CoChat
Sign Up
Cited by 47Epilepsy research and treatmentNeuroscience and Neuropharmacology ResearchAmino Acid Enzymes and Metabolism

Astroglial Glutamine Synthetase and the Pathogenesis of Mesial Temporal Lobe Epilepsy

Open access
Sandhu, Mani Ratnesh S., Gruenbaum, Benjamin F., Gruenbaum, Shaun E., Dhaher, Roni, Deshpande, Ketaki, Funaro, Melissa C., Lee, Tih-Shih W., Zaveri, Hitten P. +1 more·2021·Frontiers in Neurology
DOI 10.3389/fneur.2021.665334PMC PMC8078591
Open this paper in CoChat — free accountOpen PDF

Abstract

The enzyme glutamine synthetase (GS), also referred to as glutamate ammonia ligase, is abundant in astrocytes and catalyzes the conversion of ammonia and glutamate to glutamine. Deficiency or dysfunction of astrocytic GS in discrete brain regions have been associated with several types of epilepsy, including medically-intractable mesial temporal lobe epilepsy (MTLE), neocortical epilepsies, and glioblastoma-associated epilepsy. Moreover, experimental inhibition or deletion of GS in the entorhinal-hippocampal territory of laboratory animals causes an MTLE-like syndrome characterized by spontaneous, recurrent hippocampal-onset seizures, loss of hippocampal neurons, and in some cases comorbid depressive-like features. The goal of this review is to summarize and discuss the possible roles of astroglial GS in the pathogenesis of epilepsy.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.3389/fneur.2021.665334

Cites

3 of 3 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 82

  1. [1]Vasile F Dossi E Rouach N. Human astrocytes: structure and functions in the healthy brain. Brain Struct Funct. (2017) 222: 2017– 29. 10.1007/s00429-017-1383-5 28280934 PMC5504258 · DOI · Paper page
  2. [2]Orkand RK Nicholls JG Kuffler SW. Effect of nerve impulses on the membrane potential of glial cells in the central nervous system of amphibia. J Neurophysiol. (1966) 29: 788– 806. 10.1152/jn.1966.29.4.788 5966435 · DOI
  3. [3]Katz MJ Lasek RJ Silver J. Ontophyletics of the nervous system: development of the corpus callosum and evolution of axon tracts. Proc Natl Acad Sci USA. (1983) 80: 5936– 40. 10.1073/pnas.80.19.5936 6577462 PMC390192 · DOI
  4. [4]Magistretti PJ Pellerin L. Astrocytes couple synaptic activity to glucose utilization in the brain. Physiology. (1999) 14: 177– 82. 10.1152/physiologyonline.1999.14.5.177 11390847 · DOI
  5. [5]Verkhratsky A Steinhäuser C. Ion channels in glial cells. Brain Res Brain Res Rev. (2000) 32: 380– 412. 10.1016/S0165-0173(99)00093-4 10760549 · DOI
  6. [6]Danbolt NC. Glutamate uptake. Prog Neurobiol. (2001) 65: 1– 105. 10.1016/S0301-0082(00)00067-8 11369436 · DOI · Paper page
  7. [7]Lemke G. Glial Control of Neuronal Development. Ann Rev Neurosci. (2001) 24: 87– 105. 10.1146/annurev.neuro.24.1.87 11283306 · DOI
  8. [8]Pellerin L Bonvento G Chatton JY Pierre K Magistretti PJ. Role of neuron-glia interaction in the regulation of brain glucose utilization. Diabetes Nutr Metab. (2002) 15: 268– 73; discussion 273. 12625467
  9. [9]Benfenati V Amiry-Moghaddam M Caprini M Mylonakou MN Rapisarda C Ottersen OP. Expression and functional characterization of transient receptor potential vanilloid-related channel 4 (TRPV4) in rat cortical astrocytes. Neuroscience. (2007) 148: 876– 92. 10.1016/j.neuroscience.2007.06.039 17719182 · DOI
  10. [10]Hertz L. Astrocytic energy metabolism and glutamate formation–relevance for 13C-NMR spectroscopy and importance of cytosolic/mitochondrial trafficking. Magn Reson Imaging. (2011) 29: 1319– 29. 10.1016/j.mri.2011.04.013 21820830 · DOI
  11. [11]Schousboe A Bak LK Madsen K Waagepetersen H. Amino acid neurotransmitter synthesis and removal. In: Kettenmann H Ransom BR editors, Neuroglia, Third Edition, Oxford: Oxford University Press (2012). p. 443– 56. 10.1093/med/9780199794591.003.0035 · DOI
  12. [12]Robinson SR. Neuronal expression of glutamine synthetase in Alzheimer's disease indicates a profound impairment of metabolic interactions with astrocytes. Neurochem Int. (2000) 36: 471– 82. 10.1016/S0197-0186(99)00150-3 10733015 · DOI
  13. [13]Nedergaard M Dirnagl U. Role of glial cells in cerebral ischemia. Glia. (2005) 50: 281– 6. 10.1002/glia.20205 15846807 · DOI
  14. [14]Binder DK Steinhäuser C. Functional changes in astroglial cells in epilepsy. Glia. (2006) 54: 358– 68. 10.1002/glia.20394 16886201 · DOI
  15. [15]Sharma R Fischer MT Bauer J Felts PA Smith KJ Misu T. Inflammation induced by innate immunity in the central nervous system leads to primary astrocyte dysfunction followed by demyelination. Acta Neuropathol. (2010) 120: 223– 36. 10.1007/s00401-010-0704-z 20532539 PMC2892605 · DOI
  16. [16]Takano A Arakawa R Ito H Tateno A Takahashi H Matsumoto R. Peripheral benzodiazepine receptors in patients with chronic schizophrenia: a PET study with [11C]DAA1106. Int J Neuropsych. (2010) 13: 943– 50. 10.1017/S1461145710000313 20350336 · DOI
  17. [17]Sanacora G Treccani G Popoli M. Towards a glutamate hypothesis of depression: an emerging frontier of neuropsychopharmacology for mood disorders. Neuropharmacology. (2012) 62: 63– 77. 10.1016/j.neuropharm.2011.07.036 21827775 PMC3205453 · DOI · Paper page
  18. [19]Cohen-Gadol AA Pan JW Kim JH Spencer DD Hetherington HH. Mesial temporal lobe epilepsy: a proton magnetic resonance spectroscopy study and a histopathological analysis. J Neurosurg. (2004) 101: 613– 20. 10.3171/jns.2004.101.4.0613 15481715 · DOI
  19. [20]Rock RB Gekker G Hu S Sheng WS Cheeran M Lokensgard JR. Role of microglia in central nervous system infections. Clin Microb Rev. (2004) 17: 942– 64. 10.1128/CMR.17.4.942-964.2004 15489356 PMC523558 · DOI · Paper page
  20. [21]Martinez-Hernandez A Bell KP Norenberg MD. Glutamine synthetase: glial localization in brain. Science. (1977) 195: 1356– 8. 10.1126/science.14400 14400 · DOI
  21. [22]Haberle J Gorg B Rutsch F Schmidt E Toutain A Benoist JF. Congenital glutamine deficiency with glutamine synthetase mutations. N Engl J Med. (2005) 353: 1926– 33. 10.1056/NEJMoa050456 16267323 · DOI
  22. [23]Häberle J Görg B Toutain A Rutsch F Benoist JF Gelot A. Inborn error of amino acid synthesis: human glutamine synthetase deficiency. J Inherit Metab Dis. (2006) 29: 352– 8. 10.1007/s10545-006-0256-5 16763901 · DOI
  23. [24]Smith CD Carney JM Starke-Reed PE Oliver CN Stadtman ER Floyd RA. Excess brain protein oxidation and enzyme dysfunction in normal aging and in Alzheimer disease. Proc Natl Acad Sci USA. (1991) 88: 10540– 3. 10.1073/pnas.88.23.10540 1683703 PMC52964 · DOI · Paper page
  24. [26]Eid T Thomas MJ Spencer DD Runden-Pran E Lai JC Malthankar GV. Loss of glutamine synthetase in the human epileptogenic hippocampus: possible mechanism for raised extracellular glutamate in mesial temporal lobe epilepsy. Lancet. (2004) 363: 28– 37. 10.1016/S0140-6736(03)15166-5 14723991 · DOI
  25. [27]Bruneau EG Mccullumsmith RE Haroutunian V Davis KL Meador-Woodruff JH. Increased expression of glutaminase and glutamine synthetase mRNA in the thalamus in schizophrenia. Schizophr Res. (2005) 75: 27– 34. 10.1016/j.schres.2004.12.012 15820321 · DOI
  26. [28]Eid T Ghosh A Wang Y Beckström H Zaveri HP Lee TS. Recurrent seizures and brain pathology after inhibition of glutamine synthetase in the hippocampus in rats. Brain. (2008) 131: 2061– 70. 10.1093/brain/awn133 18669513 PMC2724901 · DOI
  27. [29]Klempan TA Sequeira A Canetti L Lalovic A Ernst C Ffrench-Mullen J. Altered expression of genes involved in ATP biosynthesis and GABAergic neurotransmission in the ventral prefrontal cortex of suicides with and without major depression. Mol Psychiatry. (2009) 14: 175– 89. 10.1038/sj.mp.4002110 17938633 · DOI · Paper page
  28. [30]Sequeira A Mamdani F Ernst C Vawter MP Bunney WE Lebel V. Global brain gene expression analysis links glutamatergic and GABAergic alterations to suicide and major depression. PLoS ONE. (2009) 4: e6585. 10.1371/journal.pone.0006585 19668376 PMC2719799 · DOI · Paper page
  29. [32]Van Der Hel WS Notenboom RG Bos IW Van Rijen PC Van Veelen CW De Graan PN. Reduced glutamine synthetase in hippocampal areas with neuron loss in temporal lobe epilepsy. Neurology. (2005) 64: 326– 33. 10.1212/01.WNL.0000149636.44660.99 15668432 · DOI
  30. [33]Wang H Huang Y Coman D Munbodh R Dhaher R Zaveri HP. Network evolution in mesial temporal lobe epilepsy revealed by diffusion tensor imaging. Epilepsia. (2017) 58: 824– 34. 10.1111/epi.13731 28378878 PMC5429866 · DOI
  31. [34]Zhou Y Dhaher R Parent M Hu QX Hassel B Yee SP. Selective deletion of glutamine synthetase in the mouse cerebral cortex induces glial dysfunction and vascular impairment that precede epilepsy and neurodegeneration. Neurochem Int. (2019) 123: 22– 33. 10.1016/j.neuint.2018.07.009 30053506 PMC8261904 · DOI
  32. [35]Sandhu MRS Dhaher R Gruenbaum SE Raaisa R Spencer DD Pavlova MK. Circadian-like rhythmicity of extracellular brain glutamate in epilepsy. Front Neurol. (2020) 11: 398. 10.3389/fneur.2020.00398 32499751 PMC7242976 · DOI
  33. [36]Elliott WH. Adenosinetriphosphate in glutamine synthesis. Nature. (1948) 161: 128– 9. 10.1038/161128a0 18900754 · DOI
  34. [37]Speck JF. The enzymatic synthesis of glutamine, a reaction utilizing adenosine triphosphate. J Biol Chem. (1949) 179: 1405– 26. 10.1016/S0021-9258(18)56802-2 18134597 · DOI
  35. [38]Wu C. Glutamine synthetase. I a comparative study of its distribution in animals and its inhibition by dl-allo-delta-hydroxylysine. Comp Biochem Physiol. (1963) 9: 335– 51. 10.1016/0010-406X(63)90169-5 14113502 · DOI
  36. [39]Olney JW Sharpe LG Feigin RD. Glutamate-induced brain damage in infant primates. J Neuropathol Exp Neurol. (1972) 31: 464– 88. 10.1097/00005072-197207000-00006 4626680 · DOI
  37. [40]Albrecht J Jones EA. Hepatic encephalopathy: molecular mechanisms underlying the clinical syndrome. J Neurol Sci. (1999) 170: 138– 46. 10.1016/S0022-510X(99)00169-0 10617392 · DOI
  38. [41]Butterworth RF. Pathophysiology of hepatic encephalopathy: a new look at ammonia. Metab Brain Dis. (2002) 17: 221– 7. 10.1023/A:1021989230535 12602499 · DOI
  39. [42]Norenberg MD Jayakumar AR Rama Rao KV Panickar KS. New concepts in the mechanism of ammonia-induced astrocyte swelling. Metab Brain Dis. (2007) 22: 219– 34. 10.1007/s11011-007-9062-5 17823859 · DOI
  40. [43]Gruenbaum S Chen E Sandhu MR Deshpande K Dhaher R Hersey D. Branched-chain amino acids and seizures: a systematic review of the literature. CNS Drugs. (2019) 33: 755– 70. 10.1007/s40263-019-00650-2 31313139 · DOI
  41. [44]Chaudhry FA Reimer RJ Edwards RH. The glutamine commute: take the N line and transfer to the A. J Cell Biol. (2002) 157: 349– 55. 10.1083/jcb.200201070 11980913 PMC2173294 · DOI
  42. [45]Jenstad M Quazi AZ Zilberter M Haglerød C Berghuis P Saddique N. System A transporter SAT2 mediates replenishment of dendritic glutamate pools controlling retrograde signaling by glutamate. Cereb Cortex. (2009) 19: 1092– 106. 10.1093/cercor/bhn151 18832333 · DOI
  43. [46]Svenneby G. Pig brain glutaminase: purification and identification of different enzyme forms. J Neurochem. (1970) 17: 1591– 9. 10.1111/j.1471-4159.1970.tb03729.x 5474660 · DOI
  44. [47]Kvamme E Torgner IA Roberg B. Kinetics and localization of brain phosphate activated glutaminase. J Neurosci Res. (2001) 66: 951– 8. 10.1002/jnr.10041 11746423 · DOI
  45. [48]Reubi J-C Van Der Berg C Cuenod M. Glutamine as precursor for the GABA and glutamate trasmitter pools. Neurosci Lett. (1978) 10: 171– 4. 10.1016/0304-3940(78)90030-7 19605275 · DOI
  46. [49]Sonnewald U Westergaard N Schousboe A Svendsen J Unsgård G Petersen S. Direct demonstration by [13C] NMR spectroscopy that glutamine from astrocytes is a precursor for GABA synthesis in neurons. Neurochem Int. (1993) 22: 19– 29. 10.1016/0197-0186(93)90064-C 8095170 · DOI
  47. [50]Schousboe A Bak LK Waagepetersen HS. Astrocytic control of biosynthesis and turnover of the neurotransmitters glutamate and GABA. Front Endocrinol. (2013) 4: 102. 10.3389/fendo.2013.00102 23966981 PMC3744088 · DOI · Paper page
  48. [52]Cooper A Plum F. Biochemsitry and Physiology of brain ammonia. Physiol Rev. (1987) 67: 440– 519. 10.1152/physrev.1987.67.2.440 2882529 · DOI
  49. [53]Cooper A Mcdonald J Gelbard A Gledhill R Duffy T. The metabolic fate of 13N-labeled ammonia in rat brain. J Biol Chem. (1979) 254: 4982– 92. 10.1016/S0021-9258(18)50550-0 36379 · DOI
  50. [54]Cooper ÅJ Mora SN Cruz NF Gelbard AS. Cerebral ammonia metabolism in hyperammonemic rats. J Neurochem. (1985) 44: 1716– 23. 10.1111/j.1471-4159.1985.tb07159.x 2859353 · DOI
  51. [55]Braet K Paemeleire K D'herde K Sanderson MJ Leybaert L. Astrocyte–endothelial cell calcium signals conveyed by two signalling pathways. Europ J Neurosci. (2001) 13: 79– 91. 10.1046/j.1460-9568.2001.01372.x 11135006 · DOI
  52. [56]Petroff OA Errante LD Kim JH Spencer DD. N-acetyl-aspartate, total creatine, and myo-inositol in the epileptogenic human hippocampus. Neurology. (2003) 60: 1646– 51. 10.1212/01.WNL.0000068020.85450.8B 12771256 · DOI
  53. [57]Kim JH Je SJ Petroff O Spencer SS Hwang JY Spencer DD. Hippocampal Glial Density in Temporal Lobe Epilepsy. Epilepsia: Wiley (2004).
  54. [58]Petroff EA Cavus I Kim JH Spencer DD. Interictal Extracellular Glutamate Concentrations Are Increased in Hippocampal Sclerosis. Wiley (2004).
  55. [59]Cavus I Kasoff WS Cassaday MP Jacob R Gueorguieva R Sherwin RS. Extracellular metabolites in the cortex and hippocampus of epileptic patients. Ann Neurol. (2005) 57: 226– 35. 10.1002/ana.20380 15668975 · DOI
  56. [60]During MJ Spencer DD. Extracellular hippocampal glutamate and spontaneous seizure in the conscious human brain. Lancet. (1993) 341: 1607– 10. 10.1016/0140-6736(93)90754-5 8099987 · DOI
  57. [61]Olney JW Collins RC Sloviter RS. Excitotoxic mechanisms of epileptic brain damage. Adv Neurol. (1986) 44: 857– 77. 3706027
  58. [62]Eid T Williamson A Lee TS Petroff OA De Lanerolle NC. Glutamate and astrocytes–key players in human mesial temporal lobe epilepsy? Epilepsia. (2008) 49 Suppl 2: 42– 52. 10.1111/j.1528-1167.2008.01492.x 18226171 · DOI
  59. [63]Petroff O.a.C. Errante LD Rothman DL Kim JH Spencer DD. Glutamate–glutamine cycling in the epileptic human hippocampus. Epilepsia. (2002) 43: 703– 10. 10.1046/j.1528-1157.2002.38901.x 12102672 · DOI
  60. [64]Steffens M Huppertz HJ Zentner J Chauzit E Feuerstein TJ. Unchanged glutamine synthetase activity and increased NMDA receptor density in epileptic human neocortex: implications for the pathophysiology of epilepsy. Neurochem Int. (2005) 47: 379– 84. 10.1016/j.neuint.2005.06.001 16095760 · DOI
  61. [65]Rosati A Poliani PL Todeschini A Cominelli M Medicina D Cenzato M. Glutamine synthetase expression as a valuable marker of epilepsy and longer survival in newly diagnosed glioblastoma multiforme. Neuro Oncol. (2013) 15: 618– 25. 10.1093/neuonc/nos338 23410662 PMC3635515 · DOI
  62. [66]Häberle J Shahbeck N Ibrahim K Hoffmann GF Ben-Omran T. Natural course of glutamine synthetase deficiency in a 3 year old patient. Mol Genet Metab. (2011) 103: 89– 91. 10.1016/j.ymgme.2011.02.001 21353613 · DOI
  63. [67]He Y Hakvoort TB Vermeulen JL Lamers WH Van Roon MA. Glutamine synthetase is essential in early mouse embryogenesis. Dev Dyn. (2007) 236: 1865– 75. 10.1002/dvdy.21185 17557305 · DOI
  64. [68]He Y Hakvoort TB Vermeulen JL Labruyère WT De Waart DR Van Der Hel WS. Glutamine synthetase deficiency in murine astrocytes results in neonatal death. Glia. (2010) 58: 741– 54. 10.1002/glia.20960 20140959 · DOI
  65. [69]Eisenberg D Gill HS Pfluegl GM Rotstein SH. Structure-function relationships of glutamine synthetases. Biochim Biophys Acta. (2000) 1477: 122– 45. 10.1016/S0167-4838(99)00270-8 10708854 · DOI
  66. [70]Wang Y Zaveri HP Lee TS Eid T. The development of recurrent seizures after continuous intrahippocampal infusion of methionine sulfoximine in rats: a video-intracranial electroencephalographic study. Exp Neurol. (2009) 220: 293– 302. 10.1016/j.expneurol.2009.08.034 19747915 PMC2989153 · DOI
  67. [71]Dhaher R Wang H Gruenbaum SE Tu N Lee TS Zaveri HP. Effects of site-specific infusions of methionine sulfoximine on the temporal progression of seizures in a rat model of mesial temporal lobe epilepsy. Epilepsy Res. (2015) 115: 45– 54. 10.1016/j.eplepsyres.2015.05.005 26220375 PMC4677790 · DOI
  68. [72]Gruenbaum SE Wang H Zaveri HP Tang AB Lee TS Eid T. Inhibition of glutamine synthetase in the central nucleus of the amygdala induces anhedonic behavior and recurrent seizures in a rat model of mesial temporal lobe epilepsy. Epilepsy Behav. (2015) 51: 96– 103. 10.1016/j.yebeh.2015.07.015 26262937 PMC4663049 · DOI
  69. [73]Spencer SS. Neural networks in human epilepsy: evidence of and implications for treatment. Epilepsia. (2002) 43: 219– 27. 10.1046/j.1528-1157.2002.26901.x 11906505 · DOI
  70. [74]Kramer MA Cash SS. Epilepsy as a disorder of cortical network organization. Neuroscientist. (2012) 18: 360– 72. 10.1177/1073858411422754 22235060 PMC3736575 · DOI
  71. [75]Dickten H Porz S Elger CE Lehnertz K. Weighted and directed interactions in evolving large-scale epileptic brain networks. Scient Rep. (2016) 6: 34824. 10.1038/srep34824 27708381 PMC5052583 · DOI
  72. [76]Bartolomei F Lagarde S Wendling F Mcgonigal A Jirsa V Guye M. Defining epileptogenic networks: contribution of SEEG and signal analysis. Epilepsia. (2017) 58: 1131– 47. 10.1111/epi.13791 28543030 · DOI
  73. [77]Spencer DD Gerrard JL Zaveri HP. The roles of surgery and technology in understanding focal epilepsy and its comorbidities. Lancet Neurol. (2018) 17: 373– 82. 10.1016/S1474-4422(18)30031-0 29553383 · DOI
  74. [78]Zaveri HP Pincus SM Goncharova Ii Duckrow RB Spencer DD Spencer SS. Localization-related epilepsy exhibits significant connectivity away from the seizure-onset area. Neuroreport. (2009) 20: 891– 5. 10.1097/WNR.0b013e32832c78e0 19424095 · DOI
  75. [79]Varotto G Tassi L Franceschetti S Spreafico R Panzica F. Epileptogenic networks of type II focal cortical dysplasia: a stereo-EEG study. Neuroimage. (2012) 61: 591– 8. 10.1016/j.neuroimage.2012.03.090 22510255 · DOI
  76. [80]Constable RT Scheinost D Finn ES Shen X Hampson M Winstanley FS. Potential use and challenges of functional connectivity mapping in intractable epilepsy. Front Neurol. (2013) 4: 39. 10.3389/fneur.2013.00039 23734143 PMC3660665 · DOI
  77. [81]Englot DJ Konrad PE Morgan VL. Regional and global connectivity disturbances in focal epilepsy, related neurocognitive sequelae, and potential mechanistic underpinnings. Epilepsia. (2016) 57: 1546– 57. 10.1111/epi.13510 27554793 PMC5056148 · DOI
  78. [82]Smith EH Schevon CA. Toward a mechanistic understanding of epileptic networks. Curr Neurol Neurosci Rep. (2016) 16: 97. 10.1007/s11910-016-0701-2 27662895 · DOI
  79. [83]Nissen IA Stam CJ Reijneveld JC Van Straaten IE Hendriks EJ Baayen JC. Identifying the epileptogenic zone in interictal resting-state MEG source-space networks. Epilepsia. (2017) 58: 137– 48. 10.1111/epi.13622 27888520 · DOI
  80. [84]Sinha N Dauwels J Kaiser M Cash SS Brandon Westover M Wang Y. Predicting neurosurgical outcomes in focal epilepsy patients using computational modelling. Brain. (2017) 140: 319– 32. 10.1093/brain/aww299 28011454 PMC5278304 · DOI
  81. [85]Tomlinson SB Porter BE Marsh ED. Interictal network synchrony and local heterogeneity predict epilepsy surgery outcome among pediatric patients. Epilepsia. (2017) 58: 402– 11. 10.1111/epi.13657 28166392 · DOI
  82. [86]Albright B Dhaher R Wang H Harb R Lee TW Zaveri H. Progressive neuronal activation accompanies epileptogenesis caused by hippocampal glutamine synthetase inhibition. Exp Neurol. (2017) 288: 122– 33. 10.1016/j.expneurol.2016.10.007 27769717 PMC5547560 · DOI

Cited by

Sorted by citations

Authors
Sandhu, M. R. S., Gruenbaum, B. F., Gruenbaum, S. E., Dhaher, R., Deshpande, K., Funaro, M. C., Lee, T.-S. W., Zaveri, H. P., & Eid, T.
Affiliations
  • Mayo Clinic (US)
  • Yale University (US)
Corresponding author
Eid, Tore
ORCID
Venue
Frontiers in Neurology
Publisher
Frontiers Media SA
Published
2021-04-13
Volume
12
Pages
665334-665334
ISSN
1664-2295 (ISSN-L)
DOI
10.3389/fneur.2021.665334
PMC
PMC8078591
OpenAlex
W3153759411
Cited by
47
References
3
Citations by year
2026: 8 · 2025: 8 · 2024: 11 · 2023: 8 · 2022: 9 · 2021: 3
FWCI
1.38
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Neurology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Citizens United for Research in Epilepsy
  • National Institutes of Health (NS058674)
  • National Institute of Neurological Disorders and Stroke (R21NS109734, R01NS109062, R01NS070824)
  • National Center for Advancing Translational Sciences (NS058674, NS070824, RR024139)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Epilepsy research and treatment
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
Keywords
glutamine synthetase, astrocytes, mesial temporal lobe epilepsy, epilepsy pathogenesis, glutamate metabolism, ammonia detoxification, entorhinal-hippocampal circuit, hippocampal neurons, neocortical epilepsy, depression-like behavior

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review