Astroglia and severe mental illness: A role for glutamate microdomains

Pathological Potential of Neuroglia: Possible New Targets for Medical Intervention

Volumn 9781493909742, Issue , 2014, Pages 373-395

  McCullumsmith, Robert E ^a   Shan, Dan ^b   Yates, Stefani ^c   Roberts, Rosalinda C ^c  

^a UNIVERSITY OF CINCINNATI   (United States)

^b UNIVERSITY OF ALABAMA AT BIRMINGHAM   (United States)

^c UNIVERSITY OF ALABAMA AT BIRMINGHAM   (United States)

Author keywords

Glutamate spillover; Glutamate transporter; Microdomain; Psychosis; Schizophrenia

Indexed keywords

EID: 84929895498     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.1007/978-1-4939-0974-2_16     Document Type: Chapter

References (157)

1. Akbarian S, Sucher NJ, Bradley D, Tafazzoli A, Trinh D, Hetrick WP, Potkin SG, Sandman CA, Bunney WE Jr, Jones EG (1996) Selective alterations in gene expression for NMDA receptor subunits in prefrontal cortex of schizophrenics. J Neurosci 16:19-30
2. Alda M, Ahrens B, Lit W, Dvorakova M, Labelle A, Zvolsky P, Jones B (1996) Age of onset in familial and sporadic schizophrenia. Acta Psychiatr Scand 93:447-450
3. Arriza JL, Kavanaugh MP, Fairman WA, Wu YN, Murdoch GH, North RA, Amara SG (1993) Cloning and expression of a human neutral amino acid transporter with structural similarity to the glutamate transporter gene family. J Biol Chem 268:15329-15332
4. Arriza JL, Eliasof S, Kavanaugh MP, Amara SG (1997) Excitatory amino acid transporter 5, a retinal glutamate transporter coupled to a chloride conductance. Proc Natl Acad Sci U S A 94:4155-4160
5. Badcock JC (2010) The cognitive neuropsychology of auditory hallucinations: a parallel auditory pathways framework. Schizophr Bull 36:576-584
6. Baker DA, Madayag A, Kristiansen LV, Meador-Woodruff JH, Haroutunian V, Raju I (2008) Contribution of cystine-glutamate antiporters to the psychotomimetic effects of phencyclidine. Neuropsychopharmacology 33:1760-1772
7. Bartha R, Williamson PC, Drost DJ, Malla A, Carr TJ, Cortese L, Canaran G, Rylett RJ, Neufeld RW (1997) Measurement of glutamate and glutamine in the medial prefrontal cortex of nevertreated schizophrenic patients and healthy controls by proton magnetic resonance spectroscopy. Arch Gen Psychiatry 54:959-965
8. Bauer D, Gupta D, Harotunian V, Meador-Woodruff JH, McCullumsmith RE (2008) Abnormal expression of glutamate transporter and transporter interacting molecules in prefrontal cortex in elderly patients with schizophrenia. Schizophr Res 104:108-120
9. Bauer D, Haroutunian V, Meador-Woodruff JH, McCullumsmith RE (2010) Abnormal glycosylation of EAAT1 and EAAT2 in prefrontal cortex of elderly patients with schizophrenia. Schizophr Res 117:92-98
10. Bellocchio EE, Reimer RJ, Fremeau RT Jr, Edwards RH (2000) Uptake of glutamate into synaptic vesicles by an inorganic phosphate transporter. Science 289:957-960
11. Beneyto M, Meador-Woodruff JH (2006) Lamina-specific abnormalities of AMPA receptor trafficking and signaling molecule transcripts in the prefrontal cortex in schizophrenia. Synapse 60:585-598
12. Beneyto M, Kristiansen LV, Oni-Orisan A, McCullumsmith RE, Meador-Woodruff JH (2007) Abnormal glutamate receptor expression in the medial temporal lobe in schizophrenia and mood disorders. Neuropsychopharmacology 32:1888-1902
13. Brainard JR, Kyner E, Rosenberg GA (1989) 13C nuclear magnetic resonance evidence for gamma-aminobutyric acid formation via pyruvate carboxylase in rat brain: a metabolic basis for compartmentation. J Neurochem 53:1285-1292
14. Bridges R, Lutgen V, Lobner D, Baker AM (2012) Thinking outside the cleft to understand synaptic activity: contribution of the cystine-glutamate antiporter (system xc-) to normal and pathological glutamatergic signaling. Pharmacol Rev 64
15. Broadbelt K, Byne W, Jones LB (2002) Evidence for a decrease in basilar dendrites of pyramidal cells in schizophrenic medial prefrontal cortex. Schizophr Res 58:75-81
16. Bruneau EG, McCullumsmith RE, Haroutunian V, Davis KL, Meador-Woodruff JH (2005) Increased expression of glutaminase and glutamine synthetase mRNA in the thalamus in schizophrenia. Schizophr Res 75:27-34
17. Buchanan RW, Carpenter WT, Sadock Be, Sadock Ve (2000) Schizophrenia: introduction and overview. Comprehensive textbook of psychiatry. Lippincott, Williams, and Wilkins, Philadelphia, pp 1096-1110
18. Burbaeva G, Savushkina OK, Dmitriev AD (1999) Brain isoforms of creatine kinase in health and mental diseases: Alzheimer's disease and schizophrenia. Vestnik Rossiiskoi akademii meditsinskikh nauk/Rossiiskaia akademiia meditsinskikh nauk, pp 20-24
19. Chalifoux JR, Carter AG (2011) Glutamate spillover promotes the generation of NMDA spikes. J Neurosci 31:16435-16446
20. Chaudhry FA, Lehre KP, van Lookeren Campagne M, Ottersen OP, Danbolt NC, Storm-Mathisen J (1995) Glutamate transporters in glial plasma membranes: highly differentiated localizations revealed by quantitative ultrastructural immunocytochemistry. Neuron 15:711-720
21. Clark JF, Doepke A, Filosa JA, Wardle RL, Lu A, Meeker TJ, Pyne-Geithman GJ (2006) N-acetylaspartate as a reservoir for glutamate. Med Hypotheses 67:506-512
22. Conradt M, Stoffel W (1997) Inhibition of the high-affinity brain glutamate transporter GLAST-1 via direct phosphorylation. J Neurochem 68:1244-1251
23. Cook EH Jr, Scherer SW (2008) Copy-number variations associated with neuropsychiatric conditions. Nature 455:919-923
24. Corti C, Crepaldi L, Mion S, Roth AL, Xuereb JH, Ferraguti F (2007) Altered dimerization of metabotropic glutamate receptor 3 in schizophrenia. Biol Psychiatry 62:747-755
25. Danbolt NC (2001) Glutamate uptake. Prog Neurobiol 65:1-105
26. Deep-Soboslay A, Benes FM, Haroutunian V, Ellis JK, Kleinman JE, Hyde TM (2011) Psychiatric brain banking: three perspectives on current trends and future directions. Biol Psychiatry 69:104-112
27. Deicken RF, Zhou L, Schuff N, Weiner MW (1997) Proton magnetic resonance spectroscopy of the anterior cingulate region in schizophrenia. Schizophr Res 27:65-71
28. Devon RS, Anderson S, Teague PW, Muir WJ, Murray V, Pelosi AJ, Blackwood DH, Porteous DJ (2001) The genomic organisation of the metabotropic glutamate receptor subtype 5 gene, and its association with schizophrenia. Mol Psychiatry 6:311-314
29. Dong E, Agis-Balboa RC, Simonini MV, Grayson DR, Costa E, Guidotti A (2005) Reelin and glutamic acid decarboxylase67 promoter remodeling in an epigenetic methionine-induced mouse model of schizophrenia. Proc Natl Acad Sci U S A 102:12578-12583
30. Drew GM, Mitchell VA, Vaughan CW (2008) Glutamate spillover modulates GABAergic synaptic transmission in the rat midbrain periaqueductal grey via metabotropic glutamate receptors and endocannabinoid signaling. J Neurosci 28:808-815
31. Farr GA, Hull M, Mellman I, Caplan MJ (2009) Membrane proteins follow multiple pathways to the basolateral cell surface in polarized epithelial cells. J Cell Biology 186:269-282
32. Figiel M, Engele J (2000) Pituitary adenylate cyclase-activating polypeptide (PACAP), a neuronderived peptide regulating glial glutamate transport and metabolism. J Neurosci 20:3596-3605
33. Figiel M, Maucher T, Rozyczka J, Bayatti N, Engele J (2003) Regulation of glial glutamate transporter expression by growth factors. Exp Neurol 183:124-135
34. Fleischhacker W (2000) Negative symptoms in patients with schizophrenia with special reference to the primary versus secondary distinction. Encephale 26(Spec No 1):12-14
35. Füllekrug J, Simons KAI (2004) Lipid rafts and apical membrane traffic. Ann N Y Acad Sci 1014:164-169
36. Gamboa C, Ortega A (2002) Insulin-like growth factor-1 increases activity and surface levels of the GLAST subtype of glutamate transporter. Neurochem Int 40:397-403
37. Genda EN, Jackson JG, Sheldon AL, Locke SF, Greco TM, O'Donnell JC, Spruce LA, Xiao R, Guo W, Putt M, Seeholzer S, Ischiropoulos H, Robinson MB (2011) Co-compartmentalization of the astroglial glutamate transporter, GLT-1, with glycolytic enzymes and mitochondria. J Neurosci 31:18275-18288
38. Ghose S, Weickert CS, Colvin SM, Coyle JT, Herman MM, Hyde TM, Kleinman JE (2004) Glutamate carboxypeptidase II gene expression in the human frontal and temporal lobe in schizophrenia. Neuropsychopharmacology 29:117-125
39. Ghose S, Gleason KA, Potts BW, Lewis-Amezcua K, Tamminga CA (2009) Differential expression of metabotropic glutamate receptors 2 and 3 in schizophrenia: a mechanism for antipsychotic drug action? Am J Psychiatry 166:812-820
40. Gigante AD, Andreazza AC, Lafer B, Yatham LN, Beasley CL, Young LT (2011) Decreased mRNA expression of uncoupling protein 2, a mitochondrial proton transporter, in post-mortem prefrontal cortex from patients with bipolar disorder and schizophrenia. Neurosci Lett 505:47-51
41. Gluck MR, Thomas RG, Davis KL, Haroutunian V (2002) Implications for altered glutamate and GABA metabolism in the dorsolateral prefrontal cortex of aged schizophrenic patients. Am J Psychiatry 159:1165-1173
42. Goff DC, Coyle JT (2001) The emerging role of glutamate in the pathophysiology and treatment of schizophrenia. Am J Psychiatry 158:1367-1377
43. Grosche J, Matyash V, Moller T, Verkhratsky A, Reichenbach A, Kettenmann H (1999) Microdomains for neuron-glia interaction: parallel fiber signaling to Bergmann glial cells. Nat Neurosci 2:139-143
44. Grosche J, Kettenmann H, Reichenbach A (2002) Bergmann glial cells form distinct morphological structures to interact with cerebellar neurons. J Neurosci Res 68:138-149
45. Gupta DS, McCullumsmith RE, Beneyto M, Haroutunian V, Davis KL, Meador-Woodruff JH (2005) Metabotropic glutamate receptor protein expression in the prefrontal cortex and striatum in schizophrenia. Synapse 57:123-131
46. Hardingham GE, Bading H (2002) Coupling of extrasynaptic NMDA receptors to a CREB shut-off pathway is developmentally regulated. Biochim Biophys Acta 1600:148-153
47. Hardingham GE, Fukunaga Y, Bading H (2002) Extrasynaptic NMDARs oppose synaptic NMDARs by triggering CREB shut-off and cell death pathways. Nat Neurosci 5:405-414
48. Harney SC, Jane DE, Anwyl R (2008) Extrasynaptic NR2D-containing NMDARs are recruited to the synapse during LTP of NMDAR-EPSCs. J Neurosci 28:11685-11694
49. Harrison PJ (2004) The hippocampus in schizophrenia: a review of the neuropathological evidence and its pathophysiological implications. Psychopharmacology 174:151-162
50. Hashimoto T, Volk DW, Eggan SM, Mirnics K, Pierri JN, Sun Z, Sampson AR, Lewis DA (2003) Gene expression deficits in a subclass of GABA neurons in the prefrontal cortex of subjects with schizophrenia. J Neurosci 23:6315-6326
51. Haydon PG, Carmignoto G (2006) Astrocyte control of synaptic transmission and neurovascular coupling. Physiol Rev 86:1009-1031
52. Healy DJ, Haroutunian V, Powchik P, Davidson M, Davis KL, Watson SJ, Meador-Woodruff JH (1998) AMPA receptor binding and subunit mRNA expression in prefrontal cortex and striatum of elderly schizophrenics. Neuropsychopharmacology 19:278-286
53. Hemler ME (2003) Tetraspanin proteins mediate cellular penetration, invasion, and fusion events and define a novel type of membrane microdomain. Ann Rev Cell Dev Biol 19:397-422
54. Hertz L (2011) Astrocytic energy metabolism and glutamate formation-relevance for 13C-NMR spectroscopy and importance of cytosolic/mitochondrial trafficking. Magn Reson Imaging 29:1319-1329
55. Hertzmann M, Reba RC, Kotlyarov EV (1990) Single photon emission computed tomography in phencyclidine and related drug abuse. Am J Psychiatry 147:255-256
56. Hollmann M, Heinemann S (1994) Cloned glutamate receptors. Annu Rev Neurosci 17:31-108
57. Hollmann M, Maron C, Heinemann S (1994) N-glycosylation site tagging suggests a three transmembrane domain topology for the glutamate receptor GluR1. Neuron 13:1331-1343
58. Horiuchi Y et al. (2012) Association of SNPs linked to increased expression of SLC1A1 with schizophrenia. American journal of medical genetics Part B. Neuropsychiatr Genet 159B:30-37
59. Huang HS, Akbarian S (2007) GAD1 mRNA expression and DNA methylation in prefrontal cortex of subjects with schizophrenia. PloS ONE 2:e809
60. Huang YH, Bergles DE (2004) Glutamate transporters bring competition to the synapse. Curr Opin Neurobiol 14:346-352
61. Huang HS, Matevossian A, Whittle C, Kim SY, Schumacher A, Baker SP, Akbarian S (2007) Prefrontal dysfunction in schizophrenia involves mixed-lineage leukemia 1-regulated histone methylation at GABAergic gene promoters. J Neurosci 27:11254-11262
62. Hutcheson NL, Reid MA, White DM, Kraguljac NV, Avsar KB, Bolding MS, Knowlton RC, den Hollander JA, Lahti AC (2012) Multimodal analysis of the hippocampus in schizophrenia using proton magnetic resonance spectroscopy and functional magnetic resonance imaging. Schizophr Res 140:136-142
63. Ibrahim HM, Hogg AJ Jr, Healy DJ, Haroutunian V, Davis KL, Meador-Woodruff JH (2000) Ionotropic glutamate receptor binding and subunit mRNA expression in thalamic nuclei in schizophrenia. Am J Psychiatry 157:1811-1823
64. Illarionova NB, Gunnarson E, Li Y, Brismar H, Bondar A, Zelenin S, Aperia A (2010) Functional and molecular interactions between aquaporins and Na, K-ATPase. Neuroscience 168:915-925
65. Jackson M, Song W, Liu MY, Jin L, Dykes-Hoberg M, Lin CI, Bowers WJ, Federoff HJ, Sternweis PC, Rothstein JD (2001) Modulation of the neuronal glutamate transporter EAAT4 by two interacting proteins. Nature 410:89-93
66. Javitt DC, Zukin SR (1991) Recent advances in the phencyclidine model of schizophrenia. Am J Psychiatry 148:1301-1308
67. Joyce JN, Meador-Woodruff JH (1997) Linking the family of D2 receptors to neuronal circuits in human brain: insights into schizophrenia. Neuropsychopharmacology 16:375-384
68. Kalandadze A, Wu Y, Fournier K, Robinson MB (2004) Identification of motifs involved in endoplasmic reticulum retention-forward trafficking of the GLT-1 subtype of glutamate transporter. J Neurosci 24:5183-5192
69. Karlsson RM, Tanaka K, Heilig M, Holmes A (2008) Loss of glial glutamate and aspartate transporter (excitatory amino acid transporter 1) causes locomotor hyperactivity and exaggerated responses to psychotomimetics: rescue by haloperidol and metabotropic glutamate 2/3 agonist. Biol Psychiatry 64:810-814
70. Karlsson RM, Tanaka K, Saksida LM, Bussey TJ, Heilig M, Holmes A (2009) Assessment of glutamate transporter GLAST (EAAT1)-deficient mice for phenotypes relevant to the negative and executive/cognitive symptoms of schizophrenia. Neuropsychopharmacology 34:1578-1589
71. Kay SR (1990) Significance of the positive-negative distinction in schizophrenia. Schizophr Bull 16:635-652
72. Kraguljac NV, Reid MA, White DM, den Hollander J, Lahti AC (2012a) Regional decoupling of N-acetyl-aspartate and glutamate in schizophrenia. Neuropsychopharmacology 37:2635-2642
73. Kraguljac NV, Reid M, White D, Jones R, den Hollander J, Lowman D, Lahti AC (2012b) Neurometabolites in schizophrenia and bipolar disorder-a systematic review and meta-analysis. Psychiatry Res 203:111-125
74. Kristiansen LV, Meador-Woodruff JH (2005) Abnormal striatal expression of transcripts encoding NMDA interacting PSD proteins in schizophrenia, bipolar disorder and major depression. Schizophr Res 78:87-93
75. Kullmann DM, Asztely F (1998) Extrasynaptic glutamate spillover in the hippocampus: evidence and implications. Trends Neurosci 21:8-14
76. Lahti AC, Tamminga CA (1995) Recent developments in the neuropharmacology of schizophrenia. Am J Health Syst Pharm 52:S5-S8
77. Laruelle M, Abi-Dargham A, Gil R, Kegeles L, Innis R (1999) Increased dopamine transmission in schizophrenia: relationship to illness phases. Biol Psychiatry 46:56-72
78. Laruelle M, Slifstein M, Huang Y (2003) Relationships between radiotracer properties and image quality in molecular imaging of the brain with positron emission tomography. Mol Imag Biol 5:363-375
79. Lauriat TL, Dracheva S, Chin B, Schmeidler J, McInnes LA, Haroutunian V (2006) Quantitative analysis of glutamate transporter mRNA expression in prefrontal and primary visual cortex in normal and schizophrenic brain. Neuroscience 137:843-851
80. Lehre KP, Danbolt NC (1998) The number of glutamate transporter subtype molecules at glutamatergic synapses: chemical and stereological quantification in young adult rat brain. J Neurosci 18:8751-8757
81. Leveille F, El Gaamouch F, Gouix E, Lecocq M, Lobner D, Nicole O, Buisson A (2008) Neuronal viability is controlled by a functional relation between synaptic and extrasynaptic NMDA receptors. FASEB J 22:4258-4271
82. Levy LM, Warr O, Attwell D (1998) Stoichiometry of the glial glutamate transporter GLT-1 expressed inducibly in a Chinese hamster ovary cell line selected for low endogenous Na+-dependent glutamate uptake. J Neurosci 18:9620-9628
83. Lewis DA, Gonzalez-Burgos G (2008) Neuroplasticity of neocortical circuits in schizophrenia. Neuropsychopharmacology 33:141-165
84. Lewis DA, Levitt P (2002) Schizophrenia as a disorder of neurodevelopment. Annu Rev Neurosci 25:409-432
85. Lewis DA, Cruz DA, Melchitzky DS, Pierri JN (2001) Lamina-specific deficits in parvalbuminimmunoreactive varicosities in the prefrontal cortex of subjects with schizophrenia: evidence for fewer projections from the thalamus. Am J Psychiatry 158:1411-1422
86. Lewis DA, Glantz LA, Pierri JN, Sweet RA (2003) Altered cortical glutamate neurotransmission in schizophrenia: evidence from morphological studies of pyramidal neurons. Ann N Y Acad Sci 1003:102-112
87. Lewis DA, Volk DW, Hashimoto T (2004) Selective alterations in prefrontal cortical GABA neurotransmission in schizophrenia: a novel target for the treatment of working memory dysfunction. Psychopharmacology 174:143-150
88. Lewis DA, Hashimoto T, Morris HM (2008) Cell and receptor type-specific alterations in markers of GABA neurotransmission in the prefrontal cortex of subjects with schizophrenia. Neurotox Res 14:237-248
89. Lin SH, Maiese K (2001) The metabotropic glutamate receptor system protects against ischemic free radical programmed cell death in rat brain endothelial cells. J Cereb Blood Flow Metab 21:262-275
90. Lozovaya N, Melnik S, Tsintsadze T, Grebenyuk S, Kirichok Y, Krishtal O (2004a) Protective cap over CA1 synapses: extrasynaptic glutamate does not reach the postsynaptic density. Brain Res 1011:195-205
91. Lozovaya NA, Grebenyuk SE, Tsintsadze T, Feng B, Monaghan DT, Krishtal OA (2004b) Extrasynaptic NR2B and NR2D subunits of NMDA receptors shape 'superslow' afterburst EPSC in rat hippocampus. J Physiol 558:451-463
92. Malarkey EB, Parpura V (2008) Mechanisms of glutamate release from astrocytes. Neurochem Int 52:142-154
93. Malenka RC, Nicoll RA (1999) Long-term potentiation-a decade of progress? Science 285:1870-1874
94. Marcaggi P, Attwell D (2007) Short- and long-term depression of rat cerebellar parallel fibre synaptic transmission mediated by synaptic crosstalk. J Physiol 578:545-550
95. Marenco S, Weinberger DR (2000) The neurodevelopmental hypothesis of schizophrenia: following a trail of evidence from cradle to grave. Dev Psychopathol 12:501-527
96. Marie H, Billups D, Bedford FK, Dumoulin A, Goyal RK, Longmore GD, Moss SJ, Attwell D (2002) The amino terminus of the glial glutamate transporter GLT-1 interacts with the LIM protein Ajuba. Mol Cell Neurosci 19:152-164
97. Marsman A, van den Heuvel MP, Klomp DW, Kahn RS, Luijten PR, Hulshoff Pol HE (2011) Glutamate in schizophrenia: a focused review and meta-analysis of 1H-MRS studies. Schizophr Bull 39:120-129
98. Massie A, Cnops L, Smolders I, McCullumsmith R, Kooijman R, Kwak S, Arckens L, Michotte Y (2008) High-affinity Na+/K+-dependent glutamate transporter EAAT4 is expressed throughout the rat fore- and midbrain. J Com Neurol 511:155-172
99. Masson J, Sagne C, Hamon M, El Mestikawy S (1999a) Neurotransmitter transporters in the central nervous system. Pharmacol Rev 51:439-464
100. Masson J, Cervera P, Cote S, Morisette J, Aidouni Z, Giros B, Hamon M, Falardeau P, Mestikawy SE (1999b) Characterization and distribution of Hxt1, a Na (+)/Cl (-)-dependent orphan transporter, in the human brain. J Neurosci Res 56:146-159
101. Matute C, Melone M, Vallejo-Illarramendi A, Conti F (2005) Increased expression of the astrocytic glutamate transporter GLT-1 in the prefrontal cortex of schizophrenics. Glia 49:451-455
102. McCullumsmith RE, Meador-Woodruff JH (2002) Striatal excitatory amino acid transporter transcript expression in schizophrenia, bipolar disorder, and major depressive disorder. Neuropsychopharmacology 26:368-375
103. McCullumsmith RE, Meador-Woodruff JH (2011) Novel approaches to the study of postmortem brain in psychiatric illness: old limitations and new challenges. Biol Psychiatry 69:127-133
104. McCullumsmith R, Clinton S, Meador-Woodruff J (2004a) Schizophrenia as a disorder of neuroplasticity. Int Rev Neurobiol 59:19-45
105. McCullumsmith RE, Clinton SM, Meador-Woodruff JH (2004b) Schizophrenia as a disorder of neuroplasticity. Int Rev Neurobiol 59:19-45
106. McCullumsmith RE, Hammond J, Funk A, Meador-Woodruff JH (2012) Recent advances in targeting the Ionotropic glutamate receptors in treating schizophrenia. Curr Pharm Biotechnol 13:1535-1542
107. McKenna MC (2011) Glutamate dehydrogenase in brain mitochondria: do lipid modifications and transient metabolon formation influence enzyme activity? Neurochem Int 59:525-533
108. Meador-Woodruff JH, Hogg AJ Jr, Smith RE (2001a) Striatal ionotropic glutamate receptor expression in schizophrenia, bipolar disorder, and major depressive disorder. Brain Res Bull 55:631-640
109. Meador-Woodruff JH, Davis KL, Haroutunian V (2001b) Abnormal kainate receptor expression in prefrontal cortex in schizophrenia. Neuropsychopharmacology 24:545-552
110. Montana V, Ni Y, Sunjara V, Hua X, Parpura V (2004) Vesicular glutamate transporter-dependent glutamate release from astrocytes. J Neurosci 24:2633-2642
111. Nakagawa T, Otsubo Y, Yatani Y, Shirakawa H, Kaneko S (2008) Mechanisms of substrate transport-induced clustering of a glial glutamate transporter GLT-1 in astroglial-neuronal cultures. Eur J Neurosci 28:1719-1730
112. Newpher TM, Ehlers MD (2009) Spine microdomains for postsynaptic signaling and plasticity. Trends Cell Biol 19:218-227
113. Nudmamud-Thanoi S, Piyabhan P, Harte MK, Cahir M, Reynolds GP (2007) Deficits of neuronal glutamatergic markers in the caudate nucleus in schizophrenia. J Neural Transm Suppl 2007:281-285
114. Ohnuma T, Augood SJ, Arai H, McKenna PJ, Emson PC (1998) Expression of the human excitatory amino acid transporter 2 and metabotropic glutamate receptors 3 and 5 in the prefrontal cortex from normal individuals and patients with schizophrenia. Brain Res Mol Brain Res 56:207-217
115. Ohnuma T, Tessler S, Arai H, Faull RL, McKenna PJ, Emson PC (2000) Gene expression of metabotropic glutamate receptor 5 and excitatory amino acid transporter 2 in the schizophrenic hippocampus. Brain Res Mol Brain Res 85:24-31
116. Patel DR, Young AM, Croucher MJ (2001) Presynaptic alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor-mediated stimulation of glutamate and GABA release in the rat striatum in vivo: a dual-label microdialysis study. Neuroscience 102:101-111
117. Patil ST, Zhang L, Martenyi F, Lowe SL, Jackson KA, Andreev BV, Avedisova AS, Bardenstein LM, Gurovich IY, Morozova MA, Mosolov SN, Neznanov NG, Reznik AM, Smulevich AB, Tochilov VA, Johnson BG, Monn JA, Schoepp DD (2007) Activation of mGlu2/3 receptors as a new approach to treat schizophrenia: a randomized phase 2 clinical trial. Nat Med 13:1102-1107
118. Potkin SG, Turner JA, Brown GG, McCarthy G, Greve DN, Glover GH, Manoach DS, Belger A, Diaz M, Wible CG, Ford JM, Mathalon DH, Gollub R, Lauriello J, O'Leary D, van Erp TG, Toga AW, Preda A, Lim KO, Fbirn (2009) Working memory and DLPFC inefficiency in schizophrenia: the FBIRN study. Schizophr Bull 35:19-31
119. Rajji TK, Mulsant BH (2008) Nature and course of cognitive function in late-life schizophrenia: a systematic review. Schizophr Res 102:122-140
120. Rajkowska G, Selemon LD, Goldman-Rakic PS (1998) Neuronal and glial somal size in the prefrontal cortex: a postmortem morphometric study of schizophrenia and Huntington disease. Arch Gen Psychiatry 55:215-224
121. Rajkowska G, Miguel-Hidalgo JJ, Makkos Z, Meltzer H, Overholser J, Stockmeier C (2002) Layer-specific reductions in GFAP-reactive astroglia in the dorsolateral prefrontal cortex in schizophrenia. Schizophr Res 57:127-138
122. Rao JS, Kellom M, Reese EA, Rapoport SI, Kim HW (2012) Dysregulated glutamate and dopamine transporters in postmortem frontal cortex from bipolar and schizophrenic patients. J Affect Disord 136:63-71
123. Regan MR, Huang YH, Kim YS, Dykes-Hoberg MI, Jin L, Watkins AM, Bergles DE, Rothstein JD (2007) Variations in promoter activity reveal a differential expression and physiology of glutamate transporters by glia in the developing and mature CNS. J Neurosci 27:6607-6619
124. Regenold WT, Pratt M, Nekkalapu S, Shapiro PS, Kristian T, Fiskum G (2012) Mitochondrial detachment of hexokinase 1 in mood and psychotic disorders: implications for brain energy metabolism and neurotrophic signaling. J Psychiatr Res 46:95-104
125. Rusakov DA, Kullmann DM (1998) Extrasynaptic glutamate diffusion in the hippocampus: ultrastructural constraints, uptake, and receptor activation. J Neurosci 18:3158-3170
126. Salt TE, Eaton SA, Turner JP (1996) Characterization of the metabotropic glutamate receptors (mGluRs) which modulate GABA-mediated inhibition in the ventrobasal thalamus. Neurochem Int 29:317-322
127. Schluter K, Figiel M, Rozyczka J, Engele J (2002) CNS region-specific regulation of glial glutamate transporter expression. Eur J Neurosci 16:836-842
128. Schoepp DD (2001) Unveiling the functions of presynaptic metabotropic glutamate receptors in the central nervous system. J Pharmacol Exp Ther 299:12-20
129. Selemon LD, Rajkowska G, Goldman-Rakic PS (1995) Abnormally high neuronal density in the schizophrenic cortex. A morphometric analysis of prefrontal area 9 and occipital area 17. Arch Gen Psychiatry 52:805-818 (discussion 819-820)
130. Sem'yanov AV (2005) Diffusional extrasynaptic neurotransmission via glutamate and GABA. Neurosci Behav Physiol 35:253-266
131. Shan D, Haroutunian V, Meador-Woodruff JH, McCullumsmith RE (2012) Expression of equilibrative nucleoside transporter type 1 protein in elderly patients with schizophrenia. Neuroreport 23:224-227
132. Shan D, Lucas EK, Drummond JB, Haroutunian V, Meador-Woodruff JH, McCullumsmith RE (2013) Abnormal expression of glutamate transporters in temporal lobe areas in elderly patients with schizophrenia. Schizophr Res 144:1-8
133. Skytt DM, Klawonn AM, Stridh MH, Pajecka K, Patruss Y, Quintana-Cabrera R, Bolanos JP, Schousboe A, Waagepetersen HS (2012) siRNA knock down of glutamate dehydrogenase in astrocytes affects glutamate metabolism leading to extensive accumulation of the neuroactive amino acids glutamate and aspartate. Neurochem Int 61:490-497
134. Smith RE, Haroutunian V, Davis KL, Meador-Woodruff JH (2001) Expression of excitatory amino acid transporter transcripts in the thalamus of subjects with schizophrenia. Am J Psychiatry 158:1393-1399
135. Somerville SM, Lahti AC, Conley RR, Roberts RC (2011) Mitochondria in the striatum of subjects with schizophrenia: relationship to treatment response. Synapse 65:215-224
136. Somerville SM, Conley RR, Roberts RC (2012) Striatal mitochondria in subjects with chronic undifferentiated vs. chronic paranoid schizophrenia. Synapse 66:29-41
137. Spat A, Fulop L, Koncz P, Szanda G (2009) When is high-Ca+ microdomain required for mitochondrial Ca+ uptake? Acta physiologica 195:139-147
138. Stobart JL, Anderson CM (2013) Multifunctional role of astrocytes as gatekeepers of neuronal energy supply. Front Cell Neurosci 7:38
139. Szabadkai G, Rizzuto R (2007) Chaperones as parts of organelle networks. Adv Exp Med Biol 594:64-77
140. Szoke A, Meary A, Trandafir A, Bellivier F, Roy I, Schurhoff F, Leboyer M (2008) Executive deficits in psychotic and bipolar disorders-implications for our understanding of schizoaffective disorder. Eur Psychiatry 23:20-25
141. Takamori S, Riedel D, Jahn R (2000) Immunoisolation of GABA-specific synaptic vesicles defines a functionally distinct subset of synaptic vesicles. J Neurosci 20:4904-4911
142. Talbot K, Ong WY, Blake DJ, Tang J, Louneva N, Carlson GC, Arnold SE (2009) Dysbindin-1 and its protein family. In: Lajtha A, Javitt D, Kantrowitz J (eds) Handbook of neurochemistry and molecular neurobiology. Springer, New York, pp 107-241
143. Tamminga C (1999) Glutamatergic aspects of schizophrenia. Br J Psychiatry Suppl 1999:12-15
144. Theberge J, Bartha R, Drost DJ, Menon RS, Malla A, Takhar J, Neufeld RW, Rogers J, Pavlosky W, Schaefer B, Densmore M, Al-Semaan Y, Williamson PC (2002) Glutamate and glutamine measured with 4. 0 T proton MRS in never-treated patients with schizophrenia and healthy volunteers. Am J Psychiatry 159:1944-1946
145. Tong G, Jahr CE (1994) Block of glutamate transporters potentiates postsynaptic excitation. Neuron 13:1195-1203
146. Tsai G, Coyle J (2002) Glutamatergic mechanisms in schizophrenia. Annu Rev Pharmacol Toxicol 42:165-179
147. Tsvetkov E, Shin RM, Bolshakov VY (2004) Glutamate uptake determines pathway specificity of long-term potentiation in the neural circuitry of fear conditioning. Neuron 41:139-151
148. Tzingounis AV, Wadiche JI (2007) Glutamate transporters: confining runaway excitation by shaping synaptic transmission. Nat Rev Neurosci 8:935-947
149. Uranova N, Orlovskaya D, Vikhreva O, Zimina I, Kolomeets N, Vostrikov V, Rachmanova V (2001) Electron microscopy of oligodendroglia in severe mental illness. Brain Res Bull 55:597-610
150. Utsunomiya-Tate N, Endou H, Kanai Y (1996) Cloning and functional characterization of a system ASC-like Na+-dependent neutral amino acid transporter. J Biol Chem 271:14883-14890
151. Volk DW, Eggan SM, Lewis DA (2010) Alterations in metabotropic glutamate receptor 1alpha and regulator of G protein signaling 4 in the prefrontal cortex in schizophrenia. Am J Psychiatry 167:1489-1498
152. Watanabe C, Sakurada T, Okuda K, Sakurada C, Ando R, Sakurada S (2003) The role of spinal nitric oxide and glutamate in nociceptive behaviour evoked by high-dose intrathecal morphine in rats. Pain 106:269-283
153. Watase K, Hashimoto K, Kano M, Yamada K, Watanabe M, Inoue Y, Okuyama S, Sakagawa T, Ogawa S, Kawashima N, Hori S, Takimoto M, Wada K, Tanaka K (1998) Motor discoordination and increased susceptibility to cerebellar injury in GLAST mutant mice. Eur J Neurosci 10:976-988
154. Weng HR, Chen JH, Pan ZZ, Nie H (2007) Glial glutamate transporter 1 regulates the spatial and temporal coding of glutamatergic synaptic transmission in spinal lamina II neurons. Neurosci 149:898-907
155. Wobrock T, Schneider M, Kadovic D, Schneider-Axmann T, Ecker UK, Retz W, Rosler M, Falkai P (2008) Reduced cortical inhibition in first-episode schizophrenia. Schizophr Res 105:252-261
156. Zanello A, Curtis L, Badan Ba M, Merlo MC (2009) Working memory impairments in first-episode psychosis and chronic schizophrenia. Psychiatry Res 165:10-18
157. Zerangue N, Kavanaugh MP (1996) Flux coupling in a neuronal glutamate transporter. Nature 383:634-637