboxylic acid cycle intermediates and different amino acids as metabolic precursors on the production of γ-PGA and analyzing the activities of the enzymes involved in the synthesis of L- and D-glutamate. Tricarboxylic acid cycle intermediates and amino acids could participate in the synthesis of γ-PGA via independent pathways in SK19.001. L-Aspartate aminotransferase, L-glutaminase and L-glutamate synthase were the enzymatic sources of L-glutamate. Glutamate racemase was responsible for the formation of D-glutamate for the synthesis of γ-PGA, and the synthetase had stereoselectivity for glutamate substrate. The enzymatic sources of L-glutamate were investigated for the first time in the glutamate-independent γ-PGA-producing strain, and multiple enzymatic sources of L-glutamate were verified in SK19.001, which will benefit efforts to improve production of γ-PGA with metabolic engineering strategies. © 2015 Society of Chemical Industry.

  6. A role for the interoceptive insular cortex in the consolidation of learned fear.

    PubMed

    Casanova, José Patricio; Madrid, Carlos; Contreras, Marco; Rodríguez, María; Vasquez, Mónica; Torrealba, Fernando

    2016-01-01

    A growing body of evidence suggests that learned fear may be related to the function of the interoceptive insular cortex. Using an auditory fear conditioning paradigm in rats, we show that the inactivation of the posterior insular cortex (pIC), the target of the interoceptive thalamus, prior to training produced a marked reduction in fear expression tested 24h later. Accordingly, post-training anisomycin infused immediately, but not 6h after, also reduced fear expression tested the following day, supporting a role for the pIC in consolidation of fear memory. The long-term (ca. a week) and reversible inactivation of the pIC with the sodium channel blocker neosaxitoxin, immediately after fear memory reactivation induced a progressive decrease in the behavioral expression of conditioned fear. In turn, we observed that fear memory reactivation is accompanied by an enhanced expression of Fos and Zif268, early genes involved in neural activity and plasticity. Taken together these data indicate that the pIC is involved in the regulation of fear memories. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. Molecular systematics of Hispaniolan pupfishes (Cyprinodontidae: Cyprinodon): implications for the biogeography of insular Caribbean fishes.

    PubMed

    Echelle, Anthony A; Fuselier, Linda; Van Den Bussche, Ronald A; Rodriguez, Carlos M L; Smith, Michael L

    2006-06-01

    We used sequence variation in the mtDNA control-region and ND2 and cyt b genes to assess the systematics and biogeography of the five species of pupfish (Cyprinodon) on Hispaniola. These include four endemics, the relatively large-bodied Cyprinodon bondi, Cyprinodon nichollsi, and Cyprinodon sp., each from a separate lake in southwestern Hispaniola, and Cyprinodon higuey from a coastal lake in eastern Hispaniola. The fifth species consists of coastal populations referable to Cyprinodon variegatus riverendi. The results indicate that Hispaniola has been invaded by at least two forms, first by a late Pliocene progenitor of Cyprinodon variegatus ovinus and the large-bodied Hispaniolan species, and, more recently, by one or more ancestral forms allied with Cyprinodon variegatus variegatus and C. v. riverendi. Levels of divergence indicate that large expanses of open sea have not acted as long-term barriers to inter-island dispersal of cyprinodontiform fishes. This study, together with the molecular systematics of other insular Caribbean fishes, indicates that most insular groups originated from late Neogene dispersal from the mainland. The patterns of mtDNA variation in Cyprinodon showed little congruence with the species/subspecies taxonomy.

  8. Involvement of the rostral agranular insular cortex in nicotine self-administration in rats.

    PubMed

    Pushparaj, Abhiram; Kim, Aaron S; Musiol, Martin; Trigo, Jose M; Le Foll, Bernard

    2015-09-01

    Our prior work demonstrated the involvement of the caudal granular subregion of the insular cortex in a rat model of nicotine self-administration. Recent studies in various animal models of addiction for nicotine and other drugs have identified a role for the rostral agranular subregion (RAIC). The current research was undertaken to examine the involvement of the RAIC in a rat model of nicotine self-administration. We investigated the inactivating effects of local infusions of a γ-aminobutyric acid agonist mixture (baclofen/muscimol) into the RAIC on nicotine self-administration under a fixed-ratio 5 (FR-5) schedule and on reinstatement of nicotine seeking induced by nicotine-associated cues in rats. We also evaluated the effects of RAIC inactivation on food self-administration under an FR5 schedule as a control. Inactivation of the RAIC decreased nicotine, but not food, self-administration. RAIC inactivation also prevented the reinstatement, after extinction, of nicotine seeking induced by nicotine-associated cues. Our study indicates that the RAIC is involved in nicotine-taking and nicotine-seeking in rats. Modulating insular cortex function appears to be a promising approach for nicotine dependence treatment.

  9. Direction-dependent activation of the insular cortex during vertical and horizontal hand movements.

    PubMed

    Rousseau, C; Fautrelle, L; Papaxanthis, C; Fadiga, L; Pozzo, T; White, O

    2016-06-14

    The planning of any motor action requires a complex multisensory processing by the brain. Gravity - immutable on Earth - has been shown to be a key input to these mechanisms. Seminal fMRI studies performed during visual perception of falling objects and self-motion demonstrated that humans represent the action of gravity in parts of the cortical vestibular system; in particular, the insular cortex and the cerebellum. However, little is known as to whether a specific neural network is engaged when processing non-visual signals relevant to gravity. We asked participants to perform vertical and horizontal hand movements without visual control, while lying in a 3T-MRI scanner. We highlighted brain regions activated in the processing of vertical movements, for which the effects of gravity changed during execution. Precisely, the left insula was activated in vertical movements and not in horizontal movements. Moreover, the network identified by contrasting vertical and horizontal movements overlapped with neural correlates previously associated to the processing of simulated self-motion and visual perception of the vertical direction. Interestingly, we found that the insular cortex activity is direction-dependent which suggests that this brain region processes the effects of gravity on the moving limbs through non-visual signals. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  10. Insular cognitive impairment at the early stage of dementia with Lewy bodies: a preliminary study.

    PubMed

    Philippi, Nathalie; Kemp, Jennifer; Constans-Erbs, Morgane; Hamdaoui, Malik; Monjoin, Laetitia; Ehrhard, Emmanuelle; Albasser, Timothée; Botzung, Anne; Demuynck, Catherine; Heim, Géraldine; Martin-Hunyadi, Catherine; Bilger, Mathias; Berly, Laetitia; Soulier, David; Cretin, Benjamin; Després, Olivier; Blanc, Frédéric

    2017-09-01

    The anterior part of the insula appears atrophied in the early stage of dementia with Lewy bodies (DLB) whereas it is not the case in early Alzheimer's disease (AD). The objective of this study was to develop neuropsychological markers supposed to reflect insular dysfunction, which would facilitate early diagnosis of DLB, namely in comparison to AD. Twelve patients with DLB, 12 patients with AD, all at the stage of Mild cognitive impairment (MCI) or mild dementia, as well as 10 Controls subjects (CS) participated in the study. Cognitive functions supposedly related to the insula were evaluated with a battery of tests: a facial expression recognition test, a test assessing the feeling of disgust with images, a test evaluating idioms' comprehension, an empathy questionnaire and a questionnaire screening for disgusting behaviors. Compared to AD patients and CS, DLB patients experienced less disgust when they were shown disgusting images, whereas their ability to recognize emotional expression of disgust appeared to be preserved. Furthermore, DLB patients seemed less empathetic than AD patients. Finally, compared to CS, DLB patients were less effective to provide an intuitive decision about idioms' signification since they needed significantly more time to answer. This preliminary study suggests the existence of a potential « insular cognitive impairment » profile in DLB at the early stage. These results provide interesting leads to develop tools facilitating the differential diagnosis of DLB and AD.

  11. Structural basis of empathy and the domain general region in the anterior insular cortex

    PubMed Central

    Mutschler, Isabella; Reinbold, Céline; Wankerl, Johanna; Seifritz, Erich; Ball, Tonio

    2013-01-01

    Empathy is key for healthy social functioning and individual differences in empathy have strong implications for manifold domains of social behavior. Empathy comprises of emotional and cognitive components and may also be closely linked to sensorimotor processes, which go along with the motivation and behavior to respond compassionately to another person's feelings. There is growing evidence for local plastic change in the structure of the healthy adult human brain in response to environmental demands or intrinsic factors. Here we have investigated changes in brain structure resulting from or predisposing to empathy. Structural MRI data of 101 healthy adult females was analyzed. Empathy in fictitious as well as real-life situations was assessed using a validated self-evaluation measure. Furthermore, empathy-related structural effects were also put into the context of a functional map of the anterior insular cortex (AIC) determined by activation likelihood estimate (ALE) meta-analysis of previous functional imaging studies. We found that gray matter (GM) density in the left dorsal AIC correlates with empathy and that this area overlaps with the domain general region (DGR) of the anterior insula that is situated in-between functional systems involved in emotion–cognition, pain, and motor tasks as determined by our meta-analysis. Thus, we propose that this insular region where we find structural differences depending on individual empathy may play a crucial role in modulating the efficiency of neural integration underlying emotional, cognitive, and sensorimotor information which is essential for global empathy. PMID:23675334

  12. Differential psychophysiological interactions of insular subdivisions during varied oropharyngeal swallowing tasks

    PubMed Central

    Humbert, Ianessa A.; McLaren, Donald G.

    2014-01-01

    Abstract The insula is a highly integrated cortical region both anatomically and functionally. It has been shown to have cognitive, social–emotional, gustatory, and sensorimotor functions. Insular involvement in both normal and abnormal swallowing behavior is well established, yet its functional connectivity is unclear. Studies of context‐dependent connectivity, or the connectivity during different task conditions, have the potential to reveal information about synaptic function of the insula. The goal of this study was to examine the functional connectivity of specific insular regions (ventral anterior, dorsal anterior, and posterior) with distant cortical regions during four swallowing conditions (water, sour, e‐stim, and visual biofeedback) using generalized psychophysiological interactions (gPPI). In 19 healthy adults, we found that the visual biofeedback condition was associated with the most and strongest increases in functional connectivity. The posterior insula/rolandic operculum regions had the largest clusters of increases in functional connectivity, but the ventral anterior insula was functionally connected to a more diverse array of cortical regions. Also, laterality assessments showed left lateralized increases in swallowing functional connectivity. Our results are aligned with reports about the insula's interconnectivity and extensive involvement in multisensory and cognitive tasks. PMID:24760502

  13. Anterior insular cortex activity to emotional salience of voices in a passive oddball paradigm

    PubMed Central

    Chen, Chenyi; Lee, Yu-Hsuan; Cheng, Yawei

    2014-01-01

    The human voice, which has a pivotal role in communication, is processed in specialized brain regions. Although a general consensus holds that the anterior insular cortex (AIC) plays a critical role in negative emotional experience, previous studies have not observed AIC activation in response to hearing disgust in voices. We used magnetoencephalography to measure the magnetic counterparts of mismatch negativity (MMNm) and P3a (P3am) in healthy adults while the emotionally meaningless syllables dada, spoken as neutral, happy, or disgusted prosodies, along with acoustically matched simple and complex tones, were presented in a passive oddball paradigm. The results revealed that disgusted relative to happy syllables elicited stronger MMNm-related cortical activities in the right AIC and precentral gyrus along with the left posterior insular cortex, supramarginal cortex, transverse temporal cortex, and upper bank of superior temporal cortex. The AIC activity specific to disgusted syllables (corrected p < 0.05) was associated with the hit rate of the emotional categorization task. These findings may clarify the neural correlates of emotional MMNm and lend support to the role of AIC in the processing of emotional salience already at the preattentive level. PMID:25346670

  14. The Cortical Signature of Central Poststroke Pain: Gray Matter Decreases in Somatosensory, Insular, and Prefrontal Cortices.

    PubMed

    Krause, T; Asseyer, S; Taskin, B; Flöel, A; Witte, A V; Mueller, K; Fiebach, J B; Villringer, K; Villringer, A; Jungehulsing, G J

    2016-01-01

    It has been proposed that cortical structural plasticity plays a crucial role in the emergence and maintenance of chronic pain. Various distinct pain syndromes have accordingly been linked to specific patterns of decreases in regional gray matter volume (GMV). However, it is not known whether central poststroke pain (CPSP) is also associated with cortical structural plasticity. To determine this, we employed T1-weighted magnetic resonance imaging at 3 T and voxel-based morphometry in 45 patients suffering from chronic subcortical sensory stroke with (n = 23) and without CPSP (n = 22), and healthy matched controls (n = 31). CPSP patients showed decreases in GMV in comparison to healthy controls, involving secondary somatosensory cortex (S2), anterior as well as posterior insular cortex, ventrolateral prefrontal and orbitofrontal cortex, temporal cortex, and nucleus accumbens. Comparing CPSP patients to nonpain patients revealed a similar but more restricted pattern of atrophy comprising S2, ventrolateral prefrontal and temporal cortex. Additionally, GMV in the ventromedial prefrontal cortex negatively correlated to pain intensity ratings. This shows for the first time that CPSP is accompanied by a unique pattern of widespread structural plasticity, which involves the sensory-discriminative areas of insular/somatosensory cortex, but also expands into prefrontal cortex and ventral striatum, where emotional aspects of pain are processed.

  15. Insular dentin formation pattern in human odontogenesis in relation to the scalloped dentino-enamel junction.

    PubMed

    Radlanski, Ralf J; Renz, Herbert

    2007-01-01

    This study is a first report on the modality of early dentin formation in respect to the scalloped pattern of the dentino-enamel junction (DEJ). We applied scanning electron microscopy (SEM), transmission electron microscopy (TEM), histological serial sections, and three-dimensional (3D) reconstructions. TEM and SEM showed scallops and secondary scallops on the DEJ of deciduous dental primordia and on deciduous teeth with the enamel cap removed. This peculiar outline of the DEJ requires a specific dentin formation pattern; histological sections showed that dentin formation began at the brims of the scallops, seen as triangular spikes in serial sections. The dentin formation front was not uniform; instead, it was characterized by multiple, insular forming centers, as revealed by our 3D reconstructions. As thicker dentin layers formed, the islands became confluent. Factors are discussed, which may lead to crimpling of the inner enamel epithelium, and maintained as the scalloped pattern of the DEJ develops. Signaling patterns in accordance with the insular dentin formation are unknown so far.

  16. Island colonization and evolution of the insular woody habit in Echium L. (Boraginaceae).

    PubMed Central

    Böhle, U R; Hilger, H H; Martin, W F

    1996-01-01

    Numerous island-inhabiting species of predominantly herbaceous angiosperm genera are woody shrubs or trees. Such "insular woodiness" is strongly manifested in the genus Echium, in which the continental species of circummediterranean distribution are herbaceous, whereas endemic species of islands along the Atlantic coast of north Africa are woody perennial shrubs. The history of 37 Echium species was traced with 70 kb of noncoding DNA determined from both chloroplast and nuclear genomes. In all, 239 polymorphic positions with 137 informative sites, in addition to 27 informative indels, were found. Island-dwelling Echium species are shown to descend from herbaceous continental ancestors via a single island colonization event that occurred < 20 million years ago. Founding colonization appears to have taken place on the Canary Islands, from which the Madeira and Cape Verde archipelagos were invaded. Colonization of island habitats correlates with a recent origin of perennial woodiness from herbaceous habit and was furthermore accompanied by intense speciation, which brought forth remarkable diversity of forms among contemporary island endemics. We argue that the origin of insular woodiness involved response to counter-selection of inbreeding depression in founding island colonies. Images Fig. 1 Fig. 3 PMID:8876207

  17. Glutamate formation via the leucine-to-glutamate pathway of rat pancreas.

    PubMed

    Schachter, David; Buteau, Jean

    2014-06-01

    The leucine-to-glutamate (Leu→Glu) pathway, which metabolizes the carbon atoms of l-leucine to form l-glutamate, was studied by incubation of rat tissue segments with l-[U-(14)C]leucine and estimation of the [(14)C]glutamate formed. Metabolism of the leucine carbon chain occurs in most rat tissues, but maximal activity of the Leu→Glu pathway for glutamate formation is limited to the thoracic aorta and pancreas. In rat aorta, the Leu→Glu pathway functions to relax the underlying smooth muscle; its functions in the pancreas are unknown. This report characterizes the Leu→Glu pathway of rat pancreas and develops methods to examine its functions. Pancreatic segments effect net formation of glutamate on incubation with l-leucine, l-glutamine, or a mix of 18 other plasma amino acids at their concentrations in normal rat plasma. Glutamate formed from leucine remains mainly in the tissue, whereas that from glutamine enters the medium. The pancreatic Leu→Glu pathway uses the leucine carbons for net glutamate formation; the α-amino group is not used; the stoichiometry is as follows: 1 mol of leucine yields 2 mol of glutamate (2 leucine carbons per glutamate) plus 2 mol of CO2. Comparison of the Leu→Glu pathway in preparations of whole pancreatic segments, isolated acini, and islets of Langerhans localizes it in the acini; relatively high activity is found in cultures of the AR42J cell line and very little in the INS-1 832/13 cell line. Pancreatic tissue glutamate concentration is homeostatically regulated in the range of ∼1-3 μmol/g wet wt. l-Valine and leucine ethyl, benzyl, and tert-butyl esters inhibit the Leu→Glu pathway without decreasing tissue total glutamate.

  18. Intracellular levels of glutamate in swollen astrocytes are preserved via neurotransmitter reuptake and de novo synthesis: implications for hyponatremia.

    PubMed

    Schober, Alexandra L; Mongin, Alexander A

    2015-10-01

    Hyponatremia and several other CNS pathologies are associated with substantial astrocytic swelling. To counteract cell swelling, astrocytes lose intracellular osmolytes, including l-glutamate and taurine, through volume-regulated anion channel. In vitro, when swollen by exposure to hypo-osmotic medium, astrocytes lose endogenous taurine faster, paradoxically, than l-glutamate or l-aspartate. Here, we explored the mechanisms responsible for differences between the rates of osmolyte release in primary rat astrocyte cultures. In radiotracer assays, hypo-osmotic efflux of preloaded [(14) C]taurine was indistinguishable from d-[(3) H]aspartate and only 30-40% faster than l-[(3) H]glutamate. However, when we used HPLC to measure the endogenous intracellular amino acid content, hypo-osmotic loss of taurine was approximately fivefold greater than l-glutamate, and no loss of l-aspartate was detected. The dramatic difference between loss of endogenous taurine and glutamate was eliminated after inhibition of both glutamate reuptake [with 300 μM dl-threo-β-benzyloxyaspartic acid (TBOA)] and glutamate synthesis by aminotransferases [with 1 mM aminooxyacetic acid (AOA)]. Treatment with TBOA+AOA made reductions in the intracellular taurine and l-glutamate levels approximately equal. Taken together, these data suggest that swollen astrocytes actively conserve intracellular glutamate via reuptake and de novo synthesis. Our findings likely also explain why in animal models of acute hyponatremia, extracellular levels of taurine are dramatically elevated with minimal impact on extracellular l-glutamate. We identified mechanisms that allow astrocytes to conserve intracellular l-glutamate (Glu) upon exposure to hypo-osmotic environment. Cell swelling activates volume-regulated anion channel (VRAC) and triggers loss of Glu, taurine (Tau), and other cytosolic amino acids. Glu is conserved via reuptake by Na(+) -dependent transporters and de novo synthesis in the reactions of

  19. Digestive physiology of the pig symposium: detection of dietary glutamate via gut-brain axis.

    PubMed

    Bannai, M; Torii, K

    2013-05-01

    Gustatory and visceral stimulation from food regulates digestion and nutrient use. Free L-glutamate (Glu) release from digested protein is responsible for umami taste perception in the gut. Moreover, monosodium Glu (MSG) is widely used as a flavor enhancer to add umami taste in various cuisines. Recent studies indicate that dietary Glu sensors and their signal transduction system exist in both gut mucosa and taste cells. Oral Glu sensing has been well studied. In this review, we focus on the role of Glu on digestion and absorption of food. Infusion of Glu into the stomach and intestine increase afferent nerve activity of the gastric and the celiac branches of the vagus nerve, respectively. Luminal Glu also evokes efferent nerve activation of the abdominal vagus nerve branches simultaneously. Additionally, intragastric infusion of Glu activates the insular cortex, limbic system, hypothalamus, nucleus tractus solitaries, and amygdala, as determined by functional magnetic resonance imaging, and is able to induce flavor-preference learning as a result of postingestive effects in rats. These results indicate that Glu signaling via gustatory and visceral pathways plays an important role in the processes of digestion, absorption, metabolism, and other physiological functions via activation of the brain.

  20. Effects of N-acetylcysteine amide (NACA), a novel thiol antioxidant against glutamate-induced cytotoxicity in neuronal cell line PC12.

    PubMed

    Penugonda, Suman; Mare, Suneetha; Goldstein, Glenn; Banks, William A; Ercal, Nuran

    2005-09-21

    Oxidative stress plays an important role in neuronal cell death associated with many different neurodegenerative conditions such as cerebral ischemia and Parkinson's disease. Elevated levels of glutamate are thought to be responsible for CNS disorders through various mechanisms causing oxidative stress induced by a nonreceptor-mediated oxidative pathway which blocks cystine uptake and results in depletion of intracellular glutathione (GSH). The newly designed amide form of N-acetylcysteine (NAC), N-acetylcysteine amide (NACA), was assessed for its ability to protect PC12 cells against oxidative toxicity induced by glutamate. NACA was shown to protect PC12 cells from glutamate (Glu) toxicity, as evaluated by LDH and MTS assays. NACA prevented glutamate-induced intracellular GSH loss. In addition, NACA restored GSH synthesis in a Glu (10 mM) plus buthionine-sulfoximine (BSO) (0.2 mM)-treated group, indicating that the intracellular GSH increase is independent of gamma-GSC (gamma-glutamylcysteinyl synthetase). The increase in levels of reactive oxygen species (ROS) induced by glutamate was significantly decreased by NACA. Measurement of malondialdehyde (MDA) showed that NACA reduced glutamate-induced elevations in levels of lipid peroxidation by-products. These results demonstrate that NACA can protect PC12 cells against glutamate cytotoxicity by inhibiting lipid peroxidation, and scavenging ROS, thus preserving intracellular GSH.

  1. 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)

  2. A Novel Amperometric Glutamate Biosensor Based on Glutamate Oxidase Adsorbed on Silicalite

    NASA Astrophysics Data System (ADS)

    Soldatkina, O. V.; Soldatkin, O. O.; Kasap, B. Ozansoy; Kucherenko, D. Yu.; Kucherenko, I. S.; Kurc, B. Akata; Dzyadevych, S. V.

    2017-04-01

    In this work, we developed a new amperometric biosensor for glutamate detection using a typical method of glutamate oxidase (GlOx) immobilization via adsorption on silicalite particles. The disc platinum electrode ( d = 0.4 mm) was used as the amperometric sensor. The procedure of biosensor preparation was optimized. The main parameters of modifying amperometric transducers with a silicalite layer were determined along with the procedure of GlOx adsorption on this layer. The biosensors based on GlOx adsorbed on silicalite demonstrated high sensitivity to glutamate. The linear range of detection was from 2.5 to 450 μM, and the limit of glutamate detection was 1 μM. It was shown that the proposed biosensors were characterized by good response reproducibility during hours of continuous work and operational stability for several days. The developed biosensors could be applied for determination of glutamate in real samples.

  3. Lysergic acid diethylamide and [-]-2,5-dimethoxy-4-methylamphetamine increase extracellular glutamate in rat prefrontal cortex.

    PubMed

    Muschamp, John W; Regina, Meredith J; Hull, Elaine M; Winter, Jerrold C; Rabin, Richard A

    2004-10-08

    The ability of hallucinogens to increase extracellular glutamate in the prefrontal cortex (PFC) was assessed by in vivo microdialysis. The hallucinogen lysergic acid diethylamide (LSD; 0.1 mg/kg, i.p.) caused a time-dependent increase in PFC glutamate that was blocked by the 5-HT(2A) antagonist M100907 (0.05 mg/kg, i.p.). Similarly, the 5-HT(2A/C) agonist [-]-2,5-dimethoxy-4-methylamphetamine (DOM; 0.6 mg/kg, i.p.), which is a phenethylamine hallucinogen, increased glutamate to 206% above saline-treated controls. When LSD (10 microM) was directly applied to the PFC by reverse dialysis, a rapid increase in PFC glutamate levels was observed. Glutamate levels in the PFC remained elevated after the drug infusion was discontinued. These data provide direct evidence in vivo for the hypothesis that an enhanced release of glutamate is a common mechanism in the action of hallucinogens.

  4. "There Are No Housewives on 'Star Trek'": A Reexamination of Exit Rights for the Children of Insular Fundamentalist Parents

    ERIC Educational Resources Information Center

    McAvoy, Paula

    2012-01-01

    In this essay, Paula McAvoy addresses the problem caused by the liberal state's necessary tolerance of insular fundamentalist groups and the concern that children raised in such groups do not have a fair opportunity to evaluate their inherited beliefs. This tension comes to the fore around disagreements over schooling and requests for religious…

  5. "There Are No Housewives on 'Star Trek'": A Reexamination of Exit Rights for the Children of Insular Fundamentalist Parents

    ERIC Educational Resources Information Center

    McAvoy, Paula

    2012-01-01

    In this essay, Paula McAvoy addresses the problem caused by the liberal state's necessary tolerance of insular fundamentalist groups and the concern that children raised in such groups do not have a fair opportunity to evaluate their inherited beliefs. This tension comes to the fore around disagreements over schooling and requests for religious…

  6. Decreased Functional Connectivity of Insular Cortex in Drug Naïve First Episode Schizophrenia: In Relation to Symptom Severity

    PubMed Central

    Pang, Lijuan; Kennedy, David; Wei, Qinling; Lv, Luxian; Gao, Jinsong; Li, Hong; Quan, Meina; Li, Xue; Yang, Yongfeng; Fan, Xiaoduo; Song, Xueqin

    2017-01-01

    Background This study was to examine the insular cortical functional connectivity in drug naïve patients with first episode schizophrenia and to explore the relationship between the connectivity and the severity of clinical symptoms. Methods Thirty-seven drug naïve patients with schizophrenia and 25 healthy controls were enrolled in this study. A seed-based approach was used to analyze the resting-state functional imaging data. Insular cortical connectivity maps were bilaterally extracted for group comparison and validated by voxel-based morphometry (VBM) analysis. Clinical symptoms were measured using the Positive and Negative Syndrome Scale (PANSS). Results There were significant reductions in the right insular cortical connectivity with the Heschl’s gyrus, anterior cingulate cortex (ACC), and caudate (p’s<0.001) in the patient group compared with the healthy control (HC) group. Reduced right insular cortical connectivity with the Heschl’s gyrus was further confirmed in the VBM analysis (FDR corrected p<0.05). Within the patient group, there was a significant positive relationship between the right insula-Heschl’s connectivity and PANSS general psychopathology scores (r = 0.384, p = 0.019). Conclusion Reduced insula-Heschl’s functional connectivity is present in drug naïve patients with first episode schizophrenia, which might be related to the manifestation of clinical symptoms. PMID:28107346

  7. 40 CFR 33.412 - Must an Insular Area or Indian Tribal Government recipient negotiate fair share objectives?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Government recipient negotiate fair share objectives? 33.412 Section 33.412 Protection of Environment... ENTERPRISES IN UNITED STATES ENVIRONMENTAL PROTECTION AGENCY PROGRAMS Fair Share Objectives § 33.412 Must an Insular Area or Indian Tribal Government recipient negotiate fair share objectives? The requirements in...

  8. 40 CFR 33.412 - Must an Insular Area or Indian Tribal Government recipient negotiate fair share objectives?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Government recipient negotiate fair share objectives? 33.412 Section 33.412 Protection of Environment... ENTERPRISES IN UNITED STATES ENVIRONMENTAL PROTECTION AGENCY PROGRAMS Fair Share Objectives § 33.412 Must an Insular Area or Indian Tribal Government recipient negotiate fair share objectives? The requirements in...

  9. 40 CFR 33.412 - Must an Insular Area or Indian Tribal Government recipient negotiate fair share objectives?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Government recipient negotiate fair share objectives? 33.412 Section 33.412 Protection of Environment... ENTERPRISES IN UNITED STATES ENVIRONMENTAL PROTECTION AGENCY PROGRAMS Fair Share Objectives § 33.412 Must an Insular Area or Indian Tribal Government recipient negotiate fair share objectives? The requirements in...

  10. How can an inert gas counterbalance a NMDA-induced glutamate release?

    PubMed

    Vallee, Nicolas; Rostain, Jean-Claude; Risso, Jean-Jacques

    2009-12-01

    Previous neurochemical studies performed in rats have revealed a decrease of striatal dopamine and glutamate induced by inert gas narcosis. We sought to establish the hypothetical role of glutamate and its main receptor, the N-methyl-d-aspartate (NMDA) receptor, in this syndrome. We aimed to counteract the nitrogen narcosis-induced glutamate and dopamine decreases by stimulating the NMDA receptor in the striatum. We used bilateral retrodialysis on awake rats, submitted to nitrogen under pressure (3 MPa). Continuous infusion of 2 mM of NMDA under normobaric conditions (0.01 MPa) (n = 8) significantly increased extracellular average levels of glutamate, aspartate, glutamine, and asparagine by 241.8%, 292.5%, 108.3%, and 195.3%, respectively. The same infusion conducted under nitrogen at 3 MPa (n = 6) revealed significant lower levels of these amino acids (n = 8/6, P > 0.001). In opposition, the NMDA-induced effects on dopamine, dihydrophenylacetic acid (DOPAC), and homovanillic acid (HVA) levels were statistically not affected by the nitrogen at 3 MPa exposure (n = 8/6, P > 0.05). Dopamine was increased by >240% on average. HVA was decreased (down to 40%), and there was no change in DOPAC levels, in both conditions. Results highlight that the NMDA receptor is not directly affected by nitrogen under pressure as indicated by the elevation in NMDA-induced dopamine release under hyperbaric nitrogen. On the other hand, the NMDA-evoked glutamate increase is counteracted by nitrogen narcosis. No improvement in motor and locomotor disturbances was observed with high striatal concentration in dopamine. Further experiments have to be done to specify why the striatal glutamate pathways, in association with the inhibition of its metabolism, only are affected by nitrogen narcosis in this study.

  11. Markers of Glutamate Synaptic Transmission and Plasticity are Increased in the Anterior Cingulate Cortex in Bipolar Disorder

    PubMed Central

    Eastwood, Sharon L.; Harrison, Paul J.

    2010-01-01

    Background Cortical glutamate levels are elevated in bipolar disorder, but the interpretation of this increase is unclear, since glutamate has metabolic as well as neurotransmitter roles. We investigated this by measuring vesicular glutamate transporter 1 (VGluT1) expression, which reflects activity at glutamate synapses. We also measured netrin-G1 and -G2 mRNAs since these genes are involved in the formation and plasticity of glutamatergic connections. Methods Using qPCR we quantified transcripts for VGluT1, netrin-G1 (isoforms G1c, G1d and G1f), and netrin-G2, in the anterior cingulate cortex from subjects with bipolar disorder (n=34), schizophrenia (n=35), and healthy controls (n=35). Results VGluT1, netrin-G2, and netrin-G1d and G1f, were increased in bipolar disorder but not in schizophrenia. Netrin-G1c did not differ between groups. Netrin-G1c and G1f expression showed left-right asymmetries. VGluT1 mRNA correlated with brain weight. Conclusions Increased VGluT1 expression is supportive of elevated glutamate neurotransmission in the anterior cingulate cortex in bipolar disorder. The netrin-G1 and netrin-G2 findings suggest there may be an underlying difference in the plasticity of the affected circuitry. PMID:20079890

  12. 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

  13. Characterization of a plant glutamate receptor activity.

    PubMed

    Teardo, Enrico; Segalla, Anna; Formentin, Elide; Zanetti, Manuela; Marin, Oriano; Giacometti, Giorgio Mario; Lo Schiavo, Fiorella; Zoratti, Mario; Szabò, Ildikò

    2010-01-01

    Bioinformatic approaches have allowed the identification of twenty genes, grouped into three subfamilies, encoding for homologues of animal ionotropic glutamate receptors (iGLRs) in the Arabidopsis thaliana model plant. Indirect evidence suggests that plant iGLRs function as non-selective cation channels. In the present work we provide biochemical and electrophysiological evidences for the chloroplast localization of glutamate receptor(s) of family 3 (iGLR3) in spinach. A specific antibody, recognizing putative receptors of family 3 locates iGLR3 to the inner envelope membrane of chloroplasts. In planar lipid bilayer experiments, purified inner envelope vesicles from spinach display a cation-selective electrophysiological activity which is inhibited by DNQX (6,7-dinitroquinoxaline-2,3-dione), considered to act as an inhibitor on both animal and plant iGLRs. These results identify for the first time the intracellular localization of plant glutamate receptor(s) and a DNQX-sensitive, glutamate-gated activity at single channel level in native membrane with properties compatible with those predicted for plant glutamate receptors. Copyright 2010 S. Karger AG, Basel.

  14. Presynaptic glutamate receptors: physiological functions and mechanisms of action.

    PubMed

    Pinheiro, Paulo S; Mulle, Christophe

    2008-06-01

    Glutamate acts on postsynaptic glutamate receptors to mediate excitatory communication between neurons. The discovery that additional presynaptic glutamate receptors can modulate neurotransmitter release has added complexity to the way we view glutamatergic synaptic transmission. Here we review evidence of a physiological role for presynaptic glutamate receptors in neurotransmitter release. We compare the physiological roles of ionotropic and metabotropic glutamate receptors in short- and long-term regulation of synaptic transmission. Furthermore, we discuss the physiological conditions that are necessary for their activation, the source of the glutamate that activates them, their mechanisms of action and their involvement in higher brain function.

  15. Monitoring of the velocity of high-affinity glutamate uptake by isolated brain nerve terminals using amperometric glutamate biosensor.

    PubMed

    Soldatkin, O; Nazarova, A; Krisanova, N; Borуsov, A; Kucherenko, D; Kucherenko, I; Pozdnyakova, N; Soldatkin, A; Borisova, T

    2015-04-01

    Glutamate is the major excitatory neurotransmitter in the central nervous system, which is involved in the main aspects of normal brain functioning. High-affinity Na(+)-dependent glutamate transporters is key proteins, which transport extracellular glutamate to the cytoplasm of nerve cells, thereby preventing continuous activation of glutamate receptors, and thus the development of neurotoxicity. Disturbance in glutamate uptake is involved in the pathogenesis of major neurological disorders. Amperometric biosensors are the most promising and successful among electrochemical biosensors. In this study, we developed (1) amperometric glutamate biosensor, (2) methodological approach for the analysis of glutamate uptake in liquid samples of isolated rat brain nerve terminals (synaptosomes). The basal level of glutamate, the initial velocity of glutamate uptake and time-dependent accumulation of glutamate by synaptosomes were determined using developed glutamate biosensor. Comparative analysis of the data with those obtained by radioactive analysis, spectrofluorimetry and ion exchange chromatography was performed. Therefore, the methodological approach for monitoring of the velocity of glutamate uptake, which takes into consideration the definite level of endogenous glutamate in nerve terminals, was developed using glutamate biosensor. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. Sex Differences in Insular Cortex Gyri Responses to the Valsalva Maneuver

    PubMed Central

    Macey, Paul M.; Rieken, Nicholas S.; Kumar, Rajesh; Ogren, Jennifer A.; Middlekauff, Holly R.; Wu, Paula; Woo, Mary A.; Harper, Ronald M.

    2016-01-01

    Sex differences in autonomic regulation may underlie cardiovascular disease variations between females and males. One key autonomic brain region is the insular cortex, which typically consists of five main gyri in each hemisphere, and shows a topographical organization of autonomic function across those gyri. The present study aims to identify possible sex differences in organization of autonomic function in the insula. We studied brain functional magnetic resonance imaging (fMRI) responses to a series of four 18-s Valsalva maneuvers in 22 healthy females (age ± SD: 50.0 ± 7.9 years) and 36 healthy males (45.3 ± 9.2 years). Comparisons of heart rate (HR) and fMRI signals were performed with repeated measures ANOVA (threshold P < 0.05 for all findings). All subjects achieved the target 30 mmHg expiratory pressure for all challenges. Typical HR responses were elicited by the maneuver, including HR increases from ~4 s into the strain period (Phase II) and rapid declines to below baseline 5–10 s, following strain release (Phase IV). Small, but significant, sex differences in HR percent change occurred during the sympathetic-dominant Phase II (female < male) and parasympathetic-dominant Phase IV (female > male, i.e., greater undershoot in males). The insular cortices showed similar patterns in all gyri, with greater signal decreases in males than females. Both sexes exhibited an anterior–posterior topographical organization of insular responses during Phase II, with anterior gyri showing higher responses than more posterior gyri. The exception was the right anterior-most gyrus in females, which had lower responses than the four other right gyri. Responses were lateralized, with right-sided dominance during Phase II in both sexes, except the right anterior-most gyrus in females, which showed lower responses than the left. The findings confirm the anterior and right-sided sympathetic dominance of the insula. Although sex

  17. Insular East Asia pig dispersal and vicariance inferred from Asian wild boar genetic evidence.

    PubMed

    Li, K Y; Li, K T; Yang, C H; Hwang, M H; Chang, S W; Lin, S M; Wu, H J; Basilio, E B; Vega, R S A; Laude, R P; Ju, Y T

    2017-04-01

    The Formosan wild boar () is an endemic subspecies in Taiwan. Understanding the origins and spread of the Formosan wild boar could help clarify East Asian wild boar dispersion. Although in situ domestication of the wild boar occurred at a number of domestication centers across East Asia, corroborating archaeological and genetic evidence of pig domestication on Taiwan is lacking, leading to domestication being described as cryptic. This characterization applies to the Lanyu pig-a domestic pig breed found on Taiwan. To better understand pig domestication, this study examines the sympatric Formosan wild boar and domestic Lanyu pig to build a model of potential wild boar domestication on Taiwan and elucidate wild boar domestication patterns in the region. To this end, a comprehensive phylogenetic study of the Formosan wild boar and the Lanyu pig was conducted on animals sourced from Taiwan, Lanyu, and the Philippines. Phylogenetic analyses were conducted using full mitochondrial control-region sequences from 345 wild boars and domestic pigs. These were studied in concert with existing reports on 206 Asian wild boars. Genetic characteristics and Bayesian phylogenetic tree results identified 2 wild boar lineages of remote phylogenetic relationship. These were Formosan wild boar lineage (FWBL) and Formosan wild boar with Lanyu sign lineage (FWBLYL). Molecular clock analyses indicate that FWBLYL diverged earlier than other insular East Asia wild boars and show that FWBLYL and FWBL diverged approximately 0.60 million years ago. This result supports boars of FWBLYL being the earliest wild boars to have spread and become isolated in insular East Asia. In addition, the study proposes 6 Asian wild boar dispersion routes during glacial periods. At least 3 of these events occurred in insular East Asia with subsequent geographical isolation after glacial recession. This isolation potentially led to allopatric differentiation of wild boar subspecies. Also, the similar genetic

  18. Impact of plasma transaminase levels on the peripheral blood glutamate levels and memory functions in healthy subjects.

    PubMed

    Kamada, Yoshihiro; Hashimoto, Ryota; Yamamori, Hidenaga; Yasuda, Yuka; Takehara, Tetsuo; Fujita, Yuko; Hashimoto, Kenji; Miyoshi, Eiji

    2016-06-01

    Blood aspartate aminotransferase (AST) and alanine transaminase (ALT) levels are the most frequently reliable biomarkers of liver injury. Although AST and ALT play central roles in glutamate production as transaminases, peripheral blood levels of AST and ALT have been regarded only as liver injury biomarkers. Glutamate is a principal excitatory neurotransmitter, which affects memory functions in the brain. In this study, we investigated the impact of blood transaminase levels on blood glutamate concentration and memory. Psychiatrically, medically, and neurologically healthy subjects (n = 514, female/male: 268/246) were enrolled in this study through local advertisements. Plasma amino acids (glutamate, glutamine, glycine, d-serine, and l-serine) were measured using a high performance liquid chromatography system. The five indices, verbal memory, visual memory, general memory, attention/concentration, and delayed recall of the Wechsler Memory Scale-Revised were used to measure memory functions. Both plasma AST and ALT had a significant positive correlation with plasma glutamate levels. Plasma AST and ALT levels were significantly negatively correlated with four of five memory functions, and plasma glutamate was significantly negatively correlated with three of five memory functions. Multivariate analyses demonstrated that plasma AST, ALT, and glutamate levels were significantly correlated with memory functions even after adjustment for gender and education. As far as we know, this is the first report which could demonstrate the impact of blood transaminase levels on blood glutamate concentration and memory functions in human. These findings are important for the interpretation of obesity-induced metabolic syndrome with elevated transaminases and cognitive dysfunction.

  19. Glutamate excitotoxicity induced by orally administered propionic acid, a short chain fatty acid can be ameliorated by bee pollen.

    PubMed

    El-Ansary, Afaf; Al-Salem, Huda S; Asma, Alqahtani; Al-Dbass, Abeer

    2017-05-22

    Rodent models may guide investigations towards identifying either environmental neuro-toxicants or drugs with neuro-therapeutic effects. This work aims to study the therapeutic effects of bee pollen on brain glutamate excitotoxicity and the impaired glutamine-glutamate- gamma amino butyric acid (GABA) circuit induced by propionic acid (PPA), a short chain fatty acid, in rat pups. Twenty-four young male Western Albino rats 3-4 weeks of age, and 45-60 g body weight were enrolled in the present study. They were grouped into four equal groups: Group 1, the control received phosphate buffered saline at the same time of PPA adminstration; Group 2, received 750 mg/kg body weight divided into 3 equal daily doses and served as acute neurotoxic dose of PPA; Group 3, received 750 mg/kg body weight divided in 10 equal doses of 75 mg/kg body weight/day, and served as the sub-acute group; and Group 4, the therapeutic group, was treated with bee pollen (50 mg/kg body weight) for 30 days after acute PPA intoxication. GABA, glutamate and glutamine were measured in the brain homogenates of the four groups. The results showed that PPA caused multiple signs of excitotoxicity, as measured by the elevation of glutamate and the glutamate/glutamine ratio and the decrease of GABA, glutamine and the GABA/glutamate ratio. Bee pollen was effective in counteracting the neurotoxic effects of PPA to a certain extent. In conclusion, bee pollen demonstrates ameliorating effects on glutamate excitotoxicity and the impaired glutamine-glutamate-GABA circuit as two etiological mechanisms in PPA-induced neurotoxicity.

  20. Acute Stress Increases Depolarization-Evoked Glutamate Release in the Rat Prefrontal/Frontal Cortex: The Dampening Action of Antidepressants

    PubMed Central

    Farisello, Pasqualina; Zappettini, Simona; Tardito, Daniela; Barbiero, Valentina S.; Bonifacino, Tiziana; Mallei, Alessandra; Baldelli, Pietro; Racagni, Giorgio; Raiteri, Maurizio; Benfenati, Fabio; Bonanno, Giambattista; Popoli, Maurizio

    2010-01-01

    Background Behavioral stress is recognized as a main risk factor for neuropsychiatric diseases. Converging evidence suggested that acute stress is associated with increase of excitatory transmission in certain forebrain areas. Aim of this work was to investigate the mechanism whereby acute stress increases glutamate release, and if therapeutic drugs prevent the effect of stress on glutamate release. Methodology/Findings Rats were chronically treated with vehicle or drugs employed for therapy of mood/anxiety disorders (fluoxetine, desipramine, venlafaxine, agomelatine) and then subjected to unpredictable footshock stress. Acute stress induced marked increase in depolarization-evoked release of glutamate from synaptosomes of prefrontal/frontal cortex in superfusion, and the chronic drug treatments prevented the increase of glutamate release. Stress induced rapid increase in the circulating levels of corticosterone in all rats (both vehicle- and drug-treated), and glutamate release increase was blocked by previous administration of selective antagonist of glucocorticoid receptor (RU 486). On the molecular level, stress induced accumulation of presynaptic SNARE complexes in synaptic membranes (both in vehicle- and drug-treated rats). Patch-clamp recordings of pyramidal neurons in the prefrontal cortex revealed that stress increased glutamatergic transmission through both pre- and postsynaptic mechanisms, and that antidepressants may normalize it by reducing release probability. Conclusions/Significance Acute footshock stress up-regulated depolarization-evoked release of glutamate from synaptosomes of prefrontal/frontal cortex. Stress-induced increase of glutamate release was dependent on stimulation of glucocorticoid receptor by corticosterone. Because all drugs employed did not block either elevation of corticosterone or accumulation of SNARE complexes, the dampening action of the drugs on glutamate release must be downstream of these processes. This novel effect of

  1. Acute stress increases depolarization-evoked glutamate release in the rat prefrontal/frontal cortex: the dampening action of antidepressants.

    PubMed

    Musazzi, Laura; Milanese, Marco; Farisello, Pasqualina; Zappettini, Simona; Tardito, Daniela; Barbiero, Valentina S; Bonifacino, Tiziana; Mallei, Alessandra; Baldelli, Pietro; Racagni, Giorgio; Raiteri, Maurizio; Benfenati, Fabio; Bonanno, Giambattista; Popoli, Maurizio

    2010-01-05

    Behavioral stress is recognized as a main risk factor for neuropsychiatric diseases. Converging evidence suggested that acute stress is associated with increase of excitatory transmission in certain forebrain areas. Aim of this work was to investigate the mechanism whereby acute stress increases glutamate release, and if therapeutic drugs prevent the effect of stress on glutamate release. Rats were chronically treated with vehicle or drugs employed for therapy of mood/anxiety disorders (fluoxetine, desipramine, venlafaxine, agomelatine) and then subjected to unpredictable footshock stress. Acute stress induced marked increase in depolarization-evoked release of glutamate from synaptosomes of prefrontal/frontal cortex in superfusion, and the chronic drug treatments prevented the increase of glutamate release. Stress induced rapid increase in the circulating levels of corticosterone in all rats (both vehicle- and drug-treated), and glutamate release increase was blocked by previous administration of selective antagonist of glucocorticoid receptor (RU 486). On the molecular level, stress induced accumulation of presynaptic SNARE complexes in synaptic membranes (both in vehicle- and drug-treated rats). Patch-clamp recordings of pyramidal neurons in the prefrontal cortex revealed that stress increased glutamatergic transmission through both pre- and postsynaptic mechanisms, and that antidepressants may normalize it by reducing release probability. Acute footshock stress up-regulated depolarization-evoked release of glutamate from synaptosomes of prefrontal/frontal cortex. Stress-induced increase of glutamate release was dependent on stimulation of glucocorticoid receptor by corticosterone. Because all drugs employed did not block either elevation of corticosterone or accumulation of SNARE complexes, the dampening action of the drugs on glutamate release must be downstream of these processes. This novel effect of antidepressants on the response to stress, shown here for

  2. Right insular damage decreases heartbeat awareness and alters cardio-visual effects on bodily self-consciousness.

    PubMed

    Ronchi, Roberta; Bello-Ruiz, Javier; Lukowska, Marta; Herbelin, Bruno; Cabrilo, Ivan; Schaller, Karl; Blanke, Olaf

    2015-04-01

    Recent evidence suggests that multisensory integration of bodily signals involving exteroceptive and interoceptive information modulates bodily aspects of self-consciousness such as self-identification and self-location. In the so-called Full Body Illusion subjects watch a virtual body being stroked while they perceive tactile stimulation on their own body inducing illusory self-identification with the virtual body and a change in self-location towards the virtual body. In a related illusion, it has recently been shown that similar changes in self-identification and self-location can be observed when an interoceptive signal is used in association with visual stimulation of the virtual body (i.e., participants observe a virtual body illuminated in synchrony with their heartbeat). Although brain imaging and neuropsychological evidence suggest that the insular cortex is a core region for interoceptive processing (such as cardiac perception and awareness) as well as for self-consciousness, it is currently not known whether the insula mediates cardio-visual modulation of self-consciousness. Here we tested the involvement of insular cortex in heartbeat awareness and cardio-visual manipulation of bodily self-consciousness in a patient before and after resection of a selective right neoplastic insular lesion. Cardio-visual stimulation induced an abnormally enhanced state of bodily self-consciousness; in addition, cardio-visual manipulation was associated with an experienced loss of the spatial unity of the self (illusory bi-location and duplication of his body), not observed in healthy subjects. Heartbeat awareness was found to decrease after insular resection. Based on these data we propose that the insula mediates interoceptive awareness as well as cardio-visual effects on bodily self-consciousness and that insular processing of interoceptive signals is an important mechanism for the experienced unity of the self. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. Late Miocene insular mice from the Tusco-Sardinian palaeobioprovince provide new insights on the palaeoecology of the Oreopithecus faunas.

    PubMed

    Casanovas-Vilar, Isaac; van Dam, Jan A; Moyà-Solà, Salvador; Rook, Lorenzo

    2011-07-01

    Oreopithecus bambolii is one of the few hominoids that evolved under insular conditions, resulting in the development of unique adaptations that have fueled an intensive debate. The palaeoenvironment associated with this great ape has been the subject of great controversy as well. On the one hand, palaeobotanical data indicate that Oreopithecus likely inhabited mixed mesophytic forests interrupted by swamps; on the other hand, an abundance of hypsodont bovids points towards the existence of dry and open environments. Here, we provide a new approach based on the ecomorphology of the extinct endemic Muridae (rats and mice) of the so-called Oreopithecus faunas. Our results show that the successive species of endemic insular murids (Huerzelerimys and Anthracomys) evolved a number of adaptations observed only in extant family members that include significant proportions of grass in their diet. While this fits the pattern exhibited by large mammals, it contrasts with the available palaeobotanical information, which indicates that grasses were minor components of the vegetation. This contradiction may be explained because these endemic murids may have been adapted to the consumption of particular food items such as hard parts of aquatic plants (as shown by some extant murid species). However, because it is unlikely that the remaining herbivore mammals were adapted to this diet as well, we favour an alternative hypothesis that takes into account the peculiar ecological conditions of insular ecosystems leading to a density-dependent selective regime with strong competition. Such a regime would promote the selection of dental adaptations to increase feeding efficiency and durability of the dentition (such as hypsodonty) as seen in some fossil insular ruminants. This hypothesis requires further testing, but may partly account for parallel evolution of dental traits in phylogenetically unrelated insular mammals.

  4. Insularity and the evolution of melanism, sexual dichromatism and body size in the worldwide-distributed barn owl.

    PubMed

    Roulin, A; Salamin, N

    2010-05-01

    Island biogeography has provided fundamental hypotheses in population genetics, ecology and evolutionary biology. Insular populations usually face different feeding conditions, predation pressure, intraspecific and interspecific competition than continental populations. This so-called island syndrome can promote the evolution of specific phenotypes like a small (or large) body size and a light (or dark) colouration as well as influence the evolution of sexual dimorphism. To examine whether insularity leads to phenotypic differentiation in a consistent way in a worldwide-distributed nonmigratory species, we compared body size, body shape and colouration between insular and continental barn owl (Tyto alba) populations by controlling indirectly for phylogeny. This species is suitable because it varies in pheomelanin-based colouration from reddish-brown to white, and it displays eumelanic black spots for which the number and size vary between individuals, populations and species. Females are on average darker pheomelanic and display more and larger eumelanic spots than males. Our results show that on islands barn owls exhibited smaller and fewer eumelanic spots and lighter pheomelanic colouration, and shorter wings than on continents. Sexual dimorphism in pheomelanin-based colouration was less pronounced on islands than continents (i.e. on islands males tended to be as pheomelanic as females), and on small islands owls were redder pheomelanic and smaller in size than owls living on larger islands. Sexual dimorphism in the size of eumelanic spots was more pronounced (i.e. females displayed much larger spots than males) in barn owls living on islands located further away from a continent. Our study indicates that insular conditions drive the evolution towards a lower degree of eumelanism, smaller body size and affects the evolution of sexual dichromatism in melanin-based colour traits. The effect of insularity was more pronounced on body size and shape than on melanic

  5. Utility Towers, Insulator Detail, Front Elevation, Side Elevation, Elevation, Double ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Utility Towers, Insulator Detail, Front Elevation, Side Elevation, Elevation, Double Pole Tower, Single Pole Tower - La Bajada Historic Trails and Roads, Approximately 1 mile East/Northeast of intersection of State Highway 16 and Indian Service Road 841, La Bajada, Santa Fe County, NM

  6. Subcortical anatomy as an anatomical and functional landmark in insulo-opercular gliomas: implications for surgical approach to the insular region.

    PubMed

    Martino, Juan; Mato, David; Marco de Lucas, Enrique; García-Porrero, Juan A; Gabarrós, Andreu; Fernández-Coello, Alejandro; Vázquez-Barquero, Alfonso

    2015-10-01

    Little attention has been given to the functional challenges of the insular approach to the resection of gliomas, despite the potential damage of essential neural networks that underlie the insula. The object of this study is to analyze the subcortical anatomy of the insular region when infiltrated by gliomas, and compare it with the normal anatomy in nontumoral hemispheres. Ten postmortem human hemispheres were dissected, with isolation of the inferior fronto-occipital fasciculus (IFOF) and the uncinate fasciculus. Probabilistic diffusion tensor imaging (DTI) tractography was used to analyze the subcortical anatomy of the insular region in 10 healthy volunteers and in 22 patients with insular Grade II and Grade III gliomas. The subcortical anatomy of the insular region in these 22 insular gliomas was compared with the normal anatomy in 20 nontumoral hemispheres. In tumoral hemispheres, the distances between the peri-insular sulci and the lateral surface of the IFOF and uncinate fasciculus were enlarged (p < 0.05). Also in tumoral hemispheres, the IFOF was identified in 10 (90.9%) of 11 patients with an extent of resection less than 80%, and in 4 (36.4%) of 11 patients with an extent of resection equal to or greater than 80% (multivariate analysis: p = 0.03). Insular gliomas grow in the space between the lateral surface of the IFOF and uncinate fasciculus and the insular surface, displacing and compressing the tracts medially. Moreover, these tracts may be completely infiltrated by the tumor, with a total disruption of the bundles. In the current study, the identification of the IFOF with DTI tractography was significantly associated with the extent of tumor resection. If the IFOF is not identified preoperatively, there is a high probability of achieving a resection greater than 80%.

  7. Effect of Right Insular Involvement on Death and Functional Outcome After Acute Ischemic Stroke in the IST-3 Trial (Third International Stroke Trial).

    PubMed

    Sposato, Luciano A; Cohen, Geoffrey; Wardlaw, Joanna M; Sandercock, Peter; Lindley, Richard I; Hachinski, Vladimir

    2016-12-01

    In patients with acute ischemic stroke, whether involvement of the insular cortex influences outcome is controversial. Much of the apparent adverse outcome may relate to such strokes usually being severe. We examined the influence of right and left insular involvement on stroke outcomes among patients from the IST-3 study (Third International Stroke Trial) who had visible ischemic stroke on neuroimaging. We used multiple logistic regression to compare outcomes of left versus right insular and noninsular strokes across strata of stroke severity, on death, proportion dead or dependent, and level of disability (ordinalized Oxford Handicap Score) at 6 months, with adjustment for the effects of age, lesion size, and presence of atrial fibrillation. Of 3035 patients recruited, 2099 had visible ischemic strokes limited to a single hemisphere on computed tomography/magnetic resonance scans. Of these, 566 and 714 had infarction of right and left insula. Six months after randomization, right insular involvement was associated with increased odds of death when compared with noninsular strokes on the left side (adjusted odds ratio, 1.83; 95% confidence interval, 1.33-2.52), whereas the adjusted odds ratio comparing mortality after insular versus noninsular strokes on the left side was not significant. Among mild/moderate strokes, outcomes for right insular involvement were worse than for left insular, but among more severe strokes, the difference in outcomes was less substantial. We found an association between right insular involvement and higher odds of death and worse functional outcome. The difference between right- and left-sided insular lesions on outcomes seemed to be most evident for mild/moderate strokes. URL: http://www.isrctn.com. Unique identifier: ISRCTN25765518. © 2016 American Heart Association, Inc.

  8. A possible role for nitric oxide in glutamate (MSG)-induced Chinese restaurant syndrome, glutamate-induced asthma, 'hot-dog headache', pugilistic Alzheimer's disease, and other disorders.

    PubMed

    Scher, W; Scher, B M

    1992-07-01

    Endogenous glutamate is thought to be a major neurotransmitter. After binding to a cell membrane receptor there can be a stimulation of what can be called the nitric oxide (NO)-mediated neurotransmission pathway (NO-MNP). The activity of the enzyme that produces NO from arginine, NO synthase, and the level of NO become elevated. NO has little activity within the cell in which it is produced, but it rapidly leaks out of that cell and produces effects in neighboring cells. The NO-MNP can be activated to release NO in endothelial cells which in turn acts on neighboring vascular smooth muscle cells to induce vasodilation. Therefore, we suggest that exogenous, ingested glutamate, like endogenous glutamate, can lead to the same stimulation of the NO-MNP in sensitive individuals which would then cause the symptoms of the Chinese restaurant syndrome and/or glutamate-induced asthma. Further, since ingested nitrite and related compounds can be metabolized to NO, NO may more directly cause the symptoms of 'hot dog headache'. In addition, it has been suggested that NO production can also be controlled in endothelial cells by fluid forces that stimulate pressure receptors. Therefore, elevations of NO and stimulation of the NO-MNP may occur due to sudden, local, alterations of blood pressure during pugilistic activities and play a role in the symptoms of pugilistic Alzheimer's disease. If these ideas are correct, then inhibitors of the NO-MNP and/or temporary reduction of the plasma level of arginine may be useful in preventing at least some of the symptoms of these disorders.

  9. Towards a glutamate hypothesis of depression

    PubMed Central

    Sanacora, Gerard; Treccani, Giulia; Popoli, Maurizio

    2011-01-01

    Half a century after the first formulation of the monoamine hypothesis, compelling evidence implies that long-term changes in an array of brain areas and circuits mediating complex cognitive-emotional behaviors represent the biological underpinnings of mood/anxiety disorders. A large number of clinical studies suggest that pathophysiology is associated with dysfunction of the predominant glutamatergic system, malfunction in the mechanisms regulating clearance and metabolism of glutamate, and cytoarchitectural/morphological maladaptive changes in a number of brain areas mediating cognitive-emotional behaviors. Concurrently, a wealth of data from animal models have shown that different types of environmental stress enhance glutamate release/transmission in limbic/cortical areas and exert powerful structural effects, inducing dendritic remodeling, reduction of synapses and possibly volumetric reductions resembling those observed in depressed patients. Because a vast majority of neurons and synapses in these areas and circuits use glutamate as neurotransmitter, it would be limiting to maintain that glutamate is in some way ‘involved’ in mood/anxiety disorders; rather it should be recognized that the glutamatergic system is a primary mediator of psychiatric pathology and, potentially, also a final common pathway for the therapeutic action of antidepressant agents. A paradigm shift from a monoamine hypothesis of depression to a neuroplasticity hypothesis focused on glutamate may represent a substantial advancement in the working hypothesis that drives research for new drugs and therapies. Importantly, despite the availability of multiple classes of drugs with monoamine-based mechanisms of action, there remains a large percentage of patients who fail to achieve a sustained remission of depressive symptoms. The unmet need for improved pharmacotherapies for treatment-resistant depression means there is a large space for the development of new compounds with novel

  10. Hetero-oligomerization of neuronal glutamate transporters.

    PubMed

    Nothmann, Doreen; Leinenweber, Ariane; Torres-Salazar, Delany; Kovermann, Peter; Hotzy, Jasmin; Gameiro, Armanda; Grewer, Christof; Fahlke, Christoph

    2011-02-04

    Excitatory amino acid transporters (EAATs) mediate the uptake of glutamate into neuronal and glial cells of the mammalian central nervous system. Two transporters expressed primarily in glia, EAAT1 and EAAT2, are crucial for glutamate homeostasis in the adult mammalian brain. Three neuronal transporters (EAAT3, EAAT4, and EAAT5) appear to have additional functions in regulating and processing cellular excitability. EAATs are assembled as trimers, and the existence of multiple isoforms raises the question of whether certain isoforms can form hetero-oligomers. Co-expression and pulldown experiments of various glutamate transporters showed that EAAT3 and EAAT4, but neither EAAT1 and EAAT2, nor EAAT2 and EAAT3 are capable of co-assembling into heterotrimers. To study the functional consequences of hetero-oligomerization, we co-expressed EAAT3 and the serine-dependent mutant R501C EAAT4 in HEK293 cells and Xenopus laevis oocytes and studied glutamate/serine transport and anion conduction using electrophysiological methods. Individual subunits transport glutamate independently of each other. Apparent substrate affinities are not affected by hetero-oligomerization. However, polarized localization in Madin-Darby canine kidney cells was different for homo- and hetero-oligomers. EAAT3 inserts exclusively into apical membranes of Madin-Darby canine kidney cells when expressed alone. Co-expression with EAAT4 results in additional appearance of basolateral EAAT3. Our results demonstrate the existence of heterotrimeric glutamate transporters and provide novel information about the physiological impact of EAAT oligomerization.

  11. A new insular species of Rock Gecko (Cnemaspis Boulenger) from Pulau Langkawi, Kedah, Peninsular Malaysia.

    PubMed

    Grismer, L Lee; Wood, P L Jr; Quah, Evan S H; Anuar, Shahrul; Ngadi, Ehwan; Ahmad, Norhayati

    2015-07-10

    A new, diminutive species of Rock Gecko Cnemaspis mahsuriae sp. nov. of the affinis group, is described from Gunung Raya on Pulau Langkawi, Kedah, Peninsular Malaysia and is differentiated from all other species in the affinis group by having a unique combination of characters including a maximum SVL of 36.6 mm; keeled subtibials and ventrals; 21-24 paravertebral tubercles; no tubercles in the lateral caudal furrows; caudal tubercles not encircling tail; no precloacal pores; 23-26 subdigital lamellae on the fourth toe; no white ocelli in the shoulder region; no yellow postscapular band; and faint yellow bars on the flanks. Cnemaspis mahsuriae sp. nov. is a forest-dwelling species living in close sympatry or paraptry with the insular endemic C. roticanai Grismer & Chan. The Langkawi Archipelago harbors a unique mix of Malaysian and Indochinese taxa and the frequency of new discoveries from this group of islands is increasing.

  12. Conjoint activity of anterior insular and anterior cingulate cortex: awareness and response

    PubMed Central

    Critchley, Hugo D.

    2010-01-01

    There is now a wealth of evidence that anterior insular and anterior cingulate cortices have a close functional relationship, such that they may be considered together as input and output regions of a functional system. This system is typically engaged across cognitive, affective, and behavioural contexts, suggesting that it is of fundamental importance for mental life. Here, we review the literature and reinforce the case that these brain regions are crucial, firstly, for the production of subjective feelings and, secondly, for co-ordinating appropriate responses to internal and external events. This model seeks to integrate higher-order cortical functions with sensory representation and autonomic control: it is argued that feeling states emerge from the raw data of sensory (including interoceptive) inputs and are integrated through representations in conscious awareness. Correspondingly, autonomic nervous system reactivity is particularly important amongst the responses that accompany conscious experiences. Potential clinical implications are also discussed. PMID:20512367

  13. Reduction of brain and sense organs in the fossil insular bovid Myotragus.

    PubMed

    Köhler, Meike; Moyà-Solà, Salvador

    2004-01-01

    Our study of the fossil rupicaprine bovid Myotragus [Bate, 1909] from the Mediterranean island Majorca (Spain) provides evidence that this animal underwent significant changes (reduction) in the relative size of brain and sense organs after geographic isolation at the end of the Messinian Salinity Crisis (Miocene-Pliocene boundary, 5.2 Mya). The changes in the central nervous system of Myotragus parallel the pattern reported for domesticated animals, in which decrease in relative brain size is accompanied by a decrease in the relative size of their sense organs. We interpret the important size reduction of brain and sense organs in Myotragus as an adaptive strategy for more efficient energy use under the special environmental conditions of the insular ecosystem, characterized by absence of predation and limitation of trophic resources.

  14. Endoparasites of the coyote (Canis latrans), a recent migrant to insular newfoundland.

    PubMed

    Bridger, Kimberly E; Baggs, Eric M; Finney-Crawley, Jean

    2009-10-01

    This study provides the first data on the helminth fauna of the coyote (Canis latrans) in insular Newfoundland. Sixty-nine coyotes were collected between 2001 and 2003 and examined for helminths. A total of 10 helminth species were recorded: the cestodes Taenia ovis krabbei (9%), Taenia hydatigena (4%), Taenia pisiformis (1%), and Mesocestoides spp. (5%); and the nematodes Toxocara canis (19%), Toxascaris leonina (1%), Crenosoma vulpis (19%), Physaloptera rara (6%), Uncinaria stenocephala (3%), and Angiostrongylus vasorum (1%). No significant differences (P< or =0.05) were detected between sexes. Mesocestoides spp., T. canis, and C. vulpis were more prevalent in juveniles than adults. Angiostrongylus vasorum is reported in coyotes for the second time in Newfoundland, Canada.

  15. The Insular Cortex Controls Food Preferences Independently of Taste Receptor Signaling

    PubMed Central

    Oliveira-Maia, Albino J.; de Araujo, Ivan E.; Monteiro, Clara; Workman, Virginia; Galhardo, Vasco; Nicolelis, Miguel A. L.

    2012-01-01

    The insular cortex (IC) contains the primary sensory cortex for oral chemosensation including gustation, and its integrity is required for appropriate control of feeding behavior. However, it remains unknown whether the role of this brain area in food selection relies on the presence of peripheral taste input. Using multielectrode recordings, we found that the responses of populations of neurons in the IC of freely licking, sweet-blind Trpm5−/− mice are modulated by the rewarding postingestive effects of sucrose. FOS immunoreactivity analyses revealed that these responses are restricted to the dorsal insula. Furthermore, bilateral lesions in this area abolished taste-independent preferences for sucrose that can be conditioned in these Trpm5−/− animals while preserving their ability to detect sucrose. Overall, these findings demonstrate that, even in the absence of peripheral taste input, IC regulates food choices based on postingestive signals. PMID:22403530

  16. Relationship between rainfall and Aedes larval population at two insular sites in Pulau Ketam, Selangor, Malaysia.

    PubMed

    Wee, Lim Kwee; Weng, Sit Nam; Raduan, Norzahira; Wah, Sing Kong; Ming, Wong Hong; Shi, Chew Hwai; Rambli, Firdaus; Ahok, Cheryl Jacyln; Marlina, Suria; Ahmad, Nazni Wasi; Mckemy, Andrew; Vasan, S S; Lim, Lee Han

    2013-03-01

    Two insular settlements (Kampung Pulau Ketam and Kampung Sungai Lima) were selected to study the population dynamics of Aedes aegypti and Aedes albopictus mosquitoes, vectors of dengue and chikungunya infections. Ovitrap surveillance was conducted between October 2007 and October 2008. There was an inverse negative association between ovitrap index and rainfall at the time of collection, probably because rainfall increased the number of available oviposition sites. Rainfall and ovitrap index were positively associates the 25th day after rainfall occurred. A minor, second peak was observed from the 38th to the 42nd day. The first peak was consistent with the minimum 18-day period between the hatching of eggs to the first oviposition. The second minor peak could be due to the second gonotrophic cycle of the female mosquitoes. Rainfall is an important environmental factor associated with Aedes breeding at the study sites.

  17. Dengue vector surveillance in insular settlements of Pulau Ketam, Selangor, Malaysia.

    PubMed

    Lim, K W; Sit, N W; Norzahira, R; Sing, K W; Wong, H M; Chew, H S; Firdaus, R; Cheryl, J A; Suria, M; Mahathavan, M; Nazni, W A; Lee, H L; McKemy, A; Vasan, S S

    2010-08-01

    A year-long ovitrap surveillance was conducted between November 2007 and October 2008 in two insular settlements (Kampung Pulau Ketam and Kampung Sungai Lima) within the Malaysian island of Pulau Ketam. Eighty standard ovitraps were placed indoors and outdoors of randomly selected houses/locations. Results demonstrated an endemic baseline Aedes population throughout the year without weekly large fluctuations. Kampung Pulau Ketam has high Aedes aegypti and Aedes albopictus population, but only Ae. aegypti was found in Kampung Sungai Lima. Aedes aegypti showed no preference for ovitraps placed indoor versus outdoor. However, as expected, significantly more outdoor ovitraps were positive for Ae. albopictus (p<0.05). Trends in Ae. albopictus and Ae. aegypti populations mirrored each other suggesting that common factors influenced these two populations.

  18. Household waste compositional analysis variation from insular communities in the framework of waste prevention strategy plans.

    PubMed

    Zorpas, Antonis A; Lasaridi, Katia; Voukkali, Irene; Loizia, Pantelitsa; Chroni, Christina

    2015-04-01

    Waste management planning requires reliable data regarding waste generation, affecting factors on waste generation and forecasts of waste quantities based on facts. In order to decrease the environmental impacts of waste management the choice of prevention plan as well as the treatment method must be based on the features of the waste that are produced in a specific area. Factors such as culture, economic development, climate, and energy sources have an impact on waste composition; composition influences the need of collecting waste more or less frequently of waste collection and disposition. The research question was to discover the main barriers concerning the compositional analysis in Insular Communities under warm climate conditions and the findings from this study enabled the main contents of a waste management plan to be established. These included advice to residents on waste minimisation, liaison with stakeholders and the expansion of kerbside recycling schemes. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. Navigating the Island of Reil: how to understand the insular cortex.

    PubMed

    Wynford-Thomas, Ray; Powell, Rob

    2017-04-01

    Insular-onset seizures are rare and easily misdiagnosed. In this article, we aim to highlight the often distinctive semiology of seizures involving the insula with reference to three cases. We suggest three points to aid the recognition of seizures involving the insula: (1) Seizures originating in the insula frequently present with a sensation of laryngeal constriction, dyspnoea or unpleasant somatosensory symptoms; (2) Seizures involving the anterior insula may have a silent onset, but tend to propagate rapidly to motor areas causing motor or hypermotor symptoms; (3) Seizures involving the posterior insula cause somatosensory symptoms, which are normally contralateral to the seizure onset. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  20. Taste-potentiated odor aversion learning in rats with lesions of the insular cortex.

    PubMed

    Lin, Jian-You; Roman, Christopher; Reilly, Steve

    2009-11-10

    The current study assessed the influence of excitotoxic lesions of the insular cortex (IC) on taste-potentiated odor aversion (TPOA) learning. Water-deprived rats initially received a single odor-toxicosis or odor/taste-toxicosis pairing and were subsequently tested, in separate trials, with the odor and the taste stimulus. Indicating TPOA, neurologically intact rats conditioned with the odor/taste compound stimulus acquired significantly stronger odor aversions than normal rats conditioned with the odor stimulus. IC lesions disrupted TPOA, conditioned taste aversion and taste neophobia. The finding that taste did not potentiate odor aversion learning in the IC-lesioned rats provides support for the "within-compound association" analysis but is inconsistent with the "sensory-and-gate" account of TPOA learning.

  1. Forest cover of insular Southeast Asia mapped from recent satellite images of coarse spatial resolution.

    PubMed

    Stibig, Hans-Jürgen; Malingreau, Jean-Paul

    2003-11-01

    The study provides an example of mapping tropical forest cover from SPOT-Vegetation satellite images of coarse spatial resolution (1 km) for the subregion of insular Southeast Asia. A satellite image mosaic has been generated from satellite images acquired for the period 1998 to 2000. Forest cover has been mapped by unsupervised digital classification. The mapping result has then been compared to selected forest maps from the subregion, demonstrating the potential to provide basic information on forest area extent and distribution, but also on massive forest cover change in the subregional context. Forest area estimates derived from the map for the subregion have been found comparable to those compiled by FAO. The results indicate that many of the remaining tropical forests in Southeast Asia, rich in timber resources and biodiversity, may be lost in the near future if deforestation continues at present or previous rates.

  2. Combining Ca2+ imaging with -glutamate photorelease

    PubMed Central

    Canepari, Marco; De Waard, Michel; Ogden, David

    2013-01-01

    We describe simple configurations and methods to measure optical Ca2+ signals in response to photorelease of L-glutamate. This photostimulation allows activation of postsynaptic glutamate receptors without activation of voltage-gated Ca2+ channels permitting the separation and the analysis of different Ca2+ components. We give details of basic microscopy configurations and of tools to efficiently illuminate the preparation while preserving the healthy conditions of the tissues. We also suggest methodological procedures and we discuss protocols of linear optics to achieve simultaneous imaging and uncaging in relation to protocols using two photon illumination. PMID:24298028

  3. Parental Praise Correlates with Posterior Insular Cortex Gray Matter Volume in Children and Adolescents

    PubMed Central

    Matsudaira, Izumi; Yokota, Susumu; Hashimoto, Teruo; Takeuchi, Hikaru; Asano, Kohei; Asano, Michiko; Sassa, Yuko; Taki, Yasuyuki; Kawashima, Ryuta

    2016-01-01

    A positive parenting style affects psychological and cognitive development in children. Neuroimaging studies revealed that a positive parenting style influenced brain structure in children. Parental praise is a concrete behavior observed in positive parenting. Although previous psychological studies revealed a positive effect of parental praise on children, little is known about the relationship between parental praise and brain structure in children. Thus, the purpose of the present study was to determine whether there was a correlation between the parental attitude towards praising their child and gray matter volume in the children (116 boys and 109 girls; mean age, 10.6 years old). We examined the correlation between regional gray matter volume and parental praise using voxel-based morphometry (VBM) following magnetic resonance imaging (MRI). In addition, to confirm the positive effects of parental praise, we analyzed the correlation between the frequency of parental praise and personality traits in children. We showed that the parental attitude towards praising their child was significantly and positively correlated with the gray matter volume of the left posterior insular cortex in children. Moreover, we found a significant positive correlation between parental attitude towards praising their child and the personality traits of conscientiousness and openness to experience in the children. Prior studies said that gray matter volume in the posterior insula was correlated with empathy, and the functional connectivity between this area and the amygdala was associated with emotional regulation. Furthermore, the posterior insula relates to auditory function, and therefore, was likely involved in the processing of parental praise. Considering the possibility of experience-dependent plasticity, frequent parental praise would lead to increased posterior insular gray matter volume in children. Our study is the first to elucidate the relationship between a specific

  4. The influence of climatic variation and density on the survival of an insular passerine Zosterops lateralis

    PubMed Central

    Coulson, Tim; Clegg, Sonya M.

    2017-01-01

    Understanding the influence of environmental factors on population dynamics is fundamental to many areas in biology. Survival is a key factor of population biology, as it is thought to be the predominant driver of growth in long-lived passerines, which can be influenced by both biotic and abiotic environmental conditions. We used mark-recapture methods and generalized linear mixed models to test the influence of density and climatic variation, measured at a regional and local scale (Southern Oscillation Index [SOI] and rainfall, respectively), on seasonal variation in survival rates of an insular population of Silvereyes (Zosterops lateralis chlorocephalus), during a 15-year study period, off the east coast of Australia. We found overall high survival rates for adults and juveniles (81% and 59%, respectively). Local scale climate (i.e. rainfall) and density were the principal environmental factors influencing their survival, both with a negative relationship. A significant interactive effect of density and rainfall influenced survival as they both increased. However, survival remained low when density was at it highest, independent of the amount of rainfall. Nestling survival was negatively influenced by rainfall and density, positively by SOI, and chicks that hatched later in the breeding season had higher survival rates. The regional scale climate variable (i.e. SOI) did not explain survival rates as strongly as rainfall in any age class. Our results contribute to the understanding of insular avian population dynamics and the differential effects of environmental factors across age classes. Climatic predictions expect El Niño events to increase, meaning dryer conditions in eastern Australia, potentially increasing Silvereye survival across age classes. However, the long-term effect of lower rainfall on food availability is unknown; consequently, the outcome of lower rainfall on Silvereye survival rates is uncertain. PMID:28453564

  5. Pain and emotion in the insular cortex: evidence for functional reorganization in major depression.

    PubMed

    Mutschler, Isabella; Ball, Tonio; Wankerl, Johanna; Strigo, Irina A

    2012-06-29

    Major Depressive Disorder (MDD) is among the top causes of disability worldwide and many patients with depression experience pain symptoms. Little is known regarding what makes depressed persons feel like they are in pain. An increasing number of neuroimaging studies show that both physical pain and depression involve the insular cortex. The present study aimed to investigate whether emotional processing in MDD patients is topologically shifted towards the insular area(s) involved in pain processing in healthy individuals. To achieve this aim, we investigated the functional organization of the insula by conducting meta-analyses of previously published neuroimaging studies on: (1) emotion in patients with MDD, (2) emotion in healthy subjects, and (3) physical pain in healthy subjects. Our results show that the dorsal part of the insula is reproducibly activated during experimental pain in healthy individuals, with multiple separate pain-related areas aligned along its dorsal border. Regions with maximal pain-related activation likelihood estimate (ALE) were located in the posterior (left) and dorsal mid-anterior insula (left and right). Furthermore, emotion-related peaks in healthy subjects were found both in its ventral (as shown in a previous meta-analysis) and dorsal anterior part. Importantly, emotion-related peaks in depressed patients were shifted to the dorsal anterior insula, where regions related to physical pain in healthy subjects are located. This shift was reflected in the observation that median z-coordinates of emotion-related responses in the left hemisphere were significantly larger in depressed patients than in healthy controls. This shift of emotion-related responses to the dorsal insula, i.e., where pain-processing takes place in healthy subjects, may play a role in "emotional allodynia" - a notion that individuals with MDD experience pain in response to stimuli that are normally not painful. Copyright © 2012 Elsevier Ireland Ltd. All rights

  6. Predictive coding accounts of shared representations in parieto-insular networks.

    PubMed

    Ishida, Hiroaki; Suzuki, Keisuke; Grandi, Laura Clara

    2015-04-01

    The discovery of mirror neurons in the ventral premotor cortex (area F5) and inferior parietal cortex (area PFG) in the macaque monkey brain has provided the physiological evidence for direct matching of the intrinsic motor representations of the self and the visual image of the actions of others. The existence of mirror neurons implies that the brain has mechanisms reflecting shared self and other action representations. This may further imply that the neural basis self-body representations may also incorporate components that are shared with other-body representations. It is likely that such a mechanism is also involved in predicting other's touch sensations and emotions. However, the neural basis of shared body representations has remained unclear. Here, we propose a neural basis of body representation of the self and of others in both human and non-human primates. We review a series of behavioral and physiological findings which together paint a picture that the systems underlying such shared representations require integration of conscious exteroception and interoception subserved by a cortical sensory-motor network involving parieto-inner perisylvian circuits (the ventral intraparietal area [VIP]/inferior parietal area [PFG]-secondary somatosensory cortex [SII]/posterior insular cortex [pIC]/anterior insular cortex [aIC]). Based on these findings, we propose a computational mechanism of the shared body representation in the predictive coding (PC) framework. Our mechanism proposes that processes emerging from generative models embedded in these specific neuronal circuits play a pivotal role in distinguishing a self-specific body representation from a shared one. The model successfully accounts for normal and abnormal shared body phenomena such as mirror-touch synesthesia and somatoparaphrenia. In addition, it generates a set of testable experimental predictions. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. Exercise-induced decrease in insular cortex rCBF during postexercise hypotension.

    PubMed

    Lamb, Kala; Gallagher, Kevin; McColl, Roderick; Mathews, Dana; Querry, Ross; Williamson, Jon W

    2007-04-01

    The insular cortex (IC), a region of the brain involved in blood pressure (BP) modulation, shows decreases in regional cerebral blood flow (rCBF) during postexercise hypotension (PEH). To determine whether changes in IC neural activity were caused by prior exercise or by changes in BP, this investigation compared patterns of rCBF during periods of hypotension, which was induced by prior exercise (i.e., PEH) and sodium nitroprusside (SNP) infusion and a cold pressor (CP), to restore BP. Ten subjects were studied on three different days with randomly assigned conditions: i) resting baseline; ii) PEH; and iii) SNP-induced hypotension (matched to the PEH BP decrease). Data were collected for heart rate (HR) and mean BP, and rCBF was assessed using single-photon emission computed tomography (SPECT) as an index of brain activation. Using ANOVA across conditions, there were differences (P<0.05; mean +/- SD) from baseline during PEH for HR (+12 +/- 3 bpm) and mean BP (-8 +/- 2 mm Hg) and during SNP-induced hypotension (HR = +15 +/- 4 bpm; MBP = -9 +/- 2 mm Hg), with no differences between PEH and SNP. After exercise, there were decreases (P<0.05) in the leg sensorimotor area, anterior cingulate, and the right and left inferior thalamus, right inferior insula, and left anterior insular regions. During SNP-induced hypotension, there were significant increases in the right and left inferior thalamus and the right and left inferior anterior IC. CP during PEH increased BP and IC activity. Data show that reductions in IC neural activity are not caused by acute BP decreases. Findings suggest that exercise can lead to a temporary decrease in IC neural activity, which may be a significant neural factor contributing to PEH.

  8. Suppressive responses by visual food cues in postprandial activities of insular cortex as revealed by magnetoencephalography.

    PubMed

    Yoshikawa, Takahiro; Tanaka, Masaaki; Ishii, Akira; Watanabe, Yasuyoshi

    2014-06-03

    'Hara-Hachibu' in Japanese means a subjective sense by which we stop eating just before the motivation to eat is completely lost, a similar concept to caloric restriction (CR). Insular cortex is a critical platform which integrates sensory information into decision-making processes in eating behavior. We compared the responses of insular cortex, as assessed by magnetoencephalography (MEG), immediately after presentation of food images in the Fasting condition with those in the 'Hara-Hachibu' condition. Eleven healthy, right-handed males [age, 27.2±9.6 years; body mass index, 22.6±2.1kg/m(2) (mean±SD)] were enrolled in a randomized, two-crossover experiment (Fasting and 'Hara-Hachibu' conditions). Before the MEG recordings in the 'Hara-Hachibu' condition, the participants consumed rice balls as much as they judged themselves to have consumed shortly before reaching satiety. During the MEG recordings, they viewed food pictures projected on a screen. The intensities of MEG responses to viewing food pictures were significantly lower in the 'Hara-Hachibu' condition than those in the Fasting condition (P<0.05). The intensities of the MEG responses to the visual food stimuli in the 'Hara-Hachibu' condition was positively associated with the factor-3 (food tasted) (r=0.693, P=0.018) and aggregated scores (r=0.659, P=0.027) of the Power of Food Scale, a self-report measure of hedonic hunger. These findings may help to elucidate the neural basis of variability of appetite phenotypes under the condition of CR among individuals, and to develop possible strategies for the maintenance of adequate CR in daily life. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

  9. Imbalanced spontaneous brain activity in orbitofrontal-insular circuits in individuals with cognitive vulnerability to depression.

    PubMed

    Zhang, Xiaocui; Di, Xin; Lei, Hui; Yang, Juan; Xiao, Jing; Wang, Xiang; Yao, Shuqiao; Rao, Hengyi

    2016-07-01

    The hopelessness theory of depression posits that individuals with negative cognitive styles are at risk of developing depression following negative life events. The purpose of this work was to examine whether individuals with cognitive vulnerability to depression (CVD) exhibit similar spontaneous brain activity patterns as compared to patients with major depressive disorder (MDD). Subjects with CVD (N=32), drug-naïve first-episode patients with major depressive disorder (N=32), and sex-, age- and education-matched healthy controls (HCs; N=35) were subjected to resting state functional magnetic resonance imaging (RS-fMRI) and amplitudes of low-frequency fluctuation (ALFF) was compared between the groups. Pearson correlation analysis was performed between regional ALFFs and psychometric scores, namely the Cognitive Style Questionnaire (CSQ) and the Center for Epidemiologic Studies Depression (CES-D) scale scores. Significant group differences in ALFF values were observed bilaterally in the orbitofrontal cortex (OFC) and insular cortex (IC), and in the left fusiform gyrus (FFG). Compared to HCs, CVD subjects had reduced ALFFs in the bilateral OFC and increased ALFF in the bilateral IC and the left FFG, which were similar to the differences observed between the HCs and MDD patients. Compared to MDD patients, CVD subjects showed significant reduced ALFF values in right IC. Additionally, CSQ scores for the CVD group correlated with ALFF values in the left IC. We did not conduct a longitudinal study. Our findings were limited in cross-sectional analysis. A hypoactive OFC and hyperactive IC in a resting-state may underlie an imbalance in the spontaneous brain activity in orbitofrontal-insular circuits, and these differences may represent a trait-related marker of vulnerability to depression. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Cigarette smoking is associated with thinner cingulate and insular cortices in patients with severe mental illness

    PubMed Central

    Jørgensen, Kjetil Nordbø; Psychol, Cand; Skjærvø, Ingeborg; Mørch-Johnsen, Lynn; Haukvik, Unn Kristin; Lange, Elisabeth Heffermehl; Melle, Ingrid; Andreassen, Ole Andreas; Agartz, Ingrid

    2015-01-01

    Background Magnetic resonance imaging (MRI) studies show reduced cortical thickness in patients with schizophrenia and bipolar disorder. These subtle brain abnormalities may provide insight into illness mechanisms. However, environmental and lifestyle-related factors, such as cigarette smoking, may contribute to brain structure changes. Cigarette smoking is highly prevalent in patients with severe mental illness. In nonpsychiatric samples, smoking has been associated with reduced thickness in the anterior (ACC) and posterior cingulate cortices, the insular cortex (INS), the dorsolateral prefrontal cortex and the orbitofrontal cortex. Methods We examined MRI scans from patients with schizophrenia, other psychotic disorders or bipolar disorder and healthy controls using FreeSurfer. Results We included 506 patients (49% smokers) and 237 controls (20% smokers) in our study. We found reduced cortical thickness in the left rostral ACC and the left INS in smoking patients compared with nonsmoking patients, but this difference was not found among healthy controls. No dose–response relationship was found between amount of smoking and cortical thickness in these regions. Among patients, maps of thickness along the whole cortical surface revealed reduced insular thickness but no effects in other regions. Among healthy controls, similar analyses revealed increased age-related cortical thinning in the left occipital lobe among smokers compared with nonsmokers. Limitations The causal direction could not be determined owing to the cross-sectional design and lack of detailed data on smoking addiction and smoking history. Conclusion The effect of cigarette smoking should be considered in MRI studies of patients with severe mental illness. PMID:25672482

  11. Parental Praise Correlates with Posterior Insular Cortex Gray Matter Volume in Children and Adolescents.

    PubMed

    Matsudaira, Izumi; Yokota, Susumu; Hashimoto, Teruo; Takeuchi, Hikaru; Asano, Kohei; Asano, Michiko; Sassa, Yuko; Taki, Yasuyuki; Kawashima, Ryuta

    2016-01-01

    A positive parenting style affects psychological and cognitive development in children. Neuroimaging studies revealed that a positive parenting style influenced brain structure in children. Parental praise is a concrete behavior observed in positive parenting. Although previous psychological studies revealed a positive effect of parental praise on children, little is known about the relationship between parental praise and brain structure in children. Thus, the purpose of the present study was to determine whether there was a correlation between the parental attitude towards praising their child and gray matter volume in the children (116 boys and 109 girls; mean age, 10.6 years old). We examined the correlation between regional gray matter volume and parental praise using voxel-based morphometry (VBM) following magnetic resonance imaging (MRI). In addition, to confirm the positive effects of parental praise, we analyzed the correlation between the frequency of parental praise and personality traits in children. We showed that the parental attitude towards praising their child was significantly and positively correlated with the gray matter volume of the left posterior insular cortex in children. Moreover, we found a significant positive correlation between parental attitude towards praising their child and the personality traits of conscientiousness and openness to experience in the children. Prior studies said that gray matter volume in the posterior insula was correlated with empathy, and the functional connectivity between this area and the amygdala was associated with emotional regulation. Furthermore, the posterior insula relates to auditory function, and therefore, was likely involved in the processing of parental praise. Considering the possibility of experience-dependent plasticity, frequent parental praise would lead to increased posterior insular gray matter volume in children. Our study is the first to elucidate the relationship between a specific

  12. Sediment dynamics and their potential influence on insular-slope mesophotic coral ecosystems

    NASA Astrophysics Data System (ADS)

    Sherman, C.; Schmidt, W.; Appeldoorn, R.; Hutchinson, Y.; Ruiz, H.; Nemeth, M.; Bejarano, I.; Motta, J. J. Cruz; Xu, H.

    2016-10-01

    Although sediment dynamics exert a fundamental control on the character and distribution of reefs, data on sediment dynamics in mesophotic systems are scarce. In this study, sediment traps and benthic photo-transects were used to document spatial and temporal patterns of suspended-sediment and bed-load dynamics at two geomorphically distinct mesophotic coral ecosystems (MCEs) on the upper insular slope of southwest Puerto Rico. Trap accumulation rates of suspended sediment were relatively low and spatiotemporally uniform, averaging <1 mg cm-2 d-1 and never exceeding 3 mg cm-2 d-1 over the sampled period. In contrast, trap accumulation rates of downslope bed-load movement were orders of magnitude higher than suspended-sediment accumulation rates and highly variable, by orders of magnitude, both spatially and temporally. Percent sand cover within photo-transects varied over time from 10% to more than 40% providing further evidence of downslope sediment movement. In general, the more exposed, lower gradient site had higher rates of downslope sediment movement, higher sand cover and lower coral cover than the more sheltered and steep site that exhibited lower rates of downslope sediment movement, lower sand cover and higher coral cover. In most cases, trap accumulation rates of suspended sediment and bed load varied together and peaks in trap accumulation rates correspond to peaks in SWAN-modeled wave-orbital velocities, suggesting that surface waves may influence sediment dynamics even in mesophotic settings. Though variable, off-shelf transport of sediment is a continuous process occurring even during non-storm conditions. Continuous downslope sediment movement in conjunction with degree of exposure to prevailing seas and slope geomorphology are proposed to exert an important influence on the character and distribution of insular-slope MCEs.

  13. Retinal glutamate transporter changes in experimental glaucoma and after optic nerve transection in the rat.

    PubMed

    Martin, Keith R G; Levkovitch-Verbin, Hana; Valenta, Danielle; Baumrind, Lisa; Pease, Mary Ellen; Quigley, Harry A

    2002-07-01

    High levels of glutamate can be toxic to retinal ganglion cells. Effective buffering of extracellular glutamate by retinal glutamate transporters is therefore important. This study was conducted to investigate whether glutamate transporter changes occur with two models of optic nerve injury in the rat. Glaucoma was induced in one eye of 35 adult Wistar rats by translimbal diode laser treatment to the trabecular meshwork. Twenty-five more rats underwent unilateral optic nerve transection. Two glutamate transporters, GLAST (EAAT-1) and GLT-1 (EAAT-2), were studied by immunohistochemistry and quantitative Western blot analysis. Treated and control eyes were compared 3 days and 1, 4, and 6 weeks after injury. Optic nerve damage was assessed semiquantitatively in epoxy-embedded optic nerve cross sections. Trabecular laser treatment resulted in moderate intraocular pressure (IOP) elevation in all animals. After 1 to 6 weeks of experimental glaucoma, all treated eyes had significant optic nerve damage. Glutamate transporter changes were not detected by immunohistochemistry. Western blot analysis demonstrated significantly reduced GLT-1 in glaucomatous eyes compared with control eyes at 3 days (29.3% +/- 6.7%, P = 0.01), 1 week (55.5% +/- 13.6%, P = 0.02), 4 weeks (27.2% +/- 10.1%, P = 0.05), and 6 weeks (38.1% +/- 7.9%, P = 0.01; mean reduction +/- SEM, paired t-tests, n = 5 animals per group, four duplicate Western blot analyses per eye). The magnitude of the reduction in GLT-1 correlated significantly with mean IOP in the glaucomatous eye (r(2) = 0.31, P = 0.01, linear regression). GLAST was significantly reduced (33.8% +/- 8.1%, mean +/- SEM) after 4 weeks of elevated IOP (P = 0.01, paired t-test, n = 5 animals per group). In contrast to glaucoma, optic nerve transection resulted in an increase in GLT-1 compared with the control eye (P = 0.01, paired t-test, n = 15 animals). There was no significant change in GLAST after transection. GLT-1 and GLAST were significantly

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

    PubMed

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

    2005-03-28

    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.

  15. Artifactual Depression of Serum Glutamic Oxaloacetic Transaminase by Metronidazole

    PubMed Central

    Rissing, J. Peter; Newman, Cheryl; Moore, William L.

    1978-01-01

    Eighteen patients developed abnormally low serum glutamic oxaloacetic transaminase values during metronidazole therapy. Metronidazole absorbs at 340 nm, simulating reduced nicotinamide adenine dinucleotide, which is the final colorimetric product of the serum glutamic oxaloacetic transaminase assay. PMID:214030

  16. Anterior Cingulate Glutamate Is Reduced by Acamprosate Treatment in Patients With Alcohol Dependence.

    PubMed

    Frye, Mark A; Hinton, David J; Karpyak, Victor M; Biernacka, Joanna M; Gunderson, Lee J; Feeder, Scott E; Choi, Doo-Sup; Port, John D

    2016-12-01

    Although the precise drug mechanism of action of acamprosate remains unclear, its antidipsotropic effect is mediated in part through glutamatergic neurotransmission. We evaluated the effect of 4 weeks of acamprosate treatment in a cohort of 13 subjects with alcohol dependence (confirmed by a structured interview, Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision) on proton magnetic resonance spectroscopy glutamate levels in the midline anterior cingulate cortex (MACC). We compared levels of metabolites with a group of 16 healthy controls. The Pennsylvania Alcohol Craving Scale was used to assess craving intensity. At baseline, before treatment, the mean cerebrospinal fluid-corrected MACC glutamate (Glu) level was significantly elevated in subjects with alcohol dependence compared with controls (P = 0.004). Four weeks of acamprosate treatment reduced glutamate levels (P = 0.025), an effect that was not observed in subjects who did not take acamprosate. At baseline, there was a significant positive correlation between cravings, measured by the Pennsylvania Alcohol Craving Scale, and MACC (Glu) levels (P = 0.019). Overall, these data would suggest a normalizing effect of acamprosate on a hyperglutamatergic state observed in recently withdrawn patients with alcohol dependence and a positive association between MACC glutamate levels and craving intensity in early abstinence. Further research is needed to evaluate the use of these findings for clinical practice, including monitoring of craving intensity and individualized selection of treatment with antidipsotropic medications in subjects with alcohol dependence.

  17. Metabolism of Proline, Glutamate, and Ornithine in Proline Mutant Root Tips of Zea mays (L.)

    PubMed Central

    Dierks-Ventling, Christa; Tonelli, Chiara

    1982-01-01

    In excised pro1-1 mutant and corresponding normal type roots of Zea mays L. the uptake and interconversion of [14C]proline, [14C]glutamic acid, [14C]glutamine, and [14C]ornithine and their utilization for protein synthesis was measured with the intention of finding an explanation for the proline requirement of the mutant. Uptake of these four amino acids, with the exception of proline, was the same in mutant and normal roots, but utilization differed. Higher than normal utilization rates for proline and glutamic acid were noted in mutant roots leading to increased CO2 production, free amino acid interconversion, and protein synthesis. Proline was synthesized from either glutamic acid (or glutamine) or ornithine in both mutant and normal roots; it did not accumulate but rather was used for protein synthesis. Ornithine was not a good precursor for proline in either system, but was preferentially converted to arginine and glutamine, particularly in mutant roots. The pro1-1 mutant was thus not deficient in its ability to make proline. Based on these findings, and on the fact that ornithine, arginine, glutamic acid and aspartic acid are elevated as free amino acids in mutant roots, it is suggested that in the pro1-1 mutant proline catabolism prevails over proline synthesis. PMID:16662144

  18. Corticotrigeminal Projections from the Insular Cortex to the Trigeminal Caudal Subnucleus Regulate Orofacial Pain after Nerve Injury via Extracellular Signal-Regulated Kinase Activation in Insular Cortex Neurons.

    PubMed

    Wang, Jian; Li, Zhi-Hua; Feng, Ban; Zhang, Ting; Zhang, Han; Li, Hui; Chen, Tao; Cui, Jing; Zang, Wei-Dong; Li, Yun-Qing

    2015-01-01

    Cortical neuroplasticity alterations are implicated in the pathophysiology of chronic orofacial pain. However, the relationship between critical cortex excitability and orofacial pain maintenance has not been fully elucidated. We recently demonstrated a top-down corticospinal descending pain modulation pathway from the anterior cingulate cortex (ACC) to the spinal dorsal horn that could directly regulate nociceptive transmission. Thus, we aimed to investigate possible corticotrigeminal connections that directly influence orofacial nociception in rats. Infraorbital nerve chronic constriction injury (IoN-CCI) induced significant orofacial nociceptive behaviors as well as pain-related negative emotions such as anxiety/depression in rats. By combining retrograde and anterograde tract tracing, we found powerful evidence that the trigeminal caudal subnucleus (Vc), especially the superficial laminae (I/II), received direct descending projections from granular and dysgranular parts of the insular cortex (IC). Extracellular signal-regulated kinase (ERK), an important signaling molecule involved in neuroplasticity, was significantly activated in the IC following IoN-CCI. Moreover, in IC slices from IoN-CCI rats, U0126, an inhibitor of ERK activation, decreased both the amplitude and the frequency of spontaneous excitatory postsynaptic currents (sEPSCs) and reduced the paired-pulse ratio (PPR) of Vc-projecting neurons. Additionally, U0126 also reduced the number of action potentials in the Vc-projecting neurons. Finally, intra-IC infusion of U0126 obviously decreased Fos expression in the Vc, accompanied by the alleviation of both nociceptive behavior and negative emotions. Thus, the corticotrigeminal descending pathway from the IC to the Vc could directly regulate orofacial pain, and ERK deactivation in the IC could effectively alleviate neuropathic pain as well as pain-related negative emotions in IoN-CCI rats, probably through this top-down pathway. These findings may help

  19. Corticotrigeminal Projections from the Insular Cortex to the Trigeminal Caudal Subnucleus Regulate Orofacial Pain after Nerve Injury via Extracellular Signal-Regulated Kinase Activation in Insular Cortex Neurons

    PubMed Central

    Wang, Jian; Li, Zhi-Hua; Feng, Ban; Zhang, Ting; Zhang, Han; Li, Hui; Chen, Tao; Cui, Jing; Zang, Wei-Dong; Li, Yun-Qing

    2015-01-01

    Cortical neuroplasticity alterations are implicated in the pathophysiology of chronic orofacial pain. However, the relationship between critical cortex excitability and orofacial pain maintenance has not been fully elucidated. We recently demonstrated a top-down corticospinal descending pain modulation pathway from the anterior cingulate cortex (ACC) to the spinal dorsal horn that could directly regulate nociceptive transmission. Thus, we aimed to investigate possible corticotrigeminal connections that directly influence orofacial nociception in rats. Infraorbital nerve chronic constriction injury (IoN-CCI) induced significant orofacial nociceptive behaviors as well as pain-related negative emotions such as anxiety/depression in rats. By combining retrograde and anterograde tract tracing, we found powerful evidence that the trigeminal caudal subnucleus (Vc), especially the superficial laminae (I/II), received direct descending projections from granular and dysgranular parts of the insular cortex (IC). Extracellular signal-regulated kinase (ERK), an important signaling molecule involved in neuroplasticity, was significantly activated in the IC following IoN-CCI. Moreover, in IC slices from IoN-CCI rats, U0126, an inhibitor of ERK activation, decreased both the amplitude and the frequency of spontaneous excitatory postsynaptic currents (sEPSCs) and reduced the paired-pulse ratio (PPR) of Vc-projecting neurons. Additionally, U0126 also reduced the number of action potentials in the Vc-projecting neurons. Finally, intra-IC infusion of U0126 obviously decreased Fos expression in the Vc, accompanied by the alleviation of both nociceptive behavior and negative emotions. Thus, the corticotrigeminal descending pathway from the IC to the Vc could directly regulate orofacial pain, and ERK deactivation in the IC could effectively alleviate neuropathic pain as well as pain-related negative emotions in IoN-CCI rats, probably through this top–down pathway. These findings may

  20. 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. This...

  1. 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. (b...

  2. 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. (b...

  3. 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. (b...

  4. Ceftriaxone restores glutamate homeostasis and prevents relapse to cocaine seeking.

    PubMed

    Knackstedt, Lori A; Melendez, Roberto I; Kalivas, Peter W

    2010-01-01

    The cystine-glutamate exchanger is downregulated after chronic cocaine, resulting in reduced extracellular levels of nucleus accumbens glutamate. The importance of cocaine-induced loss of glutamate homeostasis is revealed by N-acetylcysteine restoring cystine-glutamate exchange and attenuating reinstatement to cocaine seeking. Another regulator of extracellular glutamate is the glial glutamate transporter GLT-1. We hypothesized that cocaine self-administration reduces GLT-1 and that GLT-1 upregulation inhibits cocaine seeking. We measured [(3)H] glutamate uptake and protein expression of GLT-1 and xCT, the catalytic subunit of the cystine-glutamate exchanger, following cocaine self-administration and 3 weeks of extinction training. We also examined the affect of ceftriaxone (previously shown to increase GLT-1) and N-acetylcysteine treatment on the expression of GLT-1 and xCT. Ceftriaxone was also tested for the capacity to inhibit cue- and cocaine-induced relapse. Cocaine self-administration reduced glutamate uptake and the expression of both GLT-1 and xCT. Ceftriaxone restored GLT-1 and xCT levels and prevented cue- and cocaine-induced reinstatement of drug seeking. N-acetylcysteine also restored GLT-1 and xCT levels. These results indicate that glutamate transport and cystine-glutamate exchange may be coregulated and provide further evidence that targeting glutamate homeostasis is a potential method for treating cocaine relapse.

  5. Localization of L-glutamate and glutamate-like receptors at the squid giant synapse.

    PubMed

    Di Cosmo, A; Nardi, G; Di Cristo, C; De Santis, A; Messenger, J B

    1999-08-28

    HPLC analysis of the amino acid contents of the second- and third-order giant fibres at the giant synapse in the stellate ganglion of the squid Loligo vulgaris shows that there are significantly higher amounts of L-glutamate and L-aspartate in the second-order (presynaptic) fibre than in the third-order (postsynaptic) fibre. Immunocytochemical staining of sections of the ganglion with an antibody raised against L-glutamate produces specific positive staining in the synaptic region of the second-order fibre. In contrast, staining with antibodies raised against glutamate-receptors (mammalian GluR1 with GluR2/3) produces positive staining in the third-order fibre at the postsynaptic region. These data provide further evidence for the hypothesis that L-glutamate is an excitatory transmitter at the giant synapse.

  6. 21 CFR 182.1500 - Monoammonium glutamate.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Monoammonium glutamate. 182.1500 Section 182.1500 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION (CONTINUED) SUBSTANCES GENERALLY RECOGNIZED AS SAFE Multiple Purpose GRAS Food...

  7. 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 Food...

  8. 21 CFR 182.1516 - Monopotassium glutamate.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Monopotassium glutamate. 182.1516 Section 182.1516 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) SUBSTANCES GENERALLY RECOGNIZED AS SAFE Multiple Purpose GRAS Food Substances § 182.1516 Monopotassium...

  9. 21 CFR 182.1500 - Monoammonium glutamate.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Monoammonium glutamate. 182.1500 Section 182.1500 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION (CONTINUED) SUBSTANCES GENERALLY RECOGNIZED AS SAFE Multiple Purpose GRAS Food...

  10. 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 Food...

  11. 21 CFR 582.1500 - Monoammonium glutamate.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 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 Food...

  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 Food...

  13. 21 CFR 182.1516 - Monopotassium glutamate.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Monopotassium glutamate. 182.1516 Section 182.1516 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION (CONTINUED) SUBSTANCES GENERALLY RECOGNIZED AS SAFE Multiple Purpose GRAS Food...

  14. 21 CFR 182.1500 - Monoammonium glutamate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Monoammonium glutamate. 182.1500 Section 182.1500 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION (CONTINUED) SUBSTANCES GENERALLY RECOGNIZED AS SAFE Multiple Purpose GRAS Food...

  15. 21 CFR 182.1516 - Monopotassium glutamate.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Monopotassium glutamate. 182.1516 Section 182.1516 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION (CONTINUED) SUBSTANCES GENERALLY RECOGNIZED AS SAFE Multiple Purpose GRAS Food...

  16. 21 CFR 582.1516 - Monopotassium glutamate.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 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 Food...

  17. 21 CFR 182.1500 - Monoammonium glutamate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Monoammonium glutamate. 182.1500 Section 182.1500 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION (CONTINUED) SUBSTANCES GENERALLY RECOGNIZED AS SAFE Multiple Purpose GRAS Food...

  18. 21 CFR 182.1516 - Monopotassium glutamate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Monopotassium glutamate. 182.1516 Section 182.1516 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION (CONTINUED) SUBSTANCES GENERALLY RECOGNIZED AS SAFE Multiple Purpose GRAS Food...

  19. 21 CFR 582.1516 - Monopotassium glutamate.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 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 Food...

  20. 21 CFR 582.1500 - Monoammonium glutamate.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 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 Food...

  1. 21 CFR 182.1516 - Monopotassium glutamate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Monopotassium glutamate. 182.1516 Section 182.1516 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION (CONTINUED) SUBSTANCES GENERALLY RECOGNIZED AS SAFE Multiple Purpose GRAS Food...

  2. 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 Food...

  3. 21 CFR 182.1500 - Monoammonium glutamate.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Monoammonium glutamate. 182.1500 Section 182.1500 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) SUBSTANCES GENERALLY RECOGNIZED AS SAFE Multiple Purpose GRAS Food Substances § 182.1500 Monoammonium...

  4. Glutamate Transmission Enhancement for Treatment of PTSD

    DTIC Science & Technology

    2010-09-01

    sessions or more of approximately 1h each to achieve significant beneficial effects. Thus, treatments that enhance the efficacy of extinction therapies...term medication. Preclinical studies have demonstrated that glutamate transmission in the amygdala is necessary for long term extinction of...fearmemories. Furthermore, d-cycloserine (DCS), a partial NMDA receptor agonist acting on the glycine modulator site, significantly enhances fear extinction

  5. 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.

  6. 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

  7. Direct effect of neuroleptics on glutamate release.

    PubMed

    Sherman, A D; Mott, J

    1984-11-01

    In studies designed to assess the pre-synaptic effects of neuroleptics in vitro, synaptosomes were prepared from several regions of rat brain. These preparations were incubated in the presence of a representative of each of the major classes of neuroleptic--chlorpromazine, haloperidol, or clozapine, or with (+) or (-)butaclamol. The calcium-specific release of endogenous glutamic acid was reduced only in synaptosomes derived from the amygdala. In this area, each of these agents [except (-)butaclamol] reduced the release of glutamic acid to a maximum of 40% in a concentration-dependent manner. When [3H]glutamine was included in the incubation media, a reduction in the released [3H]glutamate was present with 10(-8) M haloperidol, and 5 X 10(-8) M (+)butaclamol, clozapine, or chlorpromazine. (-)Butaclamol was inactive at 10(-5) M, a concentration producing complete blockade of the release of [3H]glutamic acid when active agents were included. Again, the effects were observed only in the amygdala. All agents, including (-)butaclamol blocked the uptake of [3H]glutamine into depolarized synaptosomes.

  8. Environmental drivers of megafaunal assemblage composition and biomass distribution over mainland and insular slopes of the Balearic Basin (Western Mediterranean)

    NASA Astrophysics Data System (ADS)

    Fanelli, E.; Cartes, J. E.; Papiol, V.; López-Pérez, C.

    2013-08-01

    The influence of mesoscale physical and trophic variables on deep-sea megafauna, a scale of variation often neglected in deep-sea studies, is crucial for understanding their role in the ecosystem. Drivers of megafaunal assemblage composition and biomass distribution have been investigated in two contrasting areas of the Balearic basin in the NW Mediterranean: on the mainland slope (Catalonian coasts) and on the insular slope (North of Mallorca, Balearic Islands). An experimental bottom trawl survey was carried out during summer 2010, at stations in both sub-areas located between 450 and 2200 m water depth. Environmental data were collected simultaneously: near-bottom physical parameters, and the elemental and isotopic composition of sediments. Initially, data were analysed along the whole depth gradient, and then assemblages from the two areas were compared. Analysis of the trawls showed the existence of one group associated with the upper slope (US=450-690 m), another with the middle slope (MS=1000-1300 m) and a third with the lower slope (LS=1400-2200 m). Also, significant differences in the assemblage composition were found between mainland and insular slopes at MS. Dominance by different species was evident when the two areas were compared by SIMPER analysis. The greatest fish biomass was recorded in both areas at 1000-1300 m, a zone linked to minimum temperature and maximum O2 concentration on the bottom. Near the mainland, fish assemblages were best explained (43% of total variance, DISTLM analysis) by prey availability (gelatinous zooplankton biomass). On the insular slope, trophic webs seemed less complex and were based on vertical input of surface primary production. Decapods, which reached their highest biomass values on the upper slope, were correlated with salinity and temperature in both the areas. However, while hydrographic conditions (temperature and salinity) seemed to be the most important variables over the insular slope, resource availability

  9. ¹³C-metabolic enrichment of glutamate in glutamate dehydrogenase mutants of Saccharomyces cerevisiae.

    PubMed

    Tang, Yijin; Sieg, Alex; Trotter, Pamela J

    2011-10-20

    Glutamate dehydrogenases (GDH) interconvert α-ketoglutarate and glutamate. In yeast, NADP-dependent enzymes, encoded by GDH1 and GDH3, are reported to synthesize glutamate from α-ketoglutarate, while an NAD-dependent enzyme, encoded by GDH2, catalyzes the reverse. Cells were grown in acetate/raffinose (YNAceRaf) to examine the role(s) of these enzymes during aerobic metabolism. In YNAceRaf the doubling time of wild type, gdh2Δ, and gdh3Δ cells was comparable at ∼4 h. NADP-dependent GDH activity (Gdh1p+Gdh3p) in wild type, gdh2Δ, and gdh3Δ was decreased ∼80% and NAD-dependent activity (Gdh2p) in wild type and gdh3Δ was increased ∼20-fold in YNAceRaf as compared to glucose. Cells carrying the gdh1Δ allele did not divide in YNAceRaf, yet both the NADP-dependent (Gdh3p) and NAD-dependent (Gdh2p) GDH activity was ∼3-fold higher than in glucose. Metabolism of [1,2-(13)C]-acetate and analysis of carbon NMR spectra were used to examine glutamate metabolism. Incorporation of (13)C into glutamate was nearly undetectable in gdh1Δ cells, reflecting a GDH activity at <15% of wild type. Analysis of (13)C-enrichment of glutamate carbons indicates a decreased rate of glutamate biosynthesis from acetate in gdh2Δ and gdh3Δ strains as compared to wild type. Further, the relative complexity of (13)C-isotopomers at early time points was noticeably greater in gdh3Δ as compared to wild type and gdh2Δ cells. These in vivo data show that Gdh1p is the primary GDH enzyme and Gdh2p and Gdh3p play evident roles during aerobic glutamate metabolism.

  10. Evidence for glutamate-mediated activation of hippocampal neurons by glial calcium waves.

    PubMed

    Hassinger, T D; Atkinson, P B; Strecker, G J; Whalen, L R; Dudek, F E; Kossel, A H; Kater, S B

    1995-10-01

    Communication from astrocytes to neurons has recently been reported by two laboratories, but different mechanisms were though to underlie glial calcium wave activation of associated neurons. Neuronal calcium elevation by glia observed in the present report is similar to that reported previously, where an increase in neuronal calcium was demonstrated in response to glial stimulation. In the present study hippocampal neurons plated on a confluent glial monolayer displayed a transient increase in intracellular calcium following a short delay after the passage of a wave of increased calcium in underlying glia. Activated cells displayed action potentials in response to glial waves and showed antineurofilament immunoreactivity. Finally, the N-methyl-D-aspartate glutamate receptor antagonist DL-2-amino-5-phosphonovaleric acid and the non-NMDA glutamate receptor antagonist 6,7-dinitroquinoxaline-2,3-dione significantly reduced the responsiveness of neurons to glial calcium waves. Our results indicate that hippocampal neurons growing on hippocampal or cortical astrocytes respond to glial calcium waves with elevations in calcium and increased electrical activity. Furthermore, we show that in most cases this communication appears to be mediated by ionotropic glutamate receptor channels.

  11. Does the thrifty phenotype result from chronic glutamate intoxication? A hypothesis.

    PubMed

    Hermanussen, Michael; Tresguerres, Jesus A F

    2003-01-01

    The thrifty phenotype hypothesis proposes that the epidemiological associations between poor fetal and infant growth and the subsequent development of the metabolic syndrome, result from the effects of poor nutrition in early life. The present review however, considers an opposite explanation. We hypothesize that fetal over-nutrition plays a major role in the development of the metabolic syndrome. We found evidence that the thrifty phenotype may be the consequence of fetal hyperglutamatemia. Maternal glutamate (GLU) reaches the fetal circulation, as part of the materno-fetal glutamine-glutamate exchange. Glutamine is absorbed from the maternal circulation, and deaminated for nitrogen utilization, resulting in a fetal production of GLU. GLU is extracted as it returns to the placenta. When the umbilical plasma flow is low, GLU may be trapped in the fetal circulation, and reaches neurotoxic levels. Administering GLU to newborn rodents completely destructs arcuate nucleus neurons, and results in permanently elevated plasma leptin levels that fail to adequately counter-regulate food intake. Chronic fetal exposure to elevated levels of GLU may be caused by chronic maternal over-nutrition or by reduced umbilical plasma flow. We strongly suggest abandoing the flavoring agent monosodium glutamate and reconsidering the recommended daily allowances of protein and amino acids during pregnancy.

  12. 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.

  13. TiO2 nanoparticle-induced neurotoxicity may be involved in dysfunction of glutamate metabolism and its receptor expression in mice.

    PubMed

    Ze, Xiao; Su, Mingyu; Zhao, Xiaoyang; Jiang, Hao; Hong, Jie; Yu, Xiaohong; Liu, Dong; Xu, Bingqing; Sheng, Lei; Zhou, Qiuping; Zhou, Junling; Cui, Jingwen; Li, Kai; Wang, Ling; Ze, Yuguan; Hong, Fashui

    2016-06-01

    Titanium dioxide nanoparticles (TiO2 NPs) have been used in environmental management, food, medicine, and industry. But TiO2 NPs have been demonstrated to cross the blood-brain barrier and store up in the brain organization, leading to glutamate-mediated neurotoxicity. However, the neurotoxicity in the brain is not well understood. In this study, mice were exposed to 1.25, 2.5, or 5 mg/kg body weight TiO2 NPs for 9 months, and the glutamate-glutamine cyclic pathway and expressions of glutamate receptors associated with the hippocampal neurotoxicity were investigated. Our findings showed elevations of glutamate release and phosphate-activated glutaminase activity, and reductions in glutamine and glutamine synthetase in the hippocampus following exposure to TiO2 NPs. Furthermore, TiO2 NPs significantly inhibited the expression of N-methyl-d-aspartate receptor subunits (including NR1, NR2A, and NR2B) and metabotropic glutamate receptor 2 in mouse hippocampus. These findings suggest that the imbalance of glutamate metabolism triggered inhibitions of glutamate receptor expression in the TiO2 NP-exposed hippocampus. © 2014 Wiley Periodicals, Inc. Environ Toxicol 31: 655-662, 2016. © 2014 Wiley Periodicals, Inc.

  14. The NMDA and AMPA/KA receptors are involved in glutamate-induced alterations of occludin expression and phosphorylation in brain endothelial cells.

    PubMed

    András, Ibolya E; Deli, Mária A; Veszelka, Szilvia; Hayashi, Kentaro; Hennig, Bernhard; Toborek, Michal

    2007-08-01

    Glutamate levels increase dramatically in cerebral ischemia and stroke. This may lead to opening of the blood-brain barrier (BBB) and induce further brain damage. Because endothelial tight junctions are critical elements of the BBB integrity, the aim of this study was to investigate the mechanisms of glutamate-induced alterations of the tight-junction protein occludin in cultured brain microvascular endothelial cells (BMECs). Transient exposure to glutamate resulted in cellular redistribution of occludin, followed by a decrease in the total level of this protein and diminished barrier function of BMECs. Inhibition of the N-methyl-D-aspartate (NMDA) or alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate/kainate (AMPA/KA) receptors attenuated glutamate-induced changes in occludin redistribution but not in the total protein levels. Treatment with glutamate also increased tyrosine phosphorylation and decreased threonine phosphorylation of occludin. Inhibition of the NMDA receptors by MK-801 partially protected against glutamate-induced elevation of occludin tyrosine phosphorylation. In addition, pretreatment with MK-801-attenuated glutamate-mediated disruption of endothelial barrier function. Blocking of the AMPA/KA receptors by 6,7-dinitroquinoxaline-2.3-dione (DNQX) protected against hypophosphorylation of threonine residues of occludin; however, it did not affect disruption of endothelial integrity. These findings indicate the opposite effects of the NMDA and AMPA/KA receptors on occludin phosphorylation and disruption of the BBB functions.

  15. Product Inhibition of the Fermentative Formation of Glutamic Acid

    PubMed Central

    Nunheimer, T. D.; Birnbaum, J.; Ihnen, E. D.; Demain, A. L.

    1970-01-01

    The addition of penicillin to cells of Corynebacterium glutamicum growing in 5-liter fermentors initiated the excretion of glutamic acid. The rate of glutamate production in fermentors declined continuously with time and reached 75% of the initial rate in 24 hr after penicillin had been added. The addition of glutamate to resting cell suspensions had only a slight effect on sugar utilization but caused a marked decrease in glutamate excretion. It is suggested that the high level of glutamate accumulating in the fermentation broth is responsible for inhibiting its own production. PMID:5480097

  16. Elevated Liver Enzymes

    MedlinePlus

    Symptoms Elevated liver enzymes By Mayo Clinic Staff Elevated liver enzymes may indicate inflammation or damage to cells in the liver. Inflamed or ... than normal amounts of certain chemicals, including liver enzymes, into the bloodstream, which can result in elevated ...

  17. Effects of insularity on digestion: living on islands induces shifts in physiological and morphological traits in island reptiles.

    PubMed

    Sagonas, Kostas; Pafilis, Panayiotis; Valakos, Efstratios D

    2015-10-01

    Living on islands entails numerous challenges for animals, among which resource scarcity stands out. In order to survive, animals have to optimize energy acquisition. We examined the impact of insularity on digestion comparing a series of physiological and morphological traits of adult males between insular and mainland populations of the Balkan green lizard. Island lizards had longer gastrointestinal tracts and gut passage times and higher digestive efficiencies. The dissection of the hindgut revealed an unexpected finding, the presence of cecal valves that were more frequent in island lizards. Thanks to all above islanders retain food for longer periods and thus maximize energy income and increase the amount of the extracted nutrients. That way, they secure energy income from the limited, in time and quantity, food resources of the islands.

  18. A new species of insular Rock Gecko (Genus Cnemaspis Strauch, 1887) from the Bidong Archipelago, Terengganu, Peninsular Malaysia.

    PubMed

    Grismer, L Lee; Wood, Perry L; Ahmad, Amirrudin B; Sumarli, Alexandra S-I; Vazquez, Jessika J; Ismail, Lukman H B; Nance, Ronald; Mohd-Amin, Muhammad Afif B; Othman, Mohamad N A B; Rizaijessika, Syed A; Kuss, Maria; Murdoch, Matthew; Cobos, Anthony

    2014-01-24

    A new insular species Cnemaspis bidongensis sp. nov. (Squamata: Gekkonidae), is described from Pulau Bidong, Terengganu, Peninsular Malaysia and bears a unique suite of morphological and color pattern characters that differentiate it from all other congeners. Cnemaspis bidongensis sp. nov. is the sister species to C. kendallii (Gray) and represents the fifth insular endemic species of Cnemaspis on archipelagos along the east coast of Peninsular Malaysia. This species survived massive deforestation of the small island of Bidong (260 ha) from the mid 1970s to the early 1990s when the island served as a Vietnamese refugee camp and harbored as many as 40,000 people at one time. We hypothesize that this species' generalized lifestyle contributed to its survival, allowing it to seek refuge in rocky microhabitats.

  19. Major Depressive Disorder and Alterations in Insular Cortical Activity: A Review of Current Functional Magnetic Imaging Research

    PubMed Central

    Sliz, Diane; Hayley, Shawn

    2012-01-01

    Major depressive disorder (MDD) is characterized by a dysregulated fronto-limbic network. The hyperactivation of limbic regions leads to increased attention and processing of emotional information, with a bias toward negative stimuli. Pathological ruminative behavior is a common symptom of depressive disorder whereby the individual is unable to disengage from internal mental processing of emotionally salient events. In fact, lower deactivations of the neural baseline resting state may account for the increased internal self-focus. The insular cortex, with its extensive connections to fronto-limbic and association areas has recently also been implicated to be a part of this network. Given its wide-reaching connectivity, it has been putatively implicated as an integration center of autonomic, visceromotor, emotional, and interoceptive information. The following paper will review recent imaging findings of altered insular function and connectivity in depressive pathology. PMID:23227005

  20. Effects of insularity on digestion: living on islands induces shifts in physiological and morphological traits in island reptiles

    NASA Astrophysics Data System (ADS)

    Sagonas, Kostas; Pafilis, Panayiotis; Valakos, Efstratios D.

    2015-10-01

    Living on islands entails numerous challenges for animals, among which resource scarcity stands out. In order to survive, animals have to optimize energy acquisition. We examined the impact of insularity on digestion comparing a series of physiological and morphological traits of adult males between insular and mainland populations of the Balkan green lizard. Island lizards had longer gastrointestinal tracts and gut passage times and higher digestive efficiencies. The dissection of the hindgut revealed an unexpected finding, the presence of cecal valves that were more frequent in island lizards. Thanks to all above islanders retain food for longer periods and thus maximize energy income and increase the amount of the extracted nutrients. That way, they secure energy income from the limited, in time and quantity, food resources of the islands.

  1. L-Glutamate and its Ionotropic Receptors in the Nervous System of Cephalopods

    PubMed Central

    Di Cosmo, A; Di Cristo, C; Messenger, JB

    2006-01-01

    In several species of cephalopod molluscs there is good evidence for the presence of L-glutamate in the central and peripheral nervous system and evidence for both classes of ionotropic receptor, AMPA/kainate and NMDA. The best evidence for glutamate being a transmitter in cephalopods comes from pharmacological, immunohistochemical and molecular investigations on the giant fibre system in the squid stellate ganglion. These studies confirm there are AMPA/kainate-like receptors on the third-order giant axon. In the (glial) Schwann cells associated with the giant axons both classes of glutamate receptor occur. Glutamate is an excitatory transmitter in the chromatophores and in certain somatic muscles and its action is mediated primarily via AMPA/kainate-like receptors, but at some chromatophores there are NMDA-like receptors. In the statocysts the afferent crista fibres are also glutamatergic, acting at non-NMDA receptors. In the brain (of Sepia) a neuronal NOS is activated by glutamate with subsequent production of nitric oxide and elevation of cGMP levels. This signal transduction pathway is blocked by D-AP-5, a specific antagonist of the NMDA receptor. Recently immunohistochemical analysis has demonstrated (in Sepia and Octopus) the presence of NMDAR2A /B – like receptors in motor centres, in the visual and olfactory systems and in the learning system. Physiological experiments have shown that glutamatergic transmission is involved in long term potentation (LTP) in the vertical lobe of Octopus, a brain area involved in learning. This effect seems to be mediated by non-NMDA receptors. Finally in the CNS of Sepia NMDA-mediated nitration of tyrosine residues of cytoskeletal protein such as α-tubulin, has been demonstrated. PMID:18654636

  2. HIF-1α triggers long-lasting glutamate excitotoxicity via system xc(-) in cerebral ischaemia-reperfusion.

    PubMed

    Hsieh, Chia-Hung; Lin, Yu-Jung; Chen, Wei-Ling; Huang, Yen-Chih; Chang, Chi-Wei; Cheng, Fu-Chou; Liu, Ren-Shyan; Shyu, Woei-Cherng

    2017-02-01

    Hypoxia-inducible factor 1α (HIF-1α) controls many genes involved in physiological and pathological processes. However, its roles in glutamatergic transmission and excitotoxicity are unclear. Here, we proposed that HIF-1α might contribute to glutamate-mediated excitotoxicity during cerebral ischaemia-reperfusion (CIR) and investigated its molecular mechanism. We showed that an HIF-1α conditional knockout mouse displayed an inhibition in CIR-induced elevation of extracellular glutamate and N-methyl-d-aspartate receptor (NMDAR) activation. By gene screening for glutamate transporters in cortical cells, we found that HIF-1α mainly regulates the cystine-glutamate transporter (system xc(-) ) subunit xCT by directly binding to its promoter; xCT and its function are up-regulated in the ischaemic brains of rodents and humans, and the effects lasted for several days. Genetic deletion of xCT in cortical cells of mice inhibits either oxygen glucose deprivation/reoxygenation (OGDR) or CIR-mediated glutamate excitotoxicity in vitro and in vivo. Pharmaceutical inhibition of system xc(-) by a clinically approved anti-cancer drug, sorafenib, improves infarct volume and functional outcome in rodents with CIR and its therapeutic window is at least 3 days. Taken together, these findings reveal that HIF-1α plays a role in CIR-induced glutamate excitotoxicity via the long-lasting activation of system xc(-) -dependent glutamate outflow and suggest that system xc(-) is a promising therapeutic target with an extended therapeutic window in stroke. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  3. K+ depolarization evokes ATP, adenosine and glutamate release from glia in rat hippocampus: a microelectrode biosensor study

    PubMed Central

    Heinrich, A; Andó, RD; Túri, G; Rózsa, B; Sperlágh, B

    2012-01-01

    BACKGROUND AND PURPOSE This study was undertaken to characterize the ATP, adenosine and glutamate outflow evoked by depolarization with high K+ concentrations, in slices of rat hippocampus. EXPERIMENTAL APPROACH We utilized the microelectrode biosensor technique and extracellular electrophysiological recording for the real-time monitoring of the efflux of ATP, adenosine and glutamate. KEY RESULTS ATP, adenosine and glutamate sensors exhibited transient and reversible current during depolarization with 25 mM K+, with distinct kinetics. The ecto-ATPase inhibitor ARL67156 enhanced the extracellular level of ATP and inhibited the prolonged adenosine efflux, suggesting that generation of adenosine may derive from the extracellular breakdown of ATP. Stimulation-evoked ATP, adenosine and glutamate efflux was inhibited by tetrodotoxin, while exposure to Ca2+-free medium abolished ATP and adenosine efflux from hippocampal slices. Extracellular elevation of ATP and adenosine were decreased in the presence of NMDA receptor antagonists, D-AP-5 and ifenprodil, whereas non-NMDA receptor blockade by CNQX inhibited glutamate but not ATP and adenosine efflux. The gliotoxin fluoroacetate and P2X7 receptor antagonists inhibited the K+-evoked ATP, adenosine and glutamate efflux, while carbenoxolone in low concentration and probenecid decreased only the adenosine efflux. CONCLUSIONS AND IMPLICATIONS Our results demonstrated activity-dependent gliotransmitter release in the hippocampus in response to ongoing neuronal activity. ATP and glutamate were released by P2X7 receptor activation into extracellular space. Although the increased extracellular levels of adenosine did derive from released ATP, adenosine might also be released directly via pannexin hemichannels. LINKED ARTICLE This article is commented on by Sershen, pp. 1000–1002 of this issue. To view this commentary visit http://dx.doi.org/10.1111/j.1476-5381.2012.02072.x PMID:22394324

  4. Expression of genes of lipid synthesis and altered lipid composition modulates L-glutamate efflux of Corynebacterium glutamicum.

    PubMed

    Nampoothiri, K M; Hoischen, C; Bathe, B; Möckel, B; Pfefferle, W; Krumbach, K; Sahm, H; Eggeling, L

    2002-01-01

    L-Glutamate is made with Corynebacterium glutamicum on a scale of more than 106 tons/year. Nevertheless, formation of this amino acid is enigmatic and there is very limited molecular information available to unravel the apparently complex conditions leading to L-glutamate efflux. Here, we report the isolation and overexpression of the genes involved in lipid synthesis: acp, fadD 15, cma, cls, pgsA2, cdsA, gpsA, and plsC, and the inactivation of cma and cls. In addition, the consequences for phospholipid content, temperature sensitivity, as well as detergent-independent and detergent-dependent L-glutamate efflux were quantified. An in part strong alteration of the phospholipid composition was achieved; for instance, overexpression offadD15 encoding an acyl-CoA ligase resulted in an increase of phosphatidyl inositol from 12.6 to 30.2%. All strains, except that overexpressing acp (acyl carrier protein), exhibited increased temperature sensitivity, with the strongest sensitivity present upon cls (cardiolipin synthetase) inactivation. As a consequence of the genetically modified lipid synthesis, L-glutamate efflux changed quite dramatically; for instance, overexpression of plsC (acylglycerolacyl transferase) resulted in a detergent-triggered increase of L-glutamate accumulation from 92 mM to 108 mM, whereas acp overexpression reduced the accumulation to 24 mM. With some of the overexpressed genes, substantial L-glutamate excretion even without detergent addition was obtained when the fermentation temperature was elevated. These data show that the chemical and physical properties of the cytoplasmic membrane are altered and suggest that this is a necessary precondition to achieve L-glutamate efflux.

  5. Understanding safety of glutamate in food and brain.

    PubMed

    Mallick, H N

    2007-01-01

    Glutamate is ubiquitous in nature and is present in all living organisms. It is the principal excitatory neurotransmitter in central nervous system. Glutamate is being used as food additive for enhancing flavour for over last 1200 years imparting a unique taste known as "umami" in Japanese. It is being marketed for about last 100 years. The taste of umami is now recognized as the fifth basic taste. Many of the foods used in cooking for enhancing flavour contain high amount of glutamate. Breast milk has the highest concentration of glutamate amongst all amino acids. Glutamate in high doses as gavage or parenteral injection have been reported to produce neurodegeneration in infant rodents. The neurodegeneration was not produced when gluamate was given with food. The Joint FAO/WHO Expert Committee on Food Additives, based on enumerable scientific evidence, has declared that, "glutamate as an additive in food" is not an health hazard to human being. Glutamate is used as signaling molecule not only in neuronal but also in non-neuronal tissues. Excessive accumulation of glutamate in the synaptic cleft has been associated with excitotoxicty and glutamate is implicated in number of neurological disorders. Excessive accumulation could be attributed to increase release, failure of transport system for uptake mechanism, neuronal injury due to hypoxia-ischemia, trauma and associated metabolic failures. The role blood brain barrier, vesicular glutamate and sodium dependent excitatory amino acid transporters in glutamate homeostasis are emphasized in the review.

  6. Building and Applying "Insularity Theory": Review on Knapp's Prehistoric and Protohistoric Cyprus, 2008.

    NASA Astrophysics Data System (ADS)

    Katsarou-Tzeveleki, Stella

    listing of external factors (colonization, invasions) originating in the Near East and the Aegean as sequential narrative history, and the descriptive, systemic analysis of 'materiality, production, trade, migration and colonization which have for long been the cornerstones of Cypriot archaeology' (p. 11). In contrast, he turns his attention towards the internal processes within the island society of Bronze Age Cyprus, which shape its insularity and give it a distinctive identity at this specific period, processes that lead to contextual history and formative tradition. 'To study how any society changes, at any time, it is crucial first to look at internal rather than external factors' (p. 1). Defining the concept of insularity is his aim; therefore, he begins with a number of very apposite rhetorical questions (p. 13) and identifies several individual parameters (connectivity, islandscape, social identity, ethnicity, migration, acculturation, hybridization) to which he assigns collective and individual meanings. The eight chapters that follow may be assigned, broadly, to three general units: in the first of these (ch. 1-2), Knapp offers a synthesis of these parameters in the form of a 'theory of insularity'. In the second (ch. 3-7) he formulates his revised narrative of the prehistory and social identity of the island, which involves a presentation of social and economic, rather than stylistic categories, on the basis of the parameters laid down in his theoretical scheme. Finally, in the third unit (ch. 8), he records his overall conclusions, the new cognitive experiences and concerns that have emerged from the application of his theory, both to Cyprus and to insular archaeology in the Mediterranean and on a world scale. Knapp's synthesis of the theory of insularity in the first unit is a major contribution to Mediterranean archaeology, and makes this book a seminal work. Continuing and broadening Broodbank's (2000) reasoning about the Cyclades, Knapp, with Cyprus as his

  7. Nitric Oxide Mediates Glutamate-Linked Enhancement of cGMP Levels in the Cerebellum

    NASA Astrophysics Data System (ADS)

    Bredt, David S.; Snyder, Solomon H.

    1989-11-01

    Nitric oxide, which mediates influences of numerous neurotransmitters and modulators on vascular smooth muscle and leukocytes, can be formed in the brain from arginine by an enzymatic activity that stoichiometrically generates citrulline. We show that glutamate and related amino acids, such as N-methyl-D-aspartate, markedly stimulate arginine-citrulline transformation in cerebellar slices stoichiometrically with enhancement of cGMP levels. Nω-monomethyl-L-arginine blocks the augmentation both of citrulline and cGMP with identical potencies. Arginine competitively reverses both effects of Nω-monomethyl-L-arginine with the same potencies. Hemoglobin, which complexes nitric oxide, prevents the stimulation by N-methyl-D-aspartate of cGMP levels, and superoxide dismutase, which elevates nitric oxide levels, increases cGMP formation. These data establish that nitric oxide mediates the stimulation by glutamate of cGMP formation.

  8. Nitric oxide mediates glutamate-linked enhancement of cGMP levels in the cerebellum.

    PubMed

    Bredt, D S; Snyder, S H

    1989-11-01

    Nitric oxide, which mediates influences of numerous neurotransmitters and modulators on vascular smooth muscle and leukocytes, can be formed in the brain from arginine by an enzymatic activity that stoichiometrically generates citrulline. We show that glutamate and related amino acids, such as N-methyl-D-aspartate, markedly stimulate arginine--citrulline transformation in cerebellar slices stoichiometrically with enhancement of cGMP levels. N omega-monomethyl-L-arginine blocks the augmentation both of citrulline and cGMP with identical potencies. Arginine competitively reverses both effects of N omega-monomethyl-L-arginine with the same potencies. Hemoglobin, which complexes nitric oxide, prevents the stimulation by N-methyl-D-aspartate of cGMP levels, and superoxide dismutase, which elevates nitric oxide levels, increases cGMP formation. These data establish that nitric oxide mediates the stimulation by glutamate of cGMP formation.

  9. Nitric oxide mediates glutamate-linked enhancement of cGMP levels in the cerebellum

    SciTech Connect

    Bredt, D.S.; Snyder, S.H. )

    1989-11-01

    Nitric oxide, which mediates influences of numerous neurotransmitters and modulators on vascular smooth muscle and leukocytes, can be formed in the brain from arginine by an enzymatic activity that stoichiometrically generates citrulline. The authors show that glutamate and related amino acids, such as N-methyl-D-aspartate, markedly stimulate arginine-citrulline transformation in cerebellar slices stoichiometrically with enhancement of cGMP levels. N{sup {omega}}-monomethyl-L-arginine blocks the augmentation both of citrulline and cGMP with identical potencies. Arginine competitively reverses both effects of N{sup {omega}}-monomethyl-L-arginine with the same potencies. Hemoglobin, which complexes nitric oxide, prevents the stimulation by N-methyl-D-aspartate of cGMP levels, and superoxide dismutase, which elevates nitric oxide levels, increases cGMP formation. These data establish that nitric oxide mediates the stimulation by glutamate of cGMP formation.

  10. Effect of systemic monosodium glutamate (MSG) on headache and pericranial muscle sensitivity.

    PubMed

    Baad-Hansen, L; Cairns, Be; Ernberg, M; Svensson, P

    2010-01-01

    We conducted a double-blinded, placebo-controlled, crossover study to investigate the occurrence of adverse effects such as headache as well as pain and mechanical sensitivity in pericranial muscles after oral administration of monosodium glutamate (MSG). In three sessions, 14 healthy men drank sugar-free soda that contained either MSG (75 or 150 mg/kg) or NaCl (24 mg/kg, placebo). Plasma glutamate level, pain, pressure pain thresholds and tolerance levels, blood pressure (BP), heart rate and reported adverse effects were assessed for 2 h. No muscle pain or robust changes in mechanical sensitivity were detected, but there was a significant increase in reports of headache and subjectively reported pericranial muscle tenderness after MSG. Systolic BP was elevated in the high MSG session compared with low MSG and placebo. These findings add new information to the concept of MSG headache and craniofacial pain sensitivity.

  11. Ibogaine alters synaptosomal and glial glutamate release and uptake.

    PubMed

    Leal, M B; Emanuelli, T; Porciúncula, L D; Souza, D O; Elisabetsky, E

    2001-02-12

    Ibogaine has aroused expectations as a potentially innovative medication for drug addiction. It has been proposed that antagonism of the NMDA receptor by ibogaine may be one of the mechanisms underlying its antiaddictive properties; glutamate has also been implicated in ibogaine-induced neurotoxicity. We here report the effects of ibogaine on [3H]glutamate release and uptake in cortical and cerebellar synaptosomes, as well as in cortical astrocyte cultures, from mice and rats. Ibogaine (2-1000 microM) had no effects on glutamate uptake or release by rat synaptosomes. However, ibogaine (500-1000 microM) significantly inhibited the glutamate uptake and stimulated the release of glutamate by cortical (but not cerebellar) synaptosomes of mice. In addition, ibogaine (1000 microM) nearly abolished glutamate uptake by cortical astrocyte cultures from rats and mice. The data provide direct evidence of glutamate involvement in ibogaine-induced neurotoxicity.

  12. Targeting glutamate homeostasis for potential treatment of nicotine dependence

    PubMed Central

    Alasmari, Fawaz; Al-Rejaie, Salim S.; AlSharari, Shakir D.; Sari, Youssef

    2015-01-01

    Several studies demonstrated that impairment in glutamatergic neurotransmission is linked to drug dependence and drug-seeking behavior. Increased extracellular glutamate concentration in mesocorticolimbic regions has been observed in animals developing nicotine dependence. Changes in glutamate release might be associated with stimulatory effect of nicotinic acetylcholine receptors (nAChRs) via nicotine exposure. We and others have shown increased extracellular glutamate concentration, which was associated with downregulation of the major glutamate transporter, glutamate transporter 1 (GLT-1), in brain reward regions of animals exposed to drug abuse, including nicotine and ethanol. Importantly, studies from our laboratory and others showed that upregulation of GLT-1 expression in the mesocorticolimbic brain regions may have potential therapeutic effects in drug dependence. In this review article, we discussed the effect of antagonizing presynaptic nAChRs in glutamate release, the upregulatory effect in GLT-1 expression and the role of glutamate receptors antagonists in the treatment of nicotine dependence. PMID:26589642

  13. Microsensors for in vivo Measurement of Glutamate in Brain Tissue

    PubMed Central

    Qin, Si; van der Zeyden, Miranda; Oldenziel, Weite H.; Cremers, Thomas I.F.H.; Westerink, Ben H.C.

    2008-01-01

    Several immobilized enzyme-based electrochemical biosensors for glutamate detection have been developed over the last decade. In this review, we compare first and second generation sensors. Structures, working mechanisms, interference prevention, in vitro detection characteristics and in vivo performance are summarized here for those sensors that have successfully detected brain glutamate in vivo. In brief, first generation sensors have a simpler structure and are faster in glutamate detection. They also show a better sensitivity to glutamate during calibration in vitro. For second generation sensors, besides their less precise detection, their fabrication is difficult to reproduce, even with a semi-automatic dip-coater. Both generations of sensors can detect glutamate levels in vivo, but the reported basal levels are different. In general, second generation sensors detect higher basal levels of glutamate compared with the results obtained from first generation sensors. However, whether the detected glutamate is indeed from synaptic sources is an issue that needs further attention. PMID:27873904

  14. Interregional cytogenetic comparisons in Halichoeres and Thalassoma wrasses (Labridae) of coastal and insular regions of the southwestern Atlantic.

    PubMed

    Amorim, K D J; Cioffi, M B; Bertollo, L A C; Soares, R X; Calado, L L; Borges, A T; Costa, G W W F; Molina, W F

    2017-05-10

    The distribution patterns of marine biodiversity are complex, resulting from vicariant events and species dispersion, as well as local ecological and adaptive conditions. Furthermore, the wide geographic distribution of some species may be hindered by biogeographical barriers that can interfere in the gene flow. Cytogenetic analyses in marine fishes, especially those involving populations in small remote insular environments, remain scarce. In the Western Atlantic, species of wrasses from the genera Halichoeres and Thalassoma occur in biogeographic arrangements that make it possible to analyze cytogenetic patterns between coastal and widely separated island populations. Species of these genera were punctually analyzed in some Atlantic regions. In this study, we compared several chromosomal features, such as karyotype macrostructure, heterochromatic patterns, patterns of base-specific fluorochromes, Ag-NORs, and 18S and 5S ribosomal sites in Thalassoma noronhanum, Halichoeres poeyi, and Halichoeres radiatus individuals from distinct coastal or insular regions of Atlantic. Notably, all of them are characterized by multiple 18S and 5S rDNA sites with syntenic arrangements in some chromosome pairs. Individuals of T. noronhanum (between the insular regions of Rocas Atoll and Fernando de Noronha Archipelago - FNA) and H. poeyi (coastal areas from Northeastern Brazil) show no detectable differences among their cytogenetic patterns. On the other hand, H. radiatus from FNA and São Pedro and São Paulo Archipelago exhibit differences in the frequency of rDNA sites that could suggest some level of population structuring between these insular regions. Interregional cytogenetic inventories of marine species with wide geographic distribution need to be rapidly expanded. These data will allow a better understanding of the level of chromosomal stability between vast oceanic spaces, which may be less than previously thought.

  15. A role for the insular cortex in long-term memory for context-evoked drug craving in rats.

    PubMed

    Contreras, Marco; Billeke, Pablo; Vicencio, Sergio; Madrid, Carlos; Perdomo, Guetón; González, Marcela; Torrealba, Fernando

    2012-08-01

    Drug craving critically depends on the function of the interoceptive insular cortex, and may be triggered by contextual cues. However, the role of the insula in the long-term memory linking context with drug craving remains unknown. Such a memory trace probably resides in some neocortical region, much like other declarative memories. Studies in humans and rats suggest that the insula may include such a region. Rats chronically implanted with bilateral injection cannulae into the high-order rostral agranular insular cortex (RAIC) or the primary interoceptive posterior insula (pIC) were conditioned to prefer the initially aversive compartment of a 2-compartment place preference apparatus by repeatedly pairing it to amphetamine. We found a reversible but long-lasting loss (ca. 24 days) of amphetamine-conditioned place preference (CPP) and a decreased expression in the insula of zif268, a crucial protein in memory reconsolidation, when anisomycin (ANI) was microinjected into the RAIC immediately after the reactivation of the conditioned amphetamine/context memory. ANI infusion into the RAIC without reactivation did not change CPP, whereas ANI infusion into pIC plus caused a 15 days loss of CPP. We also found a 24 days loss of CPP when we reversibly inactivated pIC during extinction trials. We interpret these findings as evidence that the insular cortex, including the RAIC, is involved in a context/drug effect association. These results add a drug-related memory function to the insular cortex to the previously found role of the pIC in the perception of craving or malaise.

  16. A Role for the Insular Cortex in Long-Term Memory for Context-Evoked Drug Craving in Rats

    PubMed Central

    Contreras, Marco; Billeke, Pablo; Vicencio, Sergio; Madrid, Carlos; Perdomo, Guetón; González, Marcela; Torrealba, Fernando

    2012-01-01

    Drug craving critically depends on the function of the interoceptive insular cortex, and may be triggered by contextual cues. However, the role of the insula in the long-term memory linking context with drug craving remains unknown. Such a memory trace probably resides in some neocortical region, much like other declarative memories. Studies in humans and rats suggest that the insula may include such a region. Rats chronically implanted with bilateral injection cannulae into the high-order rostral agranular insular cortex (RAIC) or the primary interoceptive posterior insula (pIC) were conditioned to prefer the initially aversive compartment of a 2-compartment place preference apparatus by repeatedly pairing it to amphetamine. We found a reversible but long-lasting loss (ca. 24 days) of amphetamine-conditioned place preference (CPP) and a decreased expression in the insula of zif268, a crucial protein in memory reconsolidation, when anisomycin (ANI) was microinjected into the RAIC immediately after the reactivation of the conditioned amphetamine/context memory. ANI infusion into the RAIC without reactivation did not change CPP, whereas ANI infusion into pIC plus caused a 15 days loss of CPP. We also found a 24 days loss of CPP when we reversibly inactivated pIC during extinction trials. We interpret these findings as evidence that the insular cortex, including the RAIC, is involved in a context/drug effect association. These results add a drug-related memory function to the insular cortex to the previously found role of the pIC in the perception of craving or malaise. PMID:22534623

  17. Topography of Gng2- and NetrinG2-Expression Suggests an Insular Origin of the Human Claustrum

    PubMed Central

    Pirone, Andrea; Cozzi, Bruno; Edelstein, Larry; Peruffo, Antonella; Lenzi, Carla; Quilici, Francesca; Antonini, Rita; Castagna, Maura

    2012-01-01

    The claustrum has been described in the forebrain of all mammals studied so far. It has been suggested that the claustrum plays a role in the integration of multisensory information: however, its detailed structure and function remain enigmatic. The human claustrum is a thin, irregular, sheet of grey matter located between the inner surface of the insular cortex and the outer surface of the putamen. Recently, the G-protein gamma2 subunit (Gng2) was proposed as a specific claustrum marker in the rat, and used to better delineate its anatomical boundaries and connections. Additional claustral markers proposed in mammals include Netrin-G2 in the monkey and latexin in the cat. Here we report the expression and distribution of Gng2 and Netrin-G2 in human post-mortem samples of the claustrum and adjacent structures. Gng2 immunoreactivity was detected in the neuropil of the claustrum and of the insular cortex but not in the putamen. A faint labelling was present also in the external and extreme capsules. Double-labelling experiments indicate that Gng2 is also expressed in glial cells. Netrin-G2 labelling was seen in neuronal cell bodies throughout the claustrum and the insular cortex but not in the medially adjacent putamen. No latexin immunoreactive element was detected in the claustrum or adjacent structures. Our results confirm that both the Gng2 and the Netrin-G2 proteins show an affinity to the claustrum and related formations also in the human brain. The presence of Gng2 and Netrin-G2 immunoreactive elements in the insular cortex, but not in the putamen, suggests a possible common ontogeny of the claustrum and insula. PMID:22957104

  18. Major histocompatibility complex variation in insular populations of the Egyptian vulture: inferences about the roles of genetic drift and selection.

    PubMed

    Agudo, Rosa; Alcaide, Miguel; Rico, Ciro; Lemus, Jesus A; Blanco, Guillermo; Hiraldo, Fernando; Donázar, Jose A

    2011-06-01

    Insular populations have attracted the attention of evolutionary biologists because of their morphological and ecological peculiarities with respect to their mainland counterparts. Founder effects and genetic drift are known to distribute neutral genetic variability in these demes. However, elucidating whether these evolutionary forces have also shaped adaptive variation is crucial to evaluate the real impact of reduced genetic variation in small populations. Genes of the major histocompatibility complex (MHC) are classical examples of evolutionarily relevant loci because of their well-known role in pathogen confrontation and clearance. In this study, we aim to disentangle the partial roles of genetic drift and natural selection in the spatial distribution of MHC variation in insular populations. To this end, we integrate the study of neutral (22 microsatellites and one mtDNA locus) and MHC class II variation in one mainland (Iberia) and two insular populations (Fuerteventura and Menorca) of the endangered Egyptian vulture (Neophron percnopterus). Overall, the distribution of the frequencies of individual MHC alleles (n=17 alleles from two class II B loci) does not significantly depart from neutral expectations, which indicates a prominent role for genetic drift over selection. However, our results point towards an interesting co-evolution of gene duplicates that maintains different pairs of divergent alleles in strong linkage disequilibrium on islands. We hypothesize that the co-evolution of genes may counteract the loss of genetic diversity in insular demes, maximize antigen recognition capabilities when gene diversity is reduced, and promote the co-segregation of the most efficient allele combinations to cope with local pathogen communities.

  19. Acetylated Chitosan Oligosaccharides Act as Antagonists against Glutamate-Induced PC12 Cell Death via Bcl-2/Bax Signal Pathway

    PubMed Central

    Hao, Cui; Gao, Lixia; Zhang, Yiran; Wang, Wei; Yu, Guangli; Guan, Huashi; Zhang, Lijuan; Li, Chunxia

    2015-01-01

    Chitosan oligosaccharides (COSs), depolymerized products of chitosan composed of β-(1→4) d-glucosamine units, have broad range of biological activities such as antitumour, antifungal, and antioxidant activities. In this study, peracetylated chitosan oligosaccharides (PACOs) and N-acetylated chitosan oligosaccharides (NACOs) were prepared from the COSs by chemcal modification. The structures of these monomers were identified using NMR and ESI-MS spectra. Their antagonist effects against glutamate-induced PC12 cell death were investigated. The results showed that pretreatment of PC12 cells with the PACOs markedly inhibited glutamate-induced cell death in a concentration-dependent manner. The PACOs were better glutamate antagonists compared to the COSs and the NACOs, suggesting the peracetylation is essential for the neuroprotective effects of chitosan oligosaccharides. In addition, the PACOs pretreatment significantly reduced lactate dehydrogenase release and reactive oxygen species production. It also attenuated the loss of mitochondrial membrane potential. Further studies indicated that the PACOs inhibited glutamate-induced cell death by preventing apoptosis through depressing the elevation of Bax/Bcl-2 ratio and caspase-3 activation. These results suggest that PACOs might be promising antagonists against glutamate-induced neural cell death. PMID:25775423

  20. Glutamate Acts as a Key Signal Linking Glucose Metabolism to Incretin/cAMP Action to Amplify Insulin Secretion

    PubMed Central

    Gheni, Ghupurjan; Ogura, Masahito; Iwasaki, Masahiro; Yokoi, Norihide; Minami, Kohtaro; Nakayama, Yasumune; Harada, Kazuo; Hastoy, Benoit; Wu, Xichen; Takahashi, Harumi; Kimura, Kazushi; Matsubara, Toshiya; Hoshikawa, Ritsuko; Hatano, Naoya; Sugawara, Kenji; Shibasaki, Tadao; Inagaki, Nobuya; Bamba, Takeshi; Mizoguchi, Akira; Fukusaki, Eiichiro; Rorsman, Patrik; Seino, Susumu

    2014-01-01

    Summary Incretins, hormones released by the gut after meal ingestion, are essential for maintaining systemic glucose homeostasis by stimulating insulin secretion. The effect of incretins on insulin secretion occurs only at elevated glucose concentrations and is mediated by cAMP signaling, but the mechanism linking glucose metabolism and cAMP action in insulin secretion is unknown. We show here, using a metabolomics-based approach, that cytosolic glutamate derived from the malate-aspartate shuttle upon glucose stimulation underlies the stimulatory effect of incretins and that glutamate uptake into insulin granules mediated by cAMP/PKA signaling amplifies insulin release. Glutamate production is diminished in an incretin-unresponsive, insulin-secreting β cell line and pancreatic islets of animal models of human diabetes and obesity. Conversely, a membrane-permeable glutamate precursor restores amplification of insulin secretion in these models. Thus, cytosolic glutamate represents the elusive link between glucose metabolism and cAMP action in incretin-induced insulin secretion. PMID:25373904

  1. An Ovarian Carcinoid Tumor With Peptide YY-Positive Insular Component: A Case Report and Review of the Literature.

    PubMed

    Erdenebaatar, Chimeddulam; Yamaguchi, Munekage; Saito, Fumitaka; Motooka, Chisato; Tashiro, Hironori; Katabuchi, Hidetaka

    2016-07-01

    Ovarian carcinoid tumors are uncommon and account for 1% of all carcinoid tumors. The insular type of ovarian carcinoid tumor is common in western countries; in contrast, the strumal and trabecular types seem to be common in Asian countries. Strumal and trabecular types are associated with peptide YY (PYY) production, which may cause constipation. Here, we report the case of a 70-yr-old Japanese woman with chronic constipation who was referred to Kumamoto University Hospital because of a right adnexal mass. Imaging tests suggested that the solid mass might be malignant; therefore, abdominal total hysterectomy, bilateral salpingo-oophorectomy, and omentectomy were performed. A subsequent histopathologic examination confirmed an insular carcinoid tumor with a trabecular component in the right ovary. Both components were positive for PYY but not for serotonin. The patient complained of diarrhea instead of constipation soon after the surgery. Because PYY-positive insular carcinoid tumor in the ovary has not been previously reported, we reviewed 19 reported cases of patients with PYY-positive ovarian carcinoid tumors. The origins, common histologic types and symptoms caused by specific peptides secreted in ovarian carcinoid tumors differ between western and Asian countries.

  2. In situ fluorescence imaging of glutamate-evoked mitochondrial Na+ responses in astrocytes.

    PubMed

    Bernardinelli, Yann; Azarias, Guillaume; Chatton, Jean-Yves

    2006-10-01

    Astrocytes can experience large intracellular Na+ changes following the activation of the Na+-coupled glutamate transport. The present study investigated whether cytosolic Na+ changes are transmitted to mitochondria, which could therefore influence their function and contribute to the overall intracellular Na+ regulation. Mitochondrial Na+ (Na+(mit)) changes were monitored using the Na+-sensitive fluorescent probe CoroNa Red (CR) in intact primary cortical astrocytes, as opposed to the classical isolated mitochondria preparation. The mitochondrial localization and Na+ sensitivity of the dye were first verified and indicated that it can be safely used as a selective Na+(mit) indicator. We found by simultaneously monitoring cytosolic and mitochondrial Na+ using sodium-binding benzofuran isophthalate and CR, respectively, that glutamate-evoked cytosolic Na+ elevations are transmitted to mitochondria. The resting Na+(mit) concentration was estimated at 19.0 +/- 0.8 mM, reaching 30.1 +/- 1.2 mM during 200 microM glutamate application. Blockers of conductances potentially mediating Na+ entry (calcium uniporter, monovalent cation conductances, K+(ATP) channels) were not able to prevent the Na+(mit) response to glutamate. However, Ca2+ and its exchange with Na+ appear to play an important role in mediating mitochondrial Na+ entry as chelating intracellular Ca2+ with BAPTA or inhibiting Na+/Ca2+ exchanger with CGP-37157 diminished the Na+(mit) response. Moreover, intracellular Ca2+ increase achieved by photoactivation of caged Ca2+ also induced a Na+(mit) elevation. Inhibition of mitochondrial Na/H antiporter using ethylisopropyl-amiloride caused a steady increase in Na+(mit) without increasing cytosolic Na+, indicating that Na+ extrusion from mitochondria is mediated by these exchangers. Thus, mitochondria in intact astrocytes are equipped to efficiently sense cellular Na+ signals and to dynamically regulate their Na+ content.

  3. Neuronal Activity and Glutamate Uptake Decrease Mitochondrial Mobility in Astrocytes and Position Mitochondria Near Glutamate Transporters

    PubMed Central

    Jackson, Joshua G.; O'Donnell, John C.; Takano, Hajime; Coulter, Douglas A.

    2014-01-01

    Within neurons, mitochondria are nonuniformly distributed and are retained at sites of high activity and metabolic demand. Glutamate transport and the concomitant activation of the Na+/K+-ATPase represent a substantial energetic demand on astrocytes. We hypothesized that mitochondrial mobility within astrocytic processes might be regulated by neuronal activity and glutamate transport. We imaged organotypic hippocampal slice cultures of rat, in which astrocytes maintain their highly branched morphologies and express glutamate transporters. Using time-lapse confocal microscopy, the mobility of mitochondria within individual astrocytic processes and neuronal dendrites was tracked. Within neurons, a greater percentage of mitochondria were mobile than in astrocytes. Furthermore, they moved faster and farther than in astrocytes. Inhibiting neuronal activity with tetrodotoxin (TTX) increased the percentage of mobile mitochondria in astrocytes. Mitochondrial movement in astrocytes was inhibited by vinblastine and cytochalasin D, demonstrating that this mobility depends on both the microtubule and actin cytoskeletons. Inhibition of glutamate transport tripled the percentage of mobile mitochondria in astrocytes. Conversely, application of the transporter substrate d-aspartate reversed the TTX-induced increase in the percentage of mobile mitochondria. Inhibition of reversed Na+/Ca2+ exchange also increased the percentage of mitochondria that were mobile. Last, we demonstrated that neuronal activity increases the probability that mitochondria appose GLT-1 particles within astrocyte processes, without changing the proximity of GLT-1 particles to VGLUT1. These results imply that neuronal activity and the resulting clearance of glutamate by astrocytes regulate the movement of astrocytic mitochondria and suggest a mechanism by which glutamate transporters might retain mitochondria at sites of glutamate uptake. PMID:24478345

  4. Glutamate alteration of glutamic acid decarboxylase (GAD) in GABAergic neurons: the role of cysteine proteases.

    PubMed

    Monnerie, Hubert; Le Roux, Peter D

    2008-09-01

    Brain cell vulnerability to neurologic insults varies greatly, depending on their neuronal subpopulation. Among cells that survive a pathological insult such as ischemia or brain trauma, some may undergo morphological and/or biochemical changes that could compromise brain function. We previously reported that surviving cortical GABAergic neurons exposed to glutamate in vitro displayed an NMDA receptor (NMDAR)-mediated alteration in the levels of the GABA synthesizing enzyme glutamic acid decarboxylase (GAD65/67) [Monnerie, H., Le Roux, P., 2007. Reduced dendrite growth and altered glutamic acid decarboxylase (GAD) 65- and 67-kDa isoform protein expression from mouse cortical GABAergic neurons following excitotoxic injury in vitro. Exp. Neurol. 205, 367-382]. In this study, we examined the mechanisms by which glutamate excitotoxicity caused a change in cortical GABAergic neurons' GAD protein levels. Removing extracellular calcium prevented the NMDAR-mediated decrease in GAD protein levels, measured using Western blot techniques, whereas inhibiting calcium entry through voltage-gated calcium channels had no effect. Glutamate's effect on GAD protein isoforms was significantly attenuated by preincubation with the cysteine protease inhibitor N-Acetyl-L-Leucyl-L-Leucyl-L-norleucinal (ALLN). Using class-specific protease inhibitors, we observed that ALLN's effect resulted from the blockade of calpain and cathepsin protease activities. Cell-free proteolysis assay confirmed that both proteases were involved in glutamate-induced alteration in GAD protein levels. Together these results suggest that glutamate-induced excitotoxic stimulation of NMDAR in cultured cortical neurons leads to altered GAD protein levels from GABAergic neurons through intracellular calcium increase and protease activation including calpain and cathepsin. Biochemical alterations in surviving cortical GABAergic neurons in various disease states may contribute to the altered balance between excitation

  5. Modafinil attenuates reinstatement of cocaine seeking: role for cystine-glutamate exchange and metabotropic glutamate receptors.

    PubMed

    Mahler, Stephen V; Hensley-Simon, Megan; Tahsili-Fahadan, Pouya; LaLumiere, Ryan T; Thomas, Charles; Fallon, Rebecca V; Kalivas, Peter W; Aston-Jones, Gary

    2014-01-01

    Modafinil may be useful for treating stimulant abuse, but the mechanisms by which it acts to do so are unknown. Indeed, a primary effect of modafinil is to inhibit dopamine transport, which typically promotes rather than inhibits motivated behavior. Therefore, we examined the role of nucleus accumbens extracellular glutamate and the group II metabotropic glutamate receptor (mGluR2/3) in modafinil effects. One group of rats was trained to self-administer cocaine for 10 days and extinguished, then given priming injections of cocaine to elicit reinstatement. Modafinil (300 mg/kg, intraperitoneal) inhibited reinstated cocaine seeking (but did not alter extinction responding by itself), and this effect was prevented by pre-treatment with bilateral microinjections of the mGluR2/3 antagonist LY-341495 (LY) into nucleus accumbens core. No reversal of modafinil effects was seen after unilateral accumbens core LY, or bilateral LY in the rostral pole of accumbens. Next, we sought to explore effects of modafinil on extracellular glutamate levels in accumbens after chronic cocaine. Separate rats were administered non-contingent cocaine, and after 3 weeks of withdrawal underwent accumbens microdialysis. Modafinil increased extracellular accumbens glutamate in chronic cocaine, but not chronic saline-pre-treated animals. This increase was prevented by reverse dialysis of cystine-glutamate exchange or voltage-dependent calcium channel antagonists. Voltage-dependent sodium channel blockade partly attenuated the increase in glutamate, but mGluR1 blockade did not. We conclude that modafinil increases extracellular glutamate in nucleus accumbens from glial and neuronal sources in cocaine-exposed rats, which may be important for its mGluR2/3-mediated antirelapse properties. © 2012 The Authors, Addiction Biology © 2012 Society for the Study of Addiction.

  6. Modafinil Attenuates Reinstatement of Cocaine Seeking: Role for Cystine-Glutamate Exchange and Metabotropic Glutamate Receptors

    PubMed Central

    Mahler, Stephen V; Hensley-Simon, Megan; Tahsili-Fahadan, Pouya; LaLumiere, Ryan T; Thomas, Charles; Fallon, Rebecca V; Kalivas, Peter W; Aston-Jones, Gary

    2012-01-01

    Modafinil may be useful for treating stimulant abuse, but the mechanisms by which it does so are unknown. Indeed, a primary effect of modafinil is to inhibit dopamine transport, which typically promotes rather than inhibits motivated behavior. Therefore, we examined the role of nucleus accumbens extracellular glutamate and the group II metabotropic glutamate receptor (mGluR2/3) in modafinil effects. One group of rats was trained to self-administer cocaine for 10 days and extinguished, then given priming injections of cocaine to elicit reinstatement. Modafinil (300 mg/kg, i.p.) inhibited reinstated cocaine-seeking (but did not alter extinction responding by itself), and this effect was prevented by pretreatment with bilateral microinjections of the mGluR2/3 antagonist LY-341495 (LY) into nucleus accumbens core. No reversal of modafinil effects was seen after unilateral accumbens core LY, or bilateral LY in the rostral pole of accumbens. Next, we sought to explore effects of modafinil on extracellular glutamate levels in accumbens after chronic cocaine. Separate rats were administered non-contingent cocaine, and after 3 weeks of withdrawal underwent accumbens microdialysis. Modafinil increased extracellular accumbens glutamate in chronic cocaine, but not chronic saline pretreated animals. This increase was prevented by reverse dialysis of cystine-glutamate exchange or voltage-dependent calcium channel antagonists. Voltage-dependent sodium channel blockade partly attenuated the increase in glutamate, but mGluR1 blockade did not. We conclude that modafinil increases extracellular glutamate in nucleus accumbens from glial and neuronal sources in cocaine-exposed rats, which may be important for its mGluR2/3-mediated anti-relapse properties. PMID:23017017

  7. Sertraline reduces glutamate uptake in human platelets.

    PubMed

    Rodrigues, Débora Olmedo; Bristot, Ivi Juliana; Klamt, Fábio; Frizzo, Marcos Emílio

    2015-12-01

    Mitochondrial damage and declines in ATP levels have been recently attributed to sertraline. The effects of sertraline on different parameters were investigated in washed platelets from 18 healthy male volunteers, after 24h of drug exposure. Sertraline toxicity was observed only at the highest concentrations, 30 and 100 μM, which significantly reduced platelet viability to 76 ± 3% and 20 ± 2%, respectively. The same concentrations significantly decreased total ATP to 73 ± 3% and 13 ± 2%, respectively. Basal values of glycogen were not significantly affected by sertraline treatment. Glutamate uptake was significantly reduced after treatment with 3, 30 and 100 μM, by 28 ± 6%, 32 ± 5% and 54 ± 4%, respectively. Our data showed that sertraline at therapeutic concentrations does not compromise platelet viability and ATP levels, but they suggest that in a situation where extracellular glutamate levels are potentially increased, sertraline might aggravate an excitotoxic condition. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Metabotropic Glutamate Receptors: Physiology, Pharmacology, and Disease

    PubMed Central

    Niswender, Colleen M.; Conn, P. Jeffrey

    2010-01-01

    The metabotropic glutamate receptors (mGluRs) are family C G-protein-coupled receptors that participate in the modulation of synaptic transmission and neuronal excitability throughout the central nervous system. The mGluRs bind glutamate within a large extracellular domain and transmit signals through the receptor protein to intracellular signaling partners. A great deal of progress has been made in determining the mechanisms by which mGluRs are activated, proteins with which they interact, and orthosteric and allosteric ligands that can modulate receptor activity. The widespread expression of mGluRs makes these receptors particularly attractive drug targets, and recent studies continue to validate the therapeutic utility of mGluR ligands in neurological and psychiatric disorders such as Alzheimer’s disease, Parkinson’s disease, anxiety, depression, and schizophrenia. PMID:20055706

  9. 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

  10. Striatal glutamate antagonism induces contralateral neglect.

    PubMed

    Schuller, J J; Tran, D D; Marshall, J F

    1998-03-30

    To assess the role of striatal glutamatergic synapses in mediating sensorimotor orientation behavior, glutamate receptor antagonists were infused into the left striatum of awake rats and behavioral orientation to contralateral and ipsilateral stimuli were quantified. The AMPA-kainate antagonist, DNQX, and the NMDA antagonist, CPP, both induced a large asymmetry in responding, such that the rats oriented much less to stimuli presented contralateral to the antagonist infusions. Furthermore, intrastriatal glutamate antagonist infusions increased the occurrence of incorrect responses, or turning away from a contralaterally-presented stimulus. In a separate experiment, intrastriatal DNQX was shown to block kainic acid (KA)-induced Fos expression in the striatum, but not in adjacent cerebral cortex, suggesting that the diffusion of this drug is restricted to the striatum.

  11. 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

  12. Potentiation of lead-induced cell death in PC12 cells by glutamate: protection by N-acetylcysteine amide (NACA), a novel thiol antioxidant.

    PubMed

    Penugonda, Suman; Mare, Suneetha; Lutz, P; Banks, William A; Ercal, Nuran

    2006-10-15

    Oxidative stress has been implicated as an important factor in many neurological diseases. Oxidative toxicity in a number of these conditions is induced by excessive glutamate release and subsequent glutamatergic neuronal stimulation. This, in turn, causes increased generation of reactive oxygen species (ROS), oxidative stress, excitotoxicity, and neuronal damage. Recent studies indicate that the glutamatergic neurotransmitter system is involved in lead-induced neurotoxicity. Therefore, this study aimed to (1) investigate the potential effects of glutamate on lead-induced PC12 cell death and (2) elucidate whether the novel thiol antioxidant N-acetylcysteine amide (NACA) had any protective abilities against such cytotoxicity. Our results suggest that glutamate (1 mM) potentiates lead-induced cytotoxicity by increased generation of ROS, decreased proliferation (MTS), decreased glutathione (GSH) levels, and depletion of cellular adenosine-triphosphate (ATP). Consistent with its ability to decrease ATP levels and induce cell death, lead also increased caspase-3 activity, an effect potentiated by glutamate. Exposure to glutamate and lead elevated the cellular malondialdehyde (MDA) levels and phospholipase-A(2) (PLA(2)) activity and diminished the glutamine synthetase (GS) activity. NACA protected PC12 cells from the cytotoxic effects of glutamate plus lead, as evaluated by MTS assay. NACA reduced the decrease in the cellular ATP levels and restored the intracellular GSH levels. The increased levels of ROS and MDA in glutamate-lead treated cells were significantly decreased by NACA. In conclusion, our data showed that glutamate potentiated the effects of lead-induced PC12 cell death by a mechanism involving mitochondrial dysfunction (ATP depletion) and oxidative stress. NACA had a protective role against the combined toxic effects of glutamate and lead by inhibiting lipid peroxidation and scavenging ROS, thus preserving intracellular GSH.

  13. Potentiation of lead-induced cell death in PC12 cells by glutamate: Protection by N-acetylcysteine amide (NACA), a novel thiol antioxidant

    SciTech Connect

    Penugonda, Suman; Mare, Suneetha; Lutz, P.; Banks, William A.; Ercal, Nuran . E-mail: nercal@umr.edu

    2006-10-15

    Oxidative stress has been implicated as an important factor in many neurological diseases. Oxidative toxicity in a number of these conditions is induced by excessive glutamate release and subsequent glutamatergic neuronal stimulation. This, in turn, causes increased generation of reactive oxygen species (ROS), oxidative stress, excitotoxicity, and neuronal damage. Recent studies indicate that the glutamatergic neurotransmitter system is involved in lead-induced neurotoxicity. Therefore, this study aimed to (1) investigate the potential effects of glutamate on lead-induced PC12 cell death and (2) elucidate whether the novel thiol antioxidant N-acetylcysteine amide (NACA) had any protective abilities against such cytotoxicity. Our results suggest that glutamate (1 mM) potentiates lead-induced cytotoxicity by increased generation of ROS, decreased proliferation (MTS), decreased glutathione (GSH) levels, and depletion of cellular adenosine-triphosphate (ATP). Consistent with its ability to decrease ATP levels and induce cell death, lead also increased caspase-3 activity, an effect potentiated by glutamate. Exposure to glutamate and lead elevated the cellular malondialdehyde (MDA) levels and phospholipase-A{sub 2} (PLA{sub 2}) activity and diminished the glutamine synthetase (GS) activity. NACA protected PC12 cells from the cytotoxic effects of glutamate plus lead, as evaluated by MTS assay. NACA reduced the decrease in the cellular ATP levels and restored the intracellular GSH levels. The increased levels of ROS and MDA in glutamate-lead treated cells were significantly decreased by NACA. In conclusion, our data showed that glutamate potentiated the effects of lead-induced PC12 cell death by a mechanism involving mitochondrial dysfunction (ATP depletion) and oxidative stress. NACA had a protective role against the combined toxic effects of glutamate and lead by inhibiting lipid peroxidation and scavenging ROS, thus preserving intracellular GSH.

  14. Kinetic studies of dogfish liver glutamate dehydrogenase.

    PubMed Central

    Electricwala, A H; Dickinson, F M

    1979-01-01

    Initial-rate studies were made of the oxidation of L-glutamate by NAD+ and NADP+ catalysed by highly purified preparations of dogfish liver glutamate dehydrogenase. With NAD+ as coenzyme the kinetics show the same features of coenzyme activation as seen with the bovine liver enzyme [Engel & Dalziel (1969) Biochem. J. 115, 621--631]. With NADP+ as coenzyme, initial rates are much slower than with NAD+, and Lineweaver--Burk plots are linear over extended ranges of substrate and coenzyme concentration. Stopped-flow studies with NADP+ as coenzyme give no evidence for the accumulation of significant concentrations of NADPH-containing complexes with the enzyme in the steady state. Protection studies against inactivation by pyridoxal 5'-phosphate indicate that NAD+ and NADP+ give the same degree of protection in the presence of sodium glutarate. The results are used to deduce information about the mechanism of glutamate oxidation by the enzyme. Initial-rate studies of the reductive amination of 2-oxoglutarate by NADH and NADPH catalysed by dogfish liver glutamate dehydrogenase showed that the kinetic features of the reaction are very similar with both coenzymes, but reactions with NADH are much faster. The data show that a number of possible mechanisms for the reaction may be discarded, including the compulsory mechanism (previously proposed for the enzyme) in which the sequence of binding is NAD(P)H, NH4+ and 2-oxoglutarate. The kinetic data suggest either a rapid-equilibrium random mechanism or the compulsory mechanism with the binding sequence NH4+, NAD(P)H, 2-oxoglutarate. However, binding studies and protection studies indicate that coenzyme and 2-oxoglutarate do bind to the free enzyme. PMID:35153

  15. Mechanism of glutamate uptake in Zymomonas mobilis.

    PubMed Central

    Ruhrmann, J; Krämer, R

    1992-01-01

    The energetics of the anaerobic gram-negative bacterium Zymomonas mobilis, a well-known ethanol-producing organism, is based solely on synthesis of 1 mol of ATP per mol of glucose by the Entner-Doudoroff pathway. When grown in the presence of glucose as a carbon and energy source, Z. mobilis had a cytosolic ATP content of 3.5 to 4 mM. Because of effective pH homeostasis, the components of the proton motive force strongly depended on the external pH. At pH 5.5, i.e., around the optimal pH for growth, the proton motive force was about -135 mV and was composed of a pH gradient of 0.6 pH units (internal pH 6.1) and a membrane potential of about -100 mV. Measurement of these parameters was complicated since ionophores and lipophilic probes were ineffective in this organism. So far, only glucose transport by facilitated diffusion is well characterized for Z. mobilis. We investigated a constitutive secondary glutamate uptake system. Glutamate can be used as a nitrogen source for Z. mobilis. Transport of glutamate at pH 5.5 shows a relatively high Vmax of 40 mumol.min-1.g (dry mass) of cells-1 and a low affinity (Km = 1.05 mM). Glutamate is taken up by a symport with two H+ ions, leading to substantial accumulation in the cytosol at low pH values. PMID:1332937

  16. Glutamate dehydrogenase (RocG) in Bacillus licheniformis WX-02: Enzymatic properties and specific functions in glutamic acid synthesis for poly-γ-glutamic acid production.

    PubMed

    Tian, Guangming; Wang, Qin; Wei, Xuetuan; Ma, Xin; Chen, Shouwen

    2017-04-01

    Poly-γ-glutamic acid (γ-PGA), a natural biopolymer, is widely used in cosmetics, medicine, food, water treatment, and agriculture owing to its features of moisture sequestration, cation chelation, non-toxicity and biodegradability. Intracellular glutamic acid, the substrate of γ-PGA, is a limiting factor for high yield in γ-PGA production. Bacillus subtilis and Bacillus licheniformis are both important γ-PGA producing strains, and B. subtilis synthesizes glutamic acid in vivo using the unique GOGAT/GS pathway. However, little is known about the glutamate synthesis pathway in B. licheniformis. The aim of this work was to characterize the glutamate dehydrogenase (RocG) in glutamic acid synthesis from B. licheniformis with both in vivo and in vitro experiments. By re-directing the carbon flux distribution, the rocG gene deletion mutant WX-02ΔrocG produced intracellular glutamic acid with a concentration of 90ng/log(CFU), which was only 23.7% that of the wild-type WX-02 (380ng/log(CFU)). Furthermore, the γ-PGA yield of mutant WX-02ΔrocG was 5.37g/L, a decrease of 45.3% compared to the wild type (9.82g/L). In vitro enzymatic assays of RocG showed that RocG has higher affinity for 2-oxoglutarate than glutamate, and the glutamate synthesis rate was far above degradation. This is probably the first study to reveal the glutamic acid synthesis pathway and the specific functions of RocG in B. licheniformis. The results indicate that γ-PGA production can be enhanced through improving intracellular glutamic acid synthesis.

  17. Local enhancement and social foraging in a non-social insular lizard.

    PubMed

    Pérez-Cembranos, Ana; Pérez-Mellado, Valentín

    2015-05-01

    Even in solitary foragers, conspecifics can provide reliable information about food location. The insular lizard Podarcis lilfordi is a solitary species with high population densities that sometimes aggregate around rich food patches. Its diet includes novel and unpredictable resources, such as carcasses or plants, whose exploitation quickly became widespread among the population. We tested the use of social information by lizards through some field experiments in which they had to choose one of the two pieces of fruit. Probably due to local enhancement, lizards preferred to feed on the piece of fruit where conspecifics or lizard-shaped models were already present. Conspecifics' behaviour, but also their mere presence, seems to be a valuable source of information to decide where to feed. Lizards also showed a strong attraction to conspecifics, even in the absence of food. Maybe the presence of a group is interpreted as an indirect cue for the presence of food. The group size was not important to females, but males had a significantly higher attraction towards groups with three conspecifics. We discuss some characteristics of P. lilfordi at Aire Island that can explain the development of the observed social foraging, as well as their possible consequences.

  18. Increased cellular activity in rat insular cortex after water and salt ingestion induced by fluid depletion.

    PubMed

    Pastuskovas, Cinthia V; Cassell, Martin D; Johnson, Alan Kim; Thunhorst, Robert L

    2003-04-01

    Insular cortex (IC) receives inputs from multiple sensory systems, including taste, and from receptors that monitor body electrolyte and fluid balance and blood pressure. This work analyzed metabolic activity of IC cells after water and sodium ingestion induced by sodium depletion. Rats were injected with the diuretic furosemide (10 mg/kg body wt), followed 5 min later by injections of the angiotensin-converting enzyme inhibitor captopril (5 mg/kg body wt). After 90 min, some rats received water and 0.3 M NaCl to drink for 2 h while others did not. A third group had access to water and saline but was not depleted of fluids. All rats were killed for processing of brain tissue for Fos-immunoreactivity (Fos-ir). Nondepleted animals had weak-to-moderate levels of Fos-ir within subregions of IC. Fluid-depleted rats without fluid access had significantly increased Fos-ir in all areas of IC. Levels of Fos-ir were highest in fluid-depleted rats that drank water and sodium. Fos-ir levels were highest in anterior regions of IC and lowest in posterior regions of IC. These results implicate visceral, taste, and/or postingestional factors in the increased metabolic activity of cells in IC.

  19. Central role for the insular cortex in mediating conditioned responses to anticipatory cues

    PubMed Central

    Kusumoto-Yoshida, Ikue; Liu, Haixin; Chen, Billy T.; Fontanini, Alfredo; Bonci, Antonello

    2015-01-01

    Reward-related circuits are fundamental for initiating feeding on the basis of food-predicting cues, whereas gustatory circuits are believed to be involved in the evaluation of food during consumption. However, accumulating evidence challenges such a rigid separation. The insular cortex (IC), an area largely studied in rodents for its role in taste processing, is involved in representing anticipatory cues. Although IC responses to anticipatory cues are well established, the role of IC cue-related activity in mediating feeding behaviors is poorly understood. Here, we examined the involvement of the IC in the expression of cue-triggered food approach in mice trained with a Pavlovian conditioning paradigm. We observed a significant change in neuronal firing during presentation of the cue. Pharmacological silencing of the IC inhibited food port approach. Such a behavior could be recapitulated by temporally selective inactivation during the cue. These findings represent the first evidence, to our knowledge, that cue-evoked neuronal activity in the mouse IC modulates behavioral output, and demonstrate a causal link between cue responses and feeding behaviors. PMID:25583486

  20. Palaeoenvironments of insular Southeast Asia during the Last Glacial Period: a savanna corridor in Sundaland?

    NASA Astrophysics Data System (ADS)

    Bird, Michael I.; Taylor, David; Hunt, Chris

    2005-11-01

    Consideration of a range of evidence from geomorphology, palynology, biogeography and vegetation/climate modelling suggests that a north-south 'savanna corridor' did exist through the continent of Sundaland (modern insular Indonesia and Malaysia) through the Last Glacial Period (LGP) at times of lowered sea-level, as originally proposed by Heaney [1991. Climatic Change 19, 53-61]. A minimal interpretation of the size of this corridor requires a narrow but continuous zone of open 'savanna' vegetation 50-150 km wide, running along the sand-covered divide between the modern South China and Java Seas. This area formed a land bridge between the Malaysian Peninsula and the major islands of Sumatra, Java and Borneo. The savanna corridor connected similar open vegetation types north and south of the equator, and served as a barrier to the dispersal of rainforest-dependent species between Sumatra and Borneo. A maximal interpretation of the available evidence is compatible with the existence of a broad savanna corridor, with forest restricted to refugia primarily in Sumatra, Borneo and the continental shelf beneath the modern South China Sea. This savanna corridor may have provided a convenient route for the rapid early dispersal of modern humans through the region and on into Australasia.

  1. Salvinorin A reduces neuropathic nociception in the insular cortex of the rat.

    PubMed

    Coffeen, U; Canseco-Alba, A; Simón-Arceo, K; Almanza, A; Mercado, F; León-Olea, M; Pellicer, F

    2017-10-04

    Neuropathic pain is one of the most important challenges in public health. The search for novel treatments is important for an adequate relief without adverse effects. In this sense salvinorin A (SA), the main diterpene of the medicinal plant Salvia divinorum is an important antinociceptive compound, which acts as a potent agonist of kappa opioid receptor (KOR) and cannabinoid CB1 receptors. We evaluated nociceptive responses in a neuropathic pain model induced by the sciatic nerve ligature (SNL) in the right hind paw, after the microinjection of SA, Salvinorin B (SB), KOR and CB1 antagonists directly in the insular cortex (IC) in male wistar rats. We found a potent antinociceptive effect with the administration of SA. Moreover, this effect was blocked by the administration of a KOR antagonist as well as the administration of a CB1 antagonist. Salvinorin A has a potent antinociceptive effect when is administered centrally in the IC by the interaction with KOR and CB1 receptors. We show evidence on the effectiveness of the administration of salvinorin A in the IC in a rodent model of neuropathic pain. These results support the use of novel compounds like SA as a therapeutic alternative for neuropathic pain relief. © 2017 European Pain Federation - EFIC®.

  2. Assemblage of Necrophagous Diptera in Atlantic Insular Environments and Response to Different Levels of Human Presence.

    PubMed

    Carmo, R F R; Vasconcelos, S D

    2016-10-01

    Islands act as natural laboratories for ecological studies to explain bioinvasion processes and, in this scenario, necrophagous Diptera have never been used as model organisms. This study aimed to (i) describe assemblages of necrophagous Diptera (Calliphoridae and Sarcophagidae) in two insular environments of different origins and distances from mainland, (ii) investigate the effect of anthropogenic impact on the assemblage of carrion flies, (iii) to quantify the establishment of invasive species in the two islands, and (iv) to infer about the conservation status of the islands based on the ecological parameters. Sampling was performed in 2011-2012, in the dry and rainy season. Insects were collected by using traps with chicken liver or sardine baits. In each island, environments exposed to different degrees of human impact were sampled. Ecological analyses were carried out to characterize the assemblages of Calliphoridae and Sarcophagidae, with emphasis on the relation between native and invasive species. In total, 99,862 adults of 21 species of blow flies and flesh flies were collected. Overall abundance in the oceanic island was higher than in the continental island, although the richness of species was higher in the latter. The type of bait did not influence diversity of species sampled in either island. No difference was observed in total richness of both families according to the gradient of anthropogenic impact, in both islands. The invasive species Chrysomya megacephala (Fabricius) was classified as dominant in all environments, irrespective of the anthropogenic impact, which raises concern about the conservation status of each island.

  3. Anthropogenic and Climatic Influence on Vegetation Fires in Peatland of Insular Southeast Asia

    NASA Astrophysics Data System (ADS)

    Liew, S.; Miettinen, J.; Salinas Cortijo, S. V.

    2011-12-01

    Fire is traditionally used as a tool in land clearing by farmers and shifting cultivators in Southeast Asia. However, the small scale clearing of land is increasingly being replaced by modern large-scale conversion of forests into plantations/agricultural land, usually also by fires. Fires get out of control in periods of extreme drought, especially during the El Nino periods, resulting in severe episodes of transboundary air pollution in the form of smoke haze. We use the MODIS active fires product (hotspots) to establish correlations between the temporal and spatial patterns of vegetation fires with climatic variables, land cover change and soil type (peat or non-peat) in the western part of Insular Southeast Asia for a decade from 2001 to 2010. Fire occurrence exhibits a negative correlation with rainfall, and is more severe overall during the El-Nino periods. However, not all regions are equally affected by El-Nino. In Southern Sumatra and Southern Borneo the correlation with El-Nino is high. However, fires in some regions such as the peatland in Riau, Jambi and Sarawak do not appear to be influenced by El-Nino. These regions are also experiencing rapid conversion of forest to large scale plantations.

  4. A molecular mechanism underlying gustatory memory trace for an association in the insular cortex

    PubMed Central

    Adaikkan, Chinnakkaruppan; Rosenblum, Kobi

    2015-01-01

    Events separated in time are associatively learned in trace conditioning, recruiting more neuronal circuits and molecular mechanisms than in delay conditioning. However, it remains unknown whether a given sensory memory trace is being maintained as a unitary item to associate. Here, we used conditioned taste aversion learning in the rat model, wherein animals associate a novel taste with visceral nausea, and demonstrate that there are two parallel memory traces of a novel taste: a short-duration robust trace, lasting approximately 3 hr, and a parallel long-duration weak one, lasting up to 8 hr, and dependent on the strong trace for its formation. Moreover, only the early robust trace is maintained by a NMDAR-dependent CaMKII- AMPAR pathway in the insular cortex. These findings suggest that a memory trace undergoes rapid modifications, and that the mechanisms underlying trace associative learning differ when items in the memory are experienced at different time points. DOI: http://dx.doi.org/10.7554/eLife.07582.001 PMID:26452094

  5. Volumetric growth analysis of an insular dysembryoplastic neuroepithelial tumor over a 10-year follow-up

    PubMed Central

    Uno, Takehiro; Kinoshita, Masashi; Furuta, Takuya; Miyashita, Katsuyoshi; Sabit, Hemragul; Nakada, Mitsutoshi

    2016-01-01

    Background: Dysembryoplastic neuroepithelial tumors (DNETs) are benign tumors characterized by a cortical location; they result in symptoms of drug-resistant partial seizures in children. The development of DNETs is poorly understood because most of them are resected immediately upon diagnosis without any observation period owing to the intractable seizures. Case Description: We report the first DNET case with the growth rate analyzed in the natural course of development for a period of 10 years. The patient was a right-handed man who was initially referred to another hospital with mild head injury when he was 8 years old. A tumor located in the right insular cortex was incidentally detected on magnetic resonance imaging (MRI) and followed-up with annual MRI for 10 years. Conclusion: In this case, the volume of the DNET increased in direct proportion to the length of time in its clinical course. The tumor doubling time was approximately 10 years. This case suggests DNET is a slow-growing but not stable tumor. PMID:28194304

  6. Household waste compositional analysis variation from insular communities in the framework of waste prevention strategy plans

    SciTech Connect

    Zorpas, Antonis A.; Lasaridi, Katia; Voukkali, Irene; Loizia, Pantelitsa; Chroni, Christina

    2015-04-15

    Highlights: • Waste framework directive has set clear waste prevention procedures. • Household Compositional analysis. • Waste management plans. • Zero waste approach. • Waste generation. - Abstract: Waste management planning requires reliable data regarding waste generation, affecting factors on waste generation and forecasts of waste quantities based on facts. In order to decrease the environmental impacts of waste management the choice of prevention plan as well as the treatment method must be based on the features of the waste that are produced in a specific area. Factors such as culture, economic development, climate, and energy sources have an impact on waste composition; composition influences the need of collecting waste more or less frequently of waste collection and disposition. The research question was to discover the main barriers concerning the compositional analysis in Insular Communities under warm climate conditions and the findings from this study enabled the main contents of a waste management plan to be established. These included advice to residents on waste minimisation, liaison with stakeholders and the expansion of kerbside recycling schemes.

  7. The avian fossil record in Insular Southeast Asia and its implications for avian biogeography and palaeoecology

    PubMed Central

    2014-01-01

    Excavations and studies of existing collections during the last decades have significantly increased the abundance as well as the diversity of the avian fossil record for Insular Southeast Asia. The avian fossil record covers the Eocene through the Holocene, with the majority of bird fossils Pleistocene in age. Fossil bird skeletal remains represent at least 63 species in 54 genera and 27 families, and two ichnospecies are represented by fossil footprints. Birds of prey, owls and swiftlets are common elements. Extinctions seem to have been few, suggesting continuity of avian lineages since at least the Late Pleistocene, although some shifts in species ranges have occurred in response to climatic change. Similarities between the Late Pleistocene avifaunas of Flores and Java suggest a dispersal route across southern Sundaland. Late Pleistocene assemblages of Niah Cave (Borneo) and Liang Bua (Flores) support the rainforest refugium hypothesis in Southeast Asia as they indicate the persistence of forest cover, at least locally, throughout the Late Pleistocene and Holocene. PMID:24688871

  8. Differential role of insular cortex muscarinic and NMDA receptors in one-trial appetitive taste learning.

    PubMed

    Parkes, Shauna L; De la Cruz, Vanesa; Bermúdez-Rattoni, Federico; Coutureau, Etienne; Ferreira, Guillaume

    2014-12-01

    Our current understanding of the neurobiology of taste learning and memory has been greatly facilitated by the use of a reliable behavioural model, conditioned taste aversion (CTA). This model has revealed that the insular cortex (IC), specifically muscarinic and N-methyl-d-aspartate (NMDA) receptor activation in the IC, is critical for the formation of aversive taste memories. In contrast, current models of appetitive taste learning are less adequate, relying on the use of neophobic tastes (attenuation of neophobia) or on the integration of appetitive and aversive taste memories (latent inhibition of CTA). While these models have implicated IC muscarinic receptors, the involvement of NMDA receptors in the IC remains unclear. Here, we examined the role of both muscarinic and NMDA receptors in appetitive taste learning using a simple paradigm that is independent of neophobic and aversive components. First, we demonstrated that a single exposure to a novel taste, saccharin 0.1%, is sufficient to promote an appetitive taste memory as revealed by an increase in saccharin consumption during the second presentation. This increase was blocked by bilateral infusion in the IC of the muscarinic receptor antagonist, scopolamine. In contrast, infusion of the NMDA receptor antagonist, AP5, did not block appetitive taste learning but did abolish CTA. Therefore, common and distinct molecular substrates within the IC mediate appetitive versus aversive learning about the same taste.