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Sample records for activation augments nmda

  1. ERK activation causes epilepsy by stimulating NMDA receptor activity

    Nateri, Abdolrahman S.; Raivich, Gennadij; Gebhardt, Christine; Da Costa, Clive; Naumann, Heike; Vreugdenhil, Martin; Makwana, Milan; Brandner, Sebastian; Adams, Ralf H.; Jefferys, John G. R.; Kann, Oliver; Behrens, Axel

    2007-01-01

    The ERK MAPK signalling pathway is a highly conserved kinase cascade linking transmembrane receptors to downstream effector mechanisms. To investigate the function of ERK in neurons, a constitutively active form of MEK1 (caMEK1) was conditionally expressed in the murine brain, which resulted in ERK activation and caused spontaneous epileptic seizures. ERK activation stimulated phosphorylation of eukaryotic translation initiation factor 4E (eIF4E) and augmented NMDA receptor 2B (NR2B) protein ...

  2. NMDA receptor activation by spontaneous glutamatergic neurotransmission.

    Espinosa, Felipe; Kavalali, Ege T

    2009-05-01

    Under physiological conditions N-methyl-D-aspartate (NMDA) receptor activation requires coincidence of presynaptic glutamate release and postsynaptic depolarization due to the voltage-dependent block of these receptors by extracellular Mg(2+). Therefore spontaneous neurotransmission in the absence of action potential firing is not expected to lead to significant NMDA receptor activation. Here we tested this assumption in layer IV neurons in neocortex at their resting membrane potential (approximately -67 mV). In long-duration stable recordings, we averaged a large number of miniature excitatory postsynaptic currents (mEPSCs, >100) before or after application of dl-2 amino 5-phosphonovaleric acid, a specific blocker of NMDA receptors. The difference between the two mEPSC waveforms showed that the NMDA current component comprises approximately 20% of the charge transfer during an average mEPSC detected at rest. Importantly, the contribution of the NMDA component was markedly enhanced at membrane potentials expected for the depolarized up states (approximately -50 mV) that cortical neurons show during slow oscillations in vivo. In addition, partial block of the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor component of the mEPSCs did not cause a significant reduction in the NMDA component, indicating that potential AMPA receptor-driven local depolarizations did not drive NMDA receptor activity at rest. Collectively these results indicate that NMDA receptors significantly contribute to signaling at rest in the absence of dendritic depolarizations or concomitant AMPA receptor activity. PMID:19261712

  3. NMDA Receptor Activation by Spontaneous Glutamatergic Neurotransmission

    Espinosa, Felipe; Kavalali, Ege T.

    2009-01-01

    Under physiological conditions N-methyl-d-aspartate (NMDA) receptor activation requires coincidence of presynaptic glutamate release and postsynaptic depolarization due to the voltage-dependent block of these receptors by extracellular Mg2+. Therefore spontaneous neurotransmission in the absence of action potential firing is not expected to lead to significant NMDA receptor activation. Here we tested this assumption in layer IV neurons in neocortex at their resting membrane potential (approxi...

  4. NMDA receptor activity in neuropsychiatric disorders

    ShaheenELakhan

    2013-06-01

    Full Text Available N-Methyl-D-aspartate (NMDA receptors play a variety of physiologic roles and their proper signaling is essential for cellular homeostasis. Any disruption in this pathway, leading to either enhanced or decreased activity, may result in the manifestation of neuropsychiatric pathologies such as schizophrenia, mood disorders, substance induced psychosis, Huntington's disease, Alzheimer's disease, and neuropsychiatric systemic lupus erythematosus. Here, we explore the notion that the overlap in activity of at least one biochemical pathway, the NMDA receptor pathway, may be the link to understanding the overlap in psychotic symptoms between diseases. This review intends to present a broad overview of those neuropsychiatric disorders for which alternations in NMDA receptor activity is prominent thus suggesting that continued direction of pharmaceutical intervention to this pathway may present a viable option for managing symptoms.

  5. Chronic hyperammonemia induces tonic activation of NMDA receptors in cerebellum.

    ElMlili, Nisrin; Boix, Jordi; Ahabrach, Hanan; Rodrigo, Regina; Errami, Mohammed; Felipo, Vicente

    2010-02-01

    Reduced function of the glutamate--nitric oxide (NO)--cGMP pathway is responsible for some cognitive alterations in rats with hyperammonemia and hepatic encephalopathy. Hyperammonemia impairs the pathway in cerebellum by increasing neuronal nitric oxide synthase (nNOS) phosphorylation in Ser847 by calcium-calmodulin-dependent protein kinase II (CaMKII), reducing nNOS activity, and by reducing nNOS amount in synaptic membranes, which reduces its activation following NMDA receptors activation. The reason for increased CaMKII activity in hyperammonemia remains unknown. We hypothesized that it would be as a result of increased tonic activation of NMDA receptors. The aims of this work were to assess: (i) whether tonic NMDA activation receptors is increased in cerebellum in chronic hyperammonemia in vivo; and (ii) whether this tonic activation is responsible for increased CaMKII activity and reduced activity of nNOS and of the glutamate--NO--cGMP pathway. Blocking NMDA receptors with MK-801 increases cGMP and NO metabolites in cerebellum in vivo and in slices from hyperammonemic rats. This is because of reduced phosphorylation and activity of CaMKII, leading to normalization of nNOS phosphorylation and activity. MK-801 also increases nNOS in synaptic membranes and reduces it in cytosol. This indicates that hyperammonemia increases tonic activation of NMDA receptors leading to reduced activity of nNOS and of the glutamate--NO--cGMP pathway. PMID:20002515

  6. Interplay between non-NMDA and NMDA receptor activation during oscillatory wave propagation: Analyses of caffeine-induced oscillations in the visual cortex of rats.

    Yoshimura, Hiroshi; Sugai, Tokio; Kato, Nobuo; Tominaga, Takashi; Tominaga, Yoko; Hasegawa, Takahiro; Yao, Chenjuan; Akamatsu, Tetsuya

    2016-07-01

    Generation and propagation of oscillatory activities in cortical networks are important features of the brain. However, many issues related to oscillatory phenomena are unclear. We previously reported neocortical oscillation following caffeine treatment of rat brain slices. Input to the primary visual cortex (Oc1) generates N-methyl-d-aspartate (NMDA) receptor-dependent oscillations, and we proposed that the oscillatory signals originate in the secondary visual cortex (Oc2). Because non-NMDA and NMDA receptors cooperate in synaptic transmission, non-NMDA receptors may also play an important role in oscillatory activities. Here we investigated how non-NMDA receptor activities contribute to NMDA receptor-dependent oscillations by using optical recording methods. After induction of stable oscillations with caffeine application, blockade of NMDA receptors abolished the late stable oscillatory phase, but elicited 'hidden' non-NMDA receptor-dependent oscillation during the early depolarizing phase. An interesting finding is that the origin of the non-NMDA receptor-dependent oscillation moved from the Oc1, during the early phase, toward the origin of the NMDA receptor-dependent oscillation that is fixed in the Oc2. In addition, the frequency of the non-NMDA receptor-dependent oscillation was higher than that of the NMDA receptor-dependent oscillation. Thus, in one course of spatiotemporal oscillatory activities, the relative balance in receptor activities between non-NMDA and NMDA receptors gradually changes, and this may be due to the different kinetics of the two receptor types. These results suggest that interplay between the two receptor types in the areas of Oc1 and Oc2 may play an important role in oscillatory signal communication. PMID:27136667

  7. Formation and maintenance of ventilatory long-term facilitation require NMDA but not non-NMDA receptors in awake rats

    McGuire, Michelle; Liu, Chun; Cao, Ying; Ling, Liming

    2008-01-01

    N-methyl-d-aspartate (NMDA) receptor antagonism in the phrenic motonucleus area eliminates phrenic long-term facilitation (pLTF; a persistent augmentation of phrenic nerve activity after episodic hypoxia) in anesthetized rats. However, whether NMDA antagonism can eliminate ventilatory LTF (vLTF) in awake rats is unclear. The role of non-NMDA receptors in LTF is also unknown. Serotonin receptor antagonism before, but not after, episodic hypoxia eliminates pLTF, suggesting that serotonin recept...

  8. A quantitative method to assess extrasynaptic NMDA receptor function in the protective effect of synaptic activity against neurotoxicity

    Bading Hilmar

    2008-01-01

    Full Text Available Abstract Background Extrasynaptic NMDA receptors couple to a CREB shut-off pathway and cause cell death, whereas synaptic NMDA receptors and nuclear calcium signaling promote CREB-mediated transcription and neuronal survival. The distribution of NMDA receptors (synaptic versus extrasynaptic may be an important parameter that determines the susceptibility of neurons to toxic insults. Changes in receptor surface expression towards more extrasynaptic NMDA receptors may lead to neurodegeneration, whereas a reduction of extrasynaptic NMDA receptors may render neurons more resistant to death. A quantitative assessment of extrasynaptic NMDA receptors in individual neurons is needed in order to investigate the role of NMDA receptor distribution in neuronal survival and death. Results Here we refined and verified a protocol previously used to isolate the effects of extrasynaptic NMDA receptors using the NMDA receptor open channel blocker, MK-801. Using this method we investigated the possibility that the known neuroprotective shield built up in hippocampal neurons after a period of action potential bursting and stimulation of synaptic NMDA receptors is due to signal-induced trafficking of extrasynaptic NMDA receptors or a reduction in extrasynaptic NMDA receptor function. We found that extrasynaptic NMDA receptor-mediated calcium responses and whole cell currents recorded under voltage clamp were surprisingly invariable and did not change even after prolonged (16 to 24 hours periods of bursting and synaptic NMDA receptor activation. Averaging a large number of calcium imaging traces yielded a small (6% reduction of extrasynaptic NMDA receptor-mediated responses in hippocampal neurons that were pretreated with prolonged bursting. Conclusion The slight reduction in extrasynaptic NMDA receptor function following action potential bursting and synaptic NMDA receptor stimulation could contribute to but is unlikely to fully account for activity

  9. In vitro neuronal network activity in NMDA receptor encephalitis

    Jantzen Sabine U

    2013-02-01

    Full Text Available Abstract Background Anti-NMDA-encephalitis is caused by antibodies against the N-methyl-D-aspartate receptor (NMDAR and characterized by a severe encephalopathy with psychosis, epileptic seizures and autonomic disturbances. It predominantly occurs in young women and is associated in 59% with an ovarian teratoma. Results We describe effects of cerebrospinal fluid (CSF from an anti-N-methyl-D-aspartate receptor (NMDAR encephalitis patient on in vitro neuronal network activity (ivNNA. In vitro NNA of dissociated primary rat cortical populations was recorded by the microelectrode array (MEA system. The 23-year old patient was severely affected but showed an excellent recovery following multimodal immunomodulatory therapy and removal of an ovarian teratoma. Patient CSF (pCSF taken during the initial weeks after disease onset suppressed global spike- and burst rates of ivNNA in contrast to pCSF sampled after clinical recovery and decrease of NMDAR antibody titers. The synchrony of pCSF-affected ivNNA remained unaltered during the course of the disease. Conclusion Patient CSF directly suppresses global activity of neuronal networks recorded by the MEA system. In contrast, pCSF did not regulate the synchrony of ivNNA suggesting that NMDAR antibodies selectively regulate distinct parameters of ivNNA while sparing their functional connectivity. Thus, assessing ivNNA could represent a new technique to evaluate functional consequences of autoimmune encephalitis-related CSF changes.

  10. NMDA modulates oligodendrocyte differentiation of subventricular zone cells through PKC activation

    Fabio eCavaliere

    2013-12-01

    Full Text Available Multipotent cells from the juvenile subventricular zone (SVZ possess the ability to differentiate into new neural cells. Depending on local signals, SVZ can generate new neurons, astrocytes or oligodendrocytes. We previously demonstrated that activation of NMDA receptors in SVZ progenitors increases the rate of oligodendrocyte differentiation. Here we investigated the mechanisms involved in NMDA receptor-dependent differentiation. Using functional studies performed with the reporter gene luciferase we found that activation of NMDA receptor stimulates PKC. In turn, stimulation of PKC precedes the activation of NADPH oxidase (NOX as demonstrated by translocation of the p67phox subunit to the cellular membrane. We propose that NOX2 is involved in the transduction of the signal from NMDA receptors through PKC activation as the inhibitor gp91 reduced their pro-differentiation effect. In addition, our data and that from other groups suggest that signaling through the NMDA receptor/PKC/NOX2 cascade generates ROS that activate the PI3/mTOR pathway and finally leads to the generation of new oligodendrocytes.

  11. Clozapine functions through the prefrontal cortex serotonin 1A receptor to heighten neuronal activity via calmodulin kinase II-NMDA receptor interactions.

    Purkayastha, Sudarshana; Ford, Jason; Kanjilal, Baishali; Diallo, Souleymane; Del Rosario Inigo, Joseph; Neuwirth, Lorenz; El Idrissi, Abdeslem; Ahmed, Zaghloul; Wieraszko, Andrzej; Azmitia, Efrain C; Banerjee, Probal

    2012-02-01

    Aberrant dopamine release in the prefrontal cortex (PFC) is believed to underlie schizophrenia, but the mechanistic pathway through which a widely used antipsychotic, clozapine (Clz), evokes neurotransmitter-releasing electrical stimulation is unclear. We analyzed Clz-evoked regulation of neuronal activity in the PFC by stimulating axons in layers IV and V and recording the electrical effect in the post-synaptic pyramidal cells of layers II and III. We observed a Clz-evoked increase in population spike (PS), which was mediated by serotonin 1A receptor (5-HT(1A)-R), phospholipase Cβ, and Ca(2+)/calmodulin-dependent protein kinase II (CaMKII). Immunoblotting demonstrated that the Clz-activation of CaMKII was 5-HT(1A)-R-mediated. Intriguingly, the NMDA receptor (NMDA-R) antagonist (±)2-amino-5-phosphonovaleric acid (APV) eliminated the Clz-mediated increase in PS, suggesting that the 5-HT(1A)-R, NMDA-R and CaMKII form a synergistic triad, which boosts excitatory post-synaptic potential (EPSP), thereby enhancing PS. In corroboration, Clz as well as NMDA augmented field EPSP (fEPSP), and WAY100635 (a 5-HT(1A)-R antagonist), APV, and a CaMKII inhibitor eliminated this increase. As previously shown, CaMKII binds to the NMDA-R 2B (NR2B) subunit to become constitutively active, thereby inducing α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA) receptor recruitment to the post-synaptic membrane and an increase in fEPSP. Co-immunoprecipitation demonstrated that Clz potentiates interactions among CaMKII, NR2B, and 5-HT(1A)-R, possibly in the membrane rafts of the post-synaptic density (PSD), because pretreatment with methyl-β-cyclodextrin (MCD), an agent that disrupts rafts, inhibited both co-immunoprecipitation as well as fEPSP. In summary, Clz functions in the PFC by orchestrating a synergism among 5-HT(1A)-R, CaMKII, and NMDA-R, which augments excitability in the PFC neurons of layers II/III. PMID:22044428

  12. NMDA-receptor activation but not ion flux is required for amyloid-beta induced synaptic depression.

    Albert Tamburri

    Full Text Available Alzheimer disease is characterized by a gradual decrease of synaptic function and, ultimately, by neuronal loss. There is considerable evidence supporting the involvement of oligomeric amyloid-beta (Aβ in the etiology of Alzheimer's disease. Historically, AD research has mainly focused on the long-term changes caused by Aβ rather than analyzing its immediate effects. Here we show that acute perfusion of hippocampal slice cultures with oligomeric Aβ depresses synaptic transmission within 20 minutes. This depression is dependent on synaptic stimulation and the activation of NMDA-receptors, but not on NMDA-receptor mediated ion flux. It, therefore, appears that Aβ dependent synaptic depression is mediated through a use-dependent metabotropic-like mechanism of the NMDA-receptor, but does not involve NMDA-receptor mediated synaptic transmission, i.e. it is independent of calcium flux through the NMDA-receptor.

  13. Activation of N-methyl-D-aspartate (NMDA) receptors in the dorsal vagal complex lowers glucose production.

    Lam, Carol K L; Chari, Madhu; Su, Brenda B; Cheung, Grace W C; Kokorovic, Andrea; Yang, Clair S; Wang, Penny Y T; Lai, Teresa Y Y; Lam, Tony K T

    2010-07-16

    Diabetes is characterized by hyperglycemia due partly to increased hepatic glucose production. The hypothalamus regulates hepatic glucose production in rodents. However, it is currently unknown whether other regions of the brain are sufficient in glucose production regulation. The N-methyl-D-aspartate (NMDA) receptor is composed of NR1 and NR2 subunits, which are activated by co-agonist glycine and glutamate or aspartate, respectively. Here we report that direct administration of either co-agonist glycine or NMDA into the dorsal vagal complex (DVC), targeting the nucleus of the solitary tract, lowered glucose production in vivo. Direct infusion of the NMDA receptor blocker MK-801 into the DVC negated the metabolic effect of glycine. To evaluate whether NR1 subunit of the NMDA receptor mediates the effect of glycine, NR1 in the DVC was inhibited by DVC NR1 antagonist 7-chlorokynurenic acid or DVC shRNA-NR1. Pharmacological and molecular inhibition of DVC NR1 negated the metabolic effect of glycine. To evaluate whether the NMDA receptors mediate the effects of NR2 agonist NMDA, DVC NMDA receptors were inhibited by antagonist D-2-amino-5-phosphonovaleric acid (D-APV). DVC D-APV fully negated the ability of DVC NMDA to lower glucose production. Finally, hepatic vagotomy negated the DVC glycine ability to lower glucose production. These findings demonstrate that activation of NR1 and NR2 subunits of the NMDA receptors in the DVC is sufficient to trigger a brain-liver axis to lower glucose production, and suggest that DVC NMDA receptors serve as a therapeutic target for diabetes and obesity. PMID:20448042

  14. Ethanol-withdrawal seizures are controlled by tissue plasminogen activator via modulation of NR2B-containing NMDA receptors

    Pawlak, Robert; Melchor, Jerry P.; Matys, Tomasz; Skrzypiec, Anna E.; Strickland, Sidney

    2005-01-01

    Chronic ethanol abuse causes up-regulation of NMDA receptors, which underlies seizures and brain damage upon ethanol withdrawal (EW). Here we show that tissue-plasminogen activator (tPA), a protease implicated in neuronal plasticity and seizures, is induced in the limbic system by chronic ethanol consumption, temporally coinciding with up-regulation of NMDA receptors. tPA interacts with NR2B-containing NMDA receptors and is required for up-regulation of the NR2B subunit in response to ethanol...

  15. Progressive brain damage, synaptic reorganization and NMDA activation in a model of epileptogenic cortical dysplasia.

    Francesca Colciaghi

    Full Text Available Whether severe epilepsy could be a progressive disorder remains as yet unresolved. We previously demonstrated in a rat model of acquired focal cortical dysplasia, the methylazoxymethanol/pilocarpine - MAM/pilocarpine - rats, that the occurrence of status epilepticus (SE and subsequent seizures fostered a pathologic process capable of modifying the morphology of cortical pyramidal neurons and NMDA receptor expression/localization. We have here extended our analysis by evaluating neocortical and hippocampal changes in MAM/pilocarpine rats at different epilepsy stages, from few days after onset up to six months of chronic epilepsy. Our findings indicate that the process triggered by SE and subsequent seizures in the malformed brain i is steadily progressive, deeply altering neocortical and hippocampal morphology, with atrophy of neocortex and CA regions and progressive increase of granule cell layer dispersion; ii changes dramatically the fine morphology of neurons in neocortex and hippocampus, by increasing cell size and decreasing both dendrite arborization and spine density; iii induces reorganization of glutamatergic and GABAergic networks in both neocortex and hippocampus, favoring excitatory vs inhibitory input; iv activates NMDA regulatory subunits. Taken together, our data indicate that, at least in experimental models of brain malformations, severe seizure activity, i.e., SE plus recurrent seizures, may lead to a widespread, steadily progressive architectural, neuronal and synaptic reorganization in the brain. They also suggest the mechanistic relevance of glutamate/NMDA hyper-activation in the seizure-related brain pathologic plasticity.

  16. The Effects of NMDA Antagonists on Neuronal Activity in Cat Spinal Cord Evoked by Acute Inflammation in the Knee Joint.

    Schaible, Hans-Georg; Grubb, Blair D.; Neugebauer, Volker; Oppmann, Maria

    1991-01-01

    In alpha-chloralose-anaesthetized, spinalized cats we examined the effects of NMDA antagonists on the discharges of 71 spinal neurons which had afferent input from the knee joint. These neurons were rendered hyperexcitable by acute arthritis in the knee induced by kaolin and carrageenan. They were located in the deep dorsal and ventral horn and some of them had ascending axons. The N-methyl-d-aspartate (NMDA) antagonists ketamine and d-2-amino-5-phosphonovalerate (AP5), were administered ionophoretically, and ketamine was also administered intravenously. In some of the experiments the antagonists were tested against the agonists NMDA and quisqualate. The effects of the NMDA antagonists consisted of a significant reduction in the resting activity of neurons and/or the responses of the same neurons to mechanical stimulation of the inflamed knee. Intravenous ketamine was most effective in suppressing the resting and mechanically evoked activity in 25 of 26 neurons tested. Ionophoretically applied ketamine had a suppressive effect in 11 of 21 neurons, and AP5 decreased activity in 17 of 24 cells. The reduction in the resting and/or the mechanically evoked discharges was achieved with doses of the antagonists which suppressed the responses to NMDA but not those to quisqualate. These results suggest that NMDA receptors are involved in the enhanced responses and basal activity of spinal neurons induced by inflammation in the periphery. PMID:12106256

  17. Ethanol enhances neurosteroidogenesis in hippocampal pyramidal neurons by paradoxical NMDA receptor activation.

    Tokuda, Kazuhiro; Izumi, Yukitoshi; Zorumski, Charles F

    2011-07-01

    Using an antibody against 5α-reduced neurosteroids, predominantly allopregnanolone, we found that immunostaining in the CA1 region of rat hippocampal slices was confined to pyramidal neurons. This neurosteroid staining was increased following 15 min administration of 60 mm but not 20 mm ethanol, and the enhancement was blocked by finasteride and dutasteride, selective inhibitors of 5α-reductase, a key enzyme required for allopregnanolone synthesis. Consistent with a prior report indicating that N-methyl-D-aspartate (NMDA) receptor (NMDAR) activation can promote steroid production, we observed that D-2-amino-5-phosphonovalerate (APV), a competitive NMDAR antagonist, blocked the effects of 60 mm ethanol on staining. We previously reported that 60 mm ethanol inhibits the induction of long-term potentiation (LTP), a cellular model for memory formation, in the CA1 region. In the present study, LTP inhibition by 60 mm ethanol was also overcome by both the 5α-reductase inhibitors and by APV. Furthermore, the effects of ethanol on neurosteroid production and LTP were mimicked by a low concentration of NMDA (1 μm), and the ability of NMDA to inhibit LTP and to enhance neurosteroid staining was reversed by finasteride and dutasteride, as well as by APV. These results indicate that ethanol paradoxically enhances GABAergic neurosteroid production by activation of unblocked NMDARs and that acute LTP inhibition by ethanol represents a form of NMDAR-mediated metaplasticity. PMID:21734282

  18. Voltage-clamp frequency domain analysis of NMDA-activated neurons.

    Moore, L E; Hill, R H; Grillner, S

    1993-02-01

    1. Voltage and current-clamp steps were added to a sum of sine waves to measure the tetrodotoxin-insensitive membrane properties of neurons in the intact lamprey spinal cord. A systems analysis in the frequency domain was carried out on two types of cells that have very different morphologies in order to investigate the structural dependence of their electrophysiological properties. The method explicitly takes into account the geometrical shapes of (i) nearly spherical dorsal cells with one or two processes and (ii) motoneurons and interneurons that have branched dendritic structures. Impedance functions were analysed to obtain the cable properties of these in situ neurons. These measurements show that branched neurons are not isopotential and, therefore, a conventional voltage-clamp analysis is not valid. 2. The electrophysiological data from branched neurons were curve-fitted with a lumped soma-equivalent cylinder model consisting of eight equal compartments coupled to an isopotential cell body to obtain membrane parameters for both passive and active properties. The analysis provides a quantitative description of both the passive electrical properties imposed by the geometrical structure of neurons and the voltage-dependent ionic conductances determined by ion channel kinetics. The model fitting of dorsal cells was dominated by a one-compartment resistance and capacitance in parallel (RC) corresponding to the spherical, non-branched shape of these cells. Branched neurons required a model that contained both an RC compartment and a cable that reflected the structure of the cells. At rest, the electrotonic length of the cable was about two. Uniformly distributed voltage-dependent ionic conductance sites were adequate to describe the data at different membrane potentials. 3. The frequency domain admittance method in conjunction with a step voltage clamp was used to control and measure the oscillatory behavior induced by N-methyl-D-aspartate (NMDA) on lamprey spinal

  19. EFFECT OF ELECTROACUPUNCTURE ON MYOCARDIAL ISCHEMIA INDUCED CHANGES OF CARDIAC SYMPATHETIC ACTIVITY AND INVOLVEMENT OF SPINIAL δ-OPIOID,NMDA-AND NON-NMDA RECEPTORS IN THE RABBIT

    刘俊岭; 高永辉; 陈淑萍

    2003-01-01

    Aim: To observe the effect of electroacupuncture (EA) on acute myocardial ischemia (AMI) induced changes of cardiac sympathetic discharges and the effects of some related receptors in the spinal cord. Methods: A total of 53 rabbits anesthetized with mixture solution of 25% urethane (420 mg/kg) and 1.5% chloralose (50 mg/kg)were used in this study. AMI was induced by occlusion of the ventricular branch of the left coronary artery. Discharges of the left cardiac sympathetic nerve were recorded by using a bipolar platinum electrode. Bilateral "Ximen"(PC 40)and "Kongzhui"(LU 6) were stimulated electrically by using an EA therapeutic apparatus or an electrical stimulator.DPDPE δ-opiate receptor agonist, 20 nmol, 10 μL, n= 8), Naltrindole Hydrochloride (δ-opiate receptor antagonist, 20nmol, 10 μL, n=8), DAP5 (NMDA receptor antagonist, 5 nmol, 10 μL, n=9) and CNQX (non-NMDA receptor antagonist, 5 nmol, 10 μL, n=8) were respectively injected into the thoracic subarachnoid space of the spinal cord in different groups, followed by observing their effects on changes of sympathetic activity evoked by EA of the abovementioned acupoints. Results: ① After AMI, sympathetic discharges increased (200.56± 79.89%) in 10 cases and decreased (- 59.34 ±7.06% ) in other 9 cases in comparison with their individual basal values. After EA of "Ximen" (PC 4)and "Kongzhui" (Lu 6), AMI-induced increase and decrease changes of the sympathetic activity were suppressed significantly, but the effect of EA of LU-6 was weaker than that of EA of PC-4.②Following EA of PC-4 and LU-6, sympathetic discharges increased significantly in 2 and 4 cases, decreased apparently in 7 and 3 cases, and had no striking changes in 1 and 3 cases respectively. The mean reaction threshold of sympathetic activity after EA of PC-4 and LU-6were 2.1 ± 0.65 mA and 3.28± 1.13 mA separately.③ After pre-treatment with DPDPE, the reaction threshold of the cardiac sympathetic activity to EA of PC-4 elevated

  20. Formation and maintenance of ventilatory long-term facilitation require NMDA but not non-NMDA receptors in awake rats.

    McGuire, Michelle; Liu, Chun; Cao, Ying; Ling, Liming

    2008-09-01

    N-methyl-d-aspartate (NMDA) receptor antagonism in the phrenic motonucleus area eliminates phrenic long-term facilitation (pLTF; a persistent augmentation of phrenic nerve activity after episodic hypoxia) in anesthetized rats. However, whether NMDA antagonism can eliminate ventilatory LTF (vLTF) in awake rats is unclear. The role of non-NMDA receptors in LTF is also unknown. Serotonin receptor antagonism before, but not after, episodic hypoxia eliminates pLTF, suggesting that serotonin receptors are required for induction, but not maintenance, of pLTF. However, because NMDA and non-NMDA ionotropic glutamate receptors are directly involved in mediating the inspiratory drive to phrenic, hypoglossal, and intercostal motoneurons, we hypothesized that these receptors are required for both formation and maintenance of vLTF. vLTF, induced by five episodes of 5-min poikilocapnic hypoxia (10% O(2)) with 5-min normoxia intervals, was measured with plethysmography in conscious adult male Sprague-Dawley rats. Either (+/-)-2-amino-5-phosphonovaleric acid (APV; NMDA antagonist, 1.5 mg/kg) or 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; non-NMDA antagonist, 10 mg/kg) was systemically (ip) injected approximately 30 min before hypoxia. APV was also injected immediately after or 20 min after episodic hypoxia in additional groups. As control, vehicle was similarly injected in each rat 1-2 days before. Regardless of being injected before or after episodic hypoxia, vehicle did not alter vLTF ( approximately 23%), whereas APV eliminated vLTF while having little effect on baseline ventilation or hypoxic ventilatory response. In contrast, CNQX enhanced vLTF ( approximately 34%) while decreasing baseline ventilation. Collectively, these results suggest that activation of NMDA but not non-NMDA receptors is necessary for formation and maintenance of vLTF in awake rats. PMID:18583381

  1. Abelson tyrosine kinase links PDGFbeta receptor activation to cytoskeletal regulation of NMDA receptors in CA1 hippocampal neurons

    Beazely Michael A

    2008-12-01

    Full Text Available Abstract Background We have previously demonstrated that PDGF receptor activation indirectly inhibits N-methyl-D-aspartate (NMDA currents by modifying the cytoskeleton. PDGF receptor ligand is also neuroprotective in hippocampal slices and cultured neurons. PDGF receptors are tyrosine kinases that control a variety of signal transduction pathways including those mediated by PLCγ. In fibroblasts Src and another non-receptor tyrosine kinase, Abelson kinase (Abl, control PDGF receptor regulation of cytoskeletal dynamics. The mechanism whereby PDGF receptor regulates cytoskeletal dynamics in central neurons remains poorly understood. Results Intracellular applications of active Abl, but not heat-inactivated Abl, decreased NMDA-evoked currents in isolated hippocampal neurons. This mimics the effects of PDGF receptor activation in these neurons. The Abl kinase inhibitor, STI571, blocked the inhibition of NMDA currents by Abl. We demonstrate that PDGF receptors can activate Abl kinase in hippocampal neurons via mechanisms similar to those observed previously in fibroblasts. Furthermore, PDGFβ receptor activation alters the subcellular localization of Abl. Abl kinase is linked to actin cytoskeletal dynamics in many systems. We show that the inhibition of NMDA receptor currents by Abl kinase is blocked by the inclusion of the Rho kinase inhibitor, Y-27632, and that activation of Abl correlates with an increase in ROCK tyrosine phosphorylation. Conclusion This study demonstrates that PDGFβ receptors act via an interaction with Abl kinase and Rho kinase to regulated cytoskeletal regulation of NMDA receptor channels in CA1 pyramidal neurons.

  2. Metabotropic glutamate receptor 5, but not 1, modulates NMDA receptor-mediated activation of neuronal nitric oxide synthase.

    Llansola, Marta; Felipo, Vicente

    2010-03-01

    In cerebellar neurons in culture, activation of group I metabotropic glutamate receptors (mGluRs) prevents glutamate and NMDA-induced neuronal death, indicating that it interferes with the excitotoxic mechanisms leading to death. However, it is not known which step of these mechanisms is affected by mGluRs. The aims of this work were to assess: (a) whether activation of group I mGluRs (mGluR1 or mGluR5) impairs NMDA-induced activation of the glutamate-nitric oxide-cGMP pathway; (b) which mGluR (1 or 5) is responsible for this impairment and (c) whether impairment of the pathway occurs at the level of activation of soluble guanylate cyclase by nitric oxide or of activation of neuronal nitric oxide synthase (nNOS) by NMDA. It is shown that activation of mGluR1 enhances the function of the glutamate-nitric oxide-cGMP pathway by increasing activation of soluble guanylate cyclase by nitric oxide. In contrast, mGluR5 activation inhibits the glutamate-nitric oxide-cGMP pathway by reducing NMDA-induced activation of nNOS. This is due to reduced NMDA-induced increase in cAMP, reduced activation of Akt by cAMP and of nNOS by Akt. The impairment of activation of the glutamate-NO-cGMP pathway by activation of mGluR5 would contribute to its neuroprotective effect against excitotoxicity in cerebellar neurons in culture. PMID:20043967

  3. Current and calcium responses to local activation of axonal NMDA receptors in developing cerebellar molecular layer interneurons.

    Bénédicte Rossi

    Full Text Available In developing cerebellar molecular layer interneurons (MLIs, NMDA increases spontaneous GABA release. This effect had been attributed to either direct activation of presynaptic NMDA receptors (preNMDARs or an indirect pathway involving activation of somato-dendritic NMDARs followed by passive spread of somatic depolarization along the axon and activation of axonal voltage dependent Ca(2+ channels (VDCCs. Using Ca(2+ imaging and electrophysiology, we searched for preNMDARs by uncaging NMDAR agonists either broadly throughout the whole field or locally at specific axonal locations. Releasing either NMDA or glutamate in the presence of NBQX using short laser pulses elicited current transients that were highly sensitive to the location of the spot and restricted to a small number of varicosities. The signal was abolished in the presence of high Mg(2+ or by the addition of APV. Similar paradigms yielded restricted Ca(2+ transients in interneurons loaded with a Ca(2+ indicator. We found that the synaptic effects of NMDA were not inhibited by blocking VDCCs but were impaired in the presence of the ryanodine receptor antagonist dantrolene. Furthermore, in voltage clamped cells, bath applied NMDA triggers Ca(2+ elevations and induces neurotransmitter release in the axonal compartment. Our results suggest the existence of preNMDARs in developing MLIs and propose their involvement in the NMDA-evoked increase in GABA release by triggering a Ca(2+-induced Ca(2+ release process mediated by presynaptic Ca(2+ stores. Such a mechanism is likely to exert a crucial role in various forms of Ca(2+-mediated synaptic plasticity.

  4. ARLearn: Learning activities and interaction in augmented reality

    Ternier, Stefaan; Tabuenca, Bernardo; Specht, Marcus

    2013-01-01

    Ternier, S., Tabuenca, B., & Specht, M. (2012). ARLearn: Learning activities and interaction in augmented reality. In M. Specht, J. Multisilta, & M. Sharples (Eds.), Proceedings of the Mobile Augmented Reality for Education Workshop (pp. 10-13). October, 16-17, 2012, Helsinki, Finland.

  5. Frequency-specific response facilitation of supra and infragranular barrel cortical neurons depends on NMDA receptor activation in rats.

    Barros-Zulaica, N; Castejon, C; Nuñez, A

    2014-10-01

    Sensory experience has a profound effect on neocortical neurons. Passive stimulation of whiskers or sensory deprivation from whiskers can induce long-lasting changes in neuronal responses or modify the receptive field in adult animals. We recorded barrel cortical neurons in urethane-anesthetized rats in layers 2/3 or 5/6 to determine if repetitive stimulation would induce long-lasting response facilitation. Air-puff stimulation (20-ms duration, 40 pulses at 0.5-8Hz) was applied to a single whisker. This repetitive stimulation increased tactile responses in layers 2/3 and 5/6 for 60min. Moreover, the functional coupling (coherence) between the sensory stimulus and the neural response also increased after the repetitive stimulation in neurons showing response facilitation. The long-lasting response facilitation was due to activation of N-methyl-d-aspartate (NMDA) receptors because it was reduced by APV ((2R)-amino-5-phosphonovaleric acid, (2R)-amino-5-phosphonopentanoate) and MK801 application. Inactivation of layer 2/3 also blocked response facilitation in layer 5/6, suggesting that layer 2/3 may be fundamental in this synaptic plasticity processes. Moreover, i.p. injection of eserine augmented the number of layer 2/3 neurons expressing long-lasting response facilitation; this effect was blocked by atropine, suggesting that muscarinic receptor activation favors the induction of the response facilitation. Our data indicate that physiologically repetitive stimulation of a single whisker at the frequency at which rats move their whiskers during exploration of the environment induces long-lasting response facilitation improving sensory processing. PMID:25281880

  6. Dynamic changes in cytosolic ATP levels in cultured glutamatergic neurons during NMDA-induced synaptic activity supported by glucose or lactate

    Lange, Sofie Cecilie; Winkler, Ulrike; Andresen, Lars;

    2015-01-01

    biosensor Ateam1.03YEMK. While inducing synaptic activity by subjecting cultured neurons to two 30 s pulses of NMDA (30 µM) with a 4 min interval, changes in relative ATP levels were measured in the presence of lactate (1 mM), glucose (2.5 mM) or the combination of the two. ATP levels reversibly declined...... following NMDA-induced neurotransmission activity, as indicated by a reversible 10-20 % decrease in the response of the biosensor. The responses were absent when the NMDA receptor antagonist memantine was present. In the presence of lactate alone, the ATP response dropped significantly more than in the...

  7. Synthesis of pregnane 3-carboxylic acids via Pd-catalyzed alkoxycarbonylation and their effect on NMDA receptor activity

    Šťastná, Eva; Chodounská, Hana; Pouzar, Vladimír; Borovská, Jiřina; Vyklický ml., Ladislav

    2011-01-01

    Roč. 76, č. 9 (2011), s. 1141-1161. ISSN 0010-0765 R&D Projects: GA ČR(CZ) GA203/08/1498; GA ČR(CZ) GA309/07/0271 Institutional research plan: CEZ:AV0Z40550506; CEZ:AV0Z50110509 Keywords : neurosteroids * carboxylic acid * alkoxycarbonylation * steroids * NMDA receptor activity Subject RIV: CC - Organic Chemistry Impact factor: 1.283, year: 2011

  8. Interaction of neurosteroids with NMDA receptors: Current Insight into Structure-Activity Relationships and Their Neuroprotective Effect

    Kudová, Eva; Chodounská, Hana; Slavíková, Barbora; Kapras, Vojtěch; Valeš, Karel; Rambousek, Lukáš; Borovská, Jiřina; Vyklický, Vojtěch; Krausová, Barbora; Vyklický ml., Ladislav

    Torino : -, 2013. [International Meeting Steroids and Nervous System /7./. 16.02.2013-20.02.2013, Toronto] R&D Projects: GA TA ČR(CZ) TE01020028; GA ČR(CZ) GAP303/12/1464 Institutional support: RVO:61388963 ; RVO:67985823 Keywords : neurosteroid * NMDA-receptor * structure-activity relationship * pregnanolone Subject RIV: CC - Organic Chemistry; ED - Physiology (FGU-C)

  9. Activation of N-Methyl-d-aspartate (NMDA) Receptors in the Dorsal Vagal Complex Lowers Glucose Production*

    Lam, Carol K. L.; Chari, Madhu; Su, Brenda B.; Cheung, Grace W.C.; Kokorovic, Andrea; Yang, Clair S.; Wang, Penny Y. T.; Lai, Teresa Y.Y.; Lam, Tony K.T.

    2010-01-01

    Diabetes is characterized by hyperglycemia due partly to increased hepatic glucose production. The hypothalamus regulates hepatic glucose production in rodents. However, it is currently unknown whether other regions of the brain are sufficient in glucose production regulation. The N-methyl-d-aspartate (NMDA) receptor is composed of NR1 and NR2 subunits, which are activated by co-agonist glycine and glutamate or aspartate, respectively. Here we report that direct administration of either co-ag...

  10. Tumor necrosis factor alpha stimulates NMDA receptor activity in mouse cortical neurons resulting in ERK-dependent death

    Jara, Javier H.; Singh, Brij B.; Floden, Angela M.; Combs, Colin K.

    2007-01-01

    Multiple cytokines are secreted in the brain during pro-inflammatory conditions and likely affect neuron survival. Previously, we demonstrated that glutamate and tumor necrosis factor alpha (TNFα) kill neurons via activation of the N-methyl-d-aspartate (NMDA) and TNFα receptors, respectively. This report continues characterizing the signaling cross-talk pathway initiated during this inflammation-related mechanism of death. Stimulation of mouse cortical neuron cultures with TNFα results in a t...

  11. NMDA receptor subunit expression and PAR2 receptor activation in colospinal afferent neurons (CANs during inflammation induced visceral hypersensitivity

    Caudle Robert M

    2009-09-01

    Full Text Available Abstract Background Visceral hypersensitivity is a clinical observation made when diagnosing patients with functional bowel disorders. The cause of visceral hypersensitivity is unknown but is thought to be attributed to inflammation. Previously we demonstrated that a unique set of enteric neurons, colospinal afferent neurons (CANs, co-localize with the NR1 and NR2D subunits of the NMDA receptor as well as with the PAR2 receptor. The aim of this study was to determine if NMDA and PAR2 receptors expressed on CANs contribute to visceral hypersensitivity following inflammation. Recently, work has suggested that dorsal root ganglion (DRG neurons expressing the transient receptor potential vanilloid-1 (TRPV1 receptor mediate inflammation induced visceral hypersensitivity. Therefore, in order to study CAN involvement in visceral hypersensitivity, DRG neurons expressing the TRPV1 receptor were lesioned with resiniferatoxin (RTX prior to inflammation and behavioural testing. Results CANs do not express the TRPV1 receptor; therefore, they survive following RTX injection. RTX treatment resulted in a significant decrease in TRPV1 expressing neurons in the colon and immunohistochemical analysis revealed no change in peptide or receptor expression in CANs following RTX lesioning as compared to control data. Behavioral studies determined that both inflamed non-RTX and RTX animals showed a decrease in balloon pressure threshold as compared to controls. Immunohistochemical analysis demonstrated that the NR1 cassettes, N1 and C1, of the NMDA receptor on CANs were up-regulated following inflammation. Furthermore, inflammation resulted in the activation of the PAR2 receptors expressed on CANs. Conclusion Our data show that inflammation causes an up-regulation of the NMDA receptor and the activation of the PAR2 receptor expressed on CANs. These changes are associated with a decrease in balloon pressure in response to colorectal distension in non-RTX and RTX lesioned

  12. Augmenting Learning Activities with Contextual Information Scent

    Li, Nan

    2015-01-01

    Students often have information needs while carrying out a multitude of learning activities at universities. When information is needed for investigating a problem, the student may interrupt the work and switch to an information seeking task. As Internet connectivity becomes ubiquitous, searching information has been routinized and integrated in the learning experience. However, information needs are not always fully recognized, or they can not be well articulated. A MOOC student may perceive...

  13. Differential Involvement of Amygdala and Cortical NMDA Receptors Activation upon Encoding in Odor Fear Memory

    Hegoburu, Chloé; Parrot, Sandrine; Ferreira, Guilaume; Mouly, Anne-Marie

    2014-01-01

    Although the basolateral amygdala (BLA) plays a crucial role for the acquisition of fear memories, sensory cortices are involved in their long-term storage in rats. However, the time course of their respective involvement has received little investigation. Here we assessed the role of the glutamatergic N-methyl-D-aspartate (NMDA) receptors in the…

  14. Pregnanolone 3alpha-Hemiesters - Novel Anionic Steroid Inhibitors of Activated NMDA Receptors

    Slavíková, Barbora; Chodounská, Hana; Vyklický, Vojtěch; Borovská, Jiřina; Krausová, Barbora; Vyklický ml., Ladislav; Kudová, Eva

    Kanazawa : -, 2012. [International Congress on Hormonal Steroids and Hormones and Cancer /15./. 15.11.2012-17.11.2012, Kanazawa] R&D Projects: GA ČR(CZ) GAP303/12/1464; GA TA ČR(CZ) TE01020028 Institutional support: RVO:61388963 ; RVO:67985823 Keywords : NMDA receptors * neurosteroids Subject RIV: CC - Organic Chemistry

  15. MARK/Par1 Kinase Is Activated Downstream of NMDA Receptors through a PKA-Dependent Mechanism

    Bernard, Laura P.; Zhang, Huaye

    2015-01-01

    The Par1 kinases, also known as microtubule affinity-regulating kinases (MARKs), are important for the establishment of cell polarity from worms to mammals. Dysregulation of these kinases has been implicated in autism, Alzheimer’s disease and cancer. Despite their important function in health and disease, it has been unclear how the activity of MARK/Par1 is regulated by signals from cell surface receptors. Here we show that MARK/Par1 is activated downstream of NMDA receptors in primary hippoc...

  16. Structure-activity relationships of N-substituted 4-(trifluoromethoxy)benzamidines with affinity for GluN2B-containing NMDA receptors.

    Beinat, Corinne; Banister, Samuel D; Hoban, Jane; Tsanaktsidis, John; Metaxas, Athanasios; Windhorst, Albert D; Kassiou, Michael

    2014-02-01

    GluN2B subtype-selective NMDA antagonists represent promising therapeutic targets for the symptomatic treatment of multiple CNS pathologies. A series of N-benzyl substituted benzamidines were synthesised and the benzyl ring was further replaced with various polycyclic moieties. Compounds were evaluated for activity at GluN2B containing NMDA receptors where analogues 9, 12, 16 and 18 were the most potent of the series, replacement of the benzyl ring with polycycles resulted in a complete loss of activity. PMID:24412068

  17. MARK/Par1 Kinase Is Activated Downstream of NMDA Receptors through a PKA-Dependent Mechanism.

    Laura P Bernard

    Full Text Available The Par1 kinases, also known as microtubule affinity-regulating kinases (MARKs, are important for the establishment of cell polarity from worms to mammals. Dysregulation of these kinases has been implicated in autism, Alzheimer's disease and cancer. Despite their important function in health and disease, it has been unclear how the activity of MARK/Par1 is regulated by signals from cell surface receptors. Here we show that MARK/Par1 is activated downstream of NMDA receptors in primary hippocampal neurons. Further, we show that this activation is dependent on protein kinase A (PKA, through the phosphorylation of Ser431 of Par4/LKB1, the major upstream kinase of MARK/Par1. Together, our data reveal a novel mechanism by which MARK/Par1 is activated at the neuronal synapse.

  18. Preferential Inhibition of Tonically over Phasically Activated NMDA Receptors by Pregnane Derivatives

    Vyklický, Vojtěch; Smejkalová, Tereza; Krausová, Barbora; Balík, Aleš; Kořínek, Miloslav; Borovská, Jiřina; Horák, Martin; Chvojková, Markéta; Kletečková, Lenka; Valeš, Karel; Černý, Jiří; Nekardová, Michaela; Chodounská, Hana; Kudová, Eva; Vyklický ml., Ladislav

    2016-01-01

    Roč. 36, č. 7 (2016), s. 2161-2175. ISSN 0270-6474 R&D Projects: GA ČR(CZ) GAP303/12/1464; GA ČR(CZ) GBP304/12/G069; GA TA ČR(CZ) TE01020028; GA ČR(CZ) GBP208/12/G016; GA MŠk(CZ) EE2.3.30.0025; GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:67985823 ; RVO:61388963 Keywords : memantine * neuroprotection * neurosteroid * NMDA receptor * pregnanolone sulfate * synaptic transmission Subject RIV: ED - Physiology Impact factor: 6.344, year: 2014

  19. Augmented reality to enhance an active telepresence system

    Wheeler, Alison; Pretlove, John R. G.; Parker, Graham A.

    1996-12-01

    Tasks carried out remotely via a telerobotic system are typically complex, occur in hazardous environments and require fine control of the robot's movements. Telepresence systems provide the teleoperator with a feeling of being physically present at the remote site. Stereoscopic video has been successfully applied to telepresence vision systems to increase the operator's perception of depth in the remote scene and this sense of presence can be further enhanced using computer generated stereo graphics to augment the visual information presented to the operator. The Mechatronic Systems and Robotics Research Group have over seven years developed a number of high performance active stereo vision systems culminating in the latest, a four degree-of-freedom stereohead. This carries two miniature color cameras and is controlled in real time by the motion of the operator's head, who views the stereoscopic video images on an immersive head mounted display or stereo monitor. The stereohead is mounted on a mobile robot, the movement of which is controlled by a joystick interface. This paper describes the active telepresence system and the development of a prototype augmented reality (AR) application to enhance the operator's sense of presence at the remote site. The initial enhancements are a virtual map and compass to aid navigation in degraded visual conditions and a virtual cursor that provides a means for the operator to interact with the remote environment. The results of preliminary experiments using the initial enhancements are presented.

  20. Stress-restress evokes sustained iNOS activity and altered GABA levels and NMDA receptors in rat hippocampus

    Harvey, Brian H; Oosthuizen, Frasia; Brand, Linda;

    2004-01-01

    RATIONALE: Stress-related glucocorticoid and glutamate release have been implicated in hippocampal atrophy evident in patients with post-traumatic stress disorder (PTSD). Glutamatergic mechanisms activate nitric oxide synthase (NOS), while gamma-amino-butyric acid (GABA) may inhibit both...... glutamatergic and nitrergic transmission. Animal studies support a role for NOS in stress. OBJECTIVES: We have studied the role of NOS and glucocorticoids, as well as inhibitory and excitatory transmitters, in a putative animal model of PTSD that emphasizes repeated trauma. METHODS: Hippocampal NOS activity, N......-methyl-D-aspartate (NMDA) receptor binding characteristics and GABA levels were studied in Sprague-Dawley rats 21 days after exposure to a stress-restress paradigm, using radiometric analysis, radioligand studies and high-performance liquid chromatography (HPLC) analysis with electrochemical detection, respectively...

  1. Abdomen and spinal cord segmentation with augmented active shape models.

    Xu, Zhoubing; Conrad, Benjamin N; Baucom, Rebeccah B; Smith, Seth A; Poulose, Benjamin K; Landman, Bennett A

    2016-07-01

    Active shape models (ASMs) have been widely used for extracting human anatomies in medical images given their capability for shape regularization of topology preservation. However, sensitivity to model initialization and local correspondence search often undermines their performances, especially around highly variable contexts in computed-tomography (CT) and magnetic resonance (MR) images. In this study, we propose an augmented ASM (AASM) by integrating the multiatlas label fusion (MALF) and level set (LS) techniques into the traditional ASM framework. Using AASM, landmark updates are optimized globally via a region-based LS evolution applied on the probability map generated from MALF. This augmentation effectively extends the searching range of correspondent landmarks while reducing sensitivity to the image contexts and improves the segmentation robustness. We propose the AASM framework as a two-dimensional segmentation technique targeting structures with one axis of regularity. We apply AASM approach to abdomen CT and spinal cord (SC) MR segmentation challenges. On 20 CT scans, the AASM segmentation of the whole abdominal wall enables the subcutaneous/visceral fat measurement, with high correlation to the measurement derived from manual segmentation. On 28 3T MR scans, AASM yields better performances than other state-of-the-art approaches in segmenting white/gray matter in SC. PMID:27610400

  2. Activation of NMDA receptors leads to phosphorylation of TRPV1 S800 by protein kinase C and A-Kinase anchoring protein 150 in rat trigeminal ganglia

    Lee, Jongseok; Chung, Man-Kyo; Ro, Jin Y.

    2012-01-01

    A-Kinase anchoring protein 150 (AKAP150) is required for the phosphorylation of transient receptor potential cation channel subfamily V member 1 (TRPV1) by PKA or PKC in sensory neurons and, hence, affects TRPV1-dependent hyperalgesia under pathological conditions. Recently, we showed that the activation of N-methyl-d-aspartate (NMDA) receptors sensitizes TRPV1 by enhancing serine phosphorylation through PKC in trigeminal nociceptors. In this study, we extended this observation by investigati...

  3. Potentiation of NMDA receptor-mediated transmission in striatal cholinergic interneurons.

    Oswald, Manfred J; Schulz, Jan M; Kelsch, Wolfgang; Oorschot, Dorothy E; Reynolds, John N J

    2015-01-01

    Pauses in the tonic firing of striatal cholinergic interneurons (CINs) emerge during reward-related learning in response to conditioning of a neutral cue. We have previously reported that augmenting the postsynaptic response to cortical afferents in CINs is coupled to the emergence of a cell-intrinsic afterhyperpolarization (AHP) underlying pauses in tonic activity. Here we investigated in a bihemispheric rat-brain slice preparation the mechanisms of synaptic plasticity of excitatory afferents to CINs and the association with changes in the AHP. We found that high frequency stimulation (HFS) of commissural corticostriatal afferents from the contralateral hemisphere induced a robust long-term depression (LTD) of postsynaptic potentials (PSP) in CINs. Depression of the PSP of smaller magnitude and duration was observed in response to HFS of the ipsilateral white matter or cerebral cortex. In Mg(2+)-free solution HFS induced NMDA receptor-dependent potentiation of the PSP, evident in both the maximal slope and amplitude of the PSP. The increase in maximal slope corroborates previous findings, and was blocked by antagonism of either D1-like dopamine receptors with SCH23390 or D2-like dopamine receptors with sulpiride during HFS in Mg(2+)-free solution. Potentiation of the slower PSP amplitude component was due to augmentation of the NMDA receptor-mediated potential as this was completely reversed on subsequent application of the NMDA receptor antagonist AP5. HFS similarly potentiated NMDA receptor currents isolated by blockade of AMPA/kainate receptors with CNQX. The plasticity-induced increase in the slow PSP component was directly associated with an increase in the subsequent AHP. Thus plasticity of cortical afferent synapses is ideally suited to influence the cue-induced firing dynamics of CINs, particularly through potentiation of NMDA receptor-mediated synaptic transmission. PMID:25914618

  4. Dexras1 a unique ras-GTPase interacts with NMDA receptor activity and provides a novel dissociation between anxiety, working memory and sensory gating.

    Carlson, G C; Lin, R E; Chen, Y; Brookshire, B R; White, R S; Lucki, I; Siegel, S J; Kim, S F

    2016-05-13

    Dexras1 is a novel GTPase that acts at a confluence of signaling mechanisms associated with psychiatric and neurological disease including NMDA receptors, NOS1AP and nNOS. Recent work has shown that Dexras1 mediates iron trafficking and NMDA-dependent neurodegeneration but a role for Dexras1 in normal brain function or psychiatric disease has not been studied. To test for such a role, mice with germline knockout (KO) of Dexras1 were assayed for behavioral abnormalities as well as changes in NMDA receptor subunit protein expression. Because Dexras1 is up-regulated during stress or by dexamethasone treatment, we included measures associated with emotion including anxiety and depression. Baseline anxiety-like measures (open field and zero maze) were not altered, nor were depression-like behavior (tail suspension). Measures of memory function yielded mixed results, with no changes in episodic memory (novel object recognition) but a significant decrement on working memory (T-maze). Alternatively, there was an increase in pre-pulse inhibition (PPI), without concomitant changes in either startle amplitude or locomotor activity. PPI data are consistent with the direction of change seen following exposure to dopamine D2 antagonists. An examination of NMDA subunit expression levels revealed an increased expression of the NR2A subunit, contrary to previous studies demonstrating down-regulation of the receptor following antipsychotic exposure (Schmitt et al., 2003) and up-regulation after exposure to isolation rearing (Turnock-Jones et al., 2009). These findings suggest a potential role for Dexras1 in modulating a selective subset of psychiatric symptoms, possibly via its interaction with NMDARs and/or other disease-related binding-partners. Furthermore, data suggest that modulating Dexras1 activity has contrasting effects on emotional, sensory and cognitive domains. PMID:26946266

  5. Differences in rat dorsal striatal NMDA and AMPA receptors following acute and repeated cocaine-induced locomotor activation.

    Dorothy J Yamamoto

    Full Text Available Sprague-Dawley rats can be classified as low or high cocaine responders (LCRs or HCRs, respectively based on their locomotor activity induced by an acute low dose of cocaine. Upon repeated cocaine exposure, LCRs display greater locomotor sensitization, reward, and reinforcement than HCRs. Altered glutamate receptor expression in the brain reward pathway has been linked to locomotor sensitization and addiction. To determine if such changes contribute to the differential development of locomotor sensitization, we examined protein levels of total, phosphorylated, and cell surface glutamate N-methyl D-aspartate (NMDA and α-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA receptors (Rs following acute or repeated cocaine (10 mg/kg, i.p. in LCRs, HCRs and saline controls. Three areas involved in the development and expression of locomotor sensitization were investigated: the ventral tegmental area (VTA, nucleus accumbens (NAc and dorsal striatum (dSTR. Our results revealed differences only in the dSTR, where we found that after acute cocaine, GluN2B(Tyr-1472 phosphorylation was significantly greater in LCRs, compared to HCRs and controls. Additionally in dSTR, after repeated cocaine, we observed significant increases in total GluA1, phosphorylated GluA1(Ser-845, and cell surface GluA1 in all cocaine-treated animals vs. controls. The acute cocaine-induced increases in NMDARs in dSTR of LCRs may help to explain the more ready development of locomotor sensitization and susceptibility to addiction-like behaviors in rats that initially exhibit little or no cocaine-induced activation, whereas the AMPAR increases after repeated cocaine may relate to recruitment of more dorsal striatal circuits and maintenance of the marked cocaine-induced locomotor activation observed in all of the rats.

  6. NMDA receptors in hyperammonemia and hepatic encephalopathy.

    Llansola, Marta; Rodrigo, Regina; Monfort, Pilar; Montoliu, Carmina; Kosenko, Elena; Cauli, Omar; Piedrafita, Blanca; El Mlili, Nisrin; Felipo, Vicente

    2007-12-01

    The NMDA type of glutamate receptors modulates learning and memory. Excessive activation of NMDA receptors leads to neuronal degeneration and death. Hyperammonemia and liver failure alter the function of NMDA receptors and of some associated signal transduction pathways. The alterations are different in acute and chronic hyperammonemia and liver failure. Acute intoxication with large doses of ammonia (and probably acute liver failure) leads to excessive NMDA receptors activation, which is responsible for ammonia-induced death. In contrast, chronic hyperammonemia induces adaptive responses resulting in impairment of signal transduction associated to NMDA receptors. The function of the glutamate-nitric oxide-cGMP pathway is impaired in brain in vivo in animal models of chronic liver failure or hyperammonemia and in homogenates from brains of patients died in hepatic encephalopathy. The impairment of this pathway leads to reduced cGMP and contributes to impaired cognitive function in hepatic encephalopathy. Learning ability is reduced in animal models of chronic liver failure and hyperammonemia and is restored by pharmacological manipulation of brain cGMP by administering phosphodiesterase inhibitors (zaprinast or sildenafil) or cGMP itself. NMDA receptors are therefore involved both in death induced by acute ammonia toxicity (and likely by acute liver failure) and in cognitive impairment in hepatic encephalopathy. PMID:17701332

  7. Novel anionic steroid inhibitors of phasically and tonically activated NMDA receptors

    Kudová, Eva; Chodounská, Hana; Slavíková, Barbora; Vyklický, Vojtěch; Borovská, Jiřina; Krausová, Barbora; Vyklický ml., Ladislav

    2012-01-01

    Roč. 106, - (2012), s778-s778. ISSN 0009-2770. [EuCheMS Chemistry Congress /4./. 26.08.2012-30.08.2012, Prague] Institutional research plan: CEZ:AV0Z40550506; CEZ:AV0Z50110509 Keywords : steroids * receptors * lipophilicity * structure-activity relationships Subject RIV: CC - Organic Chemistry

  8. Essential role of presynaptic NMDA receptors in activity-dependent BDNF secretion and corticostriatal LTP.

    Park, Hyungju; Popescu, Andrei; Poo, Mu-ming

    2014-12-01

    Activation of N-methyl-D-aspartate subtype of glutamate receptors (NMDARs) in postsynaptic dendrites is required for long-term potentiation (LTP) of many excitatory synapses, but the role of presynaptic axonal NMDARs in synaptic plasticity remains to be clarified. Here we report that axonal NMDARs play an essential role in LTP induction at mouse corticostriatal synapses by triggering activity-induced presynaptic secretion of brain-derived neurotrophic factor (BDNF). Genetic depletion of either BDNF or the NMDAR subunit GluN1 specifically in cortical axons abolished corticostriatal LTP in response to theta burst stimulation (TBS). Furthermore, functional axonal NMDARs were required for TBS-triggered prolonged axonal Ca(2+) elevation and BDNF secretion, supporting the notion that activation of axonal NMDARs induces BDNF secretion via enhancing Ca(2+) signals in the presynaptic nerve terminals. These results demonstrate that presynaptic NMDARs are equally important as postsynaptic NMDARs in LTP induction of corticostriatal synapses due to their role in mediating activity-induced presynaptic BDNF secretion. PMID:25467984

  9. Antidepressant activity of fluoxetine in the zinc deficiency model in rats involves the NMDA receptor complex.

    Doboszewska, Urszula; Szewczyk, Bernadeta; Sowa-Kućma, Magdalena; Młyniec, Katarzyna; Rafało, Anna; Ostachowicz, Beata; Lankosz, Marek; Nowak, Gabriel

    2015-01-01

    The zinc deficiency animal model of depression has been proposed; however, it has not been validated in a detailed manner. We have recently shown that depression-like behavior induced by dietary zinc restriction is associated with up-regulation of hippocampal N-methyl-d-aspartate receptor (NMDAR). Here we examined the effects of chronic administration of a selective serotonin reuptake inhibitor, fluoxetine (FLX), on behavioral and biochemical alterations (within NMDAR signaling pathway) induced by zinc deficiency. Male Sprague Dawley rats were fed a zinc adequate diet (ZnA, 50mg Zn/kg) or a zinc deficient diet (ZnD, 3mg Zn/kg) for 4 weeks. Then, FLX treatment (10mg/kg, i.p.) begun. Following 2 weeks of FLX administration the behavior of the rats was examined in the forced swim test (FST) and the spontaneous locomotor activity test. Twenty four hours later tissue was harvested. The proteins of NMDAR (GluN1, GluN2A and GluN2B) or AMPAR (GluA1) subunits, p-CREB and BDNF in the hippocampus (Western blot) and serum zinc level (TXRF) were examined. Depression-like behavior induced by ZnD in the FST was sensitive to chronic treatment with FLX. ZnD increased levels of GluN1, GluN2A, GluN2B and decreased pS485-GluA1, p-CREB and BDNF proteins. Administration of FLX counteracted the zinc restriction-induced changes in serum zinc level and hippocampal GluN1, GluN2A, GluN2B and p-CREB but not BDNF or pS845-GluA1 protein levels. This finding adds new evidence to the predictive validity of the proposed zinc deficiency model of depression. Antidepressant-like activity of FLX in the zinc deficiency model is associated with NMDAR complex. PMID:25845739

  10. Nitric oxide-induced activation of NF-κB-mediated NMDA-induced CTP:phosphocholine cytidylyltransferase alpha expression inhibition in A549 cells.

    Li, Lian; Shen, Li; She, Hua; Yue, Shaojie; Feng, Dandan; Luo, Ziqiang

    2011-02-01

    Pulmonary surfactant is a lipoprotein complex on the alveolar surface. It reduces the surface tension at the air-water interface and stabilizes the alveoli during expiration. Surfactant deficiency or dysfunction is associated with occurrence and development of many pulmonary diseases. Family members of CTP:phosphocholine cytidylyltransferase are rate-limiting enzymes for surfactant phospholipid synthesis. We had reported recently that the expression of CTP:phosphocholine cytidylyltransferase alpha (CCT-α) was inhibited during N-methyl-D: -aspartic acid (NMDA)-induced lung injury. But the molecular mechanism underlining remains elusive. In this work, we reported that NMDA induced nitric oxide synthase (NOS) activation and nuclear factor-kB (NF-κB) subunit p65 nuclear translocation in A549 cells, which were responsible for decreased (CCT-α) expression. Furthermore, NOS activation and elevated NO production are upstream regulators for p65 nuclear translocation and (CCT-α) expression inhibition. Our results provided important clues for further elucidating the mechanisms underlying glutamate-induced lung injury. PMID:20661636

  11. Acquisition of specific response-outcome associations requires NMDA receptor activation in the basolateral amygdala but not in the insular cortex.

    Parkes, Shauna L; Ferreira, Guillaume; Coutureau, Etienne

    2016-02-01

    The basolateral amygdala (BLA) and the gustatory region of the insular cortex (IC) are required for the encoding and retrieval of outcome value. Here, we examined if these regions are also necessary to learn associations between actions and their outcomes. Hungry rats were first trained to press two levers for a common outcome. Next, specific response-outcome (R-O) associations were introduced such that each response now earned a distinct food outcome. Prior to each specific R-O training session, rats received a bilateral infusion of the N-methyl-d-aspartate (NMDA) receptor antagonist, DL-APV, into either the BLA or the IC. One of the two outcomes was then devalued immediately prior to a choice test. Inhibition of NMDA receptor activity in the BLA, but not the IC, during the acquisition of specific R-O associations abolished selective devaluation. These results indicate that the BLA is critical for learning the association between actions and their specific consequences. PMID:26740161

  12. Frontopolar activity and connectivity support dynamic conscious augmentation of creative state.

    Green, Adam E; Cohen, Michael S; Raab, Hillary A; Yedibalian, Christopher G; Gray, Jeremy R

    2015-03-01

    No ability is more valued in the modern innovation-fueled economy than thinking creatively on demand, and the "thinking cap" capacity to augment state creativity (i.e., to try and succeed at thinking more creatively) is of broad importance for education and a rich mental life. Although brain-based creativity research has focused on static individual differences in trait creativity, less is known about changes in creative state within an individual. How does the brain augment state creativity when creative thinking is required? Can augmented creative state be consciously engaged and disengaged dynamically across time? Using a novel "thin slice" creativity paradigm in 55 fMRI participants performing verb-generation, we successfully cued large, conscious, short-duration increases in state creativity, indexed quantitatively by a measure of semantic distance derived via latent semantic analysis. A region of left frontopolar cortex, previously associated with creative integration of semantic information, exhibited increased activity and functional connectivity to anterior cingulate gyrus and right frontopolar cortex during cued augmentation of state creativity. Individual differences in the extent of increased activity in this region predicted individual differences in the extent to which participants were able to successfully augment state creative performance after accounting for trait creativity and intelligence. PMID:25394198

  13. NMDA receptors mediate synaptic competition in culture.

    Kevin She

    Full Text Available BACKGROUND: Activity through NMDA type glutamate receptors sculpts connectivity in the developing nervous system. This topic is typically studied in the visual system in vivo, where activity of inputs can be differentially regulated, but in which individual synapses are difficult to visualize and mechanisms governing synaptic competition can be difficult to ascertain. Here, we develop a model of NMDA-receptor dependent synaptic competition in dissociated cultured hippocampal neurons. METHODOLOGY/PRINCIPAL FINDINGS: GluN1 -/- (KO mouse hippocampal neurons lacking the essential NMDA receptor subunit were cultured alone or cultured in defined ratios with wild type (WT neurons. The absence of functional NMDA receptors did not alter neuron survival. Synapse development was assessed by immunofluorescence for postsynaptic PSD-95 family scaffold and apposed presynaptic vesicular glutamate transporter VGlut1. Synapse density was specifically enhanced onto minority wild type neurons co-cultured with a majority of GluN1 -/- neighbour neurons, both relative to the GluN1 -/- neighbours and relative to sister pure wild type cultures. This form of synaptic competition was dependent on NMDA receptor activity and not conferred by the mere physical presence of GluN1. In contrast to these results in 10% WT and 90% KO co-cultures, synapse density did not differ by genotype in 50% WT and 50% KO co-cultures or in 90% WT and 10% KO co-cultures. CONCLUSIONS/SIGNIFICANCE: The enhanced synaptic density onto NMDA receptor-competent neurons in minority coculture with GluN1 -/- neurons represents a cell culture paradigm for studying synaptic competition. Mechanisms involved may include a retrograde 'reward' signal generated by WT neurons, although in this paradigm there was no 'punishment' signal against GluN1 -/- neurons. Cell culture assays involving such defined circuits may help uncover the rules and mechanisms of activity-dependent synaptic competition in the

  14. Optimal placement of active elements in control augmented structural synthesis

    Sepulveda, A. E.; Jin, I. M.; Schmit, L. A., Jr.

    1992-01-01

    A methodology for structural/control synthesis is presented in which the optimal location of active members is treated in terms of (0,1) variables. Structural member sizes, control gains and (0,1) placement variables are treated simultaneously as design variables. Optimization is carried out by generating and solving a sequence of explicit approximate problems using a branch and bound strategy. Intermediate design variable and intermediate response quantity concepts are used to enhance the quality of the approximate design problems. Numerical results for example problems are presented to illustrate the efficacy of the design procedure set forth.

  15. Osmotic Edema Rapidly Increases Neuronal Excitability Through Activation of NMDA Receptor-Dependent Slow Inward Currents in Juvenile and Adult Hippocampus.

    Lauderdale, Kelli; Murphy, Thomas; Tung, Tina; Davila, David; Binder, Devin K; Fiacco, Todd A

    2015-01-01

    Cellular edema (cell swelling) is a principal component of numerous brain disorders including ischemia, cortical spreading depression, hyponatremia, and epilepsy. Cellular edema increases seizure-like activity in vitro and in vivo, largely through nonsynaptic mechanisms attributable to reduction of the extracellular space. However, the types of excitability changes occurring in individual neurons during the acute phase of cell volume increase remain unclear. Using whole-cell patch clamp techniques, we report that one of the first effects of osmotic edema on excitability of CA1 pyramidal cells is the generation of slow inward currents (SICs), which initiate after approximately 1 min. Frequency of SICs increased as osmolarity decreased in a dose-dependent manner. Imaging of real-time volume changes in astrocytes revealed that neuronal SICs occurred while astrocytes were still in the process of swelling. SICs evoked by cell swelling were mainly nonsynaptic in origin and NMDA receptor-dependent. To better understand the relationship between SICs and changes in neuronal excitability, recordings were performed in increasingly physiological conditions. In the absence of any added pharmacological reagents or imposed voltage clamp, osmotic edema induced excitatory postsynaptic potentials and burst firing over the same timecourse as SICs. Like SICs, action potentials were blocked by NMDAR antagonists. Effects were more pronounced in adult (8-20 weeks old) compared with juvenile (P15-P21) mice. Together, our results indicate that cell swelling triggered by reduced osmolarity rapidly increases neuronal excitability through activation of NMDA receptors. Our findings have important implications for understanding nonsynaptic mechanisms of epilepsy in relation to cell swelling and reduction of the extracellular space. PMID:26489684

  16. Augmented active surface model for the recovery of small structures in CT.

    Bradshaw, Andrew Philip; Taubman, David S; Todd, Michael J; Magnussen, John S; Halmagyi, G Michael

    2013-11-01

    This paper devises an augmented active surface model for the recovery of small structures in a low resolution and high noise setting, where the role of regularization is especially important. The emphasis here is on evaluating performance using real clinical computed tomography (CT) data with comparisons made to an objective ground truth acquired using micro-CT. In this paper, we show that the application of conventional active contour methods to small objects leads to non-optimal results because of the inherent properties of the energy terms and their interactions with one another. We show that the blind use of a gradient magnitude based energy performs poorly at these object scales and that the point spread function (PSF) is a critical factor that needs to be accounted for. We propose a new model that augments the external energy with prior knowledge by incorporating the PSF and the assumption of reasonably constant underlying CT numbers. PMID:24048014

  17. Imaging the PCP site of the NMDA ion channel

    Waterhouse, Rikki N. E-mail: rnw7@columbia.edu

    2003-11-01

    The N-methyl-D-aspartate (NMDA) ion channel plays a role in neuroprotection, neurodegeneration, long-term potentiation, memory, and cognition. It is implicated in the pathophysiology of several neurological and neuropsychiatric disorders including Parkinson's Disease, Huntington's Chorea, schizophrenia, alcoholism and stroke. The development of effective radiotracers for the study of NMDA receptors is critical for our understanding of their function, and their modulation by endogenousr substances or therapeutic drugs. Since the NMDA/PCP receptor lies within the channel, it is a unique target and is theoretically accessible only when the channel is in the active and 'open' state, but not when it is in the inactive or 'closed' state. The physical location of the NMDA/PCP receptor not only makes it an important imaging target but also complicates the development of suitable PET and SPECT radiotracers for this site. An intimate understanding of the biochemical, pharmacological, physiological and behavioral processes associated with the NMDA ion channel is essential to develop improved imaging agents. This review outlines progress made towards the development of radiolabeled agents for PCP sites of the NMDA ion channel. In addition, the animal and pharmacological models used for in vitro and in vivo assessment of NMDA receptor targeted agents are discussed.

  18. Imaging the PCP site of the NMDA ion channel

    The N-methyl-D-aspartate (NMDA) ion channel plays a role in neuroprotection, neurodegeneration, long-term potentiation, memory, and cognition. It is implicated in the pathophysiology of several neurological and neuropsychiatric disorders including Parkinson's Disease, Huntington's Chorea, schizophrenia, alcoholism and stroke. The development of effective radiotracers for the study of NMDA receptors is critical for our understanding of their function, and their modulation by endogenousr substances or therapeutic drugs. Since the NMDA/PCP receptor lies within the channel, it is a unique target and is theoretically accessible only when the channel is in the active and 'open' state, but not when it is in the inactive or 'closed' state. The physical location of the NMDA/PCP receptor not only makes it an important imaging target but also complicates the development of suitable PET and SPECT radiotracers for this site. An intimate understanding of the biochemical, pharmacological, physiological and behavioral processes associated with the NMDA ion channel is essential to develop improved imaging agents. This review outlines progress made towards the development of radiolabeled agents for PCP sites of the NMDA ion channel. In addition, the animal and pharmacological models used for in vitro and in vivo assessment of NMDA receptor targeted agents are discussed

  19. Proteolytically modified human beta 2-microglobulin augments the specific cytotoxic activity in murine mixed lymphocyte culture

    Nissen, Mogens Holst; Claësson, M H

    1987-01-01

    (M-beta 2-m) bind to murine lymphocytes expressing H-2 class I antigens; M-beta 2-m, when added at day 0 and 1 of culture in nanomolar concentrations to a one-way murine allogeneic mixed lymphocyte culture (MLC) augments the generation of specific cytotoxic T lymphocytes; M-beta 2-m increases the...... endogenous production of interleukin 2 in the MLC culture; monoclonal antibody which reacts with both the native beta 2-m and M-beta 2-m molecule blocks the augmentation of cytotoxic T lymphocyte production induced by M-beta 2-m; murine as well as human MLC responder cells can proteolytically modify native...... human beta 2-m; and the modifying activity of murine MLC responder cells was blocked in an intermediary step by an alloantibody, which reacts specifically with murine major histocompatibility complex, class I-associated beta 2-m. These findings suggest that the modification process is preceded by an...

  20. Concept of an immersive assistance system with augmented reality for the support of manual activities in radioactive production environments

    The thesis on an immersive assistance system concept with augmented reality for the support of manual activities in radioactive production environments covers the following topics: analysis of the situation: production and use of radioactive materials, problem analysis of the work in the production facilities, necessity of manual activities, automation, prediction in hot cells; status of research and development; assistance system concept, immersive camera system; augmented reality support in hot cells; economic evaluation and generalization.

  1. 洛伐他汀通过抑制Calpain和CDK5的过度激活减轻NMDA的毒性损害%Lovastatin attenuates Calpain and CDK5 over-activation induced by NMDA

    马涛; 许著一; 姚晴宇; 孔岳南

    2012-01-01

    Objective To observe the effect of lovastatin on the excitotoxicity induced by NMDA in cortical neurons in rats and to investigate the underlying mechanism. Methods Cortical neurons prepared from E17 rats were assigned into 4 groups:NMDA group (addition of 100 μmol/L of NMDA for 15 minutes),LOV group (pretreatment of the neurons for 3 days with 500 nmol/L of LOV),LOV+NMDA group (pretreatment of the neurons for 3 days with 500 nmol/L of LOV and addition of 100 μmol/L of NMDA for 15 minutes) and untreated group (addition of isodose solvent).Cell viability was evaluated with the trypan blue dye exclusion test,the morphology and number of neurons were assessed with MAP-2 immunofluorescence staining,and the level of protein was measured with Western blotting assay. Results Trypan blue staining demonstrated that the pretreatment with 500 nmol/L of lovastatin for 3 days significantly protected the neurons against the excitotoxicity induced by NMDA (P<0.05 vs NMDA).Immunofluorescence staining demonstrated the number of MAP-2 positive neurons decreased and the surviving neurons showed a loss of MAP-2 positive dendrites after NMDA treatment (P<0.05 vs untreated),which were not observed after lovastatin pretreatment (P<0.05 vs NMDA).Excitotoxicity was mediated in part by the Calpain over-activation and the subsequent protein truncation events on Calpain substrate, CDK5 co-activator P35 to P25 cleavage. Lovastatin pretreatment remarkably suppressed Calpain over-activation and the conversion from P35 to P25 in response to NMDA exposure as detected by Western blotting analysis (P<0.05 vs NMDA). Conclusions Lovastatin significantly attenuates the excitotoxicity induced by NMDA. The neuroprotection of lovastatin may be mediated by blocking the Calpain and CDK5 over-activation.%目的 探讨洛伐他汀(LOV)对N-甲基-D-天门冬氨酸(NMDA)诱导的大鼠皮质神经元兴奋性毒性损害的神经保护作用及可能机制. 方法 原代培养的大鼠皮质神经

  2. Characterisation of the Redox Sensitive NMDA Receptor

    Alzahrani, Ohood

    2016-05-01

    Glucose entry into the brain and its subsequent metabolism to L-lactate, regulated by astrocytes, plays a major role in synaptic plasticity and memory formation. A recent study has shown that L-lactate produced by the brain upon stimulation of glycolysis, and glycogen-derived L-lactate from astrocytes and its transport into neurons, is crucial for memory formation. A recent study revealed the molecular mechanisms that underlie the role of L-lactate in neuronal plasticity and long-term memory formation. L-lactate was shown to induce a cascade of molecular events via modulation of redox-sensitive N-Methyl-D-aspartate (NMDA) receptor activity that was mimicked by nicotinamide adenine dinucleotide hydride (NADH) co-enzyme. This indicated that changes in cellular redox state, following L-lactate transport inside the cells and its subsequent metabolism, production of NADH, and favouring a reduced state are the key effects of L-lactate. Therefore, we are investigating the role of L-lactate in modulating NMDA receptor function via redox modulatory sites. Accordingly, crucial redox-sensitive cysteine residues, Cys320 and Cys87, of the NR2A NMDA receptor subunit are mutated using site-directed mutation, transfected, and expressed in HEK293 cells. This cellular system will then be used to characterise and monitor its activity upon Llactate stimulation, compared to the wild type. This will be achieved by calcium imaging, using fluorescent microscopy. Our data shows that L-lactate potentiated NMDA receptor activity and increased intracellular calcium influx in NR1/NR2A wild type compared to the control condition (WT NR1/NR2A perfused with (1μM) glutamate and (1μM) glycine agonist only), showing faster response initiation and slower decay rate of the calcium signal to the baseline. Additionally, stimulating with L-lactate associated with greater numbers of cells having high fluorescent intensity (peak amplitude) compared to the control. Furthermore, L-lactate rescued the

  3. Combined chronic blockade of hyper-active L-type calcium channels and NMDA receptors ameliorates HIV-1 associated hyper-excitability of mPFC pyramidal neurons.

    Khodr, Christina E; Chen, Lihua; Dave, Sonya; Al-Harthi, Lena; Hu, Xiu-Ti

    2016-10-01

    Human Immunodeficiency Virus type 1 (HIV-1) infection induces neurological and neuropsychological deficits, which are associated with dysregulation of the medial prefrontal cortex (mPFC) and other vulnerable brain regions. We evaluated the impact of HIV infection in the mPFC and the therapeutic potential of targeting over-active voltage-gated L-type Ca(2+) channels (L-channel) and NMDA receptors (NMDAR), as modeled in HIV-1 transgenic (Tg) rats. Whole-cell patch-clamp recording was used to assess the membrane properties and voltage-sensitive Ca(2+) potentials (Ca(2+) influx) in mPFC pyramidal neurons. Neurons from HIV-1 Tg rats displayed reduced rheobase, spike amplitude and inwardly-rectifying K(+) influx, increased numbers of action potentials, and a trend of aberrant firing compared to those from non-Tg control rats. Neuronal hyper-excitation was associated with abnormally-enhanced Ca(2+) influx (independent of NMDAR), which was eliminated by acute L-channel blockade. Combined chronic blockade of over-active L-channels and NMDARs with open-channel blockers abolished HIV effects on spiking, aberrant firing and Ca(2+) potential half-amplitude duration, though not the reduced inward rectification. In contrast, individual chronic blockade of over-active L-channels or NMDARs did not alleviate HIV-induced mPFC hyper-excitability. These studies demonstrate that HIV alters mPFC neuronal activity by dysregulating membrane excitability and Ca(2+) influx through the L-channels. This renders these neurons more susceptible and vulnerable to excitatory stimuli, and could contribute to HIV-associated neuropathogenesis. Combined targeting of over-active L-channels/NMDARs alleviates HIV-induced dysfunction of mPFC pyramidal neurons, emphasizing a potential novel therapeutic strategy that may effectively decrease HIV-induced Ca(2+) dysregulation in the mPFC. PMID:27326669

  4. Augmentation and Maximization of Per-Capita Call Active Space Through Chorusing in Anuran Amphibians

    Fox, James Henderson

    It is poorly understood why anuran males form choruses. Although various reasons have been proposed, empirical support is lacking. This study proposed, developed, and evaluated the chorus active space (CAS) augmentation theory, which states that anuran choruses are formed and organized so as to augment and maximize per-capita CAS beyond that which could be achieved by an isolated male. This study involved three phases. First, computer models of hypothetical choruses indicated that CAS, as defined, is necessarily augmented for chorusing males. These models provided the necessary information from which optimal interindividual distances (IIDs), corresponding to maximal CASs, could be estimated differentially for linear and planar chorus configurations. The second phase examined Acris crepitans and Hyla cinerea choruses for optimal intermale spacing. A. crepitans, which utilizes mixed chorus geometries (either linear or planar, depending on available resources), cannot optimize IID within any observed pond-type breeding site; however, observed spacing would be optimal along a stream bank, where chorusing often occurs, for a chorus population of 61, approximately the minimum value at which CAS characteristics are stabile. H. cinerea males, which form only planar choruses, space orders of magnitude closer than optimal. Suboptimal spacing in this species is understandable, considering the would-be size of an optimally spaced chorus. In the final phase of this study, a database of CAS-related data was compiled mostly from published sources and was examined for variable relationships predicted on the basis of CAS augmentation theory. The findings suggest that very few planar geometry species may maximize CAS; whereas, a much larger number of mixed geometry species, perhaps as well as linear geometry species, may maximize CAS. These findings loosely agree with the field study findings and suggest that CAS augmentation theory applies to at least a subset of anuran species and

  5. N-Methyl-D-aspartic Acid (NMDA in the nervous system of the amphioxus Branchiostoma lanceolatum

    Garcia-Fernàndez Jordi

    2007-12-01

    Full Text Available Abstract Background NMDA (N-methyl-D-aspartic acid is a widely known agonist for a class of glutamate receptors, the NMDA type. Synthetic NMDA elicits very strong activity for the induction of hypothalamic factors and hypophyseal hormones in mammals. Moreover, endogenous NMDA has been found in rat, where it has a role in the induction of GnRH (Gonadotropin Releasing Hormone in the hypothalamus, and of LH (Luteinizing Hormone and PRL (Prolactin in the pituitary gland. Results In this study we show evidence for the occurrence of endogenous NMDA in the amphioxus Branchiostoma lanceolatum. A relatively high concentration of NMDA occurs in the nervous system of this species (3.08 ± 0.37 nmol/g tissue in the nerve cord and 10.52 ± 1.41 nmol/g tissue in the cephalic vesicle. As in rat, in amphioxus NMDA is also biosynthesized from D-aspartic acid (D-Asp by a NMDA synthase (also called D-aspartate methyl transferase. Conclusion Given the simplicity of the amphioxus nervous and endocrine systems compared to mammalian, the discovery of NMDA in this protochordate is important to gain insights into the role of endogenous NMDA in the nervous and endocrine systems of metazoans and particularly in the chordate lineage.

  6. How does the Augmented Reality Manual enhance cognitive activity while doing complex maintenance tasks?: Augmented Tutorial Overlaid Manual (ATOM)

    It has been more than a decade since the concept of Augmented Reality (AR) was introduced. Many related technologies, such as tracking and display, to animate this concept have improved to certain levels. AR is well suited for interaction with the cognitive vision system. In contrast to the virtual reality, AR applications enrich the perceived reality with additional visual information which ranges from text annotation and object highlighting to complex 3D objects. AR has been tested its potentiality in various forms of applications. For example, visitors wear Head Mount Display (HMD) to see virtual guides explaining artifacts in a museum or soldiers are informed geographical features about unfamiliar operation sites. Recently, researchers tried to use AR as a means of teaching or training apparatus; however, there are still some technical obstacles to put this fascinating technology into practice. In this study, we will use Cognitive Load Theory (CLT) to design a manual of pump maintenance and convert it to AR technology to propose a proto type of an on-line AR maintenance manual to prove its possibility as an interactive learning tool

  7. How does the Augmented Reality Manual enhance cognitive activity while doing complex maintenance tasks?: Augmented Tutorial Overlaid Manual (ATOM)

    Yim, Ho Bin; Seong, Poong Hyun [Korea Advanced Institute of Technology and Science, Daejeon (Korea, Republic of)

    2008-10-15

    It has been more than a decade since the concept of Augmented Reality (AR) was introduced. Many related technologies, such as tracking and display, to animate this concept have improved to certain levels. AR is well suited for interaction with the cognitive vision system. In contrast to the virtual reality, AR applications enrich the perceived reality with additional visual information which ranges from text annotation and object highlighting to complex 3D objects. AR has been tested its potentiality in various forms of applications. For example, visitors wear Head Mount Display (HMD) to see virtual guides explaining artifacts in a museum or soldiers are informed geographical features about unfamiliar operation sites. Recently, researchers tried to use AR as a means of teaching or training apparatus; however, there are still some technical obstacles to put this fascinating technology into practice. In this study, we will use Cognitive Load Theory (CLT) to design a manual of pump maintenance and convert it to AR technology to propose a proto type of an on-line AR maintenance manual to prove its possibility as an interactive learning tool.

  8. Requirement of JIP scaffold proteins for NMDA-mediated signal transduction

    Kennedy, Norman J.; Martin, Gilles; Ehrhardt, Anka G.; Cavanagh-Kyros, Julie; Kuan, Chia-Yi; Rakic, Pasko; Richard A Flavell; Treistman, Steven N.; Davis, Roger J

    2007-01-01

    JIP scaffold proteins are implicated in the regulation of protein kinase signal transduction pathways. To test the physiological role of these scaffold proteins, we examined the phenotype of compound mutant mice that lack expression of JIP proteins. These mice were found to exhibit severe defects in N-methyl-D-aspartic acid (NMDA) receptor function, including decreased NMDA-evoked current amplitude, cytoplasmic Ca++, and gene expression. The decreased NMDA receptor activity in JIP-deficient n...

  9. Open Augmented Reality Standards: Current Activities in Standards- Development Organizations%Open Augmented Reality Standards: Current Activities in Standards- Development Organizations

    Christine Perey

    2012-01-01

    Augmented reality (AR) has emerged from research laboratories and is now being accepted in other domains as an attractive way of visualizing information. Before AR can be used in the mass market, there are a number of obstacles that need to be overcome. Several of these can be overcome by adopting open standards. A global grassroots community seeking open, interoperable AR content and experiences began to take shape in early 2010. This community is working collaboratively to reduce the barriers to the flow of data from content provider to AR end user. Standards development organizations and industry groups that provide open interfaces for AR meet regularly to provide updates, identify complementary work, and seek harmonization. The community also identifies deployer and implementer needs, communicates requirements, and discusses emerging challenges that could be resolved with standards. In this article, we describe current activities in international standards-development organizations. We summarize the AR standards gap analysis and shed light on special considerations for using standards in mobile AR.

  10. M-CSF potently augments RANKL-induced resorption activation in mature human osteoclasts.

    Jason M Hodge

    Full Text Available Macrophage-CSF (M-CSF is critical for osteoclast (OC differentiation and is reported to enhance mature OC survival and motility. However, its role in the regulation of bone resorption, the main function of OCs, has not been well characterised. To address this we analysed short-term cultures of fully differentiated OCs derived from human colony forming unit-granulocyte macrophages (CFU-GM. When cultured on dentine, OC survival was enhanced by M-CSF but more effectively by receptor activator of NFκB ligand (RANKL. Resorption was entirely dependent on the presence of RANKL. Co-treatment with M-CSF augmented RANKL-induced resorption in a concentration-dependent manner with a (200-300% stimulation at 25 ng/mL, an effect observed within 4-6 h. M-CSF co-treatment also increased number of resorption pits and F-actin sealing zones, but not the number of OCs or pit size, indicating stimulation of the proportion of OCs activated. M-CSF facilitated RANKL-induced activation of c-fos and extracellular signal-regulated kinase (ERK 1/2 phosphorylation, but not NFκB nor nuclear factor of activated T-cells, cytoplasmic-1 (NFATc1. The mitogen-activated protein kinase kinase (MEK 1 inhibitor PD98059 partially blocked augmentation of resorption by M-CSF. Our results reveal a previously unidentified role of M-CSF as a potent stimulator of mature OC resorbing activity, possibly mediated via ERK upstream of c-fos.

  11. Active Learning based on the use of Augmented Reality Outline of Possible Applications: Serious Games, Scientific Experiments, Confronting Studies with Creation, Training for Carrying out Technical Skills

    Cieutat, Jean-Marc; Hugues, Olivier; Ghouaiel, Nehla

    2012-01-01

    This paper looks at augmented reality as a support for active learning. Fourth areas of application are studied: serious games, scientific experiments, confronting study results with creation and training for carrying out technical skills. After introducing a new proposed augmented reality definition, we illustrate each area with original examples like an augmented reality serious game to understand electromagnetic phenomena and their applications in electrical engineering or still an augment...

  12. Perlecan domain 1 recombinant proteoglycan augments BMP-2 activity and osteogenesis

    DeCarlo Arthur A

    2012-09-01

    Full Text Available Abstract Background Many growth factors, such as bone morphogenetic protein (BMP-2, have been shown to interact with polymers of sulfated disacharrides known as heparan sulfate (HS glycosaminoglycans (GAGs, which are found on matrix and cell-surface proteoglycans throughout the body. HS GAGs, and some more highly sulfated forms of chondroitin sulfate (CS, regulate cell function by serving as co-factors, or co-receptors, in GF interactions with their receptors, and HS or CS GAGs have been shown to be necessary for inducing signaling and GF activity, even in the osteogenic lineage. Unlike recombinant proteins, however, HS and CS GAGs are quite heterogenous due, in large part, to post-translational addition, then removal, of sulfate groups to various positions along the GAG polymer. We have, therefore, investigated whether it would be feasible to deliver a DNA pro-drug to generate a soluble HS/CS proteoglycan in situ that would augment the activity of growth-factors, including BMP-2, in vivo. Results Utilizing a purified recombinant human perlecan domain 1 (rhPln.D1 expressed from HEK 293 cells with HS and CS GAGs, tight binding and dose-enhancement of rhBMP-2 activity was demonstrated in vitro. In vitro, the expressed rhPln.D1 was characterized by modification with sulfated HS and CS GAGs. Dose-enhancement of rhBMP-2 by a pln.D1 expression plasmid delivered together as a lyophilized single-phase on a particulate tricalcium phosphate scaffold for 6 or more weeks generated up to 9 fold more bone volume de novo on the maxillary ridge in a rat model than in control sites without the pln.D1 plasmid. Using a significantly lower BMP-2 dose, this combination provided more than 5 times as much maxillary ridge augmentation and greater density than rhBMP-2 delivered on a collagen sponge (InFuse™. Conclusions A recombinant HS/CS PG interacted strongly and functionally with BMP-2 in binding and cell-based assays, and, in vivo, the pln.247 expression plasmid

  13. Dual contribution of NR2B subunit of NMDA receptor and SK3 Ca(2+)-activated K+ channel to genetic predisposition to anorexia nervosa.

    Koronyo-Hamaoui, Maya; Frisch, Amos; Stein, Daniel; Denziger, Yardena; Leor, Shani; Michaelovsky, Elena; Laufer, Neil; Carel, Cynthia; Fennig, Silvana; Mimouni, Mark; Ram, Anca; Zubery, Eynat; Jeczmien, Pablo; Apter, Alan; Weizman, Abraham; Gak, Eva

    2007-01-01

    Since identification of the genetic component in anorexia nervosa (AN), genes that partake in serotonergic and dopaminergic systems and in hormonal and weight regulation have been suggested as potential candidates for AN susceptibility. We propose another set of candidate genes. Those are genes that are involved in the signaling pathway using NMDA-R and SK channels and have been suggested as possible effectors of NMDA-R driven signaling. The role of NMDA-R in the etiology of schizophrenia has already been substantiated on various levels. Several studies based on population and family groups have implicated SK3 in schizophrenia and more recently in AN as well. Our study group consisted of 90 AN family trios. We examined the transmission of two potentially functional polymorphisms, 5073T>G polymorphism in the gene encoding the NR2B subunit of NMDA-R and CAG repeats in the coding region of SK3 channel gene. Using HHRR and TDT approaches, we found that both polymorphisms were preferentially transmitted to AN offspring (TDT yielded chi(2)=5.01, p=0.025 for NR2B 5073G alleles and chi(2)=11.75, p19 repeats). Distribution analysis of the combined NR2B/SK3 genotypes suggests that the contribution of both polymorphisms to AN risk is independent and cumulative (OR=2.44 for NR2B GG genotype and OR=3.01 for SK3 SL and LL genotypes, and OR=6.8 for the combined NR2B/SK3 genotypes including high-risk alleles). These findings point to the contribution of genes associated with the NMDA-R signaling pathway to predisposition and development of AN. PMID:16157352

  14. Aspirin augments carotid-cardiac baroreflex sensitivity during muscle mechanoreflex and metaboreflex activation in humans.

    Drew, Rachel C; Muller, Matthew D; Blaha, Cheryl A; Mast, Jessica L; Herr, Michael D; Stocker, Sean D; Sinoway, Lawrence I

    2013-10-15

    Muscle mechanoreflex activation decreases the sensitivity of carotid baroreflex (CBR)-heart rate (HR) control during local metabolite accumulation in humans. However, the contribution of thromboxane A2 (TXA2) toward this response is unknown. Therefore, the effect of inhibiting TXA2 production via low-dose aspirin on CBR-HR sensitivity during muscle mechanoreflex and metaboreflex activation in humans was examined. Twelve young subjects performed two trials during two visits, preceded by 7 days' low-dose aspirin (81 mg) or placebo. One trial involved 3-min passive calf stretch (mechanoreflex) during 7.5-min limb circulatory occlusion (CO). In another trial, CO was preceded by 1.5 min of 70% maximal voluntary contraction isometric calf exercise to accumulate metabolites during CO and stretch (mechanoreflex and metaboreflex). HR (ECG) and mean arterial pressure (Finometer) were recorded. CBR function was assessed using rapid neck pressures ranging from +40 to -80 mmHg. Aspirin significantly decreased baseline thromboxane B2 production by 84 ± 4% (P aspirin, stretch with metabolite accumulation significantly augmented maximal gain (GMAX) and operating point gain (GOP) of CBR-HR (GMAX; -0.71 ± 0.14 vs. -0.37 ± 0.08 and GOP; -0.69 ± 0.13 vs. -0.35 ± 0.12 beats·min(-1)·mmHg(-1) for aspirin and placebo, respectively; P aspirin and placebo during stretch with metabolite accumulation. In conclusion, these findings suggest that low-dose aspirin augments CBR-HR sensitivity during concurrent muscle mechanoreflex and metaboreflex activation in humans. This increased sensitivity appears linked to reduced TXA2 production, which likely plays a role in metabolite sensitization of muscle mechanoreceptors. PMID:23970529

  15. In vitro augmentation of natural killer cell activity by manganese chloride

    The in vitro cultivation of murine spleen cells with MnCl2 resulted in the enhancement of natural killer (NK) cell activity as measured in a 4-h 51Cr-release assay. Optimal enhancement of NK activity was observed at concentrations of 10-20 μg MnCl2/culture (72-144 μM Mn2+). Enhancement of NK activity by MnCl2 was not associated with any changes in the number or viability of cells following culture. The addition of antiasialo GM1 antibody and complement to spleen cell cultures completely abrogated the enhancement of NK activity by MnCl2. The enhancement of NK activity by MnCl2 in vitro was accompanied by interferon induction. The addition of rabbit antimouse interferon to spleen cells cultured with MnCl2 reduced NK activity. NK activity in cultures treated with MnCl2 was also reduced upon removal of plastic adherent cells. However, restoration of enhanced NK activity by addition of adherent cells to nonadherent cells in the presence of MnCl2 was not observed. Similar effects of NK activity were observed with polyinosinic-polycytidylic acid (Poly I x C), a known interferon inducer and NK enhancer. The results demonstrate that murine splenic NK activity is enhanced in vitro by MnCl2 and that this enhancement may be mediated by interferon induction. The results also suggest that in vitro enhancement of NK activity by MnCl2, as with Poly I x C, may require participation of an adherent cell population for NK augmentation

  16. β-endorphin augments the cytolytic activity and interferon production of natural killer cells

    The in vitro effects of the neurohormone β-endorphin (b-end) on natural killer (NK) activity and interferon (IFN) production mediated by large granular lymphocytes (LGL) were investigated. LGL-enriched fractions from peripheral blood mononuclear cells (PBMC) from normal human volunteers were obtained by fractionation over discontinuous Percoll gradients. LGL were preincubated with or without various concentrations of b-end or the closely related peptides α-endorphin (a-end), γ-endorphin (g-end), or D-ALA2-β-endorphin (D-ALA2-b-end), a synthetic b-end analogue. NK activity was assayed on 51Cr-labeled K562 target cells. Preincubation of LGL effectors (but not K562 targets) for 2 to 18 hr with concentrations of b-end between 10-7 M and 10-10 M produced significant augmentation of NK cytolytic activity (mean percentage increase: 63%). The classic opiate antagonist naloxone blocked the enhancing effect when used at a 100-fold molar excess relative to b-end. These findings demonstrate that b-end enhances NK activity and IFN production of purified LGL, and suggests that b-end might bind to an opioid receptor on LGL that can be blocked by naloxone. These results lend support to the concepts of regulation of the immune response by neurohormones and the functional relationship between the nervous and immune systems

  17. Nicotine-activated descending facilitation on spinal NMDA-dependent reflex potentiation from pontine tegmentum in rats.

    Pan, Shwu-Fen; Peng, Hsien-Yu; Chen, Chi-Chung; Chen, Mei-Jung; Lee, Shin-Da; Cheng, Chen-Li; Shyu, Jyh-Cherng; Liao, Jiuan-Miaw; Chen, Gin-Den; Lin, Tzer-Bin

    2008-05-01

    This study was conducted to investigate the possible neurotransmitter that activates the descending pathways coming from the dorsolateral pontine tegmentum (DPT) to modulate spinal pelvic-urethra reflex potentiation. External urethra sphincter electromyogram (EUSE) activity in response to test stimulation (TS, 1/30 Hz) and repetitive stimulation (RS, 1 Hz) on the pelvic afferent nerve of 63 anesthetized rats were recorded with or without microinjection of nicotinic cholinergic receptor (nAChR) agonists, ACh and nicotine, to the DPT. TS evoked a baseline reflex activity with a single action potential (1.00 +/- 0.00 spikes/stimulation, n = 40), whereas RS produced a long-lasting reflex potentiation (16.14 +/- 0.96 spikes/stimulation, n = 40) that was abolished by d-2-amino-5-phosphonovaleric acid (1.60 +/- 0.89 spikes/stimulation, n = 40) and was attenuated by 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo (F) quinoxaline (7.10 +/- 0.84 spikes/stimulation, n = 40). ACh and nicotine microinjections to DPT both produced facilitation on the RS-induced reflex potentiation (23.57 +/- 2.23 and 28.29 +/- 2.36 spikes/stimulation, P acid-dependent reflex potentiation via descending serotonergic neurotransmission. This descending modulation may have physiological/pathological relevance in the neural controls of urethral closure. PMID:18287401

  18. An Augmented Reality Approach to Integrate Practical Activities in E-Learning Systems

    EL KABTANE Hamada

    2016-02-01

    Full Text Available In the past, the term E-learning was mentioned to any learning method that used electronic machine for the distribution. With the evolution and the apparition of the internet, the term e learning has been evolved and referred to the online courses. There are a lot of platform which serves to distribute and manage the learning content. In some domain learners need to use some equipment and useful product for purpose completing the image built in the theoretical part by the practical activity part. However, most of those platforms suffer from a lack in tools that offer practical activities for learners. Using videos, virtual laboratories or distance control of real equipment as solutions to solve this lack were proposed but still limited. The mixed reality as new technology promised to create a virtual environment where the learner is an actor and can interact with the virtual objects. This article present an approach for developing integrated E-learning systems, helping to carry out the practical work by establishing a virtual laboratory that all tools and products can be manipulated by learners and teachers like in real practical activity, based on an augmented reality system.

  19. Augmented postcard

    Bernik , Aleš

    2012-01-01

    The aim of this thesis is the examination of augmented reality technology, which allows us mixing real and virtual elements. Augmented reality is a relatively new technology which is becoming more widespread, thanks to a fairly reasonable price of smart phones. Here we presents the types of augmented reality, the necessary technology and their advantages and disadvantages, its current use in applications, and software for building augmented reality applications. The thesis is mainly focuse...

  20. Adenoviral augmentation of elafin protects the lung against acute injury mediated by activated neutrophils and bacterial infection.

    Simpson, A J; Wallace, W A; Marsden, M E; Govan, J R; Porteous, D J; Haslett, C; Sallenave, J M

    2001-08-01

    During acute pulmonary infection, tissue injury may be secondary to the effects of bacterial products or to the effects of the host inflammatory response. An attractive strategy for tissue protection in this setting would combine antimicrobial activity with inhibition of human neutrophil elastase (HNE), a key effector of neutrophil-mediated tissue injury. We postulated that genetic augmentation of elafin (an endogenous inhibitor of HNE with intrinsic antimicrobial activity) could protect the lung against acute inflammatory injury without detriment to host defense. A replication-deficient adenovirus encoding elafin cDNA significantly protected A549 cells against the injurious effects of both HNE and whole activated human neutrophils in vitro. Intratracheal replication-deficient adenovirus encoding elafin cDNA significantly protected murine lungs against injury mediated by Pseudomonas aeruginosa in vivo. Genetic augmentation of elafin therefore has the capacity to protect the lung against the injurious effects of both bacterial pathogens resistant to conventional antibiotics and activated neutrophils. PMID:11466403

  1. Inhibition of elongation factor-2 kinase augments the antitumor activity of Temozolomide against glioma.

    Xiao-Yuan Liu

    Full Text Available BACKGROUND: Glioblastoma multiforme (GBM, the most common form of brain cancer with an average survival of less than 12 months, is a highly aggressive and fatal disease characterized by survival of glioma cells following initial treatment, invasion through the brain parenchyma and destruction of normal brain tissues, and ultimately resistance to current treatments. Temozolomide (TMZ is commonly used chemotherapy for treatment of primary and recurrent high-grade gliomas. Nevertheless, the therapeutic outcome of TMZ is often unsatisfactory. In this study, we sought to determine whether eEF-2 kinase affected the sensitivity of glioma cells to treatment with TMZ. METHODOLOGY/PRINCIPAL FINDINGS: Using RNA interference approach, a small molecule inhibitor of eEF-2 kinase, and in vitro and in vivo glioma models, we observed that inhibition of eEF-2 kinase could enhance sensitivity of glioma cells to TMZ, and that this sensitizing effect was associated with blockade of autophagy and augmentation of apoptosis caused by TMZ. CONCLUSIONS/SIGNIFICANCE: These findings demonstrated that targeting eEF-2 kinase can enhance the anti-glioma activity of TMZ, and inhibitors of this kinase may be exploited as chemo-sensitizers for TMZ in treatment of malignant glioma.

  2. Design and evaluation of augmented reality for nuclear power plant maintenance based on Cognitive activity analysis

    The goals of maintenance in nuclear power plants (NPPs) are to reduce the number of plant shutdowns, to decrease the shutdown time, to minimize the maintenance costs, and to improve nuclear safety. Furthermore, it is difficult for maintenance personnel to conduct work in NPPs due to the complexity of NPPs, safety issues and time constraints. Human errors should be prevented to achieve maintenance goals in NPPs. Therefore, it is necessary to improve working conditions by introducing support systems. Augmented Reality (AR) has the potential to assist with maintenance tasks and make maintenance personnel concentrate on the tasks, which will then the reduced human error and improve human performance. The working procedure for AR systems was designed based on the characteristics of cognitive activity, and an experiment was conducted to estimate the effectiveness of AR. The results indicated that a well-designed working procedure for AR systems was more effective than a conventional paper-based working procedure. In addition, participants made fewer errors using the designed working procedure. AR systems as maintenance support systems are beneficial technology that can improve maintenance performance by reducing cognitive loads and unnecessary movements. An AR application can be attractive and effective at supporting maintenance task

  3. Acute liver failure-induced death of rats is delayed or prevented by blocking NMDA receptors in brain.

    Cauli, Omar; Rodrigo, Regina; Boix, Jordi; Piedrafita, Blanca; Agusti, Ana; Felipo, Vicente

    2008-09-01

    Developing procedures to delay the mechanisms of acute liver failure-induced death would increase patients' survival by allowing time for liver regeneration or to receive a liver for transplantation. Hyperammonemia is a main contributor to brain herniation and mortality in acute liver failure (ALF). Acute ammonia intoxication in rats leads to N-methyl-D-aspartate (NMDA) receptor activation in brain. Blocking these receptors prevents ammonia-induced death. Ammonia-induced activation of NMDA receptors could contribute to ALF-induced death. If this were the case, blocking NMDA receptors could prevent or delay ALF-induced death. The aim of this work was to assess 1) whether ALF leads to NMDA receptors activation in brain in vivo and 2) whether blocking NMDA receptors prevents or delays ALF-induced death of rats. It is shown, by in vivo brain microdialysis, that galactosamine-induced ALF leads to NMDA receptors activation in brain. Blocking NMDA receptors by continuous administration of MK-801 or memantine through miniosmotic pumps affords significant protection against ALF-induced death, increasing the survival time approximately twofold. Also, when liver injury is not 100% lethal (1.5 g/kg galactosamine), blocking NMDA receptors increases the survival rate from 23 to 62%. This supports that blocking NMDA receptors could have therapeutic utility to improve survival of patients with ALF. PMID:18599589

  4. Leptin reverses corticosterone-induced inhibition of neural stem cell proliferation through activating the NR2B subunits of NMDA receptors

    Shi, Wen-Zhu [Anesthesia and Operation Center, Hainan Branch of Chinese PLA General Hospital, Hainan 572013 (China); Anesthesia and Operation Center, Chinese PLA General Hospital, Beijing 100853 (China); Miao, Yu-Liang [Department of Anesthesiology, PLA No. 306 Hospital, Beijing 100101 (China); Guo, Wen-Zhi [Department of Anesthesiology, Beijing Military General Hospital of Chinese People’s Liberation Army, Beijing 100700 (China); Wu, Wei, E-mail: wwzwgk@163.com [Department of Head and Neck Surgery of Otolaryngology, PLA No. 306 Hospital, Beijing 100101 (China); Li, Bao-Wei [Department of Head and Neck Surgery of Otolaryngology, PLA No. 306 Hospital, Beijing 100101 (China); An, Li-Na [Department of Anesthesiology, Armed Police General Hospital, Beijing 100039 (China); Fang, Wei-Wu [Department of Anesthesiology, PLA No. 306 Hospital, Beijing 100101 (China); Mi, Wei-Dong, E-mail: elite2005gg@163.com [Anesthesia and Operation Center, Chinese PLA General Hospital, Beijing 100853 (China)

    2014-04-25

    Highlights: • Leptin promotes the proliferation of neural stem cells isolated from embryonic mouse hippocampus. • Leptin reverses corticosterone-induced inhibition of neural stem cell proliferation. • The effects of leptin are partially mediated by upregulating NR2B subunits. - Abstract: Corticosterone inhibits the proliferation of hippocampal neural stem cells (NSCs). The removal of corticosterone-induced inhibition of NSCs proliferation has been reported to contribute to neural regeneration. Leptin has been shown to regulate brain development, improve angiogenesis, and promote neural regeneration; however, its effects on corticosterone-induced inhibition of NSCs proliferation remain unclear. Here we reported that leptin significantly promoted the proliferation of hippocampal NSCs in a concentration-dependent pattern. Also, leptin efficiently reversed the inhibition of NSCs proliferation induced by corticosterone. Interestingly, pre-treatment with non-specific NMDA antagonist MK-801, specific NR2B antagonist Ro 25-6981, or small interfering RNA (siRNA) targeting NR2B, significantly blocked the effect of leptin on corticosterone-induced inhibition of NSCs proliferation. Furthermore, corticosterone significantly reduced the protein expression of NR2B, whereas pre-treatment with leptin greatly reversed the attenuation of NR2B expression caused by corticosterone in cultured hippocampal NSCs. Our findings demonstrate that leptin reverses the corticosterone-induced inhibition of NSCs proliferation. This process is, at least partially mediated by increased expression of NR2B subunits of NMDA receptors.

  5. Leptin reverses corticosterone-induced inhibition of neural stem cell proliferation through activating the NR2B subunits of NMDA receptors

    Highlights: • Leptin promotes the proliferation of neural stem cells isolated from embryonic mouse hippocampus. • Leptin reverses corticosterone-induced inhibition of neural stem cell proliferation. • The effects of leptin are partially mediated by upregulating NR2B subunits. - Abstract: Corticosterone inhibits the proliferation of hippocampal neural stem cells (NSCs). The removal of corticosterone-induced inhibition of NSCs proliferation has been reported to contribute to neural regeneration. Leptin has been shown to regulate brain development, improve angiogenesis, and promote neural regeneration; however, its effects on corticosterone-induced inhibition of NSCs proliferation remain unclear. Here we reported that leptin significantly promoted the proliferation of hippocampal NSCs in a concentration-dependent pattern. Also, leptin efficiently reversed the inhibition of NSCs proliferation induced by corticosterone. Interestingly, pre-treatment with non-specific NMDA antagonist MK-801, specific NR2B antagonist Ro 25-6981, or small interfering RNA (siRNA) targeting NR2B, significantly blocked the effect of leptin on corticosterone-induced inhibition of NSCs proliferation. Furthermore, corticosterone significantly reduced the protein expression of NR2B, whereas pre-treatment with leptin greatly reversed the attenuation of NR2B expression caused by corticosterone in cultured hippocampal NSCs. Our findings demonstrate that leptin reverses the corticosterone-induced inhibition of NSCs proliferation. This process is, at least partially mediated by increased expression of NR2B subunits of NMDA receptors

  6. Purkinje cell NMDA receptors assume a key role in synaptic gain control in the mature cerebellum.

    Piochon, Claire; Levenes, Carole; Ohtsuki, Gen; Hansel, Christian

    2010-11-10

    A classic view in cerebellar physiology holds that Purkinje cells do not express functional NMDA receptors and that, therefore, postsynaptic NMDA receptors are not involved in the induction of long-term depression (LTD) at parallel fiber (PF) to Purkinje cell synapses. Recently, it has been demonstrated that functional NMDA receptors are postsynaptically expressed at climbing fiber (CF) to Purkinje cell synapses in mice, reaching full expression levels at ∼2 months after birth. Here, we show that in the mature mouse cerebellum LTD (induced by paired PF and CF activation), but not long-term potentiation (LTP; PF stimulation alone) at PF to Purkinje cell synapses is blocked by bath application of the NMDA receptor antagonist D-2-amino-5-phosphonovaleric acid (D-APV). A blockade of LTD, but not LTP, was also observed when the noncompetitive NMDA channel blocker MK-801 was added to the patch-pipette saline, suggesting that postsynaptically expressed NMDA receptors are required for LTD induction. Using confocal calcium imaging, we show that CF-evoked calcium transients in dendritic spines are reduced in the presence of D-APV. This observation confirms that NMDA receptor signaling occurs at CF synapses and suggests that NMDA receptor-mediated calcium transients at the CF input site might contribute to LTD induction. Finally, we performed dendritic patch-clamp recordings from rat Purkinje cells. Dendritically recorded CF responses were reduced when D-APV was bath applied. Together, these data suggest that the late developmental expression of postsynaptic NMDA receptors at CF synapses onto Purkinje cells is associated with a switch toward an NMDA receptor-dependent LTD induction mechanism. PMID:21068337

  7. Combination treatment with doxorubicin and gamitrinib synergistically augments anticancer activity through enhanced activation of Bim

    Park, Hye-Kyung; Lee, Ji-Eun; Lim, Jaehwa; Jo, Da-Eun; Park, Soo-Ah; Suh, Pann-Ghill; Kang, Byoung Heon

    2014-01-01

    Background A common approach to cancer therapy in clinical practice is the combination of several drugs to boost the anticancer activity of available drugs while suppressing their unwanted side effects. In this regard, we examined the efficacy of combination treatment with the widely-used genotoxic drug doxorubicin and the mitochondriotoxic Hsp90 inhibitor gamitrinib to exploit disparate stress signaling pathways for cancer therapy. Methods The cytotoxicity of the drugs as single agents or in...

  8. Augmented supraorbital skin sympathetic nerve activity responses to symptom trigger events in rosacea patients.

    Metzler-Wilson, Kristen; Toma, Kumika; Sammons, Dawn L; Mann, Sarah; Jurovcik, Andrew J; Demidova, Olga; Wilson, Thad E

    2015-09-01

    Facial flushing in rosacea is often induced by trigger events. However, trigger causation mechanisms are currently unclear. This study tested the central hypothesis that rosacea causes sympathetic and axon reflex-mediated alterations resulting in trigger-induced symptomatology. Twenty rosacea patients and age/sex-matched controls participated in one or a combination of symptom triggering stressors. In protocol 1, forehead skin sympathetic nerve activity (SSNA; supraorbital microneurography) was measured during sympathoexcitatory mental (2-min serial subtraction of novel numbers) and physical (2-min isometric handgrip) stress. In protocol 2, forehead skin blood flow (laser-Doppler flowmetry) and transepithelial water loss/sweat rate (capacitance hygrometry) were measured during sympathoexcitatory heat stress (whole body heating by perfusing 50°C water through a tube-lined suit). In protocol 3, cheek, forehead, forearm, and palm skin blood flow were measured during nonpainful local heating to induce axon reflex vasodilation. Heart rate (HR) and mean arterial pressure (MAP) were recorded via finger photoplethysmography to calculate cutaneous vascular conductance (CVC; flux·100/MAP). Higher patient transepithelial water loss was observed (rosacea 0.20 ± 0.02 vs. control 0.10 ± 0.01 mg·cm(-2)·min(-1), P MAP changes were not different between groups during sympathoexcitatory stressors or local heating. SSNA during early mental (32 ± 9 and 9 ± 4% increase) and physical (25 ± 4 and 5 ± 1% increase, rosacea and controls, respectively) stress was augmented in rosacea (both P < 0.05). Heat stress induced more rapid sweating and cutaneous vasodilation onset in rosacea compared with controls. No axon reflex vasodilation differences were observed between groups. These data indicate that rosacea affects SSNA and that hyperresponsiveness to trigger events appears to have a sympathetic component. PMID:26133800

  9. Simplified Model for the Activated Sludge System: WWTP Cost Minimization via an Augmented Lagrangian Pattern Search Method

    Espírito Santo, Isabel A. C. P.; Fernandes, Edite M. G. P.

    2010-09-01

    This paper aims to validate a proposed simplified model of the activated sludge system. A comparison between the classical and simplified models is made. The optimization of the operational and investment costs in order to achieve the best design is conducted using an augmented Lagrangian pattern search based algorithm. The results are similar in both models and reinforced that the simplified model is a good approach.

  10. Dual regulation by ethanol of the inhibitory effects of ketamine on spinal NMDA-induced pressor responses in rats

    Keng Nien-Tzu

    2012-02-01

    Full Text Available Abstract Background Acute exposure of ethanol (alcohol inhibits NMDA receptor function. Our previous study showed that acute ethanol inhibited the pressor responses induced by NMDA applied intrathecally; however, prolonged ethanol exposure may increase the levels of phosphorylated NMDA receptor subunits leading to changes in ethanol inhibitory potency on NMDA-induced responses. The present study was carried out to examine whether acute ethanol exposure influences the effects of ketamine, a noncompetitive NMDA receptor antagonist, on spinal NMDA-induced pressor responses. Methods The blood pressure responses induced by intrathecal injection of NMDA were recorded in urethane-anesthetized rats weighing 250-275 g. The levels of several phosphorylated residues on NMDA receptor GluN1 subunits were determined by western blot analysis. Results Intravenous injection of ethanol or ketamine inhibited spinal NMDA-induced pressor responses in a dose-dependent and reversible manner. Ketamine inhibition of NMDA-induced responses was synergistically potentiated by ethanol when ethanol was applied just before ketamine. However, ketamine inhibition was significantly reduced when applied at 10 min after ethanol administration. Western blot analysis showed that intravenous ethanol increased the levels of phosphoserine 897 on GluN1 subunits (pGluN1-serine 897, selectively phosphorylated by protein kinase A (PKA, in the lateral horn regions of spinal cord at 10 min after administration. Intrathecal administration of cAMPS-Sp, a PKA activator, at doses elevating the levels of pGluN1-serine 897, significantly blocked ketamine inhibition of spinal NMDA-induced responses. Conclusions The results suggest that ethanol may differentially regulate ketamine inhibition of spinal NMDA receptor function depending on ethanol exposure time and the resulting changes in the levels of pGluN1-serine 897.

  11. Kynurenic acid amides as novel NR2B selective NMDA receptor antagonists.

    Borza, István; Kolok, Sándor; Galgóczy, Kornél; Gere, Anikó; Horváth, Csilla; Farkas, Sándor; Greiner, István; Domány, György

    2007-01-15

    A novel series of kynurenic acid amides, ring-enlarged derivatives of indole-2-carboxamides, was prepared and identified as in vivo active NR2B subtype selective NMDA receptor antagonists. The synthesis and SAR studies are discussed. PMID:17074483

  12. Alendronate augments interleukin-1β release from macrophages infected with periodontal pathogenic bacteria through activation of caspase-1

    Nitrogen-containing bisphosphonates (NBPs) are anti-bone-resorptive drugs with inflammatory side effects that include osteomyelitis and osteonecrosis of the jaw. Oral bacteria have been considered to be a trigger for these NBP-associated jaw bone diseases. The present study examined the effects of alendronate (a typical NBP) and clodronate (a non-NBP) on the production of proinflammatory cytokines by macrophages infected with Porphyromonas gingivalis and Tannerella forsythia, which are important pathogens of periodontal diseases. Pretreatment with alendronate augmented IL-1β, but not TNFα, production by macrophages infected with P. gingivalis or T. forsythia. This augmentation of IL-1β production was inhibited by clodronate. Furthermore, caspase-1, a promoter of IL-1β production, was activated by treatment with alendronate, and caspase-1 inhibitor reduced the production of IL-1β induced by alendronate and P. gingivalis. These results suggest that NBPs augment periodontal pathogenic bacteria-induced IL-1β release via caspase-1 activation, and this phenomenon may contribute to the development of NBP-associated inflammatory side effects including jaw osteomyelitis. Co-treatment with clodronate may prevent and/or reduce these inflammatory effects induced by NBPs

  13. BDNF released during neuropathic pain potentiates NMDA receptors in primary afferent terminals.

    Chen, Wenling; Walwyn, Wendy; Ennes, Helena S; Kim, Hyeyoung; McRoberts, James A; Marvizón, Juan Carlos G

    2014-05-01

    NMDA receptors in primary afferent terminals can contribute to hyperalgesia by increasing neurotransmitter release. In rats and mice, we found that the ability of intrathecal NMDA to induce neurokinin 1 receptor (NK1R) internalization (a measure of substance P release) required a previous injection of BDNF. Selective knock-down of NMDA receptors in primary afferents decreased NMDA-induced NK1R internalization, confirming the presynaptic location of these receptors. The effect of BDNF was mediated by tropomyosin-related kinase B (trkB) receptors and not p75 neurotrophin receptors (p75(NTR) ), because it was not produced by proBDNF and was inhibited by the trkB antagonist ANA-12 but not by the p75(NTR) inhibitor TAT-Pep5. These effects are probably mediated through the truncated form of the trkB receptor as there is little expression of full-length trkB in dorsal root ganglion (DRG) neurons. Src family kinase inhibitors blocked the effect of BDNF, suggesting that trkB receptors promote the activation of these NMDA receptors by Src family kinase phosphorylation. Western blots of cultured DRG neurons revealed that BDNF increased Tyr(1472) phosphorylation of the NR2B subunit of the NMDA receptor, known to have a potentiating effect. Patch-clamp recordings showed that BDNF, but not proBDNF, increased NMDA receptor currents in cultured DRG neurons. NMDA-induced NK1R internalization was also enabled in a neuropathic pain model or by activating dorsal horn microglia with lipopolysaccharide. These effects were decreased by a BDNF scavenger, a trkB receptor antagonist and a Src family kinase inhibitor, indicating that BDNF released by microglia potentiates NMDA receptors in primary afferents during neuropathic pain. PMID:24611998

  14. Ablation of NMDA receptors enhances the excitability of hippocampal CA3 neurons.

    Fumiaki Fukushima

    Full Text Available Synchronized discharges in the hippocampal CA3 recurrent network are supposed to underlie network oscillations, memory formation and seizure generation. In the hippocampal CA3 network, NMDA receptors are abundant at the recurrent synapses but scarce at the mossy fiber synapses. We generated mutant mice in which NMDA receptors were abolished in hippocampal CA3 pyramidal neurons by postnatal day 14. The histological and cytological organizations of the hippocampal CA3 region were indistinguishable between control and mutant mice. We found that mutant mice lacking NMDA receptors selectively in CA3 pyramidal neurons became more susceptible to kainate-induced seizures. Consistently, mutant mice showed characteristic large EEG spikes associated with multiple unit activities (MUA, suggesting enhanced synchronous firing of CA3 neurons. The electrophysiological balance between fast excitatory and inhibitory synaptic transmission was comparable between control and mutant pyramidal neurons in the hippocampal CA3 region, while the NMDA receptor-slow AHP coupling was diminished in the mutant neurons. In the adult brain, inducible ablation of NMDA receptors in the hippocampal CA3 region by the viral expression vector for Cre recombinase also induced similar large EEG spikes. Furthermore, pharmacological blockade of CA3 NMDA receptors enhanced the susceptibility to kainate-induced seizures. These results raise an intriguing possibility that hippocampal CA3 NMDA receptors may suppress the excitability of the recurrent network as a whole in vivo by restricting synchronous firing of CA3 neurons.

  15. PPARα deficiency augments a ketogenic diet-induced circadian PAI-1 expression possibly through PPARγ activation in the liver

    Research highlights: → PPARα deficiency augments a ketogenic diet-induced circadian PAI-1 expression. → Hepatic expressions of PPARγ and PCG-1α are induced by a ketogenic diet. → PPARγ antagonist attenuates a ketogenic diet-induced PAI-1 expression. → Ketogenic diet advances the phase of circadian clock in a PPARα-independent manner. -- Abstract: An increased level of plasminogen activator inhibitor-1 (PAI-1) is considered a risk factor for cardiovascular diseases, and PAI-1 gene expression is under the control of molecular circadian clocks in mammals. We recently showed that PAI-1 expression is augmented in a phase-advanced circadian manner in mice fed with a ketogenic diet (KD). To determine whether peroxisome proliferator-activated receptor α (PPARα) is involved in hypofibrinolytic status induced by a KD, we examined the expression profiles of PAI-1 and circadian clock genes in PPARα-null KD mice. Chronic administration of bezafibrate induced the PAI-1 gene expression in a PPARα-dependent manner. Feeding with a KD augmented the circadian expression of PAI-1 mRNA in the hearts and livers of wild-type (WT) mice as previously described. The KD-induced mRNA expression of typical PPARα target genes such as Cyp4A10 and FGF21 was damped in PPARα-null mice. However, plasma PAI-1 concentrations were significantly more elevated in PPARα-null KD mice in accordance with hepatic mRNA levels. These observations suggest that PPARα activation is dispensable for KD-induced PAI-1 expression. We also found that hyperlipidemia, fatty liver, and the hepatic expressions of PPARγ and its coactivator PCG-1α were more effectively induced in PPARα-null, than in WT mice on a KD. Furthermore, KD-induced hepatic PAI-1 expression was significantly suppressed by supplementation with bisphenol A diglycidyl ether, a PPARγ antagonist, in both WT and PPARα-null mice. PPARγ activation seems to be involved in KD-induced hypofibrinolysis by augmenting PAI-1 gene expression

  16. A role of periaqueductal grey NR2B-containing NMDA receptor in mediating persistent inflammatory pain

    Yang Qi

    2009-12-01

    Full Text Available Abstract The midbrain periaqueductal grey (PAG is a structure known for its roles in pain transmission and modulation. Noxious stimuli potentiate the glutamate synaptic transmission and enhance glutamate NMDA receptor expression in the PAG. However, little is known about roles of NMDA receptor subunits in the PAG in processing the persistent inflammatory pain. The present study was undertaken to investigate NR2A- and NR2B-containing NMDA receptors in the PAG and their modulation to the peripheral painful inflammation. Noxious stimuli induced by hind-paw injection of complete Freund's adjuvant (CFA caused up-regulation of NR2B-containing NMDA receptors in the PAG, while NR2A-containing NMDA receptors were not altered. Whole-cell patch-clamp recordings revealed that NMDA receptor mediated mEPSCs were increased significantly in the PAG synapse during the chronic phases of inflammatory pain in mice. PAG local infusion of Ro 25-6981, an NR2B antagonist, notably prolonged the paw withdrawal latency to thermal radian heat stimuli bilaterally in rats. Hyperoside (Hyp, one of the flavonoids compound isolated from Rhododendron ponticum L., significantly reversed up-regulation of NR2B-containing NMDA receptors in the PAG and exhibited analgesic activities against persistent inflammatory stimuli in mice. Our findings provide strong evidence that up-regulation of NR2B-containing NMDA receptors in the PAG involves in the modulation to the peripheral persistent inflammatory pain.

  17. DAPK1 Interaction with NMDA Receptor NR2B Subunits Mediates Brain Damage in Stroke

    Tu, Weihong; Xu, Xin; Peng, Lisheng; Zhong, Xiaofen; Zhang, Wenfeng; Soundarapandian, Mangala M.; Balel, Cherine; Wang, Manqi; Jia, Nali; Zhang, Wen; Lew, Frank; Chan, Sic Lung; Chen, Yanfang; Lu, Youming

    2010-01-01

    SUMMARY N-methyl-D-aspartate (NMDA) receptors constitute a major subtype of glutamate receptors at extra-synaptic sites that link multiple intracellular catabolic processes responsible for irreversible neuronal death. Here, we report that cerebral ischemia recruits death-associated protein kinase 1 (DAPK1) into the NMDA receptor NR2B protein complex in the cortex of adult mice. DAPK1 directly binds with the NMDA receptor NR2B C-terminal tail consisting of amino acid 1292–1304 (NR2BCT). A constitutively active DAPK1 phosphorylates NR2B subunit at Ser-1303 and in turn enhances the NR1/NR2B receptor channel conductance. Genetic deletion of DAPK1 or administration of NR2BCT that uncouples an activated DAPK1 from an NMDA receptor NR2B subunit in vivo in mice blocks injurious Ca2+ influx through NMDA receptor channels at extrasynaptic sites and protects neurons against cerebral ischemic insults. Thus, DAPK1 physically and functionally interacts with the NMDA receptor NR2B subunit at extra-synaptic sites and this interaction acts as a central mediator for stroke damage. PMID:20141836

  18. Lip augmentation.

    Byrne, Patrick J; Hilger, Peter A

    2004-02-01

    Lip augmentation has become increasingly popular in recent years as a reflection of cultural trends emphasizing youth and beauty. Techniques to enhance the appearance of the lips have evolved with advances in biotechnology. An understanding of lip anatomy and aesthetics forms the basis for successful results. We outline the pertinent anatomy and aesthetics of the preoperative evaluation. A summary of various filler materials available is provided. Augmentation options include both injectable and open surgical techniques. The procedures and materials currently favored by the authors are described in greater detail. PMID:15034811

  19. Augmented Reality

    Kjærgaard, Hanne Wacher; Kjeldsen, Lars Peter Bech; Rahn, Annette

    2015-01-01

    This chapter describes the use of iPad-facilitated application of augmented reality in the teaching of highly complex anatomical and physiological subjects in the training of nurses at undergraduate level. The general aim of the project is to investigate the potentials of this application in term...

  20. Frequency-dependent facilitation of synaptic throughput via postsynaptic NMDA receptors in the nucleus of the solitary tract.

    Zhao, Huan; Peters, James H; Zhu, Mingyan; Page, Stephen J; Ritter, Robert C; Appleyard, Suzanne M

    2015-01-01

    Hindbrain NMDA receptors play important roles in reflexive and behavioural responses to vagal activation. NMDA receptors have also been shown to contribute to the synaptic responses of neurons in the nucleus of the solitary tract (NTS), but their exact role remains unclear. In this study we used whole cell patch-clamping techniques in rat horizontal brain slice to investigate the role of NMDA receptors in the fidelity of transmission across solitary tract afferent-NTS neuron synapses. Results show that NMDA receptors contribute up to 70% of the charge transferred across the synapse at high (>5 Hz) firing rates, but have little contribution at lower firing frequencies. Results also show that NMDA receptors critically contribute to the fidelity of transmission across these synapses during high frequency (>5 Hz) afferent discharge rates. This novel role of NMDA receptors may explain in part how primary visceral afferents, including vagal afferents, can maintain fidelity of transmission across a broad range of firing frequencies. Neurons within the nucleus of the solitary tract (NTS) receive vagal afferent innervations that initiate gastrointestinal and cardiovascular reflexes. Glutamate is the fast excitatory neurotransmitter released in the NTS by vagal afferents, which arrive there via the solitary tract (ST). ST stimulation elicits excitatory postsynaptic currents (EPSCs) in NTS neurons mediated by both AMPA- and NMDA-type glutamate receptors (-Rs). Vagal afferents exhibit a high probability of vesicle release and exhibit robust frequency-dependent depression due to presynaptic vesicle depletion. Nonetheless, synaptic throughput is maintained even at high frequencies of afferent activation. Here we test the hypothesis that postsynaptic NMDA-Rs are essential in maintaining throughput across ST-NTS synapses. Using patch clamp electrophysiology in horizontal brainstem slices, we found that NMDA-Rs, including NR2B subtypes, carry up to 70% of the charge transferred

  1. Healthy older humans exhibit augmented carotid-cardiac baroreflex sensitivity with aspirin during muscle mechanoreflex and metaboreflex activation.

    Drew, Rachel C; Blaha, Cheryl A; Herr, Michael D; Stocker, Sean D; Sinoway, Lawrence I

    2015-10-01

    Low-dose aspirin inhibits thromboxane production and augments the sensitivity of carotid baroreflex (CBR) control of heart rate (HR) during concurrent muscle mechanoreflex and metaboreflex activation in healthy young humans. However, it is unknown how aging affects this response. Therefore, the effect of low-dose aspirin on carotid-cardiac baroreflex sensitivity during muscle mechanoreflex with and without metaboreflex activation in healthy older humans was examined. Twelve older subjects (6 men and 6 women, mean age: 62 ± 1 yr) performed two trials during two visits preceded by 7 days of low-dose aspirin (81 mg) or placebo. One trial involved 3 min of passive calf stretch (mechanoreflex) during 7.5 min of limb circulatory occlusion (CO). In another trial, CO was preceded by 1.5 min of 70% maximal voluntary contraction isometric calf exercise (mechanoreflex and metaboreflex). HR (ECG) and mean arterial blood pressure (MAP; Finometer) were recorded. CBR function was assessed using rapid neck pressure application (+40 to -80 mmHg). Aspirin significantly decreased baseline thromboxane B2 production by 83 ± 4% (P aspirin, CBR-HR maximal gain and operating point gain were significantly higher during stretch with metabolite accumulation compared with placebo (maximal gain: -0.23 ± 0.03 vs. -0.14 ± 0.02 and operating point gain: -0.11 ± 0.03 vs. -0.04 ± 0.01 beats·min(-1)·mmHg(-1) for aspirin and placebo, respectively, P aspirin augments CBR-HR sensitivity during concurrent muscle mechanoreflex and metaboreflex activation in healthy older humans. This increased sensitivity appears linked to reduced thromboxane sensitization of muscle mechanoreceptors, which consequently improves CBR-HR control. PMID:26371168

  2. Human Neuroepithelial Cells Express NMDA Receptors

    Cappell B

    2003-11-01

    Full Text Available Abstract L-glutamate, an excitatory neurotransmitter, binds to both ionotropic and metabotropic glutamate receptors. In certain parts of the brain the BBB contains two normally impermeable barriers: 1 cerebral endothelial barrier and 2 cerebral epithelial barrier. Human cerebral endothelial cells express NMDA receptors; however, to date, human cerebral epithelial cells (neuroepithelial cells have not been shown to express NMDA receptor message or protein. In this study, human hypothalamic sections were examined for NMDA receptors (NMDAR expression via immunohistochemistry and murine neuroepithelial cell line (V1 were examined for NMDAR via RT-PCR and Western analysis. We found that human cerebral epithelium express protein and cultured mouse neuroepithelial cells express both mRNA and protein for the NMDA receptor. These findings may have important consequences for neuroepithelial responses during excitotoxicity and in disease.

  3. Molecular pharmacology of human NMDA receptors

    Hedegaard, Maiken; Hansen, Kasper Bø; Andersen, Karen Toftegaard;

    2012-01-01

    current knowledge of the relationship between NMDA receptor structure and function. We summarize studies on the biophysical properties of human NMDA receptors and compare these properties to those of rat orthologs. Finally, we provide a comprehensive pharmacological characterization that allows side......-by-side comparison of agonists, un-competitive antagonists, GluN2B-selective non-competitive antagonists, and GluN2C/D-selective modulators at recombinant human and rat NMDA receptors. The evaluation of biophysical properties and pharmacological probes acting at different sites on the receptor suggest that the...... binding sites and conformational changes leading to channel gating in response to agonist binding are highly conserved between human and rat NMDA receptors. In summary, the results of this study suggest that no major detectable differences exist in the pharmacological and functional properties of human...

  4. NMDA receptor function, memory, and brain aging

    Newcomer, John W.; Farber, Nuri B.; Olney, John W.

    2000-01-01

    An increasing level of N-methyl-D-aspartate (NMDA) receptor hypofunction within the brain is associated with memory and learning impairments, with psychosis, and ultimately with excitotoxic brain injury. As the brain ages, the NMDA receptor system becomes progressively hypofunctional, contributing to decreases in memory and learning performance. In those individuals destined to develop Alzheimer's disease, other abnormalities (eg, amyloidopathy and oxidative stress) interact to increase the N...

  5. Musical Peddy-Paper: A Collaborative Learning Activity Suported by Augmented Reality

    Gomes, José Duarte Cardoso; Figueiredo, Mauro Jorge Guerreiro; Amante, Lúcia da Graça Cruz Domingues; Gomes, Cristina Maria Cardoso

    2014-01-01

    Gaming activities are an integral part of the human learning process, in particular for children. Game-based learning focuses on motivation and children's engagement towards learning. Educational game-based activities are becoming effective strategies to enhance the learning process. This paper presents an educational activity focusing to merge…

  6. Membrane phospholipid augments cytochrome P4501a enzymatic activity by modulating structural conformation during detoxification of xenobiotics.

    Manik C Ghosh

    Full Text Available Cytochrome P450 is a superfamily of membrane-bound hemoprotein that gets involved with the degradation of xenobiotics and internal metabolites. Accumulated body of evidence indicates that phospholipids play a crucial role in determining the enzymatic activity of cytochrome P450 in the microenvironment by modulating its structure during detoxification; however, the structure-function relationship of cytochrome P4501A, a family of enzymes responsible for degrading lipophilic aromatic hydrocarbons, is still not well defined. Inducibility of cytochrome P4501A in cultured catfish hepatocytes in response to carbofuran, a widely used pesticide around the world, was studied earlier in our laboratory. In this present investigation, we observed that treating catfish with carbofuran augmented total phospholipid in the liver. We examined the role of phospholipid on the of cytochrome P4501A-marker enzyme which is known as ethoxyresorufin-O-deethylase (EROD in the context of structure and function. We purified the carbofuran-induced cytochrome P4501A protein from catfish liver. Subsequently, we examined the enzymatic activity of purified P4501A protein in the presence of phospholipid, and studied how the structure of purified protein was influenced in the phospholipid environment. Membrane phospholipid appeared to accelerate the enzymatic activity of EROD by changing its structural conformation and thus controlling the detoxification of xenobiotics. Our study revealed the missing link of how the cytochrome P450 restores its enzymatic activity by changing its structural conformation in the phospholipid microenvironment.

  7. Andrographolide protects against cigarette smoke-induced oxidative lung injury via augmentation of Nrf2 activity

    Guan, SP; Tee, W; Ng, DSW; Chan, TK; Peh, HY; Ho, WE; Cheng, C; Mak, JC; Wong, WSF

    2013-01-01

    BACKGROUND AND PURPOSE: Cigarette smoke is a major cause for chronic obstructive pulmonary disease (COPD). Andrographolide is an active biomolecule isolated from the plant Andrographis paniculata. Andrographolide has been shown to activate nuclear factor erythroid-2-related factor 2 (Nrf2), a redox-sensitive antioxidant transcription factor. As Nrf2 activity is reduced in COPD, we hypothesize that andrographolide may have therapeutic value for COPD. EXPERIMENTAL APPROACH: Andrographolide was ...

  8. Natural cytolytic activity in mice with natural or induced cellular defects. I. Differential ability of in vitro interleukin-2 addition to augment natural cytolytic function

    The ability of in vitro addition of recombinant interleukin 2 (rIL-2) to differentially enhance natural cytotoxicity was assessed using cells from mice with natural and induced cellular defects. In vivo treatment with most immunosuppressive or cytoreductive agents, anti-asialo-GM1 antibody, or gamma irradiation dramatically reduced in vitro cytotoxicity against natural killer (NK) sensitive targets by direct reduction in either percentage specific lysis or lytic units per spleen. In most cases, in vitro addition of rIL-2 (at concentrations causing augmented NK function in cells from naive Balb/C mice) enhanced cytotoxic activity of cells from treatment groups to a normal value but not within the rIL-2-enhanced range of nontreated animals. Additionally, cytotoxic activity of cells from animals treated with certain drugs or gamma irradiation could be augmented by rIL-2 when measured by percentage lysis but not lytic units per spleen. In vivo treatment with cyclosporin A did not affect natural cytotoxic activity and addition of rIL-2 augmented the NK activity in a similar fashion to the profile of naive cells. In experiments using cells from beige (C57Bl/6-bg) mice which have a natural defect in NK activity against YAC-1 targets, addition of rIL-2 (at concentrations causing augmented natural cytotoxic function in cells from C57Bl/6 mice) could not effectively enhance in vitro natural cytotoxic function

  9. Walky for embodied microblogging: sharing mundane activities through augmented everyday objects

    Nazzi, Elena; Sokoler, Tomas

    2011-01-01

    In this paper we present our ongoing exploration of a theoretical concept: Embodied Microblogging. Looking for a more situated way to communicate mundane activities in local communities, EM informs the design of digital technology to facilitate senior citizens in making their everyday activities ...

  10. Supplemental Immobilization of Hanford Low-Activity Waste: Cast Stone Augmented Formulation Matrix Tests

    Screening Matrix tests. A set of Cast Stone formulations were devised to augment the original screening test matrix and focus on the range of the test conditions. Fly ash and blast furnace slag were limited to either northwest or southeast and the salt solutions were narrowed to the Average and the SST Blend at the 7.8M Na concentration. To fill in the matrix, a mix ratio of 0.5 was added. In addition, two admixtures, Xypex Admix C-500 and Rheomac SF100 (silica fume), were added as an additional dry material binder in select compositions. As in the Screening Matrix, both fresh and cured properties were evaluated for the formulations. In this study, properties that were influenced by the W/DM ratio in the Screening Matrix; flow diameter, plastic viscosity, density, and compressive strength, showed consistent behavior with respect to W/DM. The leach index for highly soluble components, sodium and nitrate, were not influenced by changes in formulation or the admixtures. The leach index for both iodine and Tc-99 show an influence from the addition of the admixture, Xypex Admix C-500. Additional testing should be performed to further evaluate the influence of Xypex Admix C-500 on the leach index over a range of admixture concentrations, Cast Stone formulations, and curing and storage conditions.

  11. Supplemental Immobilization of Hanford Low-Activity Waste: Cast Stone Augmented Formulation Matrix Tests

    Cozzi, A. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL); Crawford, C. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL); Fox, K. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL); Hansen, E. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL); Roberts, K. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL)

    2015-07-20

    Matrix tests. A set of Cast Stone formulations were devised to augment the original screening test matrix and focus on the range of the test conditions. Fly ash and blast furnace slag were limited to either northwest or southeast and the salt solutions were narrowed to the Average and the SST Blend at the 7.8M Na concentration. To fill in the matrix, a mix ratio of 0.5 was added. In addition, two admixtures, Xypex Admix C-500 and Rheomac SF100 (silica fume), were added as an additional dry material binder in select compositions. As in the Screening Matrix, both fresh and cured properties were evaluated for the formulations. In this study, properties that were influenced by the W/DM ratio in the Screening Matrix; flow diameter, plastic viscosity, density, and compressive strength, showed consistent behavior with respect to W/DM. The leach index for highly soluble components, sodium and nitrate, were not influenced by changes in formulation or the admixtures. The leach index for both iodine and Tc-99 show an influence from the addition of the admixture, Xypex Admix C-500. Additional testing should be performed to further evaluate the influence of Xypex Admix C-500 on the leach index over a range of admixture concentrations, Cast Stone formulations, and curing and storage conditions.

  12. Maternal inflammation activated ROS-p38 MAPK predisposes offspring to heart damages caused by isoproterenol via augmenting ROS generation

    Zhang, Qi; Deng, Yafei; Lai, Wenjing; Guan, Xiao; Sun, Xiongshan; Han, Qi; Wang, Fangjie; Pan, Xiaodong; Ji, Yan; Luo, Hongqin; Huang, Pei; Tang, Yuan; Gu, Liangqi; Dan, Guorong; Yu, Jianhua; Namaka, Michael; Zhang, Jianxiang; Deng, Youcai; Li, Xiaohui

    2016-01-01

    Maternal inflammation contributes to the increased incidence of adult cardiovascular disease. The current study investigated the susceptibility of cardiac damage responding to isoproterenol (ISO) in adult offspring that underwent maternal inflammation (modeled by pregnant Sprague-Dawley rats with lipopolysaccharides (LPS) challenge). We found that 2 weeks of ISO treatment in adult offspring of LPS-treated mothers led to augmented heart damage, characterized by left-ventricular systolic dysfunction, cardiac hypertrophy and myocardial fibrosis. Mechanistically, prenatal exposure to LPS led to up-regulated expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidases, antioxidant enzymes, and p38 MAPK activity in left ventricular of adult offspring at resting state. ISO treatment exaggerated ROS generation, p38 MAPK activation but down-regulated reactive oxygen species (ROS) elimination capacity in the left ventricular of offspring from LPS-treated mothers, while antioxidant N-acetyl-L-cysteine (NAC) reversed these changes together with improved cardiac functions. The p38 inhibitor SB202190 alleviated the heart damage only via inhibiting the expression of NADPH oxidases. Collectively, our data demonstrated that prenatal inflammation programs pre-existed ROS activation in the heart tissue, which switches on the early process of oxidative damages on heart rapidly through a ROS-p38 MAPK-NADPH oxidase-ROS positive feedback loop in response to a myocardial hypertrophic challenge in adulthood. PMID:27443826

  13. Pomegranate Juice Augments Memory and fMRI Activity in Middle-Aged and Older Adults with Mild Memory Complaints

    Susan Y. Bookheimer

    2013-01-01

    Full Text Available Despite increasing emphasis on the potential of dietary antioxidants in preventing memory loss and on diet as a precursor of neurological health, rigorous studies investigating the cognitive effects of foods and their components are rare. Recent animal studies have reported memory and other cognitive benefits of polyphenols, found abundantly in pomegranate juice. We performed a preliminary, placebo-controlled randomized trial of pomegranate juice in older subjects with age-associated memory complaints using memory testing and functional brain activation (fMRI as outcome measures. Thirty-two subjects (28 completers were randomly assigned to drink 8 ounces of either pomegranate juice or a flavor-matched placebo drink for 4 weeks. Subjects received memory testing, fMRI scans during cognitive tasks, and blood draws for peripheral biomarkers before and after the intervention. Investigators and subjects were all blind to group membership. After 4 weeks, only the pomegranate group showed a significant improvement in the Buschke selective reminding test of verbal memory and a significant increase in plasma trolox-equivalent antioxidant capacity (TEAC and urolithin A-glucuronide. Furthermore, compared to the placebo group, the pomegranate group had increased fMRI activity during verbal and visual memory tasks. While preliminary, these results suggest a role for pomegranate juice in augmenting memory function through task-related increases in functional brain activity.

  14. Augmenting the Activity of Monoterpenoid Phenols against Fungal Pathogens Using 2-Hydroxy-4-methoxybenzaldehyde that Target Cell Wall Integrity.

    Kim, Jong H; Chan, Kathleen L; Mahoney, Noreen

    2015-01-01

    Disruption of cell wall integrity system should be an effective strategy for control of fungal pathogens. To augment the cell wall disruption efficacy of monoterpenoid phenols (carvacrol, thymol), antimycotic potency of benzaldehyde derivatives that can serve as chemosensitizing agents were evaluated against strains of Saccharomyces cerevisiae wild type (WT), slt2Δ and bck1Δ (mutants of the mitogen-activated protein kinase (MAPK) and MAPK kinase kinase, respectively, in the cell wall integrity pathway). Among fourteen compounds investigated, slt2Δ and bck1Δ showed higher susceptibility to nine benzaldehydes, compared to WT. Differential antimycotic activity of screened compounds indicated "structure-activity relationship" for targeting the cell wall integrity, where 2-hydroxy-4-methoxybenzaldehyde (2H4M) exhibited the highest antimycotic potency. The efficacy of 2H4M as an effective chemosensitizer to monoterpenoid phenols (viz., 2H4M + carvacrol or thymol) was assessed in yeasts or filamentous fungi (Aspergillus, Penicillium) according to European Committee on Antimicrobial Susceptibility Testing or Clinical Laboratory Standards Institute M38-A protocols, respectively. Synergistic chemosensitization greatly lowers minimum inhibitory or fungicidal concentrations of the co-administered compounds. 2H4M also overcame the tolerance of two MAPK mutants (sakAΔ, mpkCΔ) of Aspergillus fumigatus to fludioxonil (phenylpyrrole fungicide). Collectively, 2H4M possesses chemosensitizing capability to magnify the efficacy of monoterpenoid phenols, which improves target-based (viz., cell wall disruption) antifungal intervention. PMID:26569223

  15. An Augmented Reality-Based Mobile Learning System to Improve Students' Learning Achievements and Motivations in Natural Science Inquiry Activities

    Chiang, Tosti H. C.; Yang, Stephen J. H.; Hwang, Gwo-Jen

    2014-01-01

    In this study, an augmented reality-based mobile learning system is proposed for conducting inquiry-based learning activities. An experiment has been conducted to examine the effectiveness of the proposed approach in terms of learning achievements and motivations. The subjects were 57 fourth graders from two classes taught by the same teacher in…

  16. Downregulation of RND3/RhoE in glioblastoma patients promotes tumorigenesis through augmentation of notch transcriptional complex activity

    Activation of Notch signaling contributes to glioblastoma multiform (GBM) tumorigenesis. However, the molecular mechanism that promotes the Notch signaling augmentation during GBM genesis remains largely unknown. Identification of new factors that regulate Notch signaling is critical for tumor treatment. The expression levels of RND3 and its clinical implication were analyzed in GBM patients. Identification of RND3 as a novel factor in GBM genesis was demonstrated in vitro by cell experiments and in vivo by a GBM xenograft model. We found that RND3 expression was significantly decreased in human glioblastoma. The levels of RND3 expression were inversely correlated with Notch activity, tumor size, and tumor cell proliferation, and positively correlated with patient survival time. We demonstrated that RND3 functioned as an endogenous repressor of the Notch transcriptional complex. RND3 physically interacted with NICD, CSL, and MAML1, the Notch transcriptional complex factors, promoted NICD ubiquitination, and facilitated the degradation of these cofactor proteins. We further revealed that RND3 facilitated the binding of NICD to FBW7, a ubiquitin ligase, and consequently enhanced NICD protein degradation. Therefore, Notch transcriptional activity was inhibited. Forced expression of RND3 repressed Notch signaling, which led to the inhibition of glioblastoma cell proliferation in vitro and tumor growth in the xenograft mice in vivo. Downregulation of RND3, however, enhanced Notch signaling activity, and subsequently promoted glioma cell proliferation. Inhibition of Notch activity abolished RND3 deficiency-mediated GBM cell proliferation. We conclude that downregulation of RND3 is responsible for the enhancement of Notch activity that promotes glioblastoma genesis

  17. Enantiopure Indolo[2,3-a]quinolizidines: Synthesis and Evaluation as NMDA Receptor Antagonists

    Nuno A. L. Pereira

    2016-08-01

    Full Text Available Enantiopure tryptophanol is easily obtained from the reduction of its parent natural amino acid trypthophan (available from the chiral pool, and can be used as chiral auxiliary/inductor to control the stereochemical course of a diastereoselective reaction. Furthermore, enantiopure tryptophanol is useful for the syntheses of natural products or biological active molecules containing the aminoalcohol functionality. In this communication, we report the development of a small library of indolo[2,3-a]quinolizidines and evaluation of their activity as N-Methyl d-Aspartate (NMDA receptor antagonists. The indolo[2,3-a]quinolizidine scaffold was obtained using the following key steps: (i a stereoselective cyclocondensation of (S- or (R-tryptophanol with appropriate racemic δ-oxoesters; (ii a stereocontrolled cyclization on the indole nucleus. The synthesized enantiopure indolo[2,3-a]quinolizidines were evaluated as NMDA receptor antagonists and one compound was identified to be 2.9-fold more potent as NMDA receptor blocker than amantadine (used in the clinic for Parkinson’s disease. This compound represents a hit compound for the development of novel NMDA receptor antagonists with potential applications in neurodegenerative disorders associated with overactivation of NMDA receptors.

  18. Augmentation mammoplasty

    Seventy-five cases of breast implants have been reviewed. Two categories of abnormalities were identified: those involving the implant itself and those within the breast parenchyma. Complications of the implant itself include leakage, fibrous capsular contraction, traumatic rupture, displacement, and collapse. Concomitant breast parenchymal abnormalities include breast carcinoma, cysts, solid masses, and clusters of microcalcifications. Mammographic technique is critical and often involves manual settings and special views. Mammography and US in conjunction with physical examination play an important role in detecting breast pathology in the augmented breast

  19. Indomethacin augments lymphokine-activated killer cell generation by patients with malignant mesothelioma

    Manning, L.S.; Bowman, R.V.; Davis, M.R.; Musk, A.W.; Robinson, B.W. (Queen Elizabeth II Medical Centre, Nedlands (Australia))

    1989-10-01

    Human malignant mesothelioma (MM) cells are resistant to natural killer (NK) cell lysis but susceptible to lysis by lymphokine-activated killer (LAK) cells from control individuals. The present study was performed to determine the capacity of patients with MM (n = 22) and individuals occupationally exposed to asbestos (the major population at risk of developing this disease, n = 52) to generate LAK cells capable of effectively lysing human mesothelioma cells. Compared to controls (n = 20), both patient groups demonstrated significantly depressed LAK cell activity against mesothelioma tumor cell targets (55 +/- 3% lysis by controls vs 34 +/- 3% lysis by patients with MM, P less than 0.005; and 45 +/- 3% lysis by asbestos-exposed individuals, P less than 0.025). Addition of 10 micrograms/ml indomethacin during LAK cell generation restored normal LAK cell activity for patients with MM (52 +/- 6% lysis of cultured human MM cells, P = NS compared to controls), suggesting that the defective cytolytic cell function observed in some patients with MM is a result of prostaglandin-induced immunosuppression. The ability of indomethacin to restore suppressed LAK cell activity in patients with MM suggests that the concomitant use of this agent in ex vivo LAK cell generation and in patients undergoing interleukin/LAK cell therapy may be beneficial.

  20. NMDA Receptor Modulators in the Treatment of Drug Addiction

    Foster Olive, M.; Natali E. Nemirovsky; Tomek, Seven E.; LaCrosse, Amber L.

    2013-01-01

    Glutamate plays a pivotal role in drug addiction, and the N-methyl-d-aspartate (NMDA) glutamate receptor subtype serves as a molecular target for several drugs of abuse. In this review, we will provide an overview of NMDA receptor structure and function, followed by a review of the mechanism of action, clinical efficacy, and side effect profile of NMDA receptor ligands that are currently in use or being explored for the treatment of drug addiction. These ligands include the NMDA receptor modu...

  1. Dectin-2 Recognizes Mannosylated O-antigens of Human Opportunistic Pathogens and Augments Lipopolysaccharide Activation of Myeloid Cells.

    Wittmann, Alexandra; Lamprinaki, Dimitra; Bowles, Kristian M; Katzenellenbogen, Ewa; Knirel, Yuriy A; Whitfield, Chris; Nishimura, Takashi; Matsumoto, Naoki; Yamamoto, Kazuo; Iwakura, Yoichiro; Saijo, Shinobu; Kawasaki, Norihito

    2016-08-19

    LPS consists of a relatively conserved region of lipid A and core oligosaccharide and a highly variable region of O-antigen polysaccharide. Whereas lipid A is known to bind to the Toll-like receptor 4 (TLR4)-myeloid differentiation factor 2 (MD2) complex, the role of the O-antigen remains unclear. Here we report a novel molecular interaction between dendritic cell-associated C-type lectin-2 (Dectin-2) and mannosylated O-antigen found in a human opportunistic pathogen, Hafnia alvei PCM 1223, which has a repeating unit of [-Man-α1,3-Man-α1,2-Man-α1,2-Man-α1,2-Man-α1,3-]. H. alvei LPS induced higher levels of TNFα and IL-10 from mouse bone marrow-derived dendritic cells (BM-DCs), when compared with Salmonella enterica O66 LPS, which has a repeat of [-Gal-α1,6-Gal-α1,4-[Glc-β1,3]GalNAc-α1,3-GalNAc-β1,3-]. In a cell-based reporter assay, Dectin-2 was shown to recognize H. alvei LPS. This binding was inhibited by mannosidase treatment of H. alvei LPS and by mutations in the carbohydrate-binding domain of Dectin-2, demonstrating that H. alvei LPS is a novel glycan ligand of Dectin-2. The enhanced cytokine production by H. alvei LPS was Dectin-2-dependent, because Dectin-2 knock-out BM-DCs failed to do so. This receptor cross-talk between Dectin-2 and TLR4 involved events including spleen tyrosine kinase (Syk) activation and receptor juxtaposition. Furthermore, another mannosylated LPS from Escherichia coli O9a also bound to Dectin-2 and augmented TLR4 activation of BM-DCs. Taken together, these data indicate that mannosylated O-antigens from several Gram-negative bacteria augment TLR4 responses through interaction with Dectin-2. PMID:27358401

  2. Targeting myeloid-derived suppressor cells augments antitumor activity against lung cancer

    Srivastava MK

    2012-10-01

    Full Text Available Minu K Srivastava,1,2 Li Zhu,1,2 Marni Harris-White,2 Min Huang,1–3 Maie St John,1,3 Jay M Lee,1,3 Ravi Salgia,4 Robert B Cameron,1,3,5 Robert Strieter,6 Steven Dubinett,1–3 Sherven Sharma1–31Department of Medicine, UCLA Lung Cancer Research Program, David Geffen School of Medicine at UCLA, Los Angeles, CA, 2Molecular Gene Medicine Laboratory, Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, CA, 3Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at UCLA, Los Angeles, CA, 4Department of Medicine, University of Chicago, Chicago, IL, 5Department of Surgery, Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, CA, 6Department of Medicine, University of Virginia, Charlottesville, VA, USAAbstract: Lung cancer evades host immune surveillance by dysregulating inflammation. Tumors and their surrounding stromata produce growth factors, cytokines, and chemokines that recruit, expand, and/or activate myeloid-derived suppressor cells (MDSCs. MDSCs regulate immune responses and are frequently found in malignancy. In this review the authors discuss tumor-MDSC interactions that suppress host antitumor activities and the authors' recent findings regarding MDSC depletion that led to improved therapeutic vaccination responses against lung cancer. Despite the identification of a repertoire of tumor antigens, hurdles persist for immune-based anticancer therapies. It is likely that combined therapies that address the multiple immune deficits in cancer patients will be required for effective therapy. MDSCs play a major role in the suppression of T-cell activation and they sustain tumor growth, proliferation, and metastases. Regulation of MDSC recruitment, differentiation or expansion, and inhibition of the MDSC suppressive function with pharmacologic agents will be useful in the control of cancer growth and progression. Pharmacologic agents that regulate MDSCs may be more effective when combined with

  3. Leptin into the rostral ventral lateral medulla (RVLM) augments renal sympathetic nerve activity and blood pressure

    Barnes, Maria J.; David Harry McDougal

    2014-01-01

    Leptin is a hormone released from adipose tissue. While this hormone normally acts to reduce feeding behavior and increase energy expenditure, in obesity, resistance to these effects occurs even though the hormone is released in large amounts. Although leptin no longer works to suppress feeding in the obese, leptin retains its potent effects on other autonomic functions such as blood pressure regulation. Leptin has been associated with hypertension and increased sympathetic autonomic activ...

  4. Leptin into the rostral ventral lateral medulla (RVLM) augments renal sympathetic nerve activity and blood pressure

    Barnes, Maria J.; McDougal, David H.

    2014-01-01

    Leptin is a hormone released from adipose tissue. While this hormone normally acts to reduce feeding behavior and increase energy expenditure, in obesity, resistance to these effects occurs even though the hormone is released in large amounts. Although leptin no longer works to suppress feeding in the obese, leptin retains its potent effects on other autonomic functions such as blood pressure regulation. Leptin has been associated with hypertension and increased sympathetic autonomic activity...

  5. Benzodiazepines: rat pinealocyte binding sites and augmentation of norepinephrine-stimulated N-acetyltransferase activity

    Matthew, E.; Parfitt, A.G.; Sugden, D.; Engelhardt, D.L.; Zimmerman, E.A.; Klein, D.C.

    1984-02-01

    Studies of (/sup 3/H)diazepam binding to intact rat pineal cells were carried out in tissue culture preparations. The binding was saturable, reversible and proportional to the number of cells used. Scatchard analysis resulted in a linear plot (Kd . 23 nM, maximum binding sites (Bmax) . 1.56 pmol/mg of protein for cells in monolayer culture; Kd . 7 nM, Bmax . 1.3 pmol/mg of protein for cells in suspension culture). Inhibition constants (Ki) for clonazepam (500 nM), flunitrazepam (38 nM) and Ro-5-4864 (5 nM) indicated that the binding sites were probably of the ''peripheral'' type. In addition, the effects of diazepam on norepinephrine-stimulated N-acetyltransferase (NAT) activity were studied in organ culture and dissociated cell culture. Diazepam (10-50 microM) both prolonged and increased the magnitude of the norepinephrine-induced increase in NAT activity but did not affect the initial rate of rise of enzyme activity. The effect was dose-dependent and was also seen with clonazepam, flunitrazepam and Ro-5-4864, but not with Ro-15-1788. Diazepam, by itself, at these concentrations, had no effect on NAT, but enzyme activity was increased by higher concentrations (0.1-1 mM). Although a relationship between the (/sup 3/H)diazepam binding sites described here and the effect of benzodiazepines on NAT cannot be established from these studies, the data suggest that the benzodiazepines may alter melatonin levels through their action on NAT.

  6. Benzodiazepines: rat pinealocyte binding sites and augmentation of norepinephrine-stimulated N-acetyltransferase activity

    Studies of [3H]diazepam binding to intact rat pineal cells were carried out in tissue culture preparations. The binding was saturable, reversible and proportional to the number of cells used. Scatchard analysis resulted in a linear plot [Kd . 23 nM, maximum binding sites (Bmax) . 1.56 pmol/mg of protein for cells in monolayer culture; Kd . 7 nM, Bmax . 1.3 pmol/mg of protein for cells in suspension culture]. Inhibition constants (Ki) for clonazepam (500 nM), flunitrazepam (38 nM) and Ro-5-4864 (5 nM) indicated that the binding sites were probably of the ''peripheral'' type. In addition, the effects of diazepam on norepinephrine-stimulated N-acetyltransferase (NAT) activity were studied in organ culture and dissociated cell culture. Diazepam (10-50 microM) both prolonged and increased the magnitude of the norepinephrine-induced increase in NAT activity but did not affect the initial rate of rise of enzyme activity. The effect was dose-dependent and was also seen with clonazepam, flunitrazepam and Ro-5-4864, but not with Ro-15-1788. Diazepam, by itself, at these concentrations, had no effect on NAT, but enzyme activity was increased by higher concentrations (0.1-1 mM). Although a relationship between the [3H]diazepam binding sites described here and the effect of benzodiazepines on NAT cannot be established from these studies, the data suggest that the benzodiazepines may alter melatonin levels through their action on NAT

  7. Aeromechanical stability augmentation using semi-active friction-based lead-lag damper

    Agarwal, Sandeep

    2005-11-01

    Lead-lag dampers are present in most rotors to provide the required level of damping in all flight conditions. These dampers are a critical component of the rotor system, but they also represent a major source of maintenance cost. In present rotor systems, both hydraulic and elastomeric lead-lag dampers have been used. Hydraulic dampers are complex mechanical components that require hydraulic fluids and have high associated maintenance costs. Elastomeric dampers are conceptually simpler and provide a "dry" rotor, but are rather costly. Furthermore, their damping characteristics can degrade with time without showing external signs of failure. Hence, the dampers must be replaced on a regular basis. A semi-active friction based lead-lag damper is proposed as a replacement for hydraulic and elastomeric dampers. Damping is provided by optimized energy dissipation due to frictional forces in semi-active joints. An actuator in the joint modulates the normal force that controls energy dissipation at the frictional interfaces, resulting in large hysteretic loops. Various selective damping strategies are developed and tested for a simple system containing two different frequency modes in its response, one of which needs to be damped out. The system reflects the situation encountered in rotor response where 1P excitation is present along with the potentially unstable regressive lag motion. Simulation of the system response is obtained to compare their effectiveness. Next, a control law governing the actuation in the lag damper is designed to generate the desired level of damping for performing adaptive selective damping of individual blade lag motion. Further, conceptual design of a piezoelectric friction based lag damper for a full-scale rotor is presented and various factors affecting size, design and maintenance cost, damping capacity, and power requirements of the damper are discussed. The selective semi-active damping strategy is then studied in the context of classical

  8. Leptin into the rostral ventral lateral medulla (RVLM augments renal sympathetic nerve activity and blood pressure

    Maria J Barnes

    2014-08-01

    Full Text Available Leptin is a hormone released from adipose tissue. While this hormone normally acts to reduce feeding behavior and increase energy expenditure, in obesity, resistance to these effects occurs even though the hormone is released in large amounts. Although leptin no longer works to suppress feeding in the obese, leptin retains its potent effects on other autonomic functions such as blood pressure regulation. Leptin has been associated with hypertension and increased sympathetic autonomic activity. Therefore, leptin is emerging as a major contributor to the hypertensive state observed in obesity. Sympathetic control of blood pressure is maintained principally by autonomic reflex control circuits in the caudal brainstem. The rostral ventral-lateral medulla (RVLM is the primary regulator of the sympathetic nervous system, sending excitatory fibers to sympathetic preganglionic neurons to regulate sympathetic control over resistance vessels and blood pressure. Previous studies from our laboratory have shown that neurons in the ventral lateral medulla express leptin receptors (ObRb. Our present study using pseudo-rabies multi-synaptic retrograde tract tracing and immunohistochemical methods revealed that neurons within the RVLM that send sympathetic projections to the kidney express leptin receptors. Acute microinjection of leptin (1 and 3µg; 40nL into the RVLM evoked a significant increase in Mean Arterial Pressure (MAP and renal sympathetic nerve activity (RSNA. When the 3µg dose of leptin was preceded with a leptin antagonist, (SLAN-4; 1ng, it attenuated the cardiovascular response of leptin. Taken together, these data suggest that leptin’s actions within the RVLM may influence blood pressure and renal sympathetic nerve activity.

  9. Depression Augments Activity-Related Pain in Women but not in Men with Chronic Musculoskeletal Conditions

    Heather Adams; Pascal Thibault; Nicole Davidson; Maureen Simmonds; Ana Velly; Michael JL Sullivan

    2008-01-01

    OBJECTIVES: The primary objective of the present study was to examine the role of sex as a moderator of the relation between depression and activity-related pain.METHODS: The study sample consisted of 83 participants (42 women, 41 men) with musculoskeletal conditions. Participants were asked to lift a series of 18 canisters that varied in weight (2.9 kg, 3.4 kg and 3.9 kg) and distance from the body. Participants were asked to rate their pain while they lifted each canister and estimate the w...

  10. Effects of Anti-NMDA Antibodies on Functional Recovery and Synaptic Rearrangement Following Hemicerebellectomy.

    Laricchiuta, Daniela; Cavallucci, Virve; Cutuli, Debora; De Bartolo, Paola; Caporali, Paola; Foti, Francesca; Finke, Carsten; D'Amelio, Marcello; Manto, Mario; Petrosini, Laura

    2016-06-01

    The compensation that follows cerebellar lesions is based on synaptic modifications in many cortical and subcortical regions, although its cellular mechanisms are still unclear. Changes in glutamatergic receptor expression may represent the synaptic basis of the compensated state. We analyzed in rats the involvement of glutamatergic system of the cerebello-frontal network in the compensation following a right hemicerebellectomy. We evaluated motor performances, spatial competencies and molecular correlates in compensated hemicerebellectomized rats which in the frontal cortex contralateral to the hemicerebellectomy side received injections of anti-NMDA antibodies from patients affected by anti-NMDA encephalitis. In the compensated hemicerebellectomized rats, the frontal injections of anti-NMDA antibodies elicited a marked decompensation state characterized by slight worsening of the motor symptoms as well as severe impairment of spatial mnesic and procedural performances. Conversely, in the sham-operated group the frontal injections of anti-NMDA antibodies elicited slight motor and spatial impairment. The molecular analyses indicated that cerebellar compensatory processes were related to a relevant rearrangement of glutamatergic synapses (NMDA and AMPA receptors and other glutamatergic components) along the entire cortico-cerebellar network. The long-term maintenance of the rearranged glutamatergic activity plays a crucial role in the maintenance of recovered function. PMID:27027521

  11. New benzoyl urea derivatives as novel NR2B selective NMDA receptor antagonists.

    Borza, I; Greiner, I; Kolok, S; Galgóczy, K; Ignácz-Szendrei, Gy; Horváth, Cs; Farkas, S; Gáti, T; Háda, V; Domány, Gy

    2006-09-01

    A novel series of benzoyl urea derivatives was prepared and identified as NR2B selective NMDA receptor antagonists. The influence of the substitution of the piperidine ring on the biological activity of the compounds was studied. Compound 9 was active in the formalin test in mice. PMID:17020160

  12. Analysis of Whole-Cell NMDA Receptor Currents

    Vyklický, Vojtěch; Kořínek, Miloslav; Balík, Aleš; Smejkalová, Tereza; Krausová, Barbora; Vyklický ml., Ladislav

    Totowa: Humana Press Inc., 2016, s. 205-219. (Neuromethods. 106). ISBN 978-1-4939-2811-8 R&D Projects: GA ČR(CZ) GAP303/12/1464; GA ČR(CZ) GPP303/11/P391; GA TA ČR(CZ) TE01020028; GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:67985823 Keywords : NMDA receptor * whole-cell * kinetic analysis * desensitization * activation * deactivation * probability of channel opening * perfusion Subject RIV: FH - Neurology

  13. Cholinergic muscarinic receptor activation augments murine intestinal epithelial cell proliferation and tumorigenesis

    Previously, we showed that M3 muscarinic receptor (M3R; gene name Chrm3) deficiency attenuates murine intestinal neoplasia, supporting the hypothesis that muscarinic receptors play an important role in intestinal tumorigenesis. To test this hypothesis, in the present study we treated mice with bethanechol, a non-selective muscarinic receptor agonist without nicotinic receptor activity, and examined its effects on azoxymethane (AOM)-induced colon neoplasia. Mice were provided with drinking water containing 400 μg/mL bethanechol chloride or water without additions (control) for a total of 20 weeks, a period that included the initial 6 weeks when mice received intraperitoneal injections of AOM. When euthanized at week 20, control mice had 8.0 ± 1.3 tumors per animal, whereas bethanechol-treated mice had 10.4 ± 1.5 tumors per mouse (mean ± SE; P = 0.023), a 30% increase. Strikingly, tumor volume per animal was increased 52% in bethanechol-treated compared with control mice (179.7 ± 21.0 vs. 111. 8 ± 22.4 mm3; P = 0.047). On histological examination, bethenechol-treated mice also had more adenocarcinomas per animal (8.0 ± 1.0 vs. 4.1 ± 0.6 for control mice, P = 0.0042). Cell proliferation in both normal mucosa and adenocarcinomas was increased in bethanechol-treated compared to control mice. Also, in tumors, bethanechol treatment increased expression of Chrm3, Egfr and post-Egfr signaling molecules Myc and cyclin D1. Bethanechol treatment increased the thickness of normal colonic mucosa and the expression of selected matrix metalloproteinase (Mmp) genes, including Mmp7, Mmp10 and Mmp13. These findings support a prominent role for muscarinic receptors in colon neoplasia, and identify post-receptor signaling molecules as potential therapeutic targets

  14. Subthreshold receptive fields and baseline excitability of "silent" S1 callosal neurons in awake rabbits: contributions of AMPA/kainate and NMDA receptors.

    Swadlow, H A; Hicks, T P

    1997-07-01

    The contribution of NMDA and non-NMDA receptors to excitatory subthreshold receptive fields was examined in callosal efferent neurons (CC neurons) in primary somatosensory cortex of the fully awake rabbit. Only neurons showing no traditional (suprathreshold) receptive fields were examined. Subthreshold responses were examined by monitoring the thresholds of efferent neurons to juxtasomal current pulses (JSCPs) delivered through the recording microelectrode. Changes in threshold following a peripheral conditioning stimulus signify a subthreshold response. Using this method, excitatory postsynaptic potentials and inhibitory postsynaptic potentials are manifested as decreases and increases in JSCP threshold, respectively. NMDA and non-NMDA agonists and antagonists were administered iontophoretically via a multibarrel micropipette assembly attached to the recording/stimulating microelectrode. Receptor-selective doses of both AMPA/kainate and NMDA antagonists decreased the excitability of CC neurons in the absence of any peripheral stimulation. Threshold to JSCPs rose by a mean of 20% for both classes of antagonist. Despite the similar effects of NMDA and non-NMDA antagonists on baseline excitability, these antagonists had dramatically different effects on the subthreshold excitatory response to activation of the receptive field. Whereas receptor-selective doses of AMPA/kainate antagonists either eliminated or severely attenuated the subthreshold excitatory responses to peripheral stimulation, NMDA antagonists had little or no effect on the subthreshold evoked response. PMID:9262195

  15. Quantitative Structure-Activity Relationships of Noncompetitive Antagonists of the NMDA Receptor: A Study of a Series of MK801 Derivative Molecules Using Statistical Methods and Neural Network

    T. Lakhlifi

    2003-04-01

    Full Text Available Abstract: From a series of 50 MK801 derivative molecules, a selected set of 44 compounds was submitted to a principal components analysis (PCA, a multiple regression analysis (MRA, and a neural network (NN. This study shows that the compounds' activity correlates reasonably well with the selected descriptors encoding the chemical structures. The correlation coefficients calculated by MRA and there after by NN, r = 0.986 and r = 0.974 respectively, are fairly good to evaluate a quantitative model, and to predict activity for MK801 derivatives. To test the performance of this model, the activities of the remained set of 6 compounds are deduced from the proposed quantitative model, by NN. This study proved that the predictive power of this model is relevant.

  16. Synergy of AMPA and NMDA Receptor Currents in Dopaminergic Neurons: A Modeling Study.

    Zakharov, Denis; Lapish, Christopher; Gutkin, Boris; Kuznetsov, Alexey

    2016-01-01

    Dopaminergic (DA) neurons display two modes of firing: low-frequency tonic and high-frequency bursts. The high frequency firing within the bursts is attributed to NMDA, but not AMPA receptor activation. In our models of the DA neuron, both biophysical and abstract, the NMDA receptor current can significantly increase their firing frequency, whereas the AMPA receptor current is not able to evoke high-frequency activity and usually suppresses firing. However, both currents are produced by glutamate receptors and, consequently, are often co-activated. Here we consider combined influence of AMPA and NMDA synaptic input in the models of the DA neuron. Different types of neuronal activity (resting state, low frequency, or high frequency firing) are observed depending on the conductance of the AMPAR and NMDAR currents. In two models, biophysical and reduced, we show that the firing frequency increases more effectively if both receptors are co-activated for certain parameter values. In particular, in the more quantitative biophysical model, the maximal frequency is 40% greater than that with NMDAR alone. The dynamical mechanism of such frequency growth is explained in the framework of phase space evolution using the reduced model. In short, both the AMPAR and NMDAR currents flatten the voltage nullcline, providing the frequency increase, whereas only NMDA prevents complete unfolding of the nullcline, providing robust firing. Thus, we confirm a major role of the NMDAR in generating high-frequency firing and conclude that AMPAR activation further significantly increases the frequency. PMID:27252643

  17. Appetitive Cue-Evoked ERK Signaling in the Nucleus Accumbens Requires NMDA and D1 Dopamine Receptor Activation and Regulates CREB Phosphorylation

    Kirschmann, Erin K. Z.; Mauna, Jocelyn C.; Willis, Cory M.; Foster, Rebecca L.; Chipman, Amanda M.; Thiels, Edda

    2014-01-01

    Conditioned stimuli (CS) can modulate reward-seeking behavior. This modulatory effect can be maladaptive and has been implicated in excessive reward seeking and relapse to drug addiction. We previously demonstrated that exposure to an appetitive CS causes an increase in the activation of extracellular signal-regulated kinase (ERK) and cyclic-AMP…

  18. ARLearn: augmented reality meets augmented virtuality

    Ternier, Stefaan; Klemke, Roland; Kalz, Marco; Van Ulzen, Patricia; Specht, Marcus

    2012-01-01

    Ternier, S., Klemke, R., Kalz, M., Van Ulzen, P., & Specht, M. (2012). ARLearn: augmented reality meets augmented virtuality [Special issue]. Journal of Universal Computer Science - Technology for learning across physical and virtual spaces, 18(15), 2143-2164.

  19. Counting NMDA Receptors at the Cell Surface

    Horák, Martin; Suh, Y. H.

    Totowa: Humana Press Inc., 2016, s. 31-44. (Neuromethods. 106). ISBN 978-1-4939-2811-8 R&D Projects: GA ČR(CZ) GA14-02219S Institutional support: RVO:67985823 Keywords : NMDA receptor * ionotropic glutamate receptor * mammalian cell lines * intracellular trafficking * quantitative assay * biotinylation assay * biochemistry Subject RIV: FH - Neurology

  20. Osmotic Edema Rapidly Increases Neuronal Excitability Through Activation of NMDA Receptor-Dependent Slow Inward Currents in Juvenile and Adult Hippocampus

    Lauderdale, Kelli; Murphy, Thomas; Tung, Tina; Davila, David; Binder, Devin K.; Fiacco, Todd A.

    2015-01-01

    Cellular edema (cell swelling) is a principal component of numerous brain disorders including ischemia, cortical spreading depression, hyponatremia, and epilepsy. Cellular edema increases seizure-like activity in vitro and in vivo, largely through nonsynaptic mechanisms attributable to reduction of the extracellular space. However, the types of excitability changes occurring in individual neurons during the acute phase of cell volume increase remain unclear. Using whole-cell patch clamp techn...

  1. Clozapine Functions Through the Prefrontal Cortex Serotonin 1A Receptor to Heighten Neuronal Activity via Calmodulin Kinase II-NMDA Receptor Interactions

    Purkayastha, Sudarshana; Ford, Jason; Kanjilal, Baishali; Diallo, Souleymane; Del Rosario Inigo, Joseph; Neuwirth, Lorenz; El Idrissi, Abdelsem; Ahmed, Zaghloul; Wieraszko, Andrzej; Efrain, C.; Azmitia; Banerjee, Probal

    2011-01-01

    Aberrant dopamine release in the prefrontal cortex (PFC) is believed to underlie schizophrenia, but the mechanistic pathway through which a widely used antipsychotic, clozapine (Clz), evokes neurotransmitter-releasing electrical stimulation is unclear. We analyzed Clz-evoked regulation of neuronal activity in the PFC by stimulating axons in layers IV and V and recording the electrical effect in the postsynaptic pyramidal cells of layers II and III. We observed a Clz-evoked increase in populat...

  2. Local infusion of interleukin-6 attenuates the neurotoxic effects of NMDA on rat striatal cholinergic neurons.

    Toulmond, S; Vige, X; Fage, D; Benavides, J

    1992-09-14

    The potential neuroprotective effects of IL-6 against the excitotoxic neuronal loss induced by N-methyl-D-aspartate (NMDA) have been studied. Infusion into the rat striatum of excitotoxic amounts (250 nmol) of NMDA resulted in a 45% decrease in striatal choline acetyl transferase activity (ChAT; a marker of cholinergic neurons) and glutamate decarboxylase (GAD, a marker of GABAergic neurons) at 2 days post-injection. Co-infusion of 10 U of IL-6 reduced the loss of ChAT activity to 21% but failed to prevent the loss of GAD activity. IL-6 per se, up to the dose of 500 U, failed to affect ChAT or GAD activities. The in vivo effects of IL-6 are not mediated by a direct antagonism of NMDA toxicity, since IL-6 (up to a concentration of 500 and 5000 U/ml, respectively) did not antagonize either the increase in cyclic GMP levels resulting from NMDA receptor activation in cerebellar slices or the glutamate-induced release of lactate dehydrogenase, an index of neurotoxicity, by cultured cortical neurons. These results suggest that the increase in IL-6 levels observed in experimental brain lesions may play a role in the protection and regeneration of cholinergic neurons. PMID:1331914

  3. Stochastic hybrid model of spontaneous dendritic NMDA spikes

    Following recent advances in imaging techniques and methods of dendritic stimulation, active voltage spikes have been observed in thin dendritic branches of excitatory pyramidal neurons, where the majority of synapses occur. The generation of these dendritic spikes involves both Na+ ion channels and M-methyl-D-aspartate receptor (NMDAR) channels. During strong stimulation of a thin dendrite, the resulting high levels of glutamate, the main excitatory neurotransmitter in the central nervous system and an NMDA agonist, modify the current-voltage (I–V) characteristics of an NMDAR so that it behaves like a voltage-gated Na+ channel. Hence, the NMDARs can fire a regenerative dendritic spike, just as Na+ channels support the initiation of an action potential following membrane depolarization. However, the duration of the dendritic spike is of the order 100 ms rather than 1 ms, since it involves slow unbinding of glutamate from NMDARs rather than activation of hyperpolarizing K+ channels. It has been suggested that dendritic NMDA spikes may play an important role in dendritic computations and provide a cellular substrate for short-term memory. In this paper, we consider a stochastic, conductance-based model of dendritic NMDA spikes, in which the noise originates from the stochastic opening and closing of a finite number of Na+ and NMDA receptor ion channels. The resulting model takes the form of a stochastic hybrid system, in which membrane voltage evolves according to a piecewise deterministic dynamics that is coupled to a jump Markov process describing the opening and closing of the ion channels. We formulate the noise-induced initiation and termination of a dendritic spike in terms of a first-passage time problem, under the assumption that glutamate unbinding is negligible, which we then solve using a combination of WKB methods and singular perturbation theory. Using a stochastic phase-plane analysis we then extend our analysis to take proper account of the

  4. Nefiracetam activation of CaM kinase II and protein kinase C mediated by NMDA and metabotropic glutamate receptors in olfactory bulbectomized mice.

    Moriguchi, Shigeki; Han, Feng; Shioda, Norifumi; Yamamoto, Yui; Nakajima, Takeharu; Nakagawasai, Osamu; Tadano, Takeshi; Yeh, Jay Z; Narahashi, Toshio; Fukunaga, Kohji

    2009-07-01

    Aberrant behaviors related to learning and memory in olfactory bulbectomized (OBX) mice have been documented in the previous studies. We reported that the impairment of long-term potentiation (LTP) of hippocampal CA1 regions from OBX mice was associated with down-regulation of CaM kinase II (CaMKII) and protein kinase C (PKC) activities. We now demonstrated that the nootropic drug, nefiracetam, significantly improved spatial reference memory-related behaviors as assessed by Y-maze and novel object recognition task in OBX mice. Nefiracetam also restored hippocampal LTP injured in OBX mice. Nefiracetam treatment restored LTP-induced PKCalpha (Ser657) and NR1 (Ser896) phosphorylation as well as increase in their basal phosphorylation in the hippocampal CA1 region of OBX mice. Likewise, nefiracetam improved LTP-induced CaMKIIalpha (Thr286) autophosphorylation and GluR1 (Ser831) phosphorylation and increased their basal phosphorylation. The enhancement of PKCalpha (Ser657) and CaMKIIalpha (Thr286) autophosphorylation by nefiracetam was inhibited by treatment with (+/-)-alpha-Methyl-(4-carboxyphenyl)glycine and DL-2-Amino-5-phosphonovaleric acid, respectively. The enhancement of LTP induced by nefiracetam is inhibited by treatment with 2-methyl-6-(phenylethynyl)-pyridine, but not by treatment with LY367385, suggesting that metabotropic glutamate receptor 5 (mGluR5) but not mGluR1 is involved in the nefiracetam-induced LTP enhancement. Taken together, nefiracetam ameliorates OBX-induced deficits in memory-related behaviors and impairment of LTP in the hippocampal CA1 region through activation of NMDAR and mGluR5, thereby leading to an increase in activities of CaMKIIalpha (Thr286) and PKCalpha (Ser657), respectively. PMID:19457128

  5. Activity-induced synaptic delivery of the GluN2A-containing NMDA receptor is dependent on endoplasmic reticulum chaperone Bip and involved in fear memory.

    Zhang, Xiao-min; Yan, Xun-yi; Zhang, Bin; Yang, Qian; Ye, Mao; Cao, Wei; Qiang, Wen-bin; Zhu, Li-jun; Du, Yong-lan; Xu, Xing-xing; Wang, Jia-sheng; Xu, Fei; Lu, Wei; Qiu, Shuang; Yang, Wei; Luo, Jian-hong

    2015-07-01

    The N-methyl-D-aspartate receptor (NMDAR) in adult forebrain is a heterotetramer mainly composed of two GluN1 subunits and two GluN2A and/or GluN2B subunits. The synaptic expression and relative numbers of GluN2A- and GluN2B-containing NMDARs play critical roles in controlling Ca(2+)-dependent signaling and synaptic plasticity. Previous studies have suggested that the synaptic trafficking of NMDAR subtypes is differentially regulated, but the precise molecular mechanism is not yet clear. In this study, we demonstrated that Bip, an endoplasmic reticulum (ER) chaperone, selectively interacted with GluN2A and mediated the neuronal activity-induced assembly and synaptic incorporation of the GluN2A-containing NMDAR from dendritic ER. Furthermore, the GluN2A-specific synaptic trafficking was effectively disrupted by peptides interrupting the interaction between Bip and GluN2A. Interestingly, fear conditioning in mice was disrupted by intraperitoneal injection of the interfering peptide before training. In summary, we have uncovered a novel mechanism for the activity-dependent supply of synaptic GluN2A-containing NMDARs, and demonstrated its relevance to memory formation. PMID:26088419

  6. Ethanol Extract of Ganoderma lucidum Augments Cellular Anti-oxidant Defense through Activation of Nrf2/HO-1

    Yoo-hwan Lee

    2016-03-01

    augments the cellular anti-oxidant defense capacity through activation of Nrf2/HO-1, thereby protecting C2C12 myoblasts from H2O2-induced oxidative cytotoxicity.

  7. Developments of PET radioligands for NMDA receptors

    Aim: There has been a great demand for developments of the radioligands to visualize the N-methyl-D-aspartate (NMDA) receptors by PET/SPECT. We have recently synthesized two C-11 labeled antagonists for the glycine-binding site on NMDA receptors. The aim of this work is to examine for their in vitro and in vivo binding characteristics, and to evaluate their potentials as PET radioligands for the NMDA receptors. Materials and methods: Two C-11 labeled 4-hydroxy-2-quinolones (1 and 2) were synthesized by conventional methylation of the corresponding phenols with [11C]methyl iodide. In vitro and ex vivo quantitative autoradiographs with imaging plate, as well as animal PET, were employed in order to evaluate their in vitro and in vivo binding to the NMDA receptors. Results: The compound 1 showed the specific binding to rat brain slices with higher localization in the hippocampus and cerebral cortex than in the cerebellum. Both glycine antagonists and agonists (glycine and D-serine) inhibited the in vitro binding of 1. On the other hand, the compound 2 displayed the specific binding to rat brain slices with no regional difference. Very interestingly, glycine agonists gave no significant change in the in vitro binding of 2, while glycine antagonists strongly inhibited the binding. Ex vivo autoradiography and monkey PET studies showed that 1 localizes only in the cerebellum, whereas 2 localizes in the cortex regions than in the cerebellum. Simultaneous injection with non-radioactive 1 or 2 (2 mg/kg) reduced the radioactivity to their non-specific level. Conclusion: The present studies indicated that the structural change of 4-hydroxy-2-quinolones results in the great change in both in vitro and in vivo binding characteristics of the antagonists. We have recently reported that in vivo binding of 1 ([11C]L-703,717) is inhibited by high content of endogenous glycine and D-serine, and that 1 localizes only in the cerebellum having low content of the agonists. The present in

  8. Anti-Diabetic Activities of Jiaotaiwan in db/db Mice by Augmentation of AMPK Protein Activity and Upregulation of GLUT4 Expression

    Na Hu

    2013-01-01

    Full Text Available Jiaotaiwan (JTW, which is composed of Coptis chinensis (CC and cinnamon (CIN, is one of the most well-known traditional Chinese medicines. In this study, we investigated the antidiabetic effects and mechanism of JTW in db/db mice. Results showed that JTW significantly decreased the level of fasting blood glucose and improved glucose and insulin tolerance better than CC or CIN alone. JTW also effectively protected the pancreatic islet shape, augmented the activation of AMP-activated protein kinase (AMPK in the liver, and increased the expression of glucose transporter 4 (GLUT4 protein in skeletal muscle and white fat. AMPK and GLUT4 contributed to glucose metabolism regulation and had an essential function in the development of diabetes mellitus (DM. Therefore, the mechanisms of JTW may be related to suppressing gluconeogenesis by activating AMPK in the liver and affecting glucose uptake in surrounding tissues through the upregulation of GLUT4 protein expression. These findings provided a new insight into the antidiabetic clinical applications of JTW and demonstrated the potential of JTW as a new drug candidate for DM treatment.

  9. Neutrophil depletion after subarachnoid hemorrhage improves memory via NMDA receptors.

    Provencio, Jose Javier; Swank, Valerie; Lu, Haiyan; Brunet, Sylvain; Baltan, Selva; Khapre, Rohini V; Seerapu, Himabindu; Kokiko-Cochran, Olga N; Lamb, Bruce T; Ransohoff, Richard M

    2016-05-01

    Cognitive deficits after aneurysmal subarachnoid hemorrhage (SAH) are common and disabling. Patients who experience delayed deterioration associated with vasospasm are likely to have cognitive deficits, particularly problems with executive function, verbal and spatial memory. Here, we report neurophysiological and pathological mechanisms underlying behavioral deficits in a murine model of SAH. On tests of spatial memory, animals with SAH performed worse than sham animals in the first week and one month after SAH suggesting a prolonged injury. Between three and six days after experimental hemorrhage, mice demonstrated loss of late long-term potentiation (L-LTP) due to dysfunction of the NMDA receptor. Suppression of innate immune cell activation prevents delayed vasospasm after murine SAH. We therefore explored the role of neutrophil-mediated innate inflammation on memory deficits after SAH. Depletion of neutrophils three days after SAH mitigates tissue inflammation, reverses cerebral vasoconstriction in the middle cerebral artery, and rescues L-LTP dysfunction at day 6. Spatial memory deficits in both the short and long-term are improved and associated with a shift of NMDA receptor subunit composition toward a memory sparing phenotype. This work supports further investigating suppression of innate immunity after SAH as a target for preventative therapies in SAH. PMID:26872422

  10. Involvement of ERK in NMDA receptor-independent cortical neurotoxicity of hydrogen sulfide

    Kurokawa, Yuko; Sekiguchi, Fumiko; Kubo, Satoko; Yamasaki, Yoshiko; Matsuda, Sachi; Okamoto, Yukari; Sekimoto, Teruki; Fukatsu, Anna; Nishikawa, Hiroyuki [Division of Pharmacology and Pathophysiology, Kinki University School of Pharmacy, 3-4-1 Kowakae, Higashi-Osaka 577-8502 (Japan); Kume, Toshiaki [Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida-shimoadachi-cho, Sakyo-ku, Kyoto 606-8501 (Japan); Fukushima, Nobuyuki [Division of Molecular Neurobiology, Department of Life Sciences, Kinki University School of Science and Engineering, 3-4-1 Kowakae, Higashi-Osaka 577-8502 (Japan); Akaike, Akinori [Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida-shimoadachi-cho, Sakyo-ku, Kyoto 606-8501 (Japan); Kawabata, Atsufumi, E-mail: kawabata@phar.kindai.ac.jp [Division of Pharmacology and Pathophysiology, Kinki University School of Pharmacy, 3-4-1 Kowakae, Higashi-Osaka 577-8502 (Japan)

    2011-11-04

    Highlights: Black-Right-Pointing-Pointer Hydrogen sulfide causes NMDA receptor-independent neurotoxicity in mouse fetal cortical neurons. Black-Right-Pointing-Pointer Activation of ERK mediates the toxicity of hydrogen sulfide. Black-Right-Pointing-Pointer Apoptotic mechanisms are involved in the hydrogen-induced cell death. -- Abstract: Hydrogen sulfide (H{sub 2}S), a gasotransmitter, exerts both neurotoxicity and neuroprotection, and targets multiple molecules including NMDA receptors, T-type calcium channels and NO synthase (NOS) that might affect neuronal viability. Here, we determined and characterized effects of NaHS, an H{sub 2}S donor, on cell viability in the primary cultures of mouse fetal cortical neurons. NaHS caused neuronal death, as assessed by LDH release and trypan blue staining, but did not significantly reduce the glutamate toxicity. The neurotoxicity of NaHS was resistant to inhibitors of NMDA receptors, T-type calcium channels and NOS, and was blocked by inhibitors of MEK, but not JNK, p38 MAP kinase, PKC and Src. NaHS caused prompt phosphorylation of ERK and upregulation of Bad, followed by translocation of Bax to mitochondria and release of mitochondrial cytochrome c, leading to the nuclear condensation/fragmentation. These effects of NaHS were suppressed by the MEK inhibitor. Our data suggest that the NMDA receptor-independent neurotoxicity of H{sub 2}S involves activation of the MEK/ERK pathway and some apoptotic mechanisms.

  11. Inhibition of Acetylcholinesterase Modulates NMDA Receptor Antagonist Mediated Alterations in the Developing Brain

    Ivo Bendix

    2014-03-01

    Full Text Available Exposure to N-methyl-d-aspartate (NMDA receptor antagonists has been demonstrated to induce neurodegeneration in newborn rats. However, in clinical practice the use of NMDA receptor antagonists as anesthetics and sedatives cannot always be avoided. The present study investigated the effect of the indirect cholinergic agonist physostigmine on neurotrophin expression and the extracellular matrix during NMDA receptor antagonist induced injury to the immature rat brain. The aim was to investigate matrix metalloproteinase (MMP-2 activity, as well as expression of tissue inhibitor of metalloproteinase (TIMP-2 and brain-derived neurotrophic factor (BDNF after co-administration of the non-competitive NMDA receptor antagonist MK801 (dizocilpine and the acetylcholinesterase (AChE inhibitor physostigmine. The AChE inhibitor physostigmine ameliorated the MK801-induced reduction of BDNF mRNA and protein levels, reduced MK801-triggered MMP-2 activity and prevented decreased TIMP-2 mRNA expression. Our results indicate that AChE inhibition may prevent newborn rats from MK801-mediated brain damage by enhancing neurotrophin-associated signaling pathways and by modulating the extracellular matrix.

  12. Involvement of ERK in NMDA receptor-independent cortical neurotoxicity of hydrogen sulfide

    Highlights: ► Hydrogen sulfide causes NMDA receptor-independent neurotoxicity in mouse fetal cortical neurons. ► Activation of ERK mediates the toxicity of hydrogen sulfide. ► Apoptotic mechanisms are involved in the hydrogen-induced cell death. -- Abstract: Hydrogen sulfide (H2S), a gasotransmitter, exerts both neurotoxicity and neuroprotection, and targets multiple molecules including NMDA receptors, T-type calcium channels and NO synthase (NOS) that might affect neuronal viability. Here, we determined and characterized effects of NaHS, an H2S donor, on cell viability in the primary cultures of mouse fetal cortical neurons. NaHS caused neuronal death, as assessed by LDH release and trypan blue staining, but did not significantly reduce the glutamate toxicity. The neurotoxicity of NaHS was resistant to inhibitors of NMDA receptors, T-type calcium channels and NOS, and was blocked by inhibitors of MEK, but not JNK, p38 MAP kinase, PKC and Src. NaHS caused prompt phosphorylation of ERK and upregulation of Bad, followed by translocation of Bax to mitochondria and release of mitochondrial cytochrome c, leading to the nuclear condensation/fragmentation. These effects of NaHS were suppressed by the MEK inhibitor. Our data suggest that the NMDA receptor-independent neurotoxicity of H2S involves activation of the MEK/ERK pathway and some apoptotic mechanisms.

  13. Augmented Reality in Astrophysics

    Vogt, Frédéric P. A.; Shingles, Luke J.

    2013-01-01

    Augmented Reality consists of merging live images with virtual layers of information. The rapid growth in the popularity of smartphones and tablets over recent years has provided a large base of potential users of Augmented Reality technology, and virtual layers of information can now be attached to a wide variety of physical objects. In this article, we explore the potential of Augmented Reality for astrophysical research with two distinct experiments: (1) Augmented Posters and (2) Augmented...

  14. NMDA Receptors in Glial Cells: Pending Questions

    Džamba, Dávid; Honsa, Pavel; Anděrová, Miroslava

    2013-01-01

    Roč. 11, č. 3 (2013), s. 250-262. ISSN 1570-159X R&D Projects: GA ČR GA309/08/1381; GA ČR(CZ) GBP304/12/G069 Grant ostatní: GA UK(CZ) 604212 Institutional support: RVO:68378041 Keywords : astrocytes * ischemia * NMDA receptors Subject RIV: FH - Neurology Impact factor: 2.347, year: 2013

  15. Computational study of NMDA conductance and cortical oscillations in schizophrenia

    Kubra Komek Kirli

    2014-10-01

    Full Text Available N-methyl-D-aspartate (NMDA receptor hypofunction has been implicated in the pathophysiology of schizophrenia. The illness is also characterized by gamma oscillatory disturbances, which can be evaluated with precise frequency specificity employing auditory cortical entrainment paradigms. This computational study investigates how synaptic NMDA hypofunction may give rise to network level oscillatory deficits as indexed by entrainment paradigms. We developed a computational model of a local cortical circuit with pyramidal cells and fast-spiking interneurons (FSI, incorporating NMDA, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic (AMPA, and γ-aminobutyric acid (GABA synaptic kinetics. We evaluated the effects of varying NMDA conductance on FSIs and pyramidal cells, as well as AMPA to NMDA ratio. We also examined the differential effects across a broad range of entrainment frequencies as a function of NMDA conductance. Varying NMDA conductance onto FSIs revealed an inverted-U relation with network gamma whereas NMDA conductance onto the pyramidal cells had a more monotonic relationship. Varying NMDA vs. AMPA conductance onto FSIs demonstrated the necessity of AMPA in the generation of gamma while NMDA receptors had a modulatory role. Finally, reducing NMDA conductance onto FSI and varying the stimulus input frequency reproduced the specific reductions in gamma range (~40 Hz as observed in schizophrenia studies. Our computational study showed that reductions in NMDA conductance onto FSIs can reproduce similar disturbances in entrainment to periodic stimuli within the gamma range as reported in schizophrenia studies. These findings provide a mechanistic account of how specific cellular level disturbances can give rise to circuitry level pathophysiologic disturbance in schizophrenia.

  16. Repeated exposure to methamphetamine, cocaine or morphine induces augmentation of dopamine release in rat mesocorticolimbic slice co-cultures.

    Takayuki Nakagawa

    Full Text Available Repeated intermittent exposure to psychostimulants and morphine leads to progressive augmentation of its locomotor activating effects in rodents. Accumulating evidence suggests the critical involvement of the mesocorticolimbic dopaminergic neurons, which project from the ventral tegmental area to the nucleus accumbens and the medial prefrontal cortex, in the behavioral sensitization. Here, we examined the acute and chronic effects of psychostimulants and morphine on dopamine release in a reconstructed mesocorticolimbic system comprised of a rat triple organotypic slice co-culture of the ventral tegmental area, nucleus accumbens and medial prefrontal cortex regions. Tyrosine hydroxylase-positive cell bodies were localized in the ventral tegmental area, and their neurites projected to the nucleus accumbens and medial prefrontal cortex regions. Acute treatment with methamphetamine (0.1-1000 µM, cocaine (0.1-300 µM or morphine (0.1-100 µM for 30 min increased extracellular dopamine levels in a concentration-dependent manner, while 3,4-methylenedioxyamphetamine (0.1-1000 µM had little effect. Following repeated exposure to methamphetamine (10 µM for 30 min every day for 6 days, the dopamine release gradually increased during the 30-min treatment. The augmentation of dopamine release was maintained even after the withdrawal of methamphetamine for 7 days. Similar augmentation was observed by repeated exposure to cocaine (1-300 µM or morphine (10 and 100 µM. Furthermore, methamphetamine-induced augmentation of dopamine release was prevented by an NMDA receptor antagonist, MK-801 (10 µM, and was not observed in double slice co-cultures that excluded the medial prefrontal cortex slice. These results suggest that repeated psychostimulant- or morphine-induced augmentation of dopamine release, i.e. dopaminergic sensitization, was reproduced in a rat triple organotypic slice co-cultures. In addition, the slice co-culture system revealed that the NMDA

  17. Antagonistas de los receptores glutamatérgicos NMDA en el tratamiento del dolor crónico NMDA glutamatergic receptor antagonists for the management of chronic pain

    F. Neira

    2004-05-01

    receptores opioides mu, pero además es un antagonista no competitivo de los receptores NMDA. La utilización de la metadona permite mejorar el control del dolor al disminuir el desarrollo de tolerancia a los opioides. La memantina es un antagonista no competitivo de los receptores NMDA. Disminuye la facilitación intracortical y aumenta la inhibición intracortical. Experimentalmente ha demostrado características antinociceptivas en la fase secundaria a la inflamación inducida por la prueba de la formalina. Disminuye la hiperalgesia térmica y mecánica. Los antagonistas de los receptores NMDA, abren un nuevo horizonte en el tratamiento del dolor neuropático. Son fármacos que habitualmente requieren la asociación de otros analgésicos, normalmente actúan como coadyuvantes. Los resultados dispares de los diferentes antagonistas sobre una misma indicación, no hacen sino confirmar la complejidad de su mecanismo de acción, que no se limita a antagonizar los receptores NMDA, sino que va mucho más allá.NMDA receptors are associated to learning and memory processes, development and neural plasticity, as well as acute and chronic pain conditions. They are involved in the outset and maintenance of central sensitization associated to damage or inflammation of peripheral tissues. Glutamate is the main amino acid that stimulates the CNS, can be involved in nociceptive transmission processes at the spine level and is the main responsible for the fast synaptic transmission. The action of glutamate in the pain routes is mostly mediated by ionotropic receptors (AMPA, NMDA and kainic. The activation of NMDA receptors plays a major role in the excitatory neurotransmission and the synaptic plasticity of the CNS. Glutamate and its agonists (NMDA, AMPA or kainic acid are involved in the generation and maintenance of hyperalgesia conditions (exacerbated response to noxious stimulus and alodynia (decrease of pain threshold. The clinical effectiveness of NMDA receptor antagonists

  18. Age dependence of the rapid antidepressant and synaptic effects of acute NMDA receptor blockade

    Elena eNosyreva

    2014-12-01

    Full Text Available Ketamine is a NMDA receptor antagonist that produces rapid antidepressant responses in individuals with major depressive disorder. The antidepressant action of ketamine has been linked to blocking NMDA receptor activation at rest, which inhibits eukaryotic elongation factor2 kinase leading to desuppression of protein synthesis and synaptic potentiation in the CA1 region of the hippocampus. Here, we investigated ketamine mediated antidepressant response and the resulting synaptic potentiation in juvenile animals. We found that ketamine did not produce an antidepressant response in juvenile animals in the novelty suppressed feeding or the forced swim test. In addition ketamine application failed to trigger synaptic potentiation in hippocampal slices obtained from juvenile animals, unlike its action in slices from older animals (6-9 weeks old. The inability of ketamine to trigger an antidepressant response or subsequent synaptic plasticity processes suggests a developmental component to ketamine mediated antidepressant efficacy. We also show that the NMDAR antagonist AP5 triggers synaptic potentiation in mature hippocampus similar to the action of ketamine, demonstrating that global competitive blockade of NMDA receptors is sufficient to trigger this effect. These findings suggest that global blockade of NMDA receptors in developmentally mature hippocampal synapses are required for the antidepressant efficacy of ketamine.

  19. NMDA-induced accumulation of Shank at the postsynaptic density is mediated by CaMKII

    Highlights: • NMDA-induces accumulation of Shank at the postsynaptic density. • Shank accumulation is preferential to the distal region of the postsynaptic density. • Shank accumulation is mediated by CaMKII. - Abstract: Shank is a specialized scaffold protein present in high abundance at the postsynaptic density (PSD). Using pre-embedding immunogold electron microscopy on cultured hippocampal neurons, we had previously demonstrated further accumulation of Shank at the PSD under excitatory conditions. Here, using the same experimental protocol, we demonstrate that a cell permeable CaMKII inhibitor, tatCN21, blocks NMDA-induced accumulation of Shank at the PSD. Furthermore we show that NMDA application changes the distribution pattern of Shank at the PSD, promoting a 7–10 nm shift in the median distance of Shank labels away from the postsynaptic membrane. Inhibition of CaMKII with tatCN21 also blocks this shift in the distribution of Shank. Altogether these results imply that upon activation of NMDA receptors, CaMKII mediates accumulation of Shank, preferentially at the distal regions of the PSD complex extending toward the cytoplasm

  20. Altered excitatory-inhibitory balance in the NMDA-hypofunction model of schizophrenia

    Colin Kehrer

    2008-04-01

    Full Text Available Schizophrenia is a common psychiatric disorder of high incidence, affecting approximately 1% of the world population. The essential neurotransmitter pathology of schizophrenia remains poorly defined, despite huge advances over the past half-century in identifying neurochemical and pathological abnormalities in the disease. The dopamine/serotonin hypothesis has originally provided much of the momentum for neurochemical research in schizophrenia. In recent years, the attention has, however, shifted to the glutamate system, the major excitatory neurotransmitter in the CNS and towards a concept of functional imbalance between excitatory and inhibitory transmission at the network level in various brain regions in schizophrenia. The evidence indicating a central role for the NMDAreceptor subtype in the etiology of schizophrenia has led to the NMDA-hypofunction model of this disease and the use of phencyclidines as a means to induce the NMDA-hypofunction state in animal models. The purpose of this review is to discuss recent findings highlighting the importance of the NMDA-hypofunction model of schizophrenia, both from a clinical perspective, as well as in opening a line of research, which enables electrophysiological studies at the cellular and network level in vitro. In particular, changes in excitation-inhibition (E/I balance in the NMDA-hypofunction model of the disease and the resulting changes in network behaviours, particularly in gamma frequency oscillatory activity, will be discussed.

  1. NMDA-induced accumulation of Shank at the postsynaptic density is mediated by CaMKII

    Tao-Cheng, Jung-Hwa [EM Facility, NINDS, NIH, Bethesda, MD (United States); Yang, Yijung [Laboratory of Neurobiology, NINDS, NIH, Bethesda, MD (United States); Bayer, K. Ulrich [Department of Pharmacology, University of Colorado Denver, School of Medicine, Aurora, CO (United States); Reese, Thomas S. [Laboratory of Neurobiology, NINDS, NIH, Bethesda, MD (United States); Dosemeci, Ayse, E-mail: dosemeca@ninds.nih.gov [Laboratory of Neurobiology, NINDS, NIH, Bethesda, MD (United States)

    2014-07-18

    Highlights: • NMDA-induces accumulation of Shank at the postsynaptic density. • Shank accumulation is preferential to the distal region of the postsynaptic density. • Shank accumulation is mediated by CaMKII. - Abstract: Shank is a specialized scaffold protein present in high abundance at the postsynaptic density (PSD). Using pre-embedding immunogold electron microscopy on cultured hippocampal neurons, we had previously demonstrated further accumulation of Shank at the PSD under excitatory conditions. Here, using the same experimental protocol, we demonstrate that a cell permeable CaMKII inhibitor, tatCN21, blocks NMDA-induced accumulation of Shank at the PSD. Furthermore we show that NMDA application changes the distribution pattern of Shank at the PSD, promoting a 7–10 nm shift in the median distance of Shank labels away from the postsynaptic membrane. Inhibition of CaMKII with tatCN21 also blocks this shift in the distribution of Shank. Altogether these results imply that upon activation of NMDA receptors, CaMKII mediates accumulation of Shank, preferentially at the distal regions of the PSD complex extending toward the cytoplasm.

  2. Role of NMDA receptors in acute liver failure and ammonia toxicity: therapeutical implications.

    Rodrigo, Regina; Cauli, Omar; Boix, Jordi; ElMlili, Nisrin; Agusti, Ana; Felipo, Vicente

    2009-01-01

    Acute liver failure (ALF) may lead to rapid death unless the patients receive a liver for transplantation. However, the number of livers available is not enough and a number of patients die before a suitable liver is available for transplantation. The liver has a high capacity for regeneration which may allow complete recovery even in patients with severe liver failure. It would be therefore very useful to have procedures to prevent or delay the mechanisms by which ALF leads to death. These mechanisms are no well understood. Progression of ALF leads to multi-organ failure, systemic inflammatory response, hepatic encephalopathy, cerebral oedema and increased intracranial pressure, which seem the most important immediate causes of mortality in patients with ALF. A main contributor to these events is hyperammonemia, due to impaired ammonia detoxification in the liver. Acute hyperammonemia per se leads to death, which is mediated by activation of the NMDA type of glutamate receptors in brain and may be prevented by antagonists blocking these receptors. Acute liver failure also leads to hyperammonemia and excessive activation of NMDA receptors in brain which contributes to ALF-induced death. Sustained blocking of NMDA receptors by continuous administration of the antagonists MK-801 or memantine increases about twice the survival time of rats with severe ALF due to injection of 2.5g/kg of galactosamine. In rats with milder ALF due to injection of 1.5g/kg of galactosamine, blocking NMDA receptors increases the percentage of surviving rats from 23% to 62% and increases about twice the survival time of the rats which die. These data strongly support that blocking NMDA receptors would improve survival of patients with ALF, either by allowing more time for liver regeneration or to get a liver suitable for transplantation. PMID:19428814

  3. Investigating the influence of PFC transection and nicotine on dynamics of AMPA and NMDA receptors of VTA dopaminergic neurons

    Chen Ting

    2011-10-01

    Full Text Available Abstract Background All drugs of abuse, including nicotine, activate the mesocorticolimbic system that plays critical roles in nicotine reward and reinforcement development and triggers glutamatergic synaptic plasticity on the dopamine (DA neurons in the ventral tegmental area (VTA. The addictive behavior and firing pattern of the VTA DA neurons are thought to be controlled by the glutamatergic synaptic input from prefrontal cortex (PFC. Interrupted functional input from PFC to VTA was shown to decrease the effects of the drug on the addiction process. Nicotine treatment could enhance the AMPA/NMDA ratio in VTA DA neurons, which is thought as a common addiction mechanism. In this study, we investigate whether or not the lack of glutamate transmission from PFC to VTA could make any change in the effects of nicotine. Methods We used the traditional AMPA/NMDA peak ratio, AMPA/NMDA area ratio, and KL (Kullback-Leibler divergence analysis method for the present study. Results Our results using AMPA/NMDA peak ratio showed insignificant difference between PFC intact and transected and treated with saline. However, using AMPA/NMDA area ratio and KL divergence method, we observed a significant difference when PFC is interrupted with saline treatment. One possible reason for the significant effect that the PFC transection has on the synaptic responses (as indicated by the AMPA/NMDA area ratio and KL divergence may be the loss of glutamatergic inputs. The glutamatergic input is one of the most important factors that contribute to the peak ratio level. Conclusions Our results suggested that even within one hour after a single nicotine injection, the peak ratio of AMPA/NMDA on VTA DA neurons could be enhanced.

  4. NMDA receptors are involved in the antidepressant-like effects of capsaicin following amphetamine withdrawal in male mice.

    Amiri, Shayan; Alijanpour, Sakineh; Tirgar, Fatemeh; Haj-Mirzaian, Arya; Amini-Khoei, Hossein; Rahimi-Balaei, Maryam; Rastegar, Mojgan; Ghaderi, Marzieh; Ghazi-Khansari, Mahmoud; Zarrindast, Mohammad-Reza

    2016-08-01

    Amphetamine withdrawal (AW) is accompanied by diminished pleasure and depression which plays a key role in drug relapse and addictive behaviors. There is no efficient treatment for AW-induced depression and underpinning mechanisms were not well determined. Considering both transient receptor potential cation channel, subfamily V, member 1 (TRPV1) and N-Methyl-d-aspartate (NMDA) receptors contribute to pathophysiology of mood and addictive disorders, in this study, we investigated the role of TRPV1 and NMDA receptors in mediating depressive-like behaviors following AW in male mice. Results revealed that administration of capsaicin, TRPV1 agonist, (100μg/mouse, i.c.v.) and MK-801, NMDA receptor antagonist (0.005mg/kg, i.p.) reversed AW-induced depressive-like behaviors in forced swimming test (FST) and splash test with no effect on animals' locomotion. Co-administration of sub-effective doses of MK-801 (0.001mg/kg, i.p.) and capsaicin (10μg/mouse, i.c.v) exerted antidepressant-like effects in behavioral tests. Capsazepine, TRPV1 antagonist, (100μg/mouse, i.c.v) and NMDA, NMDA receptor agonist (7.5mg/kg, i.p.) abolished the effects of capsaicin and MK-801, respectively. None of aforementioned treatments had any effect on behavior of control animals. Collectively, our findings showed that activation of TRPV1 and blockade of NMDA receptors produced antidepressant-like effects in male mice following AW, and these receptors are involved in AW-induced depressive-like behaviors. Further, we found that rapid antidepressant-like effects of capsaicin in FST and splash test are partly mediated by NMDA receptors. PMID:27167081

  5. Neurally augmented sexual function.

    Meloy, S

    2007-01-01

    Neurally Augmented Sexual Function (NASF) is a technique utilizing epidural electrodes to restore and improve sexual function. Orgasmic dysfunction is common in adult women, affecting roughly one quarter of populations studied. Many male patients suffering from erectile dysfunction are not candidates for phosphdiesterase therapy due to concomitant nitrate therapy. Positioning the electrodes at roughly the level of the cauda equina allows for stimulation of somatic efferents and afferents as well as modifying sympathetic and parasympathetic activity. Our series of women treated by NASF is described. Our experience shows that the evaluation of potential candidates for both correctable causes and psychological screening are important considerations. PMID:17691397

  6. The NMDA receptor changes during reperfusion after local ischemia in the rat brain

    excitatory amino acids increased greatly and remained high for a few hours. NMDA receptor was activated and its ion channel opened accordingly, which produced the ischemia damage. The best time of the therapy window of brain ischemia should be within 4 h

  7. PPAR{alpha} deficiency augments a ketogenic diet-induced circadian PAI-1 expression possibly through PPAR{gamma} activation in the liver

    Oishi, Katsutaka, E-mail: k-ooishi@aist.go.jp [Biological Clock Research Group, Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki (Japan); Uchida, Daisuke [Biological Clock Research Group, Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki (Japan); Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Ibaraki (Japan); Ohkura, Naoki [Department of Clinical Molecular Biology, Faculty of Pharmaceutical Sciences, Teikyo University, Sagamihara, Kanagawa (Japan); Horie, Shuichi [Department of Clinical Biochemistry, Kagawa Nutrition University, Sakado, Saitama (Japan)

    2010-10-15

    Research highlights: {yields} PPAR{alpha} deficiency augments a ketogenic diet-induced circadian PAI-1 expression. {yields} Hepatic expressions of PPAR{gamma} and PCG-1{alpha} are induced by a ketogenic diet. {yields} PPAR{gamma} antagonist attenuates a ketogenic diet-induced PAI-1 expression. {yields} Ketogenic diet advances the phase of circadian clock in a PPAR{alpha}-independent manner. -- Abstract: An increased level of plasminogen activator inhibitor-1 (PAI-1) is considered a risk factor for cardiovascular diseases, and PAI-1 gene expression is under the control of molecular circadian clocks in mammals. We recently showed that PAI-1 expression is augmented in a phase-advanced circadian manner in mice fed with a ketogenic diet (KD). To determine whether peroxisome proliferator-activated receptor {alpha} (PPAR{alpha}) is involved in hypofibrinolytic status induced by a KD, we examined the expression profiles of PAI-1 and circadian clock genes in PPAR{alpha}-null KD mice. Chronic administration of bezafibrate induced the PAI-1 gene expression in a PPAR{alpha}-dependent manner. Feeding with a KD augmented the circadian expression of PAI-1 mRNA in the hearts and livers of wild-type (WT) mice as previously described. The KD-induced mRNA expression of typical PPAR{alpha} target genes such as Cyp4A10 and FGF21 was damped in PPAR{alpha}-null mice. However, plasma PAI-1 concentrations were significantly more elevated in PPAR{alpha}-null KD mice in accordance with hepatic mRNA levels. These observations suggest that PPAR{alpha} activation is dispensable for KD-induced PAI-1 expression. We also found that hyperlipidemia, fatty liver, and the hepatic expressions of PPAR{gamma} and its coactivator PCG-1{alpha} were more effectively induced in PPAR{alpha}-null, than in WT mice on a KD. Furthermore, KD-induced hepatic PAI-1 expression was significantly suppressed by supplementation with bisphenol A diglycidyl ether, a PPAR{gamma} antagonist, in both WT and PPAR

  8. The functional synergy between IL-12 and IL-2 involves p38 mitogen-activated protein kinase and is associated with the augmentation of STAT serine phosphorylation.

    Gollob, J A; Schnipper, C P; Murphy, E A; Ritz, J; Frank, D A

    1999-04-15

    IL-12 and IL-2 can stimulate mitogen- or CD3-activated T cells to proliferate, produce IFN-gamma, and kill tumor cells. The magnitude of these functional responses is greatly augmented when T cells are activated by the combination of IL-12 and IL-2. Although peripheral blood T cells are largely unresponsive to these cytokines without prior activation, a small subset of CD8+ T cells (CD8+CD18bright) is strongly activated by the combination of IL-12 and IL-2. In this report we show that the functional synergy between IL-12 and IL-2 in CD8+CD18bright T cells correlates with the activation of the stress kinases, p38 mitogen-activated protein (MAP) kinase and stress-activated protein kinase (SAPK)/Jun N-terminal kinase, but not with the activation of the extracellular signal-regulated kinases. The functional synergy between IL-2 and IL-12 is also associated with a prominent increase in STAT1 and STAT3 serine phosphorylation over that observed with IL-12 or IL-2 alone. By contrast, STAT tyrosine phosphorylation is not augmented over that seen with either cytokine alone. A specific inhibitor of p38 MAP kinase completely inhibits the serine phosphorylation of STAT1 and STAT3 induced by IL-12 and IL-2 and abrogates the functional synergy between IL-12 and IL-2 without affecting STAT tyrosine phosphorylation. This suggests that p38 MAP kinase may play an important role in regulating STAT serine phosphorylation in response to the combination of IL-12 and IL-2. Furthermore, these findings indicate that the optimal activation of T cells by IL-12 and IL-2 may depend on an interaction between the p38 MAP kinase and Janus kinase/STAT signaling pathways. PMID:10201984

  9. N-Methyl D-Aspartic Acid (NMDA Receptors and Depression

    Enver Yusuf Sivrioglu

    2009-06-01

    Full Text Available The monoaminergic hypothesis of depression has provided the basis for extensive research into the pathophysiology of mood disorders and has been of great significance for the development of effective antidepressants. Current antidepressant treatments not only increase serotonin and/or noradrenaline bioavailability but also originate adaptive changes increasing synaptic plasticity. Novel approaches to depression and to antidepressant therapy are now focused on intracellular targets that regulate neuroplasticity and cell survival. Accumulating evidence indicates that there is an anatomical substrate for such a devastating neuropsychiatric disease as major depression. Loss of synaptic plasticity and hippocampal atrophy appear to be prominent features of this highly prevalent disorder. A combination of genetic susceptibility and environmental factors make hippocampal neurons more vulnerable to stress. Abundant experimental evidence indicates that stress causes neuronal damage in brain regions, notably in hippocampal subfields. Stress-induced activation of glutamatergic transmission may induce neuronal cell death through excessive stimulation of N-methyl-D-aspartic acid (NMDA receptors. Recent studies mention that the increase of nitric oxide synthesis and inflammation in major depression may contribute to neurotoxicity through NMDA receptor. Both standard antidepressants and NMDA receptor antagonists are able to prevent stress-induced neuronal damage. NMDA antagonists are effective in widely used animal models of depression and some of them appear to be effective also in the few clinical trials performed to date. We are still far from understanding the complex cellular and molecular events involved in mood disorders. There appears to be an emerging role for glutamate neurotransmission in the search for the pathogenesis of major depression. Attenuation of NMDA receptor function mechanism appears to be a promising target in the search for a more

  10. AMPA receptor pHluorin-GluA2 reports NMDA receptor-induced intracellular acidification in hippocampal neurons

    Rathje, Mette; Fang, Huaqiang; Bachman, Julia L;

    2013-01-01

    NMDA receptor activation promotes endocytosis of AMPA receptors, which is an important mechanism underlying long-term synaptic depression. The pH-sensitive GFP variant pHluorin fused to the N terminus of GluA2 (pH-GluA2) has been used to assay NMDA-mediated AMPA receptor endocytosis and recycling...... fluorescence recovery was eliminated in the presence of the NHE1 inhibitor zoniporide. Our results indicate that the pH-GluA2 recycling assay is an unreliable assay for studying AMPA receptor trafficking and also suggest a role for PICK1 in regulating intracellular pH via modulation of NHE activity....

  11. Augmented Reality in Astrophysics

    Vogt, Frédéric P A

    2013-01-01

    Augmented Reality consists of merging live images with virtual layers of information. The rapid growth in the popularity of smartphones and tablets over recent years has provided a large base of potential users of Augmented Reality technology, and virtual layers of information can now be attached to a wide variety of physical objects. In this article, we explore the potential of Augmented Reality for astrophysical research with two distinct experiments: (1) Augmented Posters and (2) Augmented Articles. We demonstrate that the emerging technology of Augmented Reality can already be used and implemented without expert knowledge using currently available apps. Our experiments highlight the potential of Augmented Reality to improve the communication of scientific results in the field of astrophysics. We also present feedback gathered from the Australian astrophysics community that reveals evidence of some interest in this technology by astronomers who experimented with Augmented Posters. In addition, we discuss p...

  12. Benzimidazole-2-carboxamides as novel NR2B selective NMDA receptor antagonists.

    Borza, István; Kolok, Sándor; Gere, Anikó; Nagy, József; Fodor, László; Galgóczy, Kornél; Fetter, József; Bertha, Ferenc; Agai, Béla; Horváth, Csilla; Farkas, Sándor; Domány, György

    2006-09-01

    A novel series of benzimidazole-2-carboxamide derivatives was prepared and identified as NR2B selective NMDA receptor antagonists. The influence of some structural elements, like H-bond donor groups placed on the benzimidazole skeleton and the substitution pattern of the piperidine ring, on the biological activity was studied. Compound 6a showed excellent analgetic activity in the mouse formalin test following po administration. PMID:16782335

  13. NMDA Receptor Modulators in the Treatment of Drug Addiction

    M. Foster Olive

    2013-02-01

    Full Text Available Glutamate plays a pivotal role in drug addiction, and the N-methyl-D-aspartate (NMDA glutamate receptor subtype serves as a molecular target for several drugs of abuse. In this review, we will provide an overview of NMDA receptor structure and function, followed by a review of the mechanism of action, clinical efficacy, and side effect profile of NMDA receptor ligands that are currently in use or being explored for the treatment of drug addiction. These ligands include the NMDA receptor modulators memantine and acamprosate, as well as the partial NMDA agonist D-cycloserine. Data collected to date suggest that direct NMDA receptor modulators have relatively limited efficacy in the treatment of drug addiction, and that partial agonism of NMDA receptors may have some efficacy with regards to extinction learning during cue exposure therapy. However, the lack of consistency in results to date clearly indicates that additional studies are needed, as are studies examining novel ligands with indirect mechanisms for altering NMDA receptor function.

  14. NMDA Receptor Modulators in the Treatment of Drug Addiction

    Tomek, Seven E.; LaCrosse, Amber L.; Nemirovsky, Natali E.; Olive, M. Foster

    2013-01-01

    Glutamate plays a pivotal role in drug addiction, and the N-methyl-d-aspartate (NMDA) glutamate receptor subtype serves as a molecular target for several drugs of abuse. In this review, we will provide an overview of NMDA receptor structure and function, followed by a review of the mechanism of action, clinical efficacy, and side effect profile of NMDA receptor ligands that are currently in use or being explored for the treatment of drug addiction. These ligands include the NMDA receptor modulators memantine and acamprosate, as well as the partial NMDA agonist d-Cycloserine. Data collected to date suggest that direct NMDA receptor modulators have relatively limited efficacy in the treatment of drug addiction, and that partial agonism of NMDA receptors may have some efficacy with regards to extinction learning during cue exposure therapy. However, the lack of consistency in results to date clearly indicates that additional studies are needed, as are studies examining novel ligands with indirect mechanisms for altering NMDA receptor function. PMID:24275950

  15. NMDA Receptor Antagonism in the Lateral/Basolateral but Not Central Nucleus of the Amygdala Prevents the Induction of Facilitated Learning in Response to Stress

    Shors, Tracey J.; Mathew, Pramod R.

    1998-01-01

    Exposure to an acute stressful event facilitates classical eye-blink conditioning in the male rat. The facilitation persists for days after the stressor and its induction is prevented by antagonism of the N-methyl-d-aspartate (NMDA) type of glutamate receptor. To determine whether NMDA receptor antagonists prevent the facilitated conditioning by activity in the amygdala, a competitive antagonist, AP5, was injected bilaterally into the lateral/basolateral versus central nuclei of the amygdala....

  16. The Emergence of NMDA Receptor Metabotropic Function: Insights from Imaging

    Dore, Kim; Aow, Jonathan; Malinow, Roberto

    2016-01-01

    The NMDA receptor (R) participates in many important physiological and pathological processes. For example, its activation is required for both long-term potentiation (LTP) and long-term depression (LTD) of synaptic transmission, cellular models of learning and memory. Furthermore, it may play a role in the actions of amyloid-beta on synapses as well as in the signaling leading to cell death following stroke. Until recently, these processes were thought to be mediated by ion-flux through the receptor. Using a combination of imaging and electrophysiological approaches, ion-flux independent functions of the NMDAR were recently examined. In this review, we will discuss the role of metabotropic NMDAR function in LTD and synaptic dysfunction. PMID:27516738

  17. On the Role of Glutamate in Presynaptic Development: Possible Contributions of Presynaptic NMDA Receptors

    Karlie N. Fedder

    2015-12-01

    Full Text Available Proper formation and maturation of synapses during development is a crucial step in building the functional neural circuits that underlie perception and behavior. It is well established that experience modifies circuit development. Therefore, understanding how synapse formation is controlled by synaptic activity is a key question in neuroscience. In this review, we focus on the regulation of excitatory presynaptic terminal development by glutamate, the predominant excitatory neurotransmitter in the brain. We discuss the evidence that NMDA receptor activation mediates these effects of glutamate and present the hypothesis that local activation of presynaptic NMDA receptors (preNMDARs contributes to glutamate-dependent control of presynaptic development. Abnormal glutamate signaling and aberrant synapse development are both thought to contribute to the pathogenesis of a variety of neurodevelopmental disorders, including autism spectrum disorders, intellectual disability, epilepsy, anxiety, depression, and schizophrenia. Therefore, understanding how glutamate signaling and synapse development are linked is important for understanding the etiology of these diseases.

  18. On the Role of Glutamate in Presynaptic Development: Possible Contributions of Presynaptic NMDA Receptors.

    Fedder, Karlie N; Sabo, Shasta L

    2015-01-01

    Proper formation and maturation of synapses during development is a crucial step in building the functional neural circuits that underlie perception and behavior. It is well established that experience modifies circuit development. Therefore, understanding how synapse formation is controlled by synaptic activity is a key question in neuroscience. In this review, we focus on the regulation of excitatory presynaptic terminal development by glutamate, the predominant excitatory neurotransmitter in the brain. We discuss the evidence that NMDA receptor activation mediates these effects of glutamate and present the hypothesis that local activation of presynaptic NMDA receptors (preNMDARs) contributes to glutamate-dependent control of presynaptic development. Abnormal glutamate signaling and aberrant synapse development are both thought to contribute to the pathogenesis of a variety of neurodevelopmental disorders, including autism spectrum disorders, intellectual disability, epilepsy, anxiety, depression, and schizophrenia. Therefore, understanding how glutamate signaling and synapse development are linked is important for understanding the etiology of these diseases. PMID:26694480

  19. [Participation of receptors of the NMDA type in regulation by glutamate of alimentary motor program of the freshwater mollusc lymnaea stagnalis].

    D'iakonova, T L; D'iakonova, V E

    2010-01-01

    A possible participation of receptors of the NMDA type in regulation by glutamate of the Lymnaea stagnalis feeding program was studied in electrophysiological experiments. The specific antagonist of receptors of the N-methyl-D-aspartate (NMDA) type MK-801 has been shown to turn off the endogenous generation of the standard three-phase rhythm or the two-phase rhythm. Stimulation of receptors of this type by their specific agonist, NMDA, on the contrary, increased frequency of the alimentary rhythm and transformed it into the two-phase one. All NMDA effects are eliminated by MK-801. Apart from action on generation of central feeding rhythms, ligands of receptors of the NMDA type changes the tonical level of depolarization and activity of the alimentary circuit motoneurons. MK-801 decreased the initial level of the motoneuron B4 activity and inhibited the excitatory effect both of NMDA and of glutamate itself. There are also obtained data in favor of that earlier reported effect of transformation of the inhibitory response of neurons B4 to glutamate into the excitatory one at action of nitric oxide (NO) donors can be mediated by the specific NO effect on the activity of receptors of the NMDA type. The blocker of NMDA receptors MK-801 has been shown to inhibit the effect of transformation of the response to glutamate. The NO donor nitroprusside enhanced essentially the NMDA excitatory action, while the NO acceptor oral PTIO decreased it. The results obtained with use of ODQ, the blocker of NO-sensitive guanylyl cyclase (GC), allow thinking that effect of NO on activity of the NMDA receptors of the pond snail feeding program can be realized through the metabolic pathway GC--cGMP. On the whole, the obtained results show the pond snail receptors of the NMDA type to participate in generation and rearragement of rhythmical alimentary programs in the tonical excitatory effect on the feeding program motoneurons in the NO-dependent transformation of the glutamate response

  20. Neuroprotection, excitotoxicicity and nmda antagonists Neuroproteção, excitotoxicidade e antagonistas do NMDA

    RUBENS JOSÉ GAGLIARDI

    2000-06-01

    Full Text Available PURPOSE: To analyze the main aspects of neuroprotection and excitotoxicity. DISCUSSION: This is a significant theory on the pathophysiology of cerebral ischemia; it is based on the release of excitatory aminoacid (EAA, mainly glutamate. The sequence starts with a decrease of the blood flow and ends in neuronal death. The main stages of this reaction are herein presented and discussed. An in depth study of the effects of the excessive intracellular calcium is undertaken. Neuroprotectors (NP are a group of drugs that reduce the excitotoxicity, opposing the excessive release of EAA and its intracellular effects. Neuroprotectors represent a rational approach to stroke treatment and offer a number of potential advantages. They prevent or limit ischemia-induced damage. CONCLUSION: There are many experimental and clinical NP trials. A minimum of 800 trials are currently under study worldwide. The most important NP subgroups are: N-methyl D-aspartate (NMDA antagonists, gamma-amino butyric acid (GABA agonists, amino-hydroxy-methyl-isoxalone propionic acid (AMPA antagonists, reducers of intracellular Ca++ inhibitors of nitric oxide modulation pathway free radicals scavengers, sodium channel antagonists, glutamate release inhibitor, growth factors, hypothermia and potassium channel activators.PROPÓSITO: Analisar importantes aspectos da neuroproteção e da excitotoxicidade. DISCUSSÃO: Excitotoxicidade é teoria que explica os mecanismos básicos da fisiopatologia da isquemia cerebral; é baseada na liberação excessiva de amino-ácidos excitatórios (AAE, principalmente o glutamato. A sequência se inicia com o decréscimo do fluxo sanguíneo cerebral e termina com a morte neuronal. Os principais aspectos desta cadeia de reações são apresentados e discutidos. Os efeitos do excesso de cálcio intracelular são analisados. Neuroprotetores (NP são um grupo de drogas que reduzem a excitotoxicidade combatendo a excessiva liberação de AAE e os seus

  1. Hyperammonemia alters the modulation by different neurosteroids of the glutamate-nitric oxide-cyclic GMP pathway through NMDA- GABAA - or sigma receptors in cerebellum in vivo.

    González-Usano, Alba; Cauli, Omar; Agustí, Ana; Felipo, Vicente

    2013-04-01

    Several neurosteroids modulate the glutamate-nitric oxide (NO)-cGMP pathway in cerebellum through modulation of NMDA- GABAA - or sigma receptors. Hyperammonemia alters the concentration of several neurosteroids and impairs the glutamate-NO-cGMP pathway, leading to impaired learning ability. This work aimed to assess whether chronic hyperammonemia alters the modulation by different neurosteroids of GABAA, NMDA, and/or sigma receptors and of the glutamate-NO-cGMP pathway in cerebellum. Neurosteroids were administered through microdialysis probes, and extracellular cGMP and citrulline were measured. Then NMDA was administered to assess the effects on the glutamate-NO-cGMP pathway activation. Hyperammonemia completely modifies the effects of pregnanolone and pregnenolone. Pregnanolone acts as a GABAA receptor agonist in controls, but as an NMDA receptor antagonist in hyperammonemic rats. Pregnenolone does not induce any effect in controls, but acts as a sigma receptor agonist in hyperammonemic rats. Hyperammonemia potentiates the actions of tetrahydrodeoxy-corticosterone (THDOC) as a GABAA receptor agonist, allopregnanolone as an NMDA receptor antagonist, and pregnenolone sulfate as an NMDA receptor activation enhancer. Neurosteroids that reduce the pathway (pregnanolone, THDOC, allopregnanolone, DHEAS) may contribute to cognitive impairment in hyperammonemia and hepatic encephalopathy. Pregnenolone would impair cognitive function in hyperammonemia. Neurosteroids that restore the pathway in hyperammonemia (pregnenolone sulfate) could restore cognitive function in hyperammonemia and encephalopathy. PMID:23227932

  2. Gambierol inhibition of voltage-gated potassium channels augments spontaneous Ca2+ oscillations in cerebrocortical neurons.

    Cao, Zhengyu; Cui, Yanjun; Busse, Eric; Mehrotra, Suneet; Rainier, Jon D; Murray, Thomas F

    2014-09-01

    Gambierol is a marine polycyclic ether toxin produced by the marine dinoflagellate Gambierdiscus toxicus and is a member of the ciguatoxin toxin family. Gambierol has been demonstrated to be either a low-efficacy partial agonist/antagonist of voltage-gated sodium channels or a potent blocker of voltage-gated potassium channels (Kvs). Here we examined the influence of gambierol on intact cerebrocortical neurons. We found that gambierol produced both a concentration-dependent augmentation of spontaneous Ca(2+) oscillations, and an inhibition of Kv channel function with similar potencies. In addition, an array of selective as well as universal Kv channel inhibitors mimicked gambierol in augmenting spontaneous Ca(2+) oscillations in cerebrocortical neurons. These data are consistent with a gambierol blockade of Kv channels underlying the observed increase in spontaneous Ca(2+) oscillation frequency. We also found that gambierol produced a robust stimulation of phosphorylation of extracellular signal-regulated kinases 1/2 (ERK1/2). Gambierol-stimulated ERK1/2 activation was dependent on both inotropic [N-methyl-d-aspartate (NMDA)] and type I metabotropic glutamate receptors (mGluRs) inasmuch as MK-801 [NMDA receptor inhibitor; (5S,10R)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate], S-(4)-CGP [S-(4)-carboxyphenylglycine], and MTEP [type I mGluR inhibitors; 3-((2-methyl-4-thiazolyl)ethynyl) pyridine] attenuated the response. In addition, 2-aminoethoxydiphenylborane, an inositol 1,4,5-trisphosphate receptor inhibitor, and U73122 (1-[6-[[(17b)-3-methoxyestra-1,3,5(10)-trien-17-yl]amino]hexyl]-1H-pyrrole-2,5-dione), a phospholipase C inhibitor, both suppressed gambierol-induced ERK1/2 activation, further confirming the role of type I mGluR-mediated signaling in the observed ERK1/2 activation. Finally, we found that gambierol produced a concentration-dependent stimulation of neurite outgrowth that was mimicked by 4-aminopyridine, a universal

  3. Developmental switch in the contribution of presynaptic and postsynaptic NMDA receptors to long-term depression

    Corlew, Rebekah; Wang, Yun; Ghermazien, Haben; Erisir, Alev; Philpot, Benjamin D.

    2007-01-01

    NMDA receptor (NMDAR) activation is required for many forms of learning and memory as well as sensory system receptive field plasticity, yet the relative contribution of pre- and postsynaptic NMDARs over cortical development remains unknown. Here we demonstrate a rapid developmental loss of functional presynaptic NMDARs in the neocortex. Presynaptic NMDARs enhance neurotransmitter release at synapses onto visual cortex pyramidal cells in young mice (< postnatal day 20; P20), but they have no ...

  4. Combined stimulation of IL-2 and 4-1BB receptors augments the antitumor activity of E7 DNA vaccines by increasing Ag-specific CTL responses.

    Kim, Ha; Kwon, Byungsuk; Sin, Jeong-Im

    2013-01-01

    Human papillomavirus (HPV) infection is a major cause of cervical cancer. Here, we investigate whether concurrent therapy using HPV E7 DNA vaccines (pE7) plus IL-2 vs. IL-15 cDNA and anti-4-1BB Abs might augment antitumor activity against established tumors. IL-2 cDNA was slightly better than IL-15 cDNA as a pE7 adjuvant. Co-delivery of pE7+IL-2 cDNA increased tumor cure rates from 7% to 27%, whereas co-delivery of pE7+IL-2 cDNA with anti-4-1BB Abs increased tumor cure rates from 27% to 67% and elicited long-term memory responses. This increased activity was concomitant with increased induction of Ag-specific CTL activity and IFN-γ responses, but not with Ag-specific IgG production. Moreover, the combined stimulation of IL-2 and 4-1BB receptors with rIL-2 and anti-4-1BB Abs resulted in enhanced production of IFN-γ from Ag-specific CD8+ T cells. However, this effect was abolished by treatment with anti-IL-2 Abs and 4-1BB-Fc, suggesting that the observed effect was IL-2- and anti-4-1BB Ab-specific. A similar result was also obtained for Ag-specific CTL activity. Thus, these studies demonstrate that combined stimulation through the IL-2 and 4-1BB receptors augments the Ag-specific CD8+ CTL responses induced by pE7, increasing tumor cure rates and long-term antitumor immune memory. These findings may have implications for the design of DNA-based therapeutic vaccines against cancer. PMID:24391824

  5. Combined stimulation of IL-2 and 4-1BB receptors augments the antitumor activity of E7 DNA vaccines by increasing Ag-specific CTL responses.

    Ha Kim

    Full Text Available Human papillomavirus (HPV infection is a major cause of cervical cancer. Here, we investigate whether concurrent therapy using HPV E7 DNA vaccines (pE7 plus IL-2 vs. IL-15 cDNA and anti-4-1BB Abs might augment antitumor activity against established tumors. IL-2 cDNA was slightly better than IL-15 cDNA as a pE7 adjuvant. Co-delivery of pE7+IL-2 cDNA increased tumor cure rates from 7% to 27%, whereas co-delivery of pE7+IL-2 cDNA with anti-4-1BB Abs increased tumor cure rates from 27% to 67% and elicited long-term memory responses. This increased activity was concomitant with increased induction of Ag-specific CTL activity and IFN-γ responses, but not with Ag-specific IgG production. Moreover, the combined stimulation of IL-2 and 4-1BB receptors with rIL-2 and anti-4-1BB Abs resulted in enhanced production of IFN-γ from Ag-specific CD8+ T cells. However, this effect was abolished by treatment with anti-IL-2 Abs and 4-1BB-Fc, suggesting that the observed effect was IL-2- and anti-4-1BB Ab-specific. A similar result was also obtained for Ag-specific CTL activity. Thus, these studies demonstrate that combined stimulation through the IL-2 and 4-1BB receptors augments the Ag-specific CD8+ CTL responses induced by pE7, increasing tumor cure rates and long-term antitumor immune memory. These findings may have implications for the design of DNA-based therapeutic vaccines against cancer.

  6. Gene-Activated Matrix Comprised of Atelocollagen and Plasmid DNA Encoding BMP4 or Runx2 Promotes Rat Cranial Bone Augmentation.

    Umebayashi, Mayumi; Sumita, Yoshinori; Kawai, Yousuke; Watanabe, Sumiko; Asahina, Izumi

    2015-01-01

    To date, therapeutic method for in vivo gene delivery has not been established on bone engineering though its potential usefulness has been suggested. For clinical applications, an effective condition should be developed to transfer the genes in vivo without any transfection reagents or virus vectors. In this study, to facilitate the clinical setting of this strategy, particularly aimed at atrophic bone repair, we simply investigated whether manufactured gene-activated matrix (GAM) with atelocollagen containing a certain amount of plasmid (p) DNA encoding osteogenic proteins could augment the cranial bone in rat. GAMs were manufactured by mixing 0.02, 0.1, or 1 mg of AcGFP plasmid vectors harboring cDNA of BMP4 (pBMP4) or Runx2 (pRunx2) with 2% bovine atelocollagen and β-tricalcium phosphate granules. Before manufacturing GAMs, to determine the biological activity of generated pDNAs, we confirmed GFP expression and increased level of alkaline phosphatase activities in MC3T3-E1 cells transfected with pBMP4 or pRunx2 during culture. Then, GAMs were lyophilized and transplanted to onlay placement on the cranium. At 2 weeks of transplantation, GFP-expressing cells could be detectable in only GAMs containing 1 mg of AcGFP plasmid vectors. Then, at 4 weeks, significant bone formation was recognized in GAMs containing 1 mg of pDNAs encoding BMP4 or Runx2 but not in 0.02 or 0.1 mg of GAMs. These newly formed bone tissues surrounded by osteocalcin-stained area were augmented markedly until 8 weeks after transplantation. In contrast, minimal bone formation was observed in GAMs without harboring cDNA of osteogenic proteins. Meanwhile, when GAMs were transplanted to the cranial bone defect, bone formation was detectable in specimens containing 1 mg of pBMP4 or pRunx2 at 8 weeks as well. Thus, atelocollagen-based GAM reliably could form the engineered bone even for the vertical augmentation when containing a certain amount of plasmid vectors encoding osteogenic

  7. INFLUENCE OF NMDA AND NON-NMDA ANTAGONISTS ON ACUTE AND INFLAMMATORY PAIN IN THE TRIGEMINAL TERRITORY

    Piovesan, Elcio Juliato; Randunz, Vitor; Utiumi, Marco; Lange, Marcos Cristiano; Kowacs, Pedro André; Mulinari, Rogério Andrade; Oshinsky, Michael; Vital, Maria; Sereniki, Adriana; Fernandes, Artur Furlaneto; Silva, Lucas Leite e; Werneck, Lineu César

    2016-01-01

    NMDA and non-NMDA receptors are involved in spinal transmission of nociceptive information in physiological and pathological conditions. Our objective was to study the influence of NMDA and non-NMDA receptor antagonists on pain control in the trigeminal system using a formalin-induced orofacial pain model. Motor performance was also evaluated. Male Rattus norvegicus were pre-treated with topiramate (T) (n=8), memantine (M) (n=8), divalproex (D) (n=8) or isotonic saline solution (ISS) (n=10) intraperitoneally 30 minutes before the formalin test. Formalin 2.5% was injected into the right upper lip (V2 branch) and induced two phases: phase I (early or neurogenic) (0–3 min) and phase II (late or inflammatory) (12–30 min). For motor behavior performance we used the open-field test and measured latency to movement onset, locomotion and rearing frequencies, and immobility time. Pre-treatment of animals with M and D only attenuated nociceptive formalin behavior for phase II. T increased locomotion and rearing frequencies and reduced immobility time. Treatment with M increased immobility time and with D reduced locomotion frequency. Our results showed that the NMDA antagonist (M) is more potent than the non-NMDA antagonists (D and T) in the control of pain in the inflammatory phase. The non-NMDA topiramate improved motor performance more than did D and M, probably because T has more anxiolytic properties. PMID:19099122

  8. AUGMENTATION-RELATED BRAIN PLASTICITY

    Giovanni eDi Pino

    2014-06-01

    Full Text Available Today, the anthropomorphism of the tools and the development of neural interfaces require reconsidering the concept of human-tools interaction in the framework of human augmentation. This review analyzes the plastic process that the brain undergoes when it comes into contact with augmenting artificial sensors and effectors and, on the other hand, the changes that the use of external augmenting devices produces in the brain.Hitherto, few studies investigated the neural correlates of augmentation, but clues on it can be borrowed from logically-related paradigms: sensorimotor training, cognitive enhancement, cross-modal plasticity, sensorimotor functional substitution, use and embodiment of tools.Augmentation modifies function and structure of a number of areas, i.e. primary sensory cortices shape their receptive fields to become sensitive to novel inputs. Motor areas adapt the neuroprosthesis representation firing-rate to refine kinematics. As for normal motor outputs, the learning process recruits motor and premotor cortices and the acquisition of proficiency decreases attentional recruitment, focuses the activity on sensorimotor areas and increases the basal ganglia drive on the cortex. Augmentation deeply relies on the frontoparietal network. In particular, premotor cortex is involved in learning the control of an external effector and owns the tool motor representation, while the intraparietal sulcus extracts its visual features. In these areas, multisensory integration neurons enlarge their receptive fields to embody supernumerary limbs. For operating an anthropomorphic neuroprosthesis, the mirror system is required to understand the meaning of the action, the cerebellum for the formation of its internal model and the insula for its interoception. In conclusion, anthropomorphic sensorized devices can provide the critical sensory afferences to evolve the exploitation of tools through their embodiment, reshaping the body representation and the

  9. Augmentation-related brain plasticity

    Di Pino, Giovanni; Maravita, Angelo; Zollo, Loredana; Guglielmelli, Eugenio; Di Lazzaro, Vincenzo

    2014-01-01

    Today, the anthropomorphism of the tools and the development of neural interfaces require reconsidering the concept of human-tools interaction in the framework of human augmentation. This review analyses the plastic process that the brain undergoes when it comes into contact with augmenting artificial sensors and effectors and, on the other hand, the changes that the use of external augmenting devices produces in the brain. Hitherto, few studies investigated the neural correlates of augmentation, but clues on it can be borrowed from logically-related paradigms: sensorimotor training, cognitive enhancement, cross-modal plasticity, sensorimotor functional substitution, use and embodiment of tools. Augmentation modifies function and structure of a number of areas, i.e., primary sensory cortices shape their receptive fields to become sensitive to novel inputs. Motor areas adapt the neuroprosthesis representation firing-rate to refine kinematics. As for normal motor outputs, the learning process recruits motor and premotor cortices and the acquisition of proficiency decreases attentional recruitment, focuses the activity on sensorimotor areas and increases the basal ganglia drive on the cortex. Augmentation deeply relies on the frontoparietal network. In particular, premotor cortex is involved in learning the control of an external effector and owns the tool motor representation, while the intraparietal sulcus extracts its visual features. In these areas, multisensory integration neurons enlarge their receptive fields to embody supernumerary limbs. For operating an anthropomorphic neuroprosthesis, the mirror system is required to understand the meaning of the action, the cerebellum for the formation of its internal model and the insula for its interoception. In conclusion, anthropomorphic sensorized devices can provide the critical sensory afferences to evolve the exploitation of tools through their embodiment, reshaping the body representation and the sense of the self

  10. Confronting an augmented reality

    Munnerley, Danny; Bacon, Matt; Wilson, Anna,; Steele, James; Hedberg, John; Fitzgerald, Robert

    2012-01-01

    How can educators make use of augmented reality technologies and practices to enhance learning and why would we want to embrace such technologies anyway? How can an augmented reality help a learner confront, interpret and ultimately comprehend reality itself ? In this article, we seek to initiate a discussion that focuses on these questions, and suggest that they be used as drivers for research into effective educational applications of augmented reality. We discuss how multi-modal, sensorial...

  11. Mobile Augmented Reality Applications

    Prochazka, David; Stencl, Michael; Popelka, Ondrej; Stastny, Jiri

    2011-01-01

    Augmented reality have undergone considerable improvement in past years. Many special techniques and hardware devices were developed, but the crucial breakthrough came with the spread of intelligent mobile phones. This enabled mass spread of augmented reality applications. However mobile devices have limited hardware capabilities, which narrows down the methods usable for scene analysis. In this article we propose an augmented reality application which is using cloud computing to enable using...

  12. Mobile Augmented Reality Applications

    Prochazka, David; Popelka, Ondrej; Stastny, Jiri

    2011-01-01

    Augmented reality have undergone considerable improvement in past years. Many special techniques and hardware devices were developed, but the crucial breakthrough came with the spread of intelligent mobile phones. This enabled mass spread of augmented reality applications. However mobile devices have limited hardware capabilities, which narrows down the methods usable for scene analysis. In this article we propose an augmented reality application which is using cloud computing to enable using of more complex computational methods such as neural networks. Our goal is to create an affordable augmented reality application suitable which will help car designers in by 'virtualizing' car modifications.

  13. Stress-induced changes of hippocampal NMDA receptors: modulation by duloxetine treatment.

    Francesca Calabrese

    Full Text Available It is now well established that the glutamatergic system contributes to the pathophysiology of depression. Exposure to stress, a major precipitating factor for depression, enhances glutamate release that can contribute to structural abnormalities observed in the brain of depressed subjects. On the other hand, it has been demonstrated that NMDA antagonists, like ketamine, exert an antidepressant effect at preclinical and clinical levels. On these bases, the purpose of our study was to investigate whether chronic mild stress is associated with specific alterations of the NMDA receptor complex, in adult rats, and to establish whether concomitant antidepressant treatment could normalize such deficits. We found that chronic stress increases the expression of the obligatory GluN1 subunit, as well as of the accessory subunits GluN2A and GluN2B at transcriptional and translational levels, particularly in the ventral hippocampus. Concomitant treatment with the antidepressant duloxetine was able to normalize the increase of glutamatergic receptor subunit expression, and correct the changes in receptor phosphorylation produced by stress exposure. Our data suggest that prolonged stress, a condition that has etiologic relevance for depression, may enhance glutamate activity through post-synaptic mechanisms, by regulating NMDA receptors, and that antidepressants may in part normalize such changes. Our results provide support to the notion that antidepressants may exert their activity in the long-term also via modulation of the glutamatergic synapse.

  14. Osteosynthesis-screw augmentation by ultrasound-activated biopolymer - an ovine in vivo study assessing biocompatibility and bone-to-implant contact

    Neumann, Hanjo; Breer, Stefan; Reimers, Nils; Kasch, Richard; Schulz, Arndt-Peter; Kienast, Benjamin

    2015-01-01

    Objectives Screw fixation and fragment anchoring in osteoporotic bones is often difficult. Problems like the cut out phenomenon and implant migration in osteoporotic bones have been reported. One possibility of improving the anchoring force of screws is augmentation of the screw. Cement-augmented screws in spinal surgery could exhibit a better anchoring in osteoporotic bones. Methods The purpose of this study was to examine the effect of screw augmentation using a resorbable polymer. Ultrasou...

  15. Adaptive Augmented Reality: Plasticity of Augmentations

    Ghouaiel, Nehla; Cieutat, Jean-Marc; Jessel, Jean-Pierre

    2014-01-01

    International audience An augmented reality system is used to complete the real world with virtual objects (computer generated) so they seem to coexist in the same space as the real world. The concept of plasticity [4][5] was first introduced for Human Computer Interaction (HCI). It denotes the ability of an HCI interface to fit the context of use defined by the user, the environment and the platform. We believe that plasticity is a very important notion in the domain of augmented reality....

  16. NMDA receptors in the basolateral amygdala and gustatory neophobia

    Figueroa-Guzmán, Yazmín; Reilly, Steve

    2008-01-01

    The attenuation of gustatory neophobia occurs during repeated exposures to an initially novel taste solution that is increasingly perceived as safe and familiar. The present study examined whether NMDA receptors in the basolateral region of the amygdala (BLA) are involved in this important behavioral phenomenon. The results, which show that the attenuation, but not initial occurrence, of gustatory neophobia is dependent upon NMDA receptors in the BLA, are discussed with reference to a similar...

  17. NMDA receptors and fear extinction: implications for cognitive behavioral therapy

    Davis, Michael

    2011-01-01

    Based primarily on studies that employ Pavlovian fear conditioning, extinction of conditioned fear has been found to be mediated by N-methyl-D-aspartate (NMDA) receptors in the amygdala and medial prefrontal cortex. This led to the discovery that an NMDA partial agonist, D-cycloserine, could facilitate fear extinction when given systemically or locally into the amygdala. Because many forms of cognitive behavioral therapy depend on fear extinction, this led to the successful use of D-cycloseri...

  18. Equating of Augmented Subscores

    Sinharay, Sandip; Haberman, Shelby J.

    2011-01-01

    Recently, there has been an increasing level of interest in subscores for their potential diagnostic value. Haberman (2008b) suggested reporting an augmented subscore that is a linear combination of a subscore and the total score. Sinharay and Haberman (2008) and Sinharay (2010) showed that augmented subscores often lead to more accurate…

  19. Confronting an Augmented Reality

    Munnerley, Danny; Bacon, Matt; Wilson, Anna; Steele, James; Hedberg, John; Fitzgerald, Robert

    2012-01-01

    How can educators make use of augmented reality technologies and practices to enhance learning and why would we want to embrace such technologies anyway? How can an augmented reality help a learner confront, interpret and ultimately comprehend reality itself ? In this article, we seek to initiate a discussion that focuses on these questions, and…

  20. AUGMENTATION OF IMMUNE FUNCTIONS AND AUTOLOGOUS TUMOR-KILLING ACTIVITY BY KAPPA-SELENOCARRAGEENAN IN MICE BEARING SARCOMA 180

    Wei Hulai; Jia Zhengping; Zhao Huishun

    1998-01-01

    Objective: To study the enhancement of the immune functions and autologous tumor-killing (ATK) activity by kappa-selenocarrageenan (KSC) in mice bearing sarcoma 180. Methods: To measure the effects of KSC and/or Cyclophosphamide (Cy) on natural killer (NK) activity,lymphokine-activated killer (LAK) activity, the production of interleukin-2 (IL-2), ATK activity and the growth of sarcoma 180 (S180). Results: KSC promoted NK activity, LAK activity and ATK activity in vivo, increased IL-2 production at 40 mg/kg/d×9d. It also enhanced the antitumor action of Cy (20 mg/kg/d×9d) and offset the inhibition of Cy on immunocopetent cells. The ATK activity in splenocytes of S180-bearing mice could be induced and increased by recombinant interleukin-2 (rIL-2) in vitro. Conclusion: KSC has an up- regulating effect on the immune functions and ATK activity in tumorbearing mice. It can be used as a biological response modifier (BRM) in cancer biotherapy.

  1. Combined stimulation of the glycine and polyamine sites of the NMDA receptor attenuates NMDA blockade-induced learning deficits of rats in a 14-unit T-maze.

    Meyer, R C; Knox, J; Purwin, D A; Spangler, E L; Ingram, D K

    1998-02-01

    The present study examined the effects of multi-site activation of the glycine and polyamine sites of the NMDA receptor on memory formation in rats learning a 14-unit T-maze task. The competitive NMDA receptor antagonist, (+/-)-3-(2-carboxypiperazine-4-yl)-propyl-1-phosphonic acid (CPP, 9 mg/kg), was used to impair learning. The objectives were two-fold: (1) to investigate the effects of independent stimulation of the strychnine-insensitive glycine site or the polyamine site; (2) to investigate the effects of simultaneous activation of these two sites. Male, Fischer-344 rats were pretrained to a criterion of 13 out of 15 shock avoidances in a straight runway, and 24 h later were trained in a 14-unit T-maze that also required shock avoidance. Prior to maze training, rats received intraperitoneal (i.p.) injections of saline, saline plus CPP, CPP plus the glycine agonist, D-cycloserine (DCS, 30 or 40 mg/kg), CPP plus the polyamine agonist, spermine (SPM, 2.5 or 5 mg/kg), or CPP plus a combination of DCS (7.5 mg/kg) and SPM (0.625 mg/kg). Individual administration of either DCS or SPM attenuated the CPP-induced maze learning impairment in a dose-dependent manner. However, the combined treatment with both DCS and SPM completely reversed the learning deficit at doses five-fold less than either drug given alone. These findings provide additional evidence that the glycine and polyamine modulatory sites of the NMDA receptor are involved in memory formation. Furthermore, the potent synergistic effect resulting from combined activation of the glycine and polyamine sites would suggest a stronger interaction between these two sites than previously considered, and might provide new therapeutic approaches for enhancing glutamatergic function. PMID:9498733

  2. GluN3A promotes NMDA spiking by enhancing synaptic transmission in Huntington's disease models.

    Mahfooz, Kashif; Marco, Sonia; Martínez-Turrillas, Rebeca; Raja, Mathan K; Pérez-Otaño, Isabel; Wesseling, John F

    2016-09-01

    Age-inappropriate expression of juvenile NMDA receptors (NMDARs) containing GluN3A subunits has been linked to synapse loss and death of spiny projection neurons of the striatum (SPNs) in Huntington's disease (HD). Here we show that suppressing GluN3A expression prevents a multivariate synaptic transmission phenotype that precedes morphological signs at early prodromal stages. We start by confirming that afferent fiber stimulation elicits larger synaptic responses mediated by both AMPA receptors and NMDARs in SPNs in the YAC128 mouse model of HD. We then show that the enhancement mediated by both is fully prevented by suppressing GluN3A expression. Strong fiber-stimulation unexpectedly elicited robust NMDAR-mediated electrogenic events (termed "upstates" or "NMDA spikes"), and the effective threshold for induction was more than 2-fold lower in YAC128 SPNs because of the enhanced synaptic transmission. The threshold could be restored to control levels by suppressing GluN3A expression or by applying the weak NMDAR blocker memantine. However, the threshold was not affected by preventing glutamate spillover from synaptic clefts. Instead, long-lasting NMDAR responses interpreted previously as activation of extrasynaptic receptors by spilled-over glutamate were caused by NMDA spikes occurring in voltage clamp mode as escape potentials. Together, the results implicate GluN3A reactivation in a broad spectrum of early-stage synaptic transmission deficits in YAC128 mice; question the current concept that NMDAR mislocalization is the pathological trigger in HD; and introduce NMDA spikes as a new candidate mechanism for coupling NMDARs to neurodegeneration. PMID:27072890

  3. NMDA antagonists exert distinct effects in experimental organophosphate or carbamate poisoning in mice

    Organophosphate (OP) and carbamate acetylcholinesterase (AChE) inhibitors produce seizures and lethality in mammals. Anticonvulsant and neuroprotective properties of N-methyl-D-aspartate (NMDA) antagonists encourage the investigation of their effects in AChE inhibitor-induced poisonings. In the present study, the effects of dizocilpine (MK-801, 1 mg/kg) or 3-((RS)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP, 10 mg/kg), alone or combined with muscarinic antagonist atropine (1.8 mg/kg), on convulsant and lethal properties of an OP pesticide dichlorvos or a carbamate drug physostigmine, were studied in mice. Both dichlorvos and physostigmine induced dose-dependent seizure activity and lethality. Atropine did not prevent the occurrence of convulsions but decreased the lethal effects of both dichlorvos and physostigmine. MK-801 or CPP blocked or attenuated, respectively, dichlorvos-induced convulsions. Contrariwise, NMDA antagonists had no effect in physostigmine-induced seizures or lethality produced by dichlorvos or physostigmine. Concurrent pretreatment with atropine and either MK-801 or CPP blocked or alleviated seizures produced by dichlorvos, but not by physostigmine. Both MK-801 and CPP co-administered with atropine enhanced its antilethal effects in both dichlorvos and physostigmine poisoning. In both saline- and AChE inhibitor-treated mice, no interaction of the investigated antidotes with brain cholinesterase was found. The data indicate that both muscarinic ACh and NMDA receptor-mediated mechanisms contribute to the acute toxicity of AChE inhibitors, and NMDA receptors seem critical to OP-induced seizures

  4. Involvement of hippocampal NMDA receptors in retention of shuttle avoidance conditioning in rats

    Roesler R.

    1998-01-01

    Full Text Available The purpose of this research was to evaluate the role of hippocampal N-methyl-D-aspartate (NMDA receptors in acquisition and consolidation of memory during shuttle avoidance conditioning in rats. Adult male Wistar rats were surgically implanted with cannulae aimed at the CA1 area of the dorsal hippocampus. After recovery from surgery, animals were trained and tested in a shuttle avoidance apparatus (30 trials, 0.5-mA footshock, 24-h training-test interval. Immediately before or immediately after training, animals received a bilateral intrahippocampal 0.5-µl infusion containing 5.0 µg of the NMDA competitive receptor antagonist aminophosphonopentanoic acid (AP5 or vehicle (phosphate-buffered saline, pH 7.4. Infusion duration was 2 min per side. Pre-training infusion of AP5 impaired retention test performance (mean ± SEM number of conditioned responses (CRs during retention test session was 16.47 ± 1.78 in the vehicle group and 9.93 ± 1.59 in the AP5 group; P<0.05. Post-training infusion of AP5 did not affect retention (mean ± SEM number of conditioned responses during retention test session was 18.46 ± 1.94 in the vehicle group and 20.42 ± 2.38 in the AP5 group; P>0.10. This impairment could not be attributed to an effect on acquisition, motor activity or footshock sensitivity since AP5 affected neither training session performance measured by the number of CRs nor the number of intertrial crossings during the training session. These data suggest that NMDA receptors in the hippocampus are critical for retention of shuttle avoidance conditioning, in agreement with previous evidence showing a role of NMDA receptors in fear memory.

  5. Lactate promotes plasticity gene expression by potentiating NMDA signaling in neurons

    Yang, Jiangyan

    2014-07-28

    L-lactate is a product of aerobic glycolysis that can be used by neurons as an energy substrate. Here we report that in neurons L-lactate stimulates the expression of synaptic plasticity-related genes such as Arc, c-Fos, and Zif268 through a mechanism involving NMDA receptor activity and its downstream signaling cascade Erk1/2. L-lactate potentiates NMDA receptor-mediated currents and the ensuing increase in intracellular calcium. In parallel to this, L-lactate increases intracellular levels of NADH, thereby modulating the redox state of neurons. NADH mimics all of the effects of L-lactate on NMDA signaling, pointing to NADH increase as a primary mediator of L-lactate effects. The induction of plasticity genes is observed both in mouse primary neurons in culture and in vivo in the mouse sensory-motor cortex. These results provide insights for the understanding of the molecular mechanisms underlying the critical role of astrocyte-derived L-lactate in long-term memory and long-term potentiation in vivo. This set of data reveals a previously unidentified action of L-lactate as a signaling molecule for neuronal plasticity.

  6. Methylphenidate enhances NMDA-receptor response in medial prefrontal cortex via sigma-1 receptor: a novel mechanism for methylphenidate action.

    Chun-Lei Zhang

    Full Text Available Methylphenidate (MPH, commercially called Ritalin or Concerta, has been widely used as a drug for Attention Deficit Hyperactivity Disorder (ADHD. Noteworthily, growing numbers of young people using prescribed MPH improperly for pleasurable enhancement, take high risk of addiction. Thus, understanding the mechanism underlying high level of MPH action in the brain becomes an important goal nowadays. As a blocker of catecholamine transporters, its therapeutic effect is explained as being due to proper modulation of D1 and α2A receptor. Here we showed that higher dose of MPH facilitates NMDA-receptor mediated synaptic transmission via a catecholamine-independent mechanism, in layer V∼VI pyramidal cells of the rat medial prefrontal cortex (PFC. To indicate its postsynaptic action, we next found that MPH facilitates NMDA-induced current and such facilitation could be blocked by σ1 but not D1/5 and α2 receptor antagonists. And this MPH eliciting enhancement of NMDA-receptor activity involves PLC, PKC and IP3 receptor mediated intracellular Ca(2+ increase, but does not require PKA and extracellular Ca(2+ influx. Our additional pharmacological studies confirmed that higher dose of MPH increases locomotor activity via interacting with σ1 receptor. Together, the present study demonstrates for the first time that MPH facilitates NMDA-receptor mediated synaptic transmission via σ1 receptor, and such facilitation requires PLC/IP3/PKC signaling pathway. This novel mechanism possibly explains the underlying mechanism for MPH induced addictive potential and other psychiatric side effects.

  7. Methylphenidate enhances NMDA-receptor response in medial prefrontal cortex via sigma-1 receptor: a novel mechanism for methylphenidate action.

    Zhang, Chun-Lei; Feng, Ze-Jun; Liu, Yue; Ji, Xiao-Hua; Peng, Ji-Yun; Zhang, Xue-Han; Zhen, Xue-Chu; Li, Bao-Ming

    2012-01-01

    Methylphenidate (MPH), commercially called Ritalin or Concerta, has been widely used as a drug for Attention Deficit Hyperactivity Disorder (ADHD). Noteworthily, growing numbers of young people using prescribed MPH improperly for pleasurable enhancement, take high risk of addiction. Thus, understanding the mechanism underlying high level of MPH action in the brain becomes an important goal nowadays. As a blocker of catecholamine transporters, its therapeutic effect is explained as being due to proper modulation of D1 and α2A receptor. Here we showed that higher dose of MPH facilitates NMDA-receptor mediated synaptic transmission via a catecholamine-independent mechanism, in layer V∼VI pyramidal cells of the rat medial prefrontal cortex (PFC). To indicate its postsynaptic action, we next found that MPH facilitates NMDA-induced current and such facilitation could be blocked by σ1 but not D1/5 and α2 receptor antagonists. And this MPH eliciting enhancement of NMDA-receptor activity involves PLC, PKC and IP3 receptor mediated intracellular Ca(2+) increase, but does not require PKA and extracellular Ca(2+) influx. Our additional pharmacological studies confirmed that higher dose of MPH increases locomotor activity via interacting with σ1 receptor. Together, the present study demonstrates for the first time that MPH facilitates NMDA-receptor mediated synaptic transmission via σ1 receptor, and such facilitation requires PLC/IP3/PKC signaling pathway. This novel mechanism possibly explains the underlying mechanism for MPH induced addictive potential and other psychiatric side effects. PMID:23284812

  8. Role of Glycogen Synthase Kinase-3β in APP Hyperphosphorylation Induced by NMDA Stimulation in Cortical Neurons

    Xanthi Antoniou

    2010-01-01

    Full Text Available The phosphorylation of Amyloid Precursor Protein (APP at Thr668 plays a key role in APP metabolism that is highly relevant to AD. The c-Jun-N-terminal kinase (JNK, glycogen synthase kinase-3β (GSK-3β and cyclin-dependent kinase 5 (Cdk5 can all be responsible for this phosphorylation. These kinases are activated by excitotoxic stimuli fundamental hallmarks of AD. The exposure of cortical neurons to a high dose of NMDA (100 μM for 30’-45’ led to an increase of P-APP Thr668. During NMDA stimulation APP hyperphosphorylation has to be assigned to GSK-3β activity, since addition of L803-mts, a substrate competitive inhibitor of GSK-3β reduced APP phosphorylation induced by NMDA. On the contrary, inhibition of JNK and Cdk5 with D-JNKI1 and Roscovitine respectively did not prevent NMDA-induced P-APP increase. These data show a tight connection, in excitotoxic conditions, between APP metabolism and the GSK-3β signaling pathway.

  9. Retrieval-induced NMDA receptor-dependent Arc expression in two models of cocaine-cue memory.

    Alaghband, Yasaman; O'Dell, Steven J; Azarnia, Siavash; Khalaj, Anna J; Guzowski, John F; Marshall, John F

    2014-12-01

    The association of environmental cues with drugs of abuse results in persistent drug-cue memories. These memories contribute significantly to relapse among addicts. While conditioned place preference (CPP) is a well-established paradigm frequently used to examine the modulation of drug-cue memories, very few studies have used the non-preference-based model conditioned activity (CA) for this purpose. Here, we used both experimental approaches to investigate the neural substrates of cocaine-cue memories. First, we directly compared, in a consistent setting, the involvement of cortical and subcortical brain regions in cocaine-cue memory retrieval by quantifying activity-regulated cytoskeletal-associated (Arc) protein expression in both the CPP and CA models. Second, because NMDA receptor activation is required for Arc expression, we investigated the NMDA receptor dependency of memory persistence using the CA model. In both the CPP and CA models, drug-paired animals showed significant increases in Arc immunoreactivity in regions of the frontal cortex and amygdala compared to unpaired controls. Additionally, administration of a NMDA receptor antagonist (MK-801 or memantine) immediately after cocaine-CA memory reactivation impaired the subsequent conditioned locomotion associated with the cocaine-paired environment. The enhanced Arc expression evident in a subset of corticolimbic regions after retrieval of a cocaine-context memory, observed in both the CPP and CA paradigms, likely signifies that these regions: (i) are activated during retrieval of these memories irrespective of preference-based decisions, and (ii) undergo neuroplasticity in order to update information about cues previously associated with cocaine. This study also establishes the involvement of NMDA receptors in maintaining memories established using the CA model, a characteristic previously demonstrated using CPP. Overall, these results demonstrate the utility of the CA model for studies of cocaine

  10. Comparison of anticonvulsant effect of competitive non-NMDA and noncompetitive NMDA receptor antagonists in adult rats

    Lojková, Denisa; Živanovič, Dragana; Mareš, Pavel

    -, - (2005), s. 160-160. [Conference of the Czech Neuroscience Society /5./, The Annual Meeting of the Network of European Neuroscience Institutes. 19.11.2005-21.11.2005, Prague] R&D Projects: GA MŠk(CZ) LC554 Institutional research plan: CEZ:AV0Z50110509 Keywords : anticonvulsant effect * non-NMDA- receptor antagonist * NMDA receptor antagonist * rats Subject RIV: ED - Physiology

  11. miR-155 augments CD8+ T-cell antitumor activity in lymphoreplete hosts by enhancing responsiveness to homeostatic γc cytokines

    Ji, Yun; Wrzesinski, Claudia; Yu, Zhiya; Hu, Jinhui; Gautam, Sanjivan; Hawk, Nga V.; Telford, William G.; Palmer, Douglas C.; Franco, Zulmarie; Sukumar, Madhusudhanan; Roychoudhuri, Rahul; Clever, David; Klebanoff, Christopher A.; Surh, Charles D.; Waldmann, Thomas A.; Restifo, Nicholas P.; Gattinoni, Luca

    2015-01-01

    Lymphodepleting regimens are used before adoptive immunotherapy to augment the antitumor efficacy of transferred T cells by removing endogenous homeostatic “cytokine sinks.” These conditioning modalities, however, are often associated with severe toxicities. We found that microRNA-155 (miR-155) enabled tumor-specific CD8+ T cells to mediate profound antitumor responses in lymphoreplete hosts that were not potentiated by immune-ablation. miR-155 enhanced T-cell responsiveness to limited amounts of homeostatic γc cytokines, resulting in delayed cellular contraction and sustained cytokine production. miR-155 restrained the expression of the inositol 5-phosphatase Ship1, an inhibitor of the serine-threonine protein kinase Akt, and multiple negative regulators of signal transducer and activator of transcription 5 (Stat5), including suppressor of cytokine signaling 1 (Socs1) and the protein tyrosine phosphatase Ptpn2. Expression of constitutively active Stat5a recapitulated the survival advantages conferred by miR-155, whereas constitutive Akt activation promoted sustained effector functions. Our results indicate that overexpression of miR-155 in tumor-specific T cells can be used to increase the effectiveness of adoptive immunotherapies in a cell-intrinsic manner without the need for life-threatening, lymphodepleting maneuvers. PMID:25548153

  12. Ligation of FcγR Alters Phagosomal Processing of Protein via Augmentation of NADPH Oxidase Activity.

    Balce, Dale R; Rybicka, Joanna M; Greene, Catherine J; Ewanchuk, Benjamin W; Yates, Robin M

    2016-07-01

    Proteolysis and the reduction of disulfides, both major components of protein degradation, are profoundly influenced by phagosomal redox conditions in macrophages. We evaluated the activation of phagocytic receptors that are known to influence activation of the phagocyte NADPH oxidase (NOX2), and its effect on phagosomal protein degradation. Population-based and single phagosome analyses of phagosomal chemistries in murine macrophages revealed that activation of NOX2 via the Fcγ receptor (FcγR) during phagocytosis decreased rates of proteolysis and disulfide reduction. Immunoglobulin G (IgG)-stimulated reactive oxygen species (ROS) production and the inhibition of phagosomal proteolysis and disulfide reduction were dependent on NOX2, FcγR and protein kinase C (PKC)/spleen tyrosine kinase (Syk) signaling. In contrast, low levels of ROS production were observed following the phagocytosis of unopsonized beads, which resulted in higher rates of phagosomal proteolysis and disulfide reduction. Phagosomes displayed autonomy with respect to FcγR-mediated differences in NOX2 activation and proteolysis, as phagosomes containing unopsonized cargo retained low NOX2 activation and high proteolysis even in the presence of phagosomes containing IgG-opsonized cargo in the same macrophage. These results show that opsonization of phagocytic cargo results in vastly different phagosomal processing of proteins through the FcγR-triggered, PKC/Syk-dependent local assembly and activation of NOX2. PMID:27020146

  13. Control Augmented Structural Synthesis

    Lust, Robert V.; Schmit, Lucien A.

    1988-01-01

    A methodology for control augmented structural synthesis is proposed for a class of structures which can be modeled as an assemblage of frame and/or truss elements. It is assumed that both the plant (structure) and the active control system dynamics can be adequately represented with a linear model. The structural sizing variables, active control system feedback gains and nonstructural lumped masses are treated simultaneously as independent design variables. Design constraints are imposed on static and dynamic displacements, static stresses, actuator forces and natural frequencies to ensure acceptable system behavior. Multiple static and dynamic loading conditions are considered. Side constraints imposed on the design variables protect against the generation of unrealizable designs. While the proposed approach is fundamentally more general, here the methodology is developed and demonstrated for the case where: (1) the dynamic loading is harmonic and thus the steady state response is of primary interest; (2) direct output feedback is used for the control system model; and (3) the actuators and sensors are collocated.

  14. Negative Allosteric Modulators Selective for The NR2B Subtype of The NMDA Receptor Impair Cognition in Multiple Domains.

    Weed, Michael R; Bookbinder, Mark; Polino, Joseph; Keavy, Deborah; Cardinal, Rudolf N; Simmermacher-Mayer, Jean; Cometa, Fu-ni L; King, Dalton; Thangathirupathy, Srinivasan; Macor, John E; Bristow, Linda J

    2016-01-01

    Antidepressant activity of N-methyl-D-aspartate (NMDA) receptor antagonists and negative allosteric modulators (NAMs) has led to increased investigation of their behavioral pharmacology. NMDA antagonists, such as ketamine, impair cognition in multiple species and in multiple cognitive domains. However, studies with NR2B subtype-selective NAMs have reported mixed results in rodents including increased impulsivity, no effect on cognition, impairment or even improvement of some cognitive tasks. To date, the effects of NR2B-selective NAMs on cognitive tests have not been reported in nonhuman primates. The current study evaluated two selective NR2B NAMs, CP101,606 and BMT-108908, along with the nonselective NMDA antagonists, ketamine and AZD6765, in the nonhuman primate Cambridge Neuropsychological Test Automated Battery (CANTAB) list-based delayed match to sample (list-DMS) task. Ketamine and the two NMDA NR2B NAMs produced selective impairments in memory in the list-DMS task. AZD6765 impaired performance in a non-specific manner. In a separate cohort, CP101,606 impaired performance of the nonhuman primate CANTAB visuo-spatial Paired Associates Learning (vsPAL) task with a selective impairment at more difficult conditions. The results of these studies clearly show that systemic administration of a selective NR2B NAM can cause transient cognitive impairment in multiple cognitive domains. PMID:26105137

  15. Magnetic resonance analysis of the effects of acute ammonia intoxication on rat brain. Role of NMDA receptors.

    Cauli, Omar; López-Larrubia, Pilar; Rodrigues, Tiago B; Cerdán, Sebastián; Felipo, Vicente

    2007-11-01

    Acute ammonia intoxication leads to rapid death, which is prevented by blocking N-methyl-d-aspartate (NMDA) receptors. The subsequent mechanisms leading to death remain unclear. Brain edema seems an important step. The aim of this work was to study the effects of acute ammonia intoxication on different cerebral parameters in vivo using magnetic resonance and to assess which effects are mediated by NMDA receptors activation. To assess edema induction, we injected rats with ammonium acetate and measured apparent diffusion coefficient (ADC) in 16 brain areas. We also analyzed the effects on T1, T2, and T2* maps and whether these effects are prevented by blocking NMDA receptors. The effects of acute ammonia intoxication are different in different brain areas. T1 relaxation time is reduced in eight areas. T2 relaxation time is reduced only in ventral thalamus and globus pallidus. ADC values increased in hippocampus, caudate-putamen, substantia nigra and cerebellar cortex, reflecting vasogenic edema. ADC decreased in hypothalamus, reflecting cytotoxic edema. Myo-inositol increased in cerebellum and substantia nigra, reflecting vasogenic edema. N-acetyl-aspartate decreased in cerebellum, reflecting neuronal damage. Changes in N-acetyl-aspartate, T1 and T2 are prevented by blocking NMDA receptors with MK-801 while changes in ADC or myo-inositol (induction of edema) are not. PMID:17727627

  16. Partial involvement of NMDA receptors and glial cells in the nociceptive behaviors induced by intrathecally administered histamine.

    Mizoguchi, Hirokazu; Komatsu, Takaaki; Iwata, Yoko; Watanabe, Chizuko; Watanabe, Hiroyuki; Orito, Tohru; Katsuyama, Soh; Yonezawa, Akihiko; Onodera, Kenji; Sakurada, Tsukasa; Sakurada, Shinobu

    2011-05-16

    The involvement of spinal glial cells in the nociceptive behaviors induced by 800 pmol of histamine was determined in mice. Histamine at 800 pmol injected intrathecally (i.t.) produced nociceptive behaviors, consisting of scratching, biting and licking. The nociceptive behaviors induced by histamine were significantly suppressed by i.t. co-administration with tachykinin NK(1) receptor antagonist CP99,994 or competitive antagonist for N-methyl-d-aspartate (NMDA) receptor d-(-)-2-amino-5-phosphonovaleric acid (d-APV). The i.t. pretreatment with the glial cell inhibitor dl-fluorocitric acid or minocycline failed to affect the nociceptive behaviors induced by histamine. However, in mice pretreated i.t. with dl-fluorocitric acid or minocycline, the nociceptive behaviors induced by histamine were significantly suppressed by i.t. co-administration with CP99,994 but not d-APV. In Western blot analysis using lumbar spinal cords, i.t. treatment with 800 pmol of histamine increased the phosphorylation of the NR1 subunit of NMDA receptors. The increased phosphorylation of the NR1 subunit of NMDA receptors by histamine was abolished by i.t. pretreatment with dl-fluorocitric acid or minocycline. The present results suggest that histamine at 800 pmol elicits nociceptive behaviors through activation of the neuronal NK(1) receptor and the NR1 subunit-containing NMDA receptors on glial cells in the spinal cord. PMID:21352890

  17. Augmented reality: a review.

    Berryman, Donna R

    2012-01-01

    Augmented reality is a technology that overlays digital information on objects or places in the real world for the purpose of enhancing the user experience. It is not virtual reality, that is, the technology that creates a totally digital or computer created environment. Augmented reality, with its ability to combine reality and digital information, is being studied and implemented in medicine, marketing, museums, fashion, and numerous other areas. This article presents an overview of augmented reality, discussing what it is, how it works, its current implementations, and its potential impact on libraries. PMID:22559183

  18. Toll-like receptor agonist augments virus-like particle-mediated protection from Ebola virus with transient immune activation.

    Karen A O Martins

    Full Text Available Identifying safe and effective adjuvants is critical for the advanced development of protein-based vaccines. Pattern recognition receptor (PRR agonists are increasingly being explored as potential adjuvants, but there is concern that the efficacy of these molecules may be dependent on potentially dangerous levels of non-specific immune activation. The filovirus virus-like particle (VLP vaccine protects mice, guinea pigs, and nonhuman primates from viral challenge. In this study, we explored the impact of a stabilized dsRNA mimic, polyICLC, on VLP vaccination of C57BL/6 mice and Hartley guinea pigs. We show that at dose levels as low as 100 ng, the adjuvant increased the efficacy of the vaccine in mice. Antigen-specific, polyfunctional CD4 and CD8 T cell responses and antibody responses increased significantly upon inclusion of adjuvant. To determine whether the efficacy of polyICLC correlated with systemic immune activation, we examined serum cytokine levels and cellular activation in the draining lymph node. PolyICLC administration was associated with increases in TNFα, IL6, MCP1, MIP1α, KC, and MIP1β levels in the periphery and with the activation of dendritic cells (DCs, NK cells, and B cells. However, this activation resolved within 24 to 72 hours at efficacious adjuvant dose levels. These studies are the first to examine the polyICLC-induced enhancement of antigen-specific immune responses in the context of non-specific immune activation, and they provide a framework from which to consider adjuvant dose levels.

  19. Ethanol affects NMDA receptor signaling at climbing fiber-Purkinje cell synapses in mice and impairs cerebellar LTD.

    He, Qionger; Titley, Heather; Grasselli, Giorgio; Piochon, Claire; Hansel, Christian

    2013-03-01

    Ethanol profoundly influences cerebellar circuit function and motor control. It has recently been demonstrated that functional N-methyl-(D)-aspartate (NMDA) receptors are postsynaptically expressed at climbing fiber (CF) to Purkinje cell synapses in the adult cerebellum. Using whole cell patch-clamp recordings from mouse cerebellar slices, we examined whether ethanol can affect NMDA receptor signaling in mature Purkinje cells. NMDA receptor-mediated currents were isolated by bath application of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptor antagonist 2,3-dihydroxy-6-nitro-7-sulfamoylbenzol[f]quinoxaline (NBQX). The remaining (D)-2-amino-5-phosphonovaleric acid ((D)-APV)-sensitive current was reduced by ethanol at concentrations as low as 10 mM. At a concentration of 50 mM ethanol, the blockade of (D)-APV-sensitive CF-excitatory postsynaptic currents was significantly stronger. Ethanol also altered the waveform of CF-evoked complex spikes by reducing the afterdepolarization. This effect was not seen when NMDA receptors were blocked by (D)-APV before ethanol wash-in. In contrast to CF synaptic transmission, parallel fiber (PF) synaptic inputs were not affected by ethanol. Finally, ethanol (10 mM) impaired long-term depression (LTD) at PF to Purkinje cell synapses as induced under control conditions by paired PF and CF activity. However, LTD induced by pairing PF stimulation with depolarizing voltage steps (substituting for CF activation) was not blocked by ethanol. These observations suggest that the sensitivity of cerebellar circuit function and plasticity to low concentrations of ethanol may be caused by an ethanol-mediated impairment of NMDA receptor signaling at CF synapses onto cerebellar Purkinje cells. PMID:23221414

  20. Combination immunotherapy and active-specific tumor cell vaccination augments anti-cancer immunity in a mouse model of gastric cancer

    van den Engel Natasja K

    2011-08-01

    Full Text Available Abstract Background Active-specific immunotherapy used as an adjuvant therapeutic strategy is rather unexplored for cancers with poorly characterized tumor antigens like gastric cancer. The aim of this study was to augment a therapeutic immune response to a low immunogenic tumor cell line derived from a spontaneous gastric tumor of a CEA424-SV40 large T antigen (CEA424-SV40 TAg transgenic mouse. Methods Mice were treated with a lymphodepleting dose of cyclophosphamide prior to reconstitution with syngeneic spleen cells and vaccination with a whole tumor cell vaccine combined with GM-CSF (a treatment strategy abbreviated as LRAST. Anti-tumor activity to subcutaneous tumor challenge was examined in a prophylactic as well as a therapeutic setting and compared to corresponding controls. Results LRAST enhances tumor-specific T cell responses and efficiently inhibits growth of subsequent transplanted tumor cells. In addition, LRAST tended to slow down growth of established tumors. The improved anti-tumor immune response was accompanied by a transient decrease in the frequency and absolute number of CD4+CD25+FoxP3+ T cells (Tregs. Conclusions Our data support the concept that whole tumor cell vaccination in a lymphodepleted and reconstituted host in combination with GM-CSF induces therapeutic tumor-specific T cells. However, the long-term efficacy of the treatment may be dampened by the recurrence of Tregs. Strategies to counteract suppressive immune mechanisms are required to further evaluate this therapeutic vaccination protocol.

  1. Increased diacylglycerol kinase ζ expression in human metastatic colon cancer cells augments Rho GTPase activity and contributes to enhanced invasion

    Unraveling the signaling pathways responsible for the establishment of a metastatic phenotype in carcinoma cells is critically important for understanding the pathology of cancer. The acquisition of cell motility is a key property of metastatic tumor cells and is a prerequisite for invasion. Rho GTPases regulate actin cytoskeleton reorganization and the cellular responses required for cell motility and invasion. Diacylglycerol kinase ζ (DGKζ), an enzyme that phosphorylates diacylglycerol to yield phosphatidic acid, regulates the activity of the Rho GTPases Rac1 and RhoA. DGKζ mRNA is highly expressed in several different colon cancer cell lines, as well as in colon cancer tissue relative to normal colonic epithelium, and thus may contribute to the metastatic process. To investigate potential roles of DGKζ in cancer metastasis, a cellular, isogenic model of human colorectal cancer metastatic transition was used. DGKζ protein levels, Rac1 and RhoA activity, and PAK phosphorylation were measured in the non-metastatic SW480 adenocarcinoma cell line and its highly metastatic variant, the SW620 line. The effect of DGKζ silencing on Rho GTPase activity and invasion through Matrigel-coated Transwell inserts was studied in SW620 cells. Invasiveness was also measured in PC-3 prostate cancer and MDA-MB-231 breast cancer cells depleted of DGKζ. DGKζ protein levels were elevated approximately 3-fold in SW620 cells compared to SW480 cells. There was a concomitant increase in active Rac1 in SW620 cells, as well as substantial increases in the expression and phosphorylation of the Rac1 effector PAK1. Similarly, RhoA activity and expression were increased in SW620 cells. Knockdown of DGKζ expression in SW620 cells by shRNA-mediated silencing significantly reduced Rac1 and RhoA activity and attenuated the invasiveness of SW620 cells in vitro. DGKζ silencing in highly metastatic MDA-MB-231 breast cancer cells and PC-3 prostate cancer cells also significantly attenuated

  2. Media-Augmented Exercise Machines

    Krueger, T.

    2002-01-01

    Cardio-vascular exercise has been used to mitigate the muscle and cardiac atrophy associated with adaptation to micro-gravity environments. Several hours per day may be required. In confined spaces and long duration missions this kind of exercise is inevitably repetitive and rapidly becomes uninteresting. At the same time, there are pressures to accomplish as much as possible given the cost- per-hour for humans occupying orbiting or interplanetary. Media augmentation provides a the means to overlap activities in time by supplementing the exercise with social, recreational, training or collaborative activities and thereby reducing time pressures. In addition, the machine functions as an interface to a wide range of digital environments allowing for spatial variety in an otherwise confined environment. We hypothesize that the adoption of media augmented exercise machines will have a positive effect on psycho-social well-being on long duration missions. By organizing and supplementing exercise machines, data acquisition hardware, computers and displays into an interacting system this proposal increases functionality with limited additional mass. This paper reviews preliminary work on a project to augment exercise equipment in a manner that addresses these issues and at the same time opens possibilities for additional benefits. A testbed augmented exercise machine uses a specialty built cycle trainer as both input to a virtual environment and as an output device from it using spatialized sound, and visual displays, vibration transducers and variable resistance. The resulting interactivity increases a sense of engagement in the exercise, provides a rich experience of the digital environments. Activities in the virtual environment and accompanying physiological and psychological indicators may be correlated to track and evaluate the health of the crew.

  3. ANTIDEPRESSANT-LIKE EFFECTS OF LOW KETAMINE DOSE IS ASSOCIATED WITH INCREASED HIPPOCAMPAL AMPA/NMDA RECEPTOR DENSITY RATIO IN FEMALE WISTAR-KYOTO RATS

    Tizabi, Yousef; Bhatti, Babur H; Manaye, Kebreten F; Das, Jharna R; Akinfiresoye, Luli

    2012-01-01

    Preclinical as well as limited clinical studies indicate that ketamine, a non-competitive glutamate NMDA receptor antagonist, may exert a quick and prolonged antidepressant effect. It has been postulated that ketamine action is due to inhibition of NMDA and stimulation of AMPA receptors. Here, we sought to determine whether ketamine would exert antidepressant effects in Wistar-Kyoto (WKY) rats, a putative animal model of depression and whether this effect would be associated with changes in AMPA/NMDA receptor densities in the hippocampus. Adult female WKY rats and their control Wistar rats were subjected to acute and chronic ketamine doses and their locomotor activity (LMA) and immobility in the forced swim test (FST) were evaluated. Hippocampal AMPA and NMDA receptor densities were also measured following a chronic ketamine dose. Ketamine, both acutely (0.5–5.0 mg/kg ip) and chronically (0.5–2.5 mg/kg daily for 10 days) resulted in a dose-dependent and prolonged decrease in immobility in the FST in WKY rats only, suggesting an antidepressant-like effect in this model. Chronic treatment with an effective dose of ketamine also resulted in an increase in AMPA/NMDA receptor density ratio in the hippocampus of WKY rats. LMA was not affected by any ketamine treatment in either strain. These results indicate a rapid and lasting antidepressant-like effect of a low ketamine dose in WKY rat model of depression. Moreover, the increase in AMPA/NMDA receptor density in hippocampus could be a contributory factor to behavioral effects of ketamine. These findings suggest potential therapeutic benefit in simultaneous reduction of central NMDA and elevation of AMPA receptor function in treatment of depression. PMID:22521815

  4. Augmenting the Antifungal Activity of an Oxidizing Agent with Kojic Acid: Control of Penicillium Strains Infecting Crops

    Kim, Jong H.; Chan, Kathleen L.

    2014-01-01

    Oxidative treatment is one of the strategies for preventing Penicillium contamination in crops/foods. The antifungal efficacy of hydrogen peroxide (H2O2; oxidant) was investigated in Penicillium strains by using kojic acid (KA) as a chemosensitizing agent, which can enhance the susceptibility of pathogens to antifungal agents. Co-application of KA with H2O2 (chemosensitization) resulted in the enhancement of antifungal activity of either compound, when compared to the independent application ...

  5. Postreduction Breast Augmentation

    Hidalgo, David A.; Doft, Melissa A.

    2015-01-01

    Background: Most breast reduction patients are highly satisfied after surgery. However, there is a subset of women who seek breast augmentation years later to restore lost volume chiefly associated with weight loss and postpartum changes. Breast shape and overall aesthetics are often revised at the same time. Methods: A retrospective review was performed of 2 surgeons’ experiences with post-reduction breast augmentation. Twenty patients were identified between 2002 and 2014. An in-depth chart...

  6. Transaxillary Endoscopic Breast Augmentation

    Sim, Hyung-Bo

    2014-01-01

    The axillary technique is the most popular approach to breast augmentation among Korean women. Transaxillary breast augmentation is now conducted with sharp electrocautery dissection under direct endoscopic vision throughout the entire process. The aims of this method are clear: both a bloodless pocket and a sharp non-traumatic dissection. Round textured or anatomical cohesive gel implants have been used to make predictable well-defined inframammary creases because textured surface implants d...

  7. Marketing and Augmented Reality

    Zelený, Martin

    2010-01-01

    The main goal of this diploma thesis is to identify the usage of augmented reality in contemporary marketing practice and the expectations of marketers for the future use. This will be achieved by conducting a quantitative and qualitative research among existing creative and advertising companies. Secondary goal is introducing the concept of augmented reality from the theoretical point of view and also description of potential utilization based on known examples. The tools for the practical p...

  8. Augmented Reality im Techniktraining

    Schack, Thomas; Heinen, Thomas; Hermann, Thomas

    2007-01-01

    In den letzten Jahren wurden in Bereichen wie Robotik, Telemanipulation und Militär neue Technologien entwickelt, die als Augmented Reality (Erweiterte Realität) (Milgram et al., 1994) bezeichnet werden. Durch Augmented Reality wird die Leistungs fähigkeit der beteiligten Menschen nachweisbar unterstützt. Dabei wird die Realität eines Agenten computergestützt mit virtueller Information - auf visueller, akustischer oder taktiler Basis - in Echtzeit überlagert (erweitert). Die wesentliche Eig...

  9. Magnetohydrodynamic Augmented Propulsion Experiment

    Litchford, Ron J.; Cole, John; Lineberry, John; Chapman, Jim; Schmidt, Harold; Cook, Stephen (Technical Monitor)

    2002-01-01

    that an MHD accelerator can be an effective augmentation system for increasing engine exhaust velocity. More specifically, the experiment is intended to show that electromagnetic effects are effective at producing flow acceleration whereas electrothermal effects do not cause unacceptable heating of the working fluid. The MHD accelerator was designed as an externally diagonalized segmented Faraday channel, which will be inserted into an existing 2-tesla electromagnet. This allows the external power to be connected through two terminals thereby minimizing the complexity and cost associated with powering each segment independently. The design of the accelerator and other components in the flow path has been completed and fabrication activities are underway. This paper provides a full description of MAPX including performance analysis, design, and test plans, and current status.

  10. Confronting an augmented reality

    John Hedberg

    2012-08-01

    Full Text Available How can educators make use of augmented reality technologies and practices to enhance learning and why would we want to embrace such technologies anyway? How can an augmented reality help a learner confront, interpret and ultimately comprehend reality itself? In this article, we seek to initiate a discussion that focuses on these questions, and suggest that they be used as drivers for research into effective educational applications of augmented reality. We discuss how multi-modal, sensorial augmentation of reality links to existing theories of education and learning, focusing on ideas of cognitive dissonance and the confrontation of new realities implied by exposure to new and varied perspectives. We also discuss connections with broader debates brought on by the social and cultural changes wrought by the increased digitalisation of our lives, especially the concept of the extended mind. Rather than offer a prescription for augmentation, our intention is to throw open debate and to provoke deep thinking about what interacting with and creating an augmented reality might mean for both teacher and learner.

  11. Intraoperative Endoscopic Augmented Reality in Third Ventriculostomy

    Ciucci, Matteo

    2009-01-01

    In neurosurgery, as a result of the brain-shift, the preoperative patient models used as a intraoperative reference change. A meaningful use of the preoperative virtual models during the operation requires for a model update. The NEAR project, Neuroendoscopy towards Augmented Reality, describes a new camera calibration model for high distorted lenses and introduces the concept of active endoscopes endowed with with navigation, camera calibration, augmented reality and triangulation modules.

  12. Copper(II) oxide nanoparticles augment antifilarial activity of Albendazole: In vitro synergistic apoptotic impact against filarial parasite Setaria cervi.

    Zafar, Atif; Ahmad, Irshad; Ahmad, Ajaz; Ahmad, Masood

    2016-03-30

    Mass treatment of lymphatic filariasis with Albendazole (ABZ), a therapeutic benzimidazole, is fraught with serious limitations such as possible drug resistance and poor macrofilaricidal activity. Therefore, we need to develop new ABZ-based formulations to improve its antifilarial effectiveness. CuO nanoparticles were used as an adjuvant with ABZ to form ABZ-CuO nanocomposite, which was characterized by UV-vis spectroscopy, FT-IR, AFM and SEM. Antifilarial activity of nanocomposite was evaluated using relative motility assay and dye exclusion test in dark and under UV light. ROS generation, antioxidant levels, lipid peroxidation and DNA fragmentation in nanocomposite treated parasites were estimated. Biophysical techniques were employed to ascertain the mode of binding of nanocomposite to parasitic DNA. Nanocomposite increases parasite mortality as compared to ABZ in dark, and its antifilarial effect was increased further under UV light. Elevated ROS production and decline of parasitic-GST and GSH levels were observed in nanocomposite treated worms in dark, and these effects were pronounced further under UV light. Nanocomposite leads to higher DNA fragmentation as compared to ABZ alone. Further, we found that nanocomposite binds parasitic DNA in an intercalative manner where it generates ROS to induce DNA damage. Thus, oxidative stress production due to ROS generation and consequent DNA fragmentation leads to apoptosis in worms. This is the first report supporting CuO nanoparticles as a potential adjuvant with ABZ against filariasis along with enhanced antifilarial activity of nanocomposite under UV light. These findings, thus, indicate that development of ABZ-loaded nanoparticle compounds may serve as promising leads for filariasis treatment. PMID:26827921

  13. Competitive (AP7) and non-competitive (MK-801) NMDA receptor antagonists differentially alter glucose utilization in rat cortex

    The effects of D,L-2-amino-7-phosphonoheptanoic acid (AP7), a competitive N-methyl-D-aspartate (NMDA) receptor antagonist, and MK-801, a non-competitive NMDA receptor antagonist, on regional brain metabolism were studied in unanesthetized, freely moving rats by using the quantitative 14C2-deoxyglucose autoradiographic procedure. AP7 (338 or 901 mg/kg) produced a dose-dependent decrease of metabolic activity throughout most of the regions studied including sensory, motor, and limbic cortices. In contrast, MK-801 (0.1 or 1.0 mg/kg) resulted in a dose-dependent decrease of metabolic activity in sensory cortices, and an increase in limbic regions such as the hippocampal stratum lacunosum moleculare and entorhinal cortex. MK-801 also produced a biphasic response in agranular motor cortex, whereby the low dose increased while the high dose decreased labeling. In addition, MK-801 produced heterogeneous effects on regional cerebral metabolism in sensory cortices. Metabolic activity decreased in layer IV relative to layer Va following MK-801 treatment in primary somatosensory (SI) and visual (VI) cortices, suggesting a shift in activity from afferent fibers innervating layer IV to those innervating layer Va. MK-801 administration also decreased metabolic activity in granular SI relative to dysgranular SI, and in VI relative to secondary visual cortex (VII), thus providing a relative sparing of activity in dysgranular SI and VII. Thus, the non-competitive NMDA receptor antagonist suppressed activity from extrinsic neocortical sources, enhancing relative intracortical activity and stimulating limbic regions, while the competitive NMDA antagonist depressed metabolic activity in all cortical regions

  14. Activation of human B cells by the agonist CD40 antibody CP-870,893 and augmentation with simultaneous toll-like receptor 9 stimulation

    Rüter Jens

    2009-11-01

    capacity. Simultaneous TLR9 ligation augments the effect of CP-870,893 alone. These results provide further rationale for combining CD40 and TLR9 activation using available clinical reagents in strategies of novel tumor immunotherapy.

  15. Landfill leachate treatment using powdered activated carbon augmented sequencing batch reactor (SBR) process: Optimization by response surface methodology

    Aziz, Shuokr Qarani [School of Civil Engineering, Universiti Sains Malaysia (USM), 14300 Nibong Tebal, Penang (Malaysia); Aziz, Hamidi Abdul, E-mail: cehamidi@eng.usm.my [School of Civil Engineering, Universiti Sains Malaysia (USM), 14300 Nibong Tebal, Penang (Malaysia); Yusoff, Mohd Suffian; Bashir, Mohammed J.K. [School of Civil Engineering, Universiti Sains Malaysia (USM), 14300 Nibong Tebal, Penang (Malaysia)

    2011-05-15

    In this study, landfill leachate was treated by using the sequencing batch reactor (SBR) process. Two types of the SBR, namely non-powdered activated carbon and powdered activated carbon (PAC-SBR) were used. The influence of aeration rate and contact time on SBR and PAC-SBR performances was investigated. Removal efficiencies of chemical oxygen demand (COD), colour, ammoniacal nitrogen (NH{sub 3}-N), total dissolved salts (TDS), and sludge volume index (SVI) were monitored throughout the experiments. Response surface methodology (RSM) was applied for experimental design, analysis and optimization. Based on the results, the PAC-SBR displayed superior performance in term of removal efficiencies when compared to SBR. At the optimum conditions of aeration rate of 1 L/min and contact time of 5.5 h the PAC-SBR achieved 64.1%, 71.2%, 81.4%, and 1.33% removal of COD, colour, NH{sub 3}-N, and TDS, respectively. The SVI value of PAC-SBR was 122.2 mL/g at optimum conditions.

  16. Landfill leachate treatment using powdered activated carbon augmented sequencing batch reactor (SBR) process: optimization by response surface methodology.

    Aziz, Shuokr Qarani; Aziz, Hamidi Abdul; Yusoff, Mohd Suffian; Bashir, Mohammed J K

    2011-05-15

    In this study, landfill leachate was treated by using the sequencing batch reactor (SBR) process. Two types of the SBR, namely non-powdered activated carbon and powdered activated carbon (PAC-SBR) were used. The influence of aeration rate and contact time on SBR and PAC-SBR performances was investigated. Removal efficiencies of chemical oxygen demand (COD), colour, ammoniacal nitrogen (NH(3)-N), total dissolved salts (TDS), and sludge volume index (SVI) were monitored throughout the experiments. Response surface methodology (RSM) was applied for experimental design, analysis and optimization. Based on the results, the PAC-SBR displayed superior performance in term of removal efficiencies when compared to SBR. At the optimum conditions of aeration rate of 1L/min and contact time of 5.5h the PAC-SBR achieved 64.1%, 71.2%, 81.4%, and 1.33% removal of COD, colour, NH(3)-N, and TDS, respectively. The SVI value of PAC-SBR was 122.2 mL/g at optimum conditions. PMID:21420786

  17. Landfill leachate treatment using powdered activated carbon augmented sequencing batch reactor (SBR) process: Optimization by response surface methodology

    In this study, landfill leachate was treated by using the sequencing batch reactor (SBR) process. Two types of the SBR, namely non-powdered activated carbon and powdered activated carbon (PAC-SBR) were used. The influence of aeration rate and contact time on SBR and PAC-SBR performances was investigated. Removal efficiencies of chemical oxygen demand (COD), colour, ammoniacal nitrogen (NH3-N), total dissolved salts (TDS), and sludge volume index (SVI) were monitored throughout the experiments. Response surface methodology (RSM) was applied for experimental design, analysis and optimization. Based on the results, the PAC-SBR displayed superior performance in term of removal efficiencies when compared to SBR. At the optimum conditions of aeration rate of 1 L/min and contact time of 5.5 h the PAC-SBR achieved 64.1%, 71.2%, 81.4%, and 1.33% removal of COD, colour, NH3-N, and TDS, respectively. The SVI value of PAC-SBR was 122.2 mL/g at optimum conditions.

  18. Oxygen plasma surface modification augments poly(L-lactide-co-glycolide) cytocompatibility toward osteoblasts and minimizes immune activation of macrophages.

    Scislowska-Czarnecka, Anna; Szmigiel, Dariusz; Genet, Michel; Dupont-Gillain, Christine; Pamula, Elzbieta; Kolaczkowska, Elzbieta

    2015-12-01

    Here, we report on modification of one of the model biomedical polymers, poly L-lactide-co-glycolide (PLGA; 85:15), by reactive ion etching (RIE) oxygen plasma treatment. PLGA's major disadvantage is high hydrophobicity which restrains binding of cell-adhesive proteins and host cells. In the current approach, we aimed to answer two questions: (1) will only short (10 s) and moderate (20-200 mTorr, 45-90 W) RIE oxygen plasma treatment, leading to decrease of water contact angle by only up to 10°, sufficiently improve PLGA adherence to cells, and (2) how will this affect osteoblasts and activation of the immune system? All obtained modified PLGAs had improved hydrophilicity but unaltered roughness (as revealed by water contact angle measurements, X-ray photoelectron spectroscopy, and atomic force microscopy) resulting in significantly improved adhesion of osteoblasts (MG-63) and their low activation. Importantly, macrophages (RAW 264.7), one of the key cells initiating inflammation and bone resorption, responded significantly less vigorously to the modified polymers, expressing/releasing lower amounts of nitric oxide, matrix metalloproteinases (MMP-9), and pro-inflammatory cytokines (TNF-α, IL-6, IL-12p70, IFN-γ, IL-10). We conclude that already slight RIE oxygen plasma modification of PLGA is sufficient to improve its surface properties, and enhance cytocompatibility. Most importantly, this type of modification prevents excessive immune response. PMID:26014580

  19. BDNF released during neuropathic pain potentiates NMDA receptors in primary afferent terminals

    Chen, Wenling; Walwyn, Wendy; Ennes, Helena S.; Kim, Hyeyoung; McRoberts, James A.; Marvizón, Juan Carlos G.

    2014-01-01

    NMDA receptors in primary afferent terminals can contribute to hyperalgesia by increasing neurotransmitter release. In rats and mice, we found that the ability of intrathecal NMDA to induce neurokinin 1 receptor (NK1R) internalization (a measure of substance P release) required a previous injection of BDNF. Selective knock-down of NMDA receptors in primary afferents decreased NMDA-induced NK1R internalization, confirming the presynaptic location of these receptors. The effect of BDNF was medi...

  20. Synthesis of a Series of Novel 3,9-Disubstituted Phenanthrenes as Analogues of Known NMDA Receptor Allosteric Modulators

    Irvine, Mark W.; Fang, Guangyu; Eaves, Richard; Mayo-Martin, Maria B.; Burnell, Erica S.; Costa, Blaise M.; Culley, Georgia R.; Volianskis, Arturas; Collingridge, Graham L; Monaghan, Daniel T.; Jane, David E.

    2015-01-01

    9-Substituted phenanthrene-3-carboxylic acids have been reported to have allosteric modulatory activity at the NMDA receptor. This receptor is activated by the excitatory neurotransmitter L-glutamate and has been implicated in a range of neurological disorders such as schizophrenia, epilepsy and chronic pain and neurodegenerative disorders such as Alzheimer’s disease. Herein, the convenient synthesis of a wide range of novel 3,9-disubstituted phenanthrene derivatives starting from a few commo...

  1. Activated platelet supernatant can augment the angiogenic potential of human peripheral blood stem cells mobilized from bone marrow by G-CSF.

    Kang, Jeehoon; Hur, Jin; Kang, Jin-A; Yun, Ji-Yeon; Choi, Jae-Il; Ko, Seung Bum; Lee, Choon-Soo; Lee, Jaewon; Han, Jung-Kyu; Kim, Hyun Kyung; Kim, Hyo-Soo

    2014-10-01

    Platelets not only play a role in hemostasis, but they also promote angiogenesis and tissue recovery by releasing various cytokines and making an angiogenic milieu. Here, we examined autologous 'activated platelet supernatant (APS)' as a priming agent for stem cells; thereby enhance their pro-angiogenic potential and efficacy of stem cell-based therapy for ischemic diseases. The mobilized peripheral blood stem cells ((mob)PBSCs) were isolated from healthy volunteers after subcutaneous injection of granulocyte-colony stimulating factor. APS was collected separately from the platelet rich plasma after activation by thrombin. (mob)PBSCs were primed for 6h before analysis. Compared to naive platelet supernatants, APS had a higher level of various cytokines, such as IL8, IL17, PDGF and VEGF. APS-priming for 6h induced (mob)PBSCs to express key angiogenic factors, surface markers (i.e. CD34, CD31, and CXCR4) and integrins (integrins α5, β1 and β2). Also (mob)PBSCs were polarized toward CD14(++)/CD16(+) pro-angiogenic monocytes. The priming effect was reproduced by an in vitro reconstruction of APS. Through this phenotype, APS-priming increased cell-cell adhesion and cell-extracellular matrix adhesion. The culture supernatant of APS-primed (mob)PBSCs contained high levels of IL8, IL10, IL17 and TNFα, and augmented proliferation and capillary network formation of human umbilical vein endothelial cells. In vivo transplantation of APS-primed (mob)PBSCs into athymic mice ischemic hindlimbs and Matrigel plugs elicited vessel differentiation and tissue repair. In safety analysis, platelet activity increased after mixing with (mob)PBSCs regardless of priming, which was normalized by aspirin treatment. Collectively, our data identify that APS-priming can enhance the angiogenic potential of (mob)PBSCs, which can be used as an adjunctive strategy to improve the efficacy of cell therapy for ischemic diseases. PMID:25016235

  2. Review of passive heat transfer augmentation techniques

    Dewan, A.; Mahanta, P.; Sumithra Raju, K. [Indian Institute of Technology, Guwahati (India). Dept. of Mechanical Engineering; Suresh Kumar, P. [Indian Institute of technology, Kharagpur (India). Dept. of Oocean Engineering and Naval Architecture

    2004-12-01

    Heat transfer augmentation techniques (passive, active or a combination of passive and active methods) are commonly used in areas such as process industries, heating and cooling in evaporators, thermal power plants, air- conditioning equipment, refrigerators, radiators for space vehicles, automobiles, etc. Passive techniques, where inserts are used in the flow passage to augment the heat transfer rate, are advantageous compared with active techniques, because the insert manufacturing process is simple and these techniques can be easily employed in an existing heat exchanger. In design of compact heat exchangers, passive techniques of heat transfer augmentation can play an important role if a proper passive insert configuration can be selected according to the heat exchanger working condition (both flow and heat transfer conditions). In the past decade, several studies on the passive techniques of heat transfer augmentation have been reported. The present paper is a review on progress with the passive augmentation techniques in the recent past and will be useful to designers implementing passive augmentation techniques in heat exchange. Twisted tapes, wire coils, ribs, fins, dimples, etc., are the most commonly used passive heat transfer augmentation tools. In the present paper, emphasis is given to works dealing with twisted tapes and wire coils because, according to recent studies, these are known to be economic heat transfer augmentation tools. The former insert is found to be suitable in a laminar flow regime and the latter is suitable for turbulent flow. The thermohydraulic behaviour of an insert mainly depends on the flow conditions (laminar or turbulent) apart from the insert configurations. The present review is organized in five different sections: twisted tape in laminar flow; twisted tape in turbulent flow; wire coil in laminar flow; wire coil in turbulent flow; other inserts such as ribs, fins, dimples, etc. (author)

  3. NMDA receptor blockade in the basolateral amygdala disrupts consolidation of stimulus-reward memory and extinction learning during reinstatement of cocaine-seeking in an animal model of relapse

    Feltenstein, Matthew W.; See, Ronald E.

    2007-01-01

    Previous research from our laboratory has implicated the basolateral amygdala (BLA) complex in the acquisition and consolidation of cue-cocaine associations, as well as extinction learning, which may regulate the long-lasting control of conditioned stimuli (CS) over drug-seeking behavior. Given the well established role of NMDA glutamate receptor activation in other forms of amygdalar-based learning, we predicted that BLA-mediated drug-cue associative learning would be NMDA receptor dependent...

  4. sPLA2-IIA Augments Oxidized LDL-Induced MCP-1 Expression in Vitro Through Activation of Akt

    Yongjun Guo

    2015-10-01

    Full Text Available Background/Aims: Group IIA secretory phospholipase A2 (sPLA2-IIA has an important role in atherosclerosis. In this study, we explored whether sPLA2-IIA overexpression could promote atherosclerosis in normal environment alone or with other inflammatory factors. Methods: Human aortic smooth muscle cells (HASMCs were transduced with Lv-GFP-sPLA2-IIA, a plasmid containing sPLA2-IIA coupled with green fluorescent protein (GFP. Cells were incubated in the presence or absence of oxidized low-density lipoprotein (LDL, sPLA2 inhibitor LY315920 or PI3K/Akt inhibitor LY294002. The mRNA expression and protein secretion of monocyte chemoattractant protein-1 (MCP-1 were assessed by quantitative real-time polymerase chain reaction (QRT-PCR and enzyme-linked immunosorbent assay (ELISA, respectively. Phosphorylation of Akt was examined by western blotting. Results: Lv-GFP-sPLA2-IIA-transduced HASMCs remained fluorescent during 72 h of the study period with infection ratio of around 80%. The mRNA expression and protein secretion of MCP-1was not altered in groups of HASMCs, Lv-GFP transduced and Lv-GFP-sPLA2-IIA-transduced HASMCs (p>0.05, but was significantly increased in the presence of oxidized LDL especially in Lv-GFP-sPLA2-IIA transduction group (ppConclusions: Overexpression of sPLA2-IIA does not alter MCP-1 level at baseline, but could enhance the atherogenic effect of oxidized LDL in HASMCs, at least partly due to activation of Akt. These findings may provide a strategy for treatment of inflammatory cardiovascular diseases.

  5. PSD-95 uncoupling from NMDA receptors by Tat-N-dimer ameliorates neuronal depolarisation in cortical spreading depression

    Kucharz, Krzysztof; Søndergaard Rasmussen, Ida; Bach, Anders;

    2016-01-01

    Cortical spreading depression is associated with activation of NMDA receptors, which interact with the postsynaptic density protein 95 (PSD-95) that binds to nitric oxide synthase (nNOS). Here, we tested whether inhibition of the nNOS/PSD-95/NMDA receptor complex formation by anti-ischemic compound...... during the first hour after i.v. injection. The Tat-N-dimer suppressed stimulation-evoked synaptic activity by 2-20%, while cortical blood flow and cerebral oxygen metabolic (CMRO2) responses were preserved. During cortical spreading depression, the Tat-N-dimer reduced the average amplitude of the...... negative shift in direct current potential by 33% (4.1 mV). Furthermore, the compound diminished the average depression of spontaneous electrocorticographic activity by 11% during first 40 min of post-cortical spreading depression recovery, but did not mitigate the suppressing effect of cortical spreading...

  6. Time and space profiling of NMDA receptor co-agonist functions.

    Mothet, Jean-Pierre; Le Bail, Matildé; Billard, Jean-Marie

    2015-10-01

    The N-Methyl D-Aspartic acid (NMDA) receptors (NMDAR) are key tetrameric ionotropic glutamate receptors that transduce glutamatergic signals throughout the central nervous system (CNS) and spinal cord. Although NMDARs are diverse in their subunit composition, subcellular localization, and biophysical and pharmacological properties, their activation always requires the binding of a co-agonist that has long been thought to be glycine. However, intense research over the last decade has challenged this classical model by showing that another amino acid, d-serine, is the preferential co-agonist for a subset of synaptic NMDARs in many areas of the adult brain. Nowadays, a totally new picture of glutamatergic synapses at work is emerging where both glycine and d-serine are involved in a complex interplay to regulate NMDAR functions in the CNS following time and space constraints. The purpose of this review was to highlight the particular role of each co-agonist in modulating NMDAR-dependent activities in healthy and diseased brains. We have herein integrated our most advanced knowledge of how glycine and d-serine may orchestrate synapse dynamics and drive neuronal network activity in a time- and synapse-specific manner and how changes in synaptic availability of these amino acids may contribute to cognitive impairments such as those associated with healthy aging, epilepsy, and schizophrenia. The N-Methyl D-Aspartic acid (NMDA) subtype of glutamate receptors are central to many physiological functions and are linked to brain disorders. Their functions require glutamate and a co-agonist d-serine or glycine. After years of intense research and controversy on the identity of the amino acid that serves as the right co-agonist, we are just entering a new era of consensus where glycine and d-serine are teaming up to regulate the function of different subsets of NMDA receptors and at different synapses during different time windows of brain development. PMID:26088787

  7. Augmenting computer networks

    Bokhari, S. H.; Raza, A. D.

    1984-01-01

    Three methods of augmenting computer networks by adding at most one link per processor are discussed: (1) A tree of N nodes may be augmented such that the resulting graph has diameter no greater than 4log sub 2((N+2)/3)-2. Thi O(N(3)) algorithm can be applied to any spanning tree of a connected graph to reduce the diameter of that graph to O(log N); (2) Given a binary tree T and a chain C of N nodes each, C may be augmented to produce C so that T is a subgraph of C. This algorithm is O(N) and may be used to produce augmented chains or rings that have diameter no greater than 2log sub 2((N+2)/3) and are planar; (3) Any rectangular two-dimensional 4 (8) nearest neighbor array of size N = 2(k) may be augmented so that it can emulate a single step shuffle-exchange network of size N/2 in 3(t) time steps.

  8. Prototyping Augmented Reality

    Mullen, Tony

    2011-01-01

    Learn to create augmented reality apps using Processing open-source programming language Augmented reality (AR) is used all over, and you may not even realize it. Smartphones overlay data onto live camera views to show homes for sale, restaurants, or historical sites. American football broadcasts use AR to show the invisible first-down line on the field to TV viewers. Nike and Budweiser, among others, have used AR in ads. Now, you can learn to create AR prototypes using 3D data, Processing open-source programming language, and other languages. This unique book is an easy-to-follow guide on how

  9. Augmented reality som wearable

    Buhl, Mie; Rahn, Annette

    2015-01-01

    Artiklen omhandler design og implementering af Augmented Reality (AR) i form af en wearable i sygeplejerskeuddannelsens anatomiundervisning, mere specifikt undervisning i lungeanatomi og respiration, med fokus på potentialer for visuel læring. Projektet undersøger, hvordan en udviklet AR-applikat......Artiklen omhandler design og implementering af Augmented Reality (AR) i form af en wearable i sygeplejerskeuddannelsens anatomiundervisning, mere specifikt undervisning i lungeanatomi og respiration, med fokus på potentialer for visuel læring. Projektet undersøger, hvordan en udviklet AR...

  10. Estradiol-Induced Enhancement of Object Memory Consolidation Involves NMDA Receptors and Protein Kinase A in the Dorsal Hippocampus of Female C57BL/6 Mice

    Michael C. Lewis; Kerr, Kristin M.; Orr, Patrick T.; Frick, Karyn M.

    2008-01-01

    This study examined the role of dorsal hippocampal NMDA receptors and PKA activation in 17β-estradiol (E2)-induced enhancement of object memory consolidation. Mice explored two identical objects during training, after which they immediately received intraperitoneal injections of 0.2 mg/kg E2, and bilateral dorsal hippocampal infusions of Vehicle, the NMDA receptor antagonist APV (2.5 μg/side), or the cAMP inhibitor Rp-cAMPS (18.0 μg/side). Retention was tested 48 hours later. The enhanced obj...

  11. The participation of NMDA receptors, PKC, and MAPK in the formation of memory following operant conditioning in Lymnaea

    Rosenegger David

    2010-08-01

    Full Text Available Abstract Background Memory is the ability to store, retain, and later retrieve information that has been learned. Intermediate term memory (ITM that persists for up to 3 h requires new protein synthesis. Long term memory (LTM that persists for at least 24 h requires: DNA transcription, RNA translation, and the trafficking of newly synthesized proteins. It has been shown in a number of different model systems that NMDA receptors, protein kinase C (PKC and mitogen activated protein kinase (MAPK are all involved in the memory formation process. Results Here we show that snails trained in control conditions are capable of forming, depending on the training procedure used, either ITM or LTM. However, blockage of NMDA receptors (MK 801, inhibition of PKC (GF109203X hydrochloride and MAPK activity (UO126 prevent the formation of both ITM and LTM. Conclusions The injection of either U0126 or GF109203X, which inhibit MAPK and PKC activity respectively, 1 hour prior to training results in the inhibition of both ITM and LTM formation. We further found that NMDA receptor activity was necessary in order for both ITM and LTM formation.

  12. NMDA and non-NMDA receptors contribute to synaptic transmission between the medial geniculate body and the lateral nucleus of the amygdala.

    Li, X F; Phillips, R; LeDoux, J E

    1995-01-01

    We examined whether the NMDA class of excitatory amino acid receptors contribute to synaptic transmission in the pathway connecting the medial geniculate body (MGB) with the lateral nucleus of the amygdala (LA) using extracellular single unit recordings and microiontophoresis. Cells were identified in LA on the basis of responsivity to electrical stimulation of the MGB. For each cell, a level of current was found for the iontophoretic ejection of the NMDA antagonist AP5 that blocked responses elicited by iontophoresis of NMDA, but had no effect on responses elicited by AMPA. Iontophoresis of AP5 with this level of current blocked the excitatory response elicited by MGB stimulation in most cells tested. Microinfusion of AP5 (25, 50, or 100 microM) also blocked the responses. Additional studies tested individual cells with both AP5 and the AMPA antagonist CNQX and showed that blockade of either NMDA or AMPA receptors interferes with synaptic transmission. Finally, iontophoretic ejection of either AP5 or CNQX blocked short-latency (< 25 ms) responses elicited in LA by peripheral auditory stimulation. Together, these results suggest that the synaptic evocation of action potentials in the thalamo-amygdala pathway depends on both NMDA and non-NMDA receptors. We hypothesize that non-NMDA receptors are most likely required to depolarize the cell sufficiently to remove the blockade of NMDA channels by magnesium and NMDA receptors are required to further depolarize the membrane to the level required for action potential generation. PMID:7589322

  13. Activation of GPR119 by fatty acid agonists augments insulin release from clonal β-cells and isolated pancreatic islets and improves glucose tolerance in mice.

    Moran, Brian M; Abdel-Wahab, Yasser H A; Flatt, Peter R; McKillop, Aine M

    2014-04-01

    G-protein coupled receptor 119 (GPR119) is emerging as a potential target for the treatment of type 2 diabetes with beneficial effects on glucose homeostasis. This study assessed the insulin-secreting properties of various GPR119 agonists and the distribution of GPR119 in pancreatic islets. Endogenous ligands [oleoylethanolamide (OEA), palmitoylethanolamine (PEA)] and chemically synthetic analogues (AS-1269574, PSN-375963) were investigated in clonal BRIN-BD11 cells and mouse pancreatic islets. Secondary messenger assays such as intracellular Ca²⁺ and cAMP in response to agonists at normoglycaemic and hyperglycaemic conditions were assessed. Cytotoxicity was assessed by LDH release. AS-1269574 was the most potent and selective agonist tested in isolated islets, with an EC₅₀ value of 9.7×10⁻⁷ mol/l, enhancing insulin release maximally by 63.2%. Stimulation was also observed with GPR119 ligands; OEA (3.0×10⁻⁶ mol/l; 37.5%), PSN-375963 (2.4×10⁻⁶ mol/l; 28.7%) and PEA (1.2×10⁻⁶ mol/l; 22.2%). Results were corroborated by studies using BRIN-BD11 cells, which revealed augmentation of intracellular Ca²⁺ and cAMP. Both OEA and AS-1269574 enhanced insulin release and improved glucose tolerance in vivo in NIH Swiss mice. These results demonstrate the cellular localisation of GPR119 on islet cells (β and pancreatic polypeptide cells), its activation of the β-cell stimulus-secretion coupling pathway and glucose lowering effects in vivo. PMID:24323890

  14. Neuroprotection by NMDA receptor antagonists in a variety of neuropathologies.

    Palmer, G C

    2001-09-01

    Because of adverse reactions, early efforts to introduce high affinity competitive or use-dependent NMDA receptor antagonists into patients suffering from stroke, head trauma or epilepsy met with failure. Later it was discovered that both low affinity use-dependent NMDA receptor antagonists and compounds with selective affinity for the NR2B receptor subunit met the criteria for safe administration into patients. Furthermore, these low affinity antagonists exhibit significant mechanistic differences from their higher affinity counterparts. Success of the latter is attested to the ability of the following low affinity compounds to be marketed: 1) Cough suppressant-dextromethorphan (available for decades); 2) Parkinson's disease--amantadine, memantine and budipine; 3) Dementia--memantine; and 4) Epilepsy--felbamate. Moreover, Phase III clinical trials are ongoing with remacemide for epilepsy and Huntington's disease and head trauma for HU-211. A host of compounds are or were under evaluation for the possible treatment of stroke, head trauma, hyperalgesia and various neurodegenerative disorders. Despite the fact that other drugs with associated NMDA receptor mechanisms have reached clinical status, this review focuses only on those competitive and use-dependent NMDA receptor antagonists that reached clinical trails. The ensuing discussions link the in vivo pharmacological investigations that led to the success/mistakes/ failures for eventual testing of promising compounds in the clinic. PMID:11554551

  15. The meth brain: methamphetamines alter brain functions via NMDA receptors

    Proft, Juliane; Weiss, Norbert

    2015-01-01

    Roč. 34, č. 1 (2015), s. 1-3. ISSN 0231-5882 R&D Projects: GA ČR GA15-13556S Institutional support: RVO:61388963 Keywords : ion channel * methamphetamine * piriform cortex * NMDA receptor * AMPA receptor Subject RIV: CE - Biochemistry Impact factor: 1.173, year: 2014

  16. Collaborative augmented reality environments

    Büscher, Monika; Christensen, Michael; Grønbæk, Kaj;

    2000-01-01

    This paper describes Manufaktur, a prototype of a concept and infrastructure that goes beyond the classical CVE systems toward a collaborative augmented reality environment, where users? documents and objects appear as live representations in a 3D workspace. Manufaktur supports collaborative...

  17. Augmented Reality og kulturarv

    Nielsen, Mikkel Kirkedahl Lysholm

    2013-01-01

    Museerne står overfor at skulle omfavne den digitale kultur i håndteringen af den store mængde viden, institutionerne repræsenterer. Augmented Reality-systemer forbinder ved hjælp af moderne teknologi det virtuelle med det virkelige, og kan derfor synes som en oplagt anvendelsesmulighed i...

  18. Social isolation-induced increase in NMDA receptors in the hippocampus exacerbates emotional dysregulation in mice.

    Chang, Chih-Hua; Hsiao, Ya-Hsin; Chen, Yu-Wen; Yu, Yang-Jung; Gean, Po-Wu

    2015-04-01

    Epidemiological studies have shown that early life adverse events have long-term effects on the susceptibility to subsequent stress exposure in adolescence, but the precise mechanism is unclear. In the present study, mice on postnatal day 21-28 were randomly assigned to either a group or isolated cages for 8 weeks. The socially isolated (SI) mice exhibited a higher level of spontaneous locomotor activity, a longer duration of immobility in the forced swimming test (FST), significantly less prepulse inhibition (PPI) and an increase in aggressive (but not attack) behavior. However, acute stress markedly exacerbated the attack counts of the SI mice but did not affect the group housing (GH) mice. SI mice exhibited higher synaptosomal NR2A and NR2B levels in the hippocampus as compared to the GH mice. Whole-cell patch clamp recordings of CA1 neurons in hippocampal slices showed that the SI mice exhibited a higher input-output relationship of NMDAR-EPSCs as compared to the GH mice. Application of the NR2B -specific antagonist ifenprodil produced a greater attenuating effect on NMDAR-EPSCs in slices from the SI mice. NMDAR EPSCs recorded from the SI mice had a slower deactivation kinetic. MK-801, CPP and ifenprodil, the NMDA antagonists, reversed acute stress-induced exaggeration of aggressive and depressive behaviors. Furthermore, acute stress-induced exacerbation of attack behavior in the SI mice was abolished after the knockdown of NR2B expression. These results suggest that social isolation-induced increased expression of NMDA receptors in the hippocampus involves stress exacerbation of aggressive behaviors. Amelioration of aggressive behaviors by NMDA antagonists may open a new avenue for the treatment of psychopathologies that involve outbursts of emotional aggression in neglected children. PMID:25348768

  19. Anti-NMDA-R encephalitis: Should we consider extreme delta brush as electrical status epilepticus?

    Chanson, Eve; Bicilli, Élodie; Lauxerois, Michel; Kauffmann, Sophie; Chabanne, Russell; Ducray, François; Honnorat, Jérome; Clavelou, Pierre; Rosenberg, Sarah

    2016-02-01

    Seizures are common clinical manifestations in anti-N-methyl-d-aspartate receptor (anti-NMDA-R) encephalitis, among other neurological and psychiatric symptoms. During the course of the disease, some specific EEG patterns have been described: generalized rhythmic delta activity (GRDA) and extreme delta brush (EDB). In comatose patients, the association of these EEG abnormalities with subtle motor manifestations can suggest ongoing non-convulsive status epilepticus (NCSE). We report the case of a 28-year-old woman admitted for a clinical presentation typical of anti-NMDA-R encephalitis, which was confirmed by CSF analysis. She was rapidly intubated because of severe dysautonomia and disturbed consciousness. Clinical examination revealed subtle paroxysmal and intermittent myoclonic and tonic movements, correlated on video-EEG with GRDA and/or EDB. NCSE was then suspected, but electroclinical manifestations persisted despite many anti-epileptic drugs combinations, or reappeared when barbiturate anesthesia was decreased. In order to confirm or dismiss the diagnosis, intracranial pressure (ICP) and surface video-EEG monitoring were performed simultaneously and revealed no ICP increase, thus being strongly against a diagnosis of seizures. Sedation was progressively weaned, and clinical condition as well as EEG appearance progressively improved. Literature review revealed 11 similar cases, including 2 with focal NCSE. Of the nine other cases, NCSE diagnosis was finally excluded in 5 cases. NCSE diagnosis in association with anti-NMDA-R encephalitis is sometimes very difficult and its occurrence might be overestimated. Video-EEG is highly recommended and more invasive techniques may sometimes be necessary. PMID:26922283

  20. NMDA antagonist properties of the putative antiaddictive drug, ibogaine.

    Popik, P; Layer, R T; Fossom, L H; Benveniste, M; Geter-Douglass, B; Witkin, J M; Skolnick, P

    1995-11-01

    Both anecdotal reports in humans and preclinical studies indicate that ibogaine interrupts addiction to a variety of abused substances including alcohol, opiates, nicotine and stimulants. Based on the similarity of these therapeutic claims to recent preclinical studies demonstrating that N-methyl-D-aspartate (NMDA) antagonists attenuate addiction-related phenomena, we examined the NMDA antagonist properties of ibogaine. Pharmacologically relevant concentrations of ibogaine produce a voltage-dependent block of NMDA receptors in hippocampal cultures (Ki, 2.3 microM at -60 mV). Consistent with this observation, ibogaine competitively inhibits [3H]1-[1-(2-thienyl)-cyclohexyl]piperidine binding to rat forebrain homogenates (Ki, 1.5 microM) and blocks glutamate-induced cell death in neuronal cultures (IC50, 4.5 microM). Moreover, at doses previously reported to interfere with drug-seeking behaviors, ibogaine substitutes as a discriminative stimulus (ED50, 64.9 mg/kg) in mice trained to discriminate the prototypic voltage-dependent NMDA antagonist, dizocilpine (0.17 mg/kg), from saline. Consistent with previous reports, ibogaine reduced naloxone-precipitated jumping in morphine-dependent mice (ED50, 72 mg/kg). Although pretreatment with glycine did not affect naloxone-precipitated jumping in morphine-dependent mice, it abolished the ability of ibogaine to block naloxone-precipitated jumping. Taken together, these findings link the NMDA antagonist actions of ibogaine to a putative "antiaddictive" property of this alkaloid, its ability to reduce the expression of morphine dependence. PMID:7473163

  1. Effects of intracerebroventricular NMDA and non-NMDA receptor agonists or antagonists on general anesthesia of propofol in mice

    XU Aijun; DUAN Shiming; TIAN Yuke

    2007-01-01

    The efiects of intracerebroventricular(icv)agonists and antagonists of N-methyl-D-aspartate(NMDA)and alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptors on the general anesthesia of propofol were studied.A tohal of 144 Kunming mice,male and female with body mass of(22±3)g,were used.Part One of the Experiment:a total of 104 Kunming mice,male and female,were randomly divided into 13 groups.Intracerebroventricular artificial cerebral fluid (aCSF)or different doses of NMDA,AMPA,MK-801 or NBOX was iniected immediately after intravenously administered propofol 25 mg/kg and the recovery time following the loss of righting reflex (LORR)was recorded.Part Two of the Experiment:a total of 40 Kunming female mice were divided randomly into 5 groups and iniected with icv aCSF or NMDA.AMPA.MK-801 or NBQX after intraperitoneally administered propofol 50 mg/kg.The pain threshold of the mice was then investigated by hot-plate test(HPPT).NMDA(0.05 or 0.075μg,icv)or AMPA(0.05 μg,icv)exhibited no effects on the LORR,but NMDA(0.1 μg,icv)or AMPA(0.075 or 0.1 μg,icv)prolonged the LORR significantly compared with the aCSF group(P<0.05,P<0.01).The LORR of the 2 μg MK-801 group had no changes,while those of the 4 or 8 μg MK-801 groups were prolonged significantly.The LORR of the 0.5,2 or 4 μg NBQX groups were all prolonged significantly.NMDA 0.05 μg or AMPA 0.05 μg decreased the pain threshold slightly but did not differ in effect compared with the aCSF group;2 μg MK-801 or 0.5 μg NBQX both increased the pain threshold significantly.Our results indicate that propofol produces general anesthesia partly through an interaction with brain NMDA and AMPA receptors in mice.

  2. Augmentation Mammaplasty in Asian Women

    Cheng, Ming-Huei; Huang, Jung-Ju

    2009-01-01

    With the rapid economic development of Southeast Asia, the demand for cosmetic surgery has increased rapidly. Breast augmentation is among the most frequently performed cosmetic procedures. However, breast augmentation still has “bad press” in Southeast Asia because of not so distant catastrophes caused by direct liquid silicone injection and “Amazing Gel” augmentations. Asian patients have special characteristics that need to be taken into consideration when performing breast augmentation. T...

  3. Intracellular Ca2+ stores modulate SOCCs and NMDA receptors via tyrosine kinases in rat hippocampal neurons.

    Koss, David J; Riedel, Gernot; Platt, Bettina

    2009-07-01

    The regulation of intracellular Ca(2+) signalling by phosphorylation processes remains poorly defined, particularly with regards to tyrosine phosphorylation. Evidence from non-excitable cells implicates tyrosine phosphorylation in the activation of so-called store-operated Ca(2+) channels (SOCCs), but their involvement in neuronal Ca(2+) signalling is still elusive. In the present study, we determined the role of protein tyrosine kinases (PTKs) and tyrosine phosphatases (PTPs) in the coupling between intracellular Ca(2+) stores and SOCCs in neonatal rat hippocampal neurons by Fura-2 Ca(2+) imaging. An early Ca(2+) response from intracellular stores was triggered with thapsigargin, and followed by a secondary plasma membrane Ca(2+) response. This phase was blocked by the non-specific Ca(2+) channel blocker NiCl and the SOCC blocker, 2-aminoethoxydiphenyl borate (2-APB). Interestingly, two structurally distinct PTK inhibitors, genistein and AG126, also inhibited this secondary response. Application of the PTP inhibitor sodium orthovanadate (OV) also activated a sustained and tyrosine kinase dependent Ca(2+) response, blocked by NiCl and 2-APB. In addition, OV resulted in a Ca(2+) store dependent enhancement of NMDA responses, corresponding to, and occluding the signalling pathway for group I metabotropic glutamate receptors (mGluRs). This study provides first evidence for tyrosine based phospho-regulation of SOCCs and NMDA signalling in neurons. PMID:19423160

  4. Severely impaired learning and altered neuronal morphology in mice lacking NMDA receptors in medium spiny neurons.

    Lisa R Beutler

    Full Text Available The striatum is composed predominantly of medium spiny neurons (MSNs that integrate excitatory, glutamatergic inputs from the cortex and thalamus, and modulatory dopaminergic inputs from the ventral midbrain to influence behavior. Glutamatergic activation of AMPA, NMDA, and metabotropic receptors on MSNs is important for striatal development and function, but the roles of each of these receptor classes remain incompletely understood. Signaling through NMDA-type glutamate receptors (NMDARs in the striatum has been implicated in various motor and appetitive learning paradigms. In addition, signaling through NMDARs influences neuronal morphology, which could underlie their role in mediating learned behaviors. To study the role of NMDARs on MSNs in learning and in morphological development, we generated mice lacking the essential NR1 subunit, encoded by the Grin1 gene, selectively in MSNs. Although these knockout mice appear normal and display normal 24-hour locomotion, they have severe deficits in motor learning, operant conditioning and active avoidance. In addition, the MSNs from these knockout mice have smaller cell bodies and decreased dendritic length compared to littermate controls. We conclude that NMDAR signaling in MSNs is critical for normal MSN morphology and many forms of learning.

  5. Augmenting Clozapine With Sertindole

    Nielsen, Jimmi; Emborg, Charlotte; Gydesen, Susanne;

    2012-01-01

    study design was a 12-week, double-blind, randomized, placebo-controlled study including patients with International Statistical Classification of Diseases, 10th Revision schizophrenia (F20.0-F20.3) and treated with clozapine for at least 6 months who had not achieved sufficient response. Patients were...... Inventory, fasting glucose, lipids, and electrocardiogram. Clozapine augmentation with sertindole was not superior to placebo regarding total score or subscale score of the Positive and Negative Syndrome Scale, Clinical Global Impression, World Health Organization Quality of Life Brief, or Drug Attitude...... Inventory. No increased adverse effects compared with placebo were found. Four patients randomized to sertindole experienced a significant worsening of psychosis, and 2 of them required psychiatric admission. Metabolic parameters were unchanged during the study, but augmentation of clozapine with sertindole...

  6. Augmented Reality als Bildungsenhancement?

    Damberger, Thomas

    2015-01-01

    Die Realität, die sich mithilfe von Datenbrillen und Smartphone Applikationen in die virtuelle Welt hinein ausdehnt, erfährt eine Form des Enhancements. Ein solches Enhancement kann unter bestimmten Voraussetzungen als Bildungsenhancement verstanden werden. Der Text befasst sich mit Formen der erweiterten Realität, ferner mit dem, um was es wesentlich bei der Bildung geht und zuletzt mit den Bedingungen, die erforderlich sind, um diesem Wesentlichen mit Hilfe von augmented reality besser zum ...

  7. The importance of N-methyl-D-aspartate (NMDA) receptors in subtraction of electrosensory reafference in the dorsal nucleus of skates.

    Zhang, Zhi; Bodznick, David

    2010-08-01

    The dorsal nucleus of the little skate is a cerebellum-like sensory structure that adaptively filters out predictable electrosensory inputs. The filter's plasticity is mediated by anti-Hebbian associative depression at the synapses between parallel fibers and ascending efferent neurons (AENs). Changes in synaptic strength are indicated by the formation of a cancellation signal which is initiated by co-activation of parallel fibers and AENs, and can be reversed by parallel fiber activity in the absence of AEN activation. In other cerebellum-like sensory structures, the formation of the cancellation signal requires activation of postsynaptic NMDA receptors on the principal neurons. We demonstrate here by immunohistochemistry that the somas and the initial portion of both apical and basal dendrites of the AENs are labeled with antibodies raised against the NR1 subunit of NMDA receptors from a South American electric fish. In in vivo physiological experiments, we show that the formation of the cancellation signal induced by coupling an electrosensory stimulus to ventilatory movements or direct parallel fiber stimulation is blocked when either of the NMDA receptor antagonists 2-amino-5-phosphonovaleric acid (APV) or MK801 is injected into the molecular layer above the recorded AEN. Blocking NMDA receptors prevented formation of a cancellation signal in 79% (15/19; APV) and 60% (3/5; MK801) of the AENs. This blockage was reversible in 40% (6/15) of the AENs after APV removal. Thus, in the dorsal nucleus, the activity-dependent, long-lasting but reversible change in synaptic strength of the parallel fiber-AEN synapses appears to be an NMDA receptor-dependent process. PMID:20639432

  8. Is the shear wave sonographic elastography correlated with pain after breast augmentation with silicone implants an indication of inflammatory activity? A preliminary report

    2011-01-01

    Introduction Formation of a capsule is a natural inflammatory response to a foreign body such as a breast implant. Breast capsular contracture is the most severe complication of implant surgery. Aim To evaluate breast tissues and the periprosthetic reaction with sonoelastography. Material and methods Nineteen patients aged 20-41 underwent breast augmentation with silicone-filled implants. Their 38 breasts were evaluated before surgery, and 7 and 14 days after surgery. Whole breast stiffness w...

  9. miR-155 augments CD8+ T-cell antitumor activity in lymphoreplete hosts by enhancing responsiveness to homeostatic γc cytokines

    Ji, Yun; Wrzesinski, Claudia; Yu, Zhiya; Hu, Jinhui; Gautam, Sanjivan; Hawk, Nga V.; Telford, William G; Douglas C Palmer; Franco, Zulmarie; Sukumar, Madhusudhanan; Roychoudhuri, Rahul; Clever, David; Klebanoff, Christopher A.; Surh, Charles D.; Waldmann, Thomas A.

    2014-01-01

    We describe here a strategy based on microRNA therapeutics to augment the efficacy of T-cell–based therapies without the requirement of toxic maneuvers such as lymphodepletion preconditioning and the administration of high doses of exogenous cytokines. These findings can lead to the development of safer and more effective T-cell–based therapies for the treatment of patients with advanced cancer.

  10. Forskolin Enhances Synaptic Transmission in Rat Dorsal Striatum through NMDA Receptors and PKA in Different Phases.

    Cho, Hyeong Seok; Lee, Hyun Ho; Choi, Se Joon; Kim, Ki Jung; Jeun, Seung Hyun; Li, Qing-Zhong; Sung, Ki-Wug

    2008-12-01

    The effect of forskolin on corticostriatal synaptic transmission was examined by recording excitatory postsynaptic currents (EPSCs) in rat brain slices using the whole-cell voltage-clamp technique. Forskolin produced a dose-dependent increase of corticostriatal EPSCs (1, 3, 10, and 30 microM) immediately after its treatment, and the increase at 10 and 30 microM was maintained even after its washout. When the brain slices were pre-treated with (DL)-2-amino-5-phosphonovaleric acid (AP-V, 100 microM), an NMDA receptor antagonist, the acute effect of forskolin (10 microM) was blocked. However, after washout of forskolin, an increase of corticostriatal EPSCs was still observed even in the presence of AP-V. When KT 5720 (5 microM), a protein kinase A (PKA) inhibitor, was applied through the patch pipette, forskolin (10 microM) increased corticostriatal EPSCs, but this increase was not maintained. When forskolin was applied together with AP-V and KT 5720, both the increase and maintenance of the corticostriatal EPSCs were blocked. These results suggest that forskolin activates both NMDA receptors and PKA, however, in a different manner. PMID:19967070

  11. Kalirin Binds the NR2B Subunit of the NMDA Receptor, Altering Its Synaptic Localization and Function

    Kiraly, D. D.

    2011-08-31

    The ability of dendritic spines to change size and shape rapidly is critical in modulating synaptic strength; these morphological changes are dependent upon rearrangements of the actin cytoskeleton. Kalirin-7 (Kal7), a Rho guanine nucleotide exchange factor localized to the postsynaptic density (PSD), modulates dendritic spine morphology in vitro and in vivo. Kal7 activates Rac and interacts with several PSD proteins, including PSD-95, DISC-1, AF-6, and Arf6. Mice genetically lacking Kal7 (Kal7KO) exhibit deficient hippocampal long-term potentiation (LTP) as well as behavioral abnormalities in models of addiction and learning. Purified PSDs from Kal7KO mice contain diminished levels of NR2B, an NMDA receptor subunit that plays a critical role in LTP induction. Here we demonstrate that Kal7KO animals have decreased levels of NR2B-dependent NMDA receptor currents in cortical pyramidal neurons as well as a specific deficit in cell surface expression of NR2B. Additionally, we demonstrate that the genotypic differences in conditioned place preference and passive avoidance learning seen in Kal7KO mice are abrogated when animals are treated with an NR2B-specific antagonist during conditioning. Finally, we identify a stable interaction between the pleckstrin homology domain of Kal7 and the juxtamembrane region of NR2B preceding its cytosolic C-terminal domain. Binding of NR2B to a protein that modulates the actin cytoskeleton is important, as NMDA receptors require actin integrity for synaptic localization and function. These studies demonstrate a novel and functionally important interaction between the NR2B subunit of the NMDA receptor and Kalirin, proteins known to be essential for normal synaptic plasticity.

  12. Stereotyped initiation of retinal waves by bipolar cells via presynaptic NMDA autoreceptors.

    Zhang, Rong-Wei; Li, Xiao-Quan; Kawakami, Koichi; Du, Jiu-Lin

    2016-01-01

    Glutamatergic retinal waves, the spontaneous patterned neural activities propagating among developing retinal ganglion cells (RGCs), instruct the activity-dependent refinement of visuotopic maps. However, its initiation and underlying mechanism remain largely elusive. Here using larval zebrafish and multiple in vivo approaches, we discover that bipolar cells (BCs) are responsible for the generation of glutamatergic retinal waves. The wave originates from BC axon terminals (ATs) and propagates laterally to nearby BCs and vertically to downstream RGCs and the optic tectum. Its initiation is triggered by the activation of and consequent glutamate release from BC ATs, and is mediated by the N-methyl-D-aspartate subtype of glutamate receptors (NMDARs) expressed at these ATs. Intercellular asymmetry of NMDAR expression at BC ATs enables the preferential initiation of waves at the temporal retina, where BC ATs express more NMDARs. Thus, our findings indicate that glutamatergic retinal waves are initiated by BCs through a presynaptic NMDA autoreceptor-dependent process. PMID:27586999

  13. Molekulare Determinanten der Regulation von Kainat- und NMDA-Rezeptoren

    Schwarz, Regina

    2008-01-01

    Ionotrope Glutamatrezeptoren sind die vorherrschenden exzitatorischen Neurotransmitterrezeptoren im Zentralnervensystem der Wirbeltiere. Die vorliegende Arbeit beschäftigt sich mit der Regulation von Kainat- und NMDA-Rezeptoren. Kürzlich wurde gezeigt, dass eine Genvariante der zu den Kainat-Rezeptoren gehörenden Glutamatrezeptoruntereinheit GluR6 signifikant mit Autismus assoziiert. Im Rahmen dieser Arbeit konnte gezeigt werden, dass die Autismus-assoziierte Mutation M836I in GluR6 eine ...

  14. Steroidní modulátory NMDA receptoru

    Černý, Ivan; Pouzar, Vladimír; Chodounská, Hana

    Ĺubochňa : Národný endokrinologický a diabetologický ústav v Ĺubochni, 2010. s. 22-22. [Imunoanalýza 2010. 14.06.2010-18.06.2010, Ĺubochňa] R&D Projects: GA MŠk(CZ) LC06077 Institutional research plan: CEZ:AV0Z40550506 Keywords : NMDA receptor * steroids Subject RIV: CC - Organic Chemistry

  15. Phantomschmerz und kortikale Reorganisation: praeventive und therapeutische Effekte eines NMDA-Antagonisten

    Wiech, Katja

    2000-01-01

    Nach Amputation einer Extremität treten bei vielen Patienten Phantomschmerzen (PS) auf. Grundlage dieser Schmerzen ist eine Sensibilisierung schmerzrelevanter Strukturen, an der NMDA-Rezeptoren beteiligt sind. In der vorliegenden Studie wurde der analgetische Effekt eines NMDA-Antagonisten auf chronische PS sowie eine mögliche präventive Wirkung bei akuten Patienten untersucht. In beiden Teilstudien wurde der NMDA-Antagonist Memantine über 4 Wochen eingenommen und doppelblind gegen ein Pla...

  16. Selective Vulnerabilities of N-methyl-D-aspartate (NMDA) Receptors During Brain Aging

    Magnusson, Kathy R.; Brenna L Brim; Das, Siba R.

    2010-01-01

    N-methyl-D-aspartate (NMDA) receptors are present in high density within the cerebral cortex and hippocampus and play an important role in learning and memory. NMDA receptors are negatively affected by aging, but these effects are not uniform in many different ways. This review discusses the selective age-related vulnerabilities of different binding sites of the NMDA receptor complex, different subunits that comprise the complex, and the expression and functions of the receptor within differe...

  17. Is the acute NMDA receptor hypofunction a valid model of schizophrenia?

    Adell, Albert; Jiménez-Sánchez, Laura; López-Gil, Xavier; Romón, Tamara

    2012-01-01

    Several genetic, neurodevelopmental, and pharmacological animal models of schizophrenia have been established. This short review examines the validity of one of the most used pharmacological model of the illness, ie, the acute administration of N-methyl-D-aspartate (NMDA) receptor antagonists in rodents. In some cases, data on chronic or prenatal NMDA receptor antagonist exposure have been introduced for comparison. The face validity of acute NMDA receptor blockade is granted inasmuch as hype...

  18. Purkinje cell NMDA receptors assume a key role in synaptic gain control in the mature cerebellum

    Piochon, Claire; Levenes, Carole; Ohtsuki, Gen; Hansel, Christian

    2010-01-01

    textabstractA classic view in cerebellar physiology holds that Purkinje cells do not express functional NMDA receptors and that, therefore, postsynaptic NMDA receptors are not involved in the induction of long-term depression (LTD) at parallel fiber (PF) to Purkinje cell synapses. Recently, it has been demonstrated that functional NMDA receptors are postsynaptically expressed at climbing fiber (CF) to Purkinje cell synapses in mice, reaching full expression levels at ∼2 months after birth. He...

  19. Electrophysiological Characterization of AMPA and NMDA Receptors in Rat Dorsal Striatum

    Jeun, Seung Hyun; Cho, Hyeong Seok; Kim, Ki Jung; Li, Qing Zhong; Sung, Ki-Wug

    2009-01-01

    The striatum receives glutamatergic afferents from the cortex and thalamus, and these synaptic transmissions are mediated by α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) and N-methyl-D-aspartate (NMDA) receptors. The purpose of this study was to characterize glutamate receptors by analyzing NMDA/AMPA ratio and rectification of AMPA and NMDA excitatory postsynaptic currents (EPSCs) using a whole-cell voltage-clamp method in the dorsal striatum. Receptor antagonists were used to isol...

  20. Cell-type Specific Development of NMDA Receptors in the Interneurons of Rat Prefrontal Cortex

    Wang, Huai-Xing; Gao, Wen-Jun

    2009-01-01

    In the prefrontal cortex, N-methyl-D-aspartic acid (NMDA) receptors are critical not only for normal prefrontal functions but also for the pathological processes of schizophrenia. Little is known, however, about the developmental properties of NMDA receptors in the functionally diverse subpopulations of interneurons. We investigated the developmental changes of NMDA receptors in rat prefrontal interneurons using patch clamp recording in cortical slices. We found that fast-spiking (FS) interne...

  1. NMDA spike/plateau potentials in dendrites of thalamocortical neurons.

    Augustinaite, Sigita; Kuhn, Bernd; Helm, Paul Johannes; Heggelund, Paul

    2014-08-13

    Dendritic NMDA spike/plateau potentials, first discovered in cortical pyramidal neurons, provide supralinear integration of synaptic inputs on thin and distal dendrites, thereby increasing the impact of these inputs on the soma. The more specific functional role of these potentials has been difficult to clarify, partly due to the complex circuitry of cortical neurons. Thalamocortical (TC) neurons in the dorsal lateral geniculate nucleus participate in simpler circuits. They receive their primary afferent input from retina and send their output to visual cortex. Cortex, in turn, regulates this output through massive feedback to distal dendrites of the TC neurons. The TC neurons can operate in two modes related to behavioral states: burst mode prevailing during sleep, when T-type calcium bursts largely disrupt the transfer of signals from retina to cortex, and tonic mode, which provides reliable transfer of retinal signals to cortex during wakefulness. We studied dendritic potentials in TC neurons with combined two-photon calcium imaging and whole-cell recording of responses to local dendritic glutamate iontophoresis in acute brain slices from mice. We found that NMDA spike/plateaus can be elicited locally at distal dendrites of TC neurons. We suggest that these dendritic potentials have important functions in the cortical regulation of thalamocortical transmission. NMDA spike/plateaus can induce shifts in the functional mode from burst to tonic by blockade of T-type calcium conductances. Moreover, in tonic mode, they can facilitate the transfer of retinal signals to cortex by depolarization of TC neurons. PMID:25122891

  2. Catatonic Syndrome in Anti-NMDA Receptor Encephalitis

    Mythri, Starlin Vijay; Mathew, Vivek

    2016-01-01

    Anti-N-methyl-D-aspartate (NMDA) receptor encephalitis is a newly recognised autoimmune condition. With its typical clinical pattern, consistent association with the presence of auto antibodies and rapid improvement with immunotherapy, this condition is giving insights into the boundaries between psychiatry and other neurosciences, and is opening avenues for future research. In a young lady who presented with catatonia, we considered anti-NMDA receptor encephalitis, after ruling out other aetiologies. After a positive antibody test we treated her with immunotherapy. She showed gradual improvement in her psychotic and catatonic symptoms. Knowledge regarding the nature and function of NMDA receptors and pathophysiology of this particular encephalitis is important for psychiatric practice. The great opportunity for research in this area due to its association with psychotic disorders is evident but an appeal to temper the enthusiasm by considering the historical lessons learnt from Karl Jaspers’ critique of General Paresis of Insane, is in place. Catatonic syndrome has to be conceptualised broadly and should be recognised with a separate nosological position.

  3. Alcohol and NMDA Receptor: Current research and future direction

    Raman eChandrasekar

    2013-05-01

    Full Text Available The brain is one of the major targets of alcohol actions. Most of the excitatory synaptic transmission in the central nervous system is mediated by NMDA receptors. However, one of the most devastating effects of alcohol leads to brain shrinkage, loss of nerve cells at specific regions through a mechanism involving excitotoxicity, oxidative stress. Earlier studies have indicated that chronic exposure to ethanol both in vivo and in vitro, increases NR1 and NR2B gene expression and their polypeptide levels. The effect of alcohol and molecular changes on the regulatory process, which modulates NMDAR functions including factors altering transcription, translation, post-translational modifications and protein expression, as well as those influencing their interactions with different regulatory proteins (downstream effectors are incessantly increasing at the cellular level. Further, I discuss the various genetically altered mice approaches that have been used to study NMDA receptor subunits and their functional implication. In a recent countable review, epigenetic dimension (i.e., histone modification-induced chromatin remodeling and DNA methylation, in the process of alcohol related neuroadapation is one of the key molecular mechanisms in alcohol mediated NMDAR alteration. Here, I provide a recount on what has already been achieved, current trends and how the future research/studies of the NMDA receptor might lead to even greater engagement with many possible new insights into the neurobiology and treatment of alcoholism.

  4. MicroRNA-219 modulates NMDA receptor-mediated neurobehavioral dysfunction

    Kocerha, Jannet; Faghihi, Mohammad Ali; Lopez-Toledano, Miguel A;

    2009-01-01

    significantly modulated behavioral responses associated with disrupted NMDA receptor transmission. Furthermore, pretreatment with the antipsychotic drugs haloperidol and clozapine prevented dizocilpine-induced effects on miR-219. Taken together, these data support an integral role for miR-219 in the expression......N-methyl-D-aspartate (NMDA) glutamate receptors are regulators of fast neurotransmission and synaptic plasticity in the brain. Disruption of NMDA-mediated glutamate signaling has been linked to behavioral deficits displayed in psychiatric disorders such as schizophrenia. Recently, noncoding RNA...... of behavioral aberrations associated with NMDA receptor hypofunction....

  5. The role of NMDA receptors in human eating behavior: evidence from a case of anti-NMDA receptor encephalitis

    Perogamvros, Lampros; Schnider, Armin; Leemann, Béatrice Anne Valérie

    2012-01-01

    Research in animal models has implicated N-methyl-D-aspartate (NMDA) receptors (NMDARs) in the control of food intake. Until now, these findings have been not replicated in humans. Here we describe a 22-year-old woman with anti-NMDAR encephalitis and no prior neurological or psychiatric history. Her clinical course was marked by successive eating disorders: anorexia followed by hyperphagia. We propose that, much as they do in other animals, NMDARs in humans interact with the neuroendocrine, h...

  6. Inhibition of in vivo [(3)H]MK-801 binding by NMDA receptor open channel blockers and GluN2B antagonists in rats and mice.

    Fernandes, Alda; Wojcik, Trevor; Baireddy, Praveena; Pieschl, Rick; Newton, Amy; Tian, Yuan; Hong, Yang; Bristow, Linda; Li, Yu-Wen

    2015-11-01

    N-methyl-D-aspartate (NMDA) receptor antagonists, including open channel blockers and GluN2B receptor subtype selective antagonists, have been developed for the treatment of depression. The current study investigated effects of systemically administered NMDA channel blockers and GluN2B receptor antagonists on NMDA receptor activity in rodents using in vivo [(3)H]MK-801 binding. The receptor occupancy of GluN2B antagonists was measured using ex vivo [(3)H]Ro 25-6981 binding. Ketamine, a NMDA receptor channel blocker, produced a dose/exposure- and time-dependent inhibition of in vivo [(3)H]MK-801 binding that was maximal at ~100%. The complete inhibition of in vivo [(3)H]MK-801 binding was also observed with NMDA receptor channel blockers, AZD6765 (Lanicemine) and MK-801 (Dizocilpine). CP-101,606 (Traxoprodil), a GluN2B antagonist, produced a dose/exposure- and time-dependent inhibition of in vivo [(3)H]MK-801 binding that was maximal at ~60%. Partial inhibition was also observed with other GluN2B antagonists including MK-0657 (CERC-301), EVT-101, Ro 25-6981 and radiprodil. For all GluN2B antagonists tested, partial [(3)H]MK-801 binding inhibition was achieved at doses saturating GluN2B receptor occupancy. Combined treatment with ketamine (10mg/kg, i.p.) and Ro 25-6981(10mg/kg, i.p.) produced a level of inhibition of in vivo [(3)H]MK-801 binding that was similar to treatment with either agent alone. In conclusion, this in vivo [(3)H]MK-801 binding study shows that NMDA receptor activity in the rodent forebrain can be inhibited completely by channel blockers, but only partially (~60%) by GluN2B receptor antagonists. At doses effective in preclinical models of depression, ketamine may preferentially inhibit the same population of NMDA receptors as Ro 25-6981, namely those containing the GluN2B subunit. PMID:26325093

  7. In vitro and in vivo evaluation of polymethylene tetraamine derivatives as NMDA receptor channel blockers.

    Saiki, Ryotaro; Yoshizawa, Yuki; Minarini, Anna; Milelli, Andrea; Marchetti, Chiara; Tumiatti, Vincenzo; Toida, Toshihiko; Kashiwagi, Keiko; Igarashi, Kazuei

    2013-07-01

    The biological activities of six symmetrically substituted 2-methoxy-benzyl polymethylene tetraamines (1-4) and diphenylethyl polymethylene tetraamines (5 and 6) as N-methyl-D-aspartate (NMDA) receptor channel blockers, were evaluated in vitro and in vivo. Although all compounds exhibited stronger channel block activities in comparison to memantine in Xenopus oocytes voltage clamped at -70 mV, only compound 2 (0.4 mg/kg intravenous injection) decreased the size of brain infarction in a photochemically induced thrombosis model mice at the same extent of memantine (10mg/kg intravenous injection). Other compounds (1, 3, 4, 5 and 6) did not decrease the size of brain infarction significantly due to the limited injection doses. The present study suggests that compound 2 could represent a valuable lead compound to design low toxicity polyamines for clinical use against stroke. PMID:23692871

  8. AR DOC: Augmented reality documentaries

    Vistisen, Peter

    2014-01-01

    Augmented Reality Documentaries (AR DOC) er et ’lille’ Shareplay projekt (ansøgte midler <= 125.000 DKK), der af haft som sit formål at afprøve et unikt samarbejde omkring udforskningen af nye teknikker til augmented reality cross media løsninger, til at skabe engagerende publikumsformidling...... indenfor oplevelsesindustrien. Projektet har genereret ny viden omkring, hvordan fysisk og digital formidling kan understøttes via Augmented Reality som formidlingsformat....

  9. Rendering methods for augmented reality

    Fischer, Jan

    2006-01-01

    Augmented reality (AR) has become a promising and fast-growing application of computer graphics over the course of the last years. Augmented reality systems overlay computer-generated graphical information over the view of the real world. Several main research challenges can be identified in the field of augmented reality. These are the design of advanced display devices (e.g., head-mounted displays), camera tracking, system design, user interaction, and rendering. While a major part of the p...

  10. AUGMENTATION-RELATED BRAIN PLASTICITY

    Giovanni eDi Pino; Angelo eMaravita; Loredana eZollo; Eugenio eGuglielmelli; Vincenzo eDi Lazzaro

    2014-01-01

    Today, the anthropomorphism of the tools and the development of neural interfaces require reconsidering the concept of human-tools interaction in the framework of human augmentation. This review analyzes the plastic process that the brain undergoes when it comes into contact with augmenting artificial sensors and effectors and, on the other hand, the changes that the use of external augmenting devices produces in the brain.Hitherto, few studies investigated the neural correlates of augmentati...

  11. Augmentation-related brain plasticity

    Di Pino, Giovanni; Maravita, Angelo; Zollo, Loredana; Guglielmelli, Eugenio; Di Lazzaro, Vincenzo

    2014-01-01

    Today, the anthropomorphism of the tools and the development of neural interfaces require reconsidering the concept of human-tools interaction in the framework of human augmentation. This review analyses the plastic process that the brain undergoes when it comes into contact with augmenting artificial sensors and effectors and, on the other hand, the changes that the use of external augmenting devices produces in the brain. Hitherto, few studies investigated the neural correlates of augmentat...

  12. Augmented Reality for Science Education

    Brandt, Harald; Nielsen, Birgitte Lund; Georgsen, Marianne;

    Augmented reality (AR) holds great promise as a learning tool. So far, however, most research has looked at the technology itself – and AR has been used primarily for commercial purposes. As a learning tool, AR supports an inquiry-based approach to science education with a high level of student...... involvement. The AR-sci-project (Augmented Reality for SCIence education) addresses the issue of applying augmented reality in developing innovative science education and enhancing the quality of science teaching and learning....

  13. Augmented Sustainability Measures for Scotland

    John C. V. Pezzey; Nick Hanley; Karen Turner; Dugald Tinch

    2003-01-01

    We estimate and compare two empirical measures of the weak sustainability of an economy for the first time: the change in augmented green net national product (GNNP), and the interest on augmented genuine savings (GS). Yearly calculations are given for each measure for Scotland during 1992-99. Augmentation means including, using projections to 2020, production possibilities enabled by exogenous technical progress or changing terms of trade. In passing, we clarify the treatment of environmenta...

  14. Augmented Reality for Science Education

    Brandt, Harald; Nielsen, Birgitte Lund; Georgsen, Marianne;

    2015-01-01

    Augmented reality (AR) holds great promise as a learning tool. So far, however, most research has looked at the technology itself – and AR has been used primarily for commercial purposes. As a learning tool, AR supports an inquiry-based approach to science education with a high level of student...... involvement. The AR-sci-project (Augmented Reality for SCIence education) addresses the issue of applying augmented reality in developing innovative science education and enhancing the quality of science teaching and learning....

  15. Differential antagonism of tetramethylenedisulfotetramine-induced seizures by agents acting at NMDA and GABAA receptors

    Tetramethylenedisulfotetramine (TMDT) is a highly lethal neuroactive rodenticide responsible for many accidental and intentional poisonings in mainland China. Ease of synthesis, water solubility, potency, and difficulty to treat make TMDT a potential weapon for terrorist activity. We characterized TMDT-induced convulsions and mortality in male C57BL/6 mice. TMDT (ip) produced a continuum of twitches, clonic, and tonic–clonic seizures decreasing in onset latency and increasing in severity with increasing dose; 0.4 mg/kg was 100% lethal. The NMDA antagonist, ketamine (35 mg/kg) injected ip immediately after the first TMDT-induced seizure, did not change number of tonic–clonic seizures or lethality, but increased the number of clonic seizures. Doubling the ketamine dose decreased tonic–clonic seizures and eliminated lethality through a 60 min observation period. Treating mice with another NMDA antagonist, MK-801, 0.5 or 1 mg/kg ip, showed similar effects as low and high doses of ketamine, respectively, and prevented lethality, converting status epilepticus EEG activity to isolated interictal discharges. Treatment with these agents 15 min prior to TMDT administration did not increase their effectiveness. Post-treatment with the GABAA receptor allosteric enhancer diazepam (5 mg/kg) greatly reduced seizure manifestations and prevented lethality 60 min post-TMDT, but ictal events were evident in EEG recordings and, hours post-treatment, mice experienced status epilepticus and died. Thus, TMDT is a highly potent and lethal convulsant for which single-dose benzodiazepine treatment is inadequate in managing electrographic seizures or lethality. Repeated benzodiazepine dosing or combined application of benzodiazepines and NMDA receptor antagonists is more likely to be effective in treating TMDT poisoning. -- Highlights: ► TMDT produces convulsions and lethality at low doses in mice. ► Diazepam pre- or post-treatments inhibit TMDT-induced convulsions and death.

  16. Augmented reality system

    Lin, Chien-Liang; Su, Yu-Zheng; Hung, Min-Wei; Huang, Kuo-Cheng

    2010-08-01

    In recent years, Augmented Reality (AR)[1][2][3] is very popular in universities and research organizations. The AR technology has been widely used in Virtual Reality (VR) fields, such as sophisticated weapons, flight vehicle development, data model visualization, virtual training, entertainment and arts. AR has characteristics to enhance the display output as a real environment with specific user interactive functions or specific object recognitions. It can be use in medical treatment, anatomy training, precision instrument casting, warplane guidance, engineering and distance robot control. AR has a lot of vantages than VR. This system developed combines sensors, software and imaging algorithms to make users feel real, actual and existing. Imaging algorithms include gray level method, image binarization method, and white balance method in order to make accurate image recognition and overcome the effects of light.

  17. NASA Communications Augmentation network

    Omidyar, Guy C.; Butler, Thomas E.; Laios, Straton C.

    1990-09-01

    The NASA Communications (Nascom) Division of the Mission Operations and Data Systems Directorate (MO&DSD) is to undertake a major initiative to develop the Nascom Augmentation (NAUG) network to achieve its long-range service objectives for operational data transport to support the Space Station Freedom Program, the Earth Observing System (EOS), and other projects. The NAUG is the Nascom ground communications network being developed to accommodate the operational traffic of the mid-1990s and beyond. The NAUG network development will be based on the Open Systems Interconnection Reference Model (OSI-RM). This paper describes the NAUG network architecture, subsystems, topology, and services; addresses issues of internetworking the Nascom network with other elements of the Space Station Information System (SSIS); discusses the operations environment. This paper also notes the areas of related research and presents the current conception of how the network will provide broadband services in 1998.

  18. NAESA Augmentation Pilot Project

    Hoover, John J.

    1998-01-01

    This project was one project within the Native American Earth and Space Academy (NAESA). NAESA is a national initiative comprised of several organizations that support programs which focus on 1) enhancing the technological, scientific and pedagogical skills of K-14 teachers who instruct Native Americans, 2) enhancing the understanding and applications of science, technology, and engineering of college-bound Native Americans and teaching them general college "survival skills" (e.g., test taking, time management, study habits), 3) enhancing the scientific and pedagogical skills of the faculty of tribally-controllcd colleges and community colleges with large Native American enrollments, and 4) strengthening the critical relationships between students, their parents, tribal elders, and their communities. This Augmentation Pilot Project focused on the areas of community-school alliances and intemet technology use in teaching and learning and daily living addressing five major objectives.

  19. Augmented Virtual Reality Laboratory

    Tully-Hanson, Benjamin

    2015-01-01

    Real time motion tracking hardware has for the most part been cost prohibitive for research to regularly take place until recently. With the release of the Microsoft Kinect in November 2010, researchers now have access to a device that for a few hundred dollars is capable of providing redgreenblue (RGB), depth, and skeleton data. It is also capable of tracking multiple people in real time. For its original intended purposes, i.e. gaming, being used with the Xbox 360 and eventually Xbox One, it performs quite well. However, researchers soon found that although the sensor is versatile, it has limitations in real world applications. I was brought aboard this summer by William Little in the Augmented Virtual Reality (AVR) Lab at Kennedy Space Center to find solutions to these limitations.

  20. Magnetohydrodynamic Augmented Propulsion Experiment

    Litchford, Ron J.

    2008-01-01

    Over the past several years, efforts have been under way to design and develop an operationally flexible research facility for investigating the use of cross-field MHD accelerators as a potential thrust augmentation device for thermal propulsion systems. The baseline configuration for this high-power experimental facility utilizes a 1.5-MWe multi-gas arc-heater as a thermal driver for a 2-MWe MHD accelerator, which resides in a large-bore 2-tesla electromagnet. A preliminary design study using NaK seeded nitrogen as the working fluid led to an externally diagonalized segmented MHD channel configuration based on an expendable heat-sink design concept. The current status report includes a review of engineering/design work and performance optimization analyses and summarizes component hardware fabrication and development efforts, preliminary testing results, and recent progress toward full-up assembly and testing

  1. Augmented fish health monitoring

    The Bonneville Power Administration (BPA) initiated the Augmented Fish Health Monitoring project in 1986. This project was a five year interagency project involving fish rearing agencies in the Columbia Basin. Historically, all agencies involved with fish health in the Columbia Basin were conducting various levels of fish health monitoring, pathogen screening and collection. The goals of this project were; to identify, develop and implement a standardized level of fish health methodologies, develop a common data collection and reporting format in the area of artificial production, evaluate and monitor water quality, improve communications between agencies and provide annual evaluation of fish health information for production of healthier smolts. This completion report will contain a project evaluation, review of the goals of the project, evaluation of the specific fish health analyses, an overview of highlights of the project and concluding remarks. 8 refs., 1 fig., 4 tabs

  2. The Effect of an Augmented Reality Enhanced Mathematics Lesson on Student Achievement and Motivation

    Estapa, Anne; Nadolny, Larysa

    2015-01-01

    The purpose of the study was to assess student achievement and motivation during a high school augmented reality mathematics activity focused on dimensional analysis. Included in this article is a review of the literature on the use of augmented reality in mathematics and the combination of print with augmented reality, also known as interactive…

  3. Roles of the NMDA Receptor and EAAC1 Transporter in the Modulation of Extracellular Glutamate by Low and High Affinity AMPA Receptors in the Cerebellum in Vivo: Differential Alteration in Chronic Hyperammonemia.

    Cabrera-Pastor, Andrea; Taoro, Lucas; Llansola, Marta; Felipo, Vicente

    2015-12-16

    The roles of high- and low-affinity AMPA receptors in modulating extracellular glutamate in the cerebellum remain unclear. Altered glutamatergic neurotransmission is involved in neurological alterations in hyperammonemia, which differently affects high- and low-affinity AMPA receptors. The aims were to assess by in vivo microdialysis (a) the effects of high- and low-affinity AMPA receptor activation on extracellular glutamate in the cerebellum; (b) whether chronic hyperammonemia alters extracellular glutamate modulation by high- and/or low-affinity AMPA receptors; and (c) the contribution of NMDA receptors and EAAC1 transporter to AMPA-induced changes in extracellular glutamate. In control rats, high affinity receptor activation does not affect extracellular glutamate but increases glutamate if NMDA receptors are blocked. Low affinity AMPA receptor activation increases transiently extracellular glutamate followed by reduction below basal levels and return to basal values. The reduction is associated with transient increased membrane expression of EAAC1 and is prevented by blocking NMDA receptors. Blocking NMDA receptors with MK-801 induces a transient increase in extracellular glutamate which is associated with reduced membrane expression of EAAC1 followed by increased membrane expression of the glutamate transporter GLT-1. Chronic hyperammonemia does not affect responses to activation of low affinity AMPA receptors. Activation of high affinity AMPA receptors increases extracellular glutamate in hyperammonemic rats by an NMDA receptor-dependent mechanism. In conclusion, these results show that there is a tightly controlled interplay between AMPA and NMDA receptors and an EAAC1 transporter in controlling extracellular glutamate. Hyperammonemia alters high- but not low-affinity AMPA receptors. PMID:26428532

  4. Sensory augmentation for the blind

    Silke Manuela Kärcher

    2012-03-01

    Full Text Available Enacted theories of consciousness conjecture that perception and cognition arise from an active experience of the regular relations that are tying together the sensory stimulation of different modalities and associated motor actions. Previous experiments investigated this concept by employing the technique of sensory substitution. Building on these studies, here we test a set of hypotheses derived from this framework and investigate the utility of sensory augmentation in handicapped people. We provide a late blind subject with a new set of sensorimotor laws: A vibro-tactile belt continually signals the direction of magnetic north. The subject completed a set of behavioral tests before and after an extended training period. The tests were complemented by questionnaires and interviews. This newly supplied information improved performance on different time scales. In a pointing task we demonstrate an instant improvement of performance based on the signal provided by the device. Furthermore, the signal was helpful in relevant daily tasks, often complicated for the blind, such as keeping a direction over longer distances or taking shortcuts in familiar environments. A homing task with an additional attentional load demonstrated a significant improvement after training. The subject found the directional information highly expedient for the adjustment of his inner maps of familiar environments and describes an increase in his feeling of security when exploring unfamiliar environments with the belt. The results give evidence for a firm integration of the newly supplied signals into the behavior of this late blind subject with better navigational performance and more courageous behavior in unfamiliar environments. Most importantly, the complementary information provided by the belt lead to a positive emotional impact with enhanced feeling of security. This experimental approach demonstrates the potential of sensory augmentation devices for the help of

  5. Purkinje cell NMDA receptors assume a key role in synaptic gain control in the mature cerebellum

    C. Piochon (Claire); C. Levenes (Carole); G. Ohtsuki (Gen); C.R.W. Hansel (Christian)

    2010-01-01

    textabstractA classic view in cerebellar physiology holds that Purkinje cells do not express functional NMDA receptors and that, therefore, postsynaptic NMDA receptors are not involved in the induction of long-term depression (LTD) at parallel fiber (PF) to Purkinje cell synapses. Recently, it has b

  6. Opioid analgesics as noncompetitive N-methyl-D-aspartate (NMDA) antagonists

    Ebert, B; Thorkildsen, C; Andersen, S; Christrup, Lona Louring; Hjeds, H

    1998-01-01

    Much evidence points to the involvement of N-methyl-D-aspartate (NMDA) receptors in the development and maintainance of neuropathic pain. In neuropathic pain, there is generally involved a presumed opioid-insensitive component, which apparently can be blocked by NMDA receptor antagonists. However...

  7. Augmented Reality Comes to Physics

    Buesing, Mark; Cook, Michael

    2013-01-01

    Augmented reality (AR) is a technology used on computing devices where processor-generated graphics are rendered over real objects to enhance the sensory experience in real time. In other words, what you are really seeing is augmented by the computer. Many AR games already exist for systems such as Kinect and Nintendo 3DS and mobile apps, such as…

  8. All quiet on the neuronal front: NMDA receptor inhibition by prion protein.

    Steele, Andrew D

    2008-06-01

    The normal function of the prion protein (PrP)--the causative agent of mad cow or prion disease--has long remained out of reach. Deciphering PrP's function may help to unravel the complex chain of events triggered by PrP misfolding during prion disease. In this issue of the JCB, an exciting paper (Khosravani, H., Y. Zhang, S. Tsutsui, S. Hameed, C. Altier, J. Hamid, L. Chen, M. Villemaire, Z. Ali, F.R. Jirik, and G.W. Zamponi. 2008. J. Cell Biol. 181:551-565) connects diverse observations regarding PrP into a coherent framework whereby PrP dampens the activity of an N-methyl-D-aspartate (NMDA) receptor (NMDAR) subtype and reduces excitotoxic lesions. The findings of this study suggest that understanding the normal function of proteins associated with neurodegenerative disease may elucidate the molecular pathogenesis. PMID:18504309

  9. Design, synthesis, and pharmacological characterization of novel, potent NMDA receptor antagonists

    Conti, Paola; De Amici, Marco; Grazioso, Giovanni;

    2004-01-01

    The two diastereomeric pairs of acidic amino acids 5-(2-amino-2-carboxyethyl)-4,5-dihydroisoxazole-3-carboxylic acid (8A/8B) and 4-(2-amino-2-carboxyethyl)-5,5-dimethyl-4,5-dihydroisoxazole-3-carboxylic acid (10A/10B) were prepared via a strategy based on a 1,3-dipolar cycloaddition. The four amino...... acids were tested at ionotropic and metabotropic glutamate receptors. None of the compounds was active, neither as agonists nor as antagonists, at 1 mM on metabotropic receptors (mGluR1, -2, -4, and -5 expressed in CHO cell lines). Conversely, the pair of stereoisomers 8A/8B showed a remarkable affinity...... in in vivo tests on DBA/2 mice. Derivative 10A was inactive at all ionotropic glutamate receptors, whereas its stereoisomer 10B displayed a seizable binding to both NMDA and AMPA receptors....

  10. Augmented Reality in Sports: Today and Tomorrow

    Zafer BOZYER

    2015-08-01

    Full Text Available The rapid change experienced in the field of Information Technologies makes the informati cs more tangible in daily life. Today, it became possible to encounter with the informatics applications almost all the disciplines. As a matter of course, many informatics applications are put into the practice regarding the sports discipline. Because of the condition that the power of information processing has increased and the studies on wearable technol ogies in addition to the expert system design, augmented reality (AR has become a topic which gains imp ortance in the field of sports. There are many studies that are conducted with the aim of increasing the efficiency of physical activities done in many sports branches, ensuring a more fair management of competitions and providing the opportunity for spectators to watch the competitions in a more comfortable and efficient way. In this study; the information about the current augmented reality practices th at are used in various sports branches has been given and the mobile and interactive augmented reality practices which are possible to be seen in future have been mentioned. In addition, there is an augmented reality practice which is designed with the aim of ensuring that the shoots of sports people who are interested in archery, are more stable and of ensuring that the trainings and exercises are more efficient by stating to the sports people whether he or she is in the right position for shoot which is c alled as T shape seen at the time of releasing the arrow.

  11. Introduction to augmented and virtual reality

    Caudell, Thomas P.

    1995-12-01

    This paper introduces the field of augmented reality as a prolog to the body of papers in the remainder of this session. I describe the use of head-mounted display technologies to improve the efficiency and quality of human workers in their performance of engineering design, manufacturing, construction, testing, and maintenance activities. This technology is used to `augment' the visual field of the wearer with information necessary in the performance of the current task. The enabling technology is head-up (see-through) display head sets (HUDsets) combined with head position sensing, real world registration systems, and database access software. A primary difference between virtual reality (VR) and `augmented reality' (AR) is in the complexity of the perceived graphical objects. In AR systems, only simple wire frames, template outlines, designators, and text is displayed. An immediate result of this difference is that augmented reality systems can be driven by standard and inexpensive microprocessors. Many research issues must be addressed before this technology can be widely used, including tracking and registration, human 3D perception and reasoning, and human task performance issues.

  12. Cholesterol modulates open probability and desensitization of NMDA receptors

    Kořínek, Miloslav; Vyklický, Vojtěch; Borovská, Jiřina; Lichnerová, Katarina; Kaniaková, Martina; Krausová, Barbora; Krůšek, Jan; Balík, Aleš; Smejkalová, Tereza; Horák, Martin; Vyklický ml., Ladislav

    2015-01-01

    Roč. 593, č. 10 (2015), s. 2279-2293. ISSN 0022-3751 R&D Projects: GA ČR(CZ) GPP303/11/P391; GA ČR(CZ) GAP303/12/1464; GA ČR(CZ) GBP304/12/G069; GA ČR(CZ) GA14-02219S; GA ČR(CZ) GP14-09220P; GA TA ČR(CZ) TE01020028; GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:67985823 Keywords : NMDA receptor * glutamate-gated * cholesterol Subject RIV: ED - Physiology Impact factor: 5.037, year: 2014

  13. Stress Exacerbates Neuropathic Pain via Glucocorticoid and NMDA Receptor Activation

    Alexander, Jessica K.; DeVries, A. Courtney; KIGERL, KRISTINA A.; Dahlman, Jason M.; G.Popovich, Phillip

    2009-01-01

    There is growing recognition that psychological stress influences pain. Hormones that comprise the physiological response to stress (e.g. corticosterone; CORT) may interact with effectors of neuropathic pain. To test this hypothesis, mice received a spared nerve injury (SNI) after exposure to 60 min restraint stress. In stressed mice, allodynia was consistently increased. The mechanism(s) underlying the exacerbated pain response involves CORT acting via glucocorticoid receptors (GRs); RU486, ...

  14. Adapting Information Through Tangible Augmented Reality Interfaces

    Sinclair, Patrick; Martinez, Kirk

    2004-01-01

    Tangible augmented reality interfaces offer a hands on approach for examining objects and exploring the associated information. We describe two tangible augmented reality interfaces that can expose the adaptation of information presented to users about objects in augmented reality environments.

  15. Endogenous neurotransmitter activates N-methyl-D-aspartate receptors on differentiating neurons in embryonic cortex.

    Blanton, M G; Lo Turco, J J; Kriegstein, A R

    1990-01-01

    Before synapses form in embryonic turtle cerebral cortex, an endogenous neurotransmitter activates N-methyl-D-aspartate (NMDA) channels on neurons in the cortical plate. Throughout cortical development, these channels exhibit voltage-dependent Mg2+ blockade and are antagonized by D-2-amino-5-phosphonovaleric acid, a selective NMDA receptor antagonist. The activation in situ of these nonsynaptic NMDA channels demonstrates a potential physiological substrate for control of early neuronal differ...

  16. Designing Augmented Reality for the Classroom

    Cuendet, Sébastien; Bonnard, Quentin; Do-Lenh, Son; Dillenbourg, Pierre

    2012-01-01

    Augmented reality (AR) has recently received a lot of attention in education. Multiple AR systems for learning have been developed and tested through empirical studies often conducted in lab settings. While lab studies can be insightful, they leave out the complexity of a classroom environment. We developed three AR learning environments that have been used in genuine classroom contexts, some of them being now part of classroom regular practices. These systems and the learning activities they...

  17. Anti-tumor activities of luteolin and silibinin in glioblastoma cells: overexpression of miR-7-1-3p augmented luteolin and silibinin to inhibit autophagy and induce apoptosis in glioblastoma in vivo.

    Chakrabarti, Mrinmay; Ray, Swapan K

    2016-03-01

    Glioblastoma is the deadliest brain tumor in humans. High systemic toxicity of conventional chemotherapies prompted the search for natural compounds for controlling glioblastoma. The natural flavonoids luteolin (LUT) and silibinin (SIL) have anti-tumor activities. LUT inhibits autophagy, cell proliferation, metastasis, and angiogenesis and induces apoptosis; while SIL activates caspase-8 cascades to induce apoptosis. However, synergistic anti-tumor effects of LUT and SIL in glioblastoma remain unknown. Overexpression of tumor suppressor microRNA (miR) could enhance the anti-tumor effects of LUT and SIL. Here, we showed that 20 µM LUT and 50 µM SIL worked synergistically for inhibiting growth of two different human glioblastoma U87MG (wild-type p53) and T98G (mutant p53) cell lines and natural combination therapy was more effective than conventional chemotherapy (10 µM BCNU or 100 µM TMZ). Combination of LUT and SIL caused inhibition of growth of glioblastoma cells due to induction of significant amounts of apoptosis and complete inhibition of invasion and migration. Further, combination of LUT and SIL inhibited rapamycin (RAPA)-induced autophagy, a survival mechanism, with suppression of PKCα and promotion of apoptosis through down regulation of iNOS and significant increase in expression of the tumor suppressor miR-7-1-3p in glioblastoma cells. Our in vivo studies confirmed that overexpression of miR-7-1-3p augmented anti-tumor activities of LUT and SIL in RAPA pre-treated both U87MG and T98G tumors. In conclusion, our results clearly demonstrated that overexpression of miR-7-1-3p augmented the anti-tumor activities of LUT and SIL to inhibit autophagy and induce apoptosis for controlling growth of different human glioblastomas in vivo. PMID:26573275

  18. Zion Augmented Reality Application (ZARA): An Augmented Heritage Prototype

    Odland, Johannes Johannesen

    2007-01-01

    This paper describes the investigation and development of a virtual heritage application that employs augmented reality to disseminate a model of the Zion castle. The developed system is a flexible prototype that leverages several open source frameworks and applications.

  19. Augmented Reality Comes to Physics

    Buesing, Mark; Cook, Michael

    2013-04-01

    Augmented reality (AR) is a technology used on computing devices where processor-generated graphics are rendered over real objects to enhance the sensory experience in real time. In other words, what you are really seeing is augmented by the computer. Many AR games already exist for systems such as Kinect and Nintendo 3DS and mobile apps, such as Tagwhat and Star Chart (a must for astronomy class). The yellow line marking first downs in a televised football game2 and the enhanced puck that makes televised hockey easier to follow3 both use augmented reality to do the job.

  20. Increased NMDA and AMPA receptor densities in the anterior cingulate cortex in schizophrenia

    Full text: The anterior cingulate cortex (ACC) is a brain area of potential importance to our understanding of the pathophysiology of schizophrenia. Since a disturbed balance between excitatory and inhibitory activity is suggested to occur in the ACC in schizophrenia, the present study has focused on the analysis of binding of [3H]MK801, [3H]AMPA and [3H]kainate, radioligands which respectively label the NMDA, AMPA and kainate receptors of the ionotropic glutamate receptor family in the ACC of 10 schizophrenia patients and 10 matched controls, using quantitative autoradiography. AMPA receptor densities were higher in cortical layer II whereas NMDA receptor densities were higher in cortical layers II-III in the ACC of both control and schizophrenia group. In contrast, kainate receptors displayed the highest density in cortical layer V. [3H]AMPA binding was significantly increased by 25% in layer II in the schizophrenia group as compared to the control group. Similarly, a significant 17% increase of [3H]MK801 binding was observed in layers II-III in the schizophrenia group. No statistically significant differences were observed for [3H] kainate binding between the two groups. These results suggest that ionotropic glutamate receptors are differentially altered in the ACC of schizophrenia. The increase in [3H]AMPA and [3H]MK801 binding points to a postsynaptic compensation for impaired glutamatergic neurotransmission in the ACC in schizophrenia. Such abnormality could lead to an imbalance between the excitatory and inhibitory neurotransmission in this brain area that may contribute to the emergence of some schizophrenia symptoms. Copyright (2002) Australian Neuroscience Society

  1. Indian red scorpion venom depresses spinal synaptic transmission without involving NMDA receptors.

    Maurya, Amar N; Deshpande, Shripad B

    2010-05-14

    Stings of Indian red scorpion (Mesobuthus tamulus, MBT) produce neurological abnormalities such as convulsions and paralysis. These parameters indicate the activity at alpha-motoneuron. The present study was therefore, undertaken to evaluate the effect of MBT-venom on spinal reflexes and the involvement of N-methyl-d-aspartate (NMDA) receptors. The experiments were performed on isolated hemisected spinal cords from 4 to 6 days old rats. Stimulation of a dorsal root with supramaximal strength at 0.1Hz evoked monosynaptic (MSR) and polysynaptic reflex (PSR) potentials in the corresponding segmental ventral root. Superfusion of MBT-venom depressed the spinal reflexes in a time- and a concentration-dependent (0.1-1microg/ml) manner. MBT-venom at 0.1, 0.3 and 1.0microg/ml produced maximal depression of 55, 75 and 90% at 30, 10 and 7min, respectively. The time required to produce 50% depression (T-50) of MSR was 19.0, 8.0, and 3.6min and for PSR was 15.0, 5.6, and 2.9min at 0.1, 0.3 and 1microg/ml of venom, respectively. Pre-treatment with DL-alpha-2-amino-5-phosphonovaleric acid (APV) decreased MSR by 26% and abolished PSR. In the presence of APV, the MBT-venom-induced depression of MSR was not different from the venom only group. The results indicate that venom-induced depression of spinal reflexes did not involve NMDA receptors. PMID:20347939

  2. Understanding augmented reality concepts and applications

    Craig, Alan B

    2013-01-01

    Augmented reality is not a technology. Augmented reality is a medium. Likewise, a book on augmented reality that only addresses the technology that is required to support the medium of augmented reality falls far short of providing the background that is needed to produce, or critically consume augmented reality applications. One reads a book. One watches a movie. One experiences augmented reality. Understanding Augmented Reality addresses the elements that are required to create compelling augmented reality experiences. The technology that supports

  3. Spermine modulation of the glutamateNMDA receptors is differentially responsive to conantokins in normal and alzheimer disease human cortex

    Full text: The pharmacological characteristics of human N-methyl-D-aspartate (NMDA) receptors were examined in 12 control and 6 pathologically confirmed Alzheimer disease (AD) cases in six different brain areas, by studying their responses to MK-801, glutamate, spermine, and the NMDA receptor antagonists Ala(7)-conantokinG and Lys(7)-conantokinG. [3H]MK801 binding assays performed by standard protocols on well-washed synoptic plasma membranes showed little variation in kD in all six brain areas, including comparisons between control and matched AD cases. b MAX values showed regional differences within control and AD cases, but there was no significant difference between groups in any of the brain regions. Maximal glutamate-enhanced [3H]MK801 binding did not vary much between the brain regions or between control and AD cases, whereas maximal spermine-enhanced [3H]MK-801 binding differed significantly between certain brain regions and between control and AD cases. In absolute terms in the control cases, the activation values were much lower in the spared regions, occipital and motor cortex, than in other areas; further, areas which are susceptible to damage showed reduced spermine activation in AD cases. These regional differences in the efficacy of spermine activation might be the result of local variations in the subunit composition of the NMDA receptor. Ala(7)-conantokinG and Lys(7)-conantokinG showed slight differences in potency, with the Ala(7) compound as the more potent. Both peptides produced 100% inhibition of spermine-enhanced [3H]MK-801 binding in all brain areas, ana both gave lower IC50 values in AD cases than in control cases. The significant differences in the inhibition of spermine-enhanced [3H]MK-801 binding by the peptides between control and AD cases suggest that AD cases have a particular receptor subunit composition that is responsive to polyamines and which might make them more susceptible to excitotoxic damage. The spermine site may contribute

  4. Interferon augments the anti-fibrotic activity of an angiotensin-converting enzyme inhibitor in patients with refractory chronic hepatitis C

    Hitoshi Yoshiji; Masaharu Yamazaki; Masahisa Toyohara; Akira Mitoro; Hiroshi Fukui; Ryuichi Noguchi; Hideyuki Kojima; Yasuhide Ikenaka; Mitsuteru Kitade; Kosuke Kaji; Masahito Uemura; Junichi Yamao; Masao Fujimoto

    2006-01-01

    AIM:To evaluate the effect of combination treatment with the interferon (IFN) and angiotensin-converting enzyme inhibitor (ACE-I ) on several fibrotic indices in patients with refractory chronic hepatitis C (CHC).METHODS: Perindopril (an ACE-I; 4 mg/d) and/or natural IFN (3 MU/L; 3 times a week) were administered for 12 mo to refractory CHC patients, and several indices of serum fibrosis markers were analyzed.RESULTS:ACE-Ⅰ decreased the serum fibrosis markers,whereas single treatment with IFN did not exert these inhibitory effects. However, IFN significantly augmented the effects of ACE-Ⅰ, and the combination treatment exerted the most potent inhibitory effects. The serum levels of alanine transaminase and HCV-RNA were not significantly different between the groups, whereas the plasma level of transforming growth factor-β was significantly attenuated almost in parallel with suppression of the serum fibrosis markers.CONCLUSION:The combination therapy of an ACE-Ⅰand IFN may have a diverse effect on disease progression in patients with CHC refractory to IFN therapy through its anti-fibrotic effect.

  5. Augmenter of liver regeneration

    Gandhi Chandrashekhar R

    2012-07-01

    Full Text Available Abstract ‘Augmenter of liver regeneration’ (ALR (also known as hepatic stimulatory substance or hepatopoietin was originally found to promote growth of hepatocytes in the regenerating or injured liver. ALR is expressed ubiquitously in all organs, and exclusively in hepatocytes in the liver. ALR, a survival factor for hepatocytes, exhibits significant homology with ERV1 (essential for respiration and viability protein that is essential for the survival of the yeast, Saccharomyces cerevisiae. ALR comprises 198 to 205 amino acids (approximately 22 kDa, but is post-translationally modified to three high molecular weight species (approximately 38 to 42 kDa found in hepatocytes. ALR is present in mitochondria, cytosol, endoplasmic reticulum, and nucleus. Mitochondrial ALR may be involved in oxidative phosphorylation, but also functions as sulfhydryl oxidase and cytochrome c reductase, and causes Fe/S maturation of proteins. ALR, secreted by hepatocytes, stimulates synthesis of TNF-α, IL-6, and nitric oxide in Kupffer cells via a G-protein coupled receptor. While the 22 kDa rat recombinant ALR does not stimulate DNA synthesis in hepatocytes, the short form (15 kDa of human recombinant ALR was reported to be equipotent as or even stronger than TGF-α or HGF as a mitogen for hepatocytes. Altered serum ALR levels in certain pathological conditions suggest that it may be a diagnostic marker for liver injury/disease. Although ALR appears to have multiple functions, the knowledge of its role in various organs, including the liver, is extremely inadequate, and it is not known whether different ALR species have distinct functions. Future research should provide better understanding of the expression and functions of this enigmatic molecule.

  6. Effective Augmentation of Complex Networks.

    Wang, Jinjian; Yu, Xinghuo; Stone, Lewi

    2016-01-01

    Networks science plays an enormous role in many aspects of modern society from distributing electrical power across nations to spreading information and social networking amongst global populations. While modern networks constantly change in size, few studies have sought methods for the difficult task of optimising this growth. Here we study theoretical requirements for augmenting networks by adding source or sink nodes, without requiring additional driver-nodes to accommodate the change i.e., conserving structural controllability. Our "effective augmentation" algorithm takes advantage of clusters intrinsic to the network topology, and permits rapidly and efficient augmentation of a large number of nodes in one time-step. "Effective augmentation" is shown to work successfully on a wide range of model and real networks. The method has numerous applications (e.g. study of biological, social, power and technological networks) and potentially of significant practical and economic value. PMID:27165120

  7. Mersiline mesh in premaxillary augmentation.

    Foda, Hossam M T

    2005-01-01

    Premaxillary retrusion may distort the aesthetic appearance of the columella, lip, and nasal tip. This defect is characteristically seen in, but not limited to, patients with cleft lip nasal deformity. This study investigated 60 patients presenting with premaxillary deficiencies in which Mersiline mesh was used to augment the premaxilla. All the cases had surgery using the external rhinoplasty technique. Two methods of augmentation with Mersiline mesh were used: the Mersiline roll technique, for the cases with central symmetric deficiencies, and the Mersiline packing technique, for the cases with asymmetric deficiencies. Premaxillary augmentation with Mersiline mesh proved to be simple technically, easy to perform, and not associated with any complications. Periodic follow-up evaluation for a mean period of 32 months (range, 12-98 months) showed that an adequate degree of premaxillary augmentation was maintained with no clinically detectable resorption of the mesh implant. PMID:15959688

  8. Simultaneous breast augmentation and mastopexy

    Whidden, Peter G

    2003-01-01

    The results of combining breast augmentation and mastopexy are less predictable than those associated with mastopexy or augmentation mammoplasty alone. A method of breast skin envelope reduction is presented that allows the surgeon performing mastopexy to preview the final breast shape before committing to skin resection. This method, first described in 1978, has proven to be technically versatile and reproducible, and applicable not only to moderate (second degree) and severe (third degree) ...

  9. Selective vulnerabilities of N-methyl-D-aspartate (NMDA receptors during brain aging

    Brenna L Brim

    2010-03-01

    Full Text Available N-methyl-D-aspartate (NMDA receptors are present in high density within the cerebral cortex and hippocampus and play an important role in learning and memory. NMDA receptors are negatively affected by aging, but these effects are not uniform in many different ways. This review discusses the selective age-related vulnerabilities of different binding sites of the NMDA receptor complex, different subunits that comprise the complex, and the expression and functions of the receptor within different brain regions. Spatial reference, passive avoidance, and working memory, as well as place field stability and expansion all involve NMDA receptors. Aged animals show deficiencies in these functions, as compared to young, and some studies have identified an association between age-associated changes in the expression of NMDA receptors and poor memory performance. A number of diet and drug interventions have shown potential for reversing or slowing the effects of aging on the NMDA receptor. On the other hand, there is mounting evidence that the NMDA receptors that remain within aged individuals are not always associated with good cognitive functioning. This may be due to a compensatory response of neurons to the decline in NMDA receptor expression or a change in the subunit composition of the remaining receptors. These studies suggest that developing treatments that are aimed at preventing or reversing the effects of aging on the NMDA receptor may aid in ameliorating the memory declines that are associated with aging. However, we need to be mindful of the possibility that there may also be negative consequences in aged individuals.

  10. Erythropoietin protects adult retinal ganglion cells against NMDA-, trophic factor withdrawal-, and TNF-α-induced damage.

    Zhi-Yang Chang

    Full Text Available PURPOSE: This study aimed to evaluate the neuroprotective effect of EPO in the presence of N-methyl-d-aspartate (NMDA-, trophic factor withdrawal (TFW-, and tumor necrosis factor-alpha (TNF-α-induced toxicity on total, small, and large retinal ganglion cells (RGCs. METHODS: Retinal cells from adult rats were cultured in a medium containing brain-derived neurotrophic factor (BDNF, ciliary neurotrophic factor (CNTF, basic fibroblast growth factor (bFGF, and forskolin. Expression of RGC markers and EPOR was examined using immunocytochemistry. RGCs were classified according to their morphological properties. Cytotoxicity was induced by NMDA, TFW, or TNF-α. RGC survival was assessed by counting thy-1 and neurofilament-l double-positive cells. RESULTS: EPO offered dose-dependent (EC₅₀ = 5.7 ng/mL protection against NMDA toxicity for small RGCs; protection was not significant for large RGCs. Time-course analysis showed that the presence of EPO either before or after NMDA exposure gave effective protection. For both small and large RGCs undergoing trophic factor withdrawal, EPO at concentrations of 1, 10, or 100 ng/mL improved survival. However, EPO had to be administered soon after the onset of injury to provide effective protection. For TNF-α-induced toxicity, survival of small RGCs was seen only for the highest examined concentration (100 ng/mL of EPO, whereas large RGCs were protected at concentrations of 1, 10, or 100 ng/mL of EPO. Time-course analysis showed that pretreatment with EPO provided protection only for large RGCs; early post-treatment with EPO protected both small and large RGCs. Inhibitors of signal transduction and activators of transcription such as (STAT-5, mitogen-activated protein kinases (MAPK/extracellular-regulated kinase (ERK, and phosphatidyl inositol-3 kinase (PI3K/Akt impaired the protective effect of EPO on RGCs exposed to different insults. CONCLUSION: EPO provided neuroprotection to cultured adult rat RGCs

  11. Geo-based systems in augmented reality

    Today's life is different to the one that existed not so many years ago. Our everyday life is constantly changing. The use of new technologies play major role in this change. Augmented Reality (AR) is looking to be the 8th mass market to evolve, following print, recordings, cinema, radio, TV, the Internet and mobile. In combination with geo-based technologies, augmented reality provides a completely new way of execution of the everyday activities. This paper presents the basic concepts and key characteristics of these two technologies. Also, the paper presents an example of a use of the technologies in an application meant for students for navigation through the campus of the Faculty. (Author)

  12. Wireless Augmented Reality Prototype (WARP)

    Devereaux, A. S.

    1999-01-01

    Initiated in January, 1997, under NASA's Office of Life and Microgravity Sciences and Applications, the Wireless Augmented Reality Prototype (WARP) is a means to leverage recent advances in communications, displays, imaging sensors, biosensors, voice recognition and microelectronics to develop a hands-free, tetherless system capable of real-time personal display and control of computer system resources. Using WARP, an astronaut may efficiently operate and monitor any computer-controllable activity inside or outside the vehicle or station. The WARP concept is a lightweight, unobtrusive heads-up display with a wireless wearable control unit. Connectivity to the external system is achieved through a high-rate radio link from the WARP personal unit to a base station unit installed into any system PC. The radio link has been specially engineered to operate within the high- interference, high-multipath environment of a space shuttle or space station module. Through this virtual terminal, the astronaut will be able to view and manipulate imagery, text or video, using voice commands to control the terminal operations. WARP's hands-free access to computer-based instruction texts, diagrams and checklists replaces juggling manuals and clipboards, and tetherless computer system access allows free motion throughout a cabin while monitoring and operating equipment.

  13. Cortical excitability changes following grasping exercise augmented with electrical stimulation

    Barsi, Gergely Istvan; Popovic, Dejan B.; Tarkka, Ina M.; Sinkjær, Thomas; Grey, Michael J

    2008-01-01

    Rehabilitation with augmented electrical stimulation can enhance functional recovery after stroke, and cortical plasticity may play a role in this process. The purpose of this study was to compare the effects of three training paradigms on cortical excitability in healthy subjects. Cortical......) functional electrical stimulation (FES) of the finger flexors and extensors, (2) voluntary movement (VOL) with sensory stimulation, and (3) therapeutic FES (TFES) where the electrical stimulation augmented voluntary activation. TFES training produced a significant increase in MEP magnitude throughout the...

  14. AMPA/NMDA cooperativity and integration during a single synaptic event.

    Di Maio, Vito; Ventriglia, Francesco; Santillo, Silvia

    2016-10-01

    Coexistence of AMPA and NMDA receptors in glutamatergic synapses leads to a cooperative effect that can be very complex. This effect is dependent on many parameters including the relative and absolute number of the two types of receptors and biophysical parameters that can vary among synapses of the same cell. Herein we simulate the AMPA/NMDA cooperativity by using different number of the two types of receptors and considering the effect of the spine resistance on the EPSC production. Our results show that the relative number of NMDA with respect to AMPA produces a different degree of cooperation which depends also on the spine resistance. PMID:27299885

  15. Pentobarbitone modulation of NMDA receptors in neurones isolated from the rat olfactory brain.

    Charlesworth, P; Jacobson, I; Richards, C. D.

    1995-01-01

    1. The action of pentobarbitone on the N-methyl-D-aspartate (NMDA) receptors of neurones freshly dissociated from the olfactory bulb and olfactory tubercle has been studied using patch-clamp techniques. 2. Pentobarbitone produced a concentration-dependent depression of the currents evoked by NMDA with an IC50 value of c. 250 microM. 3. Analysis of the NMDA-evoked noise produced power spectra that could be fitted by the sum of two Lorentzians with corner frequencies of 17 and 82 Hz. Pentobarbi...

  16. Pure Laparoscopic Augmentation Ileocystoplasty

    Rafael B. Rebouças

    2014-12-01

    Full Text Available Introduction Guillain-Barre syndrome is an acute neuropathy that rarely compromises bladder function. Conservative management including clean intermittent catheterization and pharmacotherapy is the primary approach for hypocompliant contracted bladder. Surgical treatment may be used in refractory cases to improve bladder compliance and capacity in order to protect the upper urinary tract. We describe a case of pure laparoscopic augmentation ileocystoplasty in a patient affected by Guillain-Barre syndrome. Presentation A 15-year-old female, complaining of voiding dysfunction, recurrent urinary tract infection and worsening renal function for three months. A previous history of Guillain-Barre syndrome on childhood was related. A voiding cystourethrography showed a pine-cone bladder with moderate post-void residual urine. The urodynamic demonstrated a hypocompliant bladder and small bladder capacity (190mL with high detrusor pressure (54 cmH2O. Nonsurgical treatments were attempted, however unsuccessfully. The patient was placed in the exaggerated Trendelenburg position. A four-port transperitoneal technique was used. A segment of ileum approximately 15-20cm was selected and divided with its pedicle. The ileal anastomosis and creation of ileal U-shaped plate were performed laparoscopically, without staplers. Bladder mobilization and longidutinal cystotomy were performed. Enterovesical anastomosis was done with continuous running suture. A suprapubic cystostomy was placed through a 5mm trocar. Results The total operative time was 335 min. The blood loss was minimal. The patient developed ileus in the early days, diet acceptance after the fourth day and was discharged on the seventh postoperative day. The urethral catheter was removed after 2 weeks. At 6-month follow-up, a cystogram showed a significant improvement in bladder capacity. The patient adhered well to clean intermittent self-catheterization and there was no report for febrile infections

  17. Neonatal NMDA receptor blockade disrupts spike timing and glutamatergic synapses in fast spiking interneurons in a NMDA receptor hypofunction model of schizophrenia.

    Kevin S Jones

    Full Text Available The dysfunction of parvalbumin-positive, fast-spiking interneurons (FSI is considered a primary contributor to the pathophysiology of schizophrenia (SZ, but deficits in FSI physiology have not been explicitly characterized. We show for the first time, that a widely-employed model of schizophrenia minimizes first spike latency and increases GluN2B-mediated current in neocortical FSIs. The reduction in FSI first-spike latency coincides with reduced expression of the Kv1.1 potassium channel subunit which provides a biophysical explanation for the abnormal spiking behavior. Similarly, the increase in NMDA current coincides with enhanced expression of the GluN2B NMDA receptor subunit, specifically in FSIs. In this study mice were treated with the NMDA receptor antagonist, MK-801, during the first week of life. During adolescence, we detected reduced spike latency and increased GluN2B-mediated NMDA current in FSIs, which suggests transient disruption of NMDA signaling during neonatal development exerts lasting changes in the cellular and synaptic physiology of neocortical FSIs. Overall, we propose these physiological disturbances represent a general impairment to the physiological maturation of FSIs which may contribute to schizophrenia-like behaviors produced by this model.

  18. Access of inhibitory neurosteroids to the NMDA receptor

    Borovská, Jiřina; Vyklický, Vojtěch; Šťastná, Eva; Kapras, Vojtěch; Slavíková, Barbora; Horák, Martin; Chodounská, Hana; Vyklický ml., Ladislav

    2012-01-01

    Roč. 166, č. 3 (2012), s. 1069-1083. ISSN 0007-1188 R&D Projects: GA ČR(CZ) GA309/07/0271; GA ČR(CZ) GA203/08/1498; GA MŠk(CZ) 1M0517; GA MŠk(CZ) LC554; GA ČR(CZ) GAP303/11/0075; GA ČR(CZ) GAP303/12/1464 Grant ostatní: GA ČR(CZ) GD309/08/H079; GA MŠk(CZ) ED0007/01/01 Institutional research plan: CEZ:AV0Z50110509; CEZ:AV0Z40550506 Keywords : neurosteroids * NMDA receptor * patch-clamp Subject RIV: ED - Physiology Impact factor: 5.067, year: 2012

  19. An NMDA Receptor-Dependent Mechanism Underlies Inhibitory Synapse Development

    Xinglong Gu

    2016-01-01

    Full Text Available In the mammalian brain, GABAergic synaptic transmission provides inhibitory balance to glutamatergic excitatory drive and controls neuronal output. The molecular mechanisms underlying the development of GABAergic synapses remain largely unclear. Here, we report that NMDA-type ionotropic glutamate receptors (NMDARs in individual immature neurons are the upstream signaling molecules essential for GABAergic synapse development, which requires signaling via Calmodulin binding motif in the C0 domain of the NMDAR GluN1 subunit. Interestingly, in neurons lacking NMDARs, whereas GABAergic synaptic transmission is strongly reduced, the tonic inhibition mediated by extrasynaptic GABAA receptors is increased, suggesting a compensatory mechanism for the lack of synaptic inhibition. These results demonstrate a crucial role for NMDARs in specifying the development of inhibitory synapses, and suggest an important mechanism for controlling the establishment of the balance between synaptic excitation and inhibition in the developing brain.

  20. Ethanol inhibition of N-methyl-D-aspartate-activated current in mouse hippocampal neurones: whole-cell patch-clamp analysis

    Peoples, Robert W.; White, Geoffrey; Lovinger, David M.; Weight, Forrest F

    1997-01-01

    The action of ethanol on N-methyl-D-aspartate (NMDA)-activated ion current was studied in mouse hippocampal neurones in culture using whole-cell patch-clamp recording.Ethanol inhibited NMDA-activated current in a voltage-independent manner, and did not alter the reversal potential of NMDA-activated current.Concentration–response analysis of NMDA- and glycine-activated current revealed that ethanol decreased the maximal response to both agonists without affecting their EC50 values.The polyamin...

  1. Interaction between thyrotropin-releasing hormone (TRH) and NMDA-receptor-mediated responses in hypoglossal motoneurones

    Rekling, J C

    The effect of thyrotropin-releasing hormone (TRH) on the responses to excitatory amino acids was investigated in hypoglossal motoneurones in an in vitro preparation of the brainstem from guinea pigs using current clamp and discontinuous single electrode voltage clamp (dSEVC). Bath application of 20......-50 microM TRH markedly potentiated the response to iontophoretically applied NMDA, whereas no potentiation of the response to glutamate, aspartate or quisqualic acid was seen. Voltage clamp experiments showed that TRH did not increase the current flowing through NMDA channels, thus a direct modulatory role...... of TRH on NMDA channels was not a likely explanation of the potentiation. Voltage clamp studies of the current-voltage relationship showed that the potentiation of the response to NMDA and lack of potentiation of the response to quisqualic acid was a result of an interaction between the actions of...

  2. Anti-NMDA Receptor Encephalitis in the Polar Bear (Ursus maritimus) Knut.

    Prüss, H; Leubner, J; Wenke, N K; Czirják, G Á; Szentiks, C A; Greenwood, A D

    2015-01-01

    Knut the polar bear of the Berlin Zoological Garden drowned in 2011 following seizures and was diagnosed as having suffered encephalitis of unknown etiology after exhaustive pathogen screening. Using the diagnostic criteria applied to human patients, we demonstrate that Knut's encephalitis is almost identical to anti-NMDA receptor encephalitis which is a severe autoimmune disease representing the most common non-infectious encephalitis in humans. High concentrations of antibodies specific against the NR1 subunit of the NMDA receptor were detected in Knut's cerebrospinal fluid. Histological examination demonstrated very similar patterns of plasma cell infiltration and minimal neuronal loss in affected brain areas. We conclude that Knut suffered anti-NMDA receptor encephalitis making his the first reported non-human case of this treatable disease. The results suggest that anti-NMDA receptor encephalitis may be a disease of broad relevance to mammals that until now has remained undiagnosed. PMID:26313569

  3. Scaffolding of Fyn Kinase to the NMDA Receptor Determines Brain Region Sensitivity to Ethanol

    Yaka, Rami; Phamluong, Khanhky; Ron, Dorit

    2003-01-01

    Alcohol (ethanol) abuse is a major societal problem. Although ethanol is a structurally simple, diffusible molecule, its sites of action are surprisingly selective, and the molecular mechanisms underlying specificity in ethanol actions are not understood. The NMDA receptor channel is one of the main targets for ethanol in the brain. We report here that the brain region-specific compartmentalization of Fyn kinase determines NMDA receptor sensitivity to ethanol. We demonstrate that, in the hipp...

  4. Effects of combining opioids and clinically available NMDA receptor antagonists in the treatment of pain

    Snijdelaar, D.G.

    2005-01-01

    This thesis concerns the effects of combining opioids with clinically available NMDA receptor antagonists in the treatment of acute and chronic pain. There are a number of problems with the use of opioids, such as, the development of tolerance/hyperalgesia, the reduced effectiveness in (central) neuropathic pain, and troublesome adverse effects. These problems might be resolved by the combined use of opioids and clinically available drugs with N-methyl-D-aspartate (NMDA) receptor antagonist p...

  5. Anti-NMDA receptor encephalitis: an important differential diagnosis in psychosis.

    Barry, Helen

    2012-02-01

    We present four cases of confirmed anti-NMDA receptor encephalitis; three presented initially with serious psychiatric symptoms and the other developed significant psychiatric symptoms during the initial phase of illness. Brain biopsy findings of one patient are also described. Psychiatrists should consider anti-NMDA receptor encephalitis in patients presenting with psychosis and additional features of dyskinesias, seizures and catatonia, particularly where there is no previous history of psychiatric disorder.

  6. Exaggerated NMDA Mediated LTD in a Mouse Model of Down Syndrome and Pharmacological Rescuing by Memantine

    Scott-McKean, Jonah J.; Costa, Alberto C. S.

    2011-01-01

    The Ts65Dn mouse is the best-studied animal model for Down syndrome. In the experiments described here, NMDA-mediated or mGluR-mediated LTD was induced in the CA1 region of hippocampal slices from Ts65Dn and euploid control mice by bath application of 20 [mu]M NMDA for 3 min and 50 [mu]M DHPG for 5 min, respectively. We found that Ts65Dn mice…

  7. Long-term potentiation in frontal cortex: Role of NMDA-modulated polysynaptic excitatory pathways

    Sutor, Bernd; Hablitz, John H.

    1989-01-01

    The present study examined the role of N-methyl-D-aspartic acid (NMDA) receptors in synaptic plasticity in regular-spiking cells of rat frontal cortex. Intracortical stimulation, at levels subthreshold for elicitation of action potentials, evoked a late excitatory postsynaptic potential (EPSP) in layer II III neurons that was sensitive to the selective NMDA antagonist -2-amino-5-phosphonovaleric acid (APV). This late EPSP showed marked short-term frequency-dependent depression, suggesting th...

  8. Electrophysiological Characterization of AMPA and NMDA Receptors in Rat Dorsal Striatum.

    Jeun, Seung Hyun; Cho, Hyeong Seok; Kim, Ki Jung; Li, Qing Zhong; Sung, Ki-Wug

    2009-06-01

    The striatum receives glutamatergic afferents from the cortex and thalamus, and these synaptic transmissions are mediated by alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) and N-methyl-D-aspartate (NMDA) receptors. The purpose of this study was to characterize glutamate receptors by analyzing NMDA/AMPA ratio and rectification of AMPA and NMDA excitatory postsynaptic currents (EPSCs) using a whole-cell voltage-clamp method in the dorsal striatum. Receptor antagonists were used to isolate receptor or subunit specific EPSC, such as (DL)-2-amino-5-phosphonovaleric acid (APV), an NMDA receptor antagonist, ifenprodil, an NR2B antagonist, CNQX, an AMPA receptor antagonist and IEM-1460, a GluR2-lacking AMPA receptor blocker. AMPA and NMDA EPSCs were recorded at -70 and +40 mV, respectively. Rectification index was calculated by current ratio of EPSCs between +50 and -50 mV. NMDA/AMPA ratio was 0.20+/-0.05, AMPA receptor ratio of GluR2-lacking/GluR2-containing subunit was 0.26+/-0.05 and NMDA receptor ratio of NR2B/NR2A subunit was 0.32+/-0.03. The rectification index (control 2.39+/-0.27) was decreased in the presence of both APV and combination of APV and IEM-1460 (1.02+/-0.11 and 0.93+/-0.09, respectively). These results suggest that the major components of the striatal glutamate receptors are GluR2-containing AMPA receptors and NR2A-containing NMDA receptors. Our results may provide useful information for corticostriatal synaptic transmission and plasticity studies. PMID:19885039

  9. Augmented Reality Tower Technology Assessment

    Reisman, Ronald J.; Brown, David M.

    2009-01-01

    Augmented Reality technology may help improve Air Traffic Control Tower efficiency and safety during low-visibility conditions. This paper presents the assessments of five off-duty controllers who shadow-controlled' with an augmented reality prototype in their own facility. Initial studies indicated unanimous agreement that this technology is potentially beneficial, though the prototype used in the study was not adequate for operational use. Some controllers agreed that augmented reality technology improved situational awareness, had potential to benefit clearance, control, and coordination tasks and duties and could be very useful for acquiring aircraft and weather information, particularly aircraft location, heading, and identification. The strongest objections to the prototype used in this study were directed at aircraft registration errors, unacceptable optical transparency, insufficient display performance in sunlight, inadequate representation of the static environment and insufficient symbology.

  10. NR2B-containing NMDA receptors promote neural progenitor cell proliferation through CaMKIV/CREB pathway

    Highlights: → The NR2B component of the NMDARs is important for the NSPC proliferation. → pCaMKIV and pCREB exist in NSPCs. → The CaMKIV/CREB pathway mediates NSPC proliferation. -- Abstract: Accumulating evidence indicates the involvement of N-methyl-D-aspartate receptors (NMDARs) in regulating neural stem/progenitor cell (NSPC) proliferation. Functional properties of NMDARs can be markedly influenced by incorporating the regulatory subunit NR2B. Here, we aim to analyze the effect of NR2B-containing NMDARs on the proliferation of hippocampal NSPCs and to explore the mechanism responsible for this effect. NSPCs were shown to express NMDAR subunits NR1 and NR2B. The NR2B selective antagonist, Ro 25-6981, prevented the NMDA-induced increase in cell proliferation. Moreover, we demonstrated that the phosphorylation levels of calcium/calmodulin-dependent protein kinase IV (CaMKIV) and cAMP response element binding protein (CREB) were increased by NMDA treatment, whereas Ro 25-6981 decreased them. The role that NR2B-containing NMDARs plays in NSPC proliferation was abolished when CREB phosphorylation was attenuated by CaMKIV silencing. These results suggest that NR2B-containing NMDARs have a positive role in regulating NSPC proliferation, which may be mediated through CaMKIV phosphorylation and subsequent induction of CREB activation.

  11. Involvement of NMDA receptors and l-arginine/nitric oxide/cyclic guanosine monophosphate pathway in the antidepressant-like effects of topiramate in mice forced swimming test.

    Ostadhadi, Sattar; Khan, Muhammad Imran; Norouzi-Javidan, Abbas; Chamanara, Mohsen; Jazaeri, Farahnaz; Zolfaghari, Samira; Dehpour, Ahmad-Reza

    2016-04-01

    Topiramate (TPM) is an agent primarily used in the treatment of epilepsy. Using mice model of forced swimming test (FST) the current study was basically aimed to investigate the influence of TPM on depression by inhibiting NMDA receptor and nitric oxide-cGMP production. When TPM was administered in a dose of 20 and 30mg/kg by i.p. route it reduced the immobility time during FST. However this effect of TPM (30mg/kg, i.p.) in the FST was abolished when the mice were pretreated either with NMDA (75mg/kg, i.p.), or l-arginine (750mg/kg, i.p. NO precursor), or sildenafil (5mg/kg, i.p. Phosphodiesterase 5 inhibitor). The immobility time in the FST was reduced after administration of L-NAME (10mg/kg, i.p, a non-specefic NOS inhibitor), 7-nitoinidazol (30mg/kg, i.p. a nNOS inhibitor) or MK-801 (0.05mg/kg, i.p, a NMDA receptor antagonist) in combination with a subeffective dose of TPM (10mg/kg, i.p.) as compared with single use of either drug. Co-administrated of lower doses of MK-801 (0.01mg/kg) or L-NAME (1mg/kg) failed to effect immobility time. However, simultaneous administration of these two agents in the same doses with subeffective dose of TPM (10mg/kg, i.p.), reduced the immobility time during FST. None of these drugs were found to have a profound effect on the locomotor activity per se during the open field test. Taken together, our data demonstrates that TPM exhibit antidepressant-like effect which is accomplished either due to inhibition of NMDA receptors or NO-cGMP production. PMID:26988103

  12. The qEEG Signature of Selective NMDA NR2B Negative Allosteric Modulators; A Potential Translational Biomarker for Drug Development.

    Keavy, Deborah; Bristow, Linda J; Sivarao, Digavalli V; Batchelder, Margaret; King, Dalton; Thangathirupathy, Srinivasan; Macor, John E; Weed, Michael R

    2016-01-01

    The antidepressant activity of the N-methyl-D-aspartate (NMDA) receptor channel blocker, ketamine, has led to the investigation of negative allosteric modulators (NAMs) selective for the NR2B receptor subtype. The clinical development of NR2B NAMs would benefit from a translational pharmacodynamic biomarker that demonstrates brain penetration and functional inhibition of NR2B receptors in preclinical species and humans. Quantitative electroencephalography (qEEG) is a translational measure that can be used to demonstrate pharmacodynamic effects across species. NMDA receptor channel blockers, such as ketamine and phencyclidine, increase the EEG gamma power band, which has been used as a pharmacodynamic biomarker in the development of NMDA receptor antagonists. However, detailed qEEG studies with ketamine or NR2B NAMs are lacking in nonhuman primates. The aim of the present study was to determine the effects on the qEEG power spectra of the NR2B NAMs traxoprodil (CP-101,606) and BMT-108908 in nonhuman primates, and to compare them to the NMDA receptor channel blockers, ketamine and lanicemine. Cynomolgus monkeys were surgically implanted with EEG radio-telemetry transmitters, and qEEG was measured after vehicle or drug administration. The relative power for a number of frequency bands was determined. Ketamine and lanicemine increased relative gamma power, whereas the NR2B NAMs traxoprodil and BMT-108908 had no effect. Robust decreases in beta power were elicited by ketamine, traxoprodil and BMT-108908; and these agents also produced decreases in alpha power and increases in delta power at the doses tested. These results suggest that measurement of power spectra in the beta and delta bands may represent a translational pharmacodynamic biomarker to demonstrate functional effects of NR2B NAMs. The results of these studies may help guide the selection of qEEG measures that can be incorporated into early clinical evaluation of NR2B NAMs in healthy humans. PMID:27035340

  13. Control of βAR- and N-methyl-D-aspartate (NMDA) Receptor-Dependent cAMP Dynamics in Hippocampal Neurons.

    Chay, Andrew; Zamparo, Ilaria; Koschinski, Andreas; Zaccolo, Manuela; Blackwell, Kim T

    2016-02-01

    Norepinephrine, a neuromodulator that activates β-adrenergic receptors (βARs), facilitates learning and memory as well as the induction of synaptic plasticity in the hippocampus. Several forms of long-term potentiation (LTP) at the Schaffer collateral CA1 synapse require stimulation of both βARs and N-methyl-D-aspartate receptors (NMDARs). To understand the mechanisms mediating the interactions between βAR and NMDAR signaling pathways, we combined FRET imaging of cAMP in hippocampal neuron cultures with spatial mechanistic modeling of signaling pathways in the CA1 pyramidal neuron. Previous work implied that cAMP is synergistically produced in the presence of the βAR agonist isoproterenol and intracellular calcium. In contrast, we show that when application of isoproterenol precedes application of NMDA by several minutes, as is typical of βAR-facilitated LTP experiments, the average amplitude of the cAMP response to NMDA is attenuated compared with the response to NMDA alone. Models simulations suggest that, although the negative feedback loop formed by cAMP, cAMP-dependent protein kinase (PKA), and type 4 phosphodiesterase may be involved in attenuating the cAMP response to NMDA, it is insufficient to explain the range of experimental observations. Instead, attenuation of the cAMP response requires mechanisms upstream of adenylyl cyclase. Our model demonstrates that Gs-to-Gi switching due to PKA phosphorylation of βARs as well as Gi inhibition of type 1 adenylyl cyclase may underlie the experimental observations. This suggests that signaling by β-adrenergic receptors depends on temporal pattern of stimulation, and that switching may represent a novel mechanism for recruiting kinases involved in synaptic plasticity and memory. PMID:26901880

  14. MPX-004 and MPX-007: New Pharmacological Tools to Study the Physiology of NMDA Receptors Containing the GluN2A Subunit.

    Robert A Volkmann

    Full Text Available GluN2A is the most abundant of the GluN2 NMDA receptor subunits in the mammalian CNS. Physiological and genetic evidence implicate GluN2A-containing receptors in susceptibility to autism, schizophrenia, childhood epilepsy and neurodevelopmental disorders such as Rett Syndrome. However, GluN2A-selective pharmacological probes to explore the therapeutic potential of targeting these receptors have been lacking. Here we disclose a novel series of pyrazine-containing GluN2A antagonists exemplified by MPX-004 (5-(((3-chloro-4-fluorophenylsulfonamidomethyl-N-((2-methylthiazol-5-ylmethylpyrazine-2-carboxamide and MPX-007 (5-(((3-fluoro-4-fluorophenylsulfonamidomethyl-N-((2-methylthiazol-5-ylmethylmethylpyrazine-2-carboxamide. MPX-004 and MPX-007 inhibit GluN2A-containing NMDA receptors expressed in HEK cells with IC50s of 79 nM and 27 nM, respectively. In contrast, at concentrations that completely inhibited GluN2A activity these compounds have no inhibitory effect on GluN2B or GluN2D receptor-mediated responses in similar HEK cell-based assays. Potency and selectivity were confirmed in electrophysiology assays in Xenopus oocytes expressing GluN2A-D receptor subtypes. Maximal concentrations of MPX-004 and MPX-007 inhibited ~30% of the whole-cell current in rat pyramidal neurons in primary culture and MPX-004 inhibited ~60% of the total NMDA receptor-mediated EPSP in rat hippocampal slices. GluN2A-selectivity at native receptors was confirmed by the finding that MPX-004 had no inhibitory effect on NMDA receptor mediated synaptic currents in cortical slices from GRIN2A knock out mice. Thus, MPX-004 and MPX-007 offer highly selective pharmacological tools to probe GluN2A physiology and involvement in neuropsychiatric and developmental disorders.

  15. Dopamine D1 receptor-mediated NMDA receptor insertion depends on Fyn but not Src kinase pathway in prefrontal cortical neurons

    Hu Jian-Li

    2010-06-01

    Full Text Available Abstract Background Interactions between dopamine and glutamate in the prefrontal cortex are essential for cognitive functions such as working memory. Modulation of N-methyl-D-aspartic acid (NMDA receptor functions by dopamine D1 receptor is believed to play a critical role in these functions. The aim of the work reported here is to explore the signaling pathway underlying D1 receptor-mediated trafficking of NMDA receptors in cultured rat prefrontal cortical neurons. Results Activation of D1 receptor by selective agonist SKF-81297 significantly increased the expression of NR2B subunits. This effect was completely blocked by small interfering RNA knockdown of Fyn, but not Src. Under control conditions, neither Fyn nor Src knockdown exhibited significant effect on basal NR2B expression. D1 stimulation significantly enhanced NR2B insertion into plasma membrane in cultured PFC neurons, a process obstructed by Fyn, but not Src, knockdown. Conclusions Dopamine D1 receptor-mediated increase of NMDA receptors is thus Fyn kinase dependent. Targeting this signaling pathway may be useful in treating drug addiction and schizophrenia.

  16. Zero-Content Augmented Caches

    Dusser, Julien; Piquet, Thomas; Seznec, André

    2008-01-01

    It has been observed that some applications manipulate large amounts of null data. Moreover these zero data often exhibit high spatial locality. On some applications more than 20\\% of the data accesses concern null data blocks. Representing a null block in a cache on a standard cache line appears as a waste of resources. In this paper, we propose the Zero-Content Augmented cache, the ZCA cache. A ZCA cache consists of a conventional cache augmented with a specialized cache for memorizing null...

  17. Augmented reality based real-time subcutaneous vein imaging system.

    Ai, Danni; Yang, Jian; Fan, Jingfan; Zhao, Yitian; Song, Xianzheng; Shen, Jianbing; Shao, Ling; Wang, Yongtian

    2016-07-01

    A novel 3D reconstruction and fast imaging system for subcutaneous veins by augmented reality is presented. The study was performed to reduce the failure rate and time required in intravenous injection by providing augmented vein structures that back-project superimposed veins on the skin surface of the hand. Images of the subcutaneous vein are captured by two industrial cameras with extra reflective near-infrared lights. The veins are then segmented by a multiple-feature clustering method. Vein structures captured by the two cameras are matched and reconstructed based on the epipolar constraint and homographic property. The skin surface is reconstructed by active structured light with spatial encoding values and fusion displayed with the reconstructed vein. The vein and skin surface are both reconstructed in the 3D space. Results show that the structures can be precisely back-projected to the back of the hand for further augmented display and visualization. The overall system performance is evaluated in terms of vein segmentation, accuracy of vein matching, feature points distance error, duration times, accuracy of skin reconstruction, and augmented display. All experiments are validated with sets of real vein data. The imaging and augmented system produces good imaging and augmented reality results with high speed. PMID:27446690

  18. Studies on experimental and neuropathic orofacial pain, and low-dose ketamine as a probe for NMDA receptor function

    2005-01-01

    The NMDA-receptor is known to play a central role in the development of acute andchronic pain. Ketamine is a clinically available NMDA-receptor inhibitor. We examined the role of the NMDA-receptor in acute experimental and chronic neuropathic orofacial pain in humans by using ketamine as a probe. We also examined pathophysiological mechanisms in patients suffering from orofacial neuropathic pain by use of quantitative sensory-testing. In a double-blind study we compared the effects of low...

  19. Ethanol affects NMDA receptor signaling at climbing fiber-Purkinje cell synapses in mice and impairs cerebellar LTD

    He, Qionger; Titley, Heather; Grasselli, Giorgio; Piochon, Claire; Hansel, Christian

    2012-01-01

    Ethanol profoundly influences cerebellar circuit function and motor control. It has recently been demonstrated that functional N-methyl-d-aspartate (NMDA) receptors are postsynaptically expressed at climbing fiber (CF) to Purkinje cell synapses in the adult cerebellum. Using whole cell patch-clamp recordings from mouse cerebellar slices, we examined whether ethanol can affect NMDA receptor signaling in mature Purkinje cells. NMDA receptor-mediated currents were isolated by bath application of...

  20. Towards Wearable Gaze Supported Augmented Cognition

    Toshiaki Kurauchi, Andrew; Hitoshi Morimoto, Carlos; Mardanbeigi, Diako; Witzner Hansen, Dan

    reduce the amount of information and provide an appropriate mechanism for low and divided attention interaction. We claim that most current gaze interaction paradigms are not appropriate for wearable computing because they are not designed for divided attention. We have used principles suggested by the...... wearable computing community to develop a gaze supported augmented cognition application with three interaction modes. The application provides information of the person being looked at. The continuous mode updates information every time the user looks at a different face. The key activated discrete mode...

  1. C16-Ceramide Analog Combined with Pc 4 Photodynamic Therapy Evokes Enhanced Total Ceramide Accumulation, Promotion of DEVDase Activation in the Absence of Apoptosis, and Augmented Overall Cell Killing

    Duska Separovic

    2011-01-01

    Full Text Available Because of the failure of single modality approaches, combination therapy for cancer treatment is a promising alternative. Sphingolipid analogs, with or without anticancer drugs, can improve tumor response. C16-pyridinium ceramide analog LCL30, was used in combination with photodynamic therapy (PDT, an anticancer treatment modality, to test the hypothesis that the combined treatment will trigger changes in the sphingolipid profile and promote cell death. Using SCCVII mouse squamous carcinoma cells, and the silicone phthalocyanine Pc 4 for PDT, we showed that combining PDT with LCL30 (PDT/LCL30 was more effective than individual treatments in raising global ceramide levels, as well as in reducing dihydrosphingosine levels. Unlike LCL30, PDT, alone or combined, increased total dihydroceramide levels. Sphingosine levels were unaffected by LCL30, but were abolished after PDT or the combination. LCL30-triggered rise in sphingosine-1-phosphate was reversed post-PDT or the combination. DEVDase activation was evoked after PDT or LCL30, and was promoted post- PDT/LCL30. Neither mitochondrial depolarization nor apoptosis were observed after any of the treatments. Notably, treatment with the combination resulted in augmented overall cell killing. Our data demonstrate that treatment with PDT/LCL30 leads to enhanced global ceramide levels and DEVDase activation in the absence of apoptosis, and promotion of total cell killing.

  2. Augmented Reality in Science Education

    Nielsen, Birgitte Lund; Brandt, Harald; Swensen, Hakon

    2015-01-01

    Augmented reality (AR) holds great promise as a learning tool. However, most extant studies in this field have focused on the technology itself. The poster presents findings from the first stage of the AR-sci project addressing the issue of applying AR for educational purposes. Benefits and...

  3. Multiprobe molecular imaging of an NMDA receptor hypofunction rat model for glutamatergic dysfunction.

    Kosten, Lauren; Verhaeghe, Jeroen; Verkerk, Robert; Thomae, David; De Picker, Livia; Wyffels, Leonie; Van Eetveldt, Annemie; Dedeurwaerdere, Stefanie; Stroobants, Sigrid; Staelens, Steven

    2016-02-28

    There are many indications of a connection between abnormal glutamate transmission through N-methyl-d-aspartate (NMDA) receptor hypofunction and the occurrence of schizophrenia. The importance of metabotropic glutamate receptor subtype 5 (mGluR5) became generally recognized due to its physical link through anchor proteins with NMDAR. Neuroinflammation as well as the kynurenine (tryptophan catabolite; TRYCAT) pathway are equally considered as major contributors to the pathology. We aimed to investigate this interplay between glutamate release, neuronal activation and inflammatory markers, by using small-animal positron emission tomography (PET) in a rat model known to induce schizophrenia-like symptoms. Daily intraperitoneal injection of MK801 or saline were administered to induce the model together with N-Acetyl-cysteine (NAc) or saline as the treatment in 24 male Sprague Dawley rats for one month. Biweekly in vivo [(11)C]-ABP688 microPET was performed together with mGluR5 immunohistochemistry. Simultaneously, weekly in vivo [(18)F]-FDG microPET imaging data for glucose metabolism was acquired and microglial activation was investigated with biweekly in vivo [(18)F]-PBR111 scans versus OX42 immunohistochemistry. Finally, plasma samples were analyzed for TRYCAT metabolites. We show that chronic MK801 administration (and thus elevated endogenous glutamate) causes significant tissue loss in rat brain, enhances neuroinflammatory pathways and may upregulate mGluR5 expression. PMID:26803479

  4. Augmented telomerase activity, reduced telomere length and the presence of alternative lengthening of telomere in renal cell carcinoma: plausible predictive and diagnostic markers.

    Pal, Deeksha; Sharma, Ujjawal; Khajuria, Ragini; Singh, Shrawan Kumar; Kakkar, Nandita; Prasad, Rajendra

    2015-05-15

    In this study, we analyzed 100 cases of renal cell carcinoma (RCC) for telomerase activity, telomere length and alternative lengthening of telomeres (ALT) using the TRAP assay, TeloTTAGGG assay kit and immunohistochemical analysis of ALT associated promyelocytic leukemia (PML) bodies respectively. A significantly higher (P=0.000) telomerase activity was observed in 81 cases of RCC which was correlated with clinicopathological features of tumor for instance, stage (P=0.008) and grades (P=0.000) but not with the subtypes of RCC (P = 0.355). Notwithstanding, no correlation was found between telomerase activity and subtypes of RCC. Strikingly, the telomere length was found to be significantly shorter in RCC (P=0.000) to that of corresponding normal renal tissues and it is well correlated with grades (P=0.016) but not with stages (P=0.202) and subtypes (P=0.669) of RCC. In this study, telomere length was also negatively correlated with the age of patients (r(2)=0.528; P=0.000) which supports the notion that it could be used as a marker for biological aging. ALT associated PML bodies containing PML protein was found in telomerase negative cases of RCC. It suggests the presence of an ALT pathway mechanism to maintain the telomere length in telomerase negative RCC tissues which was associated with high stages of RCC, suggesting a prevalent mechanism for telomere maintenance in high stages. In conclusion, the telomerase activity and telomere length can be used as a diagnostic as well as a predictive marker in RCC. The prevalence of ALT mechanism in high stages of RCC is warranted for the development of anti-ALT inhibitors along with telomerase inhibitor against RCC as a therapeutic approach. PMID:25769384

  5. Antidepressant effect of pramipexole in mice forced swimming test: A cross talk between dopamine receptor and NMDA/nitric oxide/cGMP pathway.

    Ostadhadi, Sattar; Imran Khan, Muhammad; Norouzi-Javidan, Abbas; Dehpour, Ahmad-Reza

    2016-07-01

    Pramipexole is a dopamine D2 receptor agonist indicated for treating Parkinson disorder. This study was aimed to investigate the effect of pramipexole in forced swimming test (FST) in mice and the possible involvement of activation of D2 receptors and inhibition of N-methyl-d-aspartate (NMDA) receptors and nitric oxide-cyclic guanosine monophosphate (NO-cGMP) on this effect. Intraperitoneal administration of pramipexole (1-3mg/kg) reduced the immobility time in the FST similar to fluoxetine (20mg/kg, i.p.). This effect of pramipexole (1mg/kg, i.p.) was ceased when mice were pretreated with haloperidol (0.15mg/kg, i.p,) and sulpiride (5mg/kg, i.p) as D2 receptor antagonists, NMDA (75mg/kg,i.p.), l-arginine (750mg/kg, i.p., a substrate for nitric oxide synthase) or sildenafil (5mg/kg, i.p., a phosphodiesterase 5 inhibitor). The administration of MK-801 (0.05mg/kg, i.p., a NMDA receptor antagonist) l-NG-Nitro arginine methyl ester (l-NAME, 10mg/kg, i.p., a non-specific nitric oxide synthase (NOS) inhibitor), 7-nitroindazole (30mg/kg, i.p., a neuronal NOS inhibitor) and methylene blue (10mg/kg, i.p.), an inhibitor of both NOS and soluble guanylyl cyclase (sGC) in combination with the sub-effective dose of pramipexole (0.3mg/kg, i.p.) reduced the immobility. Altogether, our data suggest that the antidepressant-like effect of pramipexole is dependent on the activation of D2 receptor and inhibition of either NMDA receptors and/or NO-cGMP synthesis. These results contribute to the understanding of the mechanisms underlying the antidepressant-like effect of pramipexole and reinforce the role of D2 receptors, NMDA receptors and l-arginine-NO-GMP pathway in the antidepressant mechanism of this agent. PMID:27261607

  6. Bisphenol-A rapidly promotes dynamic changes in hippocampal dendritic morphology through estrogen receptor-mediated pathway by concomitant phosphorylation of NMDA receptor subunit NR2B

    Bisphenol-A (BPA) is known to be a potent endocrine disrupter. Evidence is emerging that estrogen exerts a rapid influence on hippocampal synaptic plasticity and the dendritic spine density, which requires activation of NMDA receptors. In the present study, we investigated the effects of BPA (ranging from 1 to 1000 nM), focusing on the rapid dynamic changes in dendritic filopodia and the expressions of estrogen receptor (ER) β and NMDA receptor, as well as the phosphorylation of NMDA receptor subunit NR2B in the cultured hippocampal neurons. A specific ER antagonist ICI 182,780 was used to examine the potential involvement of ERs. The results demonstrated that exposure to BPA (ranging from 10 to 1000 nM) for 30 min rapidly enhanced the motility and the density of dendritic filopodia in the cultured hippocampal neurons, as well as the phosphorylation of NR2B (pNR2B), though the expressions of NMDA receptor subunits NR1, NR2B, and ERβ were not changed. The antagonist of ERs completely inhibited the BPA-induced increases in the filopodial motility and the number of filopodia extending from dendrites. The increased pNR2B induced by BPA (100 nM) was also completely eliminated. Furthermore, BPA attenuated the effects of 17β-estradiol (17β-E2) on the dendritic filopodia outgrowth and the expression of pNR2B when BPA was co-treated with 17β-E2. The present results suggest that BPA, like 17β-E2, rapidly results in the enhanced motility and density of dendritic filopodia in the cultured hippocampal neurons with the concomitant activation of NMDA receptor subunit NR2B via an ER-mediated signaling pathway. Meanwhile, BPA suppressed the enhancement effects of 17β-E2 when it coexists with 17β-E2. These results provided important evidence suggesting the neurotoxicity of the low levels of BPA during the early postnatal development of the brain.

  7. Heavy Resistance Training and Supplementation With the Alleged Testosterone Booster Nmda has No Effect on Body Composition, Muscle Performance, and Serum Hormones Associated With the Hypothalamo-Pituitary-Gonadal Axis in Resistance-Trained Males

    Darryn S. Willoughby

    2014-03-01

    Full Text Available The effects of 28 days of heavy resistance training while ingesting the alleged testosterone-boosting supplement, NMDA, were determined on body composition, muscle strength, serum cortisol, prolactin, and hormones associated with the hypothalamo-pituitary- gonadal (HPG axis. Twenty resistance-trained males engaged in 28 days of resistance training 4 times/wk while orally ingesting daily either 1.78 g of placebo (PLAC or NMDA. Data were analyzed with separate 2 x 2 ANOVA (p 0.05 or supplementation (p > 0.05. In regard to total body mass and fat-free mass, however, each was significantly increased in both groups in response to resistance training (p 0.05. In both groups, lower-body muscle strength was significantly increased in response to resistance training (p 0.05. All serum hormones (total and free testosterone, LH, GnRH, estradiol, cortisol, prolactin were unaffected by resistance training (p > 0.05 or supplementation (p > 0.05. The gonadal hormones and cortisol and prolactin were unaffected by 28 days of NMDA supplementation and not associated with the observed increases in muscle strength and mass. At the dose provided, NMDA had no effect on HPG axis activity or ergogenic effects in skeletal muscle.

  8. Immunomodulation by vitamin B12: augmentation of CD8+ T lymphocytes and natural killer (NK) cell activity in vitamin B12-deficient patients by methyl-B12 treatment.

    Tamura, J; Kubota, K; Murakami, H; Sawamura, M; Matsushima, T; Tamura, T; Saitoh, T; Kurabayshi, H; Naruse, T

    1999-04-01

    It has been suggested that vitamin B12 (vit.B12) plays an important role in immune system regulation, but the details are still obscure. In order to examine the action of vit.B12 on cells of the human immune system, lymphocyte subpopulations and NK cell activity were evaluated in 11 patients with vit.B12 deficiency anaemia and in 13 control subjects. Decreases in the number of lymphocytes and CD8+ cells and in the proportion of CD4+ cells, an abnormally high CD4/CD8 ratio, and suppressed NK cell activity were noted in patients compared with control subjects. In all 11 patients and eight control subjects, these immune parameters were evaluated before and after methyl-B12 injection. The lymphocyte counts and number of CD8+ cells increased both in patients and in control subjects. The high CD4/CD8 ratio and suppressed NK cell activity were improved by methyl-B12 treatment. Augmentation of CD3-CD16+ cells occurred in patients after methyl-B12 treatment. In contrast, antibody-dependent cell-mediated cytotoxicity (ADCC) activity, lectin-stimulated lymphocyte blast formation, and serum levels of immunoglobulins were not changed by methyl-B12 treatment. These results indicate that vit.B12 might play an important role in cellular immunity, especially relativing to CD8+ cells and the NK cell system, which suggests effects on cytotoxic cells. We conclude that vit.B12 acts as an immunomodulator for cellular immunity. PMID:10209501

  9. Evaluation of the Interaction between NMDA Receptors of Nucleus Accumbens and Muscarinic Receptors in Memory

    Saba Taheri

    2013-02-01

    Full Text Available Background and Objectives: Whereas studies have indicated the interaction between NMDA and cholinergic systems, this study was performed with the aim of determining the role of NMDA receptors in the nucleus accumbens (NAc in scopolamine-induced amnesia.Methods: In this study, at first rats were anesthetized with intra-peritoneal injection of ketamine hydrochloride plus xylazine, and then placed in a stereotaxic apparatus. Two stainless-steel cannulas were placed 2mm above nucleus accumbens shell. All animals were allowed to recover for one week, before beginning the behavioral testing. Then, animals were trained in a step-through type inhibitory avoidance task. The drugs were injected after successful training and before testing. The animals were tested 24h after training, and the step-through latency time was measured as the memory criterion in male Wistar rats. One-way analysis of variance and Tukey’s test were used for analysis of the data. p<0.05 was considered statistically significant.Results: Intra-nucleus accumbens (intra-NAc injection of scopolamine or NMDA caused impairment in memory in rats. Although, co-administration of an ineffective dose of NMDA with an ineffective dose of scopolamine had no significant effect on memory performance, effective doses of NMDA prevented the amnesic effect of scopolamine on inhibitory avoidance memory. On the other hand, intra-NAc injection of NMDA receptor antagonist, i.e., MK-801 caused no change in memory performance by itself, and its co-administration with an effective dose of scopolamine could not prevent the impairing effect of the latter drug. Conclusion: The finding of this study indicated that NMDA receptors in the nucleus accumbens are involved in the modulation of scopolamine-induced amnesia.

  10. Influence of augmented feedback on learning upper extremity tasks after stroke

    Molier, B.I.

    2012-01-01

    With upcoming innovative technologies more possibilities arise in the application of augmented feedback in rehabilitation therapy of the hemiparetic arm after stroke. The effect of different aspects and types of augmented feedback on motor functions and motor activities of the hemiparetic arm after stroke are studied in a systematic literature review. Based on current literature it was not possible to determine which combinations of aspects and types of augmented feedback are most essential f...

  11. Augmented reality and its practical application

    ZÍTKOVÁ, Helena

    2011-01-01

    This thesis combines topic of augmented reality with tourism. For analyzing the state of the use of augmented reality was composed case studies. It was created product, which is called Guide to mobile phone.

  12. Hinokitiol Exerts Anticancer Activity through Downregulation of MMPs 9/2 and Enhancement of Catalase and SOD Enzymes: In Vivo Augmentation of Lung Histoarchitecture

    Chien-Hsun Huang

    2015-09-01

    Full Text Available Melanoma is extremely resistant to chemotherapy and the death rate is increasing hastily worldwide. Extracellular matrix promotes the migration and invasion of tumor cells through the production of matrix metalloproteinase (MMP-2 and -9. Evidence has shown that natural dietary antioxidants are capable of inhibiting cancer cell growth. Our recent studies showed that hinokitiol, a natural bioactive compound, inhibited vascular smooth muscle cell proliferation and platelets aggregation. The present study is to investigate the anticancer efficacy of hinokitiol against B16-F10 melanoma cells via modulating tumor invasion factors MMPs, antioxidant enzymes in vitro. An in vivo mice model of histological investigation was performed to study the patterns of elastic and collagen fibers. Hinokitiol inhibited the expression and activity of MMPs-2 and -9 in B16-F10 melanoma cells, as measured by western blotting and gelatin zymography, respectively. An observed increase in protein expression of MMPs 2/9 in melanoma cells was significantly inhibited by hinokitiol. Notably, hinokitiol (1–5 μM increased the activities of antioxidant enzymes catalase (CAT and superoxide dismutase (SOD from the reduction in melanoma cells. Also, hinokitiol (2–10 µM concentration dependently reduced in vitro Fenton reaction induced hydroxyl radical (OH· formation. An in vivo study showed that hinokitiol treatment increased elastic fibers (EF, collagens dispersion, and improved alveolar alterations in the lungs of B16/F10 injected mice. Overall, our findings propose that hinokitiol may be a potent anticancer candidate through down regulation of MMPs 9/2, reduction of OH· production and enhancement of antioxidant enzymes SOD and CAT.

  13. Pregnanolone glutamate, a novel use-dependent NMDA receptor inhibitor, exerts antidepressant-like properties in animal models.

    Karel eVales

    2014-04-01

    Full Text Available A number of studies demonstrated a rapid onset of an antidepressant effect of non-competitive NMDA receptor antagonists. Nonetheless, its therapeutic potential is rather limited, due to a high coincidence of negative side-effects. Therefore, the challenge seems to be in the development of NMDA receptor (NMDAR antagonists displaying antidepressant properties, and at the same time maintaining regular physiological function of the NMDAR. Previous results demonstrated that naturally occurring neurosteroid 3α5β-pregnanolone sulfate shows pronounced inhibitory action by a use-dependent mechanism on the tonically active NMDAR. The aim of the present experiments is to find out whether the treatment with pregnanolone 3αC derivatives affects behavioral response to chronic and acute stress in an animal model of depression. Adult male mice were used throughout the study. Repeated social defeat and forced swimming tests were used as animal models of depression. The effect of the drugs on the locomotor/exploratory activity in the open-field test was also tested together with an effect on anxiety in the elevated plus maze. Results showed that pregnanolone glutamate (PG did not induce hyperlocomotion, whereas both dizocilpine and ketamine significantly increased spontaneous locomotor activity in the open field. In the elevated plus maze PG displayed anxiolytic-like properties. In forced swimming PG prolonged time to the first floating. Acute treatment of PG disinhibited suppressed locomotor activity in the repeatedly defeated group-housed mice. Aggressive behavior of isolated mice was reduced after the chronic 30-day administration of PG. PG showed antidepressant-like and anxiolytic-like properties in the used tests, with minimal side-effects. Since PG combines GABAA receptor potentiation and use-dependent NMDAR inhibition, synthetic derivatives of neuroactive steroids present a promising strategy for the treatment of mood disorders.

  14. Prospects for optogenetic augmentation of brain function

    Sarah eJarvis

    2015-11-01

    Full Text Available The ability to optically control neural activity opens up possibilities for the restoration of normal function following neurological disorders. The temporal precision, spatial resolution and neuronal specificity that optogenetics offers is unequalled by other available methods, so will it be suitable for not only restoring but also extending brain function? As the first demonstrations of optically ``implanted'' novel memories emerge, we examine the suitability of optogenetics as a technique for extending neural function. While optogenetics is an effective tool for altering neural activity, the largest impediment for optogenetics in neural augmentation is our systems level understanding of brain function. Furthermore, a number of clinical limitations currently remain as substantial hurdles for the applications proposed. While neurotechnologies for treating brain disorders and interfacing with prosthetics have advanced rapidly in the past few years, partially addressing some of these critical problems, optogenetics is not yet suitable for use in humans. Instead we conclude that for the immediate future, optogenetics is the neurological equivalent of the 3D printer: its flexibility providing an ideal tool for testing and prototyping solutions for treating brain disorders and augmenting brain function.

  15. Morphine-augmented cholescintigraphy enhances duodenogastric reflux

    Morphine intervention in cholescintigraphy decreases imaging time to diagnose acute cholecystitis. Not infrequently we observe duodenogastric reflux during scintigraphy with and without morphine intervention. To evaluate occurrence of duodenogastric reflux related to morphine, we reviewed 55 patients who underwent cholescintigraphy with (32) and without (23) morphine intervention. Morphine was injected when there was bowel activity with non-visualization of the gallbladder at 60 min. Duodenogastric reflux was identified by the appearance of activity in the area just below or immediately adjacent to the tip of the left hepatic lobe laterally. Among 32 patients with morphine intervention, 19 had acute cholecystitis and 13 chronic cholecystitis. Eleven of 19 (58%) with acute cholecystitis had duodenogastric reflux and 6 of 13 (46%) had duodenogastric reflux in chronic cholecystitis. The total of duodenogastric reflux in the group with morphine injection was 53%. Two patients' duodenogastric reflux occurred before morphine injection and was more apparent after morphine was given. In the without morphine group, 3 had acute cholecystitis and 20 had chronic cholecystitis; 2 (one acute and one chronic cholecystitis) of these 23 (9%) had duodenogastric reflux. Our results indicate: occurrence of duodenogastric reflux in morphine augmented cholescintigraphy is not significantly different in cholecystitis from that in chronic cholecystitis; duodenogastric reflux in morphine augmentation occurs significantly more often than without morphine intervention (p<0.001). We conclude that cholescintigraphy with morphine enhances duodenogastric reflux. The degree of duodenogastric reflux in the acute cholecystitis patients has been more severe than in the chronic cholecystitis patients. (author)

  16. Morphine-augmented cholescintigraphy enhances duodenogastric reflux

    Shih, Wei-Jen; Magoun, S.; Wierzbinski, B.; Ryo, U-Yun [Kentucky Univ., Lexington, KY (United States). Medical Center; Lee, Jong-Kang

    1995-11-01

    Morphine intervention in cholescintigraphy decreases imaging time to diagnose acute cholecystitis. Not infrequently we observe duodenogastric reflux during scintigraphy with and without morphine intervention. To evaluate occurrence of duodenogastric reflux related to morphine, we reviewed 55 patients who underwent cholescintigraphy with (32) and without (23) morphine intervention. Morphine was injected when there was bowel activity with non-visualization of the gallbladder at 60 min. Duodenogastric reflux was identified by the appearance of activity in the area just below or immediately adjacent to the tip of the left hepatic lobe laterally. Among 32 patients with morphine intervention, 19 had acute cholecystitis and 13 chronic cholecystitis. Eleven of 19 (58%) with acute cholecystitis had duodenogastric reflux and 6 of 13 (46%) had duodenogastric reflux in chronic cholecystitis. The total of duodenogastric reflux in the group with morphine injection was 53%. Two patients` duodenogastric reflux occurred before morphine injection and was more apparent after morphine was given. In the without morphine group, 3 had acute cholecystitis and 20 had chronic cholecystitis; 2 (one acute and one chronic cholecystitis) of these 23 (9%) had duodenogastric reflux. Our results indicate: occurrence of duodenogastric reflux in morphine augmented cholescintigraphy is not significantly different in cholecystitis from that in chronic cholecystitis; duodenogastric reflux in morphine augmentation occurs significantly more often than without morphine intervention (p<0.001). We conclude that cholescintigraphy with morphine enhances duodenogastric reflux. The degree of duodenogastric reflux in the acute cholecystitis patients has been more severe than in the chronic cholecystitis patients. (author).

  17. Augmented Reality for Multi-disciplinary Collaboration

    Wang, Xiangyu; Rui

    2010-01-01

    This chapter presents a framework for multi-disciplinary collaboration. Tangible Augmented Reality has been raised as one of suitable systems for design collaboration. Furthermore, it emphasizes the advantages of Tangible Augmented Reality to illustrate the needs for integrating the Tangible User Interfaces and Augmented Reality Systems.

  18. Relationship between structure, conformational flexibility, and biological activity of agonists and antagonists at the N-methyl-D-aspartic acid subtype of excitatory amino acid receptors

    Madsen, U; Brehm, L; Schaumburg, Kjeld;

    1990-01-01

    spectroscopy and supported by computer simulations and molecular mechanics calculations. While the trans forms of 2,3-PDA and 2,4-PDA and cis-2,5-PDA show NMDA receptor agonist activities, cis-2,3-PDA and cis-2,4-PDA are NMDA antagonists. The compounds trans-2,5-PDA and cis-2,6-PDA did not interact with NMDA...

  19. Effect of paliperidone and risperidone on extracellular glutamate in the prefrontal cortex of rats exposed to prenatal immune activation or MK-801

    Roenker, Nicole L.; Gudelsky, Gary; Ahlbrand, Rebecca; Bronson, Stefanie L.; Kern, Joseph R.; Waterman, Heather; Richtand, Neil M.

    2011-01-01

    The NMDA glutamate hypofunction model of schizophrenia is based in part upon acute effects of NMDA receptor blockade in humans and rodents. Several laboratories have reported glutamate system abnormalities following prenatal exposure to immune challenge, a known environmental risk factor for schizophrenia. Here we report indices of NMDA glutamate receptor hypofunction following prenatal immune activation, as well as the effects of treatment during periadolescence with the atypical antipsychot...

  20. Synaptic and extrasynaptic NMDA receptors are gated by different endogenous coagonists.

    Papouin, Thomas; Ladépêche, Laurent; Ruel, Jérôme; Sacchi, Silvia; Labasque, Marilyne; Hanini, Marwa; Groc, Laurent; Pollegioni, Loredano; Mothet, Jean-Pierre; Oliet, Stéphane H R

    2012-08-01

    N-methyl-d-aspartate receptors (NMDARs) are located in neuronal cell membranes at synaptic and extrasynaptic locations, where they are believed to mediate distinct physiological and pathological processes. Activation of NMDARs requires glutamate and a coagonist whose nature and impact on NMDAR physiology remain elusive. We report that synaptic and extrasynaptic NMDARs are gated by different endogenous coagonists, d-serine and glycine, respectively. The regionalized availability of the coagonists matches the preferential affinity of synaptic NMDARs for d-serine and extrasynaptic NMDARs for glycine. Furthermore, glycine and d-serine inhibit NMDAR surface trafficking in a subunit-dependent manner, which is likely to influence NMDARs subcellular location. Taking advantage of this coagonist segregation, we demonstrate that long-term potentiation and NMDA-induced neurotoxicity rely on synaptic NMDARs only. Conversely, long-term depression requires both synaptic and extrasynaptic receptors. Our observations provide key insights into the operating mode of NMDARs, emphasizing functional distinctions between synaptic and extrasynaptic NMDARs in brain physiology. PMID:22863013

  1. The relation of Cx43 and NMDA to visceral sensitization in rats with irritable bowel syndrome

    Jing-yu ZHANG

    2016-01-01

    Full Text Available Objective  To study the relationship between connexin 43 (Cx43 and N-methyl-D-aspartate (NMDA receptors and visceral sensitization in the rats with irritable bowel syndrome (IBS. Methods  Thirty rats were gavaged with Triehinella spiralis to reproduce the IBS model. These rats were randomly divided into IBS group, IBS+colon distension group, and IBS+STI-571+colon distension group, and other groups of normal rats were randomized into normal group and normal+colon distension group, with 10 rats in each group. Immunofluorescent double staining were used to observe the expressions of intestine Cx43 and sacral NMDA re ceptors of rats in all the groups. Results  The Cx43 and sacral NMDA expressions in the normal group, normal+colon distension group and IBS group showed no significant changes (P>0.05, however, Cx43 and sacral NMDA expressions were significantly higher in IBS rats with colon distension as compared with those in normal group, normal+colon distension group, and IBS group (P<0.05, while they were significantly lower in the IBS+STI-571+colon distension group after STI-571 intervention (P<0.05. Conclusion  Cx43 and sacral NMDA may be the most important factor of visceral sensitization in IBS rats. DOI: 10.11855/j.issn.0577-7402.2015.12.02

  2. Effective Augmentation of Complex Networks

    Wang, Jinjian; Yu, Xinghuo; Stone, Lewi

    2016-05-01

    Networks science plays an enormous role in many aspects of modern society from distributing electrical power across nations to spreading information and social networking amongst global populations. While modern networks constantly change in size, few studies have sought methods for the difficult task of optimising this growth. Here we study theoretical requirements for augmenting networks by adding source or sink nodes, without requiring additional driver-nodes to accommodate the change i.e., conserving structural controllability. Our “effective augmentation” algorithm takes advantage of clusters intrinsic to the network topology, and permits rapidly and efficient augmentation of a large number of nodes in one time-step. “Effective augmentation” is shown to work successfully on a wide range of model and real networks. The method has numerous applications (e.g. study of biological, social, power and technological networks) and potentially of significant practical and economic value.

  3. Augmented Reality in Science Education

    Nielsen, Birgitte Lund; Brandt, Harald; Swenson, Hakon

    2015-01-01

    Augmented reality (AR) holds great promise as a learning tool. However, most extant studies in this field have focused on the technology itself. The poster presents findings from the first stage of the AR-sci project addressing the issue of applying AR for educational purposes. Benefits and chall......Augmented reality (AR) holds great promise as a learning tool. However, most extant studies in this field have focused on the technology itself. The poster presents findings from the first stage of the AR-sci project addressing the issue of applying AR for educational purposes. Benefits...... and challenges related to AR enhancing student learning in science in lower secondary school were identified by expert science teachers, ICT designers and science education researchers from four countries in a Delphi survey. Findings were condensed in a framework to categorize educational AR designs....

  4. Psychotherapy Augmentation through Preconscious Priming

    Borgeat, François; O’Connor, Kieron; Amado, Danielle; St-Pierre-Delorme, Marie-Ève

    2013-01-01

    Objective: To test the hypothesis that repeated preconscious (masked) priming of personalized positive cognitions could augment cognitive change and facilitate achievement of patients’ goals following a therapy. Methods: Twenty social phobic patients (13 women) completed a 36-weeks study beginning by 12 weeks of group behavioral therapy. After the therapy, they received 6 weeks of preconscious priming and 6 weeks of a control procedure in a randomized cross-over design. The Priming conditi...

  5. Psychotherapy augmentation through preconscious priming

    Francois eBorgeat; Kieron eO'Connor; Danielle eAmado; Marie-Eve eSt-Pierre-Delorme

    2013-01-01

    Objective: To test the hypothesis that repeated preconscious (masked) priming of personalized positive cognitions could augment cognitive change and facilitate achievement of patients’ goals following a therapy.Methods: Twenty social phobic patients (13 women) completed a 36 weeks study beginning by 12 weeks of group behavioural therapy. After the therapy, they received 6 weeks of preconscious priming and 6 weeks of a control procedure in a randomized cross-over design. The Priming condition ...

  6. Digital Augmented Reality Audio Headset

    Jussi Rämö; Vesa Välimäki

    2012-01-01

    Augmented reality audio (ARA) combines virtual sound sources with the real sonic environment of the user. An ARA system can be realized with a headset containing binaural microphones. Ideally, the ARA headset should be acoustically transparent, that is, it should not cause audible modification to the surrounding sound. A practical implementation of an ARA mixer requires a low-latency headphone reproduction system with additional equalization to compensate for the attenuation and the modified ...

  7. Augmented Reality based Factory Planning

    Pentenrieder, Katharina

    2009-01-01

    Today’s factory planning relies on the methods and tools of the Digital Factory to meet shortened product life cycles and the resulting demand for fast and flexible reengineering. However, the Digital Factory and the real production plants are often not consistent, due to incomplete or missing digital data. Augmented Reality can serve as an intuitive interface here. The technology combines real and virtual information by integrating virtual planning data seamlessly with views of the real fact...

  8. Sensor Fusion for Augmented Reality

    Gustafsson, Fredrik; Schön, Thomas; Hol, Jeroen

    2009-01-01

    The problem of estimating the position and orientation (pose) of a camera is approached by fusing measurements from inertial sensors (accelerometers and rate gyroscopes) and a camera. The sensor fusion approach described in this contribution is based on nonlinear filtering using the measurements from these complementary sensors. This way, accurate and robust pose estimates are available for the primary purpose of augmented reality applications, but with the secondary effect of reducing comput...

  9. Sensor Fusion for Augmented Reality

    Hol, Jeroen; Schön, Thomas; Gustafsson, Fredrik; Slycke, Per

    2007-01-01

    In Augmented Reality (AR), the position and orientation of the camera have to be estimated with high accuracy and low latency. This nonlinear estimation problem is studied in the present paper. The proposed solution makes use of measurements from inertial sensors and computer vision. These measurements are fused using a Kalman filtering framework, incorporating a rather detailed model for the dynamics of the camera. Experiments show that the resulting filter provides good estimates of the cam...

  10. Differential antagonism of tetramethylenedisulfotetramine-induced seizures by agents acting at NMDA and GABA{sub A} receptors

    Shakarjian, Michael P., E-mail: michael_shakarjian@nymc.edu [Department of Environmental Health Science, School of Health Sciences and Practice, Institute of Public Health, New York Medical College, Valhalla, NY, 10595 (United States); Department of Medicine, Division of Pulmonary and Critical Care Medicine, UMDNJ–Robert Wood Johnson Medical School, Piscataway, NJ 08854 (United States); Velíšková, Jana, E-mail: jana_veliskova@nymc.edu [Department of Cell Biology and Anatomy, New York Medical College, Valhalla, NY 10595 (United States); Department of Obstetrics and Gynecology, New York Medical College, Valhalla, NY 10595 (United States); Department of Neurology, New York Medical College, Valhalla, NY 10595 (United States); Stanton, Patric K., E-mail: patric_stanton@nymc.edu [Department of Cell Biology and Anatomy, New York Medical College, Valhalla, NY 10595 (United States); Department of Neurology, New York Medical College, Valhalla, NY 10595 (United States); Velíšek, Libor, E-mail: libor_velisek@nymc.edu [Department of Cell Biology and Anatomy, New York Medical College, Valhalla, NY 10595 (United States); Department of Neurology, New York Medical College, Valhalla, NY 10595 (United States); Department of Pediatrics, New York Medical College, Valhalla, NY 10595 (United States)

    2012-11-15

    Tetramethylenedisulfotetramine (TMDT) is a highly lethal neuroactive rodenticide responsible for many accidental and intentional poisonings in mainland China. Ease of synthesis, water solubility, potency, and difficulty to treat make TMDT a potential weapon for terrorist activity. We characterized TMDT-induced convulsions and mortality in male C57BL/6 mice. TMDT (ip) produced a continuum of twitches, clonic, and tonic–clonic seizures decreasing in onset latency and increasing in severity with increasing dose; 0.4 mg/kg was 100% lethal. The NMDA antagonist, ketamine (35 mg/kg) injected ip immediately after the first TMDT-induced seizure, did not change number of tonic–clonic seizures or lethality, but increased the number of clonic seizures. Doubling the ketamine dose decreased tonic–clonic seizures and eliminated lethality through a 60 min observation period. Treating mice with another NMDA antagonist, MK-801, 0.5 or 1 mg/kg ip, showed similar effects as low and high doses of ketamine, respectively, and prevented lethality, converting status epilepticus EEG activity to isolated interictal discharges. Treatment with these agents 15 min prior to TMDT administration did not increase their effectiveness. Post-treatment with the GABA{sub A} receptor allosteric enhancer diazepam (5 mg/kg) greatly reduced seizure manifestations and prevented lethality 60 min post-TMDT, but ictal events were evident in EEG recordings and, hours post-treatment, mice experienced status epilepticus and died. Thus, TMDT is a highly potent and lethal convulsant for which single-dose benzodiazepine treatment is inadequate in managing electrographic seizures or lethality. Repeated benzodiazepine dosing or combined application of benzodiazepines and NMDA receptor antagonists is more likely to be effective in treating TMDT poisoning. -- Highlights: ► TMDT produces convulsions and lethality at low doses in mice. ► Diazepam pre- or post-treatments inhibit TMDT-induced convulsions and death

  11. MRI analysis after augmentation mammoplasty

    Objective: To analyze MRI appearance after augmentation mammoplasty, and to assess the clinical value. Methods: Sixty-three cases with augmentation mammoplasty were imaged by MR scanner. MR imaging features of silicone implant and injected implant were analyzed respectively. Results 80 breasts in 40 patients were with polyacrylamide hydrogel injection. In 50 breasts, the implants were shown as irregular gel in mammary gland, pectoralis muscle, and subcutaneous tissue. Auto-fat injection in both side of breast was performed in 7 cases. Among them, fibrofatty mass was detected in 12 breasts, fat- fluid interface was seen in 6 breasts, and fat in pectoralis major was revealed in 6 breasts. Silicone implant in both side of breast was performed in 16 cases. 2 breasts in 2 ease were detected as saline-filled implants with intracapsular rupture. 14 eases were with silicone gel-filled implants, among them, 4 breasts were found to have extracapsular rupture and 10 breasts intracapsular rupture. Conclusion: MRI is a perfect method in accessing the patients with augmentation mammoplasty. (authors)

  12. Aesthetic occiput augmentation using methylmethacrylate.

    Song, Yong Tai

    2015-01-01

    Cranioplasty for only aesthetic reasons has not been commonly performed to date. However, recently there has been a new focus by the public on a more aesthetically pleasing head shape with frequent patient requests for purely aesthetic contouring of the occiput, an important definer of cosmetic head shape. For example, in Asia, where the normal cranial shape is mesocephalic or brachycephalic and often with a planar occiput, requests for its aesthetic correction are increasingly common. Accordingly, the author developed a minimally invasive occiput augmentation using methylmethacrylate. In this study, the indications for aesthetic occiput contouring were planar occiput, left-right asymmetric occiput, and grooved occiput. Under local anesthesia, soft methylmethacrylate is subperiosteally inserted through a small incision (about 5-cm length), manually and precisely contoured in situ through the scalp to the desired occipital shape. All is performed as an outpatient procedure, and a quick recovery is the case. Between March 2007 and October 2013, 959 patients received such aesthetic occiput augmentation. The mean follow-up period was 49 months (range, 3-84 months). Nearly all patients were satisfied with the outcome, and complications were very rare. Only 5 patients (0.5%) needed additional corrective procedures. The author has concluded that aesthetic occiput augmentation using methylmethacrylate yields consistent, predictable, and satisfactory results. Additional long-term follow-up is required for a final conclusion, however. PMID:25569386

  13. NMDA and AMPA/kainate glutamatergic receptors in the prelimbic medial prefrontal cortex modulate the elaborated defensive behavior and innate fear-induced antinociception elicited by GABAA receptor blockade in the medial hypothalamus.

    de Freitas, Renato Leonardo; Salgado-Rohner, Carlos José; Biagioni, Audrey Francisco; Medeiros, Priscila; Hallak, Jaime Eduardo Cecílio; Crippa, José Alexandre S; Coimbra, Norberto Cysne

    2014-06-01

    The aim of the present study was to investigate the involvement of N-methyl-d-aspartate (NMDA) and amino-3-hydroxy-5-methyl-isoxazole-4-proprionate (AMPA)/kainate receptors of the prelimbic (PL) division of the medial prefrontal cortex (MPFC) on the panic attack-like reactions evoked by γ-aminobutyric acid-A receptor blockade in the medial hypothalamus (MH). Rats were pretreated with NaCl 0.9%, LY235959 (NMDA receptor antagonist), and NBQX (AMPA/kainate receptor antagonist) in the PL at 3 different concentrations. Ten minutes later, the MH was treated with bicuculline, and the defensive responses were recorded for 10 min. The antagonism of NMDA receptors in the PL decreased the frequency and duration of all defensive behaviors evoked by the stimulation of the MH and reduced the innate fear-induced antinociception. However, the pretreatment of the PL cortex with NBQX was able to decrease only part of defensive responses and innate fear-induced antinociception. The present findings suggest that the NMDA-glutamatergic system of the PL is critically involved in panic-like responses and innate fear-induced antinociception and those AMPA/kainate receptors are also recruited during the elaboration of fear-induced antinociception and in panic attack-related response. The activation of the glutamatergic neurotransmission of PL division of the MPFC during the elaboration of oriented behavioral reactions elicited by the chemical stimulation of the MH recruits mainly NMDA receptors in comparison with AMPA/kainate receptors. PMID:23349224

  14. Tracking for Outdoor Mobile Augmented Reality: Further development of the Zion Augmented Reality Application

    Strand, Tor Egil Riegels

    2008-01-01

    This report deals with providing tracking to an outdoor mobile augmented reality system and the Zion Augmented Reality Application. ZionARA is meant to display a virtual recreation of a 13th century castle on the site it once stood through an augmented reality Head Mounted Display. Mobile outdoor augmented/mixed reality puts special demands on what kind of equipment is practical. After briefly evaluating the different existing tracking methods, a solution based on GPS and an augmented inertia...

  15. Tracking for Outdoor Mobile Augmented Reality : Further development of the Zion Augmented Reality Application

    Strand, Tor Egil Riegels

    2008-01-01

    This report deals with providing tracking to an outdoor mobile augmented reality system and the Zion Augmented Reality Application. ZionARA is meant to display a virtual recreation of a 13th century castle on the site it once stood through an augmented reality Head Mounted Display. Mobile outdoor augmented/mixed reality puts special demands on what kind of equipment is practical. After briefly evaluating the different existing tracking methods, a solution based on GPS and an augmented inertia...

  16. Treatment with dehydroepiandrosterone sulfate increases NR1 and NR2 subunits of NMDA receptors in rat hippocampus.

    E.DARTOIS; W.PINOTEAU; M.VINCENS

    2004-01-01

    Neurosteroids are present in the central nervous system (CNS) and can be allosteric modulators of neurotransmitter receptors. One of them, the dehydroepiandrosterone sulfate (DHEAS) has been shown to modulate the NMDA receptor, a subtype of glutamate receptor. These NMDA receptors are known to be involved in long-term potentiation and in learning and memory (Tsien 2000). Moreover, DHEAS has been reported

  17. TRPM4-dependent post-synaptic depolarization is essential for the induction of NMDA receptor-dependent LTP in CA1 hippocampal neurons.

    Menigoz, Aurélie; Ahmed, Tariq; Sabanov, Victor; Philippaert, Koenraad; Pinto, Silvia; Kerselaers, Sara; Segal, Andrei; Freichel, Marc; Voets, Thomas; Nilius, Bernd; Vennekens, Rudi; Balschun, Detlef

    2016-04-01

    TRPM4 is a calcium-activated but calcium-impermeable non-selective cation (CAN) channel. Previous studies have shown that TRPM4 is an important regulator of Ca(2+)-dependent changes in membrane potential in excitable and non-excitable cell types. However, its physiological significance in neurons of the central nervous system remained unclear. Here, we report that TRPM4 proteins form a CAN channel in CA1 neurons of the hippocampus and we show that TRPM4 is an essential co-activator of N-methyl-D-aspartate (NMDA) receptors (NMDAR) during the induction of long-term potentiation (LTP). Disrupting the Trpm4 gene in mice specifically eliminates NMDAR-dependent LTP, while basal synaptic transmission, short-term plasticity, and NMDAR-dependent long-term depression are unchanged. The induction of LTP in Trpm4 (-/-) neurons was rescued by facilitating NMDA receptor activation or post-synaptic membrane depolarization. Accordingly, we obtained normal LTP in Trpm4 (-/-) neurons in a pairing protocol, where post-synaptic depolarization was applied in parallel to pre-synaptic stimulation. Taken together, our data are consistent with a novel model of LTP induction in CA1 hippocampal neurons, in which TRPM4 is an essential player in a feed-forward loop that generates the post-synaptic membrane depolarization which is necessary to fully activate NMDA receptors during the induction of LTP but which is dispensable for the induction of long-term depression (LTD). These results have important implications for the understanding of the induction process of LTP and the development of nootropic medication. PMID:26631168

  18. Differential involvement of glutamatergic and catecholaminergic activity within the amygdala during taste aversion retrieval on memory expression and updating.

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

    2016-07-01

    During memory retrieval, consolidated memories are expressed and destabilized in order to maintain or update information through a memory reconsolidation process. Despite the key role of the amygdala during memory acquistion and consolidation, the participation of neurotransmitter signals in memory retrieval is poorly understood. Hence, we used conditioned taste aversion and in vivo microdialysis to evaluate changes in glutamate, norepinephrine and dopamine concentrations within the amygdala during memory retrieval. We observed that exposure to an aversive-conditioned stimulus induced an augmentation in glutamate, norepinephrine and dopamine levels within the amygdala, while exposure to a familiar and safe stimulus did not induce changes in these neurotransmitters levels. Also, we evaluated the amygdalar blockade of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), N-methyl-d-aspartate (NMDA), β-adrenergic and dopamine D1 receptors in memory retrieval and updating. Results showed that during retrieval, behavioural expression was impaired by intra-amygdalar blockade of AMPA and β-adrenergic receptors, whereas NMDA, D1 and β-adrenergic receptors blockade hindered memory updating. In summary, during conditioned taste aversion retrieval there was an increase in the extracellular levels of glutamate, norepinephrine and dopamine within the amygdala, and their receptors activity were differentially involved in the behavioural expression and memory updating during retrieval. PMID:27018173

  19. Kinetic modelling of [{sup 123}I]CNS 1261--a potential SPET tracer for the NMDA receptor

    Erlandsson, Kjell E-mail: k.erlandsson@nucmed.ucl.ac.uk; Bressan, Rodrigo A.; Mulligan, Rachel S.; Gunn, Roger N; Cunningham, Vincent J.; Owens, Jonathan; Wyper, David; Ell, Peter J.; Pilowsky, Lyn S

    2003-05-01

    N-(1-napthyl)-N'-(3-[{sup 123}I]-iodophenyl)-N-methylguanidine ([{sup 123}I]CNS 1261) is a novel SPET ligand developed for imaging the NMDA receptor intra-channel MK 801/PCP/ketamine site. Data was acquired in 7 healthy volunteers after bolus injection of [{sup 123}I]CNS 1261. Kinetic modeling showed reversible tracer binding. Arterial and venous time-activity curves overlapped after 90 min. The rank order of binding was: Thalamus > striatum > cortical regions > white matter. This distribution concurs with [{sup 11}C]-ketamine and [{sup 18}F]-memantine PET studies . These data provide a methodological basis for further direct in vivo challenge studies.

  20. In vivo evaluation of [{sup 11}C]N-(2-chloro-5-thiomethylphenyl)-N'- (3-methoxy-phenyl)-N'-methylguanidine ([{sup 11}C]GMOM) as a potential PET radiotracer for the PCP/NMDA receptor

    Waterhouse, Rikki N. E-mail: rnw7@columbia.edu; Slifstein, Mark; Dumont, Filip; Zhao Jun; Chang, Raymond C.; Sudo, Yasuhiko; Sultana, Abida; Balter, Andrew; Laruelle, Marc

    2004-10-01

    The development of imaging methods to measure changes in NMDA ion channel activation would provide a powerful means to probe the mechanisms of drugs and device based treatments (e.g., ECT) thought to alter glutamate neurotransmission. To provide a potential NMDA/PCP receptor PET tracer, we synthesized the radioligand [{sup 11}C]GMOM (K{sub i} = 5.2 {+-}0.3 nM; log P = 2.34) and evaluated this ligand in vivo in awake male rats and isoflurane anesthetized baboons. In rats, the regional brain uptake of [{sup 11}C]GMOM ranged from 0.75{+-}0.13% ID/g in the medulla and pons to 1.15{+-}0.17% ID/g in the occipital cortex. MK801 (1 mg/kg i.v.) significantly reduced (24-28%) [{sup 11}C]GMOM uptake in all regions. D-serine (10 mg/kg i.v.) increased [{sup 11}C]GMOM %ID/g values in all regions (10-24%) reaching significance in the frontal cortex and cerebellum only. The NR2B ligand RO 25-6981 (10 mg/kg i.v.) reduced [{sup 11}C]GMOM uptake significantly (24-38%) in all regions except for the cerebellum and striatum. Blood activity was 0.11{+-}0.03 %ID/g in the controls group and did not vary significantly across groups. PET imaging in isoflurane-anesthetized baboons with high specific activity [{sup 11}C]GMOM provided fairly uniform regional brain distribution volume (V{sub T}) values (12.8-17.1 ml g{sup -1}). MK801 (0.5 mg/kg, i.v., n = 1, and 1.0 mg/kg, i.v., n = 1) did not significantly alter regional V{sub T} values, indicating a lack of saturable binding. However, the potential confounding effects associated with ketamine induction of anesthesia along with isoflurane maintenance must be considered because both agents are known to reduce NMDA ion channel activation. Future and carefully designed studies, presumably utilizing an optimized NMDA/PCP site tracer, will be carried out to further explore these hypotheses. We conclude that, even though [{sup 11}C]GMOM is not an optimized PCP site radiotracer, its binding is altered in vivo in awake rats as expected by modulation of

  1. Anti-NMDA receptor encephalitis presenting as atypical anorexia nervosa: an adolescent case report.

    Mechelhoff, David; van Noort, Betteke Maria; Weschke, Bernhard; Bachmann, Christian J; Wagner, Christiane; Pfeiffer, Ernst; Winter, Sibylle

    2015-11-01

    Since 2007, more than 600 patients have been diagnosed with anti-N-methyl-D-aspartate (NMDA) receptor encephalitis, with almost 40 % of those affected being children or adolescents. In early phases of the illness, this life-threatening disease is characterized by psychiatric symptoms, such as depression, anxiety, obsessions, hallucinations or delusions. Consequently, a high percentage of patients receive psychiatric diagnoses at first, hindering the crucial early diagnosis and treatment of the anti-NMDA receptor encephalitis. We report on a 15-year-old girl initially presenting with pathological eating behaviour and significant weight loss resulting in an (atypical) anorexia nervosa (AN) diagnosis. Her early course of illness, diagnostic process, treatment and short-term outcome are described. This case report aims to raise awareness about the association between anorectic behaviour and anti-NMDA receptor encephalitis and highlight the importance of multidisciplinary teams in child and adolescent services. PMID:25663428

  2. IRSp53/BAIAP2 in dendritic spine development, NMDA receptor regulation, and psychiatric disorders.

    Kang, Jaeseung; Park, Haram; Kim, Eunjoon

    2016-01-01

    IRSp53 (also known as BAIAP2) is a multi-domain scaffolding and adaptor protein that has been implicated in the regulation of membrane and actin dynamics at subcellular structures, including filopodia and lamellipodia. Accumulating evidence indicates that IRSp53 is an abundant component of the postsynaptic density at excitatory synapses and an important regulator of actin-rich dendritic spines. In addition, IRSp53 has been implicated in diverse psychiatric disorders, including autism spectrum disorders, schizophrenia, and attention deficit/hyperactivity disorder. Mice lacking IRSp53 display enhanced NMDA (N-methyl-d-aspartate) receptor function accompanied by social and cognitive deficits, which are reversed by pharmacological suppression of NMDA receptor function. These results suggest the hypothesis that defective actin/membrane modulation in IRSp53-deficient dendritic spines may lead to social and cognitive deficits through NMDA receptor dysfunction. This article is part of the Special Issue entitled 'Synaptopathy--from Biology to Therapy'. PMID:26275848

  3. Hippocampal NMDA receptors are necessary for auditory trace fear conditioning measured with conditioned hypoalgesia in rats.

    Seo, Dong-Oh; Pang, Min-Hee; Shin, Maeng-Sik; Kim, Hyun-Taek; Choi, June-Seek

    2008-10-10

    We tested whether N-methyl-D-aspartate (NMDA) receptors in the dorsal hippocampus (DH) are critical for the acquisition of trace fear conditioning using conditioned hypoalgesia (CHA), decrease in pain reactivity, as the conditioned response (CR) instead of commonly used freezing. Infusions of the NMDA receptor antagonist, DL-2-amino-5-phosphonovaleric acid (APV) into DH prior to conditioning resulted in impaired CHA, measured with the radiant heat tail flick test, only in the trace-conditioning group when they were tested during the trace interval. The same infusion had no effect on CHA in the delay-conditioned animals. The results support that NMDA receptors in DH are critically involved in associating the CS with the US across a temporal gap. In addition, temporal specificity of the CR was revealed as CHA was induced only in the temporal vicinity of the US used for the training. PMID:18514922

  4. Early Use of the NMDA Receptor Antagonist Ketamine in Refractory and Superrefractory Status Epilepticus

    F. A. Zeiler

    2015-01-01

    Full Text Available Refractory status epilepticus (RSE and superrefractory status epilepticus (SRSE pose a difficult clinical challenge. Multiple cerebral receptor and transporter changes occur with prolonged status epilepticus leading to pharmacoresistance patterns unfavorable for conventional antiepileptics. In particular, n-methyl-d-aspartate (NMDA receptor upregulation leads to glutamate mediated excitotoxicity. Targeting these NMDA receptors may provide a novel approach to otherwise refractory seizures. Ketamine has been utilized in RSE. Recent systematic review indicates 56.5% and 63.5% cessation in seizures in adults and pediatrics, respectively. No complications were described. We should consider earlier implementation of ketamine or other NMDA receptor antagonists, for RSE. Prospective study of early implementation of ketamine should shed light on the role of such medications in RSE.

  5. Synthesis and radiofluorination of putative NMDA receptor ligands

    Kronenberg, U.

    2011-01-15

    In the course of this work on the synthesis of radioligands for the NMDA receptor the authentic standards and labeling precursors of four compounds with an amidine structure was performed. Synthesis of the precursors followed reaction conditions given in the literature and was successful. The imidoesters used for the synthesis were obtained from their nitriles in a Pinner synthesis, while 2-hydroxybenzylamine was synthesized in a reduction of 2-hydroxybenzonitrile using borane as a reducing agent. After a coupling reaction of the amine and the imidoester in DMF using triethylamine as base the precursors were obtained in good yields and purified by crystallization from methanol. The cyclic standard compound was synthesized directly from 2-(bromomethyl)- benzonitrile and 2-hydroxybenzylamine in a ring closing reaction. Similar to the other precursors, crystallization from methanol produced a pure compound. The authentic standards were synthesized starting from salicylaldehyde. In a four step synthesis the desired ortho-fluoroethoxybenzylamine was obtained in good yield. Coupling of the amine with the respective imidoester or in the case of the cyclic compound 2-(bromomethyl)-benzonitrile gave the desired product which was then purified by column chromatography or by crystallization from ethanol and water. For the labeling procedure 1-bromo-2-[{sub 18}F]fluoroethane was synthesized following a previously published pathway starting from 1,2-dibromoethane. An alternative route of radiosynthesis for this prosthetic group was tested using ethyleneglycole- 1,2-ditosylate. The labeling reaction was performed on one of the precursors testing both DMF and DMSO as solvents and using NaOH as base. Yields of N-(2-fluoroethoxybenzyl)- cinnamamidine were about 78 % at 80 C after 30 minutes in DMSO. The desired product can now be synthesized in sufficient yields for in vitro and in vivo evaluation studies. Labeling on the cyclic precursor was attempted utilizing DMSO as solvent

  6. Synthesis and radiofluorination of putative NMDA receptor ligands

    In the course of this work on the synthesis of radioligands for the NMDA receptor the authentic standards and labeling precursors of four compounds with an amidine structure was performed. Synthesis of the precursors followed reaction conditions given in the literature and was successful. The imidoesters used for the synthesis were obtained from their nitriles in a Pinner synthesis, while 2-hydroxybenzylamine was synthesized in a reduction of 2-hydroxybenzonitrile using borane as a reducing agent. After a coupling reaction of the amine and the imidoester in DMF using triethylamine as base the precursors were obtained in good yields and purified by crystallization from methanol. The cyclic standard compound was synthesized directly from 2-(bromomethyl)- benzonitrile and 2-hydroxybenzylamine in a ring closing reaction. Similar to the other precursors, crystallization from methanol produced a pure compound. The authentic standards were synthesized starting from salicylaldehyde. In a four step synthesis the desired ortho-fluoroethoxybenzylamine was obtained in good yield. Coupling of the amine with the respective imidoester or in the case of the cyclic compound 2-(bromomethyl)-benzonitrile gave the desired product which was then purified by column chromatography or by crystallization from ethanol and water. For the labeling procedure 1-bromo-2-[18F]fluoroethane was synthesized following a previously published pathway starting from 1,2-dibromoethane. An alternative route of radiosynthesis for this prosthetic group was tested using ethyleneglycole- 1,2-ditosylate. The labeling reaction was performed on one of the precursors testing both DMF and DMSO as solvents and using NaOH as base. Yields of N-(2-fluoroethoxybenzyl)- cinnamamidine were about 78 % at 80 C after 30 minutes in DMSO. The desired product can now be synthesized in sufficient yields for in vitro and in vivo evaluation studies. Labeling on the cyclic precursor was attempted utilizing DMSO as solvent, but no

  7. 14 CFR 23.672 - Stability augmentation and automatic and power-operated systems.

    2010-01-01

    ... provided for any failure in the stability augmentation system or in any other automatic or power-operated system that could result in an unsafe condition if the pilot was not aware of the failure. Warning systems must not activate the control system. (b) The design of the stability augmentation system or...

  8. Learning Physics through Play in an Augmented Reality Environment

    Enyedy, Noel; Danish, Joshua A.; Delacruz, Girlie; Kumar, Melissa

    2012-01-01

    The Learning Physics through Play Project (LPP) engaged 6-8-year old students (n = 43) in a series of scientific investigations of Newtonian force and motion including a series of augmented reality activities. We outline the two design principles behind the LPP curriculum: 1) the use of socio-dramatic, embodied play in the form of participatory…

  9. Conantokin probes of NMDA receptors in normal and Alzheimer disease human cerebral cortex

    Full text: The pharmacology of the N-methyl-D-aspartate (NMDA) receptor site was examined in pathologically affected and relatively spared regions of cerebral cortex tissue obtained at autopsy from Alzheimer disease cases and matched controls. The affinity and density of the [3H]MK-801 binding site were delineated along with the enhancement of [3H]MK-801 binding by glutamate and spermine. Sites with distinct pharmacologies were distributed regionally through the cortex. The differences could not be explained by variations in the parameters of [3H]MK-801 binding; rather, the data suggest that the subunit composition of NMDA receptors may be locally variable. Selective differences were also found between controls and Alzheimer disease cases in certain brain regions. The interactions of human NMDA sites with the Ala(7) and Lys(7) derivatives of conantokin-G (Con-G) were also characterized. Ala(7)-con-G showed the higher affinity of the two peptides, and also defined two distinct binding sites in controls. In distinction to the Ala(7) peptide, Lys(7)- con-G showed preferential binding to receptor sites in Alzheimer disease cf. control brain. Modified conantokins are useful for identifying differences in subunit composition of the NMDA receptors between brain areas. They may also have potential as protective agents against over-excitation mediated by specific NMDA receptors, which might contribute to localized brain damage in Alzheimer disease. For further characterization of the pharmacology of different NMDA receptor subunits, a mammalian expression system has been developed for the analysis of their responses to selected ligands, including conantokins. Copyright (2002) Australian Neuroscience Society

  10. S-Nitrosoglutathione and glutathione act as NMDA receptor agonists in cultured hippocampal neurons

    Ting-yu CHIN; Sheau-huei CHUEH; Pao-luh TAO

    2006-01-01

    Aim: To characterize the effect of combined pre- and postnatal morphine exposure on Af-methyl-D-aspartate receptor (NMDA) receptor signaling in hippocampal neurons of the offspring of morphine-addicted female rats. Methods: Cultured hippocampal neurons and synaptosomes were prepared from neonatal and 2-week-old offspring, respectively, of control or morphine-addicted female rats. The increase in the cytosolic Ca2+ concentration ([Ca2+]i) of cultured cells was measured using Fura-2, and glutamate release from synaptosomes was measured enzymatically. Results: Both glutamate and NMDA caused a dose-dependent increase in the [Ca2+]i. The nitric oxide (NO) donor, S-nitrosoglutathione (GSNO), but not 3-morpholinosydnonimine, sodium nitroprusside, and S-nitroso-N-acetylpenicillamine, also induced a [Ca2+]i increase. GSNO and glutathione caused a dose-dependent increase in the [Ca2+]i with respective EC50 values of 56 and 414 μmol/L. Both effects were inhibited by Mg2+ or an NMDA receptor antagonist and were unaffected by the presence of a glutamate scavenger. The other glutathione derivatives, oxidized glutathione, S-methylglutathione, S-ethylglutathione, S-propylglutathione, and S-butylglutathione, the dipeptides, Glu-Cys and Cys-Gly, and the antioxidants, dithiothreitol and mercaptoethanol, failed to induce a [Ca2+]i increase. In addition, glutathione caused a dose-dependent increase in glutamate release from synaptosomes. The maximal responses and the EC50 values for the glutamate-, NMDA-, GSNO-, and glutathione-induced [Ca2+]i increases and the glutathione-induced glutamate release were indistinguishable in the neurons of the offspring from control and morphine-addicted female rats. Conclusion: GSNO and glutathione act as NMDA receptor agonists and, in contrast to hippocampal brain slice, combined pre- and postnatal morphine exposure does not modulate NMDA receptor signaling in the cultured hippocampal neurons.

  11. Bibliography on augmentation of convective heat and mass transfer

    Heat transfer augmentation has developed into a major specialty area in heat transfer research and development. A bibliography of world literature on augmentation is presented. The literature is classified into passive augmentation techniques, which require no external power, and active techniques, which do require external power. The fourteen techniques are grouped in terms of their application to the various modes of heat transfer. Mass transfer is included for completeness. Key words are included with each citation for technique/mode identification. The total number of publications cited is 1,967, including 75 surveys of various techniques and 42 papers on performance evaluation of passive techniques. Patents are not included as they will be the subject of a future topical report

  12. Bibliography on augmentation of convective heat and mass transfer

    Bergles, A.E.; Webb, R.L.; Junkhan, G.H.; Jensen, M.K.

    1979-05-01

    Heat transfer augmentation has developed into a major specialty area in heat transfer research and development. A bibliography of world literature on augmentation is presented. The literature is classified into passive augmentation techniques, which require no external power, and active techniques, which do require external power. The fourteen techniques are grouped in terms of their application to the various modes of heat transfer. Mass transfer is included for completeness. Key words are included with each citation for technique/mode identification. The total number of publications cited is 1,967, including 75 surveys of various techniques and 42 papers on performance evaluation of passive techniques. Patents are not included as they will be the subject of a future topical report.

  13. Neuroprotective effects of vinpocetine and its major metabolite cis-apovincaminic acid on NMDA-induced neurotoxicity in a rat entorhinal cortex lesion model.

    Nyakas, Csaba; Felszeghy, Klára; Szabó, Róbert; Keijser, Jan N; Luiten, Paul G M; Szombathelyi, Zsolt; Tihanyi, Károly

    2009-01-01

    Vinpocetine (ethyl-apovincaminate, Cavinton), a synthetic derivative of the Vinca minor alkaloid vincamine, has been used now for decades for prevention and treatment of cerebrovascular diseases predisposing to development of dementia. Both vinpocetine and its main metabolite cis-apovincaminic acid (cAVA) exert a neuroprotective type of action. Bilateral N-methyl-D-aspartate (NMDA)-induced neurodegeneration in the entorhinal cortex of rat was used as a dementia model to confirm the neuroprotective action of these compounds in vivo. NMDA-lesioned rats were treated 60 min before lesion and throughout 3 postoperative days with a 10 mg/kg intraperitoneal dose of vinpocetine or cAVA. Behavioral tests started after termination of drug treatment and consisted of novel object recognition, social discrimination, and spontaneous alternation in a Y-maze, and spatial learning in the Morris water maze. At the end of behavioral testing brains were perfused with fixative and the size of the excitotoxic neuronal lesion and that of microglial activation around the lesion were assayed quantitatively on brain sections immunostained for neuron-specific nuclear protein (NeuN) and integrin CD11b, respectively. Entorhinal NMDA lesions impaired recognition of novel objects and the new social partner, and suppressed spontaneous alternation and spatial learning performance in the Morris maze. Both vinpocetine and cAVA effectively attenuated the behavioral deficits, and significantly decreased lesion size and the region of microglia activation. Both lesion-induced attention deficit and learning disabilities were markedly alleviated by vinpocetine and cAVA. The morphological findings corroborated the behavioral observations and indicated reduced lesion size and microglia activation especially after vinpocetine treatment which supports an in vivo neuroprotective mode of action of vinpocitine and a less potent action of cAVA. PMID:19492990

  14. Absence of prostaglandin E2-induced hyperalgesia in NMDA receptor ε subunit knockout mice

    Minami, Toshiaki; Sugatani, Junko; Sakimura, Kenji; Abe, Manabu; Mishina, Masayoshi; Ito, Seiji

    1997-01-01

    We have previously found that intrathecal administration of prostaglandins E2 (PGE2) and D2 (PGD2) into conscious mice induced hyperalgesia by the hot plate test. The present study investigated the involvement of N-methyl-D-aspartate (NMDA) receptor in the prostaglandin-induced hyperalgesia by use of mice lacking NMDA receptor ε1, ε4, or ε1/ε4 subunits.PGE2 induced hyperalgesia over a wide range of doses from 50 pg to 500 ng kg−1 in wild-type mice. But PGE2 could not induce hyperalgesia in ε1...

  15. Synthesis of C3, C5, and C7 pregnane derivatives and their effect on NMDA receptor responses in cultured rat hippocampal neurons

    Šťastná, Eva; Chodounská, Hana; Pouzar, Vladimír; Kapras, Vojtěch; Borovská, Jiřina; Cais, Ondřej; Vyklický ml., Ladislav

    2009-01-01

    Roč. 74, č. 2 (2009), s. 256-263. ISSN 0039-128X R&D Projects: GA ČR(CZ) GA309/07/0271; GA ČR(CZ) GA203/08/1498 Grant ostatní: GA MŠk(CZ) LC554; FP6 Photolysis(XE) LSHM-CT-2007-037765 Institutional research plan: CEZ:AV0Z40550506; CEZ:AV0Z50110509 Keywords : pregnane derivatives * NMDA receptor * structure-activity relationship * patch-clamp recording Subject RIV: CC - Organic Chemistry Impact factor: 2.905, year: 2009

  16. Webizing mobile augmented reality content

    Ahn, Sangchul; Ko, Heedong; Yoo, Byounghyun

    2014-01-01

    This paper presents a content structure for building mobile augmented reality (AR) applications in HTML5 to achieve a clean separation of the mobile AR content and the application logic for scaling as on the Web. We propose that the content structure contains the physical world as well as virtual assets for mobile AR applications as document object model (DOM) elements and that their behaviour and user interactions are controlled through DOM events by representing objects and places with a uniform resource identifier. Our content structure enables mobile AR applications to be seamlessly developed as normal HTML documents under the current Web eco-system.

  17. Digital Illumination for Augmented Studios

    Stefanie Zollmann

    2006-12-01

    Full Text Available Virtual studio technology plays an important role for modern television productions. Blue-screen matting is a common technique for integrating real actors or moderators into computer generated sceneries. Augmented reality offers the possibility to mix real and virtual in a more general context. This article proposes a new technological approach for combining real studio content with computer-generated information. Digital light projection allows a controlled spatial, temporal, chrominance and luminance modulation of illumination opening new possibilities for TV studios.

  18. Forskolin induces NMDA receptor-dependent potentiation at a central synapse in the leech.

    Grey, Kathryn B; Burrell, Brian D

    2008-05-01

    In vertebrate hippocampal neurons, application of forskolin (an adenylyl cyclase activator) and rolipram (a phosphodiesterase inhibitor) is an effective technique for inducing chemical long-term potentiation (cLTP) that is N-methyl-d-aspartate (NMDA) receptor (NMDAR)-dependent. However, it is not known whether forskolin induces a similar potentiation in invertebrate synapses. Therefore, we examined whether forskolin plus rolipram treatment could induce potentiation at a known glutamatergic synapse in the leech (Hirudo sp.), specifically between the pressure (P) mechanosensory and anterior pagoda (AP) neurons. Perfusion of isolated ganglia with forskolin (50 muM) in conjunction with rolipram (0.1 muM) in Mg(2+)-free saline significantly potentiated the P-to-AP excitatory postsynaptic potential. Application of 2-amino-5-phosphonovaleric acid (APV, 100 muM), a competitive NMDAR antagonist, blocked the potentiation, indicating P-to-AP potentiation is NMDAR-dependent. Potentiation was blocked by injection of bis-(o-aminophenoxy)-N,N,N',N'-tetraacetic acid (BAPTA, 1 mM) into the postsynaptic cell, but not by BAPTA injection into the presynaptic neuron, indicating a requirement for postsynaptic elevation of intracellular Ca(2+). Application of db-cAMP mimicked the potentiating effects of forskolin, and Rp-cAMP, an inhibitor of protein kinase A, blocked forskolin-induced potentiation. Potentiation was also blocked by autocamtide-2-related inhibitory peptide (AIP), indicating a requirement for activation of Ca(2+)/calmodulin-dependent kinase II (CaMKII). Finally, potentiation was blocked by botulinum toxin, suggesting that trafficking of glutamate receptors also plays a role in this form of synaptic plasticity. These experiments demonstrate that techniques used to induce cLTP in vertebrate synapses also induce NMDAR-dependent potentiation in the leech CNS and that many of the cellular processes that mediate LTP are conserved between vertebrate and invertebrate phyla. PMID

  19. Nitric oxide (NO and an NMDA receptor antagonist in pentylenetetrazole-induced convulsions

    Jelenković Ankica V.

    2003-01-01

    Full Text Available Controversy about proconvulsant and anticonvulsant nitric oxide (NO effects and the place of oxidative stress in convulsions, are still a matter of research. We investigated the interaction between 2-amino-5-phosphonovaleric acid (APV, a competitive N-methyl-D-aspartate (NMDA receptor antagonist and Nw-nitro-L-arginine methyl ester (L-NAME, a nonselective nitric oxide synthase (NOS antagonist, in pentylenetetrazole (PTZ-induced convulsions. Pentylenetetrazole was applied to adult Wistar rats intraperitoneally (ip in a single dose of 80 mg/kg, and L-NAME (10 µg/10 µl or APV (20 µg/10 µl intracerebroventricularly (icv, 30 and 10 minutes before PTZ, respectively. In the same manner, another group received both antagonists. Control animals were given 0.9% saline. Nw-nitro-L-arginine methyl ester exerted a weak anticonvulsant effect, preventing generalized clonic (GCC and clonic-tonic convulsions (CTC in 17% of cases. With APV protection against GCC and CTC was 100%, forelimb dystonia (FLD was decreased in 33% of cases, and time to onset of all convulsive patterns was prolonged (p<0.05 to 0.01. All effects of APV, except in CTC, were reversed by L-NAME applied prior to APV. In APV-PTZ treated animals, superoxide anion content was increased in the forebrain cortex, striatum and hippocampus, without an overwhelmed antioxidative superoxide dismutase (SOD defense system in the other treatments. When the APV-PTZ group was treated with L-NAME, both SOD activity and superoxide anion content were additionally decreased indicating that the NOS-NO system was involved in the metabolism of superoxide anions. It is suggested that clinical and biochemical effects of NO strongly depend upon the pretreatment and might lead to a wrong impression of NO contradictory activity.

  20. Agmatine attenuates reserpine-induced oral dyskinesia in mice: Role of oxidative stress, nitric oxide and glutamate NMDA receptors.

    Cunha, Andréia S; Matheus, Filipe C; Moretti, Morgana; Sampaio, Tuane B; Poli, Anicleto; Santos, Danúbia B; Colle, Dirleise; Cunha, Mauricio P; Blum-Silva, Carlos H; Sandjo, Louis P; Reginatto, Flávio H; Rodrigues, Ana Lúcia S; Farina, Marcelo; Prediger, Rui D

    2016-10-01

    Dyskinesia consists in a series of trunk, limbs and orofacial involuntary movements that can be observed following long-term pharmacological treatment in some psychotic and neurological disorders such as schizophrenia and Parkinson's disease, respectively. Agmatine is an endogenous arginine metabolite that emerges as neuromodulator and a promising agent to manage diverse central nervous system disorders by modulating nitric oxide (NO) pathway, glutamate NMDA receptors and oxidative stress. Herein, we investigated the effects of a single intraperitoneal (i.p.) administration of different agmatine doses (10, 30 or 100mg/kg) against the orofacial dyskinesia induced by reserpine (1mg/kg,s.c.) in mice by measuring the vacuous chewing movements and tongue protusion frequencies, and the duration of facial twitching. The results showed an orofacial antidyskinetic effect of agmatine (30mg/kg, i.p.) or the combined administration of sub-effective doses of agmatine (10mg/kg, i.p.) with the NMDA receptor antagonists amantadine (1mg/kg, i.p.) and MK801 (0.01mg/kg, i.p.) or the neuronal nitric oxide synthase (NOS) inhibitor 7-nitroindazole (7-NI; 0.1mg/kg, i.p.). Reserpine-treated mice displayed locomotor activity deficits in the open field and agmatine had no effect on this response. Reserpine increased nitrite and nitrate levels in cerebral cortex, but agmatine did not reverse it. Remarkably, agmatine reversed the decrease of dopamine and non-protein thiols (NPSH) levels caused by reserpine in the striatum. However, no changes were observed in striatal immunocontent of proteins related to the dopaminergic system including tyrosine hydroxylase, dopamine transporter, vesicular monoamine transporter type 2, pDARPP-32[Thr75], dopamine D1 and D2 receptors. These results indicate that the blockade of NO pathway, NMDAR and oxidative stress are possible mechanisms associated with the protective effects of agmatine against the orofacial dyskinesia induced by reserpine in mice. PMID

  1. Psychotherapy augmentation through preconscious priming

    Francois eBorgeat

    2013-03-01

    Full Text Available Objective: To test the hypothesis that repeated preconscious (masked priming of personalized positive cognitions could augment cognitive change and facilitate achievement of patients’ goals following a therapy.Methods: Twenty social phobic patients (13 women completed a 36 weeks study beginning by 12 weeks of group behavioural therapy. After the therapy, they received 6 weeks of preconscious priming and 6 weeks of a control procedure in a randomized cross-over design. The Priming condition involved listening twice daily with a passive attitude to a recording of individualized formulations of appropriate cognitions and attitudes masked by music. The Control condition involved listening to an indistinguishable recording where the formulations had been replaced by random numbers. Changes in social cognitions were measured by the Social Interaction Self Statements Test (SISST.Results: Patients improved following therapy. The Priming procedure was associated with increased positive cognitions and decreased negative cognitions on the SISST while the Control procedure was not. The Priming procedure induced more cognitive change when applied immediately after the group therapy. Conclusion: An effect of priming was observed on social phobia related cognitions in the expected direction. This self administered addition to a therapy could be seen as an augmentation strategy.

  2. Augmented reality in medical education?

    Kamphuis, Carolien; Barsom, Esther; Schijven, Marlies; Christoph, Noor

    2014-09-01

    Learning in the medical domain is to a large extent workplace learning and involves mastery of complex skills that require performance up to professional standards in the work environment. Since training in this real-life context is not always possible for reasons of safety, costs, or didactics, alternative ways are needed to achieve clinical excellence. Educational technology and more specifically augmented reality (AR) has the potential to offer a highly realistic situated learning experience supportive of complex medical learning and transfer. AR is a technology that adds virtual content to the physical real world, thereby augmenting the perception of reality. Three examples of dedicated AR learning environments for the medical domain are described. Five types of research questions are identified that may guide empirical research into the effects of these learning environments. Up to now, empirical research mainly appears to focus on the development, usability and initial implementation of AR for learning. Limited review results reflect the motivational value of AR, its potential for training psychomotor skills and the capacity to visualize the invisible, possibly leading to enhanced conceptual understanding of complex causality. PMID:24464832

  3. Periareolar Extra-Glandular Breast Augmentation

    Mohmand, Muhammad Humayun; Ahmad, Muhammad

    2013-01-01

    BACKGROUND Breast augmentation is the most frequent procedure performed according to the 2009 Quick Facts report of the American Society of Plastic Surgeons. This study presents the periareolar extra-glandular breast augmentation. METHODS From 2004 to 2010 among 32 female patients, peri-areolar incision was performed for breast augmentation. Dissection was performed in subcutaneous plane towards the inferior pole to reach the inframammary fold and was continued in the upwards direction in the...

  4. Preprint ARPPS Augmented Reality Pipeline Prospect System

    Zhang, Xiaolei; Han, Yong; Hao, DongSheng; Lv, Zhihan

    2015-01-01

    This is the preprint version of our paper on ICONIP. Outdoor augmented reality geographic information system (ARGIS) is the hot application of augmented reality over recent years. This paper concludes the key solutions of ARGIS, designs the mobile augmented reality pipeline prospect system (ARPPS), and respectively realizes the machine vision based pipeline prospect system (MVBPPS) and the sensor based pipeline prospect system (SBPPS). With the MVBPPS's realization, this paper studies the neu...

  5. Augmented Reality Using JavaScript

    Hailemichael, Aida

    2013-01-01

    The project goal was to provide a mobile application, for a venue called Kulturhuset Karelia which is located in Tammisaari Finland. In this paper, the concept of Augmented Reality technology is briefly discussed along with the mobile application for the venue. The utilisation of JavaScript for creating Augmented reality content for mobile Augmented reality browser is also demonstrated. The application was created by using Architecht API which is Jacvascript library based on the Wikitude...

  6. InAR:Inverse Augmented Reality

    Hu, Hao; Cui, Hainan

    2015-01-01

    Augmented reality is the art to seamlessly fuse virtual objects into real ones. In this short note, we address the opposite problem, the inverse augmented reality, that is, given a perfectly augmented reality scene where human is unable to distinguish real objects from virtual ones, how the machine could help do the job. We show by structure from motion (SFM), a simple 3D reconstruction technique from images in computer vision, the real and virtual objects can be easily separated in the recon...

  7. Interactive Assembly Guide using Augmented Reality

    Andersen, Martin; Andersen, Rasmus Skovgaard; Larsen, Christian Lindequist;

    2009-01-01

    This paper presents an Augmented Reality system for aiding a pump assembling process at Grundfos, one of the leading pump producers. Stable pose estimation of the pump is required in order to augment the graphics correctly. This is achieved by matching image edges with synthesized edges from CAD...... norm. A dynamic visualization of the augmented graphics provides the user with guidance. Usability tests show that the accuracy of the system is sufficient for assembling the pump....

  8. AB027. Penile augmentation: informed text briefing

    Park, Nam Cheol

    2016-01-01

    The men’s desire to have larger and longer penis have created endless medical demands throughout human history. Until up to date, various medical skills for penile augmentation have developed in aspect of experimental and clinical outcome. Recently with throwing away socially unacceptable ideas, the need for penile augmentation is considered as equivalent level with mammoplasty for breast augmentation in women for cosmetic and psychological reason. Concurrently advanced technologies in medica...

  9. RFIDice - Augmenting Tabletop Dice with RFID

    Marc Langheinrich

    2008-08-01

    Full Text Available Augmented dice allow players of tabletop games to have the result of a roll be automatically recorded by a computer, e.g., for supporting strategy games. We have built a set of three augmented-dice-prototypes based on radio frequency identification (RFID technology, which allows us to build robust, cheap, and small augmented dice. Using a corresponding readout infrastructure and a sample application, we have evaluated our approach and show its advantages over other dice augmentation methods discussed in the literature.

  10. Augmenting Locomotion in an Anthropomorphic System

    Derek Wight

    2005-02-01

    Full Text Available A powered orthosis has applications ranging from assisting the elderly to augmenting astronauts. An assistive control scheme is developed that uses the force from a slave actuator to augment the force of a master actuator. This can be used to augment a closed-loop control scheme applied to the master actuator. Initially, actuator augmentation is explored both theoretically and experimentally using a simple mechanical system. The control scheme is then applied to a scale model of human lower limbs on a stationary bicycle to investigate the feasibility of a powered orthosis using pneumatic muscle actuators.

  11. Strategies and Challenges in Simultaneous Augmentation Mastopexy.

    Spring, Michelle A; Hartmann, Emily C; Stevens, W Grant

    2015-10-01

    Simultaneous breast augmentation and mastopexy is a common procedure often considered to be one of the most difficult cosmetic breast surgeries. One-stage augmentation mastopexy was initially described more than 50 years ago. The challenge lies in the fact that the surgery has multiple opposing goals: to increasing the volume of a breast, enhance the shape, and simultaneously decrease the skin envelope. Successful outcomes in augmentation can be expected with proper planning, technique, and patient education. This article focuses on common indications for simultaneous augmentation mastopexy, techniques for safe and effective combined procedures, challenges of the procedure, and potential complications. PMID:26408440

  12. Development of radiotracers for imaging NR2B subtype NMDA receptors with positron emission tomography

    The aim of this thesis was to develop new radioactive tracers for imaging NR2B subtype NMDA receptors with positron emission tomography. Several compounds including 4-(4-fluoro-benzyl)piperidine and presenting interesting in vivo biological properties were the object of a labelling with a positrons emitter atom (11C or 18F)

  13. Differential effect of NMDA and AMPA receptor blockade on protein synthesis in the rat infarct borderzone

    Christensen, Thomas; Bruhn, T; Frank, L; Diemer, Nils Henrik

    We investigated whether the known neuroprotective effects of two selective glutamate receptor antagonists, the NMDA antagonist MK-801 and the AMPA antagonist NBQX, are reflected in the regional cerebral protein synthesis rates (CPSR) in rats with middle cerebral artery occlusion (MCAO). Rats trea...

  14. Expression of NR1 subunit of NMDA receptor in schizophrenic hippocampus

    Vrajová, M.; Peková, S.; Klaschka, Jan; Majer, E.; Šťastný, F.; Bubeníková-Valešová, V.

    Elsevier. Roč. 23, Suppl. 2 (2008), S152. ISSN 0924-9338 R&D Projects: GA MZd(CZ) NR8792 Institutional research plan: CEZ:AV0Z10300504 Keywords : NMDA receptor * NR1 subunit * schizophrenia * post-mortem studies

  15. Changes in the expression of NR1 subunit of NMDA receptor in schizophrenic hippocampus

    Vrajová, M.; Peková, S.; Klaschka, Jan; Štastný, P.

    Elsevier. Roč. 17, Suppl. 1 (2007), s237-s238. ISSN 0924-977X. [ECNP Congress /20./. 13.10.2006-17.10.2006, Vienna] Institutional research plan: CEZ:AV0Z10300504 Keywords : schizophrenia * NMDA receptor * NR1 subunit * hippocampus * gender * antipsychotics

  16. Searsia species with affinity to the N-methyl-d-aspartic acid (NMDA) receptor

    Jäger, Anna; Knap, D.M.; Nielsen, Birgitte;

    2012-01-01

    Species of Searsia are used in traditional medicine to treat epilepsy. Previous studies on S. dentata and S. pyroides have shown that this is likely mediated via the N-methyl-d-aspartic acid (NMDA) receptor. Ethanolic extracts of leaves of six Searsia species were tested in a binding assay for...... accessible Searsia species can be used in traditional medicine....

  17. Protection of DFP-induced oxidative damage and neurodegeneration by antioxidants and NMDA receptor antagonist

    Prophylactic agents acutely administered in response to anticholinesterases intoxication can prevent toxic symptoms, including fasciculations, seizures, convulsions and death. However, anticholinesterases also have long-term unknown pathophysiological effects, making rational prophylaxis/treatment problematic. Increasing evidence suggests that in addition to excessive cholinergic stimulation, organophosphate compounds such as diisopropylphosphorofluoridate (DFP) induce activation of glutamatergic neurons, generation of reactive oxygen (ROS) and nitrogen species (RNS), leading to neurodegeneration. The present study investigated multiple affectors of DFP exposure critical to cerebral oxidative damage and whether antioxidants and NMDA receptor antagonist memantine provide neuroprotection by preventing DFP-induced biochemical and morphometric changes in rat brain. Rats treated acutely with DFP (1.25 mg/kg, s.c.) developed onset of toxicity signs within 7-15 min that progressed to maximal severity of seizures and fasciculations within 60 min. At this time point, DFP caused significant (p 2-isoprostanes, F2-IsoPs; and F4-neuroprostanes, F4-NeuroPs), RNS (citrulline), and declines in high-energy phosphates (HEP) in rat cerebrum. At the same time, quantitative morphometric analysis of pyramidal neurons of the hippocampal CA1 region revealed significant (p 2-IsoPs, F4-NeuroPs, citrulline, and depletion of HEP were noted. Furthermore, attenuation in oxidative damage following antioxidants or memantine pretreatment was accompanied by rescue from dendritic degeneration of pyramidal neurons in the CA1 hippocampal area. These findings closely associated DFP-induced lipid peroxidation with dendritic degeneration of pyramidal neurons in the CA1 hippocampal area and point to possible interventions to limit oxidative injury and dendritic degeneration induced by anticholinesterase neurotoxicity.

  18. Expression of the NMDA receptor subunit GluN3A (NR3A) in the olfactory system and its regulatory role on olfaction in the adult mouse.

    Lee, Jin Hwan; Wei, Ling; Deveau, Todd C; Gu, Xiaohuan; Yu, Shan Ping

    2016-07-01

    Glutamate is an excitatory neurotransmitter in the olfactory system and its N-methyl-D-aspartate-(NMDA) receptor subunits [GluN1 (NR1), GluN2A (NR2A), and GluN2B (NR2B)] are expressed at synapses in the olfactory bulb and olfactory epithelium. Thus, glutamatergic neurons and NMDA receptors play key roles in olfaction. GluN3A (NR3A) is a unique inhibitory subunit in the NMDA receptor complex; however, the expression and functional role of GluN3A in the olfactory bulb and epithelium remain unclear. The present study examined the expression patterns of GluN3A in the olfactory bulb and epithelium and explored its functional role in the olfactory system. Immunohistochemical and Western blot analyses revealed that GluN3A is abundantly expressed in different cellular layers of the olfactory bulb and epithelium of the adult wild type (WT) mice. In littermate GluN3A knockout (GluN3A(-/-); KO) mice, the expression of olfactory marker protein normally found in mature olfactory sensory neurons was significantly reduced in the olfactory bulb and epithelium. A butyl alcohol stimulus increased immediate-early gene c-Fos expression in the olfactory system of WT mice, while this response was absent in GluN3A KO mice. The level of phosphorylated Ca(2+)/calmodulin-dependent kinase II was significantly lower in GluN3A KO mice compared to WT mice. In buried food finding test, GluN3A mice took significantly longer time to find food compared to WT mice. Consistently, impaired odor distinguishing ability was seen in GluN3A KO mice. These findings suggest that GluN3A, expressed in the adult olfactory system, plays a significant regulatory role in olfactory development and functional activity. PMID:26334321

  19. Changes in hypothalamic neurotransmitter and prostanoid levels in response to NMDA, CRF, and GLP-1 stimulation.

    Kondo, Fumio; Tachi, Masahiko; Gosho, Masahiko; Fukayama, Minoru; Yoshikawa, Kazuhiro; Okada, Shoshiro

    2015-07-01

    Determination of neuroactive substances, such as neurotransmitters and prostanoids, in the extracellular space of the living brain is a very important technique in neuroscience. The hypothalamic paraventricular nucleus (PVN) is one of the most important autonomic control centers in the brain. Recently, we demonstrated that thromboxane (Tx) A2 in the PVN may play an important role in adrenomedullary outflow evoked by N-methyl-D-aspartate (NMDA), corticotrophin-releasing factor (CRF), and glucagon-like peptide-1 (GLP-1) stimulation using microdialysis sampling and liquid chromatography-ion trap tandem mass spectrometry (LC-ITMS(n)). In the present study, we investigated whether centrally administered NMDA, CRF, and GLP-1 can release five neurotransmitters, acetylcholine (ACh), histamine, glutamate (Glu), γ-aminobutyric acid (GABA), and serotonin (5-HT), along with six prostanoids, TxB2, prostaglandin (PG) E2, PGD2, 15-deoxy-∆(12,14) (15d)-PGJ2, 6-keto-PGF1α, and PGF2α in rat PVN microdialysates after optimization of LC-ITMS(n) conditions . All stimulations increased the levels of 5-HT, TxB2, PGE2, and PGF2α (except for 5-HT stimulated with GLP-1). Only NMDA increased the levels of ACh, Glu, and GABA. Treatment with dizocilpine maleate (MK-801), a noncompetitive NMDA receptor antagonist, attenuated the NMDA-induced increase in the levels of neuroactive substances except for Glu. This is the first study to use LC-ITMS(n) to analyze neurotransmitters and prostanoids in the same microdialysates from rat PVN. PMID:25633219

  20. Phosphorylation of NMDA NR1 subunits in the myenteric plexus during TNBS induced colitis.

    Zhou, QiQi; Caudle, Robert M; Moshiree, Baharak; Price, Donald D; Verne, G Nicholas

    2006-10-01

    N-Methyl-d-aspartic acid (NMDA) receptors are known to function in the mediation of pain and have a significant role in the development of hyperalgesia following inflammation. Serine phosphorylation regulation of NMDA receptor function occurs in a variety of conditions. No studies have demonstrated a change in phosphorylation of enteric NMDA receptors following colonic inflammation. We examined the levels of NMDA NR1 phosphorylation in trinitrobenzene sulfonic acid (TNBS) induced colitis in rats and compared it to protein translation and the development of visceral hypersensitivity. We have previously, demonstrated an increase in the C1 cassette of NR1 mRNA expression at 14, 21, and 28 days following TNBS administration. In this study, we examined the NR1 serine phosphorylation at 14 days following TNBS injection. Male Sprague-Dawley rats (200-250 g) were treated with TNBS (20mg per rat) diluted in 50% ethanol (n=3) and vehicle controls of 50% ethanol (n=3). TNBS and vehicle controls were administered with a 24 gauge catheter inserted into the lumen of the rat colon. The animals were sacrificed at 14 days after induction of the colitis and their distal colon was retrieved for two-dimensional (2D) western blot analysis. Serine phosphorylation of the NR1 subunit with C1 cassette appears at 14 days after TNBS injection. In contrast, there was no NR1-C1 expression in the vehicle controls and untreated normal controls. These results suggest a role for colonic-NMDA receptor phosphorylation in the development of neuronal plasticity following colonic inflammation. Phosphorylation of NR1 may partially explain visceral hypersensitivity present during colonic inflammation. PMID:16942839

  1. The NMDA receptor NR2A subunit regulates proliferation of MKN45 human gastric cancer cells.

    Watanabe, Kanako; Kanno, Takeshi; Oshima, Tadayuki; Miwa, Hiroto; Tashiro, Chikara; Nishizaki, Tomoyuki

    2008-03-01

    The present study investigated proliferation of MKN28 and MKN45 human gastric cancer cells regulated by the N-methyl-d-aspartate (NMDA) receptor subunit. The NMDA receptor antagonist dl-2-amino-5-phosphonovaleric acid (AP5) inhibited proliferation of MKN45 cells, but not MKN28 cells. Of the NMDA subunits such as NR1, NR2 (2A, 2B, 2C, and 2D), and NR3 (3A and 3B), all the NMDA subunit mRNAs except for the NR2B subunit mRNA were expressed in both MKN28 and MKN45 cells. MKN45 cells were characterized by higher expression of the NR2A subunit mRNA and lower expression of the NR1 subunit mRNA, but MKN28 otherwise by higher expression of the NR1 subunit mRNA and lower expression of the NR2A subunit mRNA. MKN45 cell proliferation was also inhibited by silencing the NR2A subunit-targeted gene. For MKN45 cells, AP5 or knocking-down the NR2A subunit increased the proportion of cells in the G(1) phase of cell cycling and decreased the proportion in the S/G(2) phase. The results of the present study, thus, suggest that blockage of NMDA receptors including the NR2A subunit suppresses MKN45 cell proliferation due to cell cycle arrest at the G(1) phase; in other words, the NR2A subunit promotes MKN45 cell proliferation by accelerating cell cycling. PMID:18178157

  2. NGF-induced mechanical sensitization of the masseter muscle is mediated through peripheral NMDA receptors.

    Wong, H; Kang, I; Dong, X-D; Christidis, N; Ernberg, M; Svensson, P; Cairns, B E

    2014-06-01

    Intramuscular injection of nerve growth factor (NGF) in healthy humans mimics some of the symptoms of myofascial temporomandibular disorders (M-TMD). We hypothesized that NGF induces a prolonged myofascial mechanical sensitization by increasing peripheral N-methyl-d-aspartate (NMDA) receptor expression, leading to an enhanced response of muscle nociceptors to endogenous glutamate. Behavioral experiments with an injection of NGF (25 μg/ml, 10 μl) into the masseter muscle reduced the mechanical withdrawal threshold for 1 day in male rats and 5 days in female rats. These results mirror the sex-related differences found in NGF-induced mechanical sensitization in humans. Intramuscular injection with the competitive NMDA receptor antagonist dl-2-amino-5-phosphonovaleric acid (APV, 0.020 g/ml, 10 μl) reversed the mechanical sensitization in male but not in female rats. NGF increased the number of NMDA receptor subtype 2B (NR2B)-expressing rat trigeminal masseter ganglion neurons in both sexes, which peaked at 3 days post injection. There was an association between the levels of NR2B expression and NGF-induced mechanical sensitization. The average soma size of NR2B-expressing neurons increased significantly. Increased expression of neuropeptides (CGRP and SP) was observed in NR2B-expressing masseter ganglion neurons in female but not in male rats. In healthy men and women, comparable basal expression levels of NR2B and SP were found in peripheral fibers from masseter muscle microbiopsies. This study suggests that NGF-induced sensitization of masseter nociceptors is mediated, in part, by enhanced peripheral NMDA receptor expression. Measurement of peripheral NMDA receptor expression may be useful as a biomarker for M-TMD pain. PMID:24704516

  3. The NMDA receptor NR2A subunit regulates proliferation of MKN45 human gastric cancer cells

    The present study investigated proliferation of MKN28 and MKN45 human gastric cancer cells regulated by the N-methyl-D-aspartate (NMDA) receptor subunit. The NMDA receptor antagonist DL-2-amino-5-phosphonovaleric acid (AP5) inhibited proliferation of MKN45 cells, but not MKN28 cells. Of the NMDA subunits such as NR1, NR2 (2A, 2B, 2C, and 2D), and NR3 (3A and 3B), all the NMDA subunit mRNAs except for the NR2B subunit mRNA were expressed in both MKN28 and MKN45 cells. MKN45 cells were characterized by higher expression of the NR2A subunit mRNA and lower expression of the NR1 subunit mRNA, but MKN28 otherwise by higher expression of the NR1 subunit mRNA and lower expression of the NR2A subunit mRNA. MKN45 cell proliferation was also inhibited by silencing the NR2A subunit-targeted gene. For MKN45 cells, AP5 or knocking-down the NR2A subunit increased the proportion of cells in the G1 phase of cell cycling and decreased the proportion in the S/G2 phase. The results of the present study, thus, suggest that blockage of NMDA receptors including the NR2A subunit suppresses MKN45 cell proliferation due to cell cycle arrest at the G1 phase; in other words, the NR2A subunit promotes MKN45 cell proliferation by accelerating cell cycling

  4. Augmented reality for improved safety

    Stefania Pandolfi

    2016-01-01

    Sometimes, CERN experts have to operate in low visibility conditions or in the presence of possible hazards. Minimising the duration of the operation and reducing the risk of errors is therefore crucial to ensuring the safety of personnel. The EDUSAFE project integrates different technologies to create a wearable personnel safety system based on augmented reality.    The EDUSAFE integrated safety system uses a camera mounted on the helmet to monitor the working area.  In its everyday operation of machines and facilities, CERN adopts a whole set of measures and safety equipment to ensure the safety of its personnel, including personal wearable safety devices and access control systems. However, sometimes, scheduled and emergency maintenance work needs to be done in zones with potential cryogenic hazards, in the presence of radioactive equipment or simply in demanding conditions where visibility is low and moving around is difficult. The EDUSAFE Marie Curie Innovative&...

  5. Effects of ketamine-midazolam anesthesia on the expression of NMDA and AMPA receptor subunit in the peri-infarction of rat brain

    ZHANG Yue-lin; ZHANG Peng-bo; QIU Shu-dong; LIU Yong; TIAN Ying-fang; WANG Ying

    2006-01-01

    Background Activation of N-methyl-D-aspartate (NMDA) receptors and alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptors play an important role in the neurons death induced by ischemia.The mitigating effect of intravenous anesthetics on ischemic neuron injury is related to their influence on NMDA receptors. This study was performed to investigate the effect of ketamine-midazolam anesthesia on the NMDA and AMPA receptor subunits expression in the peri-infarction of ischemic rat brain and explore its potential mechanism of neuroprotection.This study was supported by National Natural Science Foundation of China (NSFC) (No.30200291).Methods Thirty Sprague Dawley (SD) rats were subjected to permanent middle cerebral artery occlusion under ketamine/atropine (100/0.05 mg/kg) or ketamine-midazolam/atropine (60/50/0.05 mg/kg) intraperitoneal anesthesia (n=15 each). Twenty-four hours after ischemia, five rats in each group were killed by injecting the above dosage of ketamine or ketamine-midazolam intraperitoneally and infarct size was measured. Twenty-four and 72 hours after ischemia, four rats in each group were killed by injecting the above dosage of ketamine or ketamine-midazolam intraperitoneally. After staining the brain tissue slices with toluidine blue, the survived neurons in the peri-infarction were observed. Also, the expression level of NMDA receptors 1 (NR1), NMDA receptors 2A (NR2A), NMDA receptors 2B (NR2B) and AMPA (GluR1 subunit) were determined by grayscale analysis in immunohistochemical stained slices.Results Compared with ketamine anesthesia, ketamine-midazolam anesthesia produced not only smaller infarct size [(24.1±4.6)% vs (38.4±4.2)%, P<0.05], but also higher neuron density (24 hours: 846± 16 vs 756±24,P<0.05; 72 hours: 882±22 vs 785± 18, P<0.05) and lower NR2A (24 hours: 123.0±4.9 vs 95.0±2.5, P<0.05; 72 hours: 77.8±4.1 vs 54.2±3.9, P<0.05) and NR2B (24 hours: 98.5±2.7 vs 76.3±2.4, P<0.05; 72hours: 67.2

  6. Mobile Platform Augmented Reality for Enhanced Operations on the International Space Station Project

    National Aeronautics and Space Administration — To develop an Augmented Reality system that runs on a small portable device to aid crew in routine maintenance activities by providing enhanced information and...

  7. Vertebral Augmentation for Osteoporotic Compression Fractures.

    Richmond, Bradford J

    2016-01-01

    Vertebral augmentation procedures such as vertebroplasty and kyphoplasty were developed to reduce pain and improve quality of life for patients with osteoporotic vertebral compression fractures. However, the use of vertebral augmentation has been debated and questioned since its inception. This article addresses some of these issues. PMID:26490134

  8. Enhancing Education through Mobile Augmented Reality

    Joan, D. R. Robert

    2015-01-01

    In this article, the author has discussed about the Mobile Augmented Reality and enhancing education through it. The aim of the present study was to give some general information about mobile augmented reality which helps to boost education. Purpose of the current study reveals the mobile networks which are used in the institution campus as well…

  9. From Augmentation Media to Meme Media.

    Tanaka, Yuzuru

    Computers as meta media are now evolving from augmentation media vehicles to meme media vehicles. While an augmentation media system provides a seamlessly integrated environment of various tools and documents, meme media system provides further functions to edit and distribute tools and documents. Documents and tools on meme media can easily…

  10. Mapping of the human NMDA receptor subunit (NMDAR1) and the proposed NMDA receptor glutamate-binding subunit (NMDARA1) to chromosomes 9q34.3 and chromosome 8, respectively

    Collins, C; Duff, C; Duncan, A M;

    1993-01-01

    A role for the N-methyl-D-aspartate (NMDA) receptor in the molecular pathology underlying Huntington disease (HD) has been proposed on the basis of neurochemical studies in HD and the ability of the NMDA receptor to mediate neuronal cell death. The molecular cloning of the human NMDA receptor...... subunit (NMDAR1) and a proposed glutamate-binding subunit of the NMDA receptor (NMDARA1) have provided an opportunity to test the hypothesis that either of these genes might be directly involved in the causation of HD. We have mapped NMDAR1 to 9q34.3 using in situ hybridization studies and NMDARA1 to...... human chromosome 8 using a somatic cell hybrid panel. Because the gene causing HD has been localized to chromosome 4p16.3, the chromosome assignments reported here are inconsistent with either of these genes playing a causative role in the molecular pathology of HD. However, it is noteworthy that the...

  11. Natural heat transfer augmentation in passive advanced BWR plants

    In the European Simplified Boiling Water Reactor (ESBWR), the long-term post-accident containment pressure is determined by the combination of non condensable gas pressure and steam pressure in the wet well gas space. Since there are no active systems for heat removal in the wet well, energy transmitted to the wet well gas space, by a variety of means, must be removed by passive heat transfer to the walls and suppression pool (SP). The cold suppression pool located below the hotter gas space provides a stable configuration in which convection currents are suppressed thus limiting heat and mass transfer between the gas space and pool. However, heat transfer to the walls results in natural circulation currents that can augment the heat and mass transfer to the pool surface. Using a simplified model, parametric studies are carried out to show that augmentation of the order of magnitude expected can significantly impact the heat and mass transfer to the pool. Additionally a review of available literature in the area of augmentation and mixed convection of this type is presented and indicates the need for additional experimental work in order to develop adequate models for heat and mass transfer augmentation in the configuration of a BWR suppression pool. (author)

  12. Augmented Reality Implementation Methods in Mainstream Applications

    Prochazka, David

    2011-01-01

    Augmented reality has became an useful tool in many areas from space exploration to military applications. Although used theoretical principles are well known for almost a decade, the augmented reality is almost exclusively used in high budget solutions with a special hardware. However, in last few years we could see rising popularity of many projects focused on deployment of the augmented reality on different mobile devices. Our article is aimed on developers who consider development of an augmented reality application for the mainstream market. Such developers will be forced to keep the application price, therefore also the development price, at reasonable level. Usage of existing image processing software library could bring a significant cut-down of the development costs. In the theoretical part of the article is presented an overview of the augmented reality application structure. Further, an approach for selection appropriate library as well as the review of the existing software libraries focused in th...

  13. Irradiated homologous costal cartilage for augmentation rhinoplasty

    Although the ideal reconstructive material for augmentation rhinoplasty continues to challenge plastic surgeons, there exists no report in the literature that confines the use of irradiated homologous costal cartilage, first reported by Dingman and Grabb in 1961, to dorsal nasal augmentation. The purpose of this paper is to present a retrospective analysis of the author's experience using irradiated homologous costal cartilage in augmentation rhinoplasty. Twenty-seven dorsal nasal augmentations were performed in 24 patients between 16 and 49 years of age with a follow-up ranging from 1 to 27 months. Good-to-excellent results were achieved in 83.3% (20 of 24). Poor results requiring revision were found in 16.7% (4 of 24). Complication rates included 7.4% infection (2 of 27) and 14.8% warping (4 of 27). The resorption rate was zero. These results compare favorably with other forms of nasal augmentation. Advantages and disadvantages of irradiated homologous costal cartilage are discussed

  14. Diffuser Augmented Horizontal Axis Tidal Current Turbines

    Nasir Mehmood

    2012-09-01

    Full Text Available The renewal energy technologies are increasingly popular to ensure future energy sustenance and address environmental issues. The tides are enormous and consistent untapped resource of renewable energy. The growing interest in exploring tidal energy has compelling reasons such as security and diversity of supply, intermittent but predictable and limited social and environmental impacts. The tidal energy industry is undergoing an increasing shift towards diffuser augmented turbines. The reason is the higher power output of diffuser augmented turbines compared to conventional open turbines. The purpose of this study is to present a comprehensive review of diffuser augmented horizontal axis tidal current turbines. The components, relative advantages, limitations and design parameters of diffuser augmented horizontal axis tidal current turbines are presented in detail. CFD simulation of NACA 0016 airfoil is carried out to explore its potential for designing a diffuser. The core issues associated with diffuser augmented horizontal axis tidal current turbines are also discussed.

  15. Potentiation of N-methyl-D-aspartate receptor-mediated neuronal injury during methamphetamine withdrawal in vitro requires co-activation of IP3 receptors.

    Smith, Katherine J; Butler, Tracy R; Self, Rachel L; Braden, Brittany B; Prendergast, Mark A

    2008-01-01

    Recent findings suggest that methamphetamine (METH) functions acutely to inhibit N-methyl-d-aspartate (NMDA) receptor function. Protracted withdrawal from METH exposure may increase the sensitivity of NMDA receptors to agonist exposure, promoting neuronal excitability. However, the relevance of METH effects on NMDA receptor activity with regard to neuronal viability has not been fully studied. The present studies examined the effects of protracted METH exposure (6 or 7 days; 1.0-100 microM) and withdrawal (1 or 7 days) on NMDA receptor-dependent neurotoxicity, determined with use of the non-vital fluorescent marker propidium iodide, in organotypic slice cultures of male and female rats. Prolonged exposure to METH (100 microM) produced only modest toxicity in the granule cell layer of the dentate gyrus. Withdrawal from METH exposure (1 or 7 days) did not produce overt neuronal injury in any region of slice cultures. Exposure to NMDA (5 microM) produced marked neurotoxicity in the CA1 pyramidal cell layer. Neither co-exposure to METH nor 1 day of METH withdrawal in combination with NMDA exposure altered NMDA-induced neurotoxicity. In contrast, protracted withdrawal from METH exposure (7 days) was associated with a marked (approximately 400%) increase in NMDA-induced neurotoxicity in CA1 region pyramidal cells. This potentiation of neurotoxicity was prevented by co-exposure to the selective NMDA receptor antagonist 5-2-amino-5-phosphonovaleric acid (20 microM) and was markedly attenuated by co-exposure of slices to xestospongin C (1 microM), an antagonist of IP(3) receptors. The results of the present studies suggest that long-term METH withdrawal functionally sensitizes the NMDA receptor to agonist exposure and requires the co-activation of NMDA and IP(3) receptors. PMID:18021755

  16. Silent NMDA receptor-mediated synapses are developmentally regulated in the dorsal horn of the rat spinal cord.

    Baba, H; Doubell, T P; Moore, K A; Woolf, C J

    2000-02-01

    In vitro whole cell patch-clamp recording techniques were utilized to study silent pure-N-methyl-D-aspartate (NMDA) receptor-mediated synaptic responses in lamina II (substantia gelatinosa, SG) and lamina III of the spinal dorsal horn. To clarify whether these synapses are present in the adult and contribute to neuropathic pain, transverse lumbar spinal cord slices were prepared from neonatal, naive adult and adult sciatic nerve transected rats. In neonatal rats, pure-NMDA receptor-mediated excitatory postsynaptic currents (EPSCs) were elicited in SG neurons either by focal intraspinal stimulation (n = 15 of 20 neurons) or focal stimulation of the dorsal root (n = 2 of 7 neurons). In contrast, in slices from naive adult rats, no silent pure-NMDA EPSCs were recorded in SG neurons following focal intraspinal stimulation (n = 27), and only one pure-NMDA EPSC was observed in lamina III (n = 23). Furthermore, in rats with chronic sciatic nerve transection, pure-NMDA EPSCs were elicited by focal intraspinal stimulation in only 2 of 45 SG neurons. Although a large increase in Abeta fiber evoked mixed alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and NMDA receptor-mediated synapses was detected after sciatic nerve injury, Abeta fiber-mediated pure-NMDA EPSCs were not evoked in SG neurons by dorsal root stimulation. Pure-NMDA receptor-mediated EPSCs are therefore a transient, developmentally regulated phenomenon, and, although they may have a role in synaptic refinement in the immature dorsal horn, they are unlikely to be involved in receptive field plasticity in the adult. PMID:10669507

  17. Input-specific synaptic plasticity in the amygdala is regulated by neuroligin-1 via postsynaptic NMDA receptors

    Jung, Sang-Yong; Kim, Juhyun; Kwon, Oh Bin; Jung, Jung Hoon; An, Kyongman; Jeong, A Young; Lee, C. Justin; Choi, Yun-Beom; Bailey, Craig H.; Kandel, Eric R.; Kim, Joung-Hun

    2010-01-01

    Despite considerable evidence for a critical role of neuroligin-1 in the specification of excitatory synapses, the cellular mechanisms and physiological roles of neuroligin-1 in mature neural circuits are poorly understood. In mutant mice deficient in neuroligin-1, or adult rats in which neuroligin-1 was depleted, we have found that neuroligin-1 stabilizes the NMDA receptors residing in the postsynaptic membrane of amygdala principal neurons, which allows for a normal range of NMDA receptor-m...

  18. Augmenting Everyday Artefacts to Support Social Interaction Among Senior Peers

    Nazzi, Elena; Sokoler, Tomas

    2015-01-01

    Novel technological possibilities emerge when tangible and social computing come together. This paper explores the potential of such technology when designing for seniors and their social interaction. Our research is guided by the concept of twitterIDo, which is to make seniors’ everyday activities...... more visible by augmenting everyday artefacts to communicate the ongoing activity they are used for. We engaged a local community of seniors in a living lab to explore the possibilities of twitterIDo in real life situations. This paper presents a series of interactive prototypes of everyday artefacts...... and displays designed to start a dialogue with the seniors on how twitterIDo-technology may fit into their everyday situations. Our findings point out how augmented everyday artefacts can make a positive difference when designing technology in a domain such the one of seniors’ and their social...

  19. Antagonistas de los receptores glutamatérgicos NMDA en el tratamiento del dolor crónico NMDA glutamatergic receptor antagonists for the management of chronic pain

    F. Neira; J. L. Ortega

    2004-01-01

    Los receptores NMDA están asociados con los procesos de aprendizaje y memoria, el desarrollo y la plasticidad neural, así como con los estados de dolor agudo y crónico. Intervienen en el inicio y mantenimiento de la sensibilización central asociada a daño o inflamación de los tejidos periféricos. El glutamato es el principal aminoácido excitatorio del SNC, puede participar en los procesos de transmisión nociceptiva a nivel espinal, siendo el principal responsable de la transmisión sináptica r...

  20. Augmented Reality for Android Platform

    Lžičař, Radek

    2011-01-01

    Tato diplomová práce se zabývá návrhem a realizací systému rozšířené reality na mobilní platformě Google Android s využitím polohových senzorů. Aplikace slouží jako navigace a zobrazuje geografické body zájmu. Práce se věnuje problematice rozšířené reality na mobilních zařízeních, návrhem vlastního frameworku a poté zmiňuje detaily implementace vybraných problémů. Nakonec je popsán způsob testování a zhodnoceny výsledky práce. This thesis describes design and implementation of augment...

  1. Augmented Reality Repair Guidance System

    Sidharth Bhatia

    2012-07-01

    Full Text Available The daily life of a common man revolves around various forms of appliances/gadgets he uses throughout the day such as a mobile phone, laptop, printer, microwave oven, washing machine, etc. Although these appliances/gadgets are taken by most of the people for granted, the problem occurs when any of these things do not work as they are expected to. Getting them to the repair shops for every small glitch is expensive as well as time consuming. Although most of the companies which produce these appliances/gadgets do supply them with basic manuals, which deal with how to solve these minor issues, but reading them and at the same time repairing the corresponding appliance/gadget can be a frustrating task at times. These problems can be reduced to a large extent if some kind of live guidance is available. In this paper we propose a method to do so with the help of an augmented reality based system that will guide the user to carry out small scale repair jobs on these gadgets. All that is required is a decent webcam and a computing device, with a processor of 1 GHz or more and a display screen.

  2. Augmented reality: past, present, future

    Inzerillo, Laura

    2013-03-01

    A great opportunity has permitted to carry out a cultural, historical, architectural and social research with great impact factor on the international cultural interest. We are talking about the realization of a museum whose the main theme is the visit and the discovery of a monument of great prestige: the monumental building the "Steri" in Palermo. The museum is divided into sub themes including the one above all, that has aroused the international interest so much that it has been presented the instance to include the museum in the cultural heritage of UNESCO. It is the realization of a museum path that regards the cells of the Inquisition, which are located just inside of some buildings of the monumental building. The project, as a whole, is faced, in a total view, between the various competences implicated: historic, chemic, architectonic, topographic, drawing, representation, virtual communication, informatics. The birth of the museum will be a sum of the results of all these disciplines involved. Methodology, implementation, fruition, virtual museum, goals, 2D graphic restitution, effects on the cultural heritage and landscape environmental, augmented reality, Surveying 2D and 3D, hi-touch screen, Photogrammetric survey, Photographic survey, representation, drawing 3D and more than this has been dealt with this research.

  3. Digital Augmented Reality Audio Headset

    Jussi Rämö

    2012-01-01

    Full Text Available Augmented reality audio (ARA combines virtual sound sources with the real sonic environment of the user. An ARA system can be realized with a headset containing binaural microphones. Ideally, the ARA headset should be acoustically transparent, that is, it should not cause audible modification to the surrounding sound. A practical implementation of an ARA mixer requires a low-latency headphone reproduction system with additional equalization to compensate for the attenuation and the modified ear canal resonances caused by the headphones. This paper proposes digital IIR filters to realize the required equalization and evaluates a real-time prototype ARA system. Measurements show that the throughput latency of the digital prototype ARA system can be less than 1.4 ms, which is sufficiently small in practice. When the direct and processed sounds are combined in the ear, a comb filtering effect is brought about and appears as notches in the frequency response. The comb filter effect in speech and music signals was studied in a listening test and it was found to be inaudible when the attenuation is 20 dB. Insert ARA headphones have a sufficient attenuation at frequencies above about 1 kHz. The proposed digital ARA system enables several immersive audio applications, such as a virtual audio tourist guide and audio teleconferencing.

  4. Mixing Augmentation of Supersonic Streams

    S. Hari; J. Kurian

    2001-01-01

    The use of passive mixing devices to enhance the mixing of supersonic streams is of importance in many aerospace and allied applications. A comparative experimental study of two such non-conventional axi symmetric supersonic nozzles for mixing augmentation is undertaken in the present study. The nozzles studied are conventional convergent divergent (c-d), ramp, and nozzle with secondary tabs at the Mach number of 1.7.The freejet characteristics of the jets from the nozzles and the confined mixing of the jets under isothermal and non-isothermal conditions were experimentally investigated. In addition, schlieren and laser light sheet methods are employed for flow visualization. Results of experiments on freejet showed rapid total pressure decay, higher jet width, and increased shear layer width in the case of jets from non-conventional nozzles. Also visualized were complex shock patterns in these jets. The confined mixing studies in both cold and hot flows confirm the increased mixing behavior of non-conventional nozzles within shorter mixing duct lengths. Laser sheet visualization clearly demonstrated the formation of streamwise vortices, which accounts for the enhanced mixing while employing the nozzles under study.

  5. Augmented reality for wafer prober

    Gilgenkrantz, Pascal

    2011-03-01

    The link between wafer manufacturing and wafer test is often weak: without common information system, Test engineers have to read locations of test structures from reference documents and search them on the wafer prober screen. Mask Data Preparation team is ideally placed to fill this gap, given its relationship with both design and manufacturing sides. With appropriate design extraction scripts and design conventions, mask engineers can provide exact wafer locations of all embedded test structures to avoid a painful camera search. Going a step further, it would be a great help to provide to wafer probers a "map" of what was build on wafers. With this idea in mind, mask design database can simply be provided to Test engineers; but the real added value would come from a true integration of real-wafer camera views and design database used for wafer manufacturing. As proven by several augmented reality applications, like Google Maps' mixed Satellite/Map view, mixing a real-world view with its theoretical model is very useful to understand the reality. The creation of such interface can only be made by a wafer prober manufacturer, given the high integration of these machines with their control panel. But many existing software libraries could be used to plot the design view matching the camera view. Standard formats for mask design are usually GDSII and OASIS (SEMI P39 standard); multiple free software and commercial viewers/editors/libraries for these formats are available.

  6. Augmented Fish Health Monitoring, 1988 Annual Report.

    Warren, James W.

    1989-08-15

    Augmented Fish Health Monitoring Contract AI79-87BP35585 was implemented on July 20, 1987. Second year activities focused on full implementation of disease surveillance activities and histopathological support services to participating state agencies. Persistent and sometimes severe disease losses were caused by infectious hematopoietic necrosis (IHN) in summer steelhead trout in Idaho and in spring chinook salmon at hatcheries on the lower Columbia River. Diagnostic capability was enhanced by the installation, for field use, of enzyme-linked immunosorbent assay (ELISA) technology at the Dworshak Fish Health Center for the detection and assay of bacterial kidney disease and by a dot-blot'' training session for virus identification at the Lower Columbia Fish Health Center. Complete diagnostic and inspection services were provided to 13 Columbia River basin National Fish hatcheries. Case history data was fully documented in a computerized data base for storage and analysis. This report briefly describes work being done to meet contract requirements for fish disease surveillance at Service facilities in the Columbia River basin. It also summarizes the health status of fish reared at those hatcheries and provides a summary of case history data for calendar year 1988. 2 refs., 4 tabs.

  7. Milnacipran inhibits glutamatergic N-Methyl-D-Aspartate receptor activity in Spinal Dorsal Horn Neurons

    Kohno Tatsuro

    2012-06-01

    Full Text Available Abstract Background Antidepressants, which are widely used for treatment of chronic pain, are thought to have antinociceptive effects by blockade of serotonin and noradrenaline reuptake. However, these drugs also interact with various receptors such as excitatory glutamatergic receptors. Thermal hyperalgesia was induced by intrathecal injection of NMDA in rats. Paw withdrawal latency was measured after intrathecal injection of antidepressants. The effects of antidepressants on the NMDA and AMPA-induced responses were examined in lamina II neurons of rat spinal cord slices using the whole-cell patch-clamp technique. The effects of milnacipran followed by application of NMDA on pERK activation were also investigated in the spinal cord. Results Intrathecal injection of milnacipran (0.1 μmol, but not citalopram (0.1 μmol and desipramine (0.1 μmol, followed by intrathecal injection of NMDA (1 μg suppressed thermal hyperalgesia. Milnacipran (100 μM reduced the amplitude of NMDA (56 ± 3 %, 64 ± 5 % of control-, but not AMPA (98 ± 5 %, 97 ± 5 % of control-mediated currents induced by exogenous application and dorsal root stimulation, respectively. Citalopram (100 μM and desipramine (30 μM had no effect on the amplitude of exogenous NMDA-induced currents. The number of pERK-positive neurons in the group treated with milnacipran (100 μM, but not citalopram (100 μM or desipramine (30 μM, followed by NMDA (100 μM was significantly lower compared with the NMDA-alone group. Conclusions The antinociceptive effect of milnacipran may be dependent on the drug’s direct modulation of NMDA receptors in the superficial dorsal horn. Furthermore, in addition to inhibiting the reuptake of monoamines, glutamate NMDA receptors are also important for analgesia induced by milnacipran.

  8. Exploring neuroprotective potential of Withania somnifera phytochemicals by inhibition of GluN2B-containing NMDA receptors: An in silico study.

    Kumar, Gaurav; Patnaik, Ranjana

    2016-07-01

    N-methyl-d-aspartate receptors (NMDARs) mediated excitotoxicity has been implicated in multi-neurodegenerative diseases. Due to lack of efficacy and adverse effects of NMDA receptor antagonists, search for herbal remedies that may act as therapeutic agents is an active area of research to combat these diseases. Withania somnifera (WS) is being used for centuries as a nerve tonic and Nootropic agents. The present study targets the in silico evaluation of the neuroprotective efficacy of W. somnifera phytochemicals by inhibition of NMDA receptor-mediated excitotoxicity through allosteric inhibition of the GluN2B containing NMDARs. We predict Blood Brain Barrier (BBB) penetration, mutagenicity, drug-likeness and Human Intestinal Absorption properties of 25 WS phytochemicals. Further, molecular docking was performed to know whether these phytochemicals inhibit the GluN2B containing NMDARs or not. The results suggest that Anaferine, Beta-Sitosterol, Withaferin A, Withanolide A, Withanolide B and Withanolide D inhibit GluN2B containing NMDARs through allosteric mode similar to the well-known selective antagonist Ifenprodil. These phytochemicals have potential as an essentially useful oral drug to counter NMDARs mediated excitotoxicity and to treat multi-neurodegenerative diseases. PMID:27241252

  9. NMDA antagonist, but not nNOS inhibitor, requires AMPA receptors in the ventromedial prefrontal cortex (vmPFC) to induce antidepressant-like effects

    Pereira, V. S.; Wegener, Gregers; Joca, S. R.

    2013-01-01

    glutamatergic and nitrergic systems of the vmPFC on the behavioral consequences induced by forced swimming (FS), an animal model of depression. Male Wistar rats (230-260g) with guide cannulas aimed at the prelimbic (PL) region of vmPFC were submitted to a 15min session of FS and, 24h later, they were submitted......Depressed individuals and stressed animals show enhanced levels of glutamate and neuronal nitric oxide synthase (nNOS) activity in limbic structures, including the vmPFC. Systemic administration of glutamatergic NMDA receptor antagonists or inhibitors of nitric oxide (NO) synthesis induces...... to a 5min session of the FS test when the immobility time (IT) was measured. Injection of LY235959 (LY; NMDA antagonist at 1, 3 and 10nmol/0.2(mu)L), NPA (nNOS inhibitor at 0.01nmol/0.2(mu)L), c-PTIO (NO scavenger at 1.0nmol/0.2(mu)L), ODQ (soluble guanylyl cyclase-sGCinhibitor at 1.0nmol/0.2(mu...

  10. NMDA receptor blockade in the basolateral amygdala disrupts consolidation of stimulus-reward memory and extinction learning during reinstatement of cocaine-seeking in an animal model of relapse.

    Feltenstein, Matthew W; See, Ronald E

    2007-11-01

    Previous research from our laboratory has implicated the basolateral amygdala (BLA) complex in the acquisition and consolidation of cue-cocaine associations, as well as extinction learning, which may regulate the long-lasting control of conditioned stimuli (CS) over drug-seeking behavior. Given the well established role of NMDA glutamate receptor activation in other forms of amygdalar-based learning, we predicted that BLA-mediated drug-cue associative learning would be NMDA receptor dependent. To test this hypothesis, male Sprague-Dawley rats self-administered i.v. cocaine (0.6 mg/kg/infusion) in the absence of explicit CS pairings (2-h sessions, 5 days), followed by a single 1-h classical conditioning (CC) session, during which they received passive infusions of cocaine discretely paired with a light+tone stimulus complex. Following additional cocaine self-administration sessions in the absence of the CS (2-h sessions, 5 days) and extinction training sessions (no cocaine or CS presentation, 2-h sessions, 7 days), the ability of the CS to reinstate cocaine-seeking on three test days was assessed. Rats received bilateral intra-BLA infusions (0.5 microl/hemisphere) of vehicle or the selective NMDA receptor antagonist, 2-amino-5-phosphonovalerate (AP-5), immediately prior to the CC session (acquisition), immediately following the CC session (consolidation), or immediately following reinstatement testing (consolidation of conditioned-cued extinction learning). AP-5 administered before or after CC attenuated subsequent CS-induced reinstatement, whereas AP-5 administered immediately following the first two reinstatement tests impaired the extinction of cocaine-seeking behavior. These results suggest that NMDA receptor-mediated mechanisms within the BLA play a crucial role in the consolidation of drug-CS associations into long-term memories that, in turn, drive cocaine-seeking during relapse. PMID:17613253

  11. The Virtuality and Reality of Augmented Reality

    Jung Yeon Ma

    2007-02-01

    Full Text Available This thesis explores the creative possibilities and implications of Augmented Reality, not just as a specific technology of computer science, but as one of high technologies that influence people’s perception and even the concepts of the real and the virtual. For a broader definition of Augmented Reality which has a unique status between virtual environment and real environment, the virtuality and the reality of Augmented Reality are discussed in an interdisciplinary context such as arts, philosophy, and film and animation studies. This approach is rooted in the belief that theory of new media ought to traverse and encompass all realms of academic categories.

  12. Comparison of excitotoxic profiles of ATPA, AMPA, KA and NMDA in organotypic hippocampal slice cultures

    Kristensen, Bjarne Winther; Noraberg, J; Zimmer, J

    2001-01-01

    ) values was found after 2 days of exposure: AMPA (3.7 mM)>NMDA (11 mM)=KA (13 mM)>ATPA (33 mM). Exposed to 30 microM ATPA, 3 microM AMPA and 10 microM NMDA, CA1 was the most susceptible subfield followed by fascia dentata and CA3. Using 8 microM KA, CA3 was the most susceptible subfield, followed by...... fascia dentata and CA1. In 100 microM concentrations, all four agonists induced the same, maximal PI uptake in all hippocampal subfields, corresponding to total neuronal degeneration. Using glutamate receptor antagonists, like GYKI 52466, NBQX and MK-801, inhibition data revealed that AMPA excitotoxicity...

  13. Thalamocortical NMDA conductances and intracortical inhibition can explain cortical temporal tuning

    Krukowski, A. E.; Miller, K. D.

    2001-01-01

    Cells in cerebral cortex fail to respond to fast-moving stimuli that evoke strong responses in the thalamic nuclei innervating the cortex. The reason for this behavior has remained a mystery. We study an experimentally motivated model of the thalamic input-recipient layer of cat primary visual cortex that accounts for many aspects of cortical orientation tuning. In this circuit, inhibition dominates over excitation, but temporal modulations of excitation and inhibition occur out of phase with one another, allowing excitation to transiently drive cells. We show that this circuit provides a natural explanation of cortical low-pass temporal frequency tuning, provided N-methyl-D-aspartate (NMDA) receptors are present in thalamocortical synapses in proportions measured experimentally. This suggests a new and unanticipated role for NMDA conductances in shaping the temporal response properties of cortical cells, and suggests that common cortical circuit mechanisms underlie both spatial and temporal response tuning.

  14. Role of NMDA Receptors in Dopamine Neurons for Plasticity and Addictive Behaviors

    Zweifel, Larry S.; Argilli, Emanuela; Bonci, Antonello; Palmiter, Richard D

    2008-01-01

    A single exposure to drugs of abuse produces an NMDA receptor (NMDAR)-dependent long-term potentiation (LTP) of AMPA receptor (AMPAR) currents in DA neurons; however, the importance of LTP for various aspects of drug addiction is unclear. To test the role of NMDAR-dependent plasticity in addictive behavior, we genetically inactivated functional NMDAR signaling exclusively in DA neurons (KO mice). Inactivation of NMDARs results in increased AMPAR-mediated transmission that is indistinguishable...

  15. Possible NMDA antagonist properties of drugs that affect high pressure neurological syndrome.

    Shuker, M. A.; Bowser-Riley, F.; Davies, S. N.

    1994-01-01

    1. Previous studies have suggested that a series of drugs modelled on part of the strychnine molecule interfere with the development of high pressure neurological syndrome (HPNS) and it was presumed that this effect was via an action on inhibitory glycinergic transmission. We have now used the rat hippocampal slice preparation to examine the possibility that some of these drugs might instead have an action at the strychnine-insensitive (SI) glycine binding site associated with the NMDA recept...

  16. Essential role of postsynaptic NMDA receptors in developmental refinement of excitatory synapses

    Zhang, Zhong-wei; Peterson, Matthew; Liu, Hong

    2012-01-01

    Neurons in the brains of newborns are usually connected with many other neurons through weak synapses. This early pattern of connectivity is refined through pruning of many immature connections and strengthening of the remaining ones. NMDA receptors (NMDARs) are essential for the development of excitatory synapses, but their role in synaptic refinement is controversial. Although chronic application of blockers or global knockdown of NMDARs disrupts developmental refinement in many parts of th...

  17. Exprese NR1 podjednotky NMDA receptoru v animálním modelu schizofrenie

    Šťastný, František; Kozmiková, I.; Klaschka, Jan; Peková, S.; Tejkalová, H.; Vrajová, M.

    2006-01-01

    Roč. 10, Suppl. 3 (2006), s. 12-15. ISSN 1211-7579 R&D Projects: GA MŠk(CZ) 1M0517; GA MZd NF7626; GA MZd NR8797 Institutional research plan: CEZ:AV0Z10300504; CEZ:AV0Z50110509 Keywords : schizofrenie * NMDA receptor * exprese NR1 podjednotky * animální model * kyselina chinolinová * prepulzní inhibice akustického úletu Subject RIV: FL - Psychiatry, Sexuology

  18. The Behavioral and Pharmacological Actions of NMDA Receptor Antagonism are Conserved in Zebrafish Larvae

    Chen, John; Patel, Roshni; Friedman, Theodore C.; Jones, Kevin S

    2010-01-01

    Dizocilpine maleate (MK-801) is one of several NMDA receptor antagonists that is widely used to pharmacologically model the symptoms of psychosis and schizophrenia in animals. MK-801 elicits behaviors in adult zebrafish (Danio rerio) that are phenotypically consistent with behaviors observed in humans and rodents exposed to tbhe drug. However, the molecular and cellular processes that mediate the psychotomimetic, cognitive and locomotive behaviors of MK-801 are unclear. We exposed zebrafish l...

  19. The Behavioral and Pharmacological Actions of NMDA Receptor Antagonism are Conserved in Zebrafish Larvae

    Chen, John; Patel, Roshni; Friedman, Theodore C.; Jones, Kevin S

    2010-01-01

    Dizocilpine maleate (MK-801) is one of several NMDA receptor antagonists that is widely used to pharmacologically model the symptoms of psychosis and schizophrenia in animals. MK-801 elicits behaviors in adult zebrafish (Danio rerio) that are phenotypically consistent with behaviors observed in humans and rodents exposed to the drug. However, the molecular and cellular processes that mediate the psychotomimetic, cognitive and locomotive behaviors of MK-801 are unclear. We exposed zebrafish la...

  20. Peripheral NMDA Receptors Mediate Antidromic Nerve Stimulation-Induced Tactile Hypersensitivity in the Rat

    Jun Ho Jang; Taick Sang Nam; Jaebeom Jun; Se Jung Jung; Dong-Wook Kim; Joong Woo Leem

    2015-01-01

    We investigated the role of peripheral NMDA receptors (NMDARs) in antidromic nerve stimulation-induced tactile hypersensitivity outside the skin area innervated by stimulated nerve. Tetanic electrical stimulation (ES) of the decentralized L5 spinal nerve, which induced enlargement of plasma extravasation, resulted in tactile hypersensitivity in the L4 plantar dermatome of the hind-paw. When intraplantar (i.pl.) injection was administered into the L4 dermatome before ES, NMDAR and group-I meta...

  1. Social Memory in Mice: Disruption with an NMDA Antagonist and Attenuation with Antipsychotic Drugs

    Gao, Xue-Min; Elmer, Gregory I.; Adams-Huet, Beverley; Tamminga, Carol A.

    2008-01-01

    Social recognition reflects the ability of one animal to learn and remember the identity of another. Animal models of social learning and memory are pertinent to several different CNS diseases involving disruptions in cognition. Moreover, the increased understanding of the basic biology of memory increases the likelihood of discovery of memory-enhancing treatments in these human diseases. In the present study, we investigated the effects of the non-competitive NMDA antagonist ketamine on soci...

  2. Nitric oxide (NO) and an NMDA receptor antagonist in pentylenetetrazole-induced convulsions

    Jelenković Ankica V.; Jovanović Marina D.; Ninković Milica; Maksimović Milan; Bošković Bogdan

    2003-01-01

    Controversy about proconvulsant and anticonvulsant nitric oxide (NO) effects and the place of oxidative stress in convulsions, are still a matter of research. We investigated the interaction between 2-amino-5-phosphonovaleric acid (APV), a competitive N-methyl-D-aspartate (NMDA) receptor antagonist and Nw-nitro-L-arginine methyl ester (L-NAME), a nonselective nitric oxide synthase (NOS) antagonist, in pentylenetetrazole (PTZ)-induced convulsions. Pentylenetetrazole was applied to adult Wistar...

  3. Oxidativer Stress als Modulator der NMDA-Rezeptorexpression auf zerebrovaskulären Endothelzellen

    Betzen, Christian

    2010-01-01

    Oxidativer Stress in Form reaktiver Sauerstoffspezies (ROS) und Exzitotoxizität durch supraphysiologische Konzentrationen des Neurotransmitters Glutamat sind nicht nur beteiligt an der Pathogenese vielzähliger neurodegenerativer Erkrankungen wie Schlaganfall, Hirntrauma, Alzheimer Demenz oder Multipler Sklerose, sondern spielen zudem eine Schlüsselrolle im dort beobachteten Zusammenbruch der Blut-Hirn-Schranke. Glutamat führt durch Stimulation neuronaler und endothelialer NMDA-Rezeptoren zu ...

  4. Synthese, biochemische und physikochemische Charakterisierung von Liganden der Glycin-Bindungsstelle des NMDA-Rezeptors

    Edinger, Carina

    2010-01-01

    Die exzitatorische Neurotransmission erfolgt über ionotrope Glutamat-Rezeptoren von denen dem NMDA-(N-Methyl-D-aspartat)-Rezeptor durch seine hohe Leitfähigkeit für Ca2+-Ionen eine besondere Rolle zugesprochen wird. Bei seiner Überaktivierung kommt es zu exzitotoxischen Prozessen, die direkt mit neurodegenerativen Erkrankungen einhergehen und nach einem Schlaganfall, bei akuten Epilepsien, Morbus Parkinson, Alzheimer Demenz aber auch im Bereich der neuropathischen Schmerzentstehung eine wicht...

  5. Cognitive dysfunction during anti-NMDA-receptor encephalitis is present in early phase of the disease

    Vahter, L.; Kannel, K.; Sorro, U.; Jaakmees, H.; Talvik, T.; Gross-Paju, K.

    2014-01-01

    Anti-NMDA-receptor encephalitis is an autoimmune disorder with a well-defined set of clinical features including psychiatric changes (anxiety, agitation, bizarre behaviour, delusional or paranoid thoughts), epileptic seizures and cognitive disturbance followed by movement disorders including orofacial dyskinesias, alterations in the level of consciousness and dysautonomia. Although the cognitive changes are not always very clear at presentation, they can persist after recovery from the acute ...

  6. Alterations in ethanol-induced behaviors and consumption in knock-in mice expressing ethanol-resistant NMDA receptors.

    Carolina R den Hartog

    Full Text Available Ethanol's action on the brain likely reflects altered function of key ion channels such as glutamatergic N-methyl-D-aspartate receptors (NMDARs. In this study, we determined how expression of a mutant GluN1 subunit (F639A that reduces ethanol inhibition of NMDARs affects ethanol-induced behaviors in mice. Mice homozygous for the F639A allele died prematurely while heterozygous knock-in mice grew and bred normally. Ethanol (44 mM; ∼0.2 g/dl significantly inhibited NMDA-mediated EPSCs in wild-type mice but had little effect on responses in knock-in mice. Knock-in mice had normal expression of GluN1 and GluN2B protein across different brain regions and a small reduction in levels of GluN2A in medial prefrontal cortex. Ethanol (0.75-2.0 g/kg; i.p. increased locomotor activity in wild-type mice but had no effect on knock-in mice while MK-801 enhanced activity to the same extent in both groups. Ethanol (2.0 g/kg reduced rotarod performance equally in both groups but knock-in mice recovered faster following a higher dose (2.5 g/kg. In the elevated zero maze, knock-in mice had a blunted anxiolytic response to ethanol (1.25 g/kg as compared to wild-type animals. No differences were noted between wild-type and knock-in mice for ethanol-induced loss of righting reflex, sleep time, hypothermia or ethanol metabolism. Knock-in mice consumed less ethanol than wild-type mice during daily limited-access sessions but drank more in an intermittent 24 h access paradigm with no change in taste reactivity or conditioned taste aversion. Overall, these data support the hypothesis that NMDA receptors are important in regulating a specific constellation of effects following exposure to ethanol.

  7. Psychological Methods for the Study of Augmented Environments

    Nosulenko, Valery N.; Samoylenko, Elena S.

    In this chapter, some psychological perspectives to study activities in Augmented Environments are outlined. Main concepts related to theories of activity are discussed namely, subjects’ goals and motives as well as tools used during its realization. It is argued that knowledge about the structure of the users’ activity facilitates elaborates the corresponding techniques of its recording and analysis. An overview of the so called “perceived quality” approach is given and the questions about what is perceived by individual (group) as the actor of digitized environment as well as about how to study the perceived quality of such environments are discussed. Several examples of results obtained using this approach are presented.

  8. Transpedicle body augmenter for vertebral augmentation in symptomatic multiple osteoporotic compression fractures

    Li Allen

    2010-01-01

    was 21 min per level, blood loss was 74 cc per level and hospitalization was 4.4 days. No patient had neurological deterioration. There was no dislodgement of implant in the final visit. Forty-eight patients (77.4% could walk within 6-8 h after operation and the others, within 24 h. The anterior vertebral restoration was 7.3 mm initially and 6.2 mm at final follow-up. Wedge angle correction was 10.4° initially and was 9.3° at final follow-up. Pain, by the visual analog scale, was 8.5 preoperatively, 2.7 at day 7 follow-up and 2.9 at final follow-up. By the questionnaire, 52 of 58 respondents reported a decrease in discomfort after TpBA and 48 of 58 patients reported a return to normal activity after operation. The final satisfaction rate was 89.7%. Discussion: The symptoms of multiple osteoporotic compression fracture may be due to unstable fracture, radiculopathy, and global traumatic kyphosis with posture changes, which can be corrected by multiple TpBA. The transpedicle body augmenter was initially stabilized by the sinking and locking mechanism and finally by bone ingrowth. Conclusions: TpBA via a minimally invasive method led to early and medium-term clinical improvements and anatomic restoration of multiple symptomatic VCFs.

  9. Novel Fluorine-Containing NMDA Antagonists for Brain Imaging: In Vitro Evaluation

    Alvarado, M.; Biegon, A.

    2001-01-01

    The NMDA receptor has been implicated in neuronal death following stroke, brain injury and neurodegenerative disorders (e.g. Alzheimer's, Parkinson's and Huntington's disease) and in physiological functions (e.g. memory and cognition). Non-competitive antagonists, such as MK- 801 and CNS-1102, that block the action of glutamate at the NMDA receptor have been shown to be neuroprotective by blocking the influx of calcium into the cells. As a result, they are being considered as therapeutic agents for the above mentioned diseases. Several Fluorine-containing novel analogs of NMDA channel blockers have been synthesized and evaluated in search of a compound suitable for 18F labeling and Positron Emission Tomography (PET). Based on in vitro binding assay studies on rat brain membranes, the novel compounds examined displayed a range of affinities. Preliminary analyses indicated that chlorine is the best halogen on the ring, and that ethyl fluoro derivatives are more potent than methyl-fluoro compounds. Further analysis based on autoradiography will be needed to examine the regional binding characteristics of the novel compounds examined in this study. Labeling with 18F will allow the use of these compounds in humans, generating new insights into mechanisms and treatment of diseases involving malfunction of the glutamatergic system in the brain.

  10. NMDA Receptors on Dopaminoceptive Neurons Are Essential for Drug-Induced Conditioned Place Preference.

    Sikora, Magdalena; Tokarski, Krzysztof; Bobula, Bartosz; Zajdel, Joanna; Jastrzębska, Kamila; Cieślak, Przemysław Eligiusz; Zygmunt, Magdalena; Sowa, Joanna; Smutek, Magdalena; Kamińska, Katarzyna; Gołembiowska, Krystyna; Engblom, David; Hess, Grzegorz; Przewlocki, Ryszard; Rodriguez Parkitna, Jan

    2016-01-01

    Plasticity of the brain's dopamine system plays a crucial role in adaptive behavior by regulating appetitive motivation and the control of reinforcement learning. In this study, we investigated drug- and natural-reward conditioned behaviors in a mouse model in which the NMDA receptor-dependent plasticity of dopaminoceptive neurons was disrupted. We generated a transgenic mouse line with inducible selective inactivation of the NR1 subunit in neurons expressing dopamine D1 receptors (the NR1(D1CreERT2) mice). Whole-cell recordings of spontaneous EPSCs on neurons in the nucleus accumbens confirmed that a population of neurons lacked the NMDA receptor-dependent component of the current. This effect was accompanied by impaired long-term potentiation in the nucleus accumbens and in the CA1 area of the ventral, but not the dorsal, hippocampus. Mutant mice did not differ from control animals when tested for pavlovian or instrumental conditioning. However, NR1(D1CreERT2) mice acquired no preference for a context associated with administration of drugs of abuse. In the conditioned place preference paradigm, mutant mice did not spend more time in the context paired with cocaine, morphine, or ethanol, although these mice acquired a preference for sucrose jelly and an aversion to naloxone injections, as normal. Thus, we observed that the selective inducible ablation of the NMDA receptors specifically blocks drug-associated context memory with no effect on positive reinforcement in general. PMID:27294197

  11. Genetic NMDA receptor deficiency disrupts acute and chronic effects of cocaine but not amphetamine.

    Ramsey, Amy J; Laakso, Aki; Cyr, Michel; Sotnikova, Tatyana D; Salahpour, Ali; Medvedev, Ivan O; Dykstra, Linda A; Gainetdinov, Raul R; Caron, Marc G

    2008-10-01

    NMDA receptor-mediated glutamate transmission is required for several forms of neuronal plasticity. Its role in the neuronal responses to addictive drugs is an ongoing subject of investigation. We report here that the acute locomotor-stimulating effect of cocaine is absent in NMDA receptor-deficient mice (NR1-KD). In contrast, their acute responses to amphetamine and to direct dopamine receptor agonists are not significantly altered. The striking attenuation of cocaine's acute effects is not likely explained by alterations in the dopaminergic system of NR1-KD mice, since most parameters of pre- and postsynaptic dopamine function are unchanged. Consistent with the behavioral findings, cocaine induces less c-Fos expression in the striatum of these mice, while amphetamine-induced c-Fos expression is intact. Furthermore, chronic cocaine-induced sensitization and conditioned place preference are attenuated and develop more slowly in mutant animals, but amphetamine's effects are not altered significantly. Our results highlight the importance of NMDA receptor-mediated glutamatergic transmission specifically in cocaine actions, and support a hypothesis that cocaine and amphetamine elicit their effects through differential actions on signaling pathways. PMID:18185498

  12. A randomized placebo-controlled trial of an NMDA receptor antagonist in sleep-disordered breathing.

    Torvaldsson, Stefan; Grote, Ludger; Peker, Yüksel; Basun, Hans; Hedner, Jan

    2005-06-01

    Hypoxemia is a powerful stimulus of glutamate release in the central nervous system (CNS) and a hallmark phenomenon in sleep disordered breathing (SDB). Glutamate effects that include neuronal damage and apoptosis following hypoxemia and apnea following microinjections in animal models are in part mediated via postjunctional N-methyl-D-aspartate (NMDA) receptors. This was a double blind, randomized, placebo-controlled single dose cross-over study of the NMDA receptor antagonist AR-R15896AR in 15 male patients with moderate to severe SDB. Seven patients received 120 mg and eight patients received 350 mg AR-R15896AR or corresponding placebo (given by 2 h infusion) starting half an hour before estimated sleep onset. AR-R15896AR concentrations were in line with the predicting kinetic model. A standard polysomnographic montage was applied. Repeated plasma samples were obtained in nine patients for analysis of plasma glutamate. Glutamate concentration in plasma did not change overnight and was unrelated to severity of SDB. Overall AHI (apnea-hypopnea index; primary efficacy variable) or investigated oxygen saturation variables were not significantly changed after AR-R15896AR at either dosage level. Side effects were mostly confined to the higher dose level and included vivid dreams, nightmares as well as in two cases mild hallucinations. The previously postulated role of glutamate in SDB could not be confirmed after AR-R15896AR induced NMDA-receptor blockade. PMID:15910512

  13. Behavioral consequences of NMDA antagonist-induced neuroapoptosis in the infant mouse brain.

    Carla M Yuede

    Full Text Available BACKGROUND: Exposure to NMDA glutamate antagonists during the brain growth spurt period causes widespread neuroapoptosis in the rodent brain. This period in rodents occurs during the first two weeks after birth, and corresponds to the third trimester of pregnancy and several years after birth in humans. The developing human brain may be exposed to NMDA antagonists through drug-abusing mothers or through anesthesia. METHODOLOGY/PRINCIPAL FINDINGS: We evaluated the long-term neurobehavioral effects of mice exposed to a single dose of the NMDA antagonist, phencyclidine (PCP, or saline, on postnatal day 2 (P2 or P7, or on both P2 and P7. PCP treatment on P2 + P7 caused more severe cognitive impairments than either single treatment. Histological examination of acute neuroapoptosis resulting from exposure to PCP indicated that the regional pattern of degeneration induced by PCP in P2 pups was different from that in P7 pups. The extent of damage when evaluated quantitatively on P7 was greater for pups previously treated on P2 compared to pups treated only on P7. CONCLUSIONS: These findings signify that PCP induces different patterns of neuroapoptosis depending on the developmental age at the time of exposure, and that exposure at two separate developmental ages causes more severe neuropathological and neurobehavioral consequences than a single treatment.

  14. Kalirin-7 is necessary for normal NMDA receptor-dependent synaptic plasticity

    Lemtiri-Chlieh Fouad

    2011-12-01

    Full Text Available Abstract Background Dendritic spines represent the postsynaptic component of the vast majority of excitatory synapses present in the mammalian forebrain. The ability of spines to rapidly alter their shape, size, number and receptor content in response to stimulation is considered to be of paramount importance during the development of synaptic plasticity. Indeed, long-term potentiation (LTP, widely believed to be a cellular correlate of learning and memory, has been repeatedly shown to induce both spine enlargement and the formation of new dendritic spines. In our studies, we focus on Kalirin-7 (Kal7, a Rho GDP/GTP exchange factor (Rho-GEF localized to the postsynaptic density that plays a crucial role in the development and maintenance of dendritic spines both in vitro and in vivo. Previous studies have shown that mice lacking Kal7 (Kal7KO have decreased dendritic spine density in the hippocampus as well as focal hippocampal-dependent learning impairments. Results We have performed a detailed electrophysiological characterization of the role of Kal7 in hippocampal synaptic plasticity. We show that loss of Kal7 results in impaired NMDA receptor-dependent LTP and long-term depression, whereas a NMDA receptor-independent form of LTP is shown to be normal in the absence of Kal7. Conclusions These results indicate that Kal7 is an essential and selective modulator of NMDA receptor-dependent synaptic plasticity in the hippocampus.

  15. Kalirin-7 is necessary for normal NMDA receptor-dependent synaptic plasticity

    Lemtiri-Chlieh, Fouad

    2011-12-19

    Background: Dendritic spines represent the postsynaptic component of the vast majority of excitatory synapses present in the mammalian forebrain. The ability of spines to rapidly alter their shape, size, number and receptor content in response to stimulation is considered to be of paramount importance during the development of synaptic plasticity. Indeed, long-term potentiation (LTP), widely believed to be a cellular correlate of learning and memory, has been repeatedly shown to induce both spine enlargement and the formation of new dendritic spines. In our studies, we focus on Kalirin-7 (Kal7), a Rho GDP/GTP exchange factor (Rho-GEF) localized to the postsynaptic density that plays a crucial role in the development and maintenance of dendritic spines both in vitro and in vivo. Previous studies have shown that mice lacking Kal7 (Kal7 KO) have decreased dendritic spine density in the hippocampus as well as focal hippocampal-dependent learning impairments.Results: We have performed a detailed electrophysiological characterization of the role of Kal7 in hippocampal synaptic plasticity. We show that loss of Kal7 results in impaired NMDA receptor-dependent LTP and long-term depression, whereas a NMDA receptor-independent form of LTP is shown to be normal in the absence of Kal7.Conclusions: These results indicate that Kal7 is an essential and selective modulator of NMDA receptor-dependent synaptic plasticity in the hippocampus. 2011 Lemtiri-Chlieh et al; licensee BioMed Central Ltd.

  16. Augmented Reality Simulations on Handheld Computers

    Squire, Kurt; Klopfer, Eric

    2007-01-01

    Advancements in handheld computing, particularly its portability, social interactivity, context sensitivity, connectivity, and individuality, open new opportunities for immersive learning environments. This article articulates the pedagogical potential of augmented reality simulations in environmental engineering education by immersing students in…

  17. Transumbilical Breast Augmentation Is Safe and Effective

    Dowden, Richard V.

    2008-01-01

    Transumbilical breast augmentation (TUBA) has proved to be safe and effective. This article highlights the advantages, disadvantages, gives an overview of the technique, discusses complications, and provides factual information to counter false negative information about the procedure.

  18. Muzzle shunt augmentation of conventional railguns

    Parker, J.V. (Los Alamos National Lab., NM (United States). Physics Div.)

    1991-01-01

    This paper reports on augmentation which is a technique for reducing the armature current and hence the armature power dissipation in a plasma armature railgun. In spite of the advantages, no large augmented railguns have been built, primarily due to the mechanical and electrical complexity introduced by the extra conductors required. it is possible to achieve some of the benefits of augmentation in a conventional railgun by diverting a fraction {phi} of the input current through a shunt path at the muzzle of the railgun. In particular, the relation between force and armature current is the same as that obtained in an n-turn, series-connected augmented railgun with n = 1/(1 {minus} {phi}). The price of this simplification is a reduction in electrical efficiency and some additional complexity in the external electrical system.

  19. Augmenting the Web through Open Hypermedia

    Bouvin, N.O.

    2003-01-01

    Based on an overview of Web augmentation and detailing the three basic approaches to extend the hypermedia functionality of the Web, the author presents a general open hypermedia framework (the Arakne framework) to augment the Web. The aim is to provide users with the ability to link, annotate, a...... otherwise structure Web pages, as they see fit. The paper further discusses the possibilities of the concept through the description of various experiments performed with an implementation of the framework, the Arakne Environment......Based on an overview of Web augmentation and detailing the three basic approaches to extend the hypermedia functionality of the Web, the author presents a general open hypermedia framework (the Arakne framework) to augment the Web. The aim is to provide users with the ability to link, annotate, and...

  20. Affordances in Mobile Augmented Reality Applications

    Tor Gjøsæter

    2014-10-01

    Full Text Available This paper explores the affordances of augmented reality content in a mobile augmented reality application. A user study was conducted by performing a multi-camera video recording of seven think aloud sessions. The think aloud sessions consisted of individual users performing tasks, exploring and experiencing a mobile augmented reality (MAR application we developed for the iOS platform named ARad. We discuss the instrumental affordances we observed when users interacted with augmented reality content, as well as more complex affordances rising from conventions from media content, AR and the traditional WIMP paradigm. We find that remediation of traditional newspaper content through the MAR medium can provide engaging, pleasing and exciting user experiences. However, the some of the content still suffers from being shoveled onto the MAR platform without adapting it properly. Finally, we discuss what content was most successfully mediated to the user and how the content impacts the user experience.