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Sample records for elevated insular glutamate

  1. Obstructive sleep apnea is associated with low GABA and high glutamate in the insular cortex.

    PubMed

    Macey, Paul M; Sarma, Manoj K; Nagarajan, Rajakumar; Aysola, Ravi; Siegel, Jerome M; Harper, Ronald M; Thomas, M Albert

    2016-08-01

    The insular cortex is injured in obstructive sleep apnea (OSA) and responds inappropriately to autonomic challenges, suggesting neural reorganization. The objective of this study was to assess whether the neural changes might result from γ-aminobutyric acid (GABA) and glutamate alterations. We studied 14 OSA patients [mean age ± standard deviation (SD): 47.5 ± 10.5 years; nine male; apnea-hypopnea index (AHI): 29.5 ± 15.6 events h(-1) ] and 22 healthy participants (47.5 ± 10.1 years; 11 male), using magnetic resonance spectroscopy to detect GABA and glutamate levels in insular cortices. We localized the cortices with anatomical scans, and measured neurochemical levels from anterior to mid-regions. Left and right anterior insular cortices showed lower GABA and higher glutamate in OSA versus healthy subjects [GABA left: OSA n = 6: 0.36 ± 0.10 (mean ± SD), healthy n = 5: 0.62 ± 0.18; P < 0.05), right: OSA n = 11: 0.27 ± 0.09, healthy n = 14: 0.45 ± 0.16; P < 0.05; glutamate left: OSA n = 6: 1.61 ± 0.32, healthy n = 8: 0.94 ± 0.34; P < 0.05, right: OSA n = 14: 1.26 ± 0.28, healthy n = 19: 1.02 ± 0.28; P < 0.05]. GABA and glutamate levels were correlated only within the healthy group in the left insula (r: -0.9, P < 0.05). The altered anterior insular levels of GABA and glutamate may modify integration and projections to autonomic areas, contributing to the impaired cardiovascular regulation in OSA.

  2. Peripherally restricted viral challenge elevates extracellular glutamate and enhances synaptic transmission in the hippocampus.

    PubMed

    Hunsberger, Holly C; Wang, Desheng; Petrisko, Tiffany J; Alhowail, Ahmad; Setti, Sharay E; Suppiramaniam, Vishnu; Konat, Gregory W; Reed, Miranda N

    2016-07-01

    Peripheral infections increase the propensity and severity of seizures in susceptible populations. We have previously shown that intraperitoneal injection of a viral mimic, polyinosinic-polycytidylic acid (PIC), elicits hypersusceptibility of mice to kainic acid (KA)-induced seizures. This study was undertaken to determine whether this seizure hypersusceptibility entails alterations in glutamate signaling. Female C57BL/6 mice were intraperitoneally injected with PIC, and after 24 h, glutamate homeostasis in the hippocampus was monitored using the enzyme-based microelectrode arrays. PIC challenge robustly increased the level of resting extracellular glutamate. While pre-synaptic potassium-evoked glutamate release was not affected, glutamate uptake was profoundly impaired and non-vesicular glutamate release was augmented, indicating functional alterations of astrocytes. Electrophysiological examination of hippocampal slices from PIC-challenged mice revealed a several fold increase in the basal synaptic transmission as compared to control slices. PIC challenge also increased the probability of pre-synaptic glutamate release as seen from a reduction of paired-pulse facilitation and synaptic plasticity as seen from an enhancement of long-term potentiation. Altogether, our results implicate a dysregulation of astrocytic glutamate metabolism and an alteration of excitatory synaptic transmission as the underlying mechanism for the development of hippocampal hyperexcitability, and consequently seizure hypersusceptibility following peripheral PIC challenge. Peripheral infections/inflammations enhance seizure susceptibility. Here, we explored the effect of peritoneal inflammation induced by a viral mimic on glutamate homeostasis and glutamatergic neurotransmission in the mouse hippocampus. We found that peritoneal inflammation elevated extracellular glutamate concentration and enhanced the probability of pre-synaptic glutamate release resulting in hyperexcitability of

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

    PubMed Central

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

    2015-01-01

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

  4. Elevated venous glutamate levels in (pre)catabolic conditions result at least partly from a decreased glutamate transport activity.

    PubMed

    Hack, V; Stütz, O; Kinscherf, R; Schykowski, M; Kellerer, M; Holm, E; Dröge, W

    1996-06-01

    Abnormally high postabsorptive venous plasma glutamate levels have been reported for several diseases that are associated with a loss of body cell mass including cancer, human/simian immunodeficiency virus infection, and amyotrophic lateral sclerosis. Studies on exchange rates in well-nourished cancer patients now show that high venous plasma glutamate levels may serve as a bona fide indicator for a decreased uptake of glutamate by the peripheral muscle tissue in the postabsorptive period and may be indicative for a precachectic state. High glutamate levels are also moderately correlated with a decreased uptake of glucose and ketone bodies. Relatively high venous glutamate levels have also been found in non-insulin-dependent diabetes mellitus and to some extent also in the cubital vein of normal elderly subjects, i.e., in conditions commonly associated with a decreased glucose tolerance and progressive loss of body cell mass.

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

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

    2016-04-01

    Anticipatory nausea (AN) is a conditioned nausea reaction experienced by chemotherapy patients upon returning to the clinic. Currently, there are no specific treatments for this phenomenon, with the classic antiemetic treatments (e.g., ondansetron) providing no relief. The rat model of AN, contextually elicited conditioned gaping reactions in rats, provides a tool for assessing potential treatments for this difficult to treat disorder. Systemically administered drugs which elevate the endocannabinoids, anandamide (AEA) and 2-arachidonoyl glycerol (2-AG), by interfering with their respective degrading enzymes, fatty acid amide hydrolase (FAAH) and monoacyl glycerol lipase (MAGL) interfere with AN in the rat model. We have shown that MAGL inhibition within the visceral insular cortex (VIC) interferes with acute nausea in the gaping model (Sticht et al., 2015). Here we report that bilateral infusion of the MAGL inhibitor, MJN110 (but neither the FAAH inhibitor, PF3845, nor ondansetron) into the VIC suppressed contextually elicited conditioned gaping, and this effect was reversed by coadministration of the CB1 antagonist, AM251. These findings suggest that 2-AG within the VIC plays a critical role in the regulation of both acute nausea and AN. Because there are currently no specific therapeutics for chemotherapy patients that develop anticipatory nausea, MAGL inhibition by MJN110 may be a candidate treatment. (PsycINFO Database Record PMID:26974857

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

    PubMed

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

    2016-04-01

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

  8. Insular cortex epilepsy: an overview.

    PubMed

    Nguyen, Dang Khoa; Nguyen, Dong Bach; Malak, Ramez; Bouthillier, Alain

    2009-08-01

    In this review the authors discuss insular cortex epilepsy, an under-recognized localization-related syndrome that may explain some temporal (but also frontal and parietal lobe) epilepsy surgery failures. The insula may generate a variety of symptoms (including visceral, motor and somatosensory) that mimic temporal, frontal or parietal lobe onset seizures. Intracerebral electrodes directly implanted in the insula are currently the only way to confirm insular seizures. Consideration should be given to exploration of the insular cortex in MRI negative patients with seizure semiology consistent with insular onset seizures. Electroencephalographers should have a low threshold to sample this region, especially in the absence of a structural lesion. Microneurosurgical technical advances allow resective surgery of the insula with relatively low morbidity. PMID:19760905

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

    PubMed Central

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

    2010-01-01

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

  10. Insular volume reduction in schizophrenia.

    PubMed

    Saze, Teruyasu; Hirao, Kazuyuki; Namiki, Chihiro; Fukuyama, Hidenao; Hayashi, Takuji; Murai, Toshiya

    2007-12-01

    Structural and functional abnormalities of the insular cortex have been reported in patients with schizophrenia. Most studies have shown that the insular volumes in schizophrenia patients are smaller than those of healthy people. As the insular cortex is functio-anatomically divided into anterior and posterior subdivisons, recent research is focused on uncovering a specific subdivisional abnormality of the insula in patients with schizophrenia. A recent ROI-based volumetric MRI study demonstrated specific left anterior insular volume reduction in chronic schizophrenia patients (Makris N, Goldstein J, Kennedy D, Hodge S, Caviness V, Faraone S, Tsuang M, Seidman L (2006) Decreased volume of left and total anterior insular lobule in schizophrenia. Schizophr Res 83:155-171). On the other hand, our VBM-based volumetric study revealed a reduction in right posterior insular volume (Yamada M, Hirao K, Namiki C, Hanakawa T, Fukuyama H, Hayashi T, Murai T (2007) Social cognition and frontal lobe pathology in schizophrenia: a voxel-based morphometric study. NeuroImage 35:292-298). In order to address these controversial results, ROI-based subdivisional volumetry was performed using the MRI images from the same population we analyzed in our previous VBM-study. The sample group comprised 20 schizophrenia patients and 20 matched healthy controls. Patients with schizophrenia showed a global reduction in insular gray matter volumes relative to healthy comparison subjects. In a simple comparison of the volumes of each subdivision between the groups, a statistically significant volume reduction in patients with schizophrenia was demonstrated only in the right posterior insula. This study suggests that insular abnormalities in schizophrenia would include anterior as well as posterior parts. Each subdivisional abnormality may impact on different aspects of the pathophysiology and psychopathology of schizophrenia; these relationships should be the focus of future research.

  11. The insular cortex: a review.

    PubMed

    Nieuwenhuys, Rudolf

    2012-01-01

    The human insular cortex forms a distinct, but entirely hidden lobe, situated in the depth of the Sylvian fissure. Here, we first review the recent literature on the connectivity and the functions of this structure. It appears that this small lobe, taking up less than 2% of the total cortical surface area, receives afferents from some sensory thalamic nuclei, is (mostly reciprocally) connected with the amygdala and with many limbic and association cortical areas, and is implicated in an astonishingly large number of widely different functions, ranging from pain perception and speech production to the processing of social emotions. Next, we embark on a long, adventurous journey through the voluminous literature on the structural organization of the insular cortex. This journey yielded the following take-home messages: (1) The meticulous, but mostly neglected publications of Rose (1928) and Brockhaus (1940) are still invaluable for our understanding of the architecture of the mammalian insular cortex. (2) The relation of the insular cortex to the adjacent claustrum is neither ontogenetical nor functional, but purely topographical. (3) The insular cortex has passed through a spectacular progressive differentiation during hominoid evolution, but the assumption of Craig (2009) that the human anterior insula has no homologue in the rhesus monkey is untenable. (4) The concept of Mesulam and Mufson (1985), that the primate insula is essentially composed of three concentrically arranged zones, agranular, dysgranular, and granular, is presumably correct, but there is at present much confusion concerning the more detailed architecture of the anterior insular cortex. (5) The large spindle-shaped cells in the fifth layer of the insular cortex, currently known as von Economo neurons (VENs), are not only confined to large-brained mammals, such as whales, elephants, apes, and humans, but also occur in monkeys and prosimians, as well as in the pygmy hippopotamus, the Atlantic

  12. Elevated intracranial dopamine impairs the glutamate-nitric oxide-cyclic guanosine monophosphate pathway in cortical astrocytes in rats with minimal hepatic encephalopathy

    PubMed Central

    DING, SAIDAN; HUANG, WEILONG; YE, YIRU; YANG, JIANJING; HU, JIANGNAN; WANG, XIAOBIN; LIU, LEPING; LU, QIN; LIN, YUANSHAO

    2014-01-01

    In a previous study by our group memory impairment in rats with minimal hepatic encephalopathy (MHE) was associated with the inhibition of the glutamate-nitric oxide-cyclic guanosine monophosphate (Glu-NO-cGMP) pathway due to elevated dopamine (DA). However, the effects of DA on the Glu-NO-cGMP pathway localized in primary cortical astrocytes (PCAs) had not been elucidated in rats with MHE. In the present study, it was identified that when the levels of DA in the cerebral cortex of rats with MHE and high-dose DA (3 mg/kg)-treated rats were increased, the co-localization of N-methyl-d-aspartate receptors subunit 1 (NMDAR1), calmodulin (CaM), nitric oxide synthase (nNOS), soluble guanylyl cyclase (sGC) and cyclic guanine monophosphate (cGMP) with the glial fibrillary acidic protein (GFAP), a marker protein of astrocytes, all significantly decreased, in both the MHE and high-dose DA-treated rats (P<0.01). Furthermore, NMDA-induced augmentation of the expression of NMDAR1, CaM, nNOS, sGC and cGMP localized in PCAs was decreased in MHE and DA-treated rats, as compared with the controls. Chronic exposure of cultured cerebral cortex PCAs to DA treatment induced a dose-dependent decrease in the concentration of intracellular calcium, nitrites and nitrates, the formation of cGMP and the expression of NMDAR1, CaM, nNOS and sGC/cGMP. High doses of DA (50 μM) significantly reduced NMDA-induced augmentation of the formation of cGMP and the contents of NMDAR1, CaM, nNOS, sGC and cGMP (P<0.01). These results suggest that the suppression of DA on the Glu-NO-cGMP pathway localized in PCAs contributes to memory impairment in rats with MHE. PMID:25059564

  13. The insular cortex: a comparative perspective.

    PubMed

    Butti, Camilla; Hof, Patrick R

    2010-06-01

    The human insular cortex is involved in a variety of viscerosensory, visceromotor, and interoceptive functions, and plays a role in complex processes such as emotions, music, and language. Across mammals, the insula has considerable morphologic variability. We review the structure and connectivity of the insula in laboratory animals (mouse, domestic cat, macaque monkey), and we present original data on the morphology and cytoarchitecture of insular cortex in less common species including a large carnivore (the Atlantic walrus, Odobenus rosmarus), two artiodactyls (the pigmy hippopotamus, Hexaprotodon liberiensis, and the Western bongo, Tragelaphus eurycerus), two cetaceans (the beluga whale, Delphinapterus leucas, and the minke whale, Balaenoptera acutorostrata), and a sirenian (the Florida manatee, Trichechus manatus latirostris). The insula shows substantial variability in shape, extent, and gyral and sulcal patterns, as well as differences in laminar organization, cellular specialization, and structural association with the claustrum. Our observations reveal that the insular cortex is extremely variable among mammals. These differences could be related to the role exerted by specific and selective pressures on cortical structure during evolution. We conclude that it is not possible to identify a general model of organization for the mammalian insular cortex. PMID:20512368

  14. Extreme insular dwarfism evolved in a mammoth.

    PubMed

    Herridge, Victoria L; Lister, Adrian M

    2012-08-22

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

  15. Extreme insular dwarfism evolved in a mammoth.

    PubMed

    Herridge, Victoria L; Lister, Adrian M

    2012-08-22

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

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

    PubMed Central

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

    2008-01-01

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

  17. Extracorporeal methods of blood glutamate scavenging: a novel therapeutic modality.

    PubMed

    Zhumadilov, Agzam; Boyko, Matthew; Gruenbaum, Shaun E; Brotfain, Evgeny; Bilotta, Federico; Zlotnik, Alexander

    2015-05-01

    Pathologically elevated glutamate concentrations in the brain's extracellular fluid are associated with several acute and chronic brain insults. Studies have demonstrated that by decreasing the concentration of glutamate in the blood, thereby increasing the concentration gradient between the brain and the blood, the rate of brain-to-blood glutamate efflux can be increased. Blood glutamate scavengers, pyruvate and oxaloacetate have shown great promise in providing neuroprotection in many animal models of acute brain insults. However, glutamate scavengers' potential systemic toxicity, side effects and pharmacokinetic properties may limit their use in clinical practice. In contrast, extracorporeal methods of blood glutamate reduction, in which glutamate is filtered from the blood and eliminated, may be an advantageous adjunct in treating acute brain insults. Here, we review the current evidence for the glutamate-lowering effects of hemodialysis, peritoneal dialysis and hemofiltration. The evidence reviewed here highlights the need for clinical trials.

  18. Neural processing of gustatory information in insular circuits.

    PubMed

    Maffei, Arianna; Haley, Melissa; Fontanini, Alfredo

    2012-08-01

    The insular cortex is the primary cortical site devoted to taste processing. A large body of evidence is available for how insular neurons respond to gustatory stimulation in both anesthetized and behaving animals. Most of the reports describe broadly tuned neurons that are involved in processing the chemosensory, physiological and psychological aspects of gustatory experience. However little is known about how these neural responses map onto insular circuits. Particularly mysterious is the functional role of the three subdivisions of the insular cortex: the granular, the dysgranular and the agranular insular cortices. In this article we review data on the organization of the local and long-distance circuits in the three subdivisions. The functional significance of these results is discussed in light of the latest electrophysiological data. A view of the insular cortex as a functionally integrated system devoted to processing gustatory, multimodal, cognitive and affective information is proposed. PMID:22554880

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

    PubMed

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

    2016-10-01

    Recent studies have provided evidence that there are two possible systems for empathy: affective empathy (AE) and cognitive empathy (CE). Neuroimaging paradigms have proven that the insular cortex is involved in empathy processing, particularly in AE. However, these observations do not provide causal evidence for the role of the insula in empathy. Although impairments in empathy have been described following insular damage in a few case studies, it is not clear whether insular cortex is involved in CE and whether these two systems are impaired independently or laterally in patients with insular gliomas. In this study, we assessed 17 patients with an insular glioma, 17 patients with a noninsular glioma, and 30 healthy controls using a method that combined a self-report empathy questionnaire with the emotion recognition task, assessment of empathy for others' pain, and the emotional perspective-taking paradigm. We found that patients with an insular glioma had lower scores for empathic concern and perspective taking than did either healthy controls or lesion controls. The patients' abilities to recognize facial emotions, perceive others' pain, and understand the emotional perspectives of others were also significantly impaired. Furthermore, we did not observe a laterality effect on either AE or CE among those with insular lesions. These findings revealed that both AE and CE are impaired in patients with an insular glioma and that the insular cortex may be a central neuroanatomical structure in both the AE and CE systems. PMID:27456973

  20. Modulation of glutamate transport and receptor binding by glutamate receptor antagonists in EAE rat brain.

    PubMed

    Sulkowski, Grzegorz; Dąbrowska-Bouta, Beata; Salińska, Elżbieta; Strużyńska, Lidia

    2014-01-01

    The etiology of multiple sclerosis (MS) is currently unknown. However, one potential mechanism involved in the disease may be excitotoxicity. The elevation of glutamate in cerebrospinal fluid, as well as changes in the expression of glutamate receptors (iGluRs and mGluRs) and excitatory amino acid transporters (EAATs), have been observed in the brains of MS patients and animals subjected to experimental autoimmune encephalomyelitis (EAE), which is the predominant animal model used to investigate the pathophysiology of MS. In the present paper, the effects of glutamatergic receptor antagonists, including amantadine, memantine, LY 367583, and MPEP, on glutamate transport, the expression of mRNA of glutamate transporters (EAATs), the kinetic parameters of ligand binding to N-methyl-D-aspartate (NMDA) receptors, and the morphology of nerve endings in EAE rat brains were investigated. The extracellular level of glutamate in the brain is primarily regulated by astrocytic glutamate transporter 1 (GLT-1) and glutamate-aspartate transporter (GLAST). Excess glutamate is taken up from the synaptic space and metabolized by astrocytes. Thus, the extracellular level of glutamate decreases, which protects neurons from excitotoxicity. Our investigations showed changes in the expression of EAAT mRNA, glutamate transport (uptake and release) by synaptosomal and glial plasmalemmal vesicle fractions, and ligand binding to NMDA receptors; these effects were partially reversed after the treatment of EAE rats with the NMDA antagonists amantadine and memantine. The antagonists of group I metabotropic glutamate receptors (mGluRs), including LY 367385 and MPEP, did not exert any effect on the examined parameters. These results suggest that disturbances in these mechanisms may play a role in the processes associated with glutamate excitotoxicity and the progressive brain damage in EAE.

  1. Deciphering arboviral emergence within insular ecosystems.

    PubMed

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

    2012-08-01

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

  2. 75 FR 20237 - Interagency Group on Insular Areas

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-19

    ..., 2010. [FR Doc. 2010-9078 Filed 4-16-10; 8:45 am] Billing code 3195-W0-P ... on Insular Areas By the authority vested in me as President by the Constitution and the laws of the United States of America, it is hereby ordered as follows: Section 1. Interagency Group on Insular...

  3. 38 CFR 3.40 - Philippine and Insular Forces.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

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

  4. 38 CFR 3.40 - Philippine and Insular Forces.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

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

  5. 38 CFR 3.40 - Philippine and Insular Forces.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

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

  6. 38 CFR 3.40 - Philippine and Insular Forces.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

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

  7. 24 CFR 92.60 - Allocation amounts for insular areas.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 24 Housing and Urban Development 1 2010-04-01 2010-04-01 false Allocation amounts for insular areas. 92.60 Section 92.60 Housing and Urban Development Office of the Secretary, Department of Housing and Urban Development HOME INVESTMENT PARTNERSHIPS PROGRAM Allocation Formula Insular Areas...

  8. 24 CFR 92.60 - Allocation amounts for insular areas.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 24 Housing and Urban Development 1 2011-04-01 2011-04-01 false Allocation amounts for insular areas. 92.60 Section 92.60 Housing and Urban Development Office of the Secretary, Department of Housing and Urban Development HOME INVESTMENT PARTNERSHIPS PROGRAM Allocation Formula Insular Areas...

  9. Glutamate receptor mGlu2 and mGlu3 knockout striata are dopamine supersensitive, with elevated D2(High) receptors and marked supersensitivity to the dopamine agonist (+)PHNO.

    PubMed

    Seeman, Philip; Battaglia, Giuseppe; Corti, Corrado; Corsi, Mauro; Bruno, Valeria

    2009-03-01

    The finding that the mGlu2/3 metabotropic glutamate receptor agonist, LY404039, improves clinical symptoms in schizophrenia warrants a search for a possible interaction between mGlu2/3 receptors and dopamine D2 receptors. Here, this topic is examined in striatal tissue of mice lacking either mGlu2 or mGlu3 receptor. Such mice are known to be behaviorally supersensitive to dopamine receptor agonists. Therefore, to determine the basis of this dopamine supersensitivity, the proportion of dopamine D2(High) receptors was measured in the striata of mGlu2 and mGlu3 receptor knockout mice. The proportion of D2(High) receptors was found to be elevated by 220% in the striata of both knockouts. To measure the functional dopamine supersensitivity, the D2 agonist (+)PHNO was used to stimulate the incorporation of GTP-gamma-S in the striatal homogenates in the presence of drugs that blocked the dopamine D1, D3, and D5 receptors. Compared with control striata, the mGlu2 receptor knockout tissues were 67-fold more sensitive to (+)PHNO, while the mGlu3 receptor knockout tissues were 17-fold more sensitive. These data suggest that group II mGlu receptors-mGlu2 receptors in particular-may normally regulate D2 receptors by reducing the proportion of high-affinity D2 receptors in membranes. Such regulation may contribute to the antipsychotic action of mGlu2/3 receptor agonists. PMID:19084908

  10. 45 CFR 97.13 - How does an insular area apply for a consolidated grant?

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 45 Public Welfare 1 2011-10-01 2011-10-01 false How does an insular area apply for a consolidated... CONSOLIDATION OF GRANTS TO THE INSULAR AREAS § 97.13 How does an insular area apply for a consolidated grant? (a) An insular area may apply for a consolidated grant in lieu of filing an individual application...

  11. 45 CFR 97.13 - How does an insular area apply for a consolidated grant?

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 45 Public Welfare 1 2010-10-01 2010-10-01 false How does an insular area apply for a consolidated... CONSOLIDATION OF GRANTS TO THE INSULAR AREAS § 97.13 How does an insular area apply for a consolidated grant? (a) An insular area may apply for a consolidated grant in lieu of filing an individual application...

  12. 34 CFR 76.131 - How does an insular area apply for a consolidated grant?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 34 Education 1 2011-07-01 2011-07-01 false How does an insular area apply for a consolidated grant... PROGRAMS How a State Applies for a Grant Consolidated Grant Applications for Insular Areas § 76.131 How does an insular area apply for a consolidated grant? (a) An Insular Area that desires to apply for...

  13. Insular cortex and neuropsychiatric disorders: a review of recent literature.

    PubMed

    Nagai, M; Kishi, K; Kato, S

    2007-09-01

    The insular cortex is located in the centre of the cerebral hemisphere, having connections with the primary and secondary somatosensory areas, anterior cingulate cortex, amygdaloid body, prefrontal cortex, superior temporal gyrus, temporal pole, orbitofrontal cortex, frontal and parietal opercula, primary and association auditory cortices, visual association cortex, olfactory bulb, hippocampus, entorhinal cortex, and motor cortex. Accordingly, dense connections exist among insular cortex neurons. The insular cortex is involved in the processing of visceral sensory, visceral motor, vestibular, attention, pain, emotion, verbal, motor information, inputs related to music and eating, in addition to gustatory, olfactory, visual, auditory, and tactile data. In this article, the literature on the relationship between the insular cortex and neuropsychiatric disorders was summarized following a computer search of the Pub-Med database. Recent neuroimaging data, including voxel based morphometry, PET and fMRI, revealed that the insular cortex was involved in various neuropsychiatric diseases such as mood disorders, panic disorders, PTSD, obsessive-compulsive disorders, eating disorders, and schizophrenia. Investigations of functions and connections of the insular cortex suggest that sensory information including gustatory, olfactory, visual, auditory, and tactile inputs converge on the insular cortex, and that these multimodal sensory information may be integrated there.

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

    ERIC Educational Resources Information Center

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

    2010-01-01

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

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

    PubMed Central

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

    2006-01-01

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

  16. Anterior insular cortex and emotional awareness.

    PubMed

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

    2013-10-15

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

  17. Anterior Insular Cortex and Emotional Awareness

    PubMed Central

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

    2014-01-01

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

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

    PubMed

    Formánek, Pavel; Vranová, Valerie; Lojková, Lea

    2015-02-01

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

  19. [Insular epilepsy: A model of cryptic epilepsy. The Lyon experience].

    PubMed

    Isnard, J

    2009-10-01

    The role of the insular lobe in temporal lobe epilepsy (TLE) has often been suggested but never directly demonstrated. In this article, we review data from recent literature and from our own stereo-electroencephalographic (SEEG) recordings in patients referred for temporal lobe epilepsy surgery. Our description of the clinical features of insular lobe seizures is based on data from video and SEEG ictal recordings and direct electric cortical stimulation in a population of 50 consecutive patients whose seizures, on the basis of scalp video EEG recordings, were suspected to originate from, or to rapidly propagate to, the perisylvian cortex. One hundred and forty-four intrainsular electrodes have been implanted in this series of patients. In six patients a stereotyped sequence of ictal symptoms could be identified on the basis of electroclinical correlations. The clinical presentation of insular lobe seizures is that of simple partial seizures occurring in full consciousness, beginning with a sensation of laryngeal constriction followed by paresthesiae that were often unpleasant and affected large cutaneous territories. These initial symptoms were eventually followed by dysarthric speech and/or elementary auditory hallucinations, and seizures often ended with focal dystonic postures. The insular origin of these symptoms was supported by the data from functional cortical mapping of the insula using direct cortical stimulations from a total of 472 intrainsular electrodes in 164 consecutive patients. We were able to reproduce several of the spontaneous ictal symptoms in the six patients with insular seizures. Moreover, from the whole set of insular stimulations that we performed it could be concluded that the insular cortex is involved in somatic, vegetative and visceral functions to which spontaneous ictal insular symptoms are related. The observation of the insular symptoms sequence at the onset of seizures in patients who are candidates for TLE surgery strongly

  20. Attenuated sensitivity to the emotions of others by insular lesion.

    PubMed

    Terasawa, Yuri; Kurosaki, Yoshiko; Ibata, Yukio; Moriguchi, Yoshiya; Umeda, Satoshi

    2015-01-01

    The insular cortex has been considered to be the neural base of visceral sensation for many years. Previous studies in psychology and cognitive neuroscience have accumulated evidence indicating that interoception is an essential factor in the subjective feeling of emotion. Recent neuroimaging studies have demonstrated that anterior insular cortex activation is associated with accessing interoceptive information and underpinning the subjective experience of emotional state. Only a small number of studies have focused on the influence of insular damage on emotion processing and interoceptive awareness. Moreover, disparate hypotheses have been proposed for the alteration of emotion processing by insular lesions. Some studies show that insular lesions yield an inability for understanding and representing disgust exclusively, but other studies suggest that such lesions modulate arousal and valence judgments for both positive and negative emotions. In this study, we examined the alteration in emotion recognition in three right insular and adjacent area damaged cases with well-preserved higher cognitive function. Participants performed an experimental task using morphed photos that ranged between neutral and emotional facial expressions (i.e., anger, sadness, disgust, and happiness). Recognition rates of particular emotions were calculated to measure emotional sensitivity. In addition, they performed heartbeat perception task for measuring interoceptive accuracy. The cases identified emotions that have high arousal level (e.g., anger) as less aroused emotions (e.g., sadness) and a case showed remarkably low interoceptive accuracy. The current results show that insular lesions lead to attenuated emotional sensitivity across emotions, rather than category-specific impairments such as to disgust. Despite the small number of cases, our findings suggest that the insular cortex modulates recognition of emotional saliency and mediates interoceptive and emotional awareness. PMID

  1. Insular Ecosystems of the Southeastern United States- A Regional Synthesis to Support Biodiversity Conservation in a Changing Climate

    USGS Publications Warehouse

    Cartwright, Jennifer M.; Wolfe, William J.

    2016-01-01

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

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

    USGS Publications Warehouse

    Cartwright, Jennifer M.; Wolfe, William J.

    2016-08-11

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

  3. The Role of the Insular Cortex in Retaliation.

    PubMed

    Emmerling, Franziska; Schuhmann, Teresa; Lobbestael, Jill; Arntz, Arnoud; Brugman, Suzanne; Sack, Alexander Thomas

    2016-01-01

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

  4. The Role of the Insular Cortex in Retaliation

    PubMed Central

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

    2016-01-01

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

  5. Glutamate and Neurodegenerative Disease

    NASA Astrophysics Data System (ADS)

    Schaeffer, Eric; Duplantier, Allen

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

  6. Glutamate signalling in roots.

    PubMed

    Forde, Brian G

    2014-03-01

    As a signalling molecule, glutamate is best known for its role as a fast excitatory neurotransmitter in the mammalian nervous system, a role that requires the activity of a family of ionotropic glutamate receptors (iGluRs). The unexpected discovery in 1998 that Arabidopsis thaliana L. possesses a family of iGluR-related (GLR) genes laid the foundations for an assessment of glutamate's potential role as a signalling molecule in plants that is still in progress. Recent advances in elucidating the function of Arabidopsis GLR receptors has revealed similarities with iGluRs in their channel properties, but marked differences in their ligand specificities. The ability of plant GLR receptors to act as amino-acid-gated Ca(2+) channels with a broad agonist profile, combined with their expression throughout the plant, makes them strong candidates for a multiplicity of amino acid signalling roles. Although root growth is inhibited in the presence of a number of amino acids, only glutamate elicits a specific sequence of changes in growth, root tip morphology, and root branching. The recent finding that the MEKK1 gene is a positive regulator of glutamate sensitivity at the root tip has provided genetic evidence for the existence in plants of a glutamate signalling pathway analogous to those found in animals. This short review will discuss the most recent advances in understanding glutamate signalling in roots, considering them in the context of previous work in plants and animals.

  7. II. Glutamine and glutamate.

    PubMed

    Tapiero, H; Mathé, G; Couvreur, P; Tew, K D

    2002-11-01

    Glutamine and glutamate with proline, histidine, arginine and ornithine, comprise 25% of the dietary amino acid intake and constitute the "glutamate family" of amino acids, which are disposed of through conversion to glutamate. Although glutamine has been classified as a nonessential amino acid, in major trauma, major surgery, sepsis, bone marrow transplantation, intense chemotherapy and radiotherapy, when its consumption exceeds its synthesis, it becomes a conditionally essential amino acid. In mammals the physiological levels of glutamine is 650 micromol/l and it is one of the most important substrate for ammoniagenesis in the gut and in the kidney due to its important role in the regulation of acid-base homeostasis. In cells, glutamine is a key link between carbon metabolism of carbohydrates and proteins and plays an important role in the growth of fibroblasts, lymphocytes and enterocytes. It improves nitrogen balance and preserves the concentration of glutamine in skeletal muscle. Deamidation of glutamine via glutaminase produces glutamate a precursor of gamma-amino butyric acid, a neurotransmission inhibitor. L-Glutamic acid is a ubiquitous amino acid present in many foods either in free form or in peptides and proteins. Animal protein may contain from 11 to 22% and plants protein as much as 40% glutamate by weight. The sodium salt of glutamic acid is added to several foods to enhance flavor. L-Glutamate is the most abundant free amino acid in brain and it is the major excitatory neurotransmitter of the vertebrate central nervous system. Most free L-glutamic acid in brain is derived from local synthesis from L-glutamine and Kreb's cycle intermediates. It clearly plays an important role in neuronal differentiation, migration and survival in the developing brain via facilitated Ca++ transport. Glutamate also plays a critical role in synaptic maintenance and plasticity. It contributes to learning and memory through use-dependent changes in synaptic efficacy and

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

    PubMed Central

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

    2016-01-01

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

  9. Report to Congress on Insular Area energy vulnerability

    SciTech Connect

    Not Available

    1994-05-01

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

  10. CREB regulates memory allocation in the insular cortex.

    PubMed

    Sano, Yoshitake; Shobe, Justin L; Zhou, Miou; Huang, Shan; Shuman, Tristan; Cai, Denise J; Golshani, Peyman; Kamata, Masakazu; Silva, Alcino J

    2014-12-01

    The molecular and cellular mechanisms of memory storage have attracted a great deal of attention. By comparison, little is known about memory allocation, the process that determines which specific neurons in a neural network will store a given memory. Previous studies demonstrated that memory allocation is not random in the amygdala; these studies showed that amygdala neurons with higher levels of the cyclic-AMP-response-element-binding protein (CREB) are more likely to be recruited into encoding and storing fear memory. To determine whether specific mechanisms also regulate memory allocation in other brain regions and whether CREB also has a role in this process, we studied insular cortical memory representations for conditioned taste aversion (CTA). In this task, an animal learns to associate a taste (conditioned stimulus [CS]) with the experience of malaise (such as that induced by LiCl; unconditioned stimulus [US]). The insular cortex is required for CTA memory formation and retrieval. CTA learning activates a subpopulation of neurons in this structure, and the insular cortex and the basolateral amygdala (BLA) interact during CTA formation. Here, we used a combination of approaches, including viral vector transfections of insular cortex, arc fluorescence in situ hybridization (FISH), and designer receptors exclusively activated by designer drugs (DREADD) system, to show that CREB levels determine which insular cortical neurons go on to encode a given conditioned taste memory.

  11. Magnetoencephalographic signatures of insular epileptic spikes based on functional connectivity.

    PubMed

    Zerouali, Younes; Pouliot, Philippe; Robert, Manon; Mohamed, Ismail; Bouthillier, Alain; Lesage, Frédéric; Nguyen, Dang K

    2016-09-01

    Failure to recognize insular cortex seizures has recently been identified as a cause of epilepsy surgeries targeting the temporal, parietal, or frontal lobe. Such failures are partly due to the fact that current noninvasive localization techniques fare poorly in recognizing insular epileptic foci. Our group recently demonstrated that magnetoencephalography (MEG) is sensitive to epileptiform spikes generated by the insula. In this study, we assessed the potential of distributed source imaging and functional connectivity analyses to distinguish insular networks underlying the generation of spikes. Nineteen patients with operculo-insular epilepsy were investigated. Each patient underwent MEG as well as T1-weighted magnetic resonance imaging (MRI) as part of their standard presurgical evaluation. Cortical sources of MEG spikes were reconstructed with the maximum entropy on the mean algorithm, and their time courses served to analyze source functional connectivity. The results indicate that the anterior and posterior subregions of the insula have specific patterns of functional connectivity mainly involving frontal and parietal regions, respectively. In addition, while their connectivity patterns are qualitatively similar during rest and during spikes, couplings within these networks are much stronger during spikes. These results show that MEG can establish functional connectivity-based signatures that could help in the diagnosis of different subtypes of insular cortex epilepsy. Hum Brain Mapp 37:3250-3261, 2016. © 2016 Wiley Periodicals, Inc. PMID:27220112

  12. Localization of abnormal discharges causing insular epilepsy by magnetoencephalography.

    PubMed

    Park, Hyeon-Mi; Nakasato, Nobukazu; Tominaga, Teiji

    2012-01-01

    The insula, one of the five cerebral lobes of the brain, is located deep within the brain and lies mainly beneath the temporal lobe. Insular epilepsy can be easily confused and misdiagnosed as temporal lobe epilepsy (TLE) because of the similar clinical symptoms and scalp electroencephalography (EEG) findings due to the insula location and neuronal connections with the temporal lobe. Magnetoencephalography (MEG) has higher sensitivity and spatial resolution than scalp EEG, and thus can often identify epileptic discharges not revealed by scalp EEG. Simultaneous scalp EEG and MEG were performed to detect and localize epileptic discharges in two patients known to have insular epilepsy associated with cavernous angioma in the insula. Epileptic discharges were detected as abnormal spikes in the EEG and MEG findings. In Patient 1, the sources of all MEG spikes detected simultaneously by EEG and MEG (E/M-spikes) were localized in the anterior temporal lobe, similar to TLE. In contrast, the sources of all MEG spikes detected only by MEG (M-spikes) were adjacent to the insular lesion. In Patient 2, the sources of all MEG spikes detected simultaneously by EEG and MEG (E/M-spikes) were localized in the anterior temporal lobe. These findings indicate that MEG allows us to detect insular activity that is undetectable by scalp EEG. In conclusion, simultaneous EEG and MEG are helpful for detecting spikes and obtaining additional information about the epileptic origin and propagation in patients with insular epilepsy. PMID:22353789

  13. Forest fires in the insular Caribbean.

    PubMed

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

    2008-12-01

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

  14. Forest fires in the insular Caribbean.

    PubMed

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

    2008-12-01

    This paper presents a summary of the forest fire reports in the insular Caribbean derived from both management reports and an analysis of publicly available Moderate Resolution Imaging Spectrodiometer (MODIS) satellite active fire products from the region. A vast difference between the amount of fires reported by land managers and fire points in the MODIS Fire Information for Resource Management System data can be observed. Future research is recommended to better understand the nature of these differences. While there is a general lack of available statistical data on forest fires in the Caribbean, a few general observations can be made: Forest fires occur mainly in dry forest types (500 to 1000 mm of mean annual rainfall). These are also the areas where most human settlements are located. Lowland high forests and montane forests with higher rainfall (1000 and more mm y(-1)) are less susceptible to forest fire, but they can burn in exceptionally dry years. Most of the dry forest ecosystems in the Caribbean can be considered to be fire-sensitive ecosystems, while the pine forests in the Caribbean (Cuba, Dominican Republic, and the Bahamas) are maintained by wildfires. In fire-sensitive ecosystems, uncontrolled burning often encourages the spread of alien invasive species. A Caribbean Fire Management Cooperation Strategy was developed between 2005 and 2006 under auspices of the Food and Agriculture Organization of the United Nations. This regional strategy aims to strengthen Caribbean fire management networking by encouraging closer collaboration among countries with similar ecological conditions. The strategy for the Caribbean identifies a number of research, training, and management activities to improve wildfire management capacity in the Caribbean. PMID:19205174

  15. Role of the insular cortex in the modulation of baroreflex sensitivity.

    PubMed

    Saleh, T M; Connell, B J

    1998-05-01

    Cervical vagal stimulation for 2 h results in a depressed baroreflex sensitivity produced by an enhanced sympathetic output, as indicated by increased plasma norepinephrine levels. The current study examined the role of the insular cortex in modulating the vagal stimulation-induced changes in baroreflex sensitivity. Male Sprague-Dawley rats were anesthetized with thiobutabarbitol sodium and instrumented for recording blood pressure, heart rate, intravenous drug administration, and vagal afferent nerve stimulation. Stereotaxic microinjections (300 nl) of either 5% lidocaine or 0.9% saline were made bilaterally into the insula. Thirty minutes after 2 h of vagal stimulation, the baroreflex was significantly depressed and plasma norepinephrine levels were significantly elevated in both groups. The baroreflex was also significantly depressed after bilateral lidocaine injections into the insula, independent of vagal stimulation. However, no significant change in plasma norepinephrine was observed, suggesting that an attenuated parasympathetic output contributed to the altered baroreflex. Taken together, the results suggest that the insular cortex modulates the cardiac baroreflex through a modulation of parasympathetic output. PMID:9612410

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

    NASA Astrophysics Data System (ADS)

    Good, Cameron H.

    2013-05-01

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

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

    PubMed Central

    Zhao, Changjiu; Gammie, Stephen C.

    2014-01-01

    Dramatic structural and functional remodeling occurs in the postpartum brain for the establishment of maternal care, which is essential for the growth and development of young offspring. Glutamate and GABA signaling are critically important in modulating multiple behavioral performances. Large scale signaling changes occur in the postpartum brain, but it is still not clear to what extent the neurotransmitters glutamate and GABA change and whether the ratio of glutamate/GABA remains balanced. In this study, we examined the glutamate/GABA-glutamine cycle in the lateral septum (LS) of postpartum female mice. In postpartum females (relative to virgins), tissue levels of glutamate and GABA were elevated in LS and increased mRNA was found for the respective enzymes producing glutamate and GABA, glutaminase (Gls) and glutamate decarboxylase 1 and 2 (Gad1 and Gad2). The common precursor, glutamine, was elevated as was the enzyme that produces it, glutamate-ammonia ligase (Glul). Additionally, glutamate, GABA, and glutamine were positively correlated and the glutamate/GABA ratio was almost identical in the postpartum and virgin females. Collectively, these findings indicate that glutamate and GABA signaling are increased and that the ratio of glutamate/GABA is well balanced in the maternal LS. The postpartum brain may provide a useful model system for understanding how glutamate and GABA are linked despite large signaling changes. Given that some mental health disorders, including depression and schizophrenia display dysregulated glutamate/GABA ratio, and there is increased vulnerability to mental disorders in mothers, it is possible that these postpartum disorders emerge when glutamate and GABA changes are not properly coordinated. PMID:25451092

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

    PubMed

    Zhao, Changjiu; Gammie, Stephen C

    2014-12-01

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

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

    ERIC Educational Resources Information Center

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

    2005-01-01

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

  20. 24 CFR 35.940 - Special requirements for insular areas.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

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

  1. 24 CFR 35.940 - Special requirements for insular areas.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

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

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

    Code of Federal Regulations, 2013 CFR

    2013-04-01

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

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

    Code of Federal Regulations, 2010 CFR

    2010-04-01

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

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

    Code of Federal Regulations, 2011 CFR

    2011-04-01

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

  5. Second Surgery in Insular Low-Grade Gliomas

    PubMed Central

    Ius, Tamara; Pauletto, Giada; Cesselli, Daniela; Isola, Miriam; Turella, Luca; Budai, Riccardo; DeMaglio, Giovanna; Eleopra, Roberto; Fadiga, Luciano; Lettieri, Christian; Pizzolitto, Stefano; Beltrami, Carlo Alberto; Skrap, Miran

    2015-01-01

    Background. Given the technical difficulties, a limited number of works have been published on insular gliomas surgery and risk factors for tumor recurrence (TR) are poorly documented. Objective. The aim of the study was to determine TR in adult patients with initial diagnosis of insular Low-Grade Gliomas (LGGs) that subsequently underwent second surgery. Methods. A consecutive series of 53 patients with insular LGGs was retrospectively reviewed; 23 patients had two operations for TR. Results. At the time of second surgery, almost half of the patients had experienced progression into high-grade gliomas (HGGs). Univariate analysis showed that TR is influenced by the following: extent of resection (EOR) (P < 0.002), ΔVT2T1 value (P < 0.001), histological diagnosis of oligodendroglioma (P = 0.017), and mutation of IDH1 (P = 0.022). The multivariate analysis showed that EOR at first surgery was the independent predictor for TR (P < 0.001). Conclusions. In patients with insular LGG the EOR at first surgery represents the major predictive factor for TR. At time of TR, more than 50% of cases had progressed in HGG, raising the question of the oncological management after the first surgery. PMID:26539503

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

    ERIC Educational Resources Information Center

    Hansen, James

    2010-01-01

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

  7. 38 CFR 3.40 - Philippine and Insular Forces.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2010-07-01 2010-07-01 false Philippine and Insular Forces. 3.40 Section 3.40 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS ADJUDICATION Pension, Compensation, and Dependency and Indemnity Compensation General § 3.40 Philippine...

  8. 24 CFR 570.441 - Citizen participation-insular areas.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...) General. An insular area jurisdiction submitting an abbreviated consolidated plan under 24 CFR 91.235... jurisdiction submitting a complete consolidated plan in accordance with 24 CFR 91.200 through 91.230 shall... Development (Continued) OFFICE OF ASSISTANT SECRETARY FOR COMMUNITY PLANNING AND DEVELOPMENT, DEPARTMENT...

  9. 24 CFR 570.441 - Citizen participation-insular areas.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ...) General. An insular area jurisdiction submitting an abbreviated consolidated plan under 24 CFR 91.235... jurisdiction submitting a complete consolidated plan in accordance with 24 CFR 91.200 through 91.230 shall... Development (Continued) OFFICE OF ASSISTANT SECRETARY FOR COMMUNITY PLANNING AND DEVELOPMENT, DEPARTMENT...

  10. 24 CFR 570.442 - Reallocations-Insular Areas.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 24 Housing and Urban Development 3 2014-04-01 2013-04-01 true Reallocations-Insular Areas. 570.442 Section 570.442 Housing and Urban Development Regulations Relating to Housing and Urban Development (Continued) OFFICE OF ASSISTANT SECRETARY FOR COMMUNITY PLANNING AND DEVELOPMENT, DEPARTMENT OF HOUSING...

  11. 24 CFR 570.442 - Reallocations-Insular Areas.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 24 Housing and Urban Development 3 2012-04-01 2012-04-01 false Reallocations-Insular Areas. 570.442 Section 570.442 Housing and Urban Development Regulations Relating to Housing and Urban Development (Continued) OFFICE OF ASSISTANT SECRETARY FOR COMMUNITY PLANNING AND DEVELOPMENT, DEPARTMENT...

  12. 24 CFR 570.441 - Citizen participation-insular areas.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ...) General. An insular area jurisdiction submitting an abbreviated consolidated plan under 24 CFR 91.235... jurisdiction submitting a complete consolidated plan in accordance with 24 CFR 91.200 through 91.230 shall... Development (Continued) OFFICE OF ASSISTANT SECRETARY FOR COMMUNITY PLANNING AND DEVELOPMENT, DEPARTMENT...

  13. 24 CFR 570.442 - Reallocations-Insular Areas.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 24 Housing and Urban Development 3 2013-04-01 2013-04-01 false Reallocations-Insular Areas. 570.442 Section 570.442 Housing and Urban Development Regulations Relating to Housing and Urban Development (Continued) OFFICE OF ASSISTANT SECRETARY FOR COMMUNITY PLANNING AND DEVELOPMENT, DEPARTMENT...

  14. 24 CFR 570.442 - Reallocations-Insular Areas.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 24 Housing and Urban Development 3 2011-04-01 2010-04-01 true Reallocations-Insular Areas. 570.442 Section 570.442 Housing and Urban Development Regulations Relating to Housing and Urban Development... URBAN DEVELOPMENT COMMUNITY FACILITIES COMMUNITY DEVELOPMENT BLOCK GRANTS Small Cities,...

  15. 24 CFR 570.442 - Reallocations-Insular Areas.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 24 Housing and Urban Development 3 2010-04-01 2010-04-01 false Reallocations-Insular Areas. 570.442 Section 570.442 Housing and Urban Development Regulations Relating to Housing and Urban... HOUSING AND URBAN DEVELOPMENT COMMUNITY FACILITIES COMMUNITY DEVELOPMENT BLOCK GRANTS Small Cities,...

  16. Production of D-Glutamate from L-Glutamate with Glutamate Racemase and L-Glutamate Oxidase.

    PubMed

    Oikawa, T; Watanabe, M; Makiura, H; Kusakabe, H; Yamade, K; Soda, K

    1999-01-01

    We studied production of D-glutamate from L-glutamate using a bioreactor consisting of two columns of sequentially connected immobilized glutamate racemase (EC 5.1.1.3, from Bacillus subtilis IFO 3336) and L-glutamate oxidase (EC 1.4.3.11, from Streptomyces sp. X119-6): L-glutamate was racemized by the glutamate racemase column, and then L-glutamate was oxidized by the L-glutamate oxidase column. Consequently only D-glutamate remained, and was easily separated from the α-ketoglutarate formed by anion-exchange chromatography. Both enzymes were highly stabilized by immobilization. The pH and temperature optima of immobilized glutamate racemase (pH 8, 40°C) were similar to those of immobilized L-glutamate oxidase (pH 7, 50°C). Accordingly, we connected the two columns tandemly to do both enzyme reactions under the same conditions. Actually 4.5 μmol of D-glutamate was produced and isolated from 10 μmol of L-glutamate, about 90% of the theoretical yield. PMID:27373918

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

    PubMed

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

    2015-12-01

    Astrocytes take up glutamate in the synaptic area subsequent to glutamatergic transmission by the aid of high affinity glutamate transporters. Glutamate is converted to glutamine or metabolized to support intermediary metabolism and energy production. Glutamate dehydrogenase (GDH) and aspartate aminotransferase (AAT) catalyze the reversible reaction between glutamate and α-ketoglutarate, which is the initial step for glutamate to enter TCA cycle metabolism. In contrast to GDH, AAT requires a concomitant interconversion of oxaloacetate and aspartate. We have investigated the role of GDH in astrocyte glutamate and glucose metabolism employing siRNA mediated knock down (KD) of GDH in cultured astrocytes using stable and radioactive isotopes for metabolic mapping. An increased level of aspartate was observed upon exposure to [U-(13) C]glutamate in astrocytes exhibiting reduced GDH activity. (13) C Labeling of aspartate and TCA cycle intermediates confirmed that the increased amount of aspartate is associated with elevated TCA cycle flux from α-ketoglutarate to oxaloacetate, i.e. truncated TCA cycle. (13) C Glucose metabolism was elevated in GDH deficient astrocytes as observed by increased de novo synthesis of aspartate via pyruvate carboxylation. In the absence of glucose, lactate production from glutamate via malic enzyme was lower in GDH deficient astrocytes. In conclusions, our studies reveal that metabolism via GDH serves an important anaplerotic role by adding net carbon to the TCA cycle. A reduction in GDH activity seems to cause the astrocytes to up-regulate activity in pathways involved in maintaining the amount of TCA cycle intermediates such as pyruvate carboxylation as well as utilization of alternate substrates such as branched chain amino acids.

  18. Social information processing following resection of the insular cortex.

    PubMed

    Boucher, Olivier; Rouleau, Isabelle; Lassonde, Maryse; Lepore, Franco; Bouthillier, Alain; Nguyen, Dang K

    2015-05-01

    The insula has been implicated in social cognition and empathy in several neuroimaging paradigms. Impairments in social information processing, including specific deficits in disgust recognition, have been described following isolated insular damage, although the evidence remains limited to a few case studies. The present study examines social cognition and empathy in a group of fifteen patients for whom the insula was removed as part of their epilepsy surgery. These patients were compared to a lesion-control group of 15 epileptic patients who had a surgery in the anterior temporal lobe that spared the insula, and to 20 healthy volunteers matched on age, sex, and education. Participants were assessed on an Emotion Recognition Task (ERT), the Reading the Mind in the Eyes test, and a self-administered empathy questionnaire. Patients who underwent insular resection showed poorer ability to recognize facial expressions of emotions and had lower scores of perspective taking on the empathy questionnaire than healthy controls. Using results from healthy controls as normative data, emotion recognition deficits were more frequent in insular patients than in both other groups. Specific emotion analyses revealed impairments in fear recognition in both groups of patients, whereas happiness and surprise recognition was only impaired in patients with insular resection. There was no evidence for a deficit in disgust recognition. The findings suggest that unilateral damage to the operculo-insular region may be associated with subtle impairments in emotion recognition, and provide further clinical evidence of a role of the insula in empathic processes. However, the description of 15 consecutive cases of insula-damaged patients with no specific deficit in disgust recognition seriously challenges the assumptions, based on previous case reports, that the insula is specifically involved in disgust processing.

  19. Electrophysiological evidence for reciprocal insulo-insular connectivity of baroreceptor-related neurons.

    PubMed

    Zhang, Z; Oppenheimer, S M

    2000-04-28

    The recent indications of specialized lateralization of cardiovascular regulation within the right and left posterior insular cortex of the rat, suggest the possibility of transcallosal connectivity between these regions. This has not been previously demonstrated using physiological techniques. Extracellular neural recordings in 34 urethane anesthetized male Sprague-Dawley rats demonstrated reciprocal interinsular antidromic and orthodromic activation, elicited with similar median onset latencies (18 ms). The corresponding conduction velocity of these fibers (0.6 m/s) suggests that they may be unmyelinated. Many of the cells showing interhemispheric connectivity also responded to baroreceptor activation, further emphasizing the connectivity pattern in baroreceptor-related units. Both 1 and 25 Hz microstimulation of the contralateral insula indicated that the most frequent orthodromic response was inhibitory, either alone or as part of a biphasic pattern including activation. Chemical stimulation of the insula using L-glutamate was associated with both excitatory and inhibitory orthodromic activation of the contralateral posterior insula, confirming that the orthodromic electrical stimulation was not solely due to activation of fibers of passage. These data suggest that the two insulae may communicate with each other to integrate and balance cardiovascular function between hemispheres. PMID:10773190

  20. Neurons in and near insular cortex are responsive to muscular contraction and have sympathetic and/or cardiac-related discharge.

    PubMed

    Ichiyama, Ronaldo M; Waldrop, Tony G; Iwamoto, Gary A

    2004-05-22

    Insular cortex (IC) is recognized as a potential site for "central command" of cardiorespiratory responses during exercise. Muscular contraction (MC) decreased the discharge rate of most IC neurons. Activity of most contraction sensitive neurons was either not altered by elevating blood pressure or showed a response converse to that of MC. IC may thus have a role in central command but the area is clearly modulated by MC. PMID:15145765

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

    PubMed Central

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

    2013-01-01

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

  2. Delayed post-conditioning reduces post-ischemic glutamate level and improves protein synthesis in brain.

    PubMed

    Bonova, Petra; Burda, Jozef; Danielisova, Viera; Nemethova, Miroslava; Gottlieb, Miroslav

    2013-05-01

    In the clinic delayed post-conditioning would represent an attractive strategy for the survival of vulnerable neurons after an ischemic event. In this paper we studied the impact of ischemia and delayed post-conditioning on blood and brain tissue concentrations of glutamate and protein synthesis. We designed two groups of animals for analysis of brain tissues and blood after global ischemia and post-conditioning, and one for analysis of blood glutamate after transient focal ischemia. Our results showed elevated blood glutamate in two models of transient brain ischemia and decreases in blood glutamate to control in the first 20min of post-conditioning recirculation followed by a consecutive drop of about 20.5% on the first day. Similarly, we recorded reduced protein synthesis in hippocampus and cortex 2 and 3days after ischemia. However, increased glutamate was registered only in the hippocampus. Post-conditioning improves protein synthesis in CA1 and dentate gyrus and, surprisingly, leads to 50% reduction in glutamate in whole hippocampus and cortex. In conclusion, ischemia leads to meaningful elevation of blood and tissue glutamate. Post-conditioning activates mechanisms resulting in rapid elimination of glutamate from brain tissue and/or in the circulatory system that could otherwise impede brain-to-blood glutamate efflux mechanisms. Moreover, post-conditioning induces protein synthesis renewing in ischemia affected tissues that could also contribute to elimination of excitotoxicity. In addition, the potential of glutamate for monitoring the progress of ischemia and efficacy of therapy was shown.

  3. Reproducibility of Neurochemical Profile Quantification in Pregenual Cingulate, Anterior Midcingulate, and Bilateral Posterior Insular Subdivisions Measured at 3 Tesla

    PubMed Central

    de Matos, Nuno M. P.; Meier, Lukas; Wyss, Michael; Meier, Dieter; Gutzeit, Andreas; Ettlin, Dominik A.; Brügger, Mike

    2016-01-01

    The current report assessed measurement reproducibility of proton magnetic resonance spectroscopy at 3 Tesla in the left and right posterior insular, pregenual anterior cingulate, and anterior midcingulate cortices. Ten healthy male volunteers aged 21–30 years were tested at four different days, of which nine were included in the data analysis. Intra- and inter-subject variability of myo-inositol, creatine, glutamate, total-choline, total-N-acetylaspartate, and combined glutamine–glutamate were calculated considering the influence of movement parameters, age, daytime of measurements, and tissue composition. Overall mean intra-/inter-subject variability for all neurochemicals combined revealed small mean coefficients of variation across the four regions: 5.3/9.05% in anterior midcingulate, 6.6/8.84% in pregenual anterior cingulate, 7.3/10.00% in left posterior and 8.2/10.55% in right posterior insula. Head movement, tissue composition and day time revealed no significant explanatory variance contribution suggesting a negligible influence on the data. A strong correlation between Cramer–Rao Lower Bounds (a measure of fitting errors) and the mean intra-subject coefficients of variation (r = 0.799, p < 0.001) outlined the importance of low fitting errors in order to obtain robust and finally meaningful measurements. The present findings confirm proton magnetic resonance spectroscopy as a reliable tool to measure brain neurochemistry in small subregions of the human brain. PMID:27445745

  4. Reproducibility of Neurochemical Profile Quantification in Pregenual Cingulate, Anterior Midcingulate, and Bilateral Posterior Insular Subdivisions Measured at 3 Tesla.

    PubMed

    de Matos, Nuno M P; Meier, Lukas; Wyss, Michael; Meier, Dieter; Gutzeit, Andreas; Ettlin, Dominik A; Brügger, Mike

    2016-01-01

    The current report assessed measurement reproducibility of proton magnetic resonance spectroscopy at 3 Tesla in the left and right posterior insular, pregenual anterior cingulate, and anterior midcingulate cortices. Ten healthy male volunteers aged 21-30 years were tested at four different days, of which nine were included in the data analysis. Intra- and inter-subject variability of myo-inositol, creatine, glutamate, total-choline, total-N-acetylaspartate, and combined glutamine-glutamate were calculated considering the influence of movement parameters, age, daytime of measurements, and tissue composition. Overall mean intra-/inter-subject variability for all neurochemicals combined revealed small mean coefficients of variation across the four regions: 5.3/9.05% in anterior midcingulate, 6.6/8.84% in pregenual anterior cingulate, 7.3/10.00% in left posterior and 8.2/10.55% in right posterior insula. Head movement, tissue composition and day time revealed no significant explanatory variance contribution suggesting a negligible influence on the data. A strong correlation between Cramer-Rao Lower Bounds (a measure of fitting errors) and the mean intra-subject coefficients of variation (r = 0.799, p < 0.001) outlined the importance of low fitting errors in order to obtain robust and finally meaningful measurements. The present findings confirm proton magnetic resonance spectroscopy as a reliable tool to measure brain neurochemistry in small subregions of the human brain. PMID:27445745

  5. Indocyanine green as an adjunct for resection of insular gliomas

    PubMed Central

    Shah, Abhidha; Rangarajan, Vithal; Kaswa, Amol; Jain, Sonal; Goel, Atul

    2016-01-01

    Objective: Many controversies exist regarding the extent of resection for insular gliomas and the timing of resection. Several techniques and adjuncts are used to maximize safety during resection of these tumors. We describe the use of indocyanine green (ICG) to identify the branches of the middle cerebral artery and discuss its utility to increase safety for resection for insular gliomas. Materials and Methods: Five patients with insular gliomas were surgically treated by the authors from June 2013 to June 2014. The patients presented with complaints of either a headache or recurring episodes of convulsions. All the patients were operated with the aid of neuronavigation and tractography. The long perforating branches of the middle cerebral artery course through the insula and pass onward to supply the corona radiata. It is essential to preserve these vessels to prevent postoperative neurological deficits. ICG (Aurogreen) was used to identify and preserve the long perforating arteries of the middle cerebral artery. Results: ICG dye correctly identified the long perforating branches of the middle cerebral artery and easily distinguished these vessels from the short perforating branches. All the branches of the middle cerebral artery that coursed through the tumor and had an onward course were preserved in all the patients. Only one patient developed a transient right sided hemiparesis that had improved at follow-up. Conclusions: Surgery for insular gliomas is challenging due to its location adjacent to eloquent areas, important white fiber tracts and the course of the middle cerebral artery within it. ICG is useful to identify and preserve the long perforating branches of the middle cerebral artery that course through the tumor and traverse onward to supply the corona radiata. PMID:27366256

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

    PubMed

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

    2015-09-01

    In the Gram-positive bacterium, Bacillus subtilis glutamate is synthesized by the glutamine synthetase and the glutamate synthase (GOGAT). During growth with carbon sources that exert carbon catabolite repression, the rocG glutamate dehydrogenase (GDH) gene is repressed and the transcription factor GltC activates the expression of the GOGAT encoding gltAB genes. In the presence of amino acids of the glutamate family, the GDH RocG is synthesized and the enzyme prevents GltC from binding to DNA. The dual control of glutamate biosynthesis allows the efficient utilization of the available nutrients. Here we provide genetic and biochemical evidence that, like RocG, also the paralogous GDH GudB can inhibit the transcription factor GltC, thereby controlling glutamate biosynthesis. Contradictory previous observations show that high level of GDH activity does not result in permanent inhibition of GltC. By controlling the intracellular levels of glutamate through feeding with exogenous arginine, we observed that the GDH-dependent control of GltC and thus expression of the gltAB genes inversely correlates with the glutamate pool. These results suggest that the B. subtilis GDHs RocG and GudB in fact act as glutamate sensors. In conclusion, the GDH-mediated control of glutamate biosynthesis seems to depend on the intracellular glutamate concentration. PMID:25711804

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

    PubMed

    Narkiewicz, O; Mamos, L

    1990-01-01

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

  8. Insular Volume Reduction in Patients with Social Anxiety Disorder

    PubMed Central

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

    2016-01-01

    Despite the fact that social anxiety disorder (SAD) is highly prevalent, there have been only a few structural imaging studies. Moreover, most of them reported about a volume reduction in amygdale, which plays a key role in the neural function of SAD. Insula is another region of interest. Its hyperactivity in regard to processing negative emotional information or interoceptive awareness has been detected in patients with SAD. Referring to these studies, we hypothesized that insular volumes might reduce in patients with SAD and made a comparison of insular volumes between 13 patients with SAD and 18 healthy controls with matched age and gender using voxel-based morphometry. As a result, we found a significant volume reduction in insula in the SAD group. Our results suggest that the patients with SAD might have an insular volume reduction apart from amygdala. Since insula plays a critical role in the pathology of SAD, more attention should be paid not only to functional study but also morphometrical study of insula. PMID:26834652

  9. Metabotropic Glutamate Receptor Dependent Cortical Plasticity in Chronic Pain.

    PubMed

    Koga, Kohei; Li, Shermaine; Zhuo, Min

    2016-01-01

    Many cortical areas play crucial roles in higher order brain functions such as pain and emotion-processing, decision-making, and cognition. Among them, anterior cingulate cortex (ACC) and insular cortex (IC) are two key areas. Glutamate mediates major excitatory transmission during long-term plasticity in both physiological and pathological conditions. Specifically related to nociceptive or pain behaviors, metabotropic glutamate subtype receptors (mGluRs) have been involved in different types of synaptic modulation and plasticity from periphery to the spinal cord. However, less is known about their functional roles in plasticity related to pain and its related behaviors within cortical regions. In this review, we first summarized previous studies of synaptic plasticity in both the ACC and IC, and discussed how mGluRs may be involved in both cortical long-term potentiation (LTP) and long-term depression (LTD)-especially in LTD. The activation of mGluRs contributes to the induction of LTD in both ACC and IC areas. The loss of LTD caused by peripheral amputation or nerve injury can be rescued by priming ACC or IC with activations of mGluR1 receptors. We also discussed the potential functional roles of mGluRs for pain-related behaviors. We propose that targeting mGluRs in the cortical areas including the ACC and IC may provide a new therapeutic strategy for the treatment of chronic pain, phantom pain or anxiety. PMID:27296638

  10. Glutamate and tumor-associated epilepsy: glial cell dysfunction in the peritumoral environment

    PubMed Central

    Buckingham, Susan C.; Robel, Stefanie

    2013-01-01

    Seizures are a serious and debilitating co-morbidity of primary brain tumors that affect most patients, yet their etiology is poorly understood. In many CNS pathologies, including epilepsy and brain injury, high levels of extracellular glutamate have been implicated in seizure generation. It has been shown that gliomas release neurotoxic levels of glutamate through their high expression of system xc-. More recently it was shown that the surrounding peritumoral cortex is spontaneously hyperexcitable. In this review, we discuss how gliomas induce changes in the surrounding environment that may further contribute to elevated extracellular glutamate and tumor-associated seizures. Peritumoral astrocytes become reactive and lose their ability to remove glutamate, while microglia, in response to signals from glioma cells, may release glutamate. In addition, gliomas increase blood brain barrier permeability, allowing seizure-inducing serum components, including glutamate, into the peritumoral region. These factors, working together or alone, may influence the frequency and severity of tumor-associated epilepsy. PMID:23385090

  11. 4-Hydroxyhexenal (HHE) impairs glutamate transport in astrocyte cultures.

    PubMed

    Lovell, Mark A; Bradley, Melissa A; Fister, Shuling X

    2012-01-01

    Multiple studies show elevations of α,β-unsaturated aldehydic by-products of lipid peroxidation including 4-hydroxynonenal and acrolein in vulnerable brain regions of subjects throughout the progression of Alzheimer's disease (AD). More recently 4-hydroxyhexenal (HHE), a diffusible α,β-unsaturated aldehyde resulting from peroxidation of ω-3 polyunsaturated fatty acids, was shown to be elevated in the hippocampus/parahippocampal gyrus (HPG) of subjects with preclinical AD (PCAD) and in late stage AD (LAD). HHE treatment of primary rat cortical neuron cultures led to a time- and concentration-dependent decrease in survival and glucose uptake. To determine if HHE also impairs glutamate uptake, primary rat astrocyte cultures were exposed to HHE for 4 hours and glutamate transport measured. Results show subtoxic (2.5 μM) HHE concentrations significantly (p < 0.05) impair glutamate uptake in primary astrocytes. Immunoprecipitation of excitatory amino acid transporter-2 (EAAT-2), the primary glutamate transporter in brain, from normal control, mild cognitive impairment (MCI), PCAD, and LAD HPG followed by quantification of HHE immunolabeling showed a significant increase in HHE positive EAAT-2 in MCI and LAD HPG. Together these data suggest HHE can significantly impair glutamate uptake and may play a role in the pathogenesis of AD. PMID:22766736

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

    PubMed Central

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

    2016-01-01

    Glutamate is not only a neurotransmitter but also an important neurotoxin in central nervous system (CNS). Chronic elevation of glutamate induces both neuronal and glial cell apoptosis. However, its effect on astrocytes is complex and still remains unclear. In this study, we investigated whether morphine, a common opioid ligand, could affect glutamate-induced apoptosis in astrocytes. Primary cultured astrocytes were incubated with glutamate in the presence/absence of morphine. It was found that morphine could reduce glutamate-induced apoptosis of astrocytes. Furthermore, glutamate activated Ca2+ release, thereby inducing endoplasmic reticulum (ER) stress in astrocytes, while morphine attenuated this deleterious effect. Using siRNA to reduce the expression of κ-opioid receptor, morphine could not effectively inhibit glutamate-stimulated Ca2+ release in astrocytes, the protective effect of morphine on glutamate-injured astrocytes was also suppressed. These results suggested that morphine could protect astrocytes from glutamate-induced apoptosis via reducing Ca2+ overload and ER stress pathways. In conclusion, this study indicated that excitotoxicity participated in the glutamate mediated apoptosis in astrocytes, while morphine attenuated this deleterious effect via regulating Ca2+ release and ER stress. PMID:27783050

  13. Insular avian adaptations on two Neotropical continental islands

    PubMed Central

    Wright, Natalie A.; Steadman, David W.

    2012-01-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

    Ruthirago, Doungporn; DeToledo, John C.

    2016-01-01

    The posterior insular cortex—a complex structure interconnecting various brain regions for different functions—is a rare location for ischemic stroke. We report a patient with isolated left posterior insular infarction who presented with multiple cognitive impairment, including impairment in semantic and phonemic verbal fluency. PMID:27365876

  16. 19 CFR 191.5 - Guantanamo Bay, insular possessions, trust territories.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 19 Customs Duties 2 2011-04-01 2011-04-01 false Guantanamo Bay, insular possessions, trust... SECURITY; DEPARTMENT OF THE TREASURY (CONTINUED) DRAWBACK General Provisions § 191.5 Guantanamo Bay, insular possessions, trust territories. Guantanamo Bay Naval Station shall be considered foreign...

  17. 19 CFR 191.5 - Guantanamo Bay, insular possessions, trust territories.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 19 Customs Duties 2 2010-04-01 2010-04-01 false Guantanamo Bay, insular possessions, trust... SECURITY; DEPARTMENT OF THE TREASURY (CONTINUED) DRAWBACK General Provisions § 191.5 Guantanamo Bay, insular possessions, trust territories. Guantanamo Bay Naval Station shall be considered foreign...

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

    PubMed

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

    2013-03-01

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

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

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... handling of certificates and the transfer of entitlements as contained in 15 CFR part 303. ... 19 Customs Duties 1 2013-04-01 2013-04-01 false Watches and watch movements from U.S. insular... STATION § 7.4 Watches and watch movements from U.S. insular possessions. (a) The issuance of...

  20. 19 CFR 7.4 - Watches and watch movements from U.S. insular possessions.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... handling of certificates and the transfer of entitlements as contained in 15 CFR part 303. ... 19 Customs Duties 1 2012-04-01 2012-04-01 false Watches and watch movements from U.S. insular... STATION § 7.4 Watches and watch movements from U.S. insular possessions. (a) The issuance of...

  1. 19 CFR 7.4 - Watches and watch movements from U.S. insular possessions.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... handling of certificates and the transfer of entitlements as contained in 15 CFR part 303. ... 19 Customs Duties 1 2010-04-01 2010-04-01 false Watches and watch movements from U.S. insular... STATION § 7.4 Watches and watch movements from U.S. insular possessions. (a) The issuance of...

  2. 19 CFR 7.4 - Watches and watch movements from U.S. insular possessions.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... handling of certificates and the transfer of entitlements as contained in 15 CFR part 303. ... 19 Customs Duties 1 2014-04-01 2014-04-01 false Watches and watch movements from U.S. insular... STATION § 7.4 Watches and watch movements from U.S. insular possessions. (a) The issuance of...

  3. 19 CFR 7.4 - Watches and watch movements from U.S. insular possessions.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... handling of certificates and the transfer of entitlements as contained in 15 CFR part 303. ... 19 Customs Duties 1 2011-04-01 2011-04-01 false Watches and watch movements from U.S. insular... STATION § 7.4 Watches and watch movements from U.S. insular possessions. (a) The issuance of...

  4. [Insular carcinoma of the thyroid. An uncommon but aggressive neoplasm].

    PubMed

    Naranjo-Gómez, José Manuel; Folqué-Gómez, Emilio; Moreno-Mata, Nicolás; Moldes-Rodríguez, Milagros; Martínez-Martínez, Patricia; González-Aragoneses, Federico; Orusco-Palomino, Eduardo

    2005-04-01

    Insular carcinoma of the thyroid is an infrequent entity, named in 1984 by Carcangiu when he described its characteristic histology. Clinically and morphologically it is considered to be in an intermediate position between well-differentiated carcinoma of the thyroid (papillary or follicular) and undifferentiated or anaplastic carcinoma of the thyroid. However, most authors believe it to be an independent entity. The prognosis of this tumor is worse than that of classic carcinoma of the thyroid, and most authors advise aggressive therapy, which in some cases can achieved prolonged survival. We describe 2 patients who experienced recurrence after treatment for the primary tumor. The recurrences were treated but the clinical courses differed.

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

    PubMed Central

    Kodama, Tohru; Siegel, Jerome M.

    2014-01-01

    Histamine neurons are active during waking and largely inactive during sleep, with minimal activity during rapid-eye movement (REM) sleep. Caffeine, the most widely used stimulant, causes a significant increase of sleep onset latency in rats and humans. We hypothesized that caffeine increases glutamate release in the posterior hypothalamus (PH) and produces increased activity of wake-active histamine neurons. Using in vivo microdialysis, we collected samples from the PH after caffeine administration in freely behaving rats. HPLC analysis and biosensor measurements showed a significant increase in glutamate levels beginning 30 min after caffeine administration. Glutamate levels remained elevated for at least 140 min. GABA levels did not significantly change over the same time period. Histamine level significantly increased beginning 30 min after caffeine administration and remained elevated for at least 140 min. Immunostaining showed a significantly elevated number of c-Fos-labeled histamine neurons in caffeine-treated rats compared with saline-treated animals. We conclude that increased glutamate levels in the PH activate histamine neurons and contribute to caffeine-induced waking and alertness. PMID:25031227

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

    PubMed

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

    2016-02-10

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

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

    PubMed

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

    2016-02-10

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

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

    PubMed

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

    2016-01-01

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

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

    PubMed

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

    2016-01-01

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

  10. Magnesium Sulfate Protects Against the Bioenergetic Consequences of Chronic Glutamate Receptor Stimulation

    PubMed Central

    Clerc, Pascaline; Young, Christina A.; Bordt, Evan A.; Grigore, Alina M.; Fiskum, Gary; Polster, Brian M.

    2013-01-01

    Extracellular glutamate is elevated following brain ischemia or trauma and contributes to neuronal injury. We tested the hypothesis that magnesium sulfate (MgSO4, 3 mM) protects against metabolic failure caused by excitotoxic glutamate exposure. Rat cortical neuron preparations treated in medium already containing a physiological concentration of Mg2+ (1 mM) could be segregated based on their response to glutamate (100 µM). Type I preparations responded with a decrease or small transient increase in oxygen consumption rate (OCR). Type II neurons responded with >50% stimulation in OCR, indicating a robust response to increased energy demand without immediate toxicity. Pre-treatment with MgSO4 improved the initial bioenergetic response to glutamate and ameliorated subsequent loss of spare respiratory capacity, measured following addition of the uncoupler FCCP, in Type I but not Type II neurons. Spare respiratory capacity in Type I neurons was also improved by incubation with MgSO4 or NMDA receptor antagonist MK801 in the absence of glutamate treatment. This finding indicates that the major difference between Type I and Type II preparations is the amount of endogenous glutamate receptor activity. Incubation of Type II neurons with 5 µM glutamate prior to excitotoxic (100 µM) glutamate exposure recapitulated a Type I phenotype. MgSO4 protected against an excitotoxic glutamate-induced drop in neuronal ATP both with and without prior 5 µM glutamate exposure. Results indicate that MgSO4 protects against chronic moderate glutamate receptor stimulation and preserves cellular ATP following treatment with excitotoxic glutamate. PMID:24236167

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

    PubMed

    Wang, Zhong-Feng; Yang, Xiong-Li

    2016-08-25

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

  12. Altered pain and thermal sensation in subjects with isolated parietal and insular cortical lesions

    PubMed Central

    Veldhuijzen, D.S.; Greenspan, J.D; Kim, J.H.; Lenz, F.A.

    2009-01-01

    Studies of sensory function following cortical lesions have often included lesions which multiple cortical, white matter, and thalamic structures. We now test the hypothesis that lesions anatomically constrained to particular insular and parietal structures and their subjacent white matter are associated with different patterns of sensory loss. Sensory loss was measured by quantitative sensory testing (QST), and evaluated statistically with respect to normal values. All seven subjects with insular and/or parietal lesions demonstrated thermal hypoesthesia, although the etiology of the lesions was heterogeneous. Cold and heat hypoalgesia were only found in the subject with the most extensive parietal and insular lesion, which occurred in utero. Cold allodynia occurred clinically and by thresholds in two subjects with isolated ischemic lesions of the posterior insular/ retroinsular cortex, and by thresholds in two subjects with a lesion of parietal cortex with little or no insular involvement. Central pain occurred in the two subjects with clinical allodynia secondary to isolated lesions of the posterior insular/retroinsular cortex, which spared the anterior and posterior parietal cortex. These results suggest that nonpainful cold and heat sensations are jointly mediated by parietal and insular cortical structures so that lesions anywhere in this system may diminish sensitivity. In contrast, thermal pain is more robust requiring larger cortical lesions of these same structures to produce hypoalgesia. In addition, cold allodynia can result from restricted lesions that also produce thermal hypoesthesia, but not from all such lesions. PMID:19939715

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

    PubMed

    Anderson, Robert P; Handley, Charles O

    2002-05-01

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

  14. The association of insular stroke with lesion volume.

    PubMed

    Kodumuri, Nishanth; Sebastian, Rajani; Davis, Cameron; Posner, Joseph; Kim, Eun Hye; Tippett, Donna C; Wright, Amy; Hillis, Argye E

    2016-01-01

    The insula has been implicated in many sequelae of stroke. It is the area most commonly infarcted in people with post-stroke arrhythmias, loss of thermal sensation, hospital acquired pneumonia, and apraxia of speech. We hypothesized that some of these results reflect the fact that: (1) ischemic strokes that involve the insula are larger than strokes that exclude the insula (and therefore are associated with more common and persistent deficits); and (2) insular involvement is a marker of middle cerebral artery (MCA) occlusion. We analyzed MRI scans of 861 patients with acute ischemic hemispheric strokes unselected for functional deficits, and compared infarcts involving the insula to infarcts not involving the insula using t-tests for continuous variables and chi square tests for dichotomous variables. Mean infarct volume was larger for infarcts including the insula (n = 232) versus excluding the insula (n = 629): 65.8 ± 78.8 versus 10.2 ± 15.9 cm(3) (p < 0.00001). Even when we removed lacunar infarcts, mean volume of non-lacunar infarcts that included insula (n = 775) were larger than non-lacunar infarcts (n = 227) that excluded insula: 67.0 cm(3) ± 79.2 versus 11.5 cm(3) ± 16.7 (p < 0.00001). Of infarcts in the 90th percentile for volume, 87% included the insula (χ(2) = 181.8; p < 0.00001). Furthermore, 79.0% infarcts due to MCA occlusion included the insula; 78.5% of infarcts without MCA occlusion excluded the insula (χ(2) = 93.1; p < 0.0001). The association between insular damage and acute or chronic sequelae likely often reflects the fact that insular infarct is a marker of large infarcts caused by occlusion of the MCA more than a specific role of the insula in a range of functions. Particularly in acute stroke, some deficits may also be due to ischemia of the MCA or ICA territory caused by large vessel occlusion. PMID:26909326

  15. Glutamic acid as anticancer agent: An overview.

    PubMed

    Dutta, Satyajit; Ray, Supratim; Nagarajan, K

    2013-10-01

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

  16. Computational Studies of Glutamate Transporters

    PubMed Central

    Setiadi, Jeffry; Heinzelmann, Germano; Kuyucak, Serdar

    2015-01-01

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

  17. Bicyclic glutamic acid derivatives.

    PubMed

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

    2006-05-15

    For the second-generation asymmetric synthesis of the trans-tris(homoglutamic) acids via Strecker reaction of chiral ketimines, the cyanide addition as the key stereodifferentiating step produces mixtures of diastereomeric alpha-amino nitrile esters the composition of which is independent of the reaction temperature and the type of the solvent, respectively. The subsequent hydrolysis is exclusively achieved with concentrated H(2)SO(4) yielding diastereomeric mixtures of three secondary alpha-amino alpha-carbamoyl-gamma-esters and two diastereomeric cis-fused angular alpha-carbamoyl gamma-lactams as bicyclic glutamic acid derivatives, gained from in situ stereomer differentiating cyclisation of the secondary cis-alpha-amino alpha-carbamoyl-gamma-esters. Separation was achieved by CC. The pure secondary trans-alpha-amino alpha-carbamoyl-gamma-esters cyclise on heating and treatment with concentrated H(2)SO(4), respectively, to diastereomeric cis-fused angular secondary alpha-amino imides. Their hydrogenolysis led to the enantiomeric cis-fused angular primary alpha-amino imides. The configuration of all compounds was completely established by NMR methods, CD-spectra, and by X-ray analyses of the (alphaR,1R,5R)-1-carbamoyl-2-(1-phenylethyl)-2-azabicyclo[3.3.0]octan-3-one and of the trans-alphaS,1S,2R-2-ethoxycarbonylmethyl-1-(1-phenylethylamino)cyclopentanecarboxamide. PMID:16596563

  18. Reduced insular volume in attention deficit hyperactivity disorder

    PubMed Central

    Lopez-Larson, Melissa Patricia; King, Jace Bradford; Terry, Janine; McGlade, Erin Catherine; Yurgelun-Todd, Deborah

    2014-01-01

    The aim of this study was to evaluate whether structural differences in the insula and anterior cingulate (ACC), two critical areas of the “salience network,” co-exist in adolescents with ADHD compared to healthy controls (HC). In addition we aimed to determine if structural changes within these regions correlate with attention and inhibitory function. Nineteen adolescents with ADHD and 25 HC received MRI scans on a 3T magnet. Morphometric analysis was performed with FreeSurfer. Youths with ADHD were found to have a bilateral reduction in anterior insular (AIC) gray matter volumes compared to HC. Furthermore, the left AIC was found to positively correlate with oppositional symptoms, while the right AIC was found to associate with both attention problems and inhibition. To our knowledge this is the first report of a bilateral reduction in AIC volumes in ADHD. Our findings suggest a role for the insula in modulating attention and inhibitory capacity in ADHD. PMID:23142193

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

    PubMed

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

    2015-03-01

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

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

    PubMed Central

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

    2011-01-01

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

  1. Role of the insular cortex in taste familiarity.

    PubMed

    Moraga-Amaro, Rodrigo; Cortés-Rojas, Andrés; Simon, Felipe; Stehberg, Jimmy

    2014-03-01

    Determining the role of the main gustatory cortical area within the insular cortex (IC), in conditioned taste aversion (CTA) has been elusive due to effective compensatory mechanisms that allow animals to learn in spite of lacking IC. IC lesions performed before CTA training induces mild if any memory impairments, while IC lesions done weeks after CTA produce amnesia. IC lesions before taste presentation have also been shown not to affect taste familiarity learning (attenuation of neophobia). This lack of effect could be either explained by compensation from other brain areas or by a lack of involvement of the IC in taste familiarity. To assess this issue, rats were bilaterally IC lesioned with ibotenic acid (200-300 nl.; 15 mg/ml) one week before or after taste familiarity, using either a preferred (0.1%) or a non-preferred (0.5%) saccharin solution. Rats lesioned before familiarity showed a decrease in neophobia to both solutions but no difference in their familiarity curve or their slope. When animals were familiarized and then IC lesioned, both IC lesioned groups treated the solutions as familiar, showing no differences from sham animals in their retention of familiarity. However, both lesioned groups showed increased latent inhibition (or impaired CTA) when CTA trained after repeated pre-exposures. The role of the IC in familiarity was also assessed using temporary inactivation of the IC, using bilateral micro-infusions of sodium channel blocker bupivacaine before each of 3 saccharin daily presentations. Intra-insular bupivacaine had no effects on familiarity acquisition, but did impair CTA learning in a different group of rats micro-infused before saccharin presentation in a CTA training protocol. Our data indicate that the IC is not essentially involved in acquisition or retention of taste familiarity, suggesting regional dissociation of areas involved in CTA and taste familiarity.

  2. Mesophotic communities of the insular shelf at Tutuila, American Samoa

    NASA Astrophysics Data System (ADS)

    Bare, A. Y.; Grimshaw, K. L.; Rooney, J. J.; Sabater, M. G.; Fenner, D.; Carroll, B.

    2010-06-01

    An investigation into the insular shelf and submerged banks surrounding Tutuila, American Samoa, was conducted using a towed camera system. Surveys confirmed the presence of zooxanthellate scleractinian coral communities at mesophotic depths (30-110 m). Quantification of video data, separated into 10-m-depth intervals, yielded a vertical, landward-to-seaward and horizontal distribution of benthic assemblages. Hard substrata composed a majority of bottom cover in shallow water, whereas unconsolidated sediments dominated the deep insular shelf and outer reef slopes. Scleractinian coral cover was highest atop mid-shelf patch reefs and on the submerged bank tops in depths of 30-50 m. Macroalgal cover was highest near shore and on reef slopes approaching the bank tops at 50-60 m. Percent cover of scleractinian coral colony morphology revealed a number of trends. Encrusting corals belonging to the genus Montipora were most abundant at shallow depths with cover gradually decreasing as depth increased. Massive corals, such as Porites spp., displayed a similar trend. Percent cover values of plate-like corals formed a normal distribution, with the highest cover observed in the 60-70 m depth range. Shallow plate-like corals belonged mostly to the genus Acropora and appeared to be significantly prevalent on the northeastern and eastern banks. Deeper plate-like corals on the reef slopes were dominated by Leptoseris, Pachyseris, or Montipora genera. Branching coral cover was high in the 80-110 m depth range. Columnar and free-living corals were also occasionally observed from 40-70 m.

  3. Heroin self-administration experience establishes control of ventral tegmental glutamate release by stress and environmental stimuli.

    PubMed

    Wang, Bin; You, Zhi-Bing; Wise, Roy A

    2012-12-01

    Heroin and cocaine have very different unconditioned receptor-mediated actions; however, in the brain circuitry of drug-reward and motivation, the two drugs establish common conditioned consequences. A single experience with either drug can change the sensitivity of ventral tegmental area (VTA) dopamine neurons to glutamatergic input. In the case of cocaine, repeated intravenous self-administration establishes de novo VTA glutamate release and dopaminergic activation in response to conditioned stimuli and mild footshock stress. Here we determined whether repeated self-administration of heroin would establish similar glutamate release and dopaminergic activation. Although self-administration of heroin itself did not cause VTA glutamate release, conditioned glutamate release was seen when rats expecting rewarding heroin were given nonrewarding saline in its place. Mild footshock stress also caused glutamate release in heroin-trained animals. In each case, the VTA glutamate release was accompanied by elevations in VTA dopamine levels, indicative of dopaminergic activation. In each case, infusion of the ionotropic glutamate antagonist kynurenic acid blocked the VTA dopamine release associated with VTA glutamate elevation. Although glutamate levels in the extinction and reinstatement tests were similar to those reported in cocaine studies, the effects of heroin self-administration itself were quite different from what has been seen during cocaine self-administration.

  4. 34 CFR 76.131 - How does an insular area apply for a consolidated grant?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... the Insular Area will use the funds received under the consolidated grant during the fiscal year for... consolidation of funds; and (4) Contains a budget that includes a description of the allocation of...

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

    PubMed Central

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

    2015-01-01

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

  6. Levetiracetam inhibits oligomeric Aβ-induced glutamate release from human astrocytes.

    PubMed

    Sanz-Blasco, Sara; Piña-Crespo, Juan C; Zhang, Xiaofei; McKercher, Scott R; Lipton, Stuart A

    2016-06-15

    A recently identified mechanism for oligomeric Aβ-induced glutamate release from astrocytes involves intracellular Ca elevation, potentially by Ca-dependent vesicular release. Evidence suggests that levetiracetam (LEV; Keppra), an antiepileptic drug, can improve cognitive performance in both humans with mild cognitive impairment and animal models of Alzheimer disease. Because LEV acts by modulating neurotransmitter release from neurons by interaction with synaptic vesicles, we tested the effect of LEV on Aβ-induced astrocytic release of glutamate. We used a fluorescence resonance energy transfer-based glutamate sensor (termed SuperGluSnFR), whose structure is based on the ligand-binding site of glutamate receptors, to monitor glutamate release from primary cultures of human astrocytes exposed to oligomeric amyloid-β peptide 1-42 (Aβ42). We found that LEV (10 µM) inhibited oligomeric Aβ-induced astrocytic glutamate release. In addition, we show that this Aβ-induced glutamate release from astrocytes is sensitive to tetanus neurotoxin, an inhibitor of the vesicle release machinery. Taken together, our evidence suggests that LEV inhibits Aβ-induced vesicular glutamate release from astrocytes and thus may underlie, at least in part, the ability of LEV to reduce hyperexcitability in Alzheimer disease. PMID:27183239

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

    NASA Astrophysics Data System (ADS)

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

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

  8. Altered Functional Connectivity Patterns of the Insular Subregions in Psychogenic Nonepileptic Seizures.

    PubMed

    Li, Rong; Liu, Kai; Ma, Xujing; Li, Zhiqiang; Duan, Xujun; An, Dongmei; Gong, Qiyong; Zhou, Dong; Chen, Huafu

    2015-07-01

    Neuroimaging studies have demonstrated that psychogenic nonepileptic seizures (PNES) are characterized by unstable cognitive-emotional and motor system, which is engaged in hyperactivity of limbic regions and sensorimotor area. The insula, which is a part of the limbic system, includes various subregions with some distinct connectivity patterns separately. However, whether these insular subregions show different connectivity patterns respectively in PNES remains largely unknown. We aimed to investigate the functional connectivity (FC) of insular subregions in PNES and extend the understanding of the complex pathophysiological mechanisms of this disease. A resting-state FC based on the insular subregions were conducted in 18 patients and 20 healthy controls. We examined the differences in FC values between PNES patients and controls using two sample t test. Our results showed patients had significantly stronger FC between insular subregions and sensorimotor network, lingual gyrus, superior parietal gyrus and putamen, which suggested a hyperlink pattern of insular subregions involved in abnormal emotion regulation, cognitive processes and motor function in PNES. Pearson correlation analysis between the mean FC values within abnormal regions and the frequency of PNES further indicated PNES exhibited abnormal functional organization whose stressful emotion of patients have great direct influence on their motor functions. The differentially impaired functional connectivity patterns of insular subregions might provide new insights into the complex neurological mechanism of PNES.

  9. Insular carcinoma: a distinct de novo entity among follicular carcinomas of the thyroid gland.

    PubMed

    Pilotti, S; Collini, P; Mariani, L; Placucci, M; Bongarzone, I; Vigneri, P; Cipriani, S; Falcetta, F; Miceli, R; Pierotti, M A; Rilke, F

    1997-12-01

    We reclassified 720 nonmedullary invasive thyroid carcinomas diagnosed and treated between 1975 and 1993. Twenty-seven cases met the criteria of insular carcinoma and 29 cases those of widely invasive follicular carcinoma. Comparison of these histotypes with respect to pathologic stage and overall, relative, and visceral metastasis-free survival showed a significant association between histotype and pT and pN categories. In particular, pT4 (p < 0.001) and pN1 (p < 0.001) categories were more frequent in the insular carcinoma histotype. By contrast, no significant differences in overall, relative, or visceral metastasis-free survival were observed between insular carcinoma and widely invasive follicular carcinoma. Molecular analysis by polymerase chain reaction-single-strand conformation polymorphism demonstrated RAS gene family point mutations in five of eight cases analyzed in each of the two histotypes, with a high proportion of CAA-->AAA transversion at codon 61 of the N-RAS gene in insular carcinoma. These findings suggest that insular carcinoma represents a de novo entity distinct from widely invasive follicular carcinoma, that widely invasive follicular carcinoma has biologic characteristics more consistent with poorly differentiated than well-differentiated carcinomas, and that both insular carcinoma and widely invasive follicular carcinoma share similar molecular alterations.

  10. Dopaminergic modulation of impulsive decision making in the rat insular cortex.

    PubMed

    Pattij, Tommy; Schetters, Dustin; Schoffelmeer, Anton N M

    2014-08-15

    Neuroimaging studies have implicated the insular cortex in cognitive processes including decision making. Nonetheless, little is known about the mechanisms by which the insula contributes to impulsive decision making. In this regard, the dopamine system is known to be importantly involved in decision making processes, including impulsive decision making. The aim of the current set of experiments was to further elucidate the importance of dopamine signaling in the agranular insular cortex in impulsive decision making. This compartment of the insular cortex is highly interconnected with brain areas such as the medial prefrontal cortex, amygdala and ventral striatum which are implicated in decision making processes. Male rats were trained in a delay-discounting task and upon stable baseline performance implanted with bilateral cannulae in the agranular insular cortex. Intracranial infusions of the dopamine D1 receptor antagonist SCH23390 and dopamine D2 receptor antagonist eticlopride revealed that particularly blocking dopamine D1 receptors centered on the insular cortex promoted impulsive decision making. Together, the present results demonstrate an important role of the agranular insular cortex in impulsive decision making and, more specifically, highlight the contribution of dopamine D1-like receptors.

  11. Glutamate receptors at atomic resolution

    SciTech Connect

    Mayer, Mark L.

    2010-12-03

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

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

    USGS Publications Warehouse

    Maciolek, J.A.

    1983-01-01

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

  13. Vestibular and visual responses in human posterior insular cortex.

    PubMed

    Frank, Sebastian M; Baumann, Oliver; Mattingley, Jason B; Greenlee, Mark W

    2014-11-15

    The central hub of the cortical vestibular network in humans is likely localized in the region of posterior lateral sulcus. An area characterized by responsiveness to visual motion has previously been described at a similar location and named posterior insular cortex (PIC). Currently it is not known whether PIC processes vestibular information as well. We localized PIC using visual motion stimulation in functional magnetic resonance imaging (fMRI) and investigated whether PIC also responds to vestibular stimuli. To this end, we designed an MRI-compatible caloric stimulation device that allowed us to stimulate bithermally with hot temperature in one ear and simultaneously cold temperature in the other or with warm temperatures in both ears for baseline. During each trial, participants indicated the presence or absence of self-motion sensations. We found activation in PIC during periods of self motion when vestibular stimulation was carried out with minimal visual input. In combined visual-vestibular stimulation area PIC was activated in a similar fashion during congruent and incongruent stimulation conditions. Our results show that PIC not only responds to visual motion but also to vestibular stimuli related to the sensation of self motion. We suggest that PIC is part of the cortical vestibular network and plays a role in the integration of visual and vestibular stimuli for the perception of self motion.

  14. Posterior insular cortex is necessary for conditioned inhibition of fear.

    PubMed

    Foilb, Allison R; Flyer-Adams, Johanna G; Maier, Steven F; Christianson, John P

    2016-10-01

    Veridical detection of safety versus danger is critical to survival. Learned signals for safety inhibit fear, and so when presented, reduce fear responses produced by danger signals. This phenomenon is termed conditioned inhibition of fear. Here, we report that CS+/CS- fear discrimination conditioning over 5 days in rats leads the CS- to become a conditioned inhibitor of fear, as measured by the classic tests of conditioned inhibition: summation and retardation of subsequent fear acquisition. We then show that NMDA-receptor antagonist AP5 injected to posterior insular cortex (IC) before training completely prevented the acquisition of a conditioned fear inhibitor, while intra-AP5 to anterior and medial IC had no effect. To determine if the IC contributes to the recall of learned fear inhibition, injections of the GABAA agonist muscimol were made to posterior IC before a summation test. This resulted in fear inhibition per se, which obscured inference to the effect of IC inactivation with recall of the safety cue. Control experiments sought to determine if the role of the IC in conditioned inhibition learning could be reduced to simpler fear discrimination function, but fear discrimination and recall were unaffected by AP5 or muscimol, respectively, in the posterior IC. These data implicate a role of posterior IC in the learning of conditioned fear inhibitors. PMID:27523750

  15. The Insular Cortex and the Regulation of Cardiac Function.

    PubMed

    Oppenheimer, Stephen; Cechetto, David

    2016-04-01

    Cortical representation of the heart challenges the orthodox view that cardiac regulation is confined to stereotyped, preprogrammed and rigid responses to exteroceptive or interoceptive environmental stimuli. The insula has been the region most studied in this regard; the results of clinical, experimental, and functional radiological studies show a complex interweave of activity with patterns dynamically varying regarding lateralization and antero-posterior distribution of responsive insular regions. Either acting alone or together with other cortical areas including the anterior cingulate, medial prefrontal, and orbito-frontal cortices as part of a concerted network, the insula can imbue perceptions with autonomic color providing emotional salience, and aiding in learning and behavioral decision choice. In these functions, cardiovascular input and the right anterior insula appear to play an important, if not pivotal role. At a more basic level, the insula gauges cardiovascular responses to exteroceptive and interoceptive stimuli, taking into account memory, cognitive, and reflexive constructs thereby ensuring appropriate survival responses and maintaining emotional and physiological homeostasis. When acquired derangements to the insula occur after stroke, during a seizure or from abnormal central processing of interoceptive or exteroceptive environmental cues as in psychiatric disorders, serious consequences can arise including cardiac electrophysiological, structural and contractile dysfunction and sudden cardiac death. PMID:27065176

  16. Allozyme Variation in the Endangered Insular Endemic Castilleja grisea

    PubMed Central

    HELENURM, KAIUS; WEST, RACHEL; BURCKHALTER, STEVEN J.

    2005-01-01

    • Background and Aims Genetic diversity in Castilleja grisea, an endangered, perennial herb endemic to San Clemente Island, California was investigated. Subsequent to the elimination of goats from the island in 1992, many populations of C. grisea have reappeared and have been increasing in size. • Methods Nineteen populations were surveyed for their genotype at 19 allozyme loci. • Key Results At the taxon level, 57·9 % of loci are polymorphic with AP = 3·09 and HE = 0·137. Populations averaged 33·0 % polymorphic loci with AP = 2·43 and HE = 0·099. Most variation is found within rather than among populations (GST = 0·128), although differentiation among populations is significant. Genetic identities range from I = 0·960 to I = 1·000 with mean I = 0·990. There is no significant relationship between genetic and geographic distance. Gene flow among populations is Nm = 2·50 based on private alleles and Nm = 1·70 based on FST. Outcrossing rates based on fixation indices average t = 1·01, indicating a primarily outcrossed mating system. • Conclusions The observed genetic variation is moderately high, unusually so for an insular endemic species, suggesting that C. grisea may not have lost substantial genetic variation during 150 years of overgrazing, and indicating that it is unlikely to be endangered by genetic factors. PMID:15820989

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

    PubMed Central

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

    2016-01-01

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

  18. 21 CFR 182.1045 - Glutamic acid.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

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

  19. 21 CFR 182.1045 - Glutamic acid.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Glutamic acid. 182.1045 Section 182.1045 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN....1045 Glutamic acid. (a) Product. Glutamic acid. (b) (c) Limitations, restrictions, or explanation....

  20. 21 CFR 182.1045 - Glutamic acid.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

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

  1. 21 CFR 182.1045 - Glutamic acid.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Glutamic acid. 182.1045 Section 182.1045 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN....1045 Glutamic acid. (a) Product. Glutamic acid. (b) (c) Limitations, restrictions, or explanation....

  2. 21 CFR 182.1045 - Glutamic acid.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Glutamic acid. 182.1045 Section 182.1045 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN....1045 Glutamic acid. (a) Product. Glutamic acid. (b) (c) Limitations, restrictions, or explanation....

  3. 21 CFR 582.1500 - Monoammonium glutamate.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Monoammonium glutamate. 582.1500 Section 582.1500 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Additives § 582.1500 Monoammonium glutamate. (a) Product. Monoammonium glutamate. (b) Conditions of...

  4. 21 CFR 182.1500 - Monoammonium glutamate.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Monoammonium glutamate. 182.1500 Section 182.1500 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD... Substances § 182.1500 Monoammonium glutamate. (a) Product. Monoammonium glutamate. (b) Conditions of...

  5. 21 CFR 582.1500 - Monoammonium glutamate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

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

  6. 21 CFR 182.1516 - Monopotassium glutamate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Monopotassium glutamate. 182.1516 Section 182.1516 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD... Substances § 182.1516 Monopotassium glutamate. (a) Product. Monopotassium glutamate. (b) Conditions of...

  7. 21 CFR 582.1500 - Monoammonium glutamate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Monoammonium glutamate. 582.1500 Section 582.1500 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Additives § 582.1500 Monoammonium glutamate. (a) Product. Monoammonium glutamate. (b) Conditions of...

  8. 21 CFR 582.1516 - Monopotassium glutamate.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Monopotassium glutamate. 582.1516 Section 582.1516 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Additives § 582.1516 Monopotassium glutamate. (a) Product. Monopotassium glutamate. (b) Conditions of...

  9. 21 CFR 182.1500 - Monoammonium glutamate.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Monoammonium glutamate. 182.1500 Section 182.1500 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD... Substances § 182.1500 Monoammonium glutamate. (a) Product. Monoammonium glutamate. (b) Conditions of...

  10. 21 CFR 182.1516 - Monopotassium glutamate.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Monopotassium glutamate. 182.1516 Section 182.1516 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD... Substances § 182.1516 Monopotassium glutamate. (a) Product. Monopotassium glutamate. (b) Conditions of...

  11. 21 CFR 582.1516 - Monopotassium glutamate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

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

  12. 21 CFR 182.1500 - Monoammonium glutamate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

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

  13. 21 CFR 582.1516 - Monopotassium glutamate.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Monopotassium glutamate. 582.1516 Section 582.1516 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Additives § 582.1516 Monopotassium glutamate. (a) Product. Monopotassium glutamate. (b) Conditions of...

  14. 21 CFR 582.1500 - Monoammonium glutamate.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Monoammonium glutamate. 582.1500 Section 582.1500 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Additives § 582.1500 Monoammonium glutamate. (a) Product. Monoammonium glutamate. (b) Conditions of...

  15. 21 CFR 182.1516 - Monopotassium glutamate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

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

  16. 21 CFR 582.1516 - Monopotassium glutamate.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Monopotassium glutamate. 582.1516 Section 582.1516 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Additives § 582.1516 Monopotassium glutamate. (a) Product. Monopotassium glutamate. (b) Conditions of...

  17. 21 CFR 182.1500 - Monoammonium glutamate.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Monoammonium glutamate. 182.1500 Section 182.1500 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... glutamate. (a) Product. Monoammonium glutamate. (b) Conditions of use. This substance is...

  18. 21 CFR 182.1500 - Monoammonium glutamate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Monoammonium glutamate. 182.1500 Section 182.1500 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD... Substances § 182.1500 Monoammonium glutamate. (a) Product. Monoammonium glutamate. (b) Conditions of...

  19. 21 CFR 582.1516 - Monopotassium glutamate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Monopotassium glutamate. 582.1516 Section 582.1516 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Additives § 582.1516 Monopotassium glutamate. (a) Product. Monopotassium glutamate. (b) Conditions of...

  20. 21 CFR 182.1516 - Monopotassium glutamate.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Monopotassium glutamate. 182.1516 Section 182.1516 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... glutamate. (a) Product. Monopotassium glutamate. (b) Conditions of use. This substance is...

  1. 21 CFR 182.1516 - Monopotassium glutamate.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Monopotassium glutamate. 182.1516 Section 182.1516 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD... Substances § 182.1516 Monopotassium glutamate. (a) Product. Monopotassium glutamate. (b) Conditions of...

  2. 21 CFR 582.1500 - Monoammonium glutamate.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Monoammonium glutamate. 582.1500 Section 582.1500 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Additives § 582.1500 Monoammonium glutamate. (a) Product. Monoammonium glutamate. (b) Conditions of...

  3. Brain neuroprotection by scavenging blood glutamate.

    PubMed

    Zlotnik, Alexander; Gurevich, Boris; Tkachov, Sergei; Maoz, Ilana; Shapira, Yoram; Teichberg, Vivian I

    2007-01-01

    Excess glutamate in brain fluids characterizes acute brain insults such as traumatic brain injury and stroke. Its removal could prevent the glutamate excitotoxicity that causes long-lasting neurological deficits. As blood glutamate scavenging has been demonstrated to increase the efflux of excess glutamate from brain into blood, we tested the prediction that oxaloacetate-mediated blood glutamate scavenging causes neuroprotection in a pathological situation such as closed head injury (CHI), in which there is a well established deleterious increase of glutamate in brain fluids. We observed highly significant improvements of the neurological status of rats submitted to CHI following an intravenous treatment with 1 mmol oxaloacetate/100 g rat weight which decreases blood glutamate levels by 40%. No detectable therapeutic effect was obtained when rats were treated IV with 1 mmol oxaloacetate together with 1 mmol glutamate/100 g rat. The treatment with 0.005 mmol/100 g rat oxaloacetate was no more effective than saline but when it was combined with the intravenous administration of 0.14 nmol/100 g of recombinant glutamate-oxaloacetate transaminase, recovery was almost complete. Oxaloacetate provided neuroprotection when administered before CHI or at 60 min post CHI but not at 120 min post CHI. Since neurological recovery from CHI was highly correlated with the decrease of blood glutamate levels (r=0.89, P=0.001), we conclude that blood glutamate scavenging affords brain neuroprotection Blood glutamate scavenging may open now new therapeutic options.

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

    PubMed

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

    2015-02-01

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

  5. Glutamate secretion and metabotropic glutamate receptor 1 expression during Kaposi's sarcoma-associated herpesvirus infection promotes cell proliferation.

    PubMed

    Valiya Veettil, Mohanan; Dutta, Dipanjan; Bottero, Virginie; Bandyopadhyay, Chirosree; Gjyshi, Olsi; Sharma-Walia, Neelam; Dutta, Sujoy; Chandran, Bala

    2014-10-01

    Kaposi's sarcoma associated herpesvirus (KSHV) is etiologically associated with endothelial Kaposi's sarcoma (KS) and B-cell proliferative primary effusion lymphoma (PEL), common malignancies seen in immunocompromised HIV-1 infected patients. The progression of these cancers occurs by the proliferation of cells latently infected with KSHV, which is highly dependent on autocrine and paracrine factors secreted from the infected cells. Glutamate and glutamate receptors have emerged as key regulators of intracellular signaling pathways and cell proliferation. However, whether they play any role in the pathological changes associated with virus induced oncogenesis is not known. Here, we report the first systematic study of the role of glutamate and its metabotropic glutamate receptor 1 (mGluR1) in KSHV infected cell proliferation. Our studies show increased glutamate secretion and glutaminase expression during de novo KSHV infection of endothelial cells as well as in KSHV latently infected endothelial and B-cells. Increased mGluR1 expression was detected in KSHV infected KS and PEL tissue sections. Increased c-Myc and glutaminase expression in the infected cells was mediated by KSHV latency associated nuclear antigen 1 (LANA-1). In addition, mGluR1 expression regulating host RE-1 silencing transcription factor/neuron restrictive silencer factor (REST/NRSF) was retained in the cytoplasm of infected cells. KSHV latent protein Kaposin A was also involved in the over expression of mGluR1 by interacting with REST in the cytoplasm of infected cells and by regulating the phosphorylation of REST and interaction with β-TRCP for ubiquitination. Colocalization of Kaposin A with REST was also observed in KS and PEL tissue samples. KSHV infected cell proliferation was significantly inhibited by glutamate release inhibitor and mGluR1 antagonists. These studies demonstrated that elevated glutamate secretion and mGluR1 expression play a role in KSHV induced cell proliferation and

  6. Modes of glutamate receptor gating

    PubMed Central

    Popescu, Gabriela K

    2012-01-01

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

  7. Fluorescence imaging of glutamate release in neurons

    SciTech Connect

    Wang, Ziqiang; Yeung, Edward S.

    1999-12-01

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

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

    SciTech Connect

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

    1994-05-01

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

  9. The insular cortex and cardiovascular system: a new insight into the brain-heart axis.

    PubMed

    Nagai, Michiaki; Hoshide, Satoshi; Kario, Kazuomi

    2010-01-01

    The classical literature on neurocardiology has focused mainly on the subcortical regions of the central autonomic nervous system. However, recent studies have supported the notion that the cardiovascular system is regulated by cortical modulation. Modern neuroimaging data, including positron emission tomography and functional magnetic resonance imaging, have revealed that a network consisting of the insular cortex, anterior cingulate gyrus, and amygdala plays a crucial role in the regulation of central autonomic nervous system. Because the insular cortex is located in the region of the middle cerebral arteries, its structure tends to be exposed to a higher risk of cerebrovascular disease. The insular cortex damage has been associated with arrhythmia, diurnal blood pressure variation disruption (eg, a non-dipper or riser pattern), myocardial injury, and sleep disordered breathing, as well as higher plasma levels of brain natriuretic peptide, catecholamine, and glucose. This review article focuses on the role of the insular cortex as a mediator for the cardiovascular system and summarizes current knowledge on the relationships between cerebrovascular disease and cardiovascular system dysregulation. Finally, a hypothesis of the neural network involved in cortical cardiovascular modulation, including modulation of the insular cortex, is provided. PMID:20655502

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

    PubMed

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

    2016-07-01

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

  11. Insular cortex representation of dynamic mechanical allodynia in trigeminal neuropathic rats.

    PubMed

    Alvarez, Pedro; Dieb, Wisam; Hafidi, Aziz; Voisin, Daniel L; Dallel, Radhouane

    2009-01-01

    Dynamic mechanical allodynia is a widespread symptom of neuropathic pain for which mechanisms are still poorly understood. The present study investigated the organization of dynamic mechanical allodynia processing in the rat insular cortex after chronic constriction injury to the infraorbital nerve (IoN-CCI). Two weeks after unilateral IoN-CCI, rats showed a dramatic bilateral trigeminal dynamic mechanical allodynia. Light, moving stroking of the infraorbital skin resulted in strong, bilateral upregulation of extracellular-signal regulated kinase phosphorylation (pERK-1/2) in the insular cortex of IoN-CCI animals but not sham rats, in whose levels were similar to those of unstimulated IoN-CCI rats. pERK-1/2 was located in neuronal cells only. Stimulus-evoked pERK-1/2 immunopositive cell bodies displayed rostrocaudal gradient and layer selective distribution in the insula, being predominant in the rostral insula and in layers II-III of the dysgranular and to a lesser extent, of the agranular insular cortex. In layers II-III of the rostral dysgranular insular cortex, intense pERK also extended into distal dendrites, up to layer I. These results demonstrate that trigeminal nerve injury induces a significant alteration in the insular cortex processing of tactile stimuli and suggest that ERK phosphorylation contributes to the mechanisms underlying abnormal pain perception under this condition.

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    USGS Publications Warehouse

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

    1991-01-01

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

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

    PubMed

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

    2014-01-01

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

  16. Classification tree methods provide a multifactorial approach to predicting insular body size evolution in rodents.

    PubMed

    Durst, Paul A P; Roth, V Louise

    2012-04-01

    Many hypotheses have been proposed to explain size changes in insular mammals, but no single variable suffices to explain the diversity of responses, particularly within Rodentia. Here in a data set on insular rodents, we observe strong consistency in the direction of size change within islands and within species but (outside of Heteromyidae) little consistency at broader taxonomic scales. Using traits of islands and of species in a classification tree analysis, we find the most important factor predicting direction of change to be mainland body mass (large rodents decrease, small ones increase); other variables (island climate, number of rodent species, and area) were significant, although their roles as revealed by the classification tree were context dependent. Ecological interactions appear relatively uninformative, and on any given island, the largest and smallest rodent species converged or diverged in size with equal frequency. Our approach provides a promising framework for continuing examination of insular body size evolution. PMID:22437183

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

    PubMed

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

    2005-11-25

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

  18. Ligands for Ionotropic Glutamate Receptors

    NASA Astrophysics Data System (ADS)

    Swanson, Geoffrey T.; Sakai, Ryuichi

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

  19. Ligands for Ionotropic Glutamate Receptors

    PubMed Central

    Swanson, Geoffrey T.; Sakai, Ryuichi

    2010-01-01

    Marine-derived small molecules and peptides have played a central role in elaborating pharmacological specificities and neuronal functions of mammalian ionotropic glutamate receptors (iGluRs), the primary mediators of excitatory synaptic transmission in the central nervous system (CNS). As well, the pathological sequelae elicited by one class of compounds (the kainoids) constitute a widely-used animal model for human mesial temporal lobe epilepsy (mTLE). New and existing molecules could prove useful as lead compounds for the development of therapeutics for neuropathologies that have aberrant glutamatergic signaling as a central component. In this chapter we discuss natural source origins and pharmacological activities of those marine compounds that target ionotropic glutamate receptors. PMID:19184587

  20. ELEVATING MECHANISM

    DOEpatents

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

    1959-02-24

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

  1. Glutamate racemization and catabolism in Fusobacterium varium.

    PubMed

    Ramezani, Mohammad; Resmer, Kelly L; White, Robert L

    2011-07-01

    The pathways of glutamate catabolism in the anaerobic bacterium Fusobacterium varium, grown on complex, undefined medium and chemically defined, minimal medium, were investigated using specifically labelled (13)C-glutamate. The metabolic end-products acetate and butyrate were isolated from culture fluids and derivatized for analysis by nuclear magnetic resonance and mass spectrometry. On complex medium, labels from L-[1-(13)C]glutamate and L-[4-(13)C]glutamate were incorporated into C1 of acetate and equally into C1/C3 of butyrate, while label derived from L-[5-(13)C]glutamate was not incorporated. The isotopic incorporation results and the detection of glutamate mutase and 3-methylaspartate ammonia lyase in cell extracts are most consistent with the methylaspartate pathway, the best known route of glutamate catabolism in Clostridium species. When F. varium was grown on defined medium, label from L-[4-(13)C]glutamate was incorporated mainly into C4 of butyrate, demonstrating a major role for the hydroxyglutarate pathway. Upon addition of coenzyme B(12) or cobalt ion to the defined medium in replicate experiments, isotope was located equally at C1/C3 of butyrate in accord with the methylaspartate pathway. Racemization of D-glutamate and subsequent degradation of L-glutamate via the methylaspartate pathway are supported by incorporation of label into C2 of acetate and equally into C2/C4 of butyrate from D-[3-(13)C]glutamate and the detection of a cofactor-independent glutamate racemase in cell extracts. Together the results demonstrate a major role for the methylaspartate pathway of glutamate catabolism in F. varium and substantial participation of the hydroxyglutarate pathway when coenzyme B(12) is not available.

  2. A Case of Semantic Variant Primary Progressive Aphasia with Severe Insular Atrophy

    PubMed Central

    Chow, T. W.; Links, K. A.; Masterman, D. L.; Mendez, M.F.; Vinters, H. V.

    2012-01-01

    Insular degeneration has been linked to symptoms of frontotemporal dementia (FTD). Presented in this case is a patient exhibiting semantic variant primary progressive aphasia, behavioral disturbance. Upon autopsy, he was found to have severe insular atrophy. In addition, selective serotonin reuptake inhibitors (SSRIs) were ineffective in reducing symptoms of obsessive-compulsive behaviours or emotional blunting. This case suggests that Seeley et al.'s hypothesis that VEN and fork cell-rich brain regions, particularly in the insula, are targeted in additional subtypes of FTD beyond the behavioral variant. PMID:22150361

  3. Does the salience network play a cardinal role in psychosis? An emerging hypothesis of insular dysfunction

    PubMed Central

    Palaniyappan, Lena; Liddle, Peter F.

    2012-01-01

    The insular cortex is one of the brain regions that show consistent abnormalities in both structural and functional neuroimaging studies of schizophrenia. In healthy individuals, the insula has been implicated in a myriad of physiologic functions. The anterior cingulate cortex (ACC) and insula together constitute the salience network, an intrinsic large-scale network showing strong functional connectivity. Considering the insula as a functional unit along with the ACC provides an integrated understanding of the role of the insula in information processing. In this review, we bring together evidence from imaging studies to understand the role of the salience network in schizophrenia and propose a model of insular dysfunction in psychosis. PMID:21693094

  4. Distinct Excitation to Pulpal Stimuli between Somatosensory and Insular Cortices.

    PubMed

    Nakamura, H; Shirakawa, T; Koshikawa, N; Kobayashi, M

    2016-02-01

    Somatosensory information from the dental pulp is processed in the primary (S1) and secondary somatosensory cortex (S2) and in the insular oral region (IOR). Stimulation of maxillary incisor and molar initially induces excitation in S2/IOR, rostrodorsal to the mandibular incisor and molar pulp-responding regions. Although S1 and S2/IOR play their own roles in nociceptive information processing, the anatomical and physiological differences in the temporal activation kinetics, dependency on stimulation intensity, and additive or summative effects of simultaneous pulpal stimulation are still unknown. This information contributes not only to understanding topographical organization but also to speculating about the roles of S1 and S2/IOR in clinical aspects of pain regulation. In vivo optical imaging enables investigation of the spatiotemporal profiles of cortical excitation with high resolution. We determined the distinct features of optical responses to nociceptive stimulation of dental pulps between S1 and S2/IOR. In comparison to S1, optical signals in S2/IOR showed a larger amplitude with a shorter rise time and a longer decay time responding to maxillary molar pulp stimulation. The latency of excitation in S2/IOR was shorter than in S1. S2/IOR exhibited a lower threshold to evoke optical responses than S1, and the peak amplitude was larger in S2/IOR than in S1. Unexpectedly, the topography of S1 that responded to maxillary and mandibular incisor and molar pulps overlapped with the most ventral sites in S1 that was densely stained with cytochrome oxidase. An additive effect was observed in both S1 and S2/IOR after simultaneous stimulation of bilateral maxillary molar pulps but not after contralateral maxillary and mandibular molar pulp stimulation. These findings suggest that S2/IOR is more sensitive for detecting dental pulp sensation and codes stimulation intensity more precisely than S1. In addition, contra- and ipsilateral dental pulp nociception converges

  5. Transient mitochondrial permeability transition mediates excitotoxicity in glutamate-sensitive NSC34D motor neuron-like cells

    PubMed Central

    Liu, Xiaoyun; Xu, Shangcheng; Wang, Pei; Wang, Wang

    2015-01-01

    Excitotoxicity plays a critical role in neurodegenerative disease. Cytosolic calcium overload and mitochondrial dysfunction are among the major mediators of high level glutamate-induced neuron death. Here, we show that the transient opening of mitochondrial permeability transition pore (tMPT) bridges cytosolic calcium signaling and mitochondrial dysfunction and mediates glutamate-induced neuron death. Incubation of the differentiated motor neuron-like NSC34D cells with glutamate (1 mM) acutely induces cytosolic calcium transient (30% increase). Glutamate also stimulates tMPT opening, as reflected by a 2-fold increase in the frequency of superoxide flash, a bursting superoxide production event in individual mitochondria coupled to tMPT opening. The glutamate-induced tMPT opening is attenuated by suppressing cytosolic calcium influx and abolished by inhibiting mitochondrial calcium uniporter (MCU) with Ru360 (100 µM) or MCU shRNA. Further, increased cytosolic calcium is sufficient to induce tMPT in a mitochondrial calcium dependent manner. Finally, chronic glutamate incubation (24 hr) persistently elevates the probability of tMPT opening, promotes oxidative stress and induces neuron death. Attenuating tMPT activity or inhibiting MCU protects NSC34D cells from glutamate-induced cell death. These results indicate that high level glutamate-induced neuron toxicity is mediated by tMPT, which connects increased cytosolic calcium signal to mitochondrial dysfunction. PMID:26024861

  6. The glutamate homeostasis hypothesis of addiction.

    PubMed

    Kalivas, Peter W

    2009-08-01

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

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

    PubMed

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

    2014-04-16

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

  8. Scavenging of blood glutamate for enhancing brain-to-blood glutamate efflux.

    PubMed

    Li, Yunhong; Hou, Xiaolin; Qi, Qi; Wang, Le; Luo, Lan; Yang, Shaoqi; Zhang, Yumei; Miao, Zhenhua; Zhang, Yanli; Wang, Fei; Wang, Hongyan; Huang, Weidong; Wang, Zhenhai; Shen, Ying; Wang, Yin

    2014-01-01

    The presence of excess glutamate in the brain interstitial fluid characterizes several acute pathological conditions of the brain, including traumatic brain injury and stroke. It has been demonstrated that it is possible to eliminate excess glutamate in the brain by decreasing blood glutamate levels and, accordingly, accelerating the brain-to-blood glutamate efflux. It is feasible to accomplish this process by activating blood resident enzymes in the presence of the respective glutamate cosubstrates. In the present study, several glutamate cosubstrates and cofactors were studied in an attempt to identify the optimal conditions to reduce blood glutamate levels. The administration of a mixture of 1 mM pyruvate and oxaloacetate (Pyr/Oxa) for 1 h decreased blood glutamate levels by ≤50%. The addition of lipoamide to this mixture resulted in a further reduction in blood glutamate levels of >80%. In addition, in vivo experiments showed that lipoamide together with Pyr/Oxa is able to decrease blood glutamate levels to a greater extent than Pyr/Oxa alone, and accordingly, this enhances the glutamate efflux from the brain to the blood. These results may outline a novel neuroprotective strategy with increased effectiveness for the removal of excess brain glutamate in various neurodegenerative conditions.

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

    PubMed Central

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

    2014-01-01

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

  10. Bidirectional modulation of cocaine-expectancy by phasic glutamate fluctuations in the nucleus accumbens

    PubMed Central

    Suto, Nobuyoshi; Elmer, Greg I.; Wang, Bin; You, Zhi-Bing; Wise, Roy A.

    2013-01-01

    While glutamate in the nucleus accumbens (NAS) contributes to the promotion of drug-seeking by drug-predictive cues, it also appears to play a role in the inhibition of drug-seeking following extinction procedures. Thus we measured extracellular fluctuations of NAS glutamate in response to discriminative stimuli that signaled either cocaine availability or cocaine omission. We trained rats to self-administer intravenous cocaine and then to recognize discriminative odor cues that predicted either sessions where cocaine was available or alternating sessions where it was not (saline substituted for cocaine). Whereas responding in cocaine availability sessions remained stable, responding in cocaine omission sessions progressively declined to chance levels. We then determined the effects of each odor cue on extracellular glutamate in the core and shell subregions of NAS preceding and accompanying lever-pressing under an extinction condition. Glutamate levels were elevated in both core and shell by the availability odor and depressed in the core but not the shell by the omission odor. Infusion of kynurenic acid (an antagonist for ionotropic glutamate receptors) into core but not shell suppressed responding associated with the availability odor, but had no effect on the suppression associated with the omission odor. Thus cocaine-predictive cues appear to promote cocaine-seeking in part by elevating glutamatergic neurotransmission in the core of NAS, whereas cocaine-omission cues appear to suppress cocaine-seeking in part by depressing glutamatergic receptor activation in the same region. PMID:23699516

  11. 76 FR 38370 - Western Pacific Fisheries; Approval of a Marine Conservation Plan for Pacific Insular Areas...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-30

    ... Marine Conservation Plan for Pacific Insular Areas; Western Pacific Sustainable Fisheries Fund AGENCY...: Jarad Makaiau, Sustainable Fisheries, NMFS Pacific Islands Regional Office, 808-944-2108. SUPPLEMENTARY... Sustainable Fisheries Fund (Fund) for use by the Council. Additionally, amounts received by the...

  12. Evidence of Conjoint Activation of the Anterior Insular and Cingulate Cortices during Effortful Tasks.

    PubMed

    Engström, Maria; Karlsson, Thomas; Landtblom, Anne-Marie; Craig, A D Bud

    2014-01-01

    The ability to perform effortful tasks is a topic that has received considerable interest in the research of higher functions of the human brain. Neuroimaging studies show that the anterior insular and the anterior cingulate cortices are involved in a multitude of cognitive tasks that require mental effort. In this study, we investigated brain responses to effort using cognitive tasks with task-difficulty modulations and functional magnetic resonance imaging (fMRI). We hypothesized that effortful performance involves modulation of activation in the anterior insular and the anterior cingulate cortices, and that the modulation correlates with individual performance levels. Healthy participants performed tasks probing verbal working memory capacity using the reading span task, and visual perception speed using the inspection time task. In the fMRI analysis, we focused on identifying effort-related brain activation. The results showed that working memory and inspection time performances were directly related. The bilateral anterior insular and anterior cingulate cortices showed significantly increased activation during each task with common portions that were active across both tasks. We observed increased brain activation in the right anterior insula and the anterior cingulate cortex in participants with low working memory performance. In line with the reported results, we suggest that activation in the anterior insular and cingulate cortices is consistent with the neural efficiency hypothesis (Neubauer).

  13. FMRI of ventral and dorsal processing streams in basic reading processes: insular sensitivity to phonology.

    PubMed

    Borowsky, Ron; Cummine, Jacqueline; Owen, William J; Friesen, Chris Kelland; Shih, Francis; Sarty, Gordon E

    2006-01-01

    Most current models of the neurophysiology of basic reading processes agree on a system involving two cortical streams: a ventral stream (occipital-temporal) used when accessing familiar words encoded in lexical memory, and a dorsal stream (occipital-parietal-frontal) used when phonetically decoding words (i.e., mapping sublexical spelling onto sounds). The models diverge, however, on the issue of whether the insular cortex is involved. The present fMRI study required participants to read aloud exception words (e.g., 'one', which must be read via lexical memory) and pseudohomophones (e.g., 'wun', which must be read via sublexical spelling to sound translation) to examine the processing streams as well as the insular cortex, and their relationship to lexical and sublexical reading processes. The present study supports the notion of independent ventral-lexical and dorsal-sublexical streams, and further suggests the insular cortex to be sensitive to phonological processing (particularly sublexical spelling-sound translation). These latter findings illuminate the nature of insular activity during reading, which must be explored further in future studies, and accounted for in models of the neurophysiology of reading.

  14. Hyperacusis following unilateral damage to the insular cortex: a three-case report.

    PubMed

    Boucher, Olivier; Turgeon, Christine; Champoux, Sara; Ménard, Lucie; Rouleau, Isabelle; Lassonde, Maryse; Lepore, Franco; Nguyen, Dang K

    2015-05-01

    The insula is a multisensory area involved in various brain functions, including central auditory processing. However, its specific role in auditory function remains unclear. Here we report three cases of persistent hypersensitivity to auditory stimuli following damage to the insular cortex, using behavioral and neurophysiological measures. Two patients who complained of auditory disturbance since they suffered an isolated unilateral insular stroke, and one epileptic patient who underwent right insular resection for control of drug-resistant seizures, were involved in this study. These patients, all young adult women, were tested for auditory function more than one year after brain injury, and were compared to 10 healthy control participants matched for age, sex, and education. The assessment included pure-tone detection and speech detection in quiet, loudness discomfort levels, random gap detection, recognition of frequency and duration patterns, binaural separation, dichotic listening, as well as late-latency auditory event-related potentials (ERPs). Each patient showed mild or moderate hyperacusis, as revealed by decreased loudness discomfort levels, which was more important on the side of lesion in two cases. Tests of temporal processing also revealed impairments, in concordance with previous findings. ERPs of two patients were characterised by increased amplitude of the P3b component elicited during a two-tone auditory oddball detection task. This study is the first to report cases of persistent hyperacusis following damage to the insular cortex, and suggests that the insula is involved in modulating the perceived intensity of the incoming auditory stimuli during late-stage processing.

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

    PubMed

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

    2014-02-01

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

  16. 76 FR 66035 - Proposed Information Collection; Comment Request; Application for Insular Watch and Jewelry...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-25

    ... Watch and Jewelry Program Benefits AGENCY: International Trade Administration. ACTION: Notice. SUMMARY... Departments of Commerce and the Interior (Departments) to administer the distribution of watch duty-exemptions and watch and jewelry duty-refunds to program producers in the U.S. insular possessions and...

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

    USGS Publications Warehouse

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

    2016-01-01

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

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

    ERIC Educational Resources Information Center

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

    2008-01-01

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

  19. 47 CFR 54.101 - Supported services for rural, insular and high cost areas.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

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

  20. Maternal inflammation leads to impaired glutamate homeostasis and up-regulation of glutamate carboxypeptidase II in activated microglia in the fetal/newborn rabbit brain.

    PubMed

    Zhang, Zhi; Bassam, Bassam; Thomas, Ajit G; Williams, Monica; Liu, Jinhuan; Nance, Elizabeth; Rojas, Camilo; Slusher, Barbara S; Kannan, Sujatha

    2016-10-01

    Astrocyte dysfunction and excessive activation of glutamatergic systems have been implicated in a number of neurologic disorders, including periventricular leukomalacia (PVL) and cerebral palsy (CP). However, the role of chorioamnionitis on glutamate homeostasis in the fetal and neonatal brains is not clearly understood. We have previously shown that intrauterine endotoxin administration results in intense microglial 'activation' and increased pro-inflammatory cytokines in the periventricular region (PVR) of the neonatal rabbit brain. In this study, we assessed the effect of maternal inflammation on key components of the glutamate pathway and its relationship to astrocyte and microglial activation in the fetal and neonatal New Zealand white rabbit brain. We found that intrauterine endotoxin exposure at gestational day 28 (G28) induced acute and prolonged glutamate elevation in the PVR of fetal (G29, 1day post-injury) and postnatal day 1 (PND1, 3days post-injury) brains along with prominent morphological changes in the astrocytes (soma hypertrophy and retracted processes) in the white matter tracts. There was a significant increase in glutaminase and N-Methyl-d-Aspartate receptor (NMDAR) NR2 subunit expression along with decreased glial L-glutamate transporter 1 (GLT-1) in the PVR at G29, that would promote acute dysregulation of glutamate homeostasis. This was accompanied with significantly decreased TGF-β1 at PND1 in CP kits indicating ongoing neuroinflammation. We also show for the first time that glutamate carboxypeptidase II (GCPII) was significantly increased in the activated microglia at the periventricular white matter area in both G29 and PND1 CP kits. This was confirmed by in vitro studies demonstrating that LPS activated primary microglia markedly upregulate GCPII enzymatic activity. These results suggest that maternal intrauterine endotoxin exposure results in early onset and long-lasting dysregulation of glutamate homeostasis, which may be mediated by

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

    PubMed

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

    2016-02-01

    Phosphoenolpyruvate carboxylase (PEPC) in Corynebacterium glutamicum ATCC13032, a glutamic-acid producing actinobacterium, is subject to feedback inhibition by metabolic intermediates such as aspartic acid and 2-oxoglutaric acid, which implies the importance of PEPC in replenishing oxaloacetic acid into the TCA cycle. Here, we investigated the effects of feedback-insensitive PEPC on glutamic acid production. A single amino-acid substitution in PEPC, D299N, was found to relieve the feedback control by aspartic acid, but not by 2-oxoglutaric acid. A simple mutant, strain R1, having the D299N substitution in PEPC was constructed from ATCC 13032 using the double-crossover chromosome replacement technique. Strain R1 produced glutamic acid at a concentration of 31.0 g/L from 100 g/L glucose in a jar fermentor culture under biotin-limited conditions, which was significantly higher than that of the parent, 26.0 g/L (1.19-fold), indicative of the positive effect of desensitized PEPC on glutamic acid production. Another mutant, strain DR1, having both desensitized PEPC and PYK-gene deleted mutations, was constructed in a similar manner using strain D1 with a PYK-gene deleted mutation as the parent. This mutation had been shown to enhance glutamic acid production in our previous study. Although marginal, strain D1 produced higher glutamic acid, 28.8 g/L, than ATCC13032 (1.11-fold). In contrast, glutamic acid production by strain DR-1 was elevated up to 36.9 g/L, which was 1.42-fold higher than ATCC13032 and significantly higher than the other three strains. The results showed a synergistic effect of these two mutations on glutamic acid production in C. glutamicum. PMID:26168906

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

    PubMed

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

    2016-02-01

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

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

    PubMed

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

    2016-03-01

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

  4. Effect of insulin on muscle glutamate uptake

    PubMed Central

    Aoki, T. T.; Brennan, M. F.; Müller, W. A.; Moore, F. D.; Cahill, G. F.

    1972-01-01

    For decades, investigators concerned with protein metabolism in man have performed detailed amino acid analyses of human plasma obtained under a wide range of experimental situations. A large body of information has been used to calculated rates of protein synthesis and proteolysis. During the course of an investigation of the effect of intrabrachial artery infusion of insulin (70 μU/min per kg body weight) on glutamate uptake by human forearm muscle, it was discovered that plasma arterio-deep venous glutamate difference analysis failed to document any increase in the uptake of this amino acid, suggesting that insulin had little influence on glutamate uptake by muscle. However, whole blood glutamate analyses, performed on the same blood samples, revealed that (a) the resting muscle uptake of glutamate is smaller than previously reported and (b) insulin is capable of markedly increasing glutamate uptake by muscle from whole blood. Since the hematocrit was obtained on all samples, detailed analyses of the various compartments in which glutamate could be found were performed. It was determined that circulating blood cells have a dynamic role in glutamate transport. These data underscore the need for both whole blood and plasma amino acid analysis in investigations concerned with protein synthesis and/or amino acid flux, for analysis of plasma samples alone could be misleading as illustrated in the present study. Images PMID:5080414

  5. Glutamate: Tastant and Neuromodulator in Taste Buds.

    PubMed

    Vandenbeuch, Aurelie; Kinnamon, Sue C

    2016-07-01

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

  6. Glutamate-based antidepressants: preclinical psychopharmacology.

    PubMed

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

    2013-06-15

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

  7. 75 FR 10463 - Office of Insular Affairs; Allocation of Duty-Exemptions for Calendar Year 2010 for Watch...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-08

    ... Changes in Watch, Watch Movement and Jewelry Program for the U.S. Insular Possessions, 65 FR 8048... producer allocation Belair Quartz, Inc 500,000 The balance of the units allocated to the USVI is...

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

    PubMed

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

    2013-01-01

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

  9. Monocular Elevation Deficiency - Double Elevator Palsy

    MedlinePlus

    ... Eye Terms Conditions Frequently Asked Questions Español Condiciones Chinese Conditions Monocular Elevation Deficiency/ Double Elevator Palsy En Español Read in Chinese What is monocular elevation deficiency (Double Elevator Palsy)? ...

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

    PubMed Central

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

    2016-01-01

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

  11. Genetic variation influences glutamate concentrations in brains of patients with multiple sclerosis

    PubMed Central

    Srinivasan, Radhika; Khankhanian, Pouya; Okuda, Darin T.; Nelson, Sarah J.; Matthews, Paul M.; Hauser, Stephen L.; Oksenberg, Jorge R.; Pelletier, Daniel

    2010-01-01

    Glutamate is the main excitatory neurotransmitter in the mammalian brain. Appropriate transmission of nerve impulses through glutamatergic synapses is required throughout the brain and forms the basis of many processes including learning and memory. However, abnormally high levels of extracellular brain glutamate can lead to neuroaxonal cell death. We have previously reported elevated glutamate levels in the brains of patients suffering from multiple sclerosis. Here two complementary analyses to assess the extent of genomic control over glutamate levels were used. First, a genome-wide association analysis in 382 patients with multiple sclerosis using brain glutamate concentration as a quantitative trait was conducted. In a second approach, a protein interaction network was used to find associated genes within the same pathway. The top associated marker was rs794185 (P < 6.44 × 10−7), a non-coding single nucleotide polymorphism within the gene sulphatase modifying factor 1. Our pathway approach identified a module composed of 70 genes with high relevance to glutamate biology. Individuals carrying a higher number of associated alleles from genes in this module showed the highest levels of glutamate. These individuals also showed greater decreases in N-acetylaspartate and in brain volume over 1 year of follow-up. Patients were then stratified by the amount of annual brain volume loss and the same approach was performed in the ‘high’ (n = 250) and ‘low’ (n = 132) neurodegeneration groups. The association with rs794185 was highly significant in the group with high neurodegeneration. Further, results from the network-based pathway analysis remained largely unchanged even after stratification. Results from these analyses indicated that variance in the activity of neurochemical pathways implicated in neurodegeneration is explained, at least in part, by the inheritance of common genetic polymorphisms. Spectroscopy-based imaging provides a novel quantitative

  12. Mitochondrial transporters involved in oleic acid utilization and glutamate metabolism in yeast.

    PubMed

    Trotter, Pamela J; Adamson, Amy L; Ghrist, Angela C; Rowe, Lindsay; Scott, Lori R; Sherman, Matthew P; Stites, Nicole C; Sun, Yue; Tawiah-Boateng, Mary Anne; Tibbetts, Anne S; Wadington, Megan C; West, Aaron C

    2005-10-01

    Utilization of fatty acids such as oleic acid as sole carbon source by the yeast Saccharomyces cerevisiae requires coordinated function of peroxisomes, where the fatty acids are degraded, and the mitochondria, where oxidation is completed. We identified two mitochondrial oxodicarboxylate transporters, Odc1p and Odc2p, as important in efficient utilization of oleic acid in yeast [Tibbetts et al., Arch. Biochem. Biophys. 406 (2002) 96-104]. Yet, the growth phenotype of odc1delta odc2delta strains indicated that additional transporter(s) were also involved. Here, we identify two putative transporter genes, YMC1 and YMC2, as able to suppress the odc1delta odc2delta growth phenotype. The mRNA levels for both are elevated in the presence of glycerol or oleic acid, as compared to glucose. Ymc1p and Ymc2p are localized to the mitochondria in oleic acid-grown cells. Deletion of all four transporters (quad mutant) prevents growth on oleic acid as sole carbon source, while growth on acetate is retained. It is known that the glutamate-sensitive retrograde signaling pathway is important for upregulation of peroxisomal function in response to oleic acid and the oxodicarboxylate alpha-ketoglutarate is transported out of the mitochondria for synthesis of glutamate. So, citric acid cycle function and glutamate synthesis were examined in transporter mutants. The quad mutant has significantly decreased citrate synthase activity and whole cell alpha-ketoglutarate levels, while isocitrate dehydrogenase activity is unaffected and glutamate dehydrogenase activity is increased 10-fold. Strains carrying only two or three transporter deletions exhibit intermediate affects. 13C NMR metabolic enrichment experiments confirm a defect in glutamate biosynthesis in the quad mutant and, in double and triple mutants, suggest increased cycling of the glutamate backbone in the mitochondria before export. Taken together these studies indicate that these four transporters have overlapping activity, and

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2016-05-25

    Internet gaming disorder is defined as excessive and compulsive use of the internet to engage in games that leads to clinically significant psychosocial impairment. We tested the hypothesis that individuals with internet gaming disorder would be less sensitive to high-risk situations and show aberrant brain activation related to risk prediction processing. Young adults with internet gaming disorder underwent functional MRI while performing a risky decision-making task. The healthy control group showed stronger activations within the dorsal attention network and the anterior insular cortex, which were not found in the internet gaming disorder group. Our findings imply that young adults with internet gaming disorder show impaired anterior insular activation during risky decision making, which might make them vulnerable when they need to adapt new behavioral strategies in high-risk situations. PMID:27092470

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

    PubMed

    Durst, Paul A P; Roth, V Louise

    2015-07-01

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

  16. Behavioural Variant Frontotemporal Dementia with Bilateral Insular Hypometabolism: A Case Report.

    PubMed

    Mahapatra, Ananya; Sood, Mamta; Bhad, Roshan; Tripathi, Manjari

    2016-04-01

    Fronto-Temporal Dementia (FTD) is a cluster of syndromes, characterized by progressive deterioration of cognition, language and/or behavioural changes associated with degeneration of the frontal and temporal lobes. A 53-year-old man was admitted with a history of gradually progressive behavioural disturbances, disinhibition, unprovoked anger outbursts, apathy, disorganised behaviour and impaired self-care. A clinical diagnosis of Fronto temporal Dementia (behavioural variant) was made. Extensive investigations found no abnormality except in FDG-PET scan of the brain which revealed hypo metabolism in bilateral anterior insular region. Insula is an important brain area implicated in emotional awareness and behaviour control. Hypo metabolism in insular region in the absence of any structural neuroimaging findings, in a case of behavioural variant of Fronto-temporal dementia suggest that, it might be one of the earliest neurobiological changes occurring in this disorder. PMID:27190928

  17. Behavioural Variant Frontotemporal Dementia with Bilateral Insular Hypometabolism: A Case Report

    PubMed Central

    Sood, Mamta; Bhad, Roshan; Tripathi, Manjari

    2016-01-01

    Fronto-Temporal Dementia (FTD) is a cluster of syndromes, characterized by progressive deterioration of cognition, language and/or behavioural changes associated with degeneration of the frontal and temporal lobes. A 53-year-old man was admitted with a history of gradually progressive behavioural disturbances, disinhibition, unprovoked anger outbursts, apathy, disorganised behaviour and impaired self-care. A clinical diagnosis of Fronto temporal Dementia (behavioural variant) was made. Extensive investigations found no abnormality except in FDG-PET scan of the brain which revealed hypo metabolism in bilateral anterior insular region. Insula is an important brain area implicated in emotional awareness and behaviour control. Hypo metabolism in insular region in the absence of any structural neuroimaging findings, in a case of behavioural variant of Fronto-temporal dementia suggest that, it might be one of the earliest neurobiological changes occurring in this disorder. PMID:27190928

  18. Peripheral nerve injury produces a sustained shift in the balance between glutamate release and uptake in the dorsal horn of the spinal cord

    PubMed Central

    Inquimbert, Perrine; Bartels, Karsten; Babaniyi, Olusegun B.; Barrett, Lee B.; Tegeder, Irmgard; Scholz, Joachim

    2012-01-01

    Peripheral nerve injury provokes heightened excitability of primary sensory afferents including nociceptors, and elicits ectopic activity in lesioned and neighboring intact nerve fibers. The major transmitter released by sensory afferents in the superficial dorsal horn of the spinal cord is glutamate. Glutamate is critically involved in nociceptive signaling and the development of neuropathic pain. We recorded miniature excitatory postsynaptic currents (mEPSCs) from neurons in lamina II of the rat dorsal horn to assess spontaneous synaptic activity after spared nerve injury (SNI), a model of chronic neuropathic pain. Following SNI, the frequency of mEPSCs doubled, indicating heightened glutamate release from primary afferents or spinal interneurons. Consistent with this finding, glutamate concentrations in the cerebrospinal fluid were elevated at one and four weeks after SNI. Transmitter uptake was insufficient to prevent the rise in extracellular glutamate as the expression of glutamate transporters remained unchanged or decreased. 2-Methyl-6-(phenylethynyl)pyridine hydrochloride (MPEP), an antagonist of metabotropic glutamate receptor 5 (mGluR5), reduced the frequency of mEPSCs to its preinjury level, suggesting a positive feedback mechanism that involves facilitation of transmitter release by mGluR5 activation in the presence of high extracellular glutamate. Treatment with the β-lactam antibiotic ceftriaxone increased the expression of glutamate transporter 1 (Glt1) in the dorsal horn after SNI, raised transmitter uptake and lowered extracellular glutamate. Improving glutamate clearance prevented the facilitation of transmitter release by mGluR5 and attenuated neuropathic pain-like behavior. Balancing glutamate release and uptake after nerve injury should be an important target in the management of chronic neuropathic pain. PMID:23021150

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

    PubMed

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

    2014-02-01

    Understanding the factors that contribute to loss of genetic diversity in fragmented populations is crucial for conservation measurements. Land-bridge archipelagoes offer ideal model systems for identifying the long-term effects of these factors on genetic variations in wild populations. In this study, we used nine microsatellite markers to quantify genetic diversity and differentiation of 810 pond frogs (Pelophylax nigromaculatus) from 24 islands of the Zhoushan Archipelago and three sites on nearby mainland China and estimated the effects of the island area, population size, time since island isolation, distance to the mainland and distance to the nearest larger island on reduced genetic diversity of insular populations. The mainland populations displayed higher genetic diversity than insular populations. Genetic differentiations and no obvious gene flow were detected among the frog populations on the islands. Hierarchical partitioning analysis showed that only time since island isolation (square-root-transformed) and population size (log-transformed) significantly contributed to insular genetic diversity. These results suggest that decreased genetic diversity and genetic differentiations among insular populations may have been caused by random genetic drift following isolation by rising sea levels during the Holocene. The results provide strong evidence for a relationship between retained genetic diversity and population size and time since island isolation for pond frogs on the islands, consistent with the prediction of the neutral theory for finite populations. Our study highlights the importance of the size and estimated isolation time of populations in understanding the mechanisms of genetic diversity loss and differentiation in fragmented wild populations. PMID:24351057

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed

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

    2013-06-01

    A compilation of historical and recent collections and observations of shore fishes yielded 154 recorded species for Trindade and 67 for Martin Vaz. Twelve taxa, mostly small cryptobenthic species with limited dispersal capabilities and low ecological amplitude, are endemic to this insular complex. In several cases, the seamounts of the Vitória-Trindade Chain appear to have acted as stepping stones between the mainland and islands in periods of low sea level. PMID:23731156

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

    PubMed

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

    2013-06-01

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

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

    PubMed Central

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

    2015-01-01

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

  4. Traumatic Brain Injury Increases Cortical Glutamate Network Activity by Compromising GABAergic Control

    PubMed Central

    Cantu, David; Walker, Kendall; Andresen, Lauren; Taylor-Weiner, Amaro; Hampton, David; Tesco, Giuseppina; Dulla, Chris G.

    2015-01-01

    Traumatic brain injury (TBI) is a major risk factor for developing pharmaco-resistant epilepsy. Although disruptions in brain circuitry are associated with TBI, the precise mechanisms by which brain injury leads to epileptiform network activity is unknown. Using controlled cortical impact (CCI) as a model of TBI, we examined how cortical excitability and glutamatergic signaling was altered following injury. We optically mapped cortical glutamate signaling using FRET-based glutamate biosensors, while simultaneously recording cortical field potentials in acute brain slices 2–4 weeks following CCI. Cortical electrical stimulation evoked polyphasic, epileptiform field potentials and disrupted the input–output relationship in deep layers of CCI-injured cortex. High-speed glutamate biosensor imaging showed that glutamate signaling was significantly increased in the injured cortex. Elevated glutamate responses correlated with epileptiform activity, were highest directly adjacent to the injury, and spread via deep cortical layers. Immunoreactivity for markers of GABAergic interneurons were significantly decreased throughout CCI cortex. Lastly, spontaneous inhibitory postsynaptic current frequency decreased and spontaneous excitatory postsynaptic current increased after CCI injury. Our results suggest that specific cortical neuronal microcircuits may initiate and facilitate the spread of epileptiform activity following TBI. Increased glutamatergic signaling due to loss of GABAergic control may provide a mechanism by which TBI can give rise to post-traumatic epilepsy. PMID:24610117

  5. Imbalance between Glutamate and GABA in Fmr1 Knockout Astrocytes Influences Neuronal Development

    PubMed Central

    Wang, Lu; Wang, Yan; Zhou, Shimeng; Yang, Liukun; Shi, Qixin; Li, Yujiao; Zhang, Kun; Yang, Le; Zhao, Minggao; Yang, Qi

    2016-01-01

    Fragile X syndrome (FXS) is a form of inherited mental retardation that results from the absence of the fragile X mental retardation protein (FMRP), the product of the Fmr1 gene. Numerous studies have shown that FMRP expression in astrocytes is important in the development of FXS. Although astrocytes affect neuronal dendrite development in Fmr1 knockout (KO) mice, the factors released by astrocytes are still unclear. We cultured wild type (WT) cortical neurons in astrocyte-conditioned medium (ACM) from WT or Fmr1 KO mice. Immunocytochemistry and Western blotting were performed to detect the dendritic growth of both WT and KO neurons. We determined glutamate and γ-aminobutyric acid (GABA) levels using high-performance liquid chromatography (HPLC). The total neuronal dendritic length was reduced when cultured in the Fmr1 KO ACM. This neurotoxicity was triggered by an imbalanced release of glutamate and GABA from Fmr1 KO astrocytes. We found increased glutaminase and GABA transaminase (GABA-T) expression and decreased monoamine oxidase B expression in Fmr1 KO astrocytes. The elevated levels of glutamate contributed to oxidative stress in the cultured neurons. Vigabatrin (VGB), a GABA-T inhibitor, reversed the changes caused by glutamate and GABA release in Fmr1 KO astrocytes and the abnormal behaviors in Fmr1 KO mice. Our results indicate that the imbalance in the astrocytic glutamate and GABA release may be involved in the neuropathology and the underlying symptoms of FXS, and provides a therapeutic target for treatment. PMID:27517961

  6. Haloperidol abolished glutamate release evoked by photic stimulation of the visual cortex in rats.

    PubMed

    Reyes, Elbert; Rossell, Sergio; Paredes, Daniel; Rada, Pedro; Tucci, Sonia; Gonzalez, Luis E; Hernández, Luis

    2002-07-26

    There is evidence that systemic administration of haloperidol, a dopamine receptor blocker, attenuates visual cortex evoked potentials. However, there is scarce information on cortical neurochemical changes associated with haloperidol effects on visual function. The present experiment was designed to investigate: (1) the effect of photic stimulation on glutamate release in the visual cortex; and (2) whether systemic administration of haloperidol would affect those neurochemical changes. Microdialysis probes were implanted in the occipital cortex. Glutamate levels were measured every 30 s using capillary zone electrophoresis. Extracellular glutamate levels increased to about 282% 30 s after photic stimulation started and remain elevated for the 3 min that the photic stimulation lasted. Haloperidol (1.5 and 5 mg/kg, i.p.) completely suppressed the increased of glutamate efflux during photic stimulation. Finally, it was also found that the highest dose of haloperidol (5 mg/kg) did not change glutamate basal levels. The results are discussed with reference to possible dopaminergic actions on the visual system function.

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  8. Hesperidin inhibits glutamate release and exerts neuroprotection against excitotoxicity induced by kainic acid in the hippocampus of rats.

    PubMed

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

    2015-09-01

    The citrus flavonoid hesperidin exerts neuroprotective effects and could cross the blood-brain barrier. Given the involvement of glutamate neurotoxicity in the pathogenesis of neurodegenerative disorders, this study was conducted to evaluate the potential role of hesperidin in glutamate release and glutamate neurotoxicity in the hippocampus of rats. In rat hippocampal nerve terminals (synaptosomes), hesperidin inhibited the release of glutamate and elevation of cytosolic free Ca(2+) concentration evoked by 4-aminopyridine (4-AP), but did not alter 4-AP-mediated depolarization. The inhibitory effect of hesperidin on evoked glutamate release was prevented by chelating the extracellular Ca(2+) ions and blocking the activity of Cav2.2 (N-type) and Cav2.1 (P/Q-type) channels or protein kinase C. In hippocampal slice preparations, whole-cell patch clamp experiments showed that hesperidin reduced the frequency of spontaneous excitatory postsynaptic currents without affecting their amplitude, indicating the involvement of a presynaptic mechanism. In addition, intraperitoneal (i.p.) injection of kainic acid (KA, 15 mg/kg) elevated the extracellular glutamate levels and caused considerable neuronal loss in the hippocampal CA3 area. These KA-induced alterations were attenuated by pretreatment with hesperidin (10 or 50 mg/kg, i.p.) before administering the KA. These results demonstrate that hesperidin inhibits evoked glutamate release in vitro and attenuates in vivo KA-induced neuronal death in the hippocampus. Our findings indicate that hesperidin may be a promising candidate for preventing or treating glutamate excitotoxicity related brain disorders such as neurodegenerative diseases.

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

    PubMed

    López-Colomé, Ana María; López, Edith; Mendez-Flores, Orquidia G; Ortega, Arturo

    2016-07-01

    Glutamate, the main excitatory amino acid in the vertebrate retina, is a well know activator of numerous signal transduction pathways, and has been critically involved in long-term synaptic changes acting through ionotropic and metabotropic glutamate receptors. However, recent findings underlining the importance of intensity and duration of glutamate stimuli for specific neuronal responses, including excitotoxicity, suggest a crucial role for Na(+)-dependent glutamate transporters, responsible for the removal of this neurotransmitter from the synaptic cleft, in the regulation of glutamate-induced signaling. Transporter proteins are expressed in neurons and glia cells, albeit most of glutamate uptake occurs in the glial compartment. Within the retina, Müller glia cells are in close proximity to glutamatergic synapses and participate in the recycling of glutamate through the glutamate/glutamine shuttle. In this context, we decided to investigate a plausible role of glutamate as a regulatory signal for its own transport in human retinal glia cells. To this end, we determined [(3)H]-D-aspartate uptake in cultures of spontaneously immortalized human Müller cells (MIO-M1) exposed to distinct glutamatergic ligands. A time and dose-dependent increase in the transporter activity was detected. This effect was dependent on the activation of the N-methyl D-aspartate subtype of glutamate receptors, due to a dual effect: an increase in affinity and an augmented expression of the transporter at the plasma membrane, as established via biotinylation experiments. Furthermore, a NMDA-dependent association of glutamate transporters with the cystoskeletal proteins ezrin and glial fibrillary acidic protein was also found. These results add a novel mediator of the glutamate transporter modulation and further strengthen the notion of the critical involvement of glia cells in synaptic function. PMID:27017513

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2016-10-01

    Insula and paralimbic region represent a common location for gliomas in adulthood. However, limbic and paralimbic tumors are rare in children. Reports of pediatric insular tumors are scarce in literature, and most of them are included in adult's series, so their management and outcome can be outlined only after extracting data from these reports. Due to their predominantly low grade, they usually have a benign course for some time, what make them ideal candidates for total resection. However, their intricate location and spread to key areas, including the temporal lobe, make them a surgical challenge. The transsylvian route, with or without resection of the frontal and/or temporal operculae, which requires exposure of part or all of the insula is commonly selected for insular tumor approaches. Intraoperative functional mapping is a standard procedure for resection of central region tumors in adults. In children and young individuals, awake craniotomy is not always possible and surgical planning usually relay on functional and anatomical preoperative studies. The main goal when approaching an insular tumor is to achieve the largest extent of resection to increase overall patient survival while preserving the functional status, minimizing postoperative morbidity and increasing the quality of life. The extent of resection seems to be correlated also with the control of associated (and usually intractable) epilepsy. PMID:27659830

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

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

    2015-07-21

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

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

    PubMed

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

    2015-07-21

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

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

    PubMed Central

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

    2013-01-01

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

  17. Regulation of Synaptic Transmission by Ambient Extracellular Glutamate

    PubMed Central

    FEATHERSTONE, DAVID E.; SHIPPY, SCOTT A.

    2008-01-01

    Many neuroscientists assume that ambient extracellular glutamate concentrations in the nervous system are biologically negligible under nonpathological conditions. This assumption is false. Hundreds of studies over several decades suggest that ambient extracellular glutamate levels in the intact mammalian brain are ~0.5 to ~5 μM. This has important implications. Glutamate receptors are desensitized by glutamate concentrations significantly lower than needed for receptor activation; 0.5 to 5 μM of glutamate is high enough to cause constitutive desensitization of most glutamate receptors. Therefore, most glutamate receptors in vivo may be constitutively desensitized, and ambient extracellular glutamate and receptor desensitization may be potent but generally unrecognized regulators of synaptic transmission. Unfortunately, the mechanisms regulating ambient extracellular glutamate and glutamate receptor desensitization remain poorly understood and understudied. PMID:17947494

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

    PubMed

    Y Lmaz, Demet; Karaku, Emine

    2011-12-01

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

  19. Brain glutamate decarboxylase and pyrroloquinoline quinone.

    PubMed

    Choi, S Y; Khemlani, L S; Churchich, J E

    1992-01-01

    Porcine brain glutamate decarboxylase was examined for the presence of covalently bound pyrroloquinoline quinone (PQQ). HPLC analysis of pure glutamate decarboxylase subjected to the hexanol extraction procedure gave negative results when monitored at 320 nm, the maximum of absorbance of 4-hydroxy-5-hexoxy-PQQ. Resolved glutamate decarboxylase exhibits a structureless absorption band at wavelengths longer than 300 nm which cannot be attributed to PQQ. The holoenzyme is not a pyridoxal-quinoprotein; its catalytic mechanism involves the participation of only one cofactor, i.e. pyridoxal-5-P. Free PQQ is a strong inhibitor of the decarboxylase (Ki = 13 microM) and the reaction with the protein results in spectral changes resembling those of polylysine treated with PQQ. If the concentration of free PQQ in some regions of the brain reaches the micromolar level, then PQQ might play a role in the regulation of glutamate decarboxylase activity.

  20. Mechanism for the activation of glutamate receptors

    Cancer.gov

    Scientists at the NIH have used a technique called cryo-electron microscopy to determine a molecular mechanism for the activation and desensitization of ionotropic glutamate receptors, a prominent class of neurotransmitter receptors in the brain and spina

  1. DNA nanopore translocation in glutamate solutions

    NASA Astrophysics Data System (ADS)

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

    2015-08-01

    Nanopore experiments have traditionally been carried out with chloride-based solutions. Here we introduce silver/silver-glutamate-based electrochemistry as an alternative, and study the viscosity, conductivity, and nanopore translocation characteristics of potassium-, sodium-, and lithium-glutamate solutions. We show that it has a linear response at typical voltages and can be used to detect DNA translocations through a nanopore. The glutamate anion also acts as a redox-capable thickening agent, with high-viscosity solutions capable of slowing down the DNA translocation process by up to 11 times, with a corresponding 7 time reduction in signal. These results demonstrate that glutamate can replace chloride as the primary anion in nanopore resistive pulse sensing.

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

    PubMed

    Tanaka, Kohichi

    2016-01-01

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

  3. Glutamic Acid Decarboxylation in Chlorella12

    PubMed Central

    Lane, T. R.; Stiller, Mary

    1970-01-01

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

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

    PubMed

    Jezová, D; Juránková, E; Vigas, M

    1995-11-01

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

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

    PubMed Central

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

    2014-01-01

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

  6. Ionotropic Glutamate Receptors & CNS Disorders

    PubMed Central

    Bowie, Derek

    2008-01-01

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

  7. Medroxyprogesterone acetate exacerbates glutamate excitotoxicity.

    PubMed

    Nilsen, Jon; Morales, Alison; Brinton, Roberta Diaz

    2006-07-01

    We previously demonstrated that progesterone functions as a neuroprotective agent whereas medroxyprogesterone acetate (MPA; Provera) does not. Moreover, MPA antagonized the neuroprotective and neurotrophic outcomes induced by 17beta-estradiol (E2). Towards developing effective hormone therapies for protection against neurodegeneration, we sought to determine whether formulation, chemical features or prevention versus treatment mode of exposure affected the outcome of MPA treatment in survival of primary hippocampal neurons. Results of these analyses indicated that both crystalline MPA and a pharmaceutical formulation (Depo-Provera) lacked neuroprotective efficacy, indicating that the effects were not dependent upon MPA formulation. Likewise, MPA in the prevention and treatment paradigms were equally ineffective at promoting neuronal survival, indicating that timing of MPA administration was not a factor. Further, the detrimental effects of MPA were not due to the presence of the acetate group, as medroxyprogesterone was as ineffective as MPA in promoting neuronal survival. Moreover, MPA pretreatment exacerbated neuron death induced by glutamate excitotoxicity as indicated by a 40% increase in neuron death determined by direct live/dead cell count and a commensurate increase in the number of positive cells by terminal deoxynucleotidyl transferase-mediated nick end-labeling. Collectively these results predict that the progestin formulation of hormone therapy will affect the vulnerability of the central nervous system to degenerative insults.

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

    PubMed

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

    2016-01-01

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

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

    PubMed

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

    2016-01-01

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

  10. To-and-fro optical voltage signal propagation between the insular gustatory and parietal oral somatosensory areas in rat cortex slices.

    PubMed

    Yoshimura, Hiroshi; Kato, Nobuo; Sugai, Tokio; Honjo, Makoto; Sato, Jun; Segami, Natsuki; Onoda, Norihiko

    2004-07-23

    Taste perception depends not only on special taste information processed in the insular cortex, but also on oral somesthetic processing in the parietal cortex. Many insular cortex neurons show multimodal responsiveness. Such multimodality may be enabled by signal exchange between these two cortices. By using the protocol that we have developed, a synchronized population oscillation of synaptic potentials was induced in the parietal cortex by stimulation to the insular cortex in rat neocortex slices. The spatiotemporal pattern of propagation of this oscillation was studied by recording voltage-sensitive optical signals and field potentials. The first wavelet of the oscillation was propagated from the insular stimulation site to the parietal cortex. However, the second and later wavelets propagated back from the parietal cortex to the insular cortex. The oscillation was detected in the insular cortex as well, but was actually generated in the parietal cortex. Thus, the initial peak of optical signal, sent from the insular to parietal cortex, served to generate oscillatory responses in the parietal cortex, which propagated back to the insular cortex wave-by-wave. We propose that this to-and-fro propagation may be an artificially exaggerated demonstration of an intrinsic mechanism relevant to signal exchange between the parietal and insular cortices.

  11. Elevation changes

    USGS Publications Warehouse

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

    1992-01-01

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

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

    ERIC Educational Resources Information Center

    Dougherty, Charles M; Dayan, Jean

    1982-01-01

    Describes procedures and semi-micro reaction apparatus (carbon dioxide trap) to demonstrate how a particular enzyme (L-Glutamic acid decarboxylase) may be used to determine the site or sites of labeling in its substrate (carbon-14 labeled glutamic acid). Includes calculations, solutions, and reagents used. (Author/SK)

  13. Role of glutamate receptors in the nucleus accumbens on behavioural responses to novel conflictive and non-conflictive environments in the rat.

    PubMed

    Alvarez, E O; Ruarte, M B

    2001-09-14

    The possible role of glutamic acid locally applied into the nucleus accumbens on exploratory behaviours measured in 'conflictive' and 'non-conflictive' environments was studied in adult male rats. As a model of conflictive environment, the elevated asymmetric-plus maze (APM) was used. As a model of a non-conflictive environment, a modified holeboard enriched with an object (OVM) was used. In order to characterize the possible glutamic acid receptors involved, the following antagonists were also used: AP3 (antagonist of the metabotropic glutamic acid receptor), AP7 (antagonist of NMDA glutamic acid receptor, and CNQX (antagonists of kainate/AMPA glutamic acid receptor). Results showed that injection of glutamic acid into the nucleus accumbens induced in the APM a decrease of exploration and an increase of the permanency score (non-exploratory behaviours) of the 'High and Low wall' arm. However, in the 'Two High Walls' arm, glutamic acid decreased permanency. In the OVM, no major changes in the motor activity were observed with glutamic acid. Nevertheless, the vertical activity (an index of rearing) and head-dipping were inhibited by the amino-acid treatment. In the APM, the decrease of exploration induced by glutamic acid was blocked by all three receptor antagonists. In the non-exploratory behaviours, the facilitatory effect observed in the 'High and Low walls' arm was blocked only by AP7 and CNQX. The inhibitory action of glutamic acid on the permanency score in the 'Two High Walls' arm was not blocked by the receptors antagonists. In the OVM, AP7 and CNQX were effective in blocking the inhibition of glutamic acid on the vertical activity, but in head-dipping, only AP3 and CNQX were able to block the effect of the amino acid on this behaviour. In conclusion, the present results are compatible with the concept that glutamatergic input fibres to the nucleus accumbens modulate the expression of exploratory behaviour induced by novelty in conflictive and non

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

    PubMed

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

    2004-10-01

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

  15. Glutamate Metabolism in Major Depressive Disorder

    PubMed Central

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

    2015-01-01

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

  16. Flavor Preferences Conditioned by Dietary Glutamate.

    PubMed

    Ackroff, Karen; Sclafani, Anthony

    2016-07-01

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

  17. Building and Applying "Insularity Theory": Review on Knapp's Prehistoric and Protohistoric Cyprus, 2008.

    NASA Astrophysics Data System (ADS)

    Katsarou-Tzeveleki, Stella

    listing of external factors (colonization, invasions) originating in the Near East and the Aegean as sequential narrative history, and the descriptive, systemic analysis of 'materiality, production, trade, migration and colonization which have for long been the cornerstones of Cypriot archaeology' (p. 11). In contrast, he turns his attention towards the internal processes within the island society of Bronze Age Cyprus, which shape its insularity and give it a distinctive identity at this specific period, processes that lead to contextual history and formative tradition. 'To study how any society changes, at any time, it is crucial first to look at internal rather than external factors' (p. 1). Defining the concept of insularity is his aim; therefore, he begins with a number of very apposite rhetorical questions (p. 13) and identifies several individual parameters (connectivity, islandscape, social identity, ethnicity, migration, acculturation, hybridization) to which he assigns collective and individual meanings. The eight chapters that follow may be assigned, broadly, to three general units: in the first of these (ch. 1-2), Knapp offers a synthesis of these parameters in the form of a 'theory of insularity'. In the second (ch. 3-7) he formulates his revised narrative of the prehistory and social identity of the island, which involves a presentation of social and economic, rather than stylistic categories, on the basis of the parameters laid down in his theoretical scheme. Finally, in the third unit (ch. 8), he records his overall conclusions, the new cognitive experiences and concerns that have emerged from the application of his theory, both to Cyprus and to insular archaeology in the Mediterranean and on a world scale. Knapp's synthesis of the theory of insularity in the first unit is a major contribution to Mediterranean archaeology, and makes this book a seminal work. Continuing and broadening Broodbank's (2000) reasoning about the Cyclades, Knapp, with Cyprus as his

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

    USGS Publications Warehouse

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

    2012-01-01

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

  19. Alternating skew deviation in association with anti-glutamic acid decarboxylase antibodies

    PubMed Central

    Farooq, Asim V.; Soin, Ketki; Moss, Heather E.

    2015-01-01

    The presence of an elevated anti-glutamic acid decarboxylase (GAD) antibody level has been associated with a number of eye movement abnormalities, as well as other findings including cerebellar ataxia and insulin dependent diabetes mellitus. Skew deviation in association with anti-GAD antibodies has not been previously reported. Here we report a case of alternating skew deviation along with cerebellar-brainstem signs in a patient with an elevated anti-GAD antibody titer. Follow-up neurologic evaluation after treatment with intravenous immunoglobulin revealed improvement in cerebellar-brainstem signs, while ophthalmic evaluation was stable. PMID:26594078

  20. Selection-Based Biodiversity at a Small Spatial Scale in a Low-Dispersing Insular Bird.

    PubMed

    Blondel; Dias; Perret; Maistre; Lambrechts

    1999-08-27

    The blue tit is a highly mobile small passerine found in deciduous and evergreen oaks. In mainland populations, gene flow results in local maladaptive timing of breeding in evergreen oak forests, the rarer habitat. However, on the island of Corsica, two populations only 25 kilometers apart are highly specialized and differ between the two habitat types in breeding and morphological traits. In contrast to theoretical predictions about the homogenizing effects of gene flow, this highlights evolutionary consequences of habitat diversification and isolation at a small spatial scale in insular organisms, which should be taken into account in conservation policies.

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

    PubMed

    Rimmele, Theresa S; Rosenberg, Paul A

    2016-09-01

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

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

    PubMed

    Rimmele, Theresa S; Rosenberg, Paul A

    2016-09-01

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

  3. Mood disorders: regulation by metabotropic glutamate receptors.

    PubMed

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

    2008-03-01

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

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

    PubMed Central

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

    2009-01-01

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

  5. Glutamic acid decarboxylase and glutamate receptor changes during tolerance and dependence to benzodiazepines

    PubMed Central

    Izzo, Emanuela; Auta, James; Impagnatiello, Francesco; Pesold, Christine; Guidotti, Alessandro; Costa, Erminio

    2001-01-01

    Protracted administration of diazepam elicits tolerance, whereas discontinuation of treatment results in signs of dependence. Tolerance to the anticonvulsant action of diazepam is present in an early phase (6, 24, and 36 h) but disappears in a late phase (72–96 h) of withdrawal. In contrast, signs of dependence such as decrease in open-arm entries on an elevated plus-maze and increased susceptibility to pentylenetetrazol-induced seizures were apparent 96 h (but not 12, 24, or 48 h) after diazepam withdrawal. During the first 72 h of withdrawal, tolerance is associated with changes in the expression of GABAA (γ-aminobutyric acid type A) receptor subunits (decrease in γ2 and α1; increase in α5) and with an increase of mRNA expression of the most abundant form of glutamic acid decarboxylase (GAD), GAD67. In contrast, dl-α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor GluR1 subunit mRNA and cognate protein, which are normal during the early phase of diazepam withdrawal, increase by approximately 30% in cortex and hippocampus in association with the appearance of signs of dependence 96 h after diazepam withdrawal. Immunohistochemical studies of GluR1 subunit expression with gold-immunolabeling technique reveal that the increase of GluR1 subunit protein is localized to layer V pyramidal neurons and their apical dendrites in the cortex, and to pyramidal neurons and in their dendritic fields in hippocampus. The results suggest an involvement of GABA-mediated processes in the development and maintenance of tolerance to diazepam, whereas excitatory amino acid-related processes (presumably via AMPA receptors) may be involved in the expression of signs of dependence after withdrawal. PMID:11248104

  6. Glutamic acid decarboxylase and glutamate receptor changes during tolerance and dependence to benzodiazepines.

    PubMed

    Izzo, E; Auta, J; Impagnatiello, F; Pesold, C; Guidotti, A; Costa, E

    2001-03-13

    Protracted administration of diazepam elicits tolerance, whereas discontinuation of treatment results in signs of dependence. Tolerance to the anticonvulsant action of diazepam is present in an early phase (6, 24, and 36 h) but disappears in a late phase (72-96 h) of withdrawal. In contrast, signs of dependence such as decrease in open-arm entries on an elevated plus-maze and increased susceptibility to pentylenetetrazol-induced seizures were apparent 96 h (but not 12, 24, or 48 h) after diazepam withdrawal. During the first 72 h of withdrawal, tolerance is associated with changes in the expression of GABA(A) (gamma-aminobutyric acid type A) receptor subunits (decrease in gamma(2) and alpha(1); increase in alpha(5)) and with an increase of mRNA expression of the most abundant form of glutamic acid decarboxylase (GAD), GAD(67). In contrast, dl-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor GluR1 subunit mRNA and cognate protein, which are normal during the early phase of diazepam withdrawal, increase by approximately 30% in cortex and hippocampus in association with the appearance of signs of dependence 96 h after diazepam withdrawal. Immunohistochemical studies of GluR1 subunit expression with gold-immunolabeling technique reveal that the increase of GluR1 subunit protein is localized to layer V pyramidal neurons and their apical dendrites in the cortex, and to pyramidal neurons and in their dendritic fields in hippocampus. The results suggest an involvement of GABA-mediated processes in the development and maintenance of tolerance to diazepam, whereas excitatory amino acid-related processes (presumably via AMPA receptors) may be involved in the expression of signs of dependence after withdrawal.

  7. Luminal l-glutamate enhances duodenal mucosal defense mechanisms via multiple glutamate receptors in rats

    PubMed Central

    Watanabe, Chikako; Mizumori, Misa; Kaunitz, Jonathan D.

    2009-01-01

    Presence of taste receptor families in the gastrointestinal mucosa suggests a physiological basis for local and early detection of a meal. We hypothesized that luminal l-glutamate, which is the primary nutrient conferring fundamental umami or proteinaceous taste, influences mucosal defense mechanisms in rat duodenum. We perfused the duodenal mucosa of anesthetized rats with l-glutamate (0.1–10 mM). Intracellular pH (pHi) of the epithelial cells, blood flow, and mucus gel thickness (MGT) were simultaneously and continuously measured in vivo. Some rats were pretreated with indomethacin or capsaicin. Duodenal bicarbonate secretion (DBS) was measured with flow-through pH and CO2 electrodes. We tested the effects of agonists or antagonists for metabotropic glutamate receptor (mGluR) 1 or 4 or calcium-sensing receptor (CaSR) on defense factors. Luminal l-glutamate dose dependently increased pHi and MGT but had no effect on blood flow in the duodenum. l-glutamate (10 mM)-induced cellular alkalinization and mucus secretion were inhibited by pretreatment with indomethacin or capsaicin. l-glutamate effects on pHi and MGT were mimicked by mGluR4 agonists and inhibited by an mGluR4 antagonist. CaSR agonists acidified cells with increased MGT and DBS, unlike l-glutamate. Perfusion of l-glutamate with inosinate (inosine 5′-monophosphate, 0.1 mM) enhanced DBS only in combination, suggesting synergistic activation of the l-glutamate receptor, typical of taste receptor type 1. l-leucine or l-aspartate had similar effects on DBS without any effect on pHi and MGT. Preperfusion of l-glutamate prevented acid-induced cellular injury, suggesting that l-glutamate protects the mucosa by enhancing mucosal defenses. Luminal l-glutamate may activate multiple receptors and afferent nerves and locally enhance mucosal defenses to prevent subsequent injury attributable to acid exposure in the duodenum. PMID:19643955

  8. Metabolism of Proline, Glutamate, and Ornithine in Proline Mutant Root Tips of Zea mays (L.)

    PubMed Central

    Dierks-Ventling, Christa; Tonelli, Chiara

    1982-01-01

    In excised pro1-1 mutant and corresponding normal type roots of Zea mays L. the uptake and interconversion of [14C]proline, [14C]glutamic acid, [14C]glutamine, and [14C]ornithine and their utilization for protein synthesis was measured with the intention of finding an explanation for the proline requirement of the mutant. Uptake of these four amino acids, with the exception of proline, was the same in mutant and normal roots, but utilization differed. Higher than normal utilization rates for proline and glutamic acid were noted in mutant roots leading to increased CO2 production, free amino acid interconversion, and protein synthesis. Proline was synthesized from either glutamic acid (or glutamine) or ornithine in both mutant and normal roots; it did not accumulate but rather was used for protein synthesis. Ornithine was not a good precursor for proline in either system, but was preferentially converted to arginine and glutamine, particularly in mutant roots. The pro1-1 mutant was thus not deficient in its ability to make proline. Based on these findings, and on the fact that ornithine, arginine, glutamic acid and aspartic acid are elevated as free amino acids in mutant roots, it is suggested that in the pro1-1 mutant proline catabolism prevails over proline synthesis. PMID:16662144

  9. Utility Towers, Insulator Detail, Front Elevation, Side Elevation, Elevation, Double ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Utility Towers, Insulator Detail, Front Elevation, Side Elevation, Elevation, Double Pole Tower, Single Pole Tower - La Bajada Historic Trails and Roads, Approximately 1 mile East/Northeast of intersection of State Highway 16 and Indian Service Road 841, La Bajada, Santa Fe County, NM

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

    PubMed

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

    2016-06-14

    The planning of any motor action requires a complex multisensory processing by the brain. Gravity - immutable on Earth - has been shown to be a key input to these mechanisms. Seminal fMRI studies performed during visual perception of falling objects and self-motion demonstrated that humans represent the action of gravity in parts of the cortical vestibular system; in particular, the insular cortex and the cerebellum. However, little is known as to whether a specific neural network is engaged when processing non-visual signals relevant to gravity. We asked participants to perform vertical and horizontal hand movements without visual control, while lying in a 3T-MRI scanner. We highlighted brain regions activated in the processing of vertical movements, for which the effects of gravity changed during execution. Precisely, the left insula was activated in vertical movements and not in horizontal movements. Moreover, the network identified by contrasting vertical and horizontal movements overlapped with neural correlates previously associated to the processing of simulated self-motion and visual perception of the vertical direction. Interestingly, we found that the insular cortex activity is direction-dependent which suggests that this brain region processes the effects of gravity on the moving limbs through non-visual signals. PMID:27001175

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

    PubMed

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

    2015-09-01

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

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

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

    2006-06-01

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

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

    PubMed

    Radlanski, Ralf J; Renz, Herbert

    2007-01-01

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

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

    PubMed

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

    2016-01-01

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

  17. 21 CFR 182.1047 - Glutamic acid hydrochloride.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

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

  18. 21 CFR 182.1047 - Glutamic acid hydrochloride.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Glutamic acid hydrochloride. 182.1047 Section 182.1047 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... Food Substances § 182.1047 Glutamic acid hydrochloride. (a) Product. Glutamic acid hydrochloride....

  19. 21 CFR 182.1047 - Glutamic acid hydrochloride.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Glutamic acid hydrochloride. 182.1047 Section 182.1047 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... Food Substances § 182.1047 Glutamic acid hydrochloride. (a) Product. Glutamic acid hydrochloride....

  20. 21 CFR 182.1047 - Glutamic acid hydrochloride.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Glutamic acid hydrochloride. 182.1047 Section 182.1047 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... Food Substances § 182.1047 Glutamic acid hydrochloride. (a) Product. Glutamic acid hydrochloride....

  1. Localization of L-glutamate and glutamate-like receptors at the squid giant synapse.

    PubMed

    Di Cosmo, A; Nardi, G; Di Cristo, C; De Santis, A; Messenger, J B

    1999-08-28

    HPLC analysis of the amino acid contents of the second- and third-order giant fibres at the giant synapse in the stellate ganglion of the squid Loligo vulgaris shows that there are significantly higher amounts of L-glutamate and L-aspartate in the second-order (presynaptic) fibre than in the third-order (postsynaptic) fibre. Immunocytochemical staining of sections of the ganglion with an antibody raised against L-glutamate produces specific positive staining in the synaptic region of the second-order fibre. In contrast, staining with antibodies raised against glutamate-receptors (mammalian GluR1 with GluR2/3) produces positive staining in the third-order fibre at the postsynaptic region. These data provide further evidence for the hypothesis that L-glutamate is an excitatory transmitter at the giant synapse.

  2. Circuit mapping by ultraviolet uncaging of glutamate.

    PubMed

    Shepherd, Gordon M G

    2012-09-01

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

  3. L-glutamate Receptor In Paramecium

    NASA Astrophysics Data System (ADS)

    Bernal-Martínez, Juan; Ortega-Soto, Arturo

    2004-09-01

    Behavioral, electrophysiological and biochemical experiments were performed in order to establish the presence of a glutamate receptor in the ciliate Paramecium. It was found that an AMPA/KA receptor is functionally expressed in Paramecium and that this receptor is immunologically and fillogenetically related to the AMPA/KA receptor present in vertebrates.

  4. Glutamate Mediated Astrocytic Filtering of Neuronal Activity

    PubMed Central

    Herzog, Nitzan; De Pittà, Maurizio; Jacob, Eshel Ben; Berry, Hugues; Hanein, Yael

    2014-01-01

    Neuron-astrocyte communication is an important regulatory mechanism in various brain functions but its complexity and role are yet to be fully understood. In particular, the temporal pattern of astrocyte response to neuronal firing has not been fully characterized. Here, we used neuron-astrocyte cultures on multi-electrode arrays coupled to Ca2+ imaging and explored the range of neuronal stimulation frequencies while keeping constant the amount of stimulation. Our results reveal that astrocytes specifically respond to the frequency of neuronal stimulation by intracellular Ca2+ transients, with a clear onset of astrocytic activation at neuron firing rates around 3-5 Hz. The cell-to-cell heterogeneity of the astrocyte Ca2+ response was however large and increasing with stimulation frequency. Astrocytic activation by neurons was abolished with antagonists of type I metabotropic glutamate receptor, validating the glutamate-dependence of this neuron-to-astrocyte pathway. Using a realistic biophysical model of glutamate-based intracellular calcium signaling in astrocytes, we suggest that the stepwise response is due to the supralinear dynamics of intracellular IP3 and that the heterogeneity of the responses may be due to the heterogeneity of the astrocyte-to-astrocyte couplings via gap junction channels. Therefore our results present astrocyte intracellular Ca2+ activity as a nonlinear integrator of glutamate-dependent neuronal activity. PMID:25521344

  5. Structural Features of the Glutamate Transporter Family

    PubMed Central

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

    1999-01-01

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

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

    PubMed

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

    2016-08-01

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

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

    PubMed

    Liang, Bo; Zhang, Shu; Lang, Qiaolin; Song, Jianxia; Han, Lihui; Liu, Aihua

    2015-07-16

    A novel L-glutamate biosensor was fabricated using bacteria surface-displayed glutamate dehydrogenase (Gldh-bacteria). Here the cofactor NADP(+)-specific dependent Gldh was expressed on the surface of Escherichia coli using N-terminal region of ice nucleation protein (INP) as the anchoring motif. The cell fractionation assay and SDS-PAGE analysis indicated that the majority of INP-Gldh fusion proteins were located on the surface of cells. The biosensor was fabricated by successively casting polyethyleneimine (PEI)-dispersed multi-walled carbon nanotubes (MWNTs), Gldh-bacteria and Nafion onto the glassy carbon electrode (Nafion/Gldh-bacteria/PEI-MWNTs/GCE). The MWNTs could not only significantly lower the oxidation overpotential towards NAPDH, which was the product of NADP(+) involving in the oxidation of glutamate by Gldh, but also enhanced the current response. Under the optimized experimental conditions, the current-time curve of the Nafion/Gldh-bacteria/PEI-MWNTs/GCE was performed at +0.52 V (vs. SCE) by amperometry varying glutamate concentration. The current response was linear with glutamate concentration in two ranges (10 μM-1 mM and 2-10 mM). The low limit of detection was estimated to be 2 μM glutamate (S/N=3). Moreover, the proposed biosensor is stable, specific, reproducible and simple, which can be applied to real samples detection.

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

    PubMed

    Liang, Bo; Zhang, Shu; Lang, Qiaolin; Song, Jianxia; Han, Lihui; Liu, Aihua

    2015-07-16

    A novel L-glutamate biosensor was fabricated using bacteria surface-displayed glutamate dehydrogenase (Gldh-bacteria). Here the cofactor NADP(+)-specific dependent Gldh was expressed on the surface of Escherichia coli using N-terminal region of ice nucleation protein (INP) as the anchoring motif. The cell fractionation assay and SDS-PAGE analysis indicated that the majority of INP-Gldh fusion proteins were located on the surface of cells. The biosensor was fabricated by successively casting polyethyleneimine (PEI)-dispersed multi-walled carbon nanotubes (MWNTs), Gldh-bacteria and Nafion onto the glassy carbon electrode (Nafion/Gldh-bacteria/PEI-MWNTs/GCE). The MWNTs could not only significantly lower the oxidation overpotential towards NAPDH, which was the product of NADP(+) involving in the oxidation of glutamate by Gldh, but also enhanced the current response. Under the optimized experimental conditions, the current-time curve of the Nafion/Gldh-bacteria/PEI-MWNTs/GCE was performed at +0.52 V (vs. SCE) by amperometry varying glutamate concentration. The current response was linear with glutamate concentration in two ranges (10 μM-1 mM and 2-10 mM). The low limit of detection was estimated to be 2 μM glutamate (S/N=3). Moreover, the proposed biosensor is stable, specific, reproducible and simple, which can be applied to real samples detection. PMID:26073813

  9. Behavioral deficits in adult rats treated neonatally with glutamate.

    PubMed

    Hlinák, Zdenek; Gandalovicová, Dana; Krejcí, Ivan

    2005-01-01

    The present study evaluated long-term behavioral consequences of neonatal monosodium-l-glutamate (MSG) treatment in rats. The pups received MSG (3 mg/g sc) daily from postnatal day (PD) 5-12. Data from an automatic activity monitor showed that locomotion of MSG-treated females and males aged 56 and 84 days was significantly reduced. Beginning PD 120, three behavioral tests were performed. As compared to the controls, in the elevated plus maze test, modified to evaluate the adaptive form of spatial memory, MSG-treated animals of both sex had significantly prolonged start and transfer latencies. In the social recognition test, assessing olfactory working memory, MSG-treated males displayed a reduced interest in the juvenile conspecific as the stimulus partner during both the initial exposure and re-exposure performed 30 min later. In the open field test, a significant decrease in the habituation rate was found in MSG-treated animals. Sex-dependent differences in behavioral performance were suggested in the open field and elevated plus maze tests. Behavioral changes are discussed in light of the deficits in perception and processing of visual and olfactory stimuli.

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

    ERIC Educational Resources Information Center

    McAvoy, Paula

    2012-01-01

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

  11. 3-Aminoglutarate is a "silent" false transmitter for glutamate neurons.

    PubMed

    Foster, Alan C; Chen, June; Runyan, Stephen; Dinh, Tim; Venadas, Steven; Ehring, George R; Li, Yong-Xin; Staubli, Ursula

    2015-10-01

    Understanding the storage and release of the excitatory neurotransmitter, L-glutamate by synaptic vesicles has lagged behind receptor characterizations due to a lack of pharmacological agents. We report that the glutamate analog, 3-aminoglutarate (3-AG) is a "silent" false transmitter for glutamate neurons that may be a useful tool to study storage and release mechanisms. Like L-glutamate itself, 3-AG is a high-affinity substrate for both the plasma membrane (EAATs) and vesicular (vGLUT) glutamate transporters. As such, EAATs facilitate 3-AG entry into neuronal cytoplasm allowing 3-AG to compete with L-glutamate for transport into vesicles thus reducing glutamate content. In a synaptosomal preparation, 3-AG inhibited calcium-dependent endogenous L-glutamate release. Unlike L-glutamate, 3-AG had low affinity for both ionotropic (NMDA and AMPA) and G-protein coupled (mGlu1-8) receptors. Consequently, 3-AG behaves as a "silent" false transmitter that may be used in physiological experiments to probe synaptic vesicle storage and release mechanisms for L-glutamate. The companion paper by Wu et al. (2015) describes initial experiments that explore the effects of 3-AG on glutamate synaptic transmission under physiological and pathophysiological conditions.

  12. Understanding safety of glutamate in food and brain.

    PubMed

    Mallick, H N

    2007-01-01

    Glutamate is ubiquitous in nature and is present in all living organisms. It is the principal excitatory neurotransmitter in central nervous system. Glutamate is being used as food additive for enhancing flavour for over last 1200 years imparting a unique taste known as "umami" in Japanese. It is being marketed for about last 100 years. The taste of umami is now recognized as the fifth basic taste. Many of the foods used in cooking for enhancing flavour contain high amount of glutamate. Breast milk has the highest concentration of glutamate amongst all amino acids. Glutamate in high doses as gavage or parenteral injection have been reported to produce neurodegeneration in infant rodents. The neurodegeneration was not produced when gluamate was given with food. The Joint FAO/WHO Expert Committee on Food Additives, based on enumerable scientific evidence, has declared that, "glutamate as an additive in food" is not an health hazard to human being. Glutamate is used as signaling molecule not only in neuronal but also in non-neuronal tissues. Excessive accumulation of glutamate in the synaptic cleft has been associated with excitotoxicty and glutamate is implicated in number of neurological disorders. Excessive accumulation could be attributed to increase release, failure of transport system for uptake mechanism, neuronal injury due to hypoxia-ischemia, trauma and associated metabolic failures. The role blood brain barrier, vesicular glutamate and sodium dependent excitatory amino acid transporters in glutamate homeostasis are emphasized in the review.

  13. A neuroprotective role for microRNA miR-1000 mediated by limiting glutamate excitotoxicity.

    PubMed

    Verma, Pushpa; Augustine, George J; Ammar, Mohamed-Raafet; Tashiro, Ayumu; Cohen, Stephen M

    2015-03-01

    Evidence has begun to emerge for microRNAs as regulators of synaptic signaling, specifically acting to control postsynaptic responsiveness during synaptic transmission. In this report, we provide evidence that Drosophila melanogaster miR-1000 acts presynaptically to regulate glutamate release at the synapse by controlling expression of the vesicular glutamate transporter (VGlut). Genetic deletion of miR-1000 led to elevated apoptosis in the brain as a result of glutamatergic excitotoxicity. The seed-similar miR-137 regulated VGluT2 expression in mouse neurons. These conserved miRNAs share a neuroprotective function in the brains of flies and mice. Drosophila miR-1000 showed activity-dependent expression, which might serve as a mechanism to allow neuronal activity to fine-tune the strength of excitatory synaptic transmission.

  14. Nitric oxide mediates glutamate-linked enhancement of cGMP levels in the cerebellum

    SciTech Connect

    Bredt, D.S.; Snyder, S.H. )

    1989-11-01

    Nitric oxide, which mediates influences of numerous neurotransmitters and modulators on vascular smooth muscle and leukocytes, can be formed in the brain from arginine by an enzymatic activity that stoichiometrically generates citrulline. The authors show that glutamate and related amino acids, such as N-methyl-D-aspartate, markedly stimulate arginine-citrulline transformation in cerebellar slices stoichiometrically with enhancement of cGMP levels. N{sup {omega}}-monomethyl-L-arginine blocks the augmentation both of citrulline and cGMP with identical potencies. Arginine competitively reverses both effects of N{sup {omega}}-monomethyl-L-arginine with the same potencies. Hemoglobin, which complexes nitric oxide, prevents the stimulation by N-methyl-D-aspartate of cGMP levels, and superoxide dismutase, which elevates nitric oxide levels, increases cGMP formation. These data establish that nitric oxide mediates the stimulation by glutamate of cGMP formation.

  15. Nitric Oxide Mediates Glutamate-Linked Enhancement of cGMP Levels in the Cerebellum

    NASA Astrophysics Data System (ADS)

    Bredt, David S.; Snyder, Solomon H.

    1989-11-01

    Nitric oxide, which mediates influences of numerous neurotransmitters and modulators on vascular smooth muscle and leukocytes, can be formed in the brain from arginine by an enzymatic activity that stoichiometrically generates citrulline. We show that glutamate and related amino acids, such as N-methyl-D-aspartate, markedly stimulate arginine-citrulline transformation in cerebellar slices stoichiometrically with enhancement of cGMP levels. Nω-monomethyl-L-arginine blocks the augmentation both of citrulline and cGMP with identical potencies. Arginine competitively reverses both effects of Nω-monomethyl-L-arginine with the same potencies. Hemoglobin, which complexes nitric oxide, prevents the stimulation by N-methyl-D-aspartate of cGMP levels, and superoxide dismutase, which elevates nitric oxide levels, increases cGMP formation. These data establish that nitric oxide mediates the stimulation by glutamate of cGMP formation.

  16. Glutamate availability is important in intramuscular amino acid metabolism and TCA cycle intermediates but does not affect peak oxidative metabolism.

    PubMed

    Mourtzakis, M; Graham, T E; González-Alonso, J; Saltin, B

    2008-08-01

    Muscle glutamate is central to reactions producing 2-oxoglutarate, a tricarboxylic acid (TCA) cycle intermediate that essentially expands the TCA cycle intermediate pool during exercise. Paradoxically, muscle glutamate drops approximately 40-80% with the onset of exercise and 2-oxoglutarate declines in early exercise. To investigate the physiological relationship between glutamate, oxidative metabolism, and TCA cycle intermediates (i.e., fumarate, malate, 2-oxoglutarate), healthy subjects trained (T) the quadriceps of one thigh on the single-legged knee extensor ergometer (1 h/day at 70% maximum workload for 5 days/wk), while their contralateral quadriceps remained untrained (UT). After 5 wk of training, peak oxygen consumption (VO2peak) in the T thigh was greater than that in the UT thigh (P<0.05); VO2peak was not different between the T and UT thighs with glutamate infusion. Peak exercise under control conditions revealed a greater glutamate uptake in the T thigh compared with rest (7.3+/-3.7 vs. 1.0+/-0.1 micromol.min(-1).kg wet wt(-1), P<0.05) without increase in TCA cycle intermediates. In the UT thigh, peak exercise (vs. rest) induced an increase in fumarate (0.33+/-0.07 vs. 0.02+/-0.01 mmol/kg dry wt (dw), P<0.05) and malate (2.2+/-0.4 vs. 0.5+/-0.03 mmol/kg dw, P<0.05) and a decrease in 2-oxoglutarate (12.2+/-1.6 vs. 32.4+/-6.8 micromol/kg dw, P<0.05). Overall, glutamate infusion increased arterial glutamate (P<0.05) and maintained this increase. Glutamate infusion coincided with elevated fumarate and malate (P<0.05) and decreased 2-oxoglutarate (P<0.05) at peak exercise relative to rest in the T thigh; there were no further changes in the UT thigh. Although glutamate may have a role in the expansion of the TCA cycle, glutamate and TCA cycle intermediates do not directly affect VO2peak in either trained or untrained muscle.

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  19. Spatial segregation of somato-sensory and pain activations in the human operculo-insular cortex.

    PubMed

    Mazzola, Laure; Faillenot, Isabelle; Barral, Fabrice-Guy; Mauguière, François; Peyron, Roland

    2012-03-01

    The role of operculo-insular region in the processing of somato-sensory inputs, painful or not, is now well established. However, available maps from previous literature show a substantial overlap of cortical areas activated by these stimuli, and the region referred to as the "secondary somatosensory area (SII)" is widely distributed in the parietal operculum. Differentiating SII from posterior insula cortex, which is anatomically contiguous, is not easy, explaining why the "operculo-insular" label has been introduced to describe activations by somatosensory stimuli in this cortical region. Based on the recent cyto-architectural parcellation of the human insular/SII cortices (Eickhoff et al., 2006, Kurth et al., 2010), the present study investigates with functional MRI (fMRI), whether these structural subdivisions could subserve distinct aspects of discriminative somato-sensory functions, including pain. Responses to five types of stimuli applied on the left hand of 25 healthy volunteers were considered: i) tactile stimuli; ii) passive movements; iii) innocuous cold stimuli; iv) non-noxious warm and v) heat pain. Our results show different patterns of activation depending on the type of somato-sensory stimulation. The posterior part of SII (OP1 area), contralateral to stimuli, was the only sub-region activated by all type of stimuli and might therefore be considered as a common cortical target for different types of somato-sensory inputs. Proprioceptive stimulation by passive finger movements activated the posterior part of SII (OP1 sub-region) bilaterally and the contralateral median part of insula (PreCG and MSG). Innocuous cooling activated the contralateral posterior part of SII (OP1) and the dorsal posterior and median part of insula (OP2, PostCG). Pain stimuli induced the most widespread and intense activation that was bilateral in SII (OP1, OP4) and distributed to all sub-regions of contralateral insula (except OP2) and to the anterior part of the

  20. Right insular damage decreases heartbeat awareness and alters cardio-visual effects on bodily self-consciousness.

    PubMed

    Ronchi, Roberta; Bello-Ruiz, Javier; Lukowska, Marta; Herbelin, Bruno; Cabrilo, Ivan; Schaller, Karl; Blanke, Olaf

    2015-04-01

    Recent evidence suggests that multisensory integration of bodily signals involving exteroceptive and interoceptive information modulates bodily aspects of self-consciousness such as self-identification and self-location. In the so-called Full Body Illusion subjects watch a virtual body being stroked while they perceive tactile stimulation on their own body inducing illusory self-identification with the virtual body and a change in self-location towards the virtual body. In a related illusion, it has recently been shown that similar changes in self-identification and self-location can be observed when an interoceptive signal is used in association with visual stimulation of the virtual body (i.e., participants observe a virtual body illuminated in synchrony with their heartbeat). Although brain imaging and neuropsychological evidence suggest that the insular cortex is a core region for interoceptive processing (such as cardiac perception and awareness) as well as for self-consciousness, it is currently not known whether the insula mediates cardio-visual modulation of self-consciousness. Here we tested the involvement of insular cortex in heartbeat awareness and cardio-visual manipulation of bodily self-consciousness in a patient before and after resection of a selective right neoplastic insular lesion. Cardio-visual stimulation induced an abnormally enhanced state of bodily self-consciousness; in addition, cardio-visual manipulation was associated with an experienced loss of the spatial unity of the self (illusory bi-location and duplication of his body), not observed in healthy subjects. Heartbeat awareness was found to decrease after insular resection. Based on these data we propose that the insula mediates interoceptive awareness as well as cardio-visual effects on bodily self-consciousness and that insular processing of interoceptive signals is an important mechanism for the experienced unity of the self. PMID:25676677

  1. Right insular damage decreases heartbeat awareness and alters cardio-visual effects on bodily self-consciousness.

    PubMed

    Ronchi, Roberta; Bello-Ruiz, Javier; Lukowska, Marta; Herbelin, Bruno; Cabrilo, Ivan; Schaller, Karl; Blanke, Olaf

    2015-04-01

    Recent evidence suggests that multisensory integration of bodily signals involving exteroceptive and interoceptive information modulates bodily aspects of self-consciousness such as self-identification and self-location. In the so-called Full Body Illusion subjects watch a virtual body being stroked while they perceive tactile stimulation on their own body inducing illusory self-identification with the virtual body and a change in self-location towards the virtual body. In a related illusion, it has recently been shown that similar changes in self-identification and self-location can be observed when an interoceptive signal is used in association with visual stimulation of the virtual body (i.e., participants observe a virtual body illuminated in synchrony with their heartbeat). Although brain imaging and neuropsychological evidence suggest that the insular cortex is a core region for interoceptive processing (such as cardiac perception and awareness) as well as for self-consciousness, it is currently not known whether the insula mediates cardio-visual modulation of self-consciousness. Here we tested the involvement of insular cortex in heartbeat awareness and cardio-visual manipulation of bodily self-consciousness in a patient before and after resection of a selective right neoplastic insular lesion. Cardio-visual stimulation induced an abnormally enhanced state of bodily self-consciousness; in addition, cardio-visual manipulation was associated with an experienced loss of the spatial unity of the self (illusory bi-location and duplication of his body), not observed in healthy subjects. Heartbeat awareness was found to decrease after insular resection. Based on these data we propose that the insula mediates interoceptive awareness as well as cardio-visual effects on bodily self-consciousness and that insular processing of interoceptive signals is an important mechanism for the experienced unity of the self.

  2. Acetylated chitosan oligosaccharides act as antagonists against glutamate-induced PC12 cell death via Bcl-2/Bax signal pathway.

    PubMed

    Hao, Cui; Gao, Lixia; Zhang, Yiran; Wang, Wei; Yu, Guangli; Guan, Huashi; Zhang, Lijuan; Li, Chunxia

    2015-03-12

    Chitosan oligosaccharides (COSs), depolymerized products of chitosan composed of β-(1→4) D-glucosamine units, have broad range of biological activities such as antitumour, antifungal, and antioxidant activities. In this study, peracetylated chitosan oligosaccharides (PACOs) and N-acetylated chitosan oligosaccharides (NACOs) were prepared from the COSs by chemcal modification. The structures of these monomers were identified using NMR and ESI-MS spectra. Their antagonist effects against glutamate-induced PC12 cell death were investigated. The results showed that pretreatment of PC12 cells with the PACOs markedly inhibited glutamate-induced cell death in a concentration-dependent manner. The PACOs were better glutamate antagonists compared to the COSs and the NACOs, suggesting the peracetylation is essential for the neuroprotective effects of chitosan oligosaccharides. In addition, the PACOs pretreatment significantly reduced lactate dehydrogenase release and reactive oxygen species production. It also attenuated the loss of mitochondrial membrane potential. Further studies indicated that the PACOs inhibited glutamate-induced cell death by preventing apoptosis through depressing the elevation of Bax/Bcl-2 ratio and caspase-3 activation. These results suggest that PACOs might be promising antagonists against glutamate-induced neural cell death.

  3. Acetylated Chitosan Oligosaccharides Act as Antagonists against Glutamate-Induced PC12 Cell Death via Bcl-2/Bax Signal Pathway

    PubMed Central

    Hao, Cui; Gao, Lixia; Zhang, Yiran; Wang, Wei; Yu, Guangli; Guan, Huashi; Zhang, Lijuan; Li, Chunxia

    2015-01-01

    Chitosan oligosaccharides (COSs), depolymerized products of chitosan composed of β-(1→4) d-glucosamine units, have broad range of biological activities such as antitumour, antifungal, and antioxidant activities. In this study, peracetylated chitosan oligosaccharides (PACOs) and N-acetylated chitosan oligosaccharides (NACOs) were prepared from the COSs by chemcal modification. The structures of these monomers were identified using NMR and ESI-MS spectra. Their antagonist effects against glutamate-induced PC12 cell death were investigated. The results showed that pretreatment of PC12 cells with the PACOs markedly inhibited glutamate-induced cell death in a concentration-dependent manner. The PACOs were better glutamate antagonists compared to the COSs and the NACOs, suggesting the peracetylation is essential for the neuroprotective effects of chitosan oligosaccharides. In addition, the PACOs pretreatment significantly reduced lactate dehydrogenase release and reactive oxygen species production. It also attenuated the loss of mitochondrial membrane potential. Further studies indicated that the PACOs inhibited glutamate-induced cell death by preventing apoptosis through depressing the elevation of Bax/Bcl-2 ratio and caspase-3 activation. These results suggest that PACOs might be promising antagonists against glutamate-induced neural cell death. PMID:25775423

  4. Neuronal Activity and Glutamate Uptake Decrease Mitochondrial Mobility in Astrocytes and Position Mitochondria Near Glutamate Transporters

    PubMed Central

    Jackson, Joshua G.; O'Donnell, John C.; Takano, Hajime; Coulter, Douglas A.

    2014-01-01

    Within neurons, mitochondria are nonuniformly distributed and are retained at sites of high activity and metabolic demand. Glutamate transport and the concomitant activation of the Na+/K+-ATPase represent a substantial energetic demand on astrocytes. We hypothesized that mitochondrial mobility within astrocytic processes might be regulated by neuronal activity and glutamate transport. We imaged organotypic hippocampal slice cultures of rat, in which astrocytes maintain their highly branched morphologies and express glutamate transporters. Using time-lapse confocal microscopy, the mobility of mitochondria within individual astrocytic processes and neuronal dendrites was tracked. Within neurons, a greater percentage of mitochondria were mobile than in astrocytes. Furthermore, they moved faster and farther than in astrocytes. Inhibiting neuronal activity with tetrodotoxin (TTX) increased the percentage of mobile mitochondria in astrocytes. Mitochondrial movement in astrocytes was inhibited by vinblastine and cytochalasin D, demonstrating that this mobility depends on both the microtubule and actin cytoskeletons. Inhibition of glutamate transport tripled the percentage of mobile mitochondria in astrocytes. Conversely, application of the transporter substrate d-aspartate reversed the TTX-induced increase in the percentage of mobile mitochondria. Inhibition of reversed Na+/Ca2+ exchange also increased the percentage of mitochondria that were mobile. Last, we demonstrated that neuronal activity increases the probability that mitochondria appose GLT-1 particles within astrocyte processes, without changing the proximity of GLT-1 particles to VGLUT1. These results imply that neuronal activity and the resulting clearance of glutamate by astrocytes regulate the movement of astrocytic mitochondria and suggest a mechanism by which glutamate transporters might retain mitochondria at sites of glutamate uptake. PMID:24478345

  5. Three Distinct Glutamate Decarboxylase Genes in Vertebrates

    PubMed Central

    Grone, Brian P.; Maruska, Karen P.

    2016-01-01

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

  6. The insular cortex controls food preferences independently of taste receptor signaling.

    PubMed

    Oliveira-Maia, Albino J; de Araujo, Ivan E; Monteiro, Clara; Workman, Virginia; Galhardo, Vasco; Nicolelis, Miguel A L

    2012-01-01

    The insular cortex (IC) contains the primary sensory cortex for oral chemosensation including gustation, and its integrity is required for appropriate control of feeding behavior. However, it remains unknown whether the role of this brain area in food selection relies on the presence of peripheral taste input. Using multielectrode recordings, we found that the responses of populations of neurons in the IC of freely licking, sweet-blind Trpm5(-/-) mice are modulated by the rewarding postingestive effects of sucrose. FOS immunoreactivity analyses revealed that these responses are restricted to the dorsal insula. Furthermore, bilateral lesions in this area abolished taste-independent preferences for sucrose that can be conditioned in these Trpm5(-/-) animals while preserving their ability to detect sucrose. Overall, these findings demonstrate that, even in the absence of peripheral taste input, IC regulates food choices based on postingestive signals. PMID:22403530

  7. Relationship between rainfall and Aedes larval population at two insular sites in Pulau Ketam, Selangor, Malaysia.

    PubMed

    Wee, Lim Kwee; Weng, Sit Nam; Raduan, Norzahira; Wah, Sing Kong; Ming, Wong Hong; Shi, Chew Hwai; Rambli, Firdaus; Ahok, Cheryl Jacyln; Marlina, Suria; Ahmad, Nazni Wasi; Mckemy, Andrew; Vasan, S S; Lim, Lee Han

    2013-03-01

    Two insular settlements (Kampung Pulau Ketam and Kampung Sungai Lima) were selected to study the population dynamics of Aedes aegypti and Aedes albopictus mosquitoes, vectors of dengue and chikungunya infections. Ovitrap surveillance was conducted between October 2007 and October 2008. There was an inverse negative association between ovitrap index and rainfall at the time of collection, probably because rainfall increased the number of available oviposition sites. Rainfall and ovitrap index were positively associates the 25th day after rainfall occurred. A minor, second peak was observed from the 38th to the 42nd day. The first peak was consistent with the minimum 18-day period between the hatching of eggs to the first oviposition. The second minor peak could be due to the second gonotrophic cycle of the female mosquitoes. Rainfall is an important environmental factor associated with Aedes breeding at the study sites. PMID:23691624

  8. Dengue vector surveillance in insular settlements of Pulau Ketam, Selangor, Malaysia.

    PubMed

    Lim, K W; Sit, N W; Norzahira, R; Sing, K W; Wong, H M; Chew, H S; Firdaus, R; Cheryl, J A; Suria, M; Mahathavan, M; Nazni, W A; Lee, H L; McKemy, A; Vasan, S S

    2010-08-01

    A year-long ovitrap surveillance was conducted between November 2007 and October 2008 in two insular settlements (Kampung Pulau Ketam and Kampung Sungai Lima) within the Malaysian island of Pulau Ketam. Eighty standard ovitraps were placed indoors and outdoors of randomly selected houses/locations. Results demonstrated an endemic baseline Aedes population throughout the year without weekly large fluctuations. Kampung Pulau Ketam has high Aedes aegypti and Aedes albopictus population, but only Ae. aegypti was found in Kampung Sungai Lima. Aedes aegypti showed no preference for ovitraps placed indoor versus outdoor. However, as expected, significantly more outdoor ovitraps were positive for Ae. albopictus (p<0.05). Trends in Ae. albopictus and Ae. aegypti populations mirrored each other suggesting that common factors influenced these two populations. PMID:20962714

  9. Intraoperative Neurophysiological Evidence of Hydrogen Peroxide-Induced Stroke in Insular Tumor Surgery.

    PubMed

    León Jorba, Alba; López Cuiña, Miguel; Principe, Alessandro; Villalba Martínez, Gloria

    2015-01-01

    Hydrogen peroxide (H2O2) is commonly used as a haemostatic agent in all type of surgeries. Some adverse effects have been described related to its use. However, only very few cases are published in the literature of a stroke associated with the application of this agent directly to the brain. We present the case of a patient operated on for a right insular tumor with the assistance of intraoperative neurophysiological monitoring who developed a postoperative severe hemiparesis caused by a stroke in left middle cerebral artery territory due to the irrigation with H2O2. Based on this case, we recommend avoiding the H2O2 irrigation for hemostasis in surgery for brain tumors when vascular structures are exposed.

  10. Dynamical predictions of insular hubs for social cognition and their application to stroke

    PubMed Central

    Limongi, Roberto; Tomio, Ailin; Ibanez, Agustin

    2014-01-01

    The insular cortex (IC) is considered a rich hub for context-sensitive emotions/social cognition. Patients with focal IC stroke provide unique opportunities to study socio-emotional processes. Nevertheless, Couto et al. (2013b) have recently reported controversial results regarding IC involvement in emotion and social cognition. Similarly, patients with similar lesions show high functional variability, ranging from almost totally preserved to strongly impaired behavior. Critical evidence suggests that the variability of these patients in the above domains can be explained by enhanced neuroplasticity, compensatory processes, and functional remapping after stroke. Therefore, socio-emotional processes would depend on long-distance connections between the IC and frontotemporal regions. We propose that predictive coding and effective connectivity represent a novel approach to explore functional connectivity and assess compensatory, contralateral, and subsidiary network differences among focal stroke patients. This approach would help explain why socio-emotional performance is so variable within this population. PMID:25408640

  11. Household waste compositional analysis variation from insular communities in the framework of waste prevention strategy plans.

    PubMed

    Zorpas, Antonis A; Lasaridi, Katia; Voukkali, Irene; Loizia, Pantelitsa; Chroni, Christina

    2015-04-01

    Waste management planning requires reliable data regarding waste generation, affecting factors on waste generation and forecasts of waste quantities based on facts. In order to decrease the environmental impacts of waste management the choice of prevention plan as well as the treatment method must be based on the features of the waste that are produced in a specific area. Factors such as culture, economic development, climate, and energy sources have an impact on waste composition; composition influences the need of collecting waste more or less frequently of waste collection and disposition. The research question was to discover the main barriers concerning the compositional analysis in Insular Communities under warm climate conditions and the findings from this study enabled the main contents of a waste management plan to be established. These included advice to residents on waste minimisation, liaison with stakeholders and the expansion of kerbside recycling schemes.

  12. Household waste compositional analysis variation from insular communities in the framework of waste prevention strategy plans.

    PubMed

    Zorpas, Antonis A; Lasaridi, Katia; Voukkali, Irene; Loizia, Pantelitsa; Chroni, Christina

    2015-04-01

    Waste management planning requires reliable data regarding waste generation, affecting factors on waste generation and forecasts of waste quantities based on facts. In order to decrease the environmental impacts of waste management the choice of prevention plan as well as the treatment method must be based on the features of the waste that are produced in a specific area. Factors such as culture, economic development, climate, and energy sources have an impact on waste composition; composition influences the need of collecting waste more or less frequently of waste collection and disposition. The research question was to discover the main barriers concerning the compositional analysis in Insular Communities under warm climate conditions and the findings from this study enabled the main contents of a waste management plan to be established. These included advice to residents on waste minimisation, liaison with stakeholders and the expansion of kerbside recycling schemes. PMID:25690412

  13. Conjoint activity of anterior insular and anterior cingulate cortex: awareness and response

    PubMed Central

    Critchley, Hugo D.

    2010-01-01

    There is now a wealth of evidence that anterior insular and anterior cingulate cortices have a close functional relationship, such that they may be considered together as input and output regions of a functional system. This system is typically engaged across cognitive, affective, and behavioural contexts, suggesting that it is of fundamental importance for mental life. Here, we review the literature and reinforce the case that these brain regions are crucial, firstly, for the production of subjective feelings and, secondly, for co-ordinating appropriate responses to internal and external events. This model seeks to integrate higher-order cortical functions with sensory representation and autonomic control: it is argued that feeling states emerge from the raw data of sensory (including interoceptive) inputs and are integrated through representations in conscious awareness. Correspondingly, autonomic nervous system reactivity is particularly important amongst the responses that accompany conscious experiences. Potential clinical implications are also discussed. PMID:20512367

  14. Reduction of brain and sense organs in the fossil insular bovid Myotragus.

    PubMed

    Köhler, Meike; Moyà-Solà, Salvador

    2004-01-01

    Our study of the fossil rupicaprine bovid Myotragus [Bate, 1909] from the Mediterranean island Majorca (Spain) provides evidence that this animal underwent significant changes (reduction) in the relative size of brain and sense organs after geographic isolation at the end of the Messinian Salinity Crisis (Miocene-Pliocene boundary, 5.2 Mya). The changes in the central nervous system of Myotragus parallel the pattern reported for domesticated animals, in which decrease in relative brain size is accompanied by a decrease in the relative size of their sense organs. We interpret the important size reduction of brain and sense organs in Myotragus as an adaptive strategy for more efficient energy use under the special environmental conditions of the insular ecosystem, characterized by absence of predation and limitation of trophic resources.

  15. A new insular species of Rock Gecko (Cnemaspis Boulenger) from Pulau Langkawi, Kedah, Peninsular Malaysia.

    PubMed

    Grismer, L Lee; Wood, P L Jr; Quah, Evan S H; Anuar, Shahrul; Ngadi, Ehwan; Ahmad, Norhayati

    2015-07-10

    A new, diminutive species of Rock Gecko Cnemaspis mahsuriae sp. nov. of the affinis group, is described from Gunung Raya on Pulau Langkawi, Kedah, Peninsular Malaysia and is differentiated from all other species in the affinis group by having a unique combination of characters including a maximum SVL of 36.6 mm; keeled subtibials and ventrals; 21-24 paravertebral tubercles; no tubercles in the lateral caudal furrows; caudal tubercles not encircling tail; no precloacal pores; 23-26 subdigital lamellae on the fourth toe; no white ocelli in the shoulder region; no yellow postscapular band; and faint yellow bars on the flanks. Cnemaspis mahsuriae sp. nov. is a forest-dwelling species living in close sympatry or paraptry with the insular endemic C. roticanai Grismer & Chan. The Langkawi Archipelago harbors a unique mix of Malaysian and Indochinese taxa and the frequency of new discoveries from this group of islands is increasing.

  16. Introductions do not compensate for functional and phylogenetic losses following extinctions in insular bird assemblages.

    PubMed

    Sobral, Fernando L; Lees, Alexander C; Cianciaruso, Marcus V

    2016-09-01

    The ratio of species extinctions to introductions has been comparable for many insular assemblages, suggesting that introductions could have 'compensated' for extinctions. However, the capacity for introduced species to replace ecological roles and evolutionary history lost following extinction is unclear. We investigated changes in bird functional and phylogenetic diversity in the wake of extinctions and introductions across a sample of 32 islands worldwide. We found that extinct and introduced species have comparable functional and phylogenetic alpha diversity. However, this was distributed at different positions in functional space and in the phylogeny, indicating a 'false compensation'. Introduced and extinct species did not have equivalent functional roles nor belong to similar lineages. This makes it unlikely that novel island biotas composed of introduced taxa will be able to maintain ecological roles and represent the evolutionary histories of pre-disturbance assemblages and highlights the importance of evaluating changes in alpha and beta diversity concurrently. PMID:27353518

  17. Potentiation of lead-induced cell death in PC12 cells by glutamate: Protection by N-acetylcysteine amide (NACA), a novel thiol antioxidant

    SciTech Connect

    Penugonda, Suman; Mare, Suneetha; Lutz, P.; Banks, William A.; Ercal, Nuran . E-mail: nercal@umr.edu

    2006-10-15

    Oxidative stress has been implicated as an important factor in many neurological diseases. Oxidative toxicity in a number of these conditions is induced by excessive glutamate release and subsequent glutamatergic neuronal stimulation. This, in turn, causes increased generation of reactive oxygen species (ROS), oxidative stress, excitotoxicity, and neuronal damage. Recent studies indicate that the glutamatergic neurotransmitter system is involved in lead-induced neurotoxicity. Therefore, this study aimed to (1) investigate the potential effects of glutamate on lead-induced PC12 cell death and (2) elucidate whether the novel thiol antioxidant N-acetylcysteine amide (NACA) had any protective abilities against such cytotoxicity. Our results suggest that glutamate (1 mM) potentiates lead-induced cytotoxicity by increased generation of ROS, decreased proliferation (MTS), decreased glutathione (GSH) levels, and depletion of cellular adenosine-triphosphate (ATP). Consistent with its ability to decrease ATP levels and induce cell death, lead also increased caspase-3 activity, an effect potentiated by glutamate. Exposure to glutamate and lead elevated the cellular malondialdehyde (MDA) levels and phospholipase-A{sub 2} (PLA{sub 2}) activity and diminished the glutamine synthetase (GS) activity. NACA protected PC12 cells from the cytotoxic effects of glutamate plus lead, as evaluated by MTS assay. NACA reduced the decrease in the cellular ATP levels and restored the intracellular GSH levels. The increased levels of ROS and MDA in glutamate-lead treated cells were significantly decreased by NACA. In conclusion, our data showed that glutamate potentiated the effects of lead-induced PC12 cell death by a mechanism involving mitochondrial dysfunction (ATP depletion) and oxidative stress. NACA had a protective role against the combined toxic effects of glutamate and lead by inhibiting lipid peroxidation and scavenging ROS, thus preserving intracellular GSH.

  18. Suppressive responses by visual food cues in postprandial activities of insular cortex as revealed by magnetoencephalography.

    PubMed

    Yoshikawa, Takahiro; Tanaka, Masaaki; Ishii, Akira; Watanabe, Yasuyoshi

    2014-06-01

    'Hara-Hachibu' in Japanese means a subjective sense by which we stop eating just before the motivation to eat is completely lost, a similar concept to caloric restriction (CR). Insular cortex is a critical platform which integrates sensory information into decision-making processes in eating behavior. We compared the responses of insular cortex, as assessed by magnetoencephalography (MEG), immediately after presentation of food images in the Fasting condition with those in the 'Hara-Hachibu' condition. Eleven healthy, right-handed males [age, 27.2±9.6 years; body mass index, 22.6±2.1kg/m(2) (mean±SD)] were enrolled in a randomized, two-crossover experiment (Fasting and 'Hara-Hachibu' conditions). Before the MEG recordings in the 'Hara-Hachibu' condition, the participants consumed rice balls as much as they judged themselves to have consumed shortly before reaching satiety. During the MEG recordings, they viewed food pictures projected on a screen. The intensities of MEG responses to viewing food pictures were significantly lower in the 'Hara-Hachibu' condition than those in the Fasting condition (P<0.05). The intensities of the MEG responses to the visual food stimuli in the 'Hara-Hachibu' condition was positively associated with the factor-3 (food tasted) (r=0.693, P=0.018) and aggregated scores (r=0.659, P=0.027) of the Power of Food Scale, a self-report measure of hedonic hunger. These findings may help to elucidate the neural basis of variability of appetite phenotypes under the condition of CR among individuals, and to develop possible strategies for the maintenance of adequate CR in daily life.

  19. Parental Praise Correlates with Posterior Insular Cortex Gray Matter Volume in Children and Adolescents.

    PubMed

    Matsudaira, Izumi; Yokota, Susumu; Hashimoto, Teruo; Takeuchi, Hikaru; Asano, Kohei; Asano, Michiko; Sassa, Yuko; Taki, Yasuyuki; Kawashima, Ryuta

    2016-01-01

    A positive parenting style affects psychological and cognitive development in children. Neuroimaging studies revealed that a positive parenting style influenced brain structure in children. Parental praise is a concrete behavior observed in positive parenting. Although previous psychological studies revealed a positive effect of parental praise on children, little is known about the relationship between parental praise and brain structure in children. Thus, the purpose of the present study was to determine whether there was a correlation between the parental attitude towards praising their child and gray matter volume in the children (116 boys and 109 girls; mean age, 10.6 years old). We examined the correlation between regional gray matter volume and parental praise using voxel-based morphometry (VBM) following magnetic resonance imaging (MRI). In addition, to confirm the positive effects of parental praise, we analyzed the correlation between the frequency of parental praise and personality traits in children. We showed that the parental attitude towards praising their child was significantly and positively correlated with the gray matter volume of the left posterior insular cortex in children. Moreover, we found a significant positive correlation between parental attitude towards praising their child and the personality traits of conscientiousness and openness to experience in the children. Prior studies said that gray matter volume in the posterior insula was correlated with empathy, and the functional connectivity between this area and the amygdala was associated with emotional regulation. Furthermore, the posterior insula relates to auditory function, and therefore, was likely involved in the processing of parental praise. Considering the possibility of experience-dependent plasticity, frequent parental praise would lead to increased posterior insular gray matter volume in children. Our study is the first to elucidate the relationship between a specific

  20. Colony insularity through queen control on worker social motivation in ants.

    PubMed

    Boulay, Raphaël; Katzav-Gozansky, Tamar; Vander Meer, Robert K; Hefetz, Abraham

    2003-05-01

    We investigated the relative contribution of the queen and workers to colony nestmate recognition cues and on colony insularity in the Carpenter ant Camponotus fellah. Workers were either individually isolated, preventing contact with both queen and workers (colonial deprived, CD), kept in queenless groups, allowing only worker-worker interactions (queen deprived, QD) or in queenright (QR) groups. Two weeks post-separation QD and QR workers were amicable towards each other but both rejected their CD nestmates, which suggests that the queen does not measurably influence the colony recognition cues. By contrast, aggression between QD and QR workers from the same original colony was apparent only after six months of separation. This clearly demonstrates the power of the Gestalt and indicates that the queen is not a dominant contributor to the nestmate recognition cues in this species. Aggression between nestmates was correlated with a greater hydrocarbon (HC) profile divergence for CD than for QD and QR workers, supporting the importance of worker-worker interactions in maintaining the colony Gestalt odour. While the queen does not significantly influence nestmate recognition cues, she does influence colony insularity since within 3 days QD (queenless for six months) workers from different colony origins merged to form a single queenless colony. By contrast, the corresponding QR colonies maintained their territoriality and did not merge. The originally divergent cuticular and postpharyngeal gland HC profiles became congruent following the merger. Therefore, while workers supply and blend the recognition signal, the queen affects worker-worker interaction by reducing social motivation and tolerance of alien conspecifics.

  1. Designing an Information System for the Preservation of the Insular Tropical Environment of Reunion Island

    NASA Astrophysics Data System (ADS)

    Conruyt, Noël; Sébastien, Didier; Courdier, Rémy; David, Daniel; Sébastien, Nicolas; Ralambondrainy, Tiana

    Decision-makers who wish to manage Insular Tropical Environments more efficiently need to narrow the gap between the production of scientific knowledge in universities, or other labs, and its pragmatic use by the general public and administrations. Today, one of the main challenges concerning the environment is the preservation of the biodiversity of ecosystems that suffer from urban and agricultural pressure. As we can only protect what we know, it is all the more important to share expert knowledge about habitats and species by using Internet in order to educate the public about their wealth and beauty. Based on Reunion Island, and taking into consideration an expected population growth of over 30% in the next twenty years, we are working to predict the human impact on this closed territory. To help tackle these two questions about biodiversity and land consumption, we have designed an Information System (IS) in the framework of the ETIC program. Our aim is to enhance insular tropical environment research in order to help the Reunion National Park to manage its protected territory. On the one hand, biodiversity research is handled statically, using knowledge bases and databases, to enhance Systematics and ecological university research. On the other hand, spatial planning concerns are treated dynamically, using multi-agent systems to simulate population densification movements. These software technologies have been implemented and integrated through a common architectural system in the ETIC program. They were conceived using Web Services that allow each module to communicate its functionalities and information with one another, as well as with external systems.

  2. Parental Praise Correlates with Posterior Insular Cortex Gray Matter Volume in Children and Adolescents.

    PubMed

    Matsudaira, Izumi; Yokota, Susumu; Hashimoto, Teruo; Takeuchi, Hikaru; Asano, Kohei; Asano, Michiko; Sassa, Yuko; Taki, Yasuyuki; Kawashima, Ryuta

    2016-01-01

    A positive parenting style affects psychological and cognitive development in children. Neuroimaging studies revealed that a positive parenting style influenced brain structure in children. Parental praise is a concrete behavior observed in positive parenting. Although previous psychological studies revealed a positive effect of parental praise on children, little is known about the relationship between parental praise and brain structure in children. Thus, the purpose of the present study was to determine whether there was a correlation between the parental attitude towards praising their child and gray matter volume in the children (116 boys and 109 girls; mean age, 10.6 years old). We examined the correlation between regional gray matter volume and parental praise using voxel-based morphometry (VBM) following magnetic resonance imaging (MRI). In addition, to confirm the positive effects of parental praise, we analyzed the correlation between the frequency of parental praise and personality traits in children. We showed that the parental attitude towards praising their child was significantly and positively correlated with the gray matter volume of the left posterior insular cortex in children. Moreover, we found a significant positive correlation between parental attitude towards praising their child and the personality traits of conscientiousness and openness to experience in the children. Prior studies said that gray matter volume in the posterior insula was correlated with empathy, and the functional connectivity between this area and the amygdala was associated with emotional regulation. Furthermore, the posterior insula relates to auditory function, and therefore, was likely involved in the processing of parental praise. Considering the possibility of experience-dependent plasticity, frequent parental praise would lead to increased posterior insular gray matter volume in children. Our study is the first to elucidate the relationship between a specific

  3. Colony insularity through queen control on worker social motivation in ants.

    PubMed

    Boulay, Raphaël; Katzav-Gozansky, Tamar; Vander Meer, Robert K; Hefetz, Abraham

    2003-05-01

    We investigated the relative contribution of the queen and workers to colony nestmate recognition cues and on colony insularity in the Carpenter ant Camponotus fellah. Workers were either individually isolated, preventing contact with both queen and workers (colonial deprived, CD), kept in queenless groups, allowing only worker-worker interactions (queen deprived, QD) or in queenright (QR) groups. Two weeks post-separation QD and QR workers were amicable towards each other but both rejected their CD nestmates, which suggests that the queen does not measurably influence the colony recognition cues. By contrast, aggression between QD and QR workers from the same original colony was apparent only after six months of separation. This clearly demonstrates the power of the Gestalt and indicates that the queen is not a dominant contributor to the nestmate recognition cues in this species. Aggression between nestmates was correlated with a greater hydrocarbon (HC) profile divergence for CD than for QD and QR workers, supporting the importance of worker-worker interactions in maintaining the colony Gestalt odour. While the queen does not significantly influence nestmate recognition cues, she does influence colony insularity since within 3 days QD (queenless for six months) workers from different colony origins merged to form a single queenless colony. By contrast, the corresponding QR colonies maintained their territoriality and did not merge. The originally divergent cuticular and postpharyngeal gland HC profiles became congruent following the merger. Therefore, while workers supply and blend the recognition signal, the queen affects worker-worker interaction by reducing social motivation and tolerance of alien conspecifics. PMID:12803913

  4. Predictive coding accounts of shared representations in parieto-insular networks.

    PubMed

    Ishida, Hiroaki; Suzuki, Keisuke; Grandi, Laura Clara

    2015-04-01

    The discovery of mirror neurons in the ventral premotor cortex (area F5) and inferior parietal cortex (area PFG) in the macaque monkey brain has provided the physiological evidence for direct matching of the intrinsic motor representations of the self and the visual image of the actions of others. The existence of mirror neurons implies that the brain has mechanisms reflecting shared self and other action representations. This may further imply that the neural basis self-body representations may also incorporate components that are shared with other-body representations. It is likely that such a mechanism is also involved in predicting other's touch sensations and emotions. However, the neural basis of shared body representations has remained unclear. Here, we propose a neural basis of body representation of the self and of others in both human and non-human primates. We review a series of behavioral and physiological findings which together paint a picture that the systems underlying such shared representations require integration of conscious exteroception and interoception subserved by a cortical sensory-motor network involving parieto-inner perisylvian circuits (the ventral intraparietal area [VIP]/inferior parietal area [PFG]-secondary somatosensory cortex [SII]/posterior insular cortex [pIC]/anterior insular cortex [aIC]). Based on these findings, we propose a computational mechanism of the shared body representation in the predictive coding (PC) framework. Our mechanism proposes that processes emerging from generative models embedded in these specific neuronal circuits play a pivotal role in distinguishing a self-specific body representation from a shared one. The model successfully accounts for normal and abnormal shared body phenomena such as mirror-touch synesthesia and somatoparaphrenia. In addition, it generates a set of testable experimental predictions. PMID:25447372

  5. Parental Praise Correlates with Posterior Insular Cortex Gray Matter Volume in Children and Adolescents

    PubMed Central

    Matsudaira, Izumi; Yokota, Susumu; Hashimoto, Teruo; Takeuchi, Hikaru; Asano, Kohei; Asano, Michiko; Sassa, Yuko; Taki, Yasuyuki; Kawashima, Ryuta

    2016-01-01

    A positive parenting style affects psychological and cognitive development in children. Neuroimaging studies revealed that a positive parenting style influenced brain structure in children. Parental praise is a concrete behavior observed in positive parenting. Although previous psychological studies revealed a positive effect of parental praise on children, little is known about the relationship between parental praise and brain structure in children. Thus, the purpose of the present study was to determine whether there was a correlation between the parental attitude towards praising their child and gray matter volume in the children (116 boys and 109 girls; mean age, 10.6 years old). We examined the correlation between regional gray matter volume and parental praise using voxel-based morphometry (VBM) following magnetic resonance imaging (MRI). In addition, to confirm the positive effects of parental praise, we analyzed the correlation between the frequency of parental praise and personality traits in children. We showed that the parental attitude towards praising their child was significantly and positively correlated with the gray matter volume of the left posterior insular cortex in children. Moreover, we found a significant positive correlation between parental attitude towards praising their child and the personality traits of conscientiousness and openness to experience in the children. Prior studies said that gray matter volume in the posterior insula was correlated with empathy, and the functional connectivity between this area and the amygdala was associated with emotional regulation. Furthermore, the posterior insula relates to auditory function, and therefore, was likely involved in the processing of parental praise. Considering the possibility of experience-dependent plasticity, frequent parental praise would lead to increased posterior insular gray matter volume in children. Our study is the first to elucidate the relationship between a specific

  6. Concentration-Dependent Processivity of Multiple Glutamate Ligations Catalyzed by Folylpoly-γ-glutamate Synthetase

    PubMed Central

    Tomsho, John W.; Moran, Richard G.; Coward, James K.

    2010-01-01

    Folylpoly-γ-glutamate synthetase (FPGS, EC 6.3.2.17) is an ATP-dependent ligase that catalyzes formation of poly-γ-glutamate derivatives of reduced folates and anti-folates such as methotrexate and 5,10-dideaza-5,6,7,8-tetrahydrofolate (DDAH4PteGlu1). While the chemical mechanism of the reaction catalyzed by FPGS is known, it is unknown whether single or multiple glutamate residues are added following each folate binding event. A very sensitive high performance liquid chromatography method has been used to analyze the multiple ligation reactions onto radiolabeled DDAH4PteGlu1 catalyzed by FPGS in order to distinguish between distributive or processive mechanisms of catalysis. Reaction time courses, substrate trapping, and pulse-chase experiments were used to measure folate release during multiple glutamate additions. Together, the results of these experiments indicate that hFPGS can catalyze the processive addition of approximately four glutamate residues onto DDAH4PteGlu1. The degree of processivity was determined to be dependent on the concentration of the folate substrate, thus suggesting a mechanism for the regulation of folate polyglutamate synthesis in cells. PMID:18672898

  7. Ketamine and other potential glutamate antidepressants.

    PubMed

    Dutta, Arpan; McKie, Shane; Deakin, J F William

    2015-01-30

    The need for rapid acting antidepressants is widely recognised. There has been much interest in glutamate mechanisms in major depressive disorder (MDD) as a promising target for the development of new antidepressants. A single intravenous infusion of ketamine, a N-methyl-d-aspartate (NMDA) receptor antagonist anaesthetic agent, can alleviate depressive symptoms in patients within hours of administration. The mechanism of action appears to be in part through glutamate release onto non-NMDA receptors including α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and metabotropic receptors. However these are also reported effects on 5-HT, dopamine and intracellular effects on the mammalian target of rapamycin (mTOR) pathway. The effects of SSRI (Selective Serotonin Reuptake Inhibitor) antidepressants may also involve alterations in NMDA function. The article reviews the effect of current antidepressants on NMDA and examines the efficacy and mechanism of ketamine. Response to ketamine is also discussed and comparison with other glutamate drugs including lamotrigine, amantadine, riluzole, memantine, traxoprodil, GLYX-13, MK-0657, RO4917523, AZD2066 and Coluracetam. Future studies need to link the rapid antidepressant effects seen with ketamine to inflammatory theories in MDD.

  8. New perspectives in glutamate and anxiety.

    PubMed

    Riaza Bermudo-Soriano, Carlos; Perez-Rodriguez, M Mercedes; Vaquero-Lorenzo, Concepcion; Baca-Garcia, Enrique

    2012-02-01

    Anxiety and stress-related disorders, namely posttraumatic stress disorder (PTSD), generalized anxiety disorder (GAD), obsessive-compulsive disorder (ODC), social and specific phobias, and panic disorder, are a major public health issue. A growing body of evidence suggests that glutamatergic neurotransmission may be involved in the biological mechanisms underlying stress response and anxiety-related disorders. The glutamatergic system mediates the acquisition and extinction of fear-conditioning. Thus, new drugs targeting glutamatergic neurotransmission may be promising candidates for new pharmacological treatments. In particular, N-methyl-d-aspartate receptors (NMDAR) antagonists (AP5, AP7, CGP37849, CGP39551, LY235959, NPC17742, and MK-801), NMDAR partial agonists (DCS, ACPC), α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptors (AMPARs) antagonists (topiramate), and several allosteric modulators targeting metabotropic glutamate receptors (mGluRs) mGluR1, mGluR2/3, and mGluR5, have shown anxiolytic-like effects in several animal and human studies. Several studies have suggested that polyamines (agmatine, putrescine, spermidine, and spermine) may be involved in the neurobiological mechanisms underlying stress-response and anxiety-related disorders. This could mainly be attributed to their ability to modulate ionotropic glutamate receptors, especially NR2B subunits. The aim of this review is to establish that glutamate neurotransmission and polyaminergic system play a fundamental role in the onset of anxiety-related disorders. This may open the way for new drugs that may help to treat these conditions.

  9. Corticotrigeminal Projections from the Insular Cortex to the Trigeminal Caudal Subnucleus Regulate Orofacial Pain after Nerve Injury via Extracellular Signal-Regulated Kinase Activation in Insular Cortex Neurons

    PubMed Central

    Wang, Jian; Li, Zhi-Hua; Feng, Ban; Zhang, Ting; Zhang, Han; Li, Hui; Chen, Tao; Cui, Jing; Zang, Wei-Dong; Li, Yun-Qing

    2015-01-01

    Cortical neuroplasticity alterations are implicated in the pathophysiology of chronic orofacial pain. However, the relationship between critical cortex excitability and orofacial pain maintenance has not been fully elucidated. We recently demonstrated a top-down corticospinal descending pain modulation pathway from the anterior cingulate cortex (ACC) to the spinal dorsal horn that could directly regulate nociceptive transmission. Thus, we aimed to investigate possible corticotrigeminal connections that directly influence orofacial nociception in rats. Infraorbital nerve chronic constriction injury (IoN-CCI) induced significant orofacial nociceptive behaviors as well as pain-related negative emotions such as anxiety/depression in rats. By combining retrograde and anterograde tract tracing, we found powerful evidence that the trigeminal caudal subnucleus (Vc), especially the superficial laminae (I/II), received direct descending projections from granular and dysgranular parts of the insular cortex (IC). Extracellular signal-regulated kinase (ERK), an important signaling molecule involved in neuroplasticity, was significantly activated in the IC following IoN-CCI. Moreover, in IC slices from IoN-CCI rats, U0126, an inhibitor of ERK activation, decreased both the amplitude and the frequency of spontaneous excitatory postsynaptic currents (sEPSCs) and reduced the paired-pulse ratio (PPR) of Vc-projecting neurons. Additionally, U0126 also reduced the number of action potentials in the Vc-projecting neurons. Finally, intra-IC infusion of U0126 obviously decreased Fos expression in the Vc, accompanied by the alleviation of both nociceptive behavior and negative emotions. Thus, the corticotrigeminal descending pathway from the IC to the Vc could directly regulate orofacial pain, and ERK deactivation in the IC could effectively alleviate neuropathic pain as well as pain-related negative emotions in IoN-CCI rats, probably through this top–down pathway. These findings may

  10. Corticotrigeminal Projections from the Insular Cortex to the Trigeminal Caudal Subnucleus Regulate Orofacial Pain after Nerve Injury via Extracellular Signal-Regulated Kinase Activation in Insular Cortex Neurons.

    PubMed

    Wang, Jian; Li, Zhi-Hua; Feng, Ban; Zhang, Ting; Zhang, Han; Li, Hui; Chen, Tao; Cui, Jing; Zang, Wei-Dong; Li, Yun-Qing

    2015-01-01

    Cortical neuroplasticity alterations are implicated in the pathophysiology of chronic orofacial pain. However, the relationship between critical cortex excitability and orofacial pain maintenance has not been fully elucidated. We recently demonstrated a top-down corticospinal descending pain modulation pathway from the anterior cingulate cortex (ACC) to the spinal dorsal horn that could directly regulate nociceptive transmission. Thus, we aimed to investigate possible corticotrigeminal connections that directly influence orofacial nociception in rats. Infraorbital nerve chronic constriction injury (IoN-CCI) induced significant orofacial nociceptive behaviors as well as pain-related negative emotions such as anxiety/depression in rats. By combining retrograde and anterograde tract tracing, we found powerful evidence that the trigeminal caudal subnucleus (Vc), especially the superficial laminae (I/II), received direct descending projections from granular and dysgranular parts of the insular cortex (IC). Extracellular signal-regulated kinase (ERK), an important signaling molecule involved in neuroplasticity, was significantly activated in the IC following IoN-CCI. Moreover, in IC slices from IoN-CCI rats, U0126, an inhibitor of ERK activation, decreased both the amplitude and the frequency of spontaneous excitatory postsynaptic currents (sEPSCs) and reduced the paired-pulse ratio (PPR) of Vc-projecting neurons. Additionally, U0126 also reduced the number of action potentials in the Vc-projecting neurons. Finally, intra-IC infusion of U0126 obviously decreased Fos expression in the Vc, accompanied by the alleviation of both nociceptive behavior and negative emotions. Thus, the corticotrigeminal descending pathway from the IC to the Vc could directly regulate orofacial pain, and ERK deactivation in the IC could effectively alleviate neuropathic pain as well as pain-related negative emotions in IoN-CCI rats, probably through this top-down pathway. These findings may help

  11. Glutamate involvement in calcium–dependent migration of astrocytoma cells

    PubMed Central

    2014-01-01

    Background Astrocytoma are known to have altered glutamate machinery that results in the release of large amounts of glutamate into the extracellular space but the precise role of glutamate in favoring cancer processes has not yet been fully established. Several studies suggested that glutamate might provoke active killing of neurons thereby producing space for cancer cells to proliferate and migrate. Previously, we observed that calcium promotes disassembly of integrin-containing focal adhesions in astrocytoma, thus providing a link between calcium signaling and cell migration. The aim of this study was to determine how calcium signaling and glutamate transmission cooperate to promote enhanced astrocytoma migration. Methods The wound-healing model was used to assay migration of human U87MG astrocytoma cells and allowed to monitor calcium signaling during the migration process. The effect of glutamate on calcium signaling was evaluated together with the amount of glutamate released by astrocytoma during cell migration. Results We observed that glutamate stimulates motility in serum-starved cells, whereas in the presence of serum, inhibitors of glutamate receptors reduce migration. Migration speed was also reduced in presence of an intracellular calcium chelator. During migration, cells displayed spontaneous Ca2+ transients. L-THA, an inhibitor of glutamate re-uptake increased the frequency of Ca2+ oscillations in oscillating cells and induced Ca2+ oscillations in quiescent cells. The frequency of migration-associated Ca2+ oscillations was reduced by prior incubation with glutamate receptor antagonists or with an anti-β1 integrin antibody. Application of glutamate induced increases in internal free Ca2+ concentration ([Ca2+]i). Finally we found that compounds known to increase [Ca2+]i in astrocytomas such as thapsigagin, ionomycin or the metabotropic glutamate receptor agonist t-ACPD, are able to induce glutamate release. Conclusion Our data demonstrate that

  12. Environmental drivers of megafaunal assemblage composition and biomass distribution over mainland and insular slopes of the Balearic Basin (Western Mediterranean)

    NASA Astrophysics Data System (ADS)

    Fanelli, E.; Cartes, J. E.; Papiol, V.; López-Pérez, C.

    2013-08-01

    The influence of mesoscale physical and trophic variables on deep-sea megafauna, a scale of variation often neglected in deep-sea studies, is crucial for understanding their role in the ecosystem. Drivers of megafaunal assemblage composition and biomass distribution have been investigated in two contrasting areas of the Balearic basin in the NW Mediterranean: on the mainland slope (Catalonian coasts) and on the insular slope (North of Mallorca, Balearic Islands). An experimental bottom trawl survey was carried out during summer 2010, at stations in both sub-areas located between 450 and 2200 m water depth. Environmental data were collected simultaneously: near-bottom physical parameters, and the elemental and isotopic composition of sediments. Initially, data were analysed along the whole depth gradient, and then assemblages from the two areas were compared. Analysis of the trawls showed the existence of one group associated with the upper slope (US=450-690 m), another with the middle slope (MS=1000-1300 m) and a third with the lower slope (LS=1400-2200 m). Also, significant differences in the assemblage composition were found between mainland and insular slopes at MS. Dominance by different species was evident when the two areas were compared by SIMPER analysis. The greatest fish biomass was recorded in both areas at 1000-1300 m, a zone linked to minimum temperature and maximum O2 concentration on the bottom. Near the mainland, fish assemblages were best explained (43% of total variance, DISTLM analysis) by prey availability (gelatinous zooplankton biomass). On the insular slope, trophic webs seemed less complex and were based on vertical input of surface primary production. Decapods, which reached their highest biomass values on the upper slope, were correlated with salinity and temperature in both the areas. However, while hydrographic conditions (temperature and salinity) seemed to be the most important variables over the insular slope, resource availability

  13. Transcriptional regulation through glutamate receptors: Involvement of tyrosine kinases.

    PubMed

    López-Bayghen, Esther; Aguirre, Adán; Ortega, Arturo

    2003-12-01

    Glutamate receptors play a key role in neuronal plasticity, learning and memory, and in several neuropathologies. Short-term and long-term changes in synaptic efficacy are triggered by glutamate. Although an enhanced glutamate-dependent tyrosine phosphorylation has been described in several systems, its role in membrane-to-nuclei signaling is unclear. Taking advantage of the fact that the gene encoding the chick kainate-binding protein undergoes a glutamate-dependent transcriptional regulation via an activator protein-1 (AP-1) site, we evaluated the involvement of tyrosine kinases in this process. We describe here the participation of receptor and non-receptor tyrosine kinases in the signaling cascade triggered by glutamate. Our results suggest that in Bergmann glia cells, glutamate receptors transactivate receptor tyrosine kinases, favoring the idea of a complex network of signals activated by this excitatory neurotransmitter that results in regulation of gene expression.

  14. [Determination of glutamic acid in biological material by capillary electrophoresis].

    PubMed

    Narezhnaya, E; Krukier, I; Avrutskaya, V; Degtyareva, A; Igumnova, E A

    2015-01-01

    The conditions for the identification and determination of Glutamic acid by capillary zone electrophoresis without their preliminary derivatization have been optimized. The effect of concentration of buffer electrolyte and pH on determination of Glutamic acid has been investigated. It is shown that the 5 Mm borate buffer concentration and a pH 9.15 are optimal. Quantitative determination of glutamic acid has been carried out using a linear dependence between the concentration of the analyte and the area of the peak. The accuracy and reproducibility of the determination are confirmed by the method "introduced - found". Glutamic acid has been determined in the placenta homogenate. The duration of analysis doesn't exceed 30 minutes. The results showed a decrease in the level of glutamic acid in cases of pregnancy complicated by placental insufficiency compared with the physiological, and this fact allows to consider the level of glutamic acid as a possible marker of complicated pregnancy.

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

    PubMed

    Robinson, Michael B; Jackson, Joshua G

    2016-09-01

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

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

    PubMed

    Herbst, Eric A F; Holloway, Graham P

    2016-07-01

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

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

    PubMed

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

    2015-01-01

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

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

    PubMed

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

    2015-01-01

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

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

    ERIC Educational Resources Information Center

    Pita-Almenar, Juan D.; Zou, Shengwei; Colbert, Costa M.; Eskin, Arnold

    2012-01-01

    Na[superscript +]-dependent high-affinity glutamate transporters have important roles in the maintenance of basal levels of glutamate and clearance of glutamate during synaptic transmission. Interestingly, several studies have shown that basal glutamate transport displays plasticity. Glutamate uptake increases in hippocampal slices during early…

  20. [A Patient with Acute Limbic Encephalitis Associated with Anti-Glutamate Receptor Antibodies and Subsequent Optic Neuritis].

    PubMed

    Murakami, Aya; Nakamura, Masataka; Kaneko, Satoshi; Takahashi, Yukitoshi; Kusaka, Hirofumi

    2016-03-01

    A 19-year-old woman presented with headache and fever. Cerebrospinal fluid (CSF) analysis revealed increased pressure (>200 mmH2O) and pleocytosis. Brain MRI showed high intensity in the medial part of the right temporal lobe, insular regions, and basal ganglia of the right hemisphere on fluid attenuated inversion recovery images. Based on a tentative diagnosis of limbic encephalitis caused by viral infection, acyclovir therapy was started. However, 10 days after admission, a right superior temporal quadrantanopia developed in the left eye. MRI detected abnormal intensity in the left optic nerve on short tau inversion recovery images. After three courses of steroid pulse therapy, the optic neuritis quickly improved and the patient was maintained on subsequent oral administration of prednisolone, without relapse for one year. The CSF was positive for anti-glutamate receptor (GluR) antibodies (GluN2B, GluN1, and GluD2); however, anti-N-methyl-D-aspartate receptor antibody was not detected in both serum and CSF with cell-based asseys. Compared to previously reported anti-GluR positive cases combined with optic neuritis, the clinical outcome of our patient was short, with good prognosis. Our results indicate that an autoimmune mechanism involving anti-GluR antibodies contributes to the pathogenesis of optic neuritis as well as limbic encephalitis. PMID:27001777

  1. Extracellular glutamate alters mature osteoclast and osteoblast functions.

    PubMed

    Seidlitz, Eric P; Sharma, Mohit K; Singh, Gurmit

    2010-09-01

    Glutamatergic intercellular communication is involved in many aspects of metabolic homeostasis in normal bone. In bone metastasis, the balance between bone formation and degradation is disrupted. Although the responsible mechanisms are not clear, we have previously identified that cancer cell lines used in bone tumour models secrete glutamate, suggesting that tumour-derived glutamate may disrupt sensitive signalling systems in bone. This study examines the role of glutamate in mature osteoclastic bone resorption, osteoblast differentiation, and bone nodule formation. Glutamate was found to have no effect on the survival or activity of mature osteoclasts, although glutamate transporter inhibition and receptor blockade increased the number of bone resorption pits. Furthermore, transporter inhibition increased the area of resorbed bone while significantly decreasing the number of osteoclasts. Alkaline phosphatase activity and extracellular matrix mineralization were used as measurements of osteoblast differentiation. Glutamate significantly increased osteoblast differentiation and mineralization, but transport inhibitors had no effect. These studies support earlier findings suggesting that glutamate may be more important for osteoclastogenesis than for osteoclast proliferation or functions. Since glutamate is capable of changing the differentiation and activities of both osteoclast and osteoblast cell types in bone, it is reasonable to postulate that tumour-derived glutamate may impact bone homeostasis in bone metastasis.

  2. Glutamate and neurotrophic factors in neuronal plasticity and disease.

    PubMed

    Mattson, Mark P

    2008-11-01

    Glutamate's role as a neurotransmitter at synapses has been known for 40 years, but glutamate has since been shown to regulate neurogenesis, neurite outgrowth, synaptogenesis, and neuron survival in the developing and adult mammalian nervous system. Cell-surface glutamate receptors are coupled to Ca(2+) influx and release from endoplasmic reticulum stores, which causes rapid (kinase- and protease-mediated) and delayed (transcription-dependent) responses that change the structure and function of neurons. Neurotrophic factors and glutamate interact to regulate developmental and adult neuroplasticity. For example, glutamate stimulates the production of brain-derived neurotrophic factor (BDNF), which, in turn, modifies neuronal glutamate sensitivity, Ca(2+) homeostasis, and plasticity. Neurotrophic factors may modify glutamate signaling directly, by changing the expression of glutamate receptor subunits and Ca(2+)-regulating proteins, and also indirectly by inducing the production of antioxidant enzymes, energy-regulating proteins, and antiapoptotic Bcl-2 family members. Excessive activation of glutamate receptors, under conditions of oxidative and metabolic stress, may contribute to neuronal dysfunction and degeneration in diseases ranging from stroke and Alzheimer's disease to psychiatric disorders. By enhancing neurotrophic factor signaling, environmental factors such as exercise and dietary energy restriction, and chemicals such as antidepressants may optimize glutamatergic signaling and protect against neurological disorders.

  3. The Relevance of Group II Glutamate Receptors Expression to Anxiety.

    PubMed

    Ravid, Jonathan D; Mostofsky, David I

    2016-01-01

    The interface of receptor-mediated regulation of cellular signaling and neurological outputs remains an active field of investigation. The metabotropic G protein-coupled glutamate receptors, and in particular, the group II cyclic adenosine mono-phosphate (cAMP)-lowering metabotropic glutamate receptors 2 and 3 (mGlu2/3 glutamate receptors), have gained interest as therapeutic targets in different forms of neurological disorders. This review explores mGlu2/3 glutamate receptors expression, pharmacological activation, and signaling links to anxiety, as assessed in animal models and in clinical trials. PMID:27650988

  4. Oligodendrocyte differentiation from adult multipotent stem cells is modulated by glutamate.

    PubMed

    Cavaliere, F; Urra, O; Alberdi, E; Matute, C

    2012-02-02

    We used multipotent stem cells (MSCs) derived from the young rat subventricular zone (SVZ) to study the effects of glutamate in oligodendrocyte maturation. Glutamate stimulated oligodendrocyte differentiation from SVZ-derived MSCs through the activation of specific N-methyl-D-aspartate (NMDA) receptor subunits. The effect of glutamate and NMDA on oligodendrocyte differentiation was evident in both the number of newly generated oligodendrocytes and their morphology. In addition, the levels of NMDAR1 and NMDAR2A protein increased during differentiation, whereas NMDAR2B and NMDAR3 protein levels decreased, suggesting differential expression of NMDA receptor subunits during maturation. Microfluorimetry showed that the activation of NMDA receptors during oligodendrocyte differentiation elevated cytosolic calcium levels and promoted myelination in cocultures with neurons. Moreover, we observed that stimulation of MSCs by NMDA receptors induced the generation of reactive oxygen species (ROS), which were negatively modulated by the NADPH inhibitor apocynin, and that the levels of ROS correlated with the degree of differentiation. Taken together, these findings suggest that ROS generated by NADPH oxidase by the activation of NMDA receptors promotes the maturation of oligodendrocytes and favors myelination.

  5. Oligodendrocyte differentiation from adult multipotent stem cells is modulated by glutamate

    PubMed Central

    Cavaliere, F; Urra, O; Alberdi, E; Matute, C

    2012-01-01

    We used multipotent stem cells (MSCs) derived from the young rat subventricular zone (SVZ) to study the effects of glutamate in oligodendrocyte maturation. Glutamate stimulated oligodendrocyte differentiation from SVZ-derived MSCs through the activation of specific N-methyl--aspartate (NMDA) receptor subunits. The effect of glutamate and NMDA on oligodendrocyte differentiation was evident in both the number of newly generated oligodendrocytes and their morphology. In addition, the levels of NMDAR1 and NMDAR2A protein increased during differentiation, whereas NMDAR2B and NMDAR3 protein levels decreased, suggesting differential expression of NMDA receptor subunits during maturation. Microfluorimetry showed that the activation of NMDA receptors during oligodendrocyte differentiation elevated cytosolic calcium levels and promoted myelination in cocultures with neurons. Moreover, we observed that stimulation of MSCs by NMDA receptors induced the generation of reactive oxygen species (ROS), which were negatively modulated by the NADPH inhibitor apocynin, and that the levels of ROS correlated with the degree of differentiation. Taken together, these findings suggest that ROS generated by NADPH oxidase by the activation of NMDA receptors promotes the maturation of oligodendrocytes and favors myelination. PMID:22297298

  6. Phosphene Perception Relates to Visual Cortex Glutamate Levels and Covaries with Atypical Visuospatial Awareness

    PubMed Central

    Terhune, Devin B.; Murray, Elizabeth; Near, Jamie; Stagg, Charlotte J.; Cowey, Alan; Cohen Kadosh, Roi

    2015-01-01

    Phosphenes are illusory visual percepts produced by the application of transcranial magnetic stimulation to occipital cortex. Phosphene thresholds, the minimum stimulation intensity required to reliably produce phosphenes, are widely used as an index of cortical excitability. However, the neural basis of phosphene thresholds and their relationship to individual differences in visual cognition are poorly understood. Here, we investigated the neurochemical basis of phosphene perception by measuring basal GABA and glutamate levels in primary visual cortex using magnetic resonance spectroscopy. We further examined whether phosphene thresholds would relate to the visuospatial phenomenology of grapheme-color synesthesia, a condition characterized by atypical binding and involuntary color photisms. Phosphene thresholds negatively correlated with glutamate concentrations in visual cortex, with lower thresholds associated with elevated glutamate. This relationship was robust, present in both controls and synesthetes, and exhibited neurochemical, topographic, and threshold specificity. Projector synesthetes, who experience color photisms as spatially colocalized with inducing graphemes, displayed lower phosphene thresholds than associator synesthetes, who experience photisms as internal images, with both exhibiting lower thresholds than controls. These results suggest that phosphene perception is driven by interindividual variation in glutamatergic activity in primary visual cortex and relates to cortical processes underlying individual differences in visuospatial awareness. PMID:25725043

  7. Mutant Disrupted-In-Schizophrenia 1 in astrocytes: focus on glutamate metabolism

    PubMed Central

    Abazyan, Sofya; Yang, Eun Ju; Abazyan, Bagrat; Xia, Meng; Yang, Chunxia; Rojas, Camilo; Slusher, Barbara; Sattler, Rita; Pletnikov, Mikhail

    2014-01-01

    Disrupted-In-Schizophrenia 1 (DISC1) is a genetic risk factor that has been implicated in major mental disorders. DISC1 binds to and stabilizes serine racemase (SR) to regulate production of D-serine by astrocytes, contributing to glutamate (GLU) neurotransmission. However, the possible involvement of astrocytic DISC1 in synthesis, metabolism, re-uptake or secretion of GLU remains unexplored. Thus, we studied the effects of dominant-negative mutant DISC1 on various aspects of GLU metabolism using primary astrocyte cultures and the hippocampal tissue from transgenic mice with astrocyte-restricted expression of mutant DISC1. While mutant DISC1 had no significant effects on astrocyte proliferation, GLU re-uptake, Glutaminase or Glutamate carboxypeptidase II activity, expression of mutant DISC1 was associated with increased levels of alanine-serine-cysteine transporter 2, vesicular glutamate transporters 1 and 3 in primary astrocytes and in the hippocampus as well as elevated expression of the NR1 subunit and diminished expression of the NR2A subunit of NMDA receptors in the hippocampus at postnatal day 21. Our findings indicate that decreased D-serine production by astrocytic mutant DISC1 may lead to compensatory changes in levels of the amino acid transporters and NMDA receptors in the context of tripartite synapse. PMID:25131692

  8. Phosphene Perception Relates to Visual Cortex Glutamate Levels and Covaries with Atypical Visuospatial Awareness.

    PubMed

    Terhune, Devin B; Murray, Elizabeth; Near, Jamie; Stagg, Charlotte J; Cowey, Alan; Cohen Kadosh, Roi

    2015-11-01

    Phosphenes are illusory visual percepts produced by the application of transcranial magnetic stimulation to occipital cortex. Phosphene thresholds, the minimum stimulation intensity required to reliably produce phosphenes, are widely used as an index of cortical excitability. However, the neural basis of phosphene thresholds and their relationship to individual differences in visual cognition are poorly understood. Here, we investigated the neurochemical basis of phosphene perception by measuring basal GABA and glutamate levels in primary visual cortex using magnetic resonance spectroscopy. We further examined whether phosphene thresholds would relate to the visuospatial phenomenology of grapheme-color synesthesia, a condition characterized by atypical binding and involuntary color photisms. Phosphene thresholds negatively correlated with glutamate concentrations in visual cortex, with lower thresholds associated with elevated glutamate. This relationship was robust, present in both controls and synesthetes, and exhibited neurochemical, topographic, and threshold specificity. Projector synesthetes, who experience color photisms as spatially colocalized with inducing graphemes, displayed lower phosphene thresholds than associator synesthetes, who experience photisms as internal images, with both exhibiting lower thresholds than controls. These results suggest that phosphene perception is driven by interindividual variation in glutamatergic activity in primary visual cortex and relates to cortical processes underlying individual differences in visuospatial awareness. PMID:25725043

  9. Blood glutamate scavenging as a novel neuroprotective treatment for paraoxon intoxication.

    PubMed

    Ruban, Angela; Mohar, Boaz; Jona, Ghil; Teichberg, Vivian I

    2014-02-01

    Organophosphate-induced brain damage is an irreversible neuronal injury, likely because there is no pharmacological treatment to prevent or block secondary damage processes. The presence of free glutamate (Glu) in the brain has a substantial role in the propagation and maintenance of organophosphate-induced seizures, thus contributing to the secondary brain damage. This report describes for the first time the ability of blood glutamate scavengers (BGS) oxaloacetic acid in combination with glutamate oxaloacetate transaminase to reduce the neuronal damage in an animal model of paraoxon (PO) intoxication. Our method causes a rapid decrease of blood Glu levels and creates a gradient that leads to the efflux of the excess brain Glu into the blood, thus reducing neurotoxicity. We demonstrated that BGS treatment significantly prevented the peripheral benzodiazepine receptor (PBR) density elevation, after PO exposure. Furthermore, we showed that BGS was able to rescue neurons in the piriform cortex of the treated rats. In conclusion, these results suggest that treatment with BGS has a neuroprotective effect in the PO intoxication. This is the first time that this approach is used in PO intoxication and it may be of high clinical significance for the future treatment of the secondary neurologic damage post organophosphates exposure.

  10. Comparative evaluation of N-acetylcysteine (NAC) and N-acetylcysteine amide (NACA) on glutamate and lead-induced toxicity in CD-1 mice

    PubMed Central

    Penugonda, Suman; Ercal, Nuran

    2011-01-01

    Recent studies indicate that there is interaction between the glutamatergic neurotransmitters system and lead neurotoxicity. Previously, we have demonstrated the potential effects of glutamate in lead-induced cell death in PC12 cells and the protective role of the novel thiol antioxidant, N-acetylcysteine amide (NACA). The current study 1) investigated the potential effects of glutamate on lead exposed CD-1 mice and 2) evaluated the protective effects of NACA against glutamate and lead toxicity in CD-1 mice, and 3) compared the results with N-aceytylcysteine (a well-known thiol antioxidant). Oxidative stress parameters, including glutathione (GSH), oxidized glutathione (GSSG), GSH/GSSG, and malondialdehyde (MDA) levels, were evaluated. Blood and tissue lead levels, glutamate/glutamine (Glu/Gln) ratios, GS activity, and phospholipase-A2 (PLA2) were also analyzed. Results indicated that lead and glutamate decreased GSH levels in the red blood cells, brains, livers, and kidneys. Exposure to glutamate and lead elevated the MDA levels and PLA2 activity. NACA and NAC provided protection against the detrimental effects of lead by decreasing the blood and tissue lead levels, restoring intracellular GSH levels, and decreasing the MDA levels. NACA and NAC also increased the GS activity thereby decreasing Glu/Gln levels. However, NACA appeared to have better chelating and antioxidant properties than NAC, due to its higher liphophilicity and its ability to cross the blood-brain barrier. PMID:21145953

  11. Effects of insularity on digestion: living on islands induces shifts in physiological and morphological traits in island reptiles.

    PubMed

    Sagonas, Kostas; Pafilis, Panayiotis; Valakos, Efstratios D

    2015-10-01

    Living on islands entails numerous challenges for animals, among which resource scarcity stands out. In order to survive, animals have to optimize energy acquisition. We examined the impact of insularity on digestion comparing a series of physiological and morphological traits of adult males between insular and mainland populations of the Balkan green lizard. Island lizards had longer gastrointestinal tracts and gut passage times and higher digestive efficiencies. The dissection of the hindgut revealed an unexpected finding, the presence of cecal valves that were more frequent in island lizards. Thanks to all above islanders retain food for longer periods and thus maximize energy income and increase the amount of the extracted nutrients. That way, they secure energy income from the limited, in time and quantity, food resources of the islands.

  12. Methodological issues in studying an insular, traditional population: a women's health survey among Israeli haredi (ultra-Orthodox) Jews.

    PubMed

    Rier, David A; Schwartzbaum, Avraham; Heller, Chaya

    2008-01-01

    This article describes obstacles encountered and strategies devised in planning and conducting a national telephone health survey (n = 459) of an insular, deeply traditional religious population, haredi (ultra-Orthodox Jewish) Israeli women. The paper discusses how special characteristics of this population influenced study design, sampling, data collection, and interpretation. Sampling employed polling data to identify haredi concentrations. Despite haredim's reputation for low survey participation, we achieved a 71-74% response rate (depending on the unknown eligibility of 24 phones never answered) in interviews conducted in 2003-2004. We describe our systematic attention to special aspects of haredi culture such as: modesty and speech codes; the need for rabbinic endorsement; and the importance of female, haredi interviewers. This research was initiated and managed by a community-based women's health non-governmental organization, in partnership with trained researchers. Our experiences can guide others surveying insular communities, such as traditional Muslim and Christian societies.

  13. A new species of insular Rock Gecko (Genus Cnemaspis Strauch, 1887) from the Bidong Archipelago, Terengganu, Peninsular Malaysia.

    PubMed

    Grismer, L Lee; Wood, Perry L; Ahmad, Amirrudin B; Sumarli, Alexandra S-I; Vazquez, Jessika J; Ismail, Lukman H B; Nance, Ronald; Mohd-Amin, Muhammad Afif B; Othman, Mohamad N A B; Rizaijessika, Syed A; Kuss, Maria; Murdoch, Matthew; Cobos, Anthony

    2014-01-24

    A new insular species Cnemaspis bidongensis sp. nov. (Squamata: Gekkonidae), is described from Pulau Bidong, Terengganu, Peninsular Malaysia and bears a unique suite of morphological and color pattern characters that differentiate it from all other congeners. Cnemaspis bidongensis sp. nov. is the sister species to C. kendallii (Gray) and represents the fifth insular endemic species of Cnemaspis on archipelagos along the east coast of Peninsular Malaysia. This species survived massive deforestation of the small island of Bidong (260 ha) from the mid 1970s to the early 1990s when the island served as a Vietnamese refugee camp and harbored as many as 40,000 people at one time. We hypothesize that this species' generalized lifestyle contributed to its survival, allowing it to seek refuge in rocky microhabitats.

  14. Effects of insularity on digestion: living on islands induces shifts in physiological and morphological traits in island reptiles

    NASA Astrophysics Data System (ADS)

    Sagonas, Kostas; Pafilis, Panayiotis; Valakos, Efstratios D.

    2015-10-01

    Living on islands entails numerous challenges for animals, among which resource scarcity stands out. In order to survive, animals have to optimize energy acquisition. We examined the impact of insularity on digestion comparing a series of physiological and morphological traits of adult males between insular and mainland populations of the Balkan green lizard. Island lizards had longer gastrointestinal tracts and gut passage times and higher digestive efficiencies. The dissection of the hindgut revealed an unexpected finding, the presence of cecal valves that were more frequent in island lizards. Thanks to all above islanders retain food for longer periods and thus maximize energy income and increase the amount of the extracted nutrients. That way, they secure energy income from the limited, in time and quantity, food resources of the islands.

  15. Topiramate protects against glutamate excitotoxicity via activating BDNF/TrkB-dependent ERK pathway in rodent hippocampal neurons.

    PubMed

    Mao, Xiao-Yuan; Cao, Yong-Gang; Ji, Zhong; Zhou, Hong-Hao; Liu, Zhao-Qian; Sun, Hong-Li

    2015-07-01

    Topiramate (TPM) was previously found to have neuroprotection against neuronal injury in epileptic and ischemic models. However, whether TPM protects against glutamate-induced excitotoxicity in hippocampal neurons is elusive. Our present work aimed to evaluate the protective effect of TPM against glutamate toxicity in hippocampal neurons and further figure out the potential molecular mechanisms. The in vitro glutamate excitotoxic model was prepared with 125μM glutamate for 20min. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) analysis and Hoechst 33342 staining were conducted to detect neuronal survival. The protein expressions of brain-derived neurotrophic factor (BDNF), TrkB, mitogen-activated protein kinase (MAPK) cascade (including extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and p38 MAPK), cyclic AMP response element binding protein (CREB), Bcl-2, Bax and β-actin were detected via Western blot assay. Our results demonstrated that TPM protected hippocampal neurons from glutamate toxicity. Meanwhile, the pretreatment of TPM for 10min significantly prevented the down-regulation of BDNF and the phosphorylation of TrkB. Furthermore, the elevation of phosphorylated EKR expression was significantly inhibited after blockade of TrkB by TrkB IgG, while no alterations of phosphorylated JNK and p38 MAPK were found in the cultured hippocampal neurons. Besides, it was also found that the enhanced phosphorylation of CREB was evidently reversed under excitotoxic conditions after treating with U0126 (the selective inhibitor of ERK). The protein level of Bcl-2 was also observed to be remarkably increased after TPM treatment. In conclusion, these findings implicate that TPM exerts neuroprotective effects against glutamate excitotoxicity in hippocampal neurons and its protection may be modulated through BDNF/TrkB-dependent ERK pathway.

  16. Fluctuations in nucleus accumbens extracellular glutamate and glucose during motivated glucose-drinking behavior: dissecting the neurochemistry of reward.

    PubMed

    Wakabayashi, Ken T; Myal, Stephanie E; Kiyatkin, Eugene A

    2015-02-01

    While motivated behavior involves multiple neurochemical systems, few studies have focused on the role of glutamate, the brain's excitatory neurotransmitter, and glucose, the energetic substrate of neural activity in reward-related neural processes. Here, we used high-speed amperometry with enzyme-based substrate-sensitive and control, enzyme-free biosensors to examine second-scale fluctuations in the extracellular levels of these substances in the nucleus accumbens shell during glucose-drinking behavior in trained rats. Glutamate rose rapidly after the presentation of a glucose-containing cup and before the initiation of drinking (reward seeking), decreased more slowly to levels below baseline during consumption (sensory reward), and returned to baseline when the ingested glucose reached the brain (metabolic reward). When water was substituted for glucose, glutamate rapidly increased with cup presentation and in contrast to glucose drinking, increased above baseline after rats tasted the water and refused to drink further. Therefore, extracellular glutamate show distinct changes associated with key events of motivated drinking behavior and opposite dynamics during sensory and metabolic components of reward. In contrast to glutamate, glucose increased at each stimulus and behavioral event, showing a sustained elevation during the entire behavior and a robust post-ingestion rise that correlated with the gradual return of glutamate levels to their baseline. By comparing active drinking with passive intra-gastric glucose delivery, we revealed that fluctuations in extracellular glucose are highly dynamic, reflecting a balance between rapid delivery because of neural activity, intense metabolism, and the influence of ingested glucose reaching the brain.

  17. Emotional Learning and Glutamate: Translational Perspectives

    PubMed Central

    Gillespie, Charles F.; Ressler, Kerry J.

    2009-01-01

    Anxiety disorders are a common focus of clinical concern and certain forms of anxiety may be conceptualized as disorders of emotional learning. Behavior therapies effective in the treatment of anxiety are modeled on extinction training as a means of reducing pathological anxiety. The present understanding of human anxiety has been informed by preclinical research using rodent models to study the acquisition and extinction of fear. Glutamate appears to have a central role in both of these processes. The authors review this literature and discuss novel applications of D-cycloserine, a partial N-methyl-D-aspartate agonist, for the treatment of anxiety. PMID:16400246

  18. Major histocompatibility complex variation in insular populations of the Egyptian vulture: inferences about the roles of genetic drift and selection.

    PubMed

    Agudo, Rosa; Alcaide, Miguel; Rico, Ciro; Lemus, Jesus A; Blanco, Guillermo; Hiraldo, Fernando; Donázar, Jose A

    2011-06-01

    Insular populations have attracted the attention of evolutionary biologists because of their morphological and ecological peculiarities with respect to their mainland counterparts. Founder effects and genetic drift are known to distribute neutral genetic variability in these demes. However, elucidating whether these evolutionary forces have also shaped adaptive variation is crucial to evaluate the real impact of reduced genetic variation in small populations. Genes of the major histocompatibility complex (MHC) are classical examples of evolutionarily relevant loci because of their well-known role in pathogen confrontation and clearance. In this study, we aim to disentangle the partial roles of genetic drift and natural selection in the spatial distribution of MHC variation in insular populations. To this end, we integrate the study of neutral (22 microsatellites and one mtDNA locus) and MHC class II variation in one mainland (Iberia) and two insular populations (Fuerteventura and Menorca) of the endangered Egyptian vulture (Neophron percnopterus). Overall, the distribution of the frequencies of individual MHC alleles (n=17 alleles from two class II B loci) does not significantly depart from neutral expectations, which indicates a prominent role for genetic drift over selection. However, our results point towards an interesting co-evolution of gene duplicates that maintains different pairs of divergent alleles in strong linkage disequilibrium on islands. We hypothesize that the co-evolution of genes may counteract the loss of genetic diversity in insular demes, maximize antigen recognition capabilities when gene diversity is reduced, and promote the co-segregation of the most efficient allele combinations to cope with local pathogen communities.

  19. Major histocompatibility complex variation in insular populations of the Egyptian vulture: inferences about the roles of genetic drift and selection.

    PubMed

    Agudo, Rosa; Alcaide, Miguel; Rico, Ciro; Lemus, Jesus A; Blanco, Guillermo; Hiraldo, Fernando; Donázar, Jose A

    2011-06-01

    Insular populations have attracted the attention of evolutionary biologists because of their morphological and ecological peculiarities with respect to their mainland counterparts. Founder effects and genetic drift are known to distribute neutral genetic variability in these demes. However, elucidating whether these evolutionary forces have also shaped adaptive variation is crucial to evaluate the real impact of reduced genetic variation in small populations. Genes of the major histocompatibility complex (MHC) are classical examples of evolutionarily relevant loci because of their well-known role in pathogen confrontation and clearance. In this study, we aim to disentangle the partial roles of genetic drift and natural selection in the spatial distribution of MHC variation in insular populations. To this end, we integrate the study of neutral (22 microsatellites and one mtDNA locus) and MHC class II variation in one mainland (Iberia) and two insular populations (Fuerteventura and Menorca) of the endangered Egyptian vulture (Neophron percnopterus). Overall, the distribution of the frequencies of individual MHC alleles (n=17 alleles from two class II B loci) does not significantly depart from neutral expectations, which indicates a prominent role for genetic drift over selection. However, our results point towards an interesting co-evolution of gene duplicates that maintains different pairs of divergent alleles in strong linkage disequilibrium on islands. We hypothesize that the co-evolution of genes may counteract the loss of genetic diversity in insular demes, maximize antigen recognition capabilities when gene diversity is reduced, and promote the co-segregation of the most efficient allele combinations to cope with local pathogen communities. PMID:21535276

  20. Building and Applying "Insularity Theory": Review on Knapp's Prehistoric and Protohistoric Cyprus, 2008.

    NASA Astrophysics Data System (ADS)

    Katsarou-Tzeveleki, Stella

    listing of external factors (colonization, invasions) originating in the Near East and the Aegean as sequential narrative history, and the descriptive, systemic analysis of 'materiality, production, trade, migration and colonization which have for long been the cornerstones of Cypriot archaeology' (p. 11). In contrast, he turns his attention towards the internal processes within the island society of Bronze Age Cyprus, which shape its insularity and give it a distinctive identity at this specific period, processes that lead to contextual history and formative tradition. 'To study how any society changes, at any time, it is crucial first to look at internal rather than external factors' (p. 1). Defining the concept of insularity is his aim; therefore, he begins with a number of very apposite rhetorical questions (p. 13) and identifies several individual parameters (connectivity, islandscape, social identity, ethnicity, migration, acculturation, hybridization) to which he assigns collective and individual meanings. The eight chapters that follow may be assigned, broadly, to three general units: in the first of these (ch. 1-2), Knapp offers a synthesis of these parameters in the form of a 'theory of insularity'. In the second (ch. 3-7) he formulates his revised narrative of the prehistory and social identity of the island, which involves a presentation of social and economic, rather than stylistic categories, on the basis of the parameters laid down in his theoretical scheme. Finally, in the third unit (ch. 8), he records his overall conclusions, the new cognitive experiences and concerns that have emerged from the application of his theory, both to Cyprus and to insular archaeology in the Mediterranean and on a world scale. Knapp's synthesis of the theory of insularity in the first unit is a major contribution to Mediterranean archaeology, and makes this book a seminal work. Continuing and broadening Broodbank's (2000) reasoning about the Cyclades, Knapp, with Cyprus as his

  1. Spatiotemporal dynamics of excitation in rat insular cortex: intrinsic corticocortical circuit regulates caudal-rostro excitatory propagation from the insular to frontal cortex.

    PubMed

    Fujita, S; Adachi, K; Koshikawa, N; Kobayashi, M

    2010-01-13

    The insular cortex (IC), composing unique anatomical connections, receives multi-modal sensory inputs including visceral, gustatory and somatosensory information from sensory thalamic nuclei. Axonal projections from the limbic structures, which have a profound influence on induction of epileptic activity, also converge onto the IC. However, functional connectivity underlying the physiological and pathological roles characteristic to the IC still remains unclear. The present study sought to elucidate the spatiotemporal dynamics of excitatory propagation and their cellular mechanisms in the IC using optical recording in urethane-anesthetized rats. Repetitive electrical stimulations of the IC at 50 Hz demonstrated characteristic patterns of excitatory propagation depending on the stimulation sites. Stimulation of the granular zone of the IC (GI) and other surrounding cortices such as the motor/primary sensory/secondary sensory cortices evoked round-shaped excitatory propagations, which often extended over the borders of adjacent areas, whereas excitation of the agranular and dysgranular zones in the IC (AI and DI, respectively) spread along the rostrocaudal axis parallel to the rhinal fissure. Stimulation of AI/DI often evoked excitation in the dorsolateral orbital cortex, which exhibited spatially discontinuous topography of excitatory propagation in the IC. Pharmacological manipulations using 6,7-dinitroquinoxaline-2,3(1H,4H)-dione (DNQX), a non-NMDA receptor antagonist, D-2-amino-5-phosphonovaleric acid (D-APV), an NMDA receptor antagonist, and bicuculline methiodide, a GABA(A) receptor antagonist, indicate that excitatory propagation was primarily regulated by non-NMDA and GABA(A) receptors. Microinjection of lidocaine or incision of the supragranular layers of the rostrocaudally middle part of excitatory regions suppressed excitation in the remote regions from the stimulation site, suggesting that the excitatory propagation in the IC is largely mediated by

  2. Mesenchymal stem cells protect CNS neurons against glutamate excitotoxicity by inhibiting glutamate receptor expression and function.

    PubMed

    Voulgari-Kokota, A; Fairless, R; Karamita, M; Kyrargyri, V; Tseveleki, V; Evangelidou, M; Delorme, B; Charbord, P; Diem, R; Probert, L

    2012-07-01

    Mesenchymal stem cells (MSC) promote functional recovery in experimental models of central nervous system (CNS) pathology and are currently being tested in clinical trials for stroke, multiple sclerosis and CNS injury. Their beneficial effects are attributed to the activation of endogenous CNS protection and repair processes as well as immune regulation but their mechanisms of action are poorly understood. Here we investigated the neuroprotective effects of mouse MSC in rodent MSC-neuron co-cultures and mice using models of glutamate excitotoxicity. A 24h pre-culture of mouse primary cortical neurons with MSC protected them against glutamate (NMDA) receptor-induced death and conditioned medium from MSC (MSC CM) was sufficient for this effect. Protection by MSC CM was associated with reduced mRNA levels of genes encoding NMDA receptor subunits, and increased levels for genes associated with non-neuronal and stem cell types, as shown by RT-PCR and cDNA microarray analyses. Changes in gene expression were not associated with alterations in cell lineage representation within the cultures. Further, MSC CM-mediated neuroprotection in rat retinal ganglion cells was associated with reduced glutamate-induced calcium influx. The adoptive transfer of EGFP(+)MSC in a mouse kainic acid epilepsy model also provided neuroprotection against glutamate excitotoxicity in vivo, as shown by reduced neuron damage and glial cell activation in the hippocampus. These results show that MSC mediate direct neuroprotection by reducing neuronal sensitivity to glutamate receptor ligands and altering gene expression, and suggest a link between the therapeutic effects of MSC and the activation of cell plasticity in the damaged CNS. PMID:22561409

  3. Rat odontoblasts may use glutamate to signal dentin injury.

    PubMed

    Cho, Yi Sul; Ryu, Chang Hyun; Won, Jong Hwa; Vang, Hue; Oh, Seog Bae; Ro, Jin Young; Bae, Yong Chul

    2016-10-29

    Accumulating evidence indicates that odontoblasts act as sensor cells, capable of triggering action potentials in adjacent pulpal nociceptive axons, suggesting a paracrine signaling via a currently unknown mediator. Since glutamate can mediate signaling by non-neuronal cells, and peripheral axons may express glutamate receptors (GluR), we hypothesized that the expression of high levels of glutamate, and of sensory receptors in odontoblasts, combined with an expression of GluR in adjacent pulpal axons, is the morphological basis for odontoblastic sensory signaling. To test this hypothesis, we investigated the expression of glutamate, the thermo- and mechanosensitive ion channels transient receptor potential vanilloid 1 (TRPV1), transient receptor potential ankyrin 1 (TRPA1), and TWIK-1-related K+channel (TREK-1), and the glutamate receptor mGluR5, in a normal rat dental pulp, and following dentin injury. We also examined the glutamate release from odontoblast in cell culture. Odontoblasts were enriched with glutamate, at the level as high as in adjacent pulpal axons, and showed immunoreactivity for TRPV1, TRPA1, and TREK-1. Pulpal sensory axons adjacent to odontoblasts expressed mGluR5. Both the levels of glutamate in odontoblasts, and the expression of mGluR5 in nearby axons, were upregulated following dentin injury. The extracellular glutamate concentration was increased significantly after treating of odontoblast cell line with calcium permeable ionophore, suggesting glutamate release from odontoblasts. These findings lend morphological support to the hypothesis that odontoblasts contain glutamate as a potential neuroactive substance that may activate adjacent pulpal axons, and thus contribute to dental pain and hypersensitivity.

  4. Rat odontoblasts may use glutamate to signal dentin injury.

    PubMed

    Cho, Yi Sul; Ryu, Chang Hyun; Won, Jong Hwa; Vang, Hue; Oh, Seog Bae; Ro, Jin Young; Bae, Yong Chul

    2016-10-29

    Accumulating evidence indicates that odontoblasts act as sensor cells, capable of triggering action potentials in adjacent pulpal nociceptive axons, suggesting a paracrine signaling via a currently unknown mediator. Since glutamate can mediate signaling by non-neuronal cells, and peripheral axons may express glutamate receptors (GluR), we hypothesized that the expression of high levels of glutamate, and of sensory receptors in odontoblasts, combined with an expression of GluR in adjacent pulpal axons, is the morphological basis for odontoblastic sensory signaling. To test this hypothesis, we investigated the expression of glutamate, the thermo- and mechanosensitive ion channels transient receptor potential vanilloid 1 (TRPV1), transient receptor potential ankyrin 1 (TRPA1), and TWIK-1-related K+channel (TREK-1), and the glutamate receptor mGluR5, in a normal rat dental pulp, and following dentin injury. We also examined the glutamate release from odontoblast in cell culture. Odontoblasts were enriched with glutamate, at the level as high as in adjacent pulpal axons, and showed immunoreactivity for TRPV1, TRPA1, and TREK-1. Pulpal sensory axons adjacent to odontoblasts expressed mGluR5. Both the levels of glutamate in odontoblasts, and the expression of mGluR5 in nearby axons, were upregulated following dentin injury. The extracellular glutamate concentration was increased significantly after treating of odontoblast cell line with calcium permeable ionophore, suggesting glutamate release from odontoblasts. These findings lend morphological support to the hypothesis that odontoblasts contain glutamate as a potential neuroactive substance that may activate adjacent pulpal axons, and thus contribute to dental pain and hypersensitivity. PMID:27555550

  5. 1. GREAT NORTHERN ELEVATORS. 1900 STEEL ELEVATOR WITH SQUARE BINS ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    1. GREAT NORTHERN ELEVATORS. 1900 STEEL ELEVATOR WITH SQUARE BINS (AS OPPOSED) TO THE SIMILAR STEEL ELEVATOR IN BUFFALO NEW YORK WITH ROUND ELEVATOR BINS. - Great Northern Elevator "S", Saint Louis Bay, Superior, Douglas County, WI

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

    PubMed

    Cao, Yan; Duan, Zuoying; Shi, Zhongping

    2014-02-01

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

  7. Postsynaptic activation at the squid giant synapse by photolytic release of L-glutamate from a 'caged' L-glutamate.

    PubMed Central

    Corrie, J E; DeSantis, A; Katayama, Y; Khodakhah, K; Messenger, J B; Ogden, D C; Trentham, D R

    1993-01-01

    1. Pharmacological evidence suggests L-glutamate is a strong candidate as a transmitter at the giant synapse of the squid. Postsynaptic activation at the giant synapse cannot be effected by conventional application of putative neurotransmitters by iontophoresis or perfusion, apparently because the complex structure of the synapse prevents a sufficiently rapid change in concentration at the postsynaptic membrane. Flash photolytic release of L-glutamate from a pharmacologically inert 'caged' L-glutamate pre-equilibrated in the stellate ganglion of Alloteuthis or Loligo was used to determine whether L-glutamate can produce postsynaptic activation when released rapidly in the synaptic clefts. 2. The preparation, reaction mechanism and properties of the caged L-glutamate, N-1-(2-nitrophenyl)ethoxycarbonyl-L-glutamate, are described. The product quantum yield on photolysis was 0.65 (+/- 0.05). On flash photolysis glutamate release followed a single exponential time-course in the pH range 5.5-7.8. The rate constant was proportional to [H+] and was 93 s-1 at pH 5.5 and 16 degrees C in artificial sea water (ionic strength, I = 0.68 M). 3. At pH 7.8 flash photolysis of caged glutamate pre-equilibrated in the synapse caused only a slow depolarization. A second photolytic release of L-glutamate or transsynaptic activation produced no further depolarization, suggesting desensitization and inactivation of postsynaptic mechanisms by the initial pulse of L-glutamate. 4. Synaptic transmission in the giant synapse was normal at pH 5.5. Flash photolysis at pH 5.5 caused rapid production of L-glutamate within the synaptic cleft and a fast postsynaptic depolarization which generated postsynaptic action potentials.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7901400

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

    PubMed

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

    2016-05-01

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

  9. Mammalian folylpoly-. gamma. -glutamate synthetase. 3. Specificity for folate analogues

    SciTech Connect

    George, S.; Cichowicz, D.J.; Shane, B.

    1987-01-27

    A variety of folate analogues were synthesized to explore the specificity of the folate binding site of hog liver folypolyglutamate synthetase and the requirements for catalysis. Modifications of the internal and terminal glutamate moieties of folate cause large drops in on rates and/or affinity for the protein. The only exceptions are glutamine, homocysteate, and ornithine analogues, indicating a less stringent specificity around the delta-carbon of glutamate. It is proposed that initial folate binding to the enzyme involves low-affinity interactions at a pterin and a glutamate site and that the first glutamate bound is the internal residue adjacent to the benzoyl group. Processive movement of the polyglutamate chain through the glutamate site and a possible conformational change in the protein when the terminal residue is bound would result in tight binding and would position the ..gamma..-carboxyl of the terminal glutamate in the correct position for catalysis. The 4-amino substitution of folate increases the on rate for monoglutamate derivatives but severely impairs catalysis with diglutamate derivatives. Pteroylornithine derivatives are the first potent and specific inhibitors of folylpolyglutamate synthetase to be identified and may act as analogues of reaction intermediates. Other folate derivatives with tetrahedral chemistry replacing the peptide bond, such as pteroyl-..gamma..-glutamyl-(psi,CH/sub 2/-NH)-glutamate, retain affinity for the protein but are considerably less effective inhibitors than the ornithine derivatives. Enzyme activity was assayed using (/sup 14/C)glutamate.

  10. 78 FR 76321 - Monosodium Glutamate From China and Indonesia

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-17

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

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

    PubMed

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

    2016-09-01

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

  12. 21 CFR 522.1125 - Hemoglobin glutamer-200 (bovine).

    Code of Federal Regulations, 2012 CFR

    2012-04-01

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

  13. 21 CFR 522.1125 - Hemoglobin glutamer-200 (bovine).

    Code of Federal Regulations, 2013 CFR

    2013-04-01

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

  14. 21 CFR 522.1125 - Hemoglobin glutamer-200 (bovine).

    Code of Federal Regulations, 2014 CFR

    2014-04-01

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

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

    PubMed

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

    2015-06-01

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

  16. Palaeoenvironments of insular Southeast Asia during the Last Glacial Period: a savanna corridor in Sundaland?

    NASA Astrophysics Data System (ADS)

    Bird, Michael I.; Taylor, David; Hunt, Chris

    2005-11-01

    Consideration of a range of evidence from geomorphology, palynology, biogeography and vegetation/climate modelling suggests that a north-south 'savanna corridor' did exist through the continent of Sundaland (modern insular Indonesia and Malaysia) through the Last Glacial Period (LGP) at times of lowered sea-level, as originally proposed by Heaney [1991. Climatic Change 19, 53-61]. A minimal interpretation of the size of this corridor requires a narrow but continuous zone of open 'savanna' vegetation 50-150 km wide, running along the sand-covered divide between the modern South China and Java Seas. This area formed a land bridge between the Malaysian Peninsula and the major islands of Sumatra, Java and Borneo. The savanna corridor connected similar open vegetation types north and south of the equator, and served as a barrier to the dispersal of rainforest-dependent species between Sumatra and Borneo. A maximal interpretation of the available evidence is compatible with the existence of a broad savanna corridor, with forest restricted to refugia primarily in Sumatra, Borneo and the continental shelf beneath the modern South China Sea. This savanna corridor may have provided a convenient route for the rapid early dispersal of modern humans through the region and on into Australasia.

  17. Multiarchitectonic characterization of insular, perirhinal and related regions in a basal mammal, Echinops telfairi.

    PubMed

    Künzle, H; Radtke-Schuller, S

    2000-12-01

    The rhinal cortex was investigated in the Madagascan lesser hedgehog tenrec, a basal placental mammal. This region parallels the rhinal indentation and presumably contains the equivalents of the insular and perirhinal cortices. Using cyto- and myeloarchitectural, enzyme- and immunohistochemical criteria as well as data on the connections with the olfactory bulb, the rhinal cortex was subdivided tentatively along its rostrocaudal and dorsoventral planes. An area caudally adjacent to the rhinal cortex received a prominent input from the olfactory bulb and was also preliminarily characterized in this study. Because previous studies in insectivores remained controversial with regard to the identification of the claustrum, special attention was paid to the laminar organization of the rhinal cortex and its deep cell groups. The tenrec's claustrum was identified and delineated cytoarchitecturally and by its negative acetylcholinesterase stain. Latexin, a molecular marker for characterizing infragranular and claustral cells, also helped to differentiate the claustrum from the cell groups subjacent to it. Thus, the data indicate that in poorly differentiated mammals the claustrum occupies an intermediate deep position within the width of the rhinal cortex, i.e., it is separated from the subcortical white matter by additional, still unidentified, cell groups.

  18. Insular cortex alpha1-adrenoceptors modulate the parasympathetic component of the baroreflex in unanesthetized rats.

    PubMed

    Alves, Fernando H F; Crestani, Carlos C; Resstel, Leonardo B M; Correa, Fernando M A

    2009-10-27

    The insular cortex (IC) has been reported to modulate the cardiac parasympathetic activity of the baroreflex in unanesthetized rats. However, which neurotransmitters are involved in this modulation is still unclear. In the present study, we evaluated the possible involvement of local IC-noradrenergic neurotransmission in modulating reflex bradycardiac responses. Bilateral microinjection of the selective alpha(1)-adrenoceptor antagonist WB4101 (15 nmol/100 nL), into the IC of male Wistar rats, increased the gain of reflex bradycardia in response to mean arterial pressure (MAP) increases evoked by intravenous infusion of phenylephrine. However, bilateral microinjection of equimolar doses of either the selective alpha(2)-adrenoceptor antagonist RX821002 or the non-selective beta-adrenoceptor antagonist propranolol into the IC did not affect the baroreflex response. No effects were observed in basal MAP or heart rate values after bilateral microinjection of noradrenergic antagonists into the IC, thus suggesting no tonic influence of IC-noradrenergic neurotransmission on resting cardiovascular parameters. In conclusion, these data provide evidence that local IC-noradrenergic neurotransmission has an inhibitory influence on baroreflex responses to blood pressure increase evoked by phenylephrine infusion through activation of alpha(1)-adrenoceptors. PMID:19686710

  19. N-methyl-D-aspartate receptors in the insular cortex modulate baroreflex in unanesthetized rats.

    PubMed

    Alves, Fernando H F; Crestani, Carlos C; Resstel, Leonardo B M; Correa, Fernando M A

    2009-05-11

    In the present study, we report the effect of insular cortex (IC) ablation caused by bilateral microinjection of the non-selective synaptic blocker CoCl(2) on cardiac baroreflex response in unanesthetized rats as well as the involvement of local glutamatergic neurotransmission. Unilateral (left or right) microinjection of CoCl(2) (1 nmol/ 100 nL) did not affect the bradycardiac response to blood pressure increase evoked by intravenous infusion of phenylephrine nor the tachycardiac response to blood pressure decrease caused by intravenous infusion of sodium nitroprusside, 10 min after CoCl(2). Bilateral microinjection of CoCl(2) into IC decreased the magnitude of reflex bradycardia without affecting tachycardiac responses. Baroreflex activity returned to control values 60 min after CoCl(2) microinjection, confirming its reversible effect. Further we studied the possible involvement of IC-glutamatergic neurotransmission in baroreflex modulation. We observed that bilateral microinjection of the selective NMDA receptor antagonist LY235959 (4 nmol/100 nL) into the IC decreased the magnitude of reflex bradycardia without affecting tachycardiac responses. IC treatment with the selective non-NMDA antagonist NBQX (4 nmol/100 nL) did not affect baroreflex activity. The results suggest that synapses within the IC have a tonic excitatory influence on the baroreflex parasympathetic component. Moreover, the present data suggest that local NMDA-receptors are involved in the IC-mediated tonic excitatory influence on baroreflex parasympathetic activity. PMID:19217356

  20. Differential coding of uncertain reward in rat insular and orbitofrontal cortex

    PubMed Central

    Jo, Suhyun; Jung, Min Whan

    2016-01-01

    Anterior insular and orbitofrontal cortex (AIC and OFC, respectively) are known to play important roles in decision making under risk. However, risk-related AIC neural activity has not been investigated and it is controversial whether the rodent OFC conveys genuine risk signals. To address these issues, we examined AIC and OFC neuronal activity in rats responding to five distinct auditory cues predicting water reward with different probabilities. Both structures conveyed significant neural signals for reward, value and risk, with value and risk signals conjunctively coded. However, value signals were stronger and appeared earlier in the OFC, and many risk-coding OFC neurons responded only to the cue predicting certain (100%) reward. Also, AIC neurons tended to increase their activity for a prolonged time following a negative outcome and according to previously expected value. These results show that both the AIC and OFC convey neural signals related to reward uncertainty, but in different ways. The OFC might play an important role in encoding certain reward-biased, risk-modulated subjective value, whereas the AIC might convey prolonged negative outcome and disappointment signals. PMID:27052943

  1. Anthropogenic and Climatic Influence on Vegetation Fires in Peatland of Insular Southeast Asia

    NASA Astrophysics Data System (ADS)

    Liew, S.; Miettinen, J.; Salinas Cortijo, S. V.

    2011-12-01

    Fire is traditionally used as a tool in land clearing by farmers and shifting cultivators in Southeast Asia. However, the small scale clearing of land is increasingly being replaced by modern large-scale conversion of forests into plantations/agricultural land, usually also by fires. Fires get out of control in periods of extreme drought, especially during the El Nino periods, resulting in severe episodes of transboundary air pollution in the form of smoke haze. We use the MODIS active fires product (hotspots) to establish correlations between the temporal and spatial patterns of vegetation fires with climatic variables, land cover change and soil type (peat or non-peat) in the western part of Insular Southeast Asia for a decade from 2001 to 2010. Fire occurrence exhibits a negative correlation with rainfall, and is more severe overall during the El-Nino periods. However, not all regions are equally affected by El-Nino. In Southern Sumatra and Southern Borneo the correlation with El-Nino is high. However, fires in some regions such as the peatland in Riau, Jambi and Sarawak do not appear to be influenced by El-Nino. These regions are also experiencing rapid conversion of forest to large scale plantations.

  2. Genetic drift and rapid evolution of viviparity in insular fire salamanders (Salamandra salamandra).

    PubMed

    Velo-Antón, G; Zamudio, K R; Cordero-Rivera, A

    2012-04-01

    Continental islands offer an excellent opportunity to investigate adaptive processes and to time microevolutionary changes that precede macroevolutionary events. We performed a population genetic study of the fire salamander (Salamandra salamandra), a species that displays unique intraspecific diversity of reproductive strategies, to address the microevolutionary processes leading to phenotypic and genetic differentiation of island, coastal and interior populations. We used eight microsatellite markers to estimate genetic diversity, population structure and demographic parameters in viviparous insular populations and ovoviviparous coastal and interior populations. Our results show considerable genetic differentiation (F(ST) range: 0.06-0.27), and no clear signs of gene flow among populations, except between the large and admixed interior populations. We find no support for island colonization by rafting or intentional/accidental anthropogenic introductions, indicating that rising sea levels were responsible for isolation of the island populations approximately 9000 years ago. Our study provides evidence of rapid genetic differentiation between island and coastal populations, and rapid evolution of viviparity driven by climatic selective pressures on island populations, geographic isolation with genetic drift, or a combination of these factors. Studies of these viviparous island populations in early stages of divergence help us better understand the microevolutionary processes involved in rapid phenotypic shifts. PMID:22086081

  3. Genetic drift and rapid evolution of viviparity in insular fire salamanders (Salamandra salamandra)

    PubMed Central

    Velo-Antón, G; Zamudio, K R; Cordero-Rivera, A

    2012-01-01

    Continental islands offer an excellent opportunity to investigate adaptive processes and to time microevolutionary changes that precede macroevolutionary events. We performed a population genetic study of the fire salamander (Salamandra salamandra), a species that displays unique intraspecific diversity of reproductive strategies, to address the microevolutionary processes leading to phenotypic and genetic differentiation of island, coastal and interior populations. We used eight microsatellite markers to estimate genetic diversity, population structure and demographic parameters in viviparous insular populations and ovoviviparous coastal and interior populations. Our results show considerable genetic differentiation (FST range: 0.06–0.27), and no clear signs of gene flow among populations, except between the large and admixed interior populations. We find no support for island colonization by rafting or intentional/accidental anthropogenic introductions, indicating that rising sea levels were responsible for isolation of the island populations approximately 9000 years ago. Our study provides evidence of rapid genetic differentiation between island and coastal populations, and rapid evolution of viviparity driven by climatic selective pressures on island populations, geographic isolation with genetic drift, or a combination of these factors. Studies of these viviparous island populations in early stages of divergence help us better understand the microevolutionary processes involved in rapid phenotypic shifts. PMID:22086081

  4. Sediment distribution on a storm-dominated insular shelf, Luquillo, Puerto Rico, U.S.A.

    USGS Publications Warehouse

    Schwab, W.C.; Rodriguez, R.W.; Danforthf, W.W.; Gowen, M.H.

    1996-01-01

    A sea-floor mapping investigation designed to assess the sediment distribution, the movement of the nearshore sand supply, and the fate of sediment eroded from the shoreline was conducted using high-resolution sidescan-sonar, seismic reflection, and sediment sampling techniques on the northern insular shelf of Puerto Rico, off the town of Luquillo. Sea-floor structures and the distribution of sediment texture and composition suggest that regional oceanographic processes result in a net offshore direction for cross-shelf sediment transport on the middle and outer shelf during storms. If these same processes are active on the inner shelf, mapping results indicate that this sediment is not transported seaward of a series of east-west trending Pleistocene-age eolianite ridges that outcrop on the middle shelf. The eolianite ridges may act as natural dams, preventing the removal of sediment from the nearshore area. Sand deposits behind the "dams" are up to 20 m thick on the shoreward flank of the ridges.

  5. Macroscopic connection of rat insular cortex: anatomical bases underlying its physiological functions.

    PubMed

    Kobayashi, Masayuki

    2011-01-01

    The insular cortex (IC), which lies on the dorsal bank of the rhinal fissure, receives multi-modal sensory inputs, i.e. visceral, gustatory, nociceptive and thermal information from the sensory thalamic nuclei. In contrast to other primary sensory cortices such as visual, auditory and somatosensory areas, the anatomical features of the IC are quite distinctive; more than a half of the IC is composed of agranular or dysgranular cortex, which lacks a complete granular layer (layer IV). In addition to the characteristic layer structures, the IC has dense reciprocal innervations with the limbic structures, including the amygdala and hypothalamus. Such connectivity implies that sensory information processed in the IC is profoundly related to limbic information. By enabling the visualization of functional connectivity in the central nervous system, recent advancements in optical imaging techniques have opened the possibility to elucidate the mechanisms of sensory information processing from a macroscopic perspective. In this review, anatomical and functional features of the IC are overviewed from the aspect of gustatory processing, a typical sensation processed in the IC. In addition, the recently developed optical imaging techniques and their findings in gustatory information processing are summarized. We discuss how these characteristic features of excitatory propagation in the IC play functional roles in transmitting neural excitation arising from the limbic structures to the frontal and orbital cortices. PMID:21708315

  6. Genetic drift and rapid evolution of viviparity in insular fire salamanders (Salamandra salamandra).

    PubMed

    Velo-Antón, G; Zamudio, K R; Cordero-Rivera, A

    2012-04-01

    Continental islands offer an excellent opportunity to investigate adaptive processes and to time microevolutionary changes that precede macroevolutionary events. We performed a population genetic study of the fire salamander (Salamandra salamandra), a species that displays unique intraspecific diversity of reproductive strategies, to address the microevolutionary processes leading to phenotypic and genetic differentiation of island, coastal and interior populations. We used eight microsatellite markers to estimate genetic diversity, population structure and demographic parameters in viviparous insular populations and ovoviviparous coastal and interior populations. Our results show considerable genetic differentiation (F(ST) range: 0.06-0.27), and no clear signs of gene flow among populations, except between the large and admixed interior populations. We find no support for island colonization by rafting or intentional/accidental anthropogenic introductions, indicating that rising sea levels were responsible for isolation of the island populations approximately 9000 years ago. Our study provides evidence of rapid genetic differentiation between island and coastal populations, and rapid evolution of viviparity driven by climatic selective pressures on island populations, geographic isolation with genetic drift, or a combination of these factors. Studies of these viviparous island populations in early stages of divergence help us better understand the microevolutionary processes involved in rapid phenotypic shifts.

  7. How large are the extinct giant insular rodents? New body mass estimations from teeth and bones.

    PubMed

    Moncunill-Solé, Blanca; Jordana, Xavier; Marín-Moratalla, Nekane; Moyà-Solà, Salvador; Köhler, Meike

    2014-03-01

    The island rule entails a modification of the body size of insular mammals, a character related with numerous biological and ecological variables. From the Miocene to human colonization (Holocene), Mediterranean and Canary Islands were unaltered natural ecosystems, with paleofaunas formed with endemic giant rodents among other mammals. Our aim is to create methods to estimate the body masses of fossil island rodents and address the nature of ecological pressures driving the island rule. We created regression equations based on extant rodent data and used these to estimate the body masses of the extinct species. Our results show strong correlations between teeth, cranial and postcranial measurements and body mass, except for the length of the long bones, the transversal diameter of the distal tibia and the anteroposterior diameter of the proximal tibia, where the equations were less reliable. The use of equations obtained from a more homogeneous group (suborder and family) is preferable when analyzing the area of the first molar. The new regressions were applied to estimate the body masses of some Mediterranean and Canarian fossil rodents (Canariomys, C. bravoi 1.5 kg and C. tamarani 1 kg; Hypnomys, H. morpheus 230 g and H. onicensis 200 g; and Muscardinus cyclopeus 100 g). Our results indicate that under absence of predation, resource availability (island area) is the key factor that determines the size of the Canariomys sp. However, under presence of specialized predators (birds of prey), body size evolution is less pronounced (Hypnomys sp.). PMID:24673763

  8. The avian fossil record in Insular Southeast Asia and its implications for avian biogeography and palaeoecology.

    PubMed

    Meijer, Hanneke J M

    2014-01-01

    Excavations and studies of existing collections during the last decades have significantly increased the abundance as well as the diversity of the avian fossil record for Insular Southeast Asia. The avian fossil record covers the Eocene through the Holocene, with the majority of bird fossils Pleistocene in age. Fossil bird skeletal remains represent at least 63 species in 54 genera and 27 families, and two ichnospecies are represented by fossil footprints. Birds of prey, owls and swiftlets are common elements. Extinctions seem to have been few, suggesting continuity of avian lineages since at least the Late Pleistocene, although some shifts in species ranges have occurred in response to climatic change. Similarities between the Late Pleistocene avifaunas of Flores and Java suggest a dispersal route across southern Sundaland. Late Pleistocene assemblages of Niah Cave (Borneo) and Liang Bua (Flores) support the rainforest refugium hypothesis in Southeast Asia as they indicate the persistence of forest cover, at least locally, throughout the Late Pleistocene and Holocene. PMID:24688871

  9. Household waste compositional analysis variation from insular communities in the framework of waste prevention strategy plans

    SciTech Connect

    Zorpas, Antonis A.; Lasaridi, Katia; Voukkali, Irene; Loizia, Pantelitsa; Chroni, Christina

    2015-04-15

    Highlights: • Waste framework directive has set clear waste prevention procedures. • Household Compositional analysis. • Waste management plans. • Zero waste approach. • Waste generation. - Abstract: Waste management planning requires reliable data regarding waste generation, affecting factors on waste generation and forecasts of waste quantities based on facts. In order to decrease the environmental impacts of waste management the choice of prevention plan as well as the treatment method must be based on the features of the waste that are produced in a specific area. Factors such as culture, economic development, climate, and energy sources have an impact on waste composition; composition influences the need of collecting waste more or less frequently of waste collection and disposition. The research question was to discover the main barriers concerning the compositional analysis in Insular Communities under warm climate conditions and the findings from this study enabled the main contents of a waste management plan to be established. These included advice to residents on waste minimisation, liaison with stakeholders and the expansion of kerbside recycling schemes.

  10. The avian fossil record in Insular Southeast Asia and its implications for avian biogeography and palaeoecology

    PubMed Central

    2014-01-01

    Excavations and studies of existing collections during the last decades have significantly increased the abundance as well as the diversity of the avian fossil record for Insular Southeast Asia. The avian fossil record covers the Eocene through the Holocene, with the majority of bird fossils Pleistocene in age. Fossil bird skeletal remains represent at least 63 species in 54 genera and 27 families, and two ichnospecies are represented by fossil footprints. Birds of prey, owls and swiftlets are common elements. Extinctions seem to have been few, suggesting continuity of avian lineages since at least the Late Pleistocene, although some shifts in species ranges have occurred in response to climatic change. Similarities between the Late Pleistocene avifaunas of Flores and Java suggest a dispersal route across southern Sundaland. Late Pleistocene assemblages of Niah Cave (Borneo) and Liang Bua (Flores) support the rainforest refugium hypothesis in Southeast Asia as they indicate the persistence of forest cover, at least locally, throughout the Late Pleistocene and Holocene. PMID:24688871

  11. Ductulo-insular pancreatic endocrine tumor with amyloid deposition: report of a case.

    PubMed

    Shintaku, Masayuki; Tado, Hiroki; Inayama, Kumiko; Murakami, Takaaki; Suzuki, Takahisa

    2015-04-01

    We report a case of ductulo-insular pancreatic endocrine tumor (DI-PET) in a 50-year-old woman. The patient presented with symptoms and signs of hypoglycemia, and a small tumor in the uncus of the pancreas was extirpated. The tumor predominantly consisted of a neuroendocrine tumor (NET) of grade 2, which surrounded a minor component of ductular proliferation accompanied by a desmoplastic stroma. Both components were largely juxtaposed but admixed with each other in small areas. The NET component was immunoreactive for insulin and accompanied by the marked deposition of amyloid in the stroma. The ductular component consisted of a haphazard proliferation of ductules showing mildly atypical cytological features and immunoreactivities for cytokeratins 7 and 19. DI-PET is a rare composite neoplasm that should be distinguished from mixed ductal-neuroendocrine carcinoma because of the marked differences in treatment modalities and prognoses between the tumors. DI-PET associated with stromal amyloid deposition has not been reported to date. The 'transdifferentiation' of NET cells into ductular cells is considered as the most plausible histogenetic mechanism of this tumor, although other possibilities, such as an origin from a primitive endodermal stem cell or the induction of ductular proliferation by stimulation with NET-derived humoral factors, cannot be excluded. PMID:25684418

  12. Central role for the insular cortex in mediating conditioned responses to anticipatory cues

    PubMed Central

    Kusumoto-Yoshida, Ikue; Liu, Haixin; Chen, Billy T.; Fontanini, Alfredo; Bonci, Antonello

    2015-01-01

    Reward-related circuits are fundamental for initiating feeding on the basis of food-predicting cues, whereas gustatory circuits are believed to be involved in the evaluation of food during consumption. However, accumulating evidence challenges such a rigid separation. The insular cortex (IC), an area largely studied in rodents for its role in taste processing, is involved in representing anticipatory cues. Although IC responses to anticipatory cues are well established, the role of IC cue-related activity in mediating feeding behaviors is poorly understood. Here, we examined the involvement of the IC in the expression of cue-triggered food approach in mice trained with a Pavlovian conditioning paradigm. We observed a significant change in neuronal firing during presentation of the cue. Pharmacological silencing of the IC inhibited food port approach. Such a behavior could be recapitulated by temporally selective inactivation during the cue. These findings represent the first evidence, to our knowledge, that cue-evoked neuronal activity in the mouse IC modulates behavioral output, and demonstrate a causal link between cue responses and feeding behaviors. PMID:25583486

  13. Genetic structure in insular and mainland populations of house sparrows (Passer domesticus) and their hemosporidian parasites

    PubMed Central

    Bichet, Coraline; Moodley, Yoshan; Penn, Dustin J; Sorci, Gabriele; Garnier, Stéphane

    2015-01-01

    Small and isolated populations usually exhibit low levels of genetic variability, and thus, they are expected to have a lower capacity to adapt to changes in environmental conditions, such as exposure to pathogens and parasites. Comparing the genetic variability of selectively neutral versus functional loci allows one to assess the evolutionary history of populations and their future evolutionary potential. The genes of the major histocompatibility complex (MHC) control immune recognition of parasites, and their unusually high diversity is genes which is likely driven by parasite-mediated balancing selection. Here, we examined diversity and differentiation of neutral microsatellite loci and functional MHC class I genes in house sparrows (Passer domesticus), living in six insular and six mainland populations, and we aimed to determine whether their diversity or differentiation correlates with the diversity and the prevalence of infection of hemosporidian parasites. We found that island bird populations tended to have lower neutral genetic variability, whereas MHC variability gene was similar between island and mainland populations. Similarly, island populations tended to show greater genetic differentiation than mainland populations, especially at microsatellite markers. The maintenance of MHC genetic diversity and its less marked structure in the island populations could be attributed to balancing-selection. The greater MHC differentiation among populations was negatively correlated with similarity in blood parasites (prevalence and diversity of parasite strains) between populations. Even at low prevalence and small geographical scale, haemosporidian parasites might contribute to structure the variability of immune genes among populations of hosts. PMID:25937907

  14. AxIOM: Amphipod crustaceans from insular Posidonia oceanica seagrass meadows

    PubMed Central

    Heughebaert, André; Lepoint, Gilles

    2016-01-01

    Abstract Background The Neptune grass, Posidonia oceanica (L.) Delile, 1813, is the most widespread seagrass of the Mediterranean Sea. This foundation species forms large meadows that, through habitat and trophic services, act as biodiversity hotspots. In Neptune grass meadows, amphipod crustaceans are one of the dominant groups of vagile invertebrates, forming an abundant and diverse taxocenosis. They are key ecological components of the complex, pivotal, yet critically endangered Neptune grass ecosystems. Nevertheless, comprehensive qualitative and quantitative data about amphipod fauna found in Mediterranean Neptune grass meadows remain scarce, especially in insular locations. New information Here, we provide in-depth metadata about AxIOM, a sample-based dataset published on the GBIF portal. AxIOM is based on an extensive and spatially hierarchized sampling design with multiple years, seasons, day periods, and methods. Samples were taken along the coasts of Calvi Bay (Corsica, France) and of the Tavolara-Punta Coda Cavallo Marine Protected Area (Sardinia, Italy). In total, AxIOM contains 187 samples documenting occurrence (1775 records) and abundance (10720 specimens) of amphipod crustaceans belonging to 72 species spanning 29 families. The dataset is available at http://ipt.biodiversity.be/resource?r=axiom. PMID:27660521

  15. AxIOM: Amphipod crustaceans from insular Posidonia oceanica seagrass meadows

    PubMed Central

    Heughebaert, André; Lepoint, Gilles

    2016-01-01

    Abstract Background The Neptune grass, Posidonia oceanica (L.) Delile, 1813, is the most widespread seagrass of the Mediterranean Sea. This foundation species forms large meadows that, through habitat and trophic services, act as biodiversity hotspots. In Neptune grass meadows, amphipod crustaceans are one of the dominant groups of vagile invertebrates, forming an abundant and diverse taxocenosis. They are key ecological components of the complex, pivotal, yet critically endangered Neptune grass ecosystems. Nevertheless, comprehensive qualitative and quantitative data about amphipod fauna found in Mediterranean Neptune grass meadows remain scarce, especially in insular locations. New information Here, we provide in-depth metadata about AxIOM, a sample-based dataset published on the GBIF portal. AxIOM is based on an extensive and spatially hierarchized sampling design with multiple years, seasons, day periods, and methods. Samples were taken along the coasts of Calvi Bay (Corsica, France) and of the Tavolara-Punta Coda Cavallo Marine Protected Area (Sardinia, Italy). In total, AxIOM contains 187 samples documenting occurrence (1775 records) and abundance (10720 specimens) of amphipod crustaceans belonging to 72 species spanning 29 families. The dataset is available at http://ipt.biodiversity.be/resource?r=axiom.

  16. Gene flow between insular, coastal and interior populations of brown bears in Alaska.

    PubMed

    Paetkau, D; Shields, G F; Strobeck, C

    1998-10-01

    The brown bears of coastal Alaska have been recently regarded as comprising from one to three distinct genetic groups. We sampled brown bears from each of the regions for which hypotheses of genetic uniqueness have been made, including the bears of the Kodiak Archipelago and the bears of Admiralty, Baranof and Chichagof (ABC) Islands in southeast Alaska. These samples were analysed with a suite of nuclear microsatellite markers. The 'big brown bears' of coastal Alaska were found to be part of the continuous continental distribution of brown bears, and not genetically isolated from the physically smaller 'grizzly bears' of the interior. By contrast, Kodiak brown bears appear to have experienced little or no genetic exchange with continental populations in recent generations. The bears of the ABC Islands, which have previously been shown to undergo little or no female-mediated gene flow with mainland populations, were found not to be genetically isolated from mainland bears. The data from the four insular populations indicate that female and male dispersal can be reduced or eliminated by water barriers of 2-4 km and 7 km in width, respectively.

  17. Increased cellular activity in rat insular cortex after water and salt ingestion induced by fluid depletion.

    PubMed

    Pastuskovas, Cinthia V; Cassell, Martin D; Johnson, Alan Kim; Thunhorst, Robert L

    2003-04-01

    Insular cortex (IC) receives inputs from multiple sensory systems, including taste, and from receptors that monitor body electrolyte and fluid balance and blood pressure. This work analyzed metabolic activity of IC cells after water and sodium ingestion induced by sodium depletion. Rats were injected with the diuretic furosemide (10 mg/kg body wt), followed 5 min later by injections of the angiotensin-converting enzyme inhibitor captopril (5 mg/kg body wt). After 90 min, some rats received water and 0.3 M NaCl to drink for 2 h while others did not. A third group had access to water and saline but was not depleted of fluids. All rats were killed for processing of brain tissue for Fos-immunoreactivity (Fos-ir). Nondepleted animals had weak-to-moderate levels of Fos-ir within subregions of IC. Fluid-depleted rats without fluid access had significantly increased Fos-ir in all areas of IC. Levels of Fos-ir were highest in fluid-depleted rats that drank water and sodium. Fos-ir levels were highest in anterior regions of IC and lowest in posterior regions of IC. These results implicate visceral, taste, and/or postingestional factors in the increased metabolic activity of cells in IC.

  18. [Performance of entero-insular axis in an athletic population: diet and exercise influence].

    PubMed

    Rodriguez, Carmen; Quezada-Feijoo, Maribel; Toro, Carmen; Barón-Esquivias, Gonzalo; Segura, Eduardo; Mangas, Alipio; Toro, Rocio

    2015-05-01

    Introducción: La relación existente entre el ejercicio físico y la regulación del apetito puede conducir a una mejora del rendimiento competitivo de los deportistas. Los mediadores del eje entero-insular generan señales neurohumorales que influyen en la regulación del apetito y la homeostasis energética. Objetivo: Determinar la influencia de la dieta y el ejercicio prolongado sobre los péptidos intestinales, grelina, resistina, leptina, e incretinas (GLP-1 y GIP) en una población deportista. MÉTODOS: Este es un estudio prospectivo, de intervención desarrollado desde Octubre 2012 a Marzo 2013. Se incluyeron 32 jugadores de rugby sanos. Se tomaron medidas antropométricas y muestras de sangre en el momento 0 y a los seis meses del estudio. Se distribuyeron aleatoriamente a una dieta bien proteica (DP) o mediterránea (DM) y estudiamos los niveles plasmáticos de adipoquinas e incretinas. Resultados: Las concentraciones plasmáticas de GLP- 1 y GIP presentaron un descenso (p.

  19. A molecular mechanism underlying gustatory memory trace for an association in the insular cortex

    PubMed Central

    Adaikkan, Chinnakkaruppan; Rosenblum, Kobi

    2015-01-01

    Events separated in time are associatively learned in trace conditioning, recruiting more neuronal circuits and molecular mechanisms than in delay conditioning. However, it remains unknown whether a given sensory memory trace is being maintained as a unitary item to associate. Here, we used conditioned taste aversion learning in the rat model, wherein animals associate a novel taste with visceral nausea, and demonstrate that there are two parallel memory traces of a novel taste: a short-duration robust trace, lasting approximately 3 hr, and a parallel long-duration weak one, lasting up to 8 hr, and dependent on the strong trace for its formation. Moreover, only the early robust trace is maintained by a NMDAR-dependent CaMKII- AMPAR pathway in the insular cortex. These findings suggest that a memory trace undergoes rapid modifications, and that the mechanisms underlying trace associative learning differ when items in the memory are experienced at different time points. DOI: http://dx.doi.org/10.7554/eLife.07582.001 PMID:26452094

  20. Has living on islands been so simple? Insights from the insular endemic frog Discoglossus montalentii.

    PubMed

    Bisconti, Roberta; Canestrelli, Daniele; Nascetti, Giuseppe

    2013-01-01

    Island populations have been extensively used as model systems in ecology, biogeography, conservation and evolutionary biology, owing to the several simplifying assumptions that they allow. Nevertheless, recent findings from intra-island phylogeographic studies are casting doubts on the generality of some of these underlying assumptions. We investigated the phylogeography, historical demography, and population genetic structure of the Corsican endemic frog, Discoglossus montalentii. In contrast with expectations based on its insular, restricted and continuous distribution, we found evidence of 3 phylogroups, whose rather ancient divergence (Early-Middle Pleistocene) was likely primed by climatic changes that occurred during the 'middle Pleistocene revolution'. Furthermore, their differentiation explained most (68%) of the overall genetic diversity that was observed. These results and the growing evidence from intra-island phylogeographies, suggest that island populations frequently may not conform to some long-standing assumptions, including long-term stability, range-wide panmixia and the correlation of effective population size to the island size. As a consequence, both for theoretical and for applied purposes, the extensive use of these assumptions in the study of island populations warrants a careful re-examination.

  1. Posterior insular cortex – a site of vestibular–somatosensory interaction?

    PubMed Central

    Baier, Bernhard; zu Eulenburg, Peter; Best, Christoph; Geber, Christian; Müller-Forell, Wibke; Birklein, Frank; Dieterich, Marianne

    2013-01-01

    Background In previous imaging studies the insular cortex (IC) has been identified as an essential part of the processing of a wide spectrum of perception and sensorimotor integration. Yet, there are no systematic lesion studies in a sufficient number of patients examining whether processing of vestibular and the interaction of somatosensory and vestibular signals take place in the IC. Methods We investigated acute stroke patients with lesions affecting the IC in order to fill this gap. In detail, we explored signs of a vestibular tone imbalance such as the deviation of the subjective visual vertical (SVV). We applied voxel-lesion behaviour mapping analysis in 27 patients with acute unilateral stroke. Results Our data demonstrate that patients with lesions of the posterior IC have an abnormal tilt of SVV. Furthermore, re-analysing data of 20 patients from a previous study, we found a positive correlation between thermal perception contralateral to the stroke and the severity of the SVV tilt. Conclusions We conclude that the IC is a sensory brain region where different modalities might interact. PMID:24392273

  2. The Space Elevator

    NASA Astrophysics Data System (ADS)

    Laubscher, Bryan E.

    2005-09-01

    The Space Elevator is conceived to be a carbon nanotube ribbon stretching from an Earth station in the ocean on the equator to far beyond geosynchronous altitude. This elevator co-rotates with the Earth. Climbers ascend the ribbon using power beamed from Earth to launch spacecraft in orbit or to other worlds. The requirements of the ribbon material, challenges to the building of the space elevator, deployment and the promise of the space elevator are briefly discussed in this paper.

  3. Abnormal Expression of Glutamate Transporter and Transporter Interacting Molecules in Prefrontal Cortex in Elderly Patients with Schizophrenia

    PubMed Central

    Bauer, Deborah; Gupta, Daya; Harotunian, Vahram; Meador-Woodruff, James H.; McCullumsmith, Robert E.

    2008-01-01

    Glutamate cycling is critically important for neurotransmission, and may be altered in schizophrenia. The excitatory amino acid transporters (EAATs) facilitate the reuptake of glutamate from the synaptic cleft and have a key role in glutamate cycling. We hypothesized that expression of the EAATs and the EAAT regulating proteins ARHGEF11, JWA, G protein suppressor pathway 1 (GPS1), and KIAA0302 are altered in the brain in schizophrenia. To test this, we measured expression of EAAT1, EAAT2, EAAT3, and EAAT interacting proteins in postmortem tissue from the dorsolateral prefrontal and anterior cingulate cortex of patients with schizophrenia and a comparison group using in situ hybridization and Western blot analysis. We found increased EAAT1 transcripts and decreased protein expression, increased EAAT3 transcripts and protein, and elevated protein expression of both GPS1 and KIAA0302 protein. We did not find any changes in expression of EAAT2. These data indicate that proteins involved in glutamate reuptake and cycling are altered in the cortex in schizophrenia, and may provide potential targets for future treatment strategies. PMID:18678470

  4. Glial glutamate transporters: new actors in brain signaling.

    PubMed

    López-Bayghen, Esther; Ortega, Arturo

    2011-10-01

    Glutamate, the main excitatory amino acid in the vertebrate brain, is critically involved in most of the physiological functions of the central nervous system. It has traditionally been assumed that glutamate triggers a wide array of signaling cascades through the activation of specific membrane receptors. The extracellular levels are tightly regulated to prevent neurotoxic insults. Electrogenic Na(+)-dependent glial glutamate transporters remove the bulk of the neurotransmitter from the synaptic cleft. An exquisitely ordered coupling between glutamatergic neurons and surrounding glia cells is fundamental for excitatory transmission. The glutamate/glutamine and astrocyte/neuron lactate shuttles provide the biochemical framework of this compulsory association. In this context, recent advances show that glial glutamate transporters act as signal transducers that regulate the expression of proteins involved in their compartmentalization with neurons in the so-called tripartite synapse.

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

    SciTech Connect

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

    1987-05-01

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

  6. A novel glutamate dehydrogenase from bovine brain: purification and characterization.

    PubMed

    Lee, J; Kim, S W; Cho, S W

    1995-08-01

    A soluble form of novel glutamate dehydrogenase has been purified from bovine brain. The preparation was homogeneous on sodium dodecyl sulfate-polyacrylamide gel electrophoresis and composed of six identical subunits having a subunit size of 57,500 Da. The biochemical properties of glutamate dehydrogenase such as N-terminal amino acids sequences, kinetic parameters, amino acids analysis, and optimum pH were examined in both reductive amination of alpha-ketoglutarate and oxidative deamination of glutamate. N-terminal amino acid sequences of the bovine brain enzyme showed the significant differences in the first 5 amino acids compared to other glutamate dehydrogenases from various sources. These results indicate that glutamate dehydrogenase isolated from bovine brain is a novel polypeptide.

  7. Gender differences in response of hippocampus to chronic glucocorticoid stress: role of glutamate receptors.

    PubMed

    Liu, Howard H; Payne, H Ross; Wang, Bin; Brady, Scott T

    2006-04-01

    Glucocorticoids (GC) play critical roles in the pathophysiological reactions to environmental stress. In brain, morphological changes were examined in hippocampal CA3 neurons with 2 weeks of chronic elevation of GC in male and female mice. Molecular correlates and underlying mechanisms paralleling these morphologic changes in hippocampus were investigated. Although the hippocampal neurons in the CA3 area in male mice atrophy with chronically elevated GC, female mice show minimal morphological changes with comparable GC regimens. These sexual morphological differences correlate with differences in the postsynaptic dense protein (PSD95) as well as the spectrum of glutamate receptors induced by GC treatment in male and female mice, including NMDA, AMPA, and KA receptors. These findings suggest that synaptic receptor composition is adapted to the unique physiological requirements of males and females and illuminate underlying mechanisms of GC/stress responses in the brain.

  8. Low dose of L-glutamic acid attenuated the neurological dysfunctions and excitotoxicity in bilateral common carotid artery occluded mice.

    PubMed

    Ramanathan, Muthiah; Abdul, Khadar K; Justin, Antony

    2016-10-01

    Glutamate, an excitatory neurotransmitter in the brain, produces excitotoxicity through its agonistic action on postsynaptic N-methyl-D-aspartate receptor, resulting in neurodegeneration. We hypothesized that the administration of low doses of glutamate in cerebral ischemia could attenuate the excitotoxicity in neurons through its autoreceptor regulatory mechanism, and thereby control neurodegeneration. To test the hypothesis, the effect of L-glutamic acid (L-GA) 400 μmol/l/kg was evaluated in a bilateral common carotid artery occlusion-induced global ischemic mouse model. Memantine was used as a positive control. Global ischemia in mice was induced by occlusion of both the common carotid artery (bilateral common carotid artery occlusion) for 20 min, followed by reperfusion injury. L-GA was infused slowly through the tail vein 30 min before the surgery and every 24 h thereafter until the end of the experiment. The time-dependent change in cerebral blood flow was monitored using a laser Doppler image analyzer. The neurotransmitters glutamate and γ-aminobutyric acid (GABA) and the neurobiochemicals ATP, glutathione, and nitric oxide were measured in the different regions of brain at 0, 24, 48, and 72 h after reperfusion injury. L-GA increased locomotor activity, muscle coordination, and cerebral blood flow in ischemic mice at 72 h after ischemic insult. L-GA reduced glutamate levels in the cortex, striatum, and hippocampus at 72 h, whereas GABA levels were elevated in all three brain regions studied. Further, L-GA elevated glutathione levels and attenuated nitric oxide levels, but failed to restore ATP levels 72 h after ischemia-reperfusion. We conclude that the gradual reduction of glutamate along with elevation of GABA in different brain regions could have contributed toward the neuroprotective effect of L-GA. Hence, a slow infusion of a low dose of L-GA could be beneficial in controlling excitotoxicity-induced neurodegeneration following ischemia

  9. Low dose of L-glutamic acid attenuated the neurological dysfunctions and excitotoxicity in bilateral common carotid artery occluded mice.

    PubMed

    Ramanathan, Muthiah; Abdul, Khadar K; Justin, Antony

    2016-10-01

    Glutamate, an excitatory neurotransmitter in the brain, produces excitotoxicity through its agonistic action on postsynaptic N-methyl-D-aspartate receptor, resulting in neurodegeneration. We hypothesized that the administration of low doses of glutamate in cerebral ischemia could attenuate the excitotoxicity in neurons through its autoreceptor regulatory mechanism, and thereby control neurodegeneration. To test the hypothesis, the effect of L-glutamic acid (L-GA) 400 μmol/l/kg was evaluated in a bilateral common carotid artery occlusion-induced global ischemic mouse model. Memantine was used as a positive control. Global ischemia in mice was induced by occlusion of both the common carotid artery (bilateral common carotid artery occlusion) for 20 min, followed by reperfusion injury. L-GA was infused slowly through the tail vein 30 min before the surgery and every 24 h thereafter until the end of the experiment. The time-dependent change in cerebral blood flow was monitored using a laser Doppler image analyzer. The neurotransmitters glutamate and γ-aminobutyric acid (GABA) and the neurobiochemicals ATP, glutathione, and nitric oxide were measured in the different regions of brain at 0, 24, 48, and 72 h after reperfusion injury. L-GA increased locomotor activity, muscle coordination, and cerebral blood flow in ischemic mice at 72 h after ischemic insult. L-GA reduced glutamate levels in the cortex, striatum, and hippocampus at 72 h, whereas GABA levels were elevated in all three brain regions studied. Further, L-GA elevated glutathione levels and attenuated nitric oxide levels, but failed to restore ATP levels 72 h after ischemia-reperfusion. We conclude that the gradual reduction of glutamate along with elevation of GABA in different brain regions could have contributed toward the neuroprotective effect of L-GA. Hence, a slow infusion of a low dose of L-GA could be beneficial in controlling excitotoxicity-induced neurodegeneration following ischemia.

  10. Protection of the glutamate pool concentration in enteric bacteria.

    PubMed

    Yan, Dalai

    2007-05-29

    The central nitrogen metabolic circuit in enteric bacteria consists of three enzymes: glutamine synthetase, glutamate synthase (GOGAT), and glutamate dehydrogenase (GDH). With the carbon skeleton provided by 2-oxoglutarate, ammonia/ammonium (NH(4)(+)) is assimilated into two central nitrogen intermediates, glutamate and glutamine. Although both serve as nitrogen donors for all biosynthetic needs, glutamate and glutamine play different roles. Internal glutamine serves as a sensor of external nitrogen availability, and its pool concentration decreases upon nitrogen limitation. A high glutamate pool concentration is required to maintain the internal K(+) pool. The configuration of high glutamate and low glutamine pools was disrupted in GOGAT(-) mutants under low NH(4)(+) conditions: the glutamate pool was low, the difference between glutamate and glutamine was diminished, and growth was defective. When a GOGAT(-) mutant was cultured in an NH(4)(+)-limited chemostat, two sequential spontaneous mutations occurred. Each resulted in a suppressor mutant that outgrew its predecessor in the chemostat. The first suppressor overexpressed GDH, and the second also had a partially impaired glutamine synthetase. The result was a triple mutant in which NH(4)(+) was assimilated by two enzymes instead of the normal three and yet glutamate and glutamine pools and growth were essentially normal. The results indicate preference for the usual ratio of glutamate and glutamine and the resilient and compensatory nature of the circuit on pool control. Analysis of other suppressor mutants selected on solid medium suggests that increased GDH expression is the key for rescue of the growth defect of GOGAT(-) mutants under low NH(4)(+) conditions.

  11. Prefrontal changes in the glutamate-glutamine cycle and neuronal/glial glutamate transporters in depression with and without suicide.

    PubMed

    Zhao, J; Verwer, R W H; van Wamelen, D J; Qi, X-R; Gao, S-F; Lucassen, P J; Swaab, D F

    2016-11-01

    There are indications for changes in glutamate metabolism in relation to depression or suicide. The glutamate-glutamine cycle and neuronal/glial glutamate transporters mediate the uptake of the glutamate and glutamine. The expression of various components of the glutamate-glutamine cycle and the neuronal/glial glutamate transporters was determined by qPCR in postmortem prefrontal cortex. The anterior cingulate cortex (ACC) and the dorsolateral prefrontal cortex (DLPFC) were selected from young MDD patients who had committed suicide (MDD-S; n = 17), from MDD patients who died of non-suicide related causes (MDD-NS; n = 7) and from matched control subjects (n = 12). We also compared elderly depressed patients who had not committed suicide (n = 14) with matched control subjects (n = 22). We found that neuronal located components (EAAT3, EAAT4, ASCT1, SNAT1, SNAT2) of the glutamate-glutamine cycle were increased in the ACC while the astroglia located components (EAAT1, EAAT2, GLUL) were decreased in the DLPFC of MDD-S patients. In contrast, most of the components in the cycle were increased in the DLPFC of MDD-NS patients. In conclusion, the glutamate-glutamine cycle - and thus glutamine transmission - is differentially affected in depressed suicide patients and depressed non-suicide patients in an area specific way.

  12. Translating Glutamate: From Pathophysiology to Treatment

    PubMed Central

    Javitt, Daniel C.; Schoepp, Darryle; Kalivas, Peter W.; Volkow, Nora D.; Zarate, Carlos; Merchant, Kalpana; Bear, Mark F.; Umbricht, Daniel; Hajos, Mihaly; Potter, William Z.; Lee, Chi-Ming

    2012-01-01

    The neurotransmitter glutamate is the primary excitatory neurotransmitter in mammalian brain and is responsible for most corticocortical and corticofugal neurotransmission. Disturbances in glutamatergic function have been implicated in the pathophysiology of several neuropsychiatric disorders—including schizophrenia, drug abuse and addiction, autism, and depression—that were until recently poorly understood. Nevertheless, improvements in basic information regarding these disorders have yet to translate into Food and Drug Administration–approved treatments. Barriers to translation include the need not only for improved compounds but also for improved biomarkers sensitive to both structural and functional target engagement and for improved translational models. Overcoming these barriers will require unique collaborative arrangements between pharma, government, and academia. Here, we review a recent Institute of Medicine–sponsored meeting, highlighting advances in glutamatergic theories of neuropsychiatric illness as well as remaining barriers to treatment development. PMID:21957170

  13. Untangling the glutamate dehydrogenase allosteric nightmare.

    PubMed

    Smith, Thomas J; Stanley, Charles A

    2008-11-01

    Glutamate dehydrogenase (GDH) is found in all living organisms, but only animal GDH is regulated by a large repertoire of metabolites. More than 50 years of research to better understand the mechanism and role of this allosteric network has been frustrated by its sheer complexity. However, recent studies have begun to tease out how and why this complex behavior evolved. Much of GDH regulation probably occurs by controlling a complex ballet of motion necessary for catalytic turnover and has evolved concomitantly with a long antenna-like feature of the structure of the enzyme. Ciliates, the 'missing link' in GDH evolution, might have created the antenna to accommodate changing organelle functions and was refined in humans to, at least in part, link amino acid catabolism with insulin secretion.

  14. Poly(γ-glutamic acid), coagulation? Anticoagulation?

    PubMed

    Xu, Tingting; Peng, Fang; Zhang, Tao; Chi, Bo; Xu, Hong; Mao, Chun; Feng, Shuaihui

    2016-11-01

    Poly(γ-glutamic acid) (γ-PGA) powder was usually used as hemostatic agent because of its excellent physical properties of water-absorption and water-locking. However, if γ-PGA absorbs enough water, how about its blood compatibility? Here, the other side of the coin was investigated. The anticoagulant properties of γ-PGA were characterized by in vitro coagulation tests, hemolytic assay, platelet adhesion, and platelet activation. Moreover, cytotoxicity experiments of γ-PGA were also carried out by MTT assay. Results indicated that the sufficient water-absorbed γ-PGA has good anticoagulant property and non-cytotoxicity. It means γ-PGA has good anticoagulant property, non-cytotoxicity. If γ-PGA has absorbed enough water, it can be used as an anticoagulation biomaterial. With double effects (coagulation and anticoagulation), the γ-PGA with desirable bioproperties can be readily tailored to cater to various biomedical applications. PMID:27545694

  15. Hippocampal glutamate receptors in fear memory consolidation.

    PubMed

    Cammarota, Martín; Bevilaqua, Lia R M; Bonini, Juliana S; Rossatto, Janine I; Medina, Jorge H; Izquierdo, N

    2004-01-01

    It is thought that activity-dependent changes in synaptic efficacy driven by biochemical pathways responsive to the action of the excitatory neurotransmitter glutamate are critical components of the mechanisms responsible for memory formation. In particular, the early activation of the NMDA (rNMDA) and AMPA (rAMPA) subtypes of ionotropic glutamate receptors has been demonstrated to be a necessary event for the acquisition of several types of memory. In the rat, consolidation of the long-term memory for a one-trial, step-down inhibitory avoidance task is blocked by antagonists of the rNMDA and rAMPA infused into the CA1 region of the dorsal hippocampus early after training and is associated with a rapid and reversible increase in the total number of [3H]AMPA binding sites. The learning-induced increase in [[3H]AMPA is accompanied by translocation of the GluR1 subunit of the rAMPA to the post-synaptic terminal together with its phosphorylation at Ser831. In addition, learning of the mentioned fear-motivated task induces the activation and rNMDA-dependent translocation of CaMKII to the post-synaptic density. Inhibition of this protein kinase as well as blockade of the rNMDA abolishes both the learning-induced translocation of GluR1 and its phosphorylation. Our data suggest that learning of an avoidance task enhances hippocampal rAMPA signaling through rNMDA and CaMKII-dependent mechanisms.

  16. Glutamate-dependent transcriptional regulation of GLAST: role of PKC.

    PubMed

    López-Bayghen, Esther; Ortega, Arturo

    2004-10-01

    The Na+-dependent glutamate/aspartate transporter GLAST plays a major role in the removal of glutamate from the synaptic cleft. Short-term, as well as long-term changes in transporter activity are triggered by glutamate. An important locus of regulation is the density of transporter molecules present at the plasma membrane. A substrate-dependent change in the translocation rate of the transporter molecules accounts for the short-term effect, whereas the long-term modulation apparently involves transcriptional regulation. Using cultured chick cerebellar Bergmann glial cells, we report here that glutamate receptors activation mediate a substantial reduction in the transcriptional activity of the chglast promoter through the Ca2+/diacylglicerol-dependent protein kinase (PKC) signaling cascade. Overexpression of constitutive active PKC isoforms of mimic the glutamate effect. Accordingly, increased levels of c-Jun or c-Fos, but not Jun-B, Jun-D or Fos-B, lower the chglast promoter activity. Serial deletions and electrophorectic mobility shift assays were used to define a specific region within the 5' proximal region of the chglast promoter, associated with transcriptional repression. A putative glutamate response element could be defined in the proximal promoter stretch more likely between nts -40 and -78. These results demonstrate that GLAST is under glutamate-dependent transcriptional control through PKC, and support the notion of a pivotal role of this neurotransmitter in the regulation of its own removal from the synaptic cleft, thereby modulating, mainly in the long term, glutamatergic transmission.

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

    PubMed

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

    2014-01-01

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

  18. Evidence for Glutamate as a Neuroglial Transmitter within Sensory Ganglia

    PubMed Central

    Kung, Ling-Hsuan; Gong, Kerui; Adedoyin, Mary; Ng, Johnson; Bhargava, Aditi; Ohara, Peter T.; Jasmin, Luc

    2013-01-01

    This study examines key elements of glutamatergic transmission within sensory ganglia of the rat. We show that the soma of primary sensory neurons release glutamate when depolarized. Using acute dissociated mixed neuronal/glia cultures of dorsal root ganglia (DRG) or trigeminal ganglia and a colorimetric assay, we show that when glutamate uptake by satellite glial cells (SGCs) is inhibited, KCl stimulation leads to simultaneous increase of glutamate in the culture medium. With calcium imaging we see that the soma of primary sensory neurons and SGCs respond to AMPA, NMDA, kainate and mGluR agonists, and selective antagonists block this response. Using whole cell patch-clamp technique, inward currents were recorded from small diameter (<30 µm) DRG neurons from intact DRGs (ex-vivo whole ganglion preparation) in response to local application of the above glutamate receptor agonists. Following a chronic constriction injury (CCI) of either the inferior orbital nerve or the sciatic nerve, glutamate expression increases in the trigeminal ganglia and DRG respectively. This increase occurs in neurons of all diameters and is present in the somata of neurons with injured axons as well as in somata of neighboring uninjured neurons. These data provides additional evidence that glutamate can be released within the sensory ganglion, and that the somata of primary sensory neurons as well as SGCs express functional glutamate receptors at their surface. These findings, together with our previous gene knockdown data, suggest that glutamatergic transmission within the ganglion could impact nociceptive threshold. PMID:23844184

  19. Autoimmune epilepsy: distinct subpopulations of epilepsy patients harbor serum autoantibodies to either glutamate/AMPA receptor GluR3, glutamate/NMDA receptor subunit NR2A or double-stranded DNA.

    PubMed

    Ganor, Yonatan; Goldberg-Stern, Hadassa; Lerman-Sagie, Tally; Teichberg, Vivian I; Levite, Mia

    2005-06-01

    We studied 82 patients with different types of epilepsy and 49 neurologically intact non-epileptic controls, and identified three different subpopulations of epilepsy patients bearing significantly elevated levels of autoantibodies to either GluR3B-peptide of glutamate/AMPA receptor subtype 3 (17/82; 21% of patients), or to a peptide of NR2A subunit of glutamate/NMDA receptors (15/82; 18%), or to double-stranded (ds) DNA, the hallmark of systemic lupus erythematosus (13/80; 16%). Most patients had only one antibody type, arguing against cross-reactivity. Nearly all anti-dsDNA Ab-positive patients did not harbor anti-nuclear autoantibodies. Most patients had no history of brain damage, febrile convulsions, early onset epilepsy, acute epilepsy or intractable seizures. We suggest to measure the 'autoimmune-fingerprints' of epilepsy patients for diagnostic and therapeutic purposes. PMID:15978777

  20. Sympathoexcitatory effects of estrogen in the insular cortex are mediated by GABA.

    PubMed

    Saleh, Tarek M; Connell, Barry J; Cribb, Alastair E

    2005-03-10

    The current investigation examined the effect of estrogen in the insular cortex (IC) on autonomic tone and cardiac baroreceptor reflex function and sought to determine if modulation of neurotransmission was responsible for mediating this effect. Experiments were performed in Inactin-anaesthetized, male Sprague-Dawley rats. Animals were instrumented to record blood pressure, heart rate, vagal parasympathetic and renal sympathetic nerve activities, as well as cardiac baroreflex sensitivity (BRS). Direct, bilateral injection of 17beta-estradiol (0.5 microM; 200 nl/side) into the IC resulted in a significant increase in sympathetic tone (from 10 +/- 4 to 24 +/- 3) with no significant change in blood pressure, heart rate, parasympathetic tone or BRS measured at 30 min post-injection. This estrogen-induced effect was completely blocked by the co-injection of estrogen with the estrogen receptor antagonist, ICI 182, 780 (20 microM; 200 nl/side). Co-injection of estrogen with a GABA(B), NMDA or non-NMDA receptor antagonists did not effect the estrogen-induced increase in sympathetic tone. Co-injection of a sub-threshold dose of estradiol (0.125 microM; 200 nl/side) with the GABA(A) receptor antagonist, (+)-bicuculline (0.025 microM; 200 nl/side), resulted in an additive response to increase sympathetic nerve activity. These results suggest that estrogen acts on estrogen receptors to modulate GABA(A)-receptor-mediated neurotransmission within the IC to modulate sympathetic tone. PMID:15777759

  1. Macaque Parieto-Insular Vestibular Cortex: Responses to self-motion and optic flow

    PubMed Central

    Chen, Aihua; DeAngelis, Gregory C.; Angelaki, Dora E.

    2011-01-01

    The parieto-insular vestibular cortex (PIVC) is thought to contain an important representation of vestibular information. Here we describe responses of macaque PIVC neurons to three-dimensional (3D) vestibular and optic flow stimulation. We found robust vestibular responses to both translational and rotational stimuli in the retroinsular (Ri) and adjacent secondary somatosensory (S2) cortices. PIVC neurons did not respond to optic flow stimulation, and vestibular responses were similar in darkness and during visual fixation. Cells in the upper bank and tip of the lateral sulcus (Ri and S2) responded to sinusoidal vestibular stimuli with modulation at the first harmonic frequency, and were directionally tuned. Cells in the lower bank of the lateral sulcus (mostly Ri) often modulated at the second harmonic frequency, and showed either bimodal spatial tuning or no tuning at all. All directions of 3D motion were represented in PIVC, with direction preferences distributed roughly uniformly for translation, but showing a preference for roll rotation. Spatio-temporal profiles of responses to translation revealed that half of PIVC cells followed the linear velocity profile of the stimulus, one-quarter carried signals related to linear acceleration (in the form of two peaks of direction selectivity separated in time), and a few neurons followed the derivative of linear acceleration (jerk). In contrast, mainly velocity-coding cells were found in response to rotation. Thus, PIVC comprises a large functional region in macaque areas Ri and S2, with robust responses to 3D rotation and translation, but is unlikely to play a significant role in visual/vestibular integration for self-motion perception. PMID:20181599

  2. Histaminergic effects on the frequency of repetitive spike firing in rat insular cortex.

    PubMed

    Takei, Hiroki; Song, Liqiu; Ebihara, Katsuko; Shirakawa, Tetsuo; Koshikawa, Noriaki; Kobayashi, Masayuki

    2012-06-14

    The insular cortex (IC) processes multimodal sensory information including gustatory, visceral, nociceptive, and thermal sensation, and is considered to play a role in the regulation of homeostasis. The IC receives dense histaminergic projection from the tuberomamillary nucleus in the hypothalamus, and recent studies have demonstrated that the blockage of histaminergic receptors impairs physiological functions in the IC. However, little is known about the effects of histamine on the electrophysiological properties of the IC. To explore the effects of histamine on the subthreshold responses and action potential properties in the IC, intracellular recording with a sharp glass electrode was obtained from IC pyramidal cells in cortical slice preparations. Application of histamine (30 μM) increased the frequency of repetitive spike firing in response to a long depolarizing current pulse injection; accompanied by an increase in input resistance. The frequency of repetitive spike firing was estimated by the slope of the frequency-current (f/I) curve. Histamine caused an increase from 23.3±2.3 Hz/nA to 40.3±4.3 Hz/nA. The histamine-induced facilitation of repetitive spike firing was blocked by pre-application of 50 μM cimetidine, an H(2) receptor antagonist, but not 30 μM pyrilamine, an H(1) receptor antagonist. R-α-methylhistamine (10 μM), an H(3) autoreceptor agonist, had little effect on the slope of the f/I curve. These results suggest that the histamine-induced facilitation of firing frequency is mediated via H(2) and not H(1) receptors. In addition, H(3) receptors have a minor role in the intrinsic membrane and firing properties of IC pyramidal cells.

  3. Mindfulness training modulates value signals in ventromedial prefrontal cortex through input from insular cortex.

    PubMed

    Kirk, Ulrich; Gu, Xiaosi; Harvey, Ann H; Fonagy, Peter; Montague, P Read

    2014-10-15

    Neuroimaging research has demonstrated that ventromedial prefrontal cortex (vmPFC) encodes value signals that can be modulated by top-down cognitive input such as semantic knowledge, price incentives, and monetary favors suggesting that such biases may have an identified biological basis. It has been hypothesized that mindfulness training (MT) provides one path for gaining control over such top-down influences; yet, there have been no direct tests of this hypothesis. Here, we probe the behavioral and neural effects of MT on value signals in vmPFC in a randomized longitudinal design of 8 weeks of MT on an initially naïve subject cohort. The impact of this within-subject training was assessed using two paradigms: one that employed primary rewards (fruit juice) in a simple conditioning task and another that used a well-validated art-viewing paradigm to test bias of monetary favors on preference. We show that MT behaviorally censors the top-down bias of monetary favors through a measurable influence on value signals in vmPFC. MT also modulates value signals in vmPFC to primary reward delivery. Using a separate cohort of subjects we show that 8 weeks of active control training (ACT) generates the same behavioral impact also through an effect on signals in the vmPFC. Importantly, functional connectivity analyses show that value signals in vmPFC are coupled with bilateral posterior insula in the MT groups in both paradigms, but not in the ACT groups. These results suggest that MT integrates interoceptive input from insular cortex in the context of value computations of both primary and secondary rewards.

  4. Late Quaternary seismic stratigraphy and structure of the western insular shelf margin of Puerto Rico

    NASA Astrophysics Data System (ADS)

    Hanzlik, M.; Mann, P.; Abrams, L.; Grindlay, N.

    2005-12-01

    725 km of high-resolution seismic data were collected over the insular shelf of western Puerto Rico to better understand its late Quaternary depositional and structural history. Due to low tectonic uplift rates of onshore areas in this region, well dated late Quaternary sediments and corals have only been identified in a few scattered onland localities around Puerto Rico. Seismic data from the Rio Anasco delta area of western Puerto Rico reveals four main units with characteristic stratal reflection terminations that total about 25 m in thickness. Because of a lack of well information, age estimates of these late Quaternary units are based on correlations with sea level curves derived from dated coral samples from Puerto Rico, St. Croix, and Antigua. Units include: Unit 1 - a gently folded and faulted basal section correlated to the Oliogene-early Pliocene? carbonate shelf of Puerto Rico; deeper penetration, industry MCS lines show that these rocks are deformed in a broad EW-trenching arch; Unit 2 - chaotic channel fill deposits in incisions related to the lowstand equivalent of the Rio Anasco likely formed during the Last Glacial Maximum about 25-15 ka; Unit 3 - roughly stratified deposits onlapping the top of Unit 2; these are interpreted as an estuarine facies deposited during Holocene sea level transgression; Unit 4 - highly stratified deposits related to progradation of the Anasco delta during sea level rise. The base of unit 4 is a downlap surface interpreted as a maximum flooding surface likely formed about 6 ka. East-northeast-striking faults are observed breaking the younger late Quaternary units in three separate zones off the west coast of Puerto Rico. Onland continuations of these faults have not been identified likely due to cultural overprint of natural scarps on late Quaternary floodplains.

  5. Differential structural and resting state connectivity between insular subdivisions and other pain-related brain regions.

    PubMed

    Wiech, K; Jbabdi, S; Lin, C S; Andersson, J; Tracey, I

    2014-10-01

    Functional neuroimaging studies suggest that the anterior, mid, and posterior division of the insula subserve different functions in the perception of pain. The anterior insula (AI) has predominantly been associated with cognitive-affective aspects of pain, while the mid and posterior divisions have been implicated in sensory-discriminative processing. We examined whether this functional segregation is paralleled by differences in (1) structural and (2) resting state connectivity and (3) in correlations with pain-relevant psychological traits. Analyses were restricted to the 3 insular subdivisions and other pain-related brain regions. Both type of analyses revealed largely overlapping results. The AI division was predominantly connected to the ventrolateral prefrontal cortex (structural and resting state connectivity) and orbitofrontal cortex (structural connectivity). In contrast, the posterior insula showed strong connections to the primary somatosensory cortex (SI; structural connectivity) and secondary somatosensory cortex (SII; structural and resting state connectivity). The mid insula displayed a hybrid connectivity pattern with strong connections with the ventrolateral prefrontal cortex, SII (structural and resting state connectivity) and SI (structural connectivity). Moreover, resting state connectivity revealed strong connectivity of all 3 subdivisions with the thalamus. On the behavioural level, AI structural connectivity was related to the individual degree of pain vigilance and awareness that showed a positive correlation with AI-amygdala connectivity and a negative correlation with AI-rostral anterior cingulate cortex connectivity. In sum, our findings show a differential structural and resting state connectivity for the anterior, mid, and posterior insula with other pain-relevant brain regions, which might at least partly explain their different functional profiles in pain processing.

  6. Maps Showing Composition of Surficial Sediments on the Insular Shelf of Southwestern Puerto Rico

    USGS Publications Warehouse

    Shideler, Gerald L.

    1980-01-01

    The limited availability of onshore sand deposits for use in construction appears to be a future major problem in Puerto Rico (U.S. Bureau of Mines, 1972; Committee on Puerto Rico and the Sea, 1974). Consequently, the mining of offshore sand deposits as supplemental sources of construction aggregate may becom e necessary. For this reason, the U.S. Geological Survey and the Department of Natural Resources of the Commonwealth of Puerto Rico have conducted investigations of potential offshore sand deposits on the Puerto Rico insular shelf. This report provides information on the composition of surficial sediments on the southwestern Puerto Rico shelf (fig. 1), an area that may be one of the more favorable potential sites for offshore sand resources. Water depths over most of the study area are less than 22 meters (m). The sea floor is composed of live and dead patch and fringing reefs, areas of rock exposures, and sedim ent-covered areas. The adjacent coastline includes prominent embaym ents and a conspicuous rock promontory (Cabo Rojo) connected by a tombolo to the mainland of Puerto Rico. The study area is in the belt of northeast trade winds. Waves approach the coast predominantly from the southeast, resulting in a predominantly westward littoral drift along the south coast (Grove and Trumbull, 1978). Local sand movement on the southern shelf is shown by an active sand wave field south of Bah1a Sucia in which the sand wave crests have migrated toward the southwest (Grove and Trumbull, 1978). The presence of the sand wave field suggests that large volumes of sand having potential for mining are locally present in the study area.

  7. Reduced spontaneous neuronal activity in the insular cortex and thalamus in healthy adults with insomnia symptoms.

    PubMed

    Liu, Chun-Hong; Liu, Cun-Zhi; Zhang, Jihui; Yuan, Zhen; Tang, Li-Rong; Tie, Chang-Le; Fan, Jin; Liu, Qing-Quan

    2016-10-01

    Poor sleep and insomnia have been recognized to be strongly correlated with the development of depression. The exploration of the basic mechanism of sleep disturbance could provide the basis for improved understanding and treatment of insomnia and prevention of depression. In this study, 31 subjects with insomnia symptoms as measured by the Hamilton Rating Scale for Depression (HAMD-17) and 71 age- and gender-matched subjects without insomnia symptoms were recruited to participate in a clinical trial. Using resting-state functional magnetic resonance imaging (rs-fMRI), we examined the alterations in spontaneous brain activity between the two groups. Correlations between the fractional amplitude of low frequency fluctuations (fALFF) and clinical measurements (e.g., insomnia severity and Hamilton Depression Rating Scale [HAMD] scores) were also tested in all subjects. Compared to healthy participants without insomnia symptoms, participants with insomnia symptoms showed a decreased fALFF in the left ventral anterior insula, bilateral posterior insula, left thalamus, and pons but an increased fALFF in the bilateral middle occipital gyrus and right precentral gyrus. More specifically, a significant, negative correlation of fALFF in the left thalamus with early morning awakening scores and HAMD scores in the overall sample was identified. These results suggest that insomnia symptoms are associated with altered spontaneous activity in the brain regions of several important functional networks, including the insular cortex of the salience and the thalamus of the hyperarousal network. The altered fALFF in the left thalamus supports the "hyperarousal theory" of insomnia symptoms, which could serve as a biomarker for insomnia. PMID:27425430

  8. Interhemispheric insular and inferior frontal connectivity are associated with substance abuse in a psychiatric population.

    PubMed

    Viswanath, Humsini; Velasquez, Kenia M; Savjani, Ricky; Molfese, David L; Curtis, Kaylah; Molfese, Peter J; Eagleman, David M; Baldwin, Philip R; Frueh, B Christopher; Fowler, J Christopher; Salas, Ramiro

    2015-05-01

    Substance abuse is highly comorbid with major psychiatric disorders. While the neural underpinnings of drug abuse have been studied extensively, most existing studies compare drug users without comorbidities and healthy, non-user controls. Such studies do not generalize well to typical patients with substance abuse disorders. Therefore, we studied a population of psychiatric inpatients (n = 151) with a range of mental illnesses. Psychiatric disorders were diagnosed via structured interviews. Sixty-five percent of patients met criteria for at least one substance use disorder. Patients were recruited for resting state functional connectivity (RSFC) and diffusion tensor imaging (DTI) experiments to examine the interhemispheric connectivity between brain regions hypothesized to be involved in drug addiction, namely: the inferior, medial, and superior frontal gyri; insula; striatum; and anterior cingulate cortex. The World Health Organization Alcohol, Smoking, and Substance Involvement Screening Test (WHOA) questionnaire was used to further assess drug use. An association between use of tobacco, alcohol, cocaine, sedatives, and hallucinogens with increased insular interhemispheric connectivity was observed. In addition, increased inferior frontal gyrus interhemispheric connectivity was associated with amphetamine and inhalant use. Our results suggest that increased inter-hemispheric insula connectivity is associated with the use of several drugs of abuse. Importantly, psychiatric inpatients without a history of drug dependence were used as an ecologically valid control group rather than the more typical comparison between "mentally ill vs. healthy control" populations. We suggest that dysfunction of interhemispheric connectivity of the insula and to a lesser extent of the inferior frontal gyrus, are related to drug abuse in psychiatric populations.

  9. Mindfulness training modulates value signals in ventromedial prefrontal cortex through input from insular cortex

    PubMed Central

    Kirk, Ulrich; Gu, Xiaosi; Harvey, Ann H.; Fonagy, Peter; Montague, P. Read

    2014-01-01

    Neuroimaging research has demonstrated that ventromedial prefrontal cortex (vmPFC) encodes value signals that can be modulated by top-down cognitive input such as semantic knowledge, price incentives, and monetary favors suggesting that such biases may have an identified biological basis. It has been hypothesized that mindfulness training (MT) provides one path for gaining control over such top-down influences; yet, there have been no direct tests of this hypothesis. Here, we probe the behavioral and neural effects of MT on value signals in vmPFC in a randomized longitudinal design of 8 weeks of MT on an initially naïve subject cohort. The impact of this within-subject training was assessed using two paradigms: one that employed primary rewards (fruit juice) in a simple conditioning task and another that used a well-validated art-viewing paradigm to test bias of monetary favors on preference. We show that MT behaviorally censors the top-down bias of monetary favors through a measurable influence on value signals in vmPFC. MT also modulates value signals in vmPFC to primary reward delivery. Using a separate cohort of subjects we show that 8 weeks of active control training (ACT) generates the same behavioral impact also through an effect on signals in the vmPFC. Importantly, functional connectivity analyses show that value signals in vmPFC are coupled with bilateral posterior insula in the MT groups in both paradigms, but not in the ACT groups. These results suggest that MT integrates interoceptive input from insular cortex in the context of value computations of both primary and secondary rewards. PMID:24956066

  10. Intrinsic functional connectivity of insular cortex and symptoms of sickness during acute experimental inflammation.

    PubMed

    Lekander, Mats; Karshikoff, Bianka; Johansson, Emilia; Soop, Anne; Fransson, Peter; Lundström, Johan N; Andreasson, Anna; Ingvar, Martin; Petrovic, Predrag; Axelsson, John; Nilsonne, Gustav

    2016-08-01

    Task-based fMRI has been used to study the effects of experimental inflammation on the human brain, but it remains unknown whether intrinsic connectivity in the brain at rest changes during a sickness response. Here, we investigated the effect of experimental inflammation on connectivity between areas relevant for monitoring of bodily states, motivation, and subjective symptoms of sickness. In a double-blind randomized controlled experiment, 52 healthy volunteers were injected with 0.6ng/kg LPS (lipopolysaccharide) or placebo, and participated in a resting state fMRI experiment after approximately 2h 45min. Resting state fMRI data were available from 48 participants, of which 28 received LPS and 20 received placebo. Bilateral anterior and bilateral posterior insula sections were used as seed regions and connectivity with bilateral orbitofrontal and cingulate (anterior and middle) cortices was investigated. Back pain, headache and global sickness increased significantly after as compared to before LPS, while a non-significant trend was shown for increased nausea. Compared to placebo, LPS was followed by increased connectivity between left anterior insula and left midcingulate cortex. This connectivity was significantly correlated to increase in back pain after LPS and tended to be related to increased global sickness, but was not related to increased headache or nausea. LPS did not affect the connectivity from other insular seeds. In conclusion, the finding of increased functional connectivity between left anterior insula and middle cingulate cortex suggests a potential neurophysiological mechanism that can be further tested to understand the subjective feeling of malaise and discomfort during a sickness response. PMID:26732827

  11. Quantitative Analysis of Glutamate Receptors in Glial Cells from the Cortex of GFAP/EGFP Mice Following Ischemic Injury: Focus on NMDA Receptors.

    PubMed

    Dzamba, David; Honsa, Pavel; Valny, Martin; Kriska, Jan; Valihrach, Lukas; Novosadova, Vendula; Kubista, Mikael; Anderova, Miroslava

    2015-11-01

    Cortical glial cells contain both ionotropic and metabotropic glutamate receptors. Despite several efforts, a comprehensive analysis of the entire family of glutamate receptors and their subunits present in glial cells is still missing. Here, we provide an overall picture of the gene expression of ionotropic (AMPA, kainate, NMDA) and the main metabotropic glutamate receptors in cortical glial cells isolated from GFAP/EGFP mice before and after focal cerebral ischemia. Employing single-cell RT-qPCR, we detected the expression of genes encoding subunits of glutamate receptors in GFAP/EGFP-positive (GFAP/EGFP(+)) glial cells in the cortex of young adult mice. Most of the analyzed cells expressed mRNA for glutamate receptor subunits, the expression of which, in most cases, even increased after ischemic injury. Data analyses disclosed several classes of GFAP/EGFP(+) glial cells with respect to glutamate receptors and revealed in what manner their expression correlates with the expression of glial markers prior to and after ischemia. Furthermore, we also examined the protein expression and functional significance of NMDA receptors in glial cells. Immunohistochemical analyses of all seven NMDA receptor subunits provided direct evidence that the GluN3A subunit is present in GFAP/EGFP(+) glial cells and that its expression is increased after ischemia. In situ and in vitro Ca(2+) imaging revealed that Ca(2+) elevations evoked by the application of NMDA were diminished in GFAP/EGFP(+) glial cells following ischemia. Our results provide a comprehensive description of glutamate receptors in cortical GFAP/EGFP(+) glial cells and may serve as a basis for further research on glial cell physiology and pathophysiology.

  12. Learning touch preferences with a tactile robot using dopamine modulated STDP in a model of insular cortex

    PubMed Central

    Chou, Ting-Shuo; Bucci, Liam D.; Krichmar, Jeffrey L.

    2015-01-01

    Neurorobots enable researchers to study how behaviors are produced by neural mechanisms in an uncertain, noisy, real-world environment. To investigate how the somatosensory system processes noisy, real-world touch inputs, we introduce a neurorobot called CARL-SJR, which has a full-body tactile sensory area. The design of CARL-SJR is such that it encourages people to communicate with it through gentle touch. CARL-SJR provides feedback to users by displaying bright colors on its surface. In the present study, we show that CARL-SJR is capable of learning associations between conditioned stimuli (CS; a color pattern on its surface) and unconditioned stimuli (US; a preferred touch pattern) by applying a spiking neural network (SNN) with neurobiologically inspired plasticity. Specifically, we modeled the primary somatosensory cortex, prefrontal cortex, striatum, and the insular cortex, which is important for hedonic touch, to process noisy data generated directly from CARL-SJR's tactile sensory area. To facilitate learning, we applied dopamine-modulated Spike Timing Dependent Plasticity (STDP) to our simulated prefrontal cortex, striatum, and insular cortex. To cope with noisy, varying inputs, the SNN was tuned to produce traveling waves of activity that carried spatiotemporal information. Despite the noisy tactile sensors, spike trains, and variations in subject hand swipes, the learning was quite robust. Further, insular cortex activities in the incremental pathway of dopaminergic reward system allowed us to control CARL-SJR's preference for touch direction without heavily pre-processed inputs. The emerged behaviors we found in this model match animal's behaviors wherein they prefer touch in particular areas and directions. Thus, the results in this paper could serve as an explanation on the underlying neural mechanisms for developing tactile preferences and hedonic touch. PMID:26257639

  13. 54. West elevation of portion of elevated Mainline structure (Section ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    54. West elevation of portion of elevated Mainline structure (Section F-5) over Washington Street - looking East - at the corner of Bray Street. - Boston Elevated Railway, Elevated Mainline, Washington Street, Boston, Suffolk County, MA

  14. Basolateral amygdala rapid glutamate release encodes an outcome-specific representation vital for reward-predictive cues to selectively invigorate reward-seeking actions

    PubMed Central

    Malvaez, Melissa; Greenfield, Venuz Y.; Wang, Alice S.; Yorita, Allison M.; Feng, Lili; Linker, Kay E.; Monbouquette, Harold G.; Wassum, Kate M.

    2015-01-01

    Environmental stimuli have the ability to generate specific representations of the rewards they predict and in so doing alter the selection and performance of reward-seeking actions. The basolateral amygdala participates in this process, but precisely how is unknown. To rectify this, we monitored, in near-real time, basolateral amygdala glutamate concentration changes during a test of the ability of reward-predictive cues to influence reward-seeking actions (Pavlovian-instrumental transfer). Glutamate concentration was found to be transiently elevated around instrumental reward seeking. During the Pavlovian-instrumental transfer test these glutamate transients were time-locked to and correlated with only those actions invigorated by outcome-specific motivational information provided by the reward-predictive stimulus (i.e., actions earning the same specific outcome as predicted by the presented CS). In addition, basolateral amygdala AMPA, but not NMDA glutamate receptor inactivation abolished the selective excitatory influence of reward-predictive cues over reward seeking. These data the hypothesis that transient glutamate release in the BLA can encode the outcome-specific motivational information provided by reward-predictive stimuli. PMID:26212790

  15. Relationship between increase in astrocytic GLT-1 glutamate transport and late-LTP

    PubMed Central

    Pita-Almenar, Juan D.; Zou, Shengwei; Colbert, Costa M.; Eskin, Arnold

    2012-01-01

    Na+-dependent high-affinity glutamate transporters have important roles in the maintenance of basal levels of glutamate and clearance of glutamate during synaptic transmission. Interestingly, several studies have shown that basal glutamate transport displays plasticity. Glutamate uptake increases in hippocampal slices during early long-term potentiation (E-LTP) and late long-term potentiation (L-LTP). Four issues were addressed in this research: Which glutamate transporter is responsible for the increase in glutamate uptake during L-LTP? In what cell type in the hippocampus does the increase in glutamate uptake occur? Does a single type of cell contain all the mechanisms to respond to an induction stimulus with a change in glutamate uptake? What role does the increase in glutamate uptake play during L-LTP? We have confirmed that GLT-1 is responsible for the increase in glutamate uptake during L-LTP. Also, we found that astrocytes were responsible for much, if not all, of the increase in glutamate uptake in hippocampal slices during L-LTP. Additionally, we found that cultured astrocytes alone were able to respond to an induction stimulus with an increase in glutamate uptake. Inhibition of basal glutamate uptake did not affect the induction of L-LTP, but inhibition of the increase in glutamate uptake did inhibit both the expression of L-LTP and induction of additional LTP. It seems likely that heightened glutamate transport plays an ongoing role in the ability of hippocampal circuitry to code and store information. PMID:23166293

  16. Efficient synthesis of novel glutamate homologues and investigation of their affinity and selectivity profile at ionotropic glutamate receptors.

    PubMed

    Pinto, Andrea; Tamborini, Lucia; Mastronardi, Federica; Ettari, Roberta; Romano, Diego; Nielsen, Birgitte; De Micheli, Carlo; Conti, Paola

    2014-04-15

    A convenient synthesis of four new enantiomerically pure acidic amino acids is reported and their affinity at ionotropic glutamate receptors was determined. The new compounds are higher homologues of glutamic acid in which the molecular complexity has been increased by introducing an aromatic/heteroaromatic ring, that is a phenyl or a thiophene ring, that could give additional electronic interactions with the receptors. The results of the present investigation indicate that the insertion of an aromatic/heteroaromatic ring into the amino acid skeleton of glutamate higher homologues is well tolerated and this modification could be exploited to generate a new class of NMDA antagonists. PMID:24630559

  17. The human operculo-insular cortex is pain-preferentially but not pain-exclusively activated by trigeminal and olfactory stimuli.

    PubMed

    Lötsch, Jörn; Walter, Carmen; Felden, Lisa; Nöth, Ulrike; Deichmann, Ralf; Oertel, Bruno G

    2012-01-01

    Increasing evidence about the central nervous representation of pain in the brain suggests that the operculo-insular cortex is a crucial part of the pain matrix. The pain-specificity of a brain region may be tested by administering nociceptive stimuli while controlling for unspecific activations by administering non-nociceptive stimuli. We applied this paradigm to nasal chemosensation, delivering trigeminal or olfactory stimuli, to verify the pain-specificity of the operculo-insular cortex. In detail, brain activations due to intranasal stimulation induced by non-nociceptive olfactory stimuli of hydrogen sulfide (5 ppm) or vanillin (0.8 ppm) were used to mask brain activations due to somatosensory, clearly nociceptive trigeminal stimulations with gaseous carbon dioxide (75% v/v). Functional magnetic resonance (fMRI) images were recorded from 12 healthy volunteers in a 3T head scanner during stimulus administration using an event-related design. We found that significantly more activations following nociceptive than non-nociceptive stimuli were localized bilaterally in two restricted clusters in the brain containing the primary and secondary somatosensory areas and the insular cortices consistent with the operculo-insular cortex. However, these activations completely disappeared when eliminating activations associated with the administration of olfactory stimuli, which were small but measurable. While the present experiments verify that the operculo-insular cortex plays a role in the processing of nociceptive input, they also show that it is not a pain-exclusive brain region and allow, in the experimental context, for the interpretation that the operculo-insular cortex splay a major role in the detection of and responding to salient events, whether or not these events are nociceptive or painful. PMID:22496865

  18. New threshold temperatures for the development of a North American diamondback moth (Lepidoptera: Plutellidae) population and its larval parasitoid, Diadegma insulare (Hymenoptera: Ichneumonidae).

    PubMed

    Bahar, M H; Soroka, J J; Grenkow, L; Dosdall, L M

    2014-10-01

    The currently accepted lower threshold temperature for the development of diamondback moth, Plutella xylostella (Lepidoptera: Plutellidae), the world's most destructive insect pest of cruciferous crops, is around 6.0°C, and there is no known upper threshold temperature. Neither are there established threshold temperatures for diamondback moth's major natural enemy, Diadegma insulare (Hymenoptera: Ichneumonidae). Laboratory studies were undertaken to determine the survival and development of a North American diamondback moth population and its parasitoid D. insulare at 20 constant temperatures ranging from 2.0 to 38.0°C. Diamondback moth completed development from second instar to adult within a temperature range of 4.0-37°C, and D. insulare completed its life cycle from egg to adult within a temperature range of 4.0-33°C. The developmental data were fitted into one linear and four nonlinear models. Using goodness-of-fit and the ability to estimate parameters of biological significance as selection criteria, the Wang model was the most acceptable among the nonlinear models to describe the relationship between temperature and development of both species. According to this model, the lower and upper threshold temperatures for diamondback moth were 2.1 and 38.0°C, respectively, and for D. insulare they were 2.1 and 34.0°C, respectively. Based on the Degree Day model, diamondback moth required 143 d above the lower threshold of 4.23°C to complete the life cycle, while D. insulare required 286 d above the lower threshold of 2.57°C. This study suggests that temperatures during the crop-growing seasons in North America are not limiting factors for development of either diamondback moth or D. insulare.

  19. The National Map - Elevation

    USGS Publications Warehouse

    Gesch, Dean; Evans, Gayla; Mauck, James; Hutchinson, John; Carswell, William J.

    2009-01-01

    The National Elevation Dataset (NED) is the primary elevation data product produced and distributed by the USGS. The NED provides seamless raster elevation data of the conterminous United States, Alaska, Hawaii, and the island territories. The NED is derived from diverse source data sets that are processed to a specification with a consistent resolution, coordinate system, elevation units, and horizontal and vertical datums. The NED is the logical result of the maturation of the long-standing USGS elevation program, which for many years concentrated on production of topographic map quadrangle-based digital elevation models. The NED serves as the elevation layer of The National Map, and provides basic elevation information for earth science studies and mapping applications in the United States. The NED is a multi-resolution dataset that is updated bimonthly to integrate newly available, improved elevation source data. NED data are available nationally at grid spacings of 1 arc-second (approximately 30 meters) for the conterminous United States, and at 1/3 and 1/9 arc-seconds (approximately 10 and 3 meters, respectively) for parts of the United States. Most of the NED for Alaska is available at 2-arc-second (about 60 meters) grid spacing, where only lower resolution source data exist. Part of Alaska is available at the 1/3-arc-second resolution, and plans are in development for a significant upgrade in elevation data coverage of the State over the next 5 years. Specifications for the NED include the following: *Coordinate system: Geographic (decimal degrees of latitude and longitude), *Horizontal datum: North American Datum of 1983 (NAD 83), *Vertical datum: North American Vertical Datum of 1988 (NAVD 88) over the conterminous United States and varies in other areas, and *Elevation units: Decimal meters.

  20. Glutamate neurons within the midbrain dopamine regions.

    PubMed

    Morales, M; Root, D H

    2014-12-12

    Midbrain dopamine systems play important roles in Parkinson's disease, schizophrenia, addiction, and depression. The participation of midbrain dopamine systems in diverse clinical contexts suggests these systems are highly complex. Midbrain dopamine regions contain at least three neuronal phenotypes: dopaminergic, GABAergic, and glutamatergic. Here, we review the locations, subtypes, and functions of glutamatergic neurons within midbrain dopamine regions. Vesicular glutamate transporter 2 (VGluT2) mRNA-expressing neurons are observed within each midbrain dopamine system. Within rat retrorubral field (RRF), large populations of VGluT2 neurons are observed throughout its anteroposterior extent. Within rat substantia nigra pars compacta (SNC), VGluT2 neurons are observed centrally and caudally, and are most dense within the laterodorsal subdivision. RRF and SNC rat VGluT2 neurons lack tyrosine hydroxylase (TH), making them an entirely distinct population of neurons from dopaminergic neurons. The rat ventral tegmental area (VTA) contains the most heterogeneous populations of VGluT2 neurons. VGluT2 neurons are found in each VTA subnucleus but are most dense within the anterior midline subnuclei. Some subpopulations of rat VGluT2 neurons co-express TH or glutamic acid decarboxylase (GAD), but most of the VGluT2 neurons lack TH or GAD. Different subsets of rat VGluT2-TH neurons exist based on the presence or absence of vesicular monoamine transporter 2, dopamine transporter, or D2 dopamine receptor. Thus, the capacity by which VGluT2-TH neurons may release dopamine will differ based on their capacity to accumulate vesicular dopamine, uptake extracellular dopamine, or be autoregulated by dopamine. Rat VTA VGluT2 neurons exhibit intrinsic VTA projections and extrinsic projections to the accumbens and to the prefrontal cortex. Mouse VTA VGluT2 neurons project to accumbens shell, prefrontal cortex, ventral pallidum, amygdala, and lateral habenula. Given their molecular

  1. Neuroprotective Effects of Glutamate Antagonists and Extracellular Acidity

    NASA Astrophysics Data System (ADS)

    Kaku, David A.; Giffard, Rona G.; Choi, Dennis W.

    1993-06-01

    Glutamate antagonists protect neurons from hypoxic injury both in vivo and in vitro, but in vitro studies have not been done under the acidic conditions typical of hypoxia-ischemia in vivo. Consistent with glutamate receptor antagonism, extracellular acidity reduced neuronal death in murine cortical cultures that were deprived of oxygen and glucose. Under these acid conditions, N-methyl-D-aspartate and α-amino-3-hydroxy-5-methyl-4-isox-azolepropionate-kainate antagonists further reduced neuronal death, such that some neurons tolerated prolonged oxygen and glucose deprivation almost as well as did astrocytes. Neuroprotection induced by this combination exceeded that induced by glutamate antagonists alone, suggesting that extracellular acidity has beneficial effects beyond the attenuation of ionotropic glutamate receptor activation.

  2. Bidirectional Control of Synaptic GABAAR Clustering by Glutamate and Calcium

    PubMed Central

    Bannai, Hiroko; Niwa, Fumihiro; Sherwood, Mark W.; Shrivastava, Amulya Nidhi; Arizono, Misa; Miyamoto, Akitoshi; Sugiura, Kotomi; Lévi, Sabine; Triller, Antoine; Mikoshiba, Katsuhiko

    2015-01-01

    Summary GABAergic synaptic transmission regulates brain function by establishing the appropriate excitation-inhibition (E/I) balance in neural circuits. The structure and function of GABAergic synapses are sensitive to destabilization by impinging neurotransmitters. However, signaling mechanisms that promote the restorative homeostatic stabilization of GABAergic synapses remain unknown. Here, by quantum dot single-particle tracking, we characterize a signaling pathway that promotes the stability of GABAA receptor (GABAAR) postsynaptic organization. Slow metabotropic glutamate receptor signaling activates IP3 receptor-dependent calcium release and protein kinase C to promote GABAAR clustering and GABAergic transmission. This GABAAR stabilization pathway counteracts the rapid cluster dispersion caused by glutamate-driven NMDA receptor-dependent calcium influx and calcineurin dephosphorylation, including in conditions of pathological glutamate toxicity. These findings show that glutamate activates distinct receptors and spatiotemporal patterns of calcium signaling for opposing control of GABAergic synapses. PMID:26711343

  3. A further experimental study of the antisilicotic effect of glutamate.

    PubMed Central

    Morosova, K I; Katsnelson, B A; Rotenberg YuS; Belobragina, G V

    1984-01-01

    Two groups of rats were exposed to quartz dust for six months and in addition one group was given drinking water containing 1.5% sodium glutamate while the second received only water. In the rats receiving glutamate we observed (a) evidence for a considerably reduced cytotoxic effect of the quartz on cells obtained by bronchopulmonary lavage, (b) a reduction in dust retention in the lungs, especially in the tracheobronchial lymph nodes, (c) a considerable reduction in the weight gain in the lungs and in their hydroxyproline and lipid contents, and (d) the inhibition of the formation of silicotic nodules. Polarographic studies of the oxygen consumption of peritoneal macrophages from rats receiving glutamate showed that glutamate prevents the adverse effects of quartz on mitochondrial oxidative processes. PMID:6093851

  4. Transport Mechanism of a Bacterial Homologue of Glutamate Transporters

    SciTech Connect

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

    2009-01-01

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

  5. Metabolic Control of Vesicular Glutamate Transport and Release

    PubMed Central

    Juge, Narinobu; Gray, John A.; Omote, Hiroshi; Miyaji, Takaaki; Inoue, Tsuyoshi; Hara, Chiaki; Uneyama, Hisayuki; Edwards, Robert H.; Nicoll, Roger A.; Moriyama, Yoshinori

    2010-01-01

    Fasting has been used to control epilepsy since antiquity, but the mechanism of coupling between metabolic state and excitatory neurotransmission remains unknown. Previous work has shown that the vesicular glutamate transporters (VGLUTs) required for exocytotic release of glutamate undergo an unusual form of regulation by Cl−. Using functional reconstitution of the purified VGLUTs into proteoliposomes, we now show that Cl− acts as an allosteric activator, and the ketone bodies that increase with fasting inhibit glutamate release by competing with Cl− at the site of allosteric regulation. Consistent with these observations, acetoacetate reduced quantal size at hippocampal synapses, and suppresses glutamate release and seizures evoked with 4-aminopyridine in the brain. The results indicate an unsuspected link between metabolic state and excitatory neurotransmission through anion-dependent regulation of VGLUT activity. PMID:20920794

  6. Vesicular release of glutamate from unmyelinated axons in white matter

    PubMed Central

    Ziskin, Jennifer L; Nishiyama, Akiko; Rubio, Maria; Fukaya, Masahiro; Bergles, Dwight E

    2007-01-01

    Directed fusion of transmitter-laden vesicles enables rapid intercellular signaling in the central nervous system and occurs at synapses within gray matter. Here we show that action potentials also induce the release of glutamate from axons in the corpus callosum, a white matter region responsible for interhemispheric communication. Callosal axons release glutamate by vesicular fusion, which induces quantal AMPA receptor–mediated currents in NG2+ glial progenitors at anatomically distinct axo–glial synaptic junctions. Glutamate release from axons was facilitated by repetitive stimulation and could be inhibited through activation of metabotropic autoreceptors. Although NG2+ cells form associations with nodes of Ranvier in white matter, measurements of conduction velocity indicated that unmyelinated fibers are responsible for glutamatergic signaling with NG2+ glia. This activity-dependent secretion of glutamate was prevalent in the developing and mature mouse corpus callosum, indicating that axons within white matter both conduct action potentials and engage in rapid neuron-glia communication. PMID:17293857

  7. Glutamic Acid Selective Chemical Cleavage of Peptide Bonds.

    PubMed

    Nalbone, Joseph M; Lahankar, Neelam; Buissereth, Lyssa; Raj, Monika

    2016-03-01

    Site-specific hydrolysis of peptide bonds at glutamic acid under neutral aqueous conditions is reported. The method relies on the activation of the backbone amide chain at glutamic acid by the formation of a pyroglutamyl (pGlu) imide moiety. This activation increases the susceptibility of a peptide bond toward hydrolysis. The method is highly specific and demonstrates broad substrate scope including cleavage of various bioactive peptides with unnatural amino acid residues, which are unsuitable substrates for enzymatic hydrolysis.

  8. Transport mechanism of a glutamate transporter homologue GltPh

    PubMed Central

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

    2016-01-01

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

  9. Functional architecture of olfactory ionotropic glutamate receptors

    PubMed Central

    Abuin, Liliane; Bargeton, Benoîte; Ulbrich, Maximilian H.; Isacoff, Ehud Y.; Kellenberger, Stephan; Benton, Richard

    2010-01-01

    Ionotropic glutamate receptors (iGluRs) are ligand-gated ion channels that mediate chemical communication between neurons at synapses. A variant iGluR subfamily, the Ionotropic Receptors (IRs), was recently proposed to detect environmental volatile chemicals in olfactory cilia. Here we elucidate how these peripheral chemosensors have evolved mechanistically from their iGluR ancestors. Using a Drosophila model, we demonstrate that IRs act in combinations of up to three subunits, comprising individual odor-specific receptors and one or two broadly expressed co-receptors. Heteromeric IR complex formation is necessary and sufficient for trafficking to cilia and mediating odor-evoked electrophysiological responses in vivo and in vitro. IRs display heterogeneous ion conduction specificities related to their variable pore sequences, and divergent ligand-binding domains function in odor recognition and cilia localization. Our results provide insights into the conserved and distinct architecture of these olfactory and synaptic ion channels and offer perspectives into use of IRs as genetically encoded chemical sensors. PMID:21220098

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

    PubMed

    Perfilova, V N; Tyurenkov, I N

    2016-01-01

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

  11. Reduced hippocampal glutamate in Alzheimer disease.

    PubMed

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

    2011-05-01

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

  12. [Glutamic acid as a universal extracellular signal].

    PubMed

    Yoneda, Yukio

    2015-08-01

    The prevailing view is that both glutamic (Glu) and gamma-aminobutyric (GABA) acids play a role as an amino acid neurotransmitter released from neurons. However, little attention has been paid to the possible expression and functionality of signaling machineries required for amino acidergic neurotransmission in cells other than central neurons. In line with our first demonstration of the presence of Glu receptors outside the brain, in this review I will outline our recent findings accumulated since then on the physiological and pathological significance of neuronal amino acids as an extracellular signal essential for homeostasis in a variety of phenotypic cells. In undifferentiated neural progenitor cells, for instance, functional expression is seen with different signaling machineries used for glutamatergic and GABAergic neurotransmission in neurons. Moreover, Glu plays a role in mechanisms underlying suppression of proliferation for self-replication in undifferentiated mesenchymal stem cells. There is more accumulating evidence for neuronal amino acids playing a role as an extracellular autocrine or paracrine signal commonly used in different phenotypic cells. Evaluation of drugs currently used could be thus beneficial for the efficient prophylaxis and/or the therapy of a variety of diseases relevant to disturbance of amino acid signaling in diverse organs.

  13. Podocytes: a new player for glutamate signaling.

    PubMed

    Armelloni, S; Li, M; Messa, P; Rastaldi, M P

    2012-12-01

    In the renal glomerulus, podocytes envelop the external side of the capillary basement membrane with their intertwining ramifications, and ensure elimination of metabolic waste within the urine, while proteins and important blood components are retained into the circulation. To preserve the integrity of the glomerular filter, which is constantly exposed to a high variety of stimuli, podocytes need to communicate by rapid and precise signaling, likely similar to that used by neuronal cells. In the last years, we and others have shown that podocytes are indeed molecularly equipped for communicating in a synaptic-like way, where glutamate and its receptors seem to have a pivotal role, because altering glutamatergic communication leads to podocyte damage and increased filter permeability. Major components of glutamatergic signaling are organized at foot process junctions by adhesion molecules, chiefly by nephrin, and are connected to the actin cytoskeleton, that governs the health of podocytes. Further advances in understanding podocyte physiological behavior and signaling properties have the potential to improve the knowledge of podocyte diseases, first among them idiopathic focal segmental glomerulosclerosis that still needs more precise molecular-based diagnosis and targeted treatment. PMID:23018105

  14. Nitrogen isotope effects on glutamate decarboxylase from Escherichia coli

    SciTech Connect

    Abell, L.M.; O'Leary, M.H.

    1988-05-03

    The nitrogen isotope effect on the decarboxylation of glutamic acid by glutamate decarboxylase from Escherichia coli has been measured by comparison of the isotopic composition of the amino nitrogen of the product ..gamma..-aminobutyric acid isolated after 10-20% reaction with that of the starting glutamic acid. At pH 4.7, 37 /sup 0/C, the isotope effect is k/sup 14//k/sup 15/ = 0.9855 +/- 0.0006 when compared to unprotonated glutamic acid. Interpretation of this result requires knowledge of the equilibrium nitrogen isotope effect for Schiff base formation. This equilibrium isotope effect is K/sup 14//K/sup 15/ - 0.9824 for the formation of the unprotonated Schiff base between unprotonated valine and salicylaldehyde. Analysis of the nitrogen isotope effect on decarboxylation of glutamic acid and of the previously measured carbon isotope effect on this same reaction shows that decarboxylation and Schiff base formation are jointly rate limiting. The enzyme-bound Schiff base between glutamate and pyridoxal 5'-phosphate partitions approximately 2:1 between decarboxylation and return to the starting state. The nitrogen isotope effect also reveals that the Schiff base nitrogen is protonated in this intermediate.

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

    PubMed

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

    2000-05-01

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

  16. Glutamate biosensors based on diamond and graphene platforms.

    PubMed

    Hu, Jingping; Wisetsuwannaphum, Sirikarn; Foord, John S

    2014-01-01

    l-Glutamate is one of the most important neurotransmitters in the mammalian central nervous system, playing a vital role in many physiological processes and implicated in several neurological disorders, for which monitoring of dynamic levels of extracellular glutamate in the living brain tissues may contribute to medical understanding and treatments. Electrochemical sensing of glutamate has been developed recently mainly using platinum, carbon fibre and carbon nanotube electrodes. In the present work, we explore the fabrication and properties of electrochemical glutamate sensors fabricated on doped chemical vapour deposition diamond electrodes and graphene nanoplatelet structures. The sensors incorporate platinum nanoparticles to catalyse the electrooxidation of hydrogen peroxide, glutamate oxidase to oxidise glutamate, and a layer of poly-phenylenediamine to impart selectivity. The performance of the devices was compared to a similar sensor fabricated on glassy carbon. Both the diamond and the graphene sensor showed very competitive performance compared to the majority of existing electrochemical sensors. The graphene based sensor showed the best performance of the three investigated in terms of sensitivity, linear dynamic range and long term stability, whereas it was found that the diamond device showed the best limit of detection.

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

    PubMed Central

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

    2010-01-01

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

  18. Glutamate biosensors based on diamond and graphene platforms.

    PubMed

    Hu, Jingping; Wisetsuwannaphum, Sirikarn; Foord, John S

    2014-01-01

    l-Glutamate is one of the most important neurotransmitters in the mammalian central nervous system, playing a vital role in many physiological processes and implicated in several neurological disorders, for which monitoring of dynamic levels of extracellular glutamate in the living brain tissues may contribute to medical understanding and treatments. Electrochemical sensing of glutamate has been developed recently mainly using platinum, carbon fibre and carbon nanotube electrodes. In the present work, we explore the fabrication and properties of electrochemical glutamate sensors fabricated on doped chemical vapour deposition diamond electrodes and graphene nanoplatelet structures. The sensors incorporate platinum nanoparticles to catalyse the electrooxidation of hydrogen peroxide, glutamate oxidase to oxidise glutamate, and a layer of poly-phenylenediamine to impart selectivity. The performance of the devices was compared to a similar sensor fabricated on glassy carbon. Both the diamond and the graphene sensor showed very competitive performance compared to the majority of existing electrochemical sensors. The graphene based sensor showed the best performance of the three investigated in terms of sensitivity, linear dynamic range and long term stability, whereas it was found that the diamond device showed the best limit of detection. PMID:25427169

  19. Hyperglycemia reduces functional expression of astrocytic Kir4.1 channels and glial glutamate uptake.

    PubMed

    Rivera-Aponte, D E; Méndez-González, M P; Rivera-Pagán, A F; Kucheryavykh, Y V; Kucheryavykh, L Y; Skatchkov, S N; Eaton, M J

    2015-12-01

    Diabetics are at risk for a number of serious health complications including an increased incidence of epilepsy and poorer recovery after ischemic stroke. Astrocytes play a critical role in protecting neurons by maintaining extracellular homeostasis and preventing neurotoxicity through glutamate uptake and potassium buffering. These functions are aided by the presence of potassium channels, such as Kir4.1 inwardly rectifying potassium channels, in the membranes of astrocytic glial cells. The purpose of the present study was to determine if hyperglycemia alters Kir4.1 potassium channel expression and homeostatic functions of astrocytes. We used q-PCR, Western blot, patch-clamp electrophysiology studying voltage and potassium step responses and a colorimetric glutamate clearance assay to assess Kir4.1 channel levels and homeostatic functions of rat astrocytes grown in normal and high glucose conditions. We found that astrocytes grown in high glucose (25 mM) had an approximately 50% reduction in Kir4.1 mRNA and protein expression as compared with those grown in normal glucose (5mM). These reductions occurred within 4-7 days of exposure to hyperglycemia, whereas reversal occurred between 7 and 14 days after return to normal glucose. The decrease in functional Kir channels in the astrocytic membrane was confirmed using barium to block Kir channels. In the presence of 100-μM barium, the currents recorded from astrocytes in response to voltage steps were reduced by 45%. Furthermore, inward currents induced by stepping extracellular [K(+)]o from 3 to 10mM (reflecting potassium uptake) were 50% reduced in astrocytes grown in high glucose. In addition, glutamate clearance by astrocytes grown in high glucose was significantly impaired. Taken together, our results suggest that down-regulation of astrocytic Kir4.1 channels by elevated glucose may contribute to the underlying pathophysiology of diabetes-induced CNS disorders and contribute to the poor prognosis after stroke

  20. Comparative evaluation of glutamate-sensitive radiopharmaceuticals: Technetium-99m-glutamic acid and technetium-99m-diethylenetriaminepentaacetic acid-bis(glutamate) conjugate for tumor imaging.

    PubMed

    Kakkar, Dipti; Tiwari, Anjani K; Chuttani, Krishna; Kaul, Ankur; Singh, Harpal; Mishra, Anil K

    2010-12-01

    Single-photon emission computed tomography has become a significant imaging modality with huge potential to visualize and provide information of anatomic dysfunctions that are predictive of future diseases. This imaging tool is complimented by radiopharmaceuticals/radiosubstrates that help in imaging specific physiological aspects of the human body. The present study was undertaken to explore the utility of technetium-99m (⁹⁹(m)Tc)-labeled glutamate conjugates for tumor scintigraphy. As part of our efforts to further utilize the application of chelating agents, glutamic acid was conjugated with a multidentate ligand, diethylenetriaminepentaacetic acid (DTPA). The DTPA-glutamate conjugate [DTPA-bis(Glu)] was well characterized by IR, NMR, and mass spectroscopy. The biological activity of glutamic acid was compared with its DTPA conjugate by radiocomplexation with ⁹⁹(m)Tc (labeling efficiency ≥98%). In vivo studies of both the radiolabeled complexes ⁹⁹(m)Tc-Glu and ⁹⁹(m)Tc-DTPA-bis(Glu) were then carried out, followed by gamma scintigraphy in New Zealand albino rabbits. Improved serum stability of ⁹⁹(m)Tc-labeled DTPA conjugate indicated that ⁹⁹(m)Tc remained bound to the conjugate up to 24 hours. Blood clearance showed a relatively slow washout of the DTPA conjugate when compared with the labeled glutamate. Biodistribution characteristics of the conjugate in Balb/c mice revealed that DTPA conjugation of glutamic acid favors less accumulation in the liver and bone and rapid renal clearance. Tumor scintigraphy in mice showed increasing tumor accumulation, stable up to 4 hours. These preliminary studies show that ⁹⁹(m)Tc-DTPA-bis(Glu) can be a useful radiopharmaceutical for diagnostic applications in single-photon emission computed tomography imaging.

  1. Type 1 metabotropic glutamate receptors (mGlu1) trigger the gating of GluD2 delta glutamate receptors

    PubMed Central

    Ady, Visou; Perroy, Julie; Tricoire, Ludovic; Piochon, Claire; Dadak, Selma; Chen, Xiaoru; Dusart, Isabelle; Fagni, Laurent; Lambolez, Bertrand; Levenes, Carole

    2014-01-01

    The orphan GluD2 receptor belongs to the ionotropic glutamate receptor family but does not bind glutamate. Ligand-gated GluD2 currents have never been evidenced, and whether GluD2 operates as an ion channel has been a long-standing question. Here, we show that GluD2 gating is triggered by type 1 metabotropic glutamate receptors, both in a heterologous expression system and in Purkinje cells. Thus, GluD2 is not only an adhesion molecule at synapses but also works as a channel. This gating mechanism reveals new properties of glutamate receptors that emerge from their interaction and opens unexpected perspectives regarding synaptic transmission and plasticity. PMID:24357660

  2. Impulsivity is Associated with Increased Metabolism in the Fronto-Insular Network in Parkinson’s Disease

    PubMed Central

    Tahmasian, Masoud; Rochhausen, Luisa; Maier, Franziska; Williamson, Kim L.; Drzezga, Alexander; Timmermann, Lars; Van Eimeren, Thilo; Eggers, Carsten

    2015-01-01

    Various neuroimaging studies demonstrated that the fronto-insular network is implicated in impulsive behavior. We compared glucose metabolism (as a proxy measure of neural activity) among 24 patients with Parkinson’s disease (PD) who presented with low or high levels of impulsivity based on the Barratt Impulsiveness Scale 11 (BIS) scores. Subjects underwent 18-fluorodeoxyglucose positron emission tomography (FDG-PET) and the voxel-wise group difference of FDG-metabolism was analyzed in Statistical Parametric Mapping (SPM8). Subsequently, we performed a partial correlation analysis between the FDG-metabolism and BIS scores, controlling for covariates (i.e., age, sex, severity of disease and levodopa equivalent daily doses). Voxel-wise group comparison revealed higher FDG-metabolism in the orbitofrontal cortex (OFC), anterior cingulate cortex (ACC), and right insula in patients with higher impulsivity scores. Moreover, there was a positive correlation between the FDG-metabolism and BIS scores. Our findings provide evidence that high impulsivity is associated with increased FDG-metabolism within the fronto-insular network in PD. PMID:26648853

  3. Effects of clonality on the genetic variability of rare, insular species: the case of Ruta microcarpa from the Canary Islands

    PubMed Central

    Meloni, M; Reid, A; Caujapé-Castells, J; Marrero, Á; Fernández-Palacios, J M; Mesa-Coelo, R A; Conti, E

    2013-01-01

    Many plant species combine sexual and clonal reproduction. Clonal propagation has ecological costs mainly related to inbreeding depression and pollen discounting; at the same time, species able to reproduce clonally have ecological and evolutionary advantages being able to persist when conditions are not favorable for sexual reproduction. The presence of clonality has profound consequences on the genetic structure of populations, especially when it represents the predominant reproductive strategy in a population. Theoretical studies suggest that high rate of clonal propagation should increase the effective number of alleles and heterozygosity in a population, while an opposite effect is expected on genetic differentiation among populations and on genotypic diversity. In this study, we ask how clonal propagation affects the genetic diversity of rare insular species, which are often characterized by low levels of genetic diversity, hence at risk of extinction. We used eight polymorphic microsatellite markers to study the genetic structure of the critically endangered insular endemic Ruta microcarpa. We found that clonality appears to positively affect the genetic diversity of R. microcarpa by increasing allelic diversity, polymorphism, and heterozygosity. Moreover, clonal propagation seems to be a more successful reproductive strategy in small, isolated population subjected to environmental stress. Our results suggest that clonal propagation may benefit rare species. However, the advantage of clonal growth may be only short-lived for prolonged clonal growth could ultimately lead to monoclonal populations. Some degree of sexual reproduction may be needed in a predominantly clonal species to ensure long-term viability. PMID:23789068

  4. Combined adverse effects of cascading events on systems' functionality: an insular case study, French West Indies

    NASA Astrophysics Data System (ADS)

    Desramaut, Nicolas; Wang, Justin; Gehl, Pierre; Marti, Jose; Baills, Audrey; Reveillere, Arnaud

    2013-04-01

    In our modern societies, lifelines play a vital role, even in normal conditions. Therefore, during crises, the dependency to critical infrastructures is likely to be exacerbated. Indeed, in order to provide quick emergency services to the population, systems have to be functional. However, even if not directly damaged, in order to be functional, elements of the different systems have to receive enough resources but also to be able to supply their own services. In a multi-risk approach, this necessity to take into account systemic vulnerability to assess the real impact of natural hazards on society is even made more obvious. For example, impacts of one hazard, taken separately, might not significantly affect societies, but might reduce redundancy, and therefore could increase functional vulnerability to other hazards. The present study aims at analyzing the effects of cascading events on the behaviour of interdependent systems and on the capacities of the health care system to treat the victims. In order to work on a close system, an insular context (Guadeloupe, French West Indies) has been selected. The hazard cascading scenario consists of a M6.3 earthquake striking Basse-Terre, and triggering landslides in the mountainous areas where antecedent precipitations have made the area prone to slide. Damages due to earthquakes have been estimated for the 5 considered systems (buildings, healthcare system, electrical network, water supply network and transportation). Due to their localization in mountainous areas, landslides would affect only transportation networks, with closure of roads. The inter- and intra-dependencies of systems have been modeled thanks to the I2Sim platform developed at UBC. The functionality of each element is therefore the consequence of the physical (direct damage) but also functional (indirect) damage. Analyses are performed for different strategies of resources allocations, and one of the final results is the impact of the induced landslides

  5. Aerosol optical, microphysical and radiative properties at regional background insular sites in the western Mediterranean

    NASA Astrophysics Data System (ADS)

    Sicard, Michaël; Barragan, Rubén; Dulac, François; Alados-Arboledas, Lucas; Mallet, Marc

    2016-09-01

    In the framework of the ChArMEx (the Chemistry-Aerosol Mediterranean Experiment; http://charmex.lsce.ipsl.fr/) program, the seasonal variability of the aerosol optical, microphysical and radiative properties derived from AERONET (Aerosol Robotic Network; http://aeronet.gsfc.nasa.gov/) is examined in two regional background insular sites in the western Mediterranean Basin: Ersa (Corsica Island, France) and Palma de Mallorca (Mallorca Island, Spain). A third site, Alborán (Alborán Island, Spain), with only a few months of data is considered for examining possible northeast-southwest (NE-SW) gradients of the aforementioned aerosol properties. The AERONET dataset is exclusively composed of level 2.0 inversion products available during the 5-year period 2011-2015. AERONET solar radiative fluxes are compared with ground- and satellite-based flux measurements. To the best of our knowledge this is the first time that AERONET fluxes are compared with measurements at the top of the atmosphere. Strong events (with an aerosol optical depth at 440 nm greater than 0.4) of long-range transport aerosols, one of the main drivers of the observed annual cycles and NE-SW gradients, are (1) mineral dust outbreaks predominant in spring and summer in the north and in summer in the south and (2) European pollution episodes predominant in autumn. A NE-SW gradient exists in the western Mediterranean Basin for the aerosol optical depth and especially its coarse-mode fraction, which all together produces a similar gradient for the aerosol direct radiative forcing. The aerosol fine mode is rather homogeneously distributed. Absorption properties are quite variable because of the many and different sources of anthropogenic particles in and around the western Mediterranean Basin: North African and European urban areas, the Iberian and Italian peninsulas, most forest fires and

  6. Bacterial cell-surface displaying of thermo-tolerant glutamate dehydrogenase and its application in L-glutamate assay.

    PubMed

    Song, Jianxia; Liang, Bo; Han, Dongfei; Tang, Xiangjiang; Lang, Qiaolin; Feng, Ruirui; Han, Lihui; Liu, Aihua

    2015-03-01

    In this paper, glutamate dehydrogenase (Gldh) is reported to efficiently display on Escherichia coli cell surface by using N-terminal region of ice the nucleation protein as an anchoring motif. The presence of Gldh was confirmed by SDS-PAGE and enzyme activity assay. Gldh was detected mainly in the outer membrane fraction, suggesting that the Gldh was displayed on the bacterial cell surface. The optimal temperature and pH for the bacteria cell-surface displayed Gldh (bacteria-Gldh) were 70°C and 9.0, respectively. Additionally, the fusion protein retained almost 100% of its initial enzymatic activity after 1 month incubation at 4°C. Transition metal ions could inhibit the enzyme activity to different extents, while common anions had little adverse effect on enzyme activity. Importantly, the displayed Gldh is most specific to l-glutamate reported so far. The bacterial Gldh was enabled to catalyze oxidization of l-glutamate with NADP(+) as cofactor, and the resultant NADPH can be detected spectrometrically at 340nm. The bacterial-Gldh based l-glutamate assay was established, where the absorbance at 340nm increased linearly with the increasing l-glutamate concentration within the range of 10-400μM. Further, the proposed approach was successfully applied to measure l-glutamate in real samples. PMID:25659635

  7. Among the twenty classical L-amino acids, only glutamate directly activates metabotropic glutamate receptors.

    PubMed

    Frauli, Mélanie; Neuville, Pascal; Vol, Claire; Pin, Jean-Philippe; Prézeau, Laurent

    2006-02-01

    Under pathophysiological conditions, cellular amino acids can be profusely released from cells into the cerebral interstitial space. Because several class-C G protein coupled receptors (GPCRs) display a broad natural ligand spectrum, being sensitive to more than one endogenous ligand, we wondered whether the related metabotropic glutamate (mGlu) receptors could be modulated by various types of L-amino acids, allowing them to sense large increase in extracellular amino acid concentration. Here, the agonist, antagonist and allosteric effects of the twenty classical L-amino acids were evaluated on the eight mGlu receptor subtypes. We show that, in addition to glutamate (Glu), cysteine, aspartate and asparagine also lead to the activation of mGlu3, 4 and 5. Interestingly, our data demonstrate that the effect of these three amino acids did not result from a direct activation of the receptors, but from an indirect action involving Glu-transporters/exchangers. These data first demonstrate that mGlu receptors, unlike other class-C GPCRs, display an extremely high selectivity towards one ligand. Moreover, our results also show that Glu transport systems allow mGlu receptors to sense large increase in the extracellular concentration of some amino acids. Such a system will certainly lead to a large increase in some mGlu receptor activity under pathological conditions, such as seizure, ischemia or other brain injuries. PMID:16310227

  8. [Elevated gastric lesions].

    PubMed

    de Careaga, B; Villagómez, G; Pabón, J; Calderón, O; Elío, D; Pérez, J; Martínez, M; Patiño, F; Ponce, R; Lora, J

    1986-01-01

    Elevated gastric lesions, represent an important group among gastric pathology. To establish its incidence in our experience, we studied the endoscopic reports of two important hospitals in La Paz city: Instituto de Gastroenterología Boliviano Japonés and Hospital Obrero No. 1. In order to make a good endoscopic diagnosis among different elevated lesions we use some parameters like: location, shape, size, diameter, surface of the lesion and surrounding mucosa and characteristics of the falls. 10.472 endoscopic reports were reviewed, 497 elevated gastric lesions were found, 475 corresponded to mucosal lesions (352 benign lesions and 123 malignant lesions), 11 to submucosal and 11 extragastric lesions.

  9. Diphenyl ditelluride induces anxiogenic-like behavior in rats by reducing glutamate uptake.

    PubMed

    Stangherlin, Eluza Curte; Nogueira, Cristina Wayne

    2014-06-01

    Anxiety-related disorders are a common public health issue. Several lines of evidence suggest that altered glutamatergic neurotransmission underlies anxiety. The present study evaluated the effect of diphenyl ditelluride [(PhTe)2] exposure on the behavioral performance of rats and examined whether the behavioral effects could be attributed to changes in the modulation of glutamatergic function. Rats were exposed to (PhTe)2 (subcutaneously) during 8 weeks-final dose one third LD50 (124 μg/kg). The testing schedule included elevated plus-maze, open-field, T-maze, rotorod, and Morris water maze tests. Synaptosomal basal [(3)H] glutamate release and uptake were also evaluated. The time spent in the open arm and the ratio of time spent in the open arm/total were decreased in the (PhTe)2 group. Furthermore, the [(3)H] glutamate uptake was decreased in this experimental group. The results suggest that exposure to (PhTe)2 did not change motor abilities whereas it may result in anxiogenic-like behavior, induced by changes in the glutamatergic system at the pre-synaptic level.

  10. Acrolein, a product of lipid peroxidation, inhibits glucose and glutamate uptake in primary neuronal cultures.

    PubMed

    Lovell, M A; Xie, C; Markesbery, W R

    2000-10-15

    Oxidative stress has been implicated in the pathogenesis of several neurodegenerative disorders including Alzheimer's disease (AD). Increased lipid peroxidation, decreased levels of polyunsaturated fatty acids, and increased levels of 4-hydroxynonenal (HNE), F(2)-isoprostanes, and F(4)-neuroprostanes are present in the brain in patients with AD. Acrolein, an alpha,beta-unsaturated aldehydic product of lipid peroxidation has been demonstrated to be approximately 100 times more reactive than HNE and is present in neurofibrillary tangles in the brain in AD. We recently demonstrated statistically significant elevated concentrations of extractable acrolein in the hippocampus/parahippocampal gyrus and amygdala in AD compared with age-matched control subjects. Concentrations of acrolein were two to five times those of HNE in the same samples. Treatment of hippocampal cultures with acrolein led to a time- and concentration-dependent decrease in cell survival as well as a concentration-dependent increase in intracellular calcium. In cortical neuron cultures, we now report that acrolein causes a concentration-dependent impairment of glutamate uptake and glucose transport in cortical neuron cultures. Treatment of cortical astrocyte cultures with acrolein led to the same pattern of impairment of glutamate uptake as observed in cortical neuron cultures. Collectively, these data demonstrate neurotoxicity mechanisms of arolein that might be important in the pathogenesis of neuron degeneration in AD.

  11. Metabotropic glutamate receptor ligands as potential therapeutics for addiction

    PubMed Central

    Olive, M. F.

    2009-01-01

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

  12. Current approaches to enhance glutamate transporter function and expression.

    PubMed

    Fontana, Andréia C K

    2015-09-01

    L-glutamate is the predominant excitatory neurotransmitter in the CNS and has a central role in a variety of brain functions. The termination of glutamate neurotransmission by excitatory amino acid transporters (EAATs) is essential to maintain glutamate concentration low in extracellular space and avoid excitotoxicity. EAAT2/GLT-1, being the most abundant subtype of glutamate transporter in the CNS, plays a key role in regulation of glutamate transmission. Dysfunction of EAAT2 has been correlated with various pathologies such as traumatic brain injury, stroke, amyotrophic lateral sclerosis, Alzheimer's disease, among others. Therefore, activators of the function or enhancers of the expression of EAAT2/GLT-1 could serve as a potential therapy for these conditions. Translational activators of EAAT2/GLT-1, such as ceftriaxone and LDN/OSU-0212320, have been described to have significant protective effects in animal models of amyotrophic lateral sclerosis and epilepsy. In addition, pharmacological activators of the activity of EAAT2/GLT-1 have been explored for decades and are currently emerging as promising tools for neuroprotection, having potential advantages over expression activators. This review describes the current status of the search for EAAT2/GLT-1 activators and addresses challenges and limitations that this approach might encounter. Termination of glutamate neurotransmission by glutamate transporter EAAT2 is essential to maintain homeostasis in the brain and to avoid excitotoxicity. Dysfunction of EAAT2 has been correlated with various neurological pathologies. Therefore, activators of the function or enhancers of the expression of EAAT2 (green arrows) could serve as a potential therapy for these conditions. This review describes the current status of the search for EAAT2 activators and addresses challenges and limitations of this approach. PMID:26096891

  13. Therapeutic effects of glutamic acid in piglets challenged with deoxynivalenol.

    PubMed

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

    2014-01-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

    Cisneros, Irma E; Ghorpade, Anuja

    2012-01-01

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

  16. HIV-1, methamphetamine and astrocyte glutamate regulation: combined excitotoxic implications for neuro-AIDS.

    PubMed

    Cisneros, Irma E; Ghorpade, Anuja

    2012-07-01

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

  17. 19 CFR 7.3 - Duty-free treatment of goods imported from insular possessions of the United States other than...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... for informal entry under § 143.21 of this chapter or in any case where the port director is otherwise... goods in a shipment not eligible for informal entry under § 143.21 of this chapter are sought to be... the insular possession in substantially the following form: I, (name) of (organization) do...

  18. Medicaid and CHIP: Opportunities Exist to Improve U.S. Insular Area Demographic Data That Could Be Used to Help Determine Federal Funding. GAO-09-558R

    ERIC Educational Resources Information Center

    Kohn, Linda T.

    2009-01-01

    The five largest insular areas of the United States--American Samoa, the Commonwealth of the Northern Mariana Islands (CNMI), Guam, Puerto Rico, and the U.S. Virgin Islands--receive federal funding through Medicaid and the State Children's Health Insurance Program (CHIP), joint federal-state programs that finance health care for certain low-income…

  19. Enhancement of Inhibitory Avoidance and Conditioned Taste Aversion Memory with Insular Cortex Infusions of 8-Br-cAMP: Involvement of the Basolateral Amygdala

    ERIC Educational Resources Information Center

    Miranda, Maria I.; McGaugh, James L.

    2004-01-01

    There is considerable evidence that in rats, the insular cortex (IC) and amygdala are involved in the learning and memory of aversively motivated tasks. The present experiments examined the effects of 8-Br-cAMP, an analog of cAMP, and oxotremorine, a muscarinic agonist, infused into the IC after inhibitory avoidance (IA) training and during the…

  20. The influence of ionotropic and metabotropic glutamate receptor ligands on anxiety-like effect of amphetamine withdrawal in rats.

    PubMed

    Koltunowska, D; Gibula-Bruzda, E; Kotlinska, J H

    2013-08-01

    Chronic amphetamine use results in anxiety-like states after drug cessation. The aim of the study was to determine a role of ionotropic and metabotropic glutamate receptor ligands in amphetamine-evoked withdrawal anxiety in the elevated plus-maze test in rats. In our study memantine (8 and 12 mg/kg), a noncompetitive N-methyl-d-aspartate (NMDA) receptor antagonist did not reduce amphetamine withdrawal anxiety. Acamprosate (NMDA and metabotropic glutamate 5 receptor (mGluR5) antagonist) at the dose 200 and 400mg/kg showed anxiolytic-like effect, thus increasing the percent of time spent in open arms and a number of open arm entries. mGluR5 selective antagonist, MTEP (3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]pyridine hydrochloride) and mGluR2/3 agonist, LY354740 (1S,2S,5R,6S)-2-aminobicyclo[3.1.0]hexane-2,6-dicarboxylic acid), caused effects similar to acamprosate at doses 1.25-5mg/kg and 2.5-5mg/kg, respectively. None of the glutamate ligands influenced locomotor activity of rats when given to the saline-treated group. Taking into account the positive correlation between amphetamine withdrawal-induced anxiety and relapse to amphetamine taking, our results suggest that modulation of mGluRs may prevent relapse to amphetamine and might pose a new direction in amphetamine abuse therapy. PMID:23623810

  1. Spatio-temporal characteristics of metabotropic glutamate receptor 5 traffic at or near the plasma membrane in astrocytes.

    PubMed

    Lee, William; Parpura, Vladimir

    2016-06-01

    Astrocytes can sense extracellular glutamate and respond to it by elevating their intracellular Ca(2+) levels via the activation of G-protein coupled receptors, such as metabotropic glutamate receptor 5 (mGluR5), which, during early postnatal development, is the primary receptor responsible for glutamatergic signaling in astrocytes. However, the detailed spatio-temporal characteristics of mGluR5 traffic at or near the plasma membrane of astrocytes are not well understood. To address this issue, we expressed recombinant fluorescent protein chimera of mGluR5 and used total internal reflection fluorescence microscopy on rat visual cortical astrocytes in culture. We used astrocytes lacking major processes, otherwise posing as a diffusion barrier, to infer into the general dynamics of this receptor. We found that plasmalemmal mGluR5 clusters in distinct areas, the size, and initial spatio-temporal level of occupancy of which dictated mGluR5 trafficking characteristics upon glutamate stimulation. These findings will be valuable in the interpretation of point-to-point information transfer and volume transmission between astrocytes and neurons, as well as that of paracrine signaling within astrocytic networks. PMID:27014856

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

    PubMed

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

    2016-05-27

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

  3. Light: Isometric Casing with Lens, South Elevation, North Elevation, Top ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Light: Isometric Casing with Lens, South Elevation, North Elevation, Top Plan, Base Plan; Fresnel Lens: Isometric, Elevation, Plan - Fort Washington, Fort Washington Light, Northeast side of Potomac River at Fort Washington Park, Fort Washington, Prince George's County, MD

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

    PubMed

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

    2012-01-15

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

  5. Methylphenidate Increases Glutamate Uptake in Bergmann Glial Cells.

    PubMed

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

    2015-11-01

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

  6. Ghrelin Regulates Glucose and Glutamate Transporters in Hypothalamic Astrocytes

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-03-30

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

  8. Ionotropic glutamate receptor expression in human white matter.

    PubMed

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

    2016-09-01

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

  9. Single rodent mesohabenular axons release glutamate and GABA

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2015-11-01

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

  11. The role of glutamate on the action of antidepressants.

    PubMed

    Hashimoto, Kenji

    2011-08-15

    Major depressive disorder (MDD) is a common, chronic, recurrent mental illness that affects millions of individuals worldwide. Currently available antidepressants are known to affect the monoaminergic (e.g., serotonin, norepinephrine, and dopamine) systems in the brain. Accumulating evidence suggests that the glutamatergic neurotransmission via the excitatory amino acid glutamate also plays an important role in the neurobiology and treatment of this disease. Clinical studies have demonstrated that the non-competitive N-methyl-d-aspartate (NMDA) receptor antagonist ketamine has rapid antidepressant effects in treatment-resistant patients with MDD, suggesting the role of glutamate in the pathophysiology of treatment-resistant MDD. Furthermore, a number of preclinical studies demonstrated that the agents which act at glutamate receptors such as NMDA receptors, α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors and metabotropic glutamate receptors (mGluRs) might have antidepressant-like activities in animal models of depression. In this article, the author reviews the role of glutamate in the neuron-glia communication induced by potential antidepressants.

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

    Cooper, Arthur J L; Jeitner, Thomas M

    2016-01-01

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

  14. Double Dissociation of Monoacylglycerol Lipase Inhibition and CB1 Antagonism in the Central Amygdala, Basolateral Amygdala, and the Interoceptive Insular Cortex on the Affective Properties of Acute Naloxone-Precipitated Morphine Withdrawal in Rats.

    PubMed

    Wills, Kiri L; Petrie, Gavin N; Millett, Geneva; Limebeer, Cheryl L; Rock, Erin M; Niphakis, Micah J; Cravatt, Benjamin F; Parker, Linda A

    2016-06-01

    Both CB1 receptor antagonism and agonism, in particular by 2-arachidonyl glycerol (2-AG), have been shown to reduce somatic symptoms of morphine withdrawal (MWD). Here we evaluated the effects of both systemic pretreatment with the monoacylglycerol lipase (MAGL) inhibitor MJN110 (which selectively elevates 2-AG) and central administration of both MJN110 and the CB1 antagonist (AM251) on the affective properties of MWD. Acute MWD induced place aversion occurs when naloxone is administered 24 h following a single exposure to a high dose of morphine. Systemic pretreatment with the MAGL inhibitor, MJN110, prevented the aversive effects of acute MWD by a CB1 receptor-dependent mechanism. Furthermore, in a double dissociation, AM251 infusions into the central amygdala, but MJN110 infusions into the basolateral amygdala, interfered with the naloxone-precipitated MWD induced place aversion. As well, MJN110, but not AM251, infusions into the interoceptive insular cortex (a region known to be activated in acute MWD) also prevented the establishment of the place aversion by a CB1 mechanism of action. These findings reveal the respective sites of action of systemically administered MJN110 and AM251 in regulating the aversive effects of MWD.

  15. Medial Septal NMDA Glutamate Receptors are Involved in Modulation of Blood Natural Killer Cell Activity in Rats.

    PubMed

    Podlacha, Magdalena; Glac, Wojciech; Listowska, Magdalena; Grembecka, Beata; Majkutewicz, Irena; Myślińska, Dorota; Plucińska, Karolina; Jerzemowska, Grażyna; Grzybowska, Maria; Wrona, Danuta

    2016-03-01

    The purpose of the present study was to determine the specific role of the medial septal (MS) NMDA glutamate receptors on peripheral blood natural killer cell cytotoxicity (NKCC) and their (large granular lymphocyte, LGL) number, as well as the plasma concentration of tumor necrosis factor α (TNF-α) and corticosterone in male Wistar rats exposed to elevated plus maze (EPM) stress or non-stress conditions. The NMDA groups were injected with NMDA glutamate receptor agonist (N-methyl-D-aspartate; 0.25 μg/rat), the D-AP7 group was injected with DL-2-amino-7-phosphoheptanoate (0.1 μg/rat), an antagonist of NMDA glutamate receptors, and the control Sal group with saline (0.5 μl/rat) via previously implanted cannulae into the MS. There was an increase in the NKCC, NK/LGL number and plasma TNF-α concentration after the NMDA injections, being much stronger within the rats under non-stress conditions rather than the rats exposed to EPM stress. These parameters were decreased in the D-AP7 rats, suggesting receptor/ion channel specificity. Moreover, a lower plasma corticosterone concentration within the NMDA rather than the Sal and D-AP7 groups was found. The obtained results suggest that activation of the NMDA glutamate receptors in the MS, accompanied by changes in the corticosterone and cytokine responses, may be involved in modulation of the blood natural anti-tumor response, under EPM stress and non-stress conditions. PMID:26454750

  16. [Features of glutamate dehydrogenase in fetal and adult rumen tissue].

    PubMed

    Kalachniuk, H I; Fomenko, I S; Kalachniuk, L H; Kavai, Sh; Marounek, M; Savka, O H

    2001-01-01

    Glutamate dehydrogenase (GDH) from rumen mucosa of cow fetus, liver and two forms from mucosa (bacterial and tissue) of the adult animal were partly purified and characterized. The activity of the bacterial glutamate dehydrogenase was shown to depend on qualities of a biomass of microbes, adhered on surface of rumen mucosa. All enzymes from tissues (GDHTRF, TRC, TLC), revealed the hypersensibility to increase in the concentration medium of Zn2+, guanosine triphosphate (GTP), acting here in a role of negative modulators, and also adenosine monophosphate (AMP) and leucine, which acted as activators. However, in the same concentrations these effectors do not influence the activity of the bacterial glutamate dehydrogenase. And if all tissues enzymes are highly specific to coenzyme NADH, the bacterial ones almost in 3 times is more active at NADPH use. PMID:11642036

  17. [PECULIARITIES OF THE CEREBROVASCULAR EFFECTS OF GLUTAMIC ACID].

    PubMed

    Gan'shina, T S; Kurza, E V; Kurdyumov, I N; Maslennikov, D V; Mirzoyan, R S

    2016-01-01

    Experiments on nonlinear rats subjected to global transient cerebral ischemia revealed the ability of glutamic acid to improve cerebral circulation. Consequently, the excitatory amino acid can produce adverse (neurotoxic) and positive (anti-ischemic) effects in cerebral ischemia. The cerebrovascular effect of glutamic acid in cerebral ischemia is attenuated on the background action of the MNDA receptor blocker MK-801 (0.5 mg/kg intravenously) and eliminated by bicuculline. When glutamic acid is combined with the non-competitive MNDA receptor antagonist MK-801, neither one nor another drug shows its vasodilator effect. The results are indicative of the interaction between excitatory and inhibitory systems on the level of cerebral vessels and once again confirm our previous conclusion about the decisive role of GABA(A) receptors in brain vessels in the implementation of anti-ischemic activity of endogenous compounds (melatonin) and well-known pharmacological substances (mexidol, afobazole), and new chemical compounds based on GABA-containing lipid derivatives.

  18. Glutamate transporters in brain ischemia: to modulate or not?

    PubMed Central

    Krzyżanowska, Weronika; Pomierny, Bartosz; Filip, Małgorzata; Pera, Joanna

    2014-01-01

    In this review, we briefly describe glutamate (Glu) metabolism and its specific transports and receptors in the central nervous system (CNS). Thereafter, we focus on excitatory amino acid transporters, cystine/glutamate antiporters (system xc-) and vesicular glutamate transporters, specifically addressing their location and roles in CNS and the molecular mechanisms underlying the regulation of Glu transporters. We provide evidence from in vitro or in vivo studies concerning alterations in Glu transporter expression in response to hypoxia or ischemia, including limited human data that supports the role of Glu transporters in stroke patients. Moreover, the potential to induce brain tolerance to ischemia through modulation of the expression and/or activities of Glu transporters is also discussed. Finally we present strategies involving the application of ischemic preconditioning and pharmacological agents, eg β-lactam antibiotics, amitriptyline, riluzole and N-acetylcysteine, which result in the significant protection of nervous tissues against ischemia. PMID:24681894

  19. Inflammation, glutamate, and glia in depression: a literature review.

    PubMed

    McNally, Leah; Bhagwagar, Zubin; Hannestad, Jonas

    2008-06-01

    Multiple lines of evidence suggest that inflammation and glutamate dysfunction contribute to the pathophysiology of depression. In this review we provide an overview of how these two systems may interact. Excess levels of inflammatory mediators occur in a subgroup of depressed patients. Studies of acute experimental activation of the immune system with endotoxin and of chronic activation during interferon-alpha treatment show that inflammation can cause depression. Peripheral inflammation leads to microglial activation which could interfere with excitatory amino acid metabolism leading to inappropriate glutamate receptor activation. Loss of astroglia, a feature of depression, upsets the balance of anti- and pro-inflammatory mediators and further impairs the removal of excitatory amino acids. Microglia activated by excess inflammation, astroglial loss, and inappropriate glutamate receptor activation ultimately disrupt the delicate balance of neuroprotective versus neurotoxic effects in the brain, potentially leading to depression. PMID:18567974

  20. Enzymatic production of α-ketoglutaric acid from l-glutamic acid via l-glutamate oxidase.

    PubMed

    Niu, Panqing; Dong, Xiaoxiang; Wang, Yuancai; Liu, Liming

    2014-06-10

    In this study, a novel strategy for α-ketoglutaric acid (α-KG) production from l-glutamic acid using recombinant l-glutamate oxidase (LGOX) was developed. First, by analyzing the molecular structure characteristics of l-glutamic acid and α-KG, LGOX was found to be the best catalyst for oxidizing the amino group of l-glutamic acid to a ketonic group without the need for exogenous cofactor. Then the LGOX gene was expressed in Escherichia coli BL21 (DE3) in a soluble and active form, and the recombinant LGOX activity reached to a maximum value of 0.59U/mL at pH 6.5, 30°C. Finally, the maximum α-KG concentration reached 104.7g/L from 110g/L l-glutamic acid in 24h, under the following optimum conditions: 1.5U/mL LGOX, 250U/mL catalase, 3mM MnCl2, 30°C, and pH 6.5.