Dysfunctional astrocytes as key players in the pathogenesis of central nervous system disorders

Tsacopoulos, 1996, Metabolic coupling between glia and neurons, J Neurosci, 16, 877, 10.1523/JNEUROSCI.16-03-00877.1996 Sanchez-Abarca, 2001, Oligodendrocytes use lactate as a source of energy and as a precursor of lipids, Glia, 36, 321, 10.1002/glia.1119 Brown, 2004, Energy transfer from astrocytes to axons: the role of CNS glycogen, Neurochem Int, 45, 529, 10.1016/j.neuint.2003.11.005 Kimelberg, 1995, Receptors on astrocytes—what possible functions?, Neurochem Int, 26, 27, 10.1016/0197-0186(94)00118-E Verkman, 2006, Three distinct roles of aquaporin-4 in brain function revealed by knockout mice, Biochim Biophys Acta, 1758, 1085, 10.1016/j.bbamem.2006.02.018 Butt, 2006, Inwardly rectifying potassium channels (Kir) in central nervous system glia: a special role for Kir4.1 in glial functions, J Cell Mol Med, 10, 33, 10.1111/j.1582-4934.2006.tb00289.x Amiry-Moghaddam, 2003, The molecular basis of water transport in the brain, Nat Rev, 4, 991, 10.1038/nrn1252 Anderson, 2000, Astrocyte glutamate transport: review of properties, regulation, and physiological functions, Glia, 32, 1, 10.1002/1098-1136(200010)32:1<1::AID-GLIA10>3.0.CO;2-W Doble, 1999, The role of excitotoxicity in neurodegenerative disease: implications for therapy, Pharmacol Ther, 81, 163, 10.1016/S0163-7258(98)00042-4 Shigeri, 2004, Molecular pharmacology of glutamate transporters, EAATs and VGLUTs, Brain Res Brain Res Rev, 45, 250, 10.1016/j.brainresrev.2004.04.004 Zaheer, 1995, Expression of mRNAs of multiple growth factors and receptors by astrocytes and glioma cells: detection with reverse transcription-polymerase chain reaction, Cell Mol Neurobiol, 15, 221, 10.1007/BF02073330 Helmuth, 2001, Neuroscience. Glia tell neurons to build synapses, Science, 291, 569, 10.1126/science.291.5504.569A Farina, 2007, Astrocytes are active players in cerebral innate immunity, Trends Immunol, 28, 138, 10.1016/j.it.2007.01.005 Gavrilyuk, 2002, Norepinephrine increases I kappa B alpha expression in astrocytes, J Biol Chem, 277, 29662, 10.1074/jbc.M203256200 Frohman, 2001, Autonomic regulation of neuroimmunological responses: implications for multiple sclerosis, J Clin Immunol, 21, 61, 10.1023/A:1011016124524 De Keyser, 2003, Are astrocytes central players in the pathophysiology of multiple sclerosis?, Arch Neurol, 60, 132, 10.1001/archneur.60.1.132 Bianco, 2005, Astrocyte-derived ATP induces vesicle shedding and IL-1 beta release from microglia, J Immunol, 174, 7268, 10.4049/jimmunol.174.11.7268 Farahani, 2005, Alterations in metabolism and gap junction expression may determine the role of astrocytes as “good Samaritans” or executioners, Glia, 50, 351, 10.1002/glia.20213 Scemes, 2006, Astrocyte calcium waves: what they are and what they do, Glia, 54, 716, 10.1002/glia.20374 Nedergaard, 1994, Direct signaling from astrocytes to neurons in cultures of mammalian brain cells, Science, 263, 1768, 10.1126/science.8134839 Nedergaard, 1995, Gap junctions are required for the propagation of spreading depression, J Neurobiol, 28, 433, 10.1002/neu.480280404 Cotrina, 1998, Connexins regulate calcium signaling by controlling ATP release, Proc Natl Acad Sci U S A, 95, 15735, 10.1073/pnas.95.26.15735 Nedergaard, 2003, New roles for astrocytes: redefining the functional architecture of the brain, Trends Neurosci, 26, 523, 10.1016/j.tins.2003.08.008 Deschepper, 1998, Peptide receptors on astrocytes, Front Neuroendocrinol, 19, 20, 10.1006/frne.1997.0161 Porter, 1997, Astrocytic neurotransmitter receptors in situ and in vivo, Prog Neurobiol, 51, 439, 10.1016/S0301-0082(96)00068-8 Newman, 2003, New roles for astrocytes: regulation of synaptic transmission, Trends Neurosci, 26, 536, 10.1016/S0166-2236(03)00237-6 Pasti, 1995, Long-lasting changes of calcium oscillations in astrocytes. A new form of glutamate-mediated plasticity, J Biol Chem, 270, 15203, 10.1074/jbc.270.25.15203 Sanchez-Del-Rio, 2006, New insights into migraine pathophysiology, Curr Opin Neurol, 19, 294, 10.1097/01.wco.0000227041.23694.5c Martins-Ferreira, 2000, Perspectives on spreading depression, Brain Res Brain Res Rev, 32, 215, 10.1016/S0165-0173(99)00083-1 Silberstein, 2004, Migraine pathophysiology and its clinical implications, Cephalalgia, 24, 2, 10.1111/j.1468-2982.2004.00892.x Peters, 2003, Different mechanisms promote astrocyte Ca2+ waves and spreading depression in the mouse neocortex, J Neurosci, 23, 9888, 10.1523/JNEUROSCI.23-30-09888.2003 Ayata, 2006, Suppression of cortical spreading depression in migraine prophylaxis, Ann Neurol, 59, 652, 10.1002/ana.20778 Capendeguy, 2004, Functional effects of Na+,K+-ATPase gene mutations linked to familial hemiplegic migraine, Neuromolecular Med, 6, 105, 10.1385/NMM:6:2-3:105 Binder, 2006, Functional changes in astroglial cells in epilepsy, Glia, 54, 358, 10.1002/glia.20394 Tian, 2005, An astrocytic basis of epilepsy, Nat Med, 11, 973, 10.1038/nm1277 Hinterkeuser, 2000, Astrocytes in the hippocampus of patients with temporal lobe epilepsy display changes in potassium conductances, Eur J Neurosci, 12, 2087, 10.1046/j.1460-9568.2000.00104.x Kivi, 2000, Effects of barium on stimulus-induced rises of [K+]o in human epileptic non-sclerotic and sclerotic hippocampal area CA1, Eur J Neurosci, 12, 2039, 10.1046/j.1460-9568.2000.00103.x Schroder, 2000, Functional and molecular properties of human astrocytes in acute hippocampal slices obtained from patients with temporal lobe epilepsy, Epilepsia, 41, S181, 10.1111/j.1528-1157.2000.tb01578.x Schroder, 2002, AMPA receptor-mediated modulation of inward rectifier K+ channels in astrocytes of mouse hippocampus, Mol Cell Neurosci, 19, 447, 10.1006/mcne.2001.1080 Proper, 2002, Distribution of glutamate transporters in the hippocampus of patients with pharmaco-resistant temporal lobe epilepsy, Brain, 125, 32, 10.1093/brain/awf001 Fotheringham, 2007, Association of human herpesvirus-6B with mesial temporal lobe epilepsy, PLoS Med, 4, e180, 10.1371/journal.pmed.0040180 Korn, 2005, Focal cortical dysfunction and blood-brain barrier disruption in patients with postconcussion syndrome, J Clin Neurophysiol, 22, 1, 10.1097/01.WNP.0000150973.24324.A7 Tomkins, 2001, Frequent blood-brain barrier disruption in he human cerebral cortex, Cell Mol Neurobiol, 21, 675, 10.1023/A:1015147920283 Uhlmann, 2002, Astrocyte-specific TSC1 conditional knockout mice exhibit abnormal neuronal organization and seizures, Ann Neurol, 52, 285, 10.1002/ana.10283 Wong, 2003, Impaired glial glutamate transport in a mouse tuberous sclerosis epilepsy model, Ann Neurol, 54, 251, 10.1002/ana.10648 Jansen, 2005, Epileptogenesis and reduced inward rectifier potassium current in tuberous sclerosis complex-1-deficient astrocytes, Epilepsia, 46, 1871, 10.1111/j.1528-1167.2005.00289.x Bien, 2002, The natural history of Rasmussen's encephalitis, Brain, 125, 1751, 10.1093/brain/awf176 Whitney, 2000, GluR3 autoantibodies destroy neural cells in a complement-dependent manner modulated by complement regulatory proteins, J Neurosci, 20, 7307, 10.1523/JNEUROSCI.20-19-07307.2000 Bien, 2002, Diagnosis and staging of Rasmussen's encephalitis by serial MRI and histopathology, Neurology, 58, 250, 10.1212/WNL.58.2.250 Bauer, 2007, Astrocytes are a specific immunological target in Rasmussen's encephalitis, Ann Neurol, 62, 67, 10.1002/ana.21148 Gordon, 2003, Alexander disease, Eur J Paediatr Neurol, 7, 395, 10.1016/j.ejpn.2003.09.004 Johnson, 2004, Alexander disease: a leukodystrophy caused by a mutation in GFAP, Neurochem Res, 29, 961, 10.1023/B:NERE.0000021240.30518.2c Messing, 1998, Fatal encephalopathy with astrocyte inclusions in GFAP transgenic mice, Am J Pathol, 152, 391 Brenner, 2001, Mutations in GFAP, encoding glial fibrillary acidic protein, are associated with Alexander disease, Nat Genet, 27, 117, 10.1038/83679 Messing, 2003, GFAP: functional implications gleaned from studies of genetically engineered mice, Glia, 43, 87, 10.1002/glia.10219 van der Knaap, 1995, Leukoencephalopathy with swelling and a discrepantly mild clinical course in eight children, Ann Neurol, 37, 324, 10.1002/ana.410370308 van der Knaap, 1996, Histopathology of an infantile-onset spongiform leukoencephalopathy with a discrepantly mild clinical course, Acta Neuropathol (Berl), 92, 206, 10.1007/s004010050510 Topcu, 2000, Vacuoliting megalencephalic leukoencephalopathy with subcortical cysts, mapped to chromosome 22qtel, Am J Hum Genet, 66, 733, 10.1086/302758 Boor, 2005, MLC1: a novel protein in distal astroglial processes, J Neuropathol Exp Neurol, 64, 412, 10.1093/jnen/64.5.412 Schmitt, 2003, The brain-specific protein MLC1 implicated in megalencephalic leukoencephalopathy with subcortical cysts is expressed in glial cells in the murine brain, Glia, 44, 283, 10.1002/glia.10304 van der Knaap, 2006, Vanishing white matter disease, Lancet Neurol, 5, 413, 10.1016/S1474-4422(06)70440-9 van Kollenburg, 2006, Glia-specific activation of all pathways of the unfolded protein response in vanishing white matter disease, J Neuropathol Exp Neurol, 65, 707, 10.1097/01.jnen.0000228201.27539.50 Dietrich, 2005, EIF2B5 mutations compromise GFAP+ astrocyte generation in vanishing white matter leukodystrophy, Nat Med, 11, 277, 10.1038/nm1195 Barnett, 2004, Relapsing and remitting multiple sclerosis: pathology of the newly forming lesion, Ann Neurol, 55, 458, 10.1002/ana.20016 De Keyser, 1999, Astrocytes in multiple sclerosis lack beta-2 adrenergic receptors, Neurology, 53, 1628, 10.1212/WNL.53.8.1628 De Keyser, 2004, Astrocytic beta2-adrenergic receptors and multiple sclerosis, Neurobiol Dis, 15, 331, 10.1016/j.nbd.2003.10.012 van Loo, 2006, Inhibition of transcription factor NF-kappaB in the central nervous system ameliorates autoimmune encephalomyelitis in mice, Nat Immunol, 7, 954, 10.1038/ni1372 Zeinstra, 2003, Reactive astrocytes in chronic active lesions of multiple sclerosis express costimulatory molecules B7-1 and B7-2, J Neuroimmunol, 135, 166, 10.1016/S0165-5728(02)00462-9 Zeinstra, 2000, Astrocytes in chronic active multiple sclerosis plaques express MHC class II molecules, Neuroreport, 11, 89, 10.1097/00001756-200001170-00018 Lucchinetti, 2000, Heterogeneity of multiple sclerosis lesions: implications for the pathogenesis of demyelination, Ann Neurol, 47, 707, 10.1002/1531-8249(200006)47:6<707::AID-ANA3>3.0.CO;2-Q Viehover, 2001, Neuregulin: an oligodendrocyte growth factor absent in active multiple sclerosis lesions, Dev Neurosci, 23, 377, 10.1159/000048721 Kong, 2002, Up-regulation of 5-HT2B receptor density and receptor-mediated glycogenolysis in mouse astrocytes by long-term fluoxetine administration, Neurochem Res, 27, 113, 10.1023/A:1014862808126 Mostert, 2006, Fluoxetine increases cerebral white matter NAA/Cr ratio in patients with multiple sclerosis, Neurosci Lett, 402, 22, 10.1016/j.neulet.2006.03.042 Moffett, 2007, N-Acetylaspartate in the CNS: from neurodiagnostics to neurobiology, Prog Neurobiol, 81, 89, 10.1016/j.pneurobio.2006.12.003 De Keyser, 2001, Disappearance of beta2-adrenergic receptors on astrocytes in canine distemper encephalitis: possible implications for the pathogenesis of multiple sclerosis, Neuroreport, 12, 191, 10.1097/00001756-200102120-00004 Lennon, 2004, A serum autoantibody marker of neuromyelitis optica: distinction from multiple sclerosis, Lancet, 364, 2106, 10.1016/S0140-6736(04)17551-X Lennon, 2005, IgG marker of optic-spinal multiple sclerosis binds to the aquaporin-4 water channel, J Exp Med, 202, 473, 10.1084/jem.20050304 Sinclair, 2007, Absence of aquaporin-4 expression in lesions of neuromyelitis optica but increased expression in multiple sclerosis lesions and normal-appearing white matter, Acta Neuropathol (Berl), 113, 187, 10.1007/s00401-006-0169-2 Misu, 2006, Loss of aquaporin-4 in active perivascular lesions in neuromyelitis optica: a case report, Tohoku J Exp Med, 209, 269, 10.1620/tjem.209.269 Pittock, 2006, Neuromyelitis optica brain lesions localized at sites of high aquaporin 4 expression, Arch Neurol, 63, 964, 10.1001/archneur.63.7.964 Nath, 2002, Human immunodeficiency virus (HIV) proteins in neuropathogenesis of HIV dementia, J Infect Dis, 186, S193, 10.1086/344528 Avison, 2002, Understanding pathogenesis and treatment of HIV dementia: a role for magnetic resonance?, Trends Neurosci, 25, 468, 10.1016/S0166-2236(02)02234-8 Zhou, 2004, Astrocyte activation and dysfunction and neuron death by HIV-1 Tat expression in astrocytes, Mol Cell Neurosci, 27, 296, 10.1016/j.mcn.2004.07.003 Chauhan, 2003, Intracellular human immunodeficiency virus Tat expression in astrocytes promotes astrocyte survival but induces potent neurotoxicity at distant sites via axonal transport, J Biol Chem, 278, 13512, 10.1074/jbc.M209381200 Lehky, 1995, Detection of human T-lymphotropic virus type I (HTLV-I) tax RNA in the central nervous system of HTLV-I-associated myelopathy/tropical spastic paraparesis patients by in situ hybridization, Ann Neurol, 37, 167, 10.1002/ana.410370206 Akaoka, 2001, Functional changes in astrocytes by human T-lymphotropic virus type-1 T-lymphocytes, Virus Res, 78, 57, 10.1016/S0168-1702(01)00284-2 Szymocha, 2000, Human T-cell lymphotropic virus type 1-infected T lymphocytes impair catabolism and uptake of glutamate by astrocytes via Tax-1 and tumor necrosis factor alpha, J Virol, 74, 6433, 10.1128/JVI.74.14.6433-6441.2000 Donati, 2005, Variant-specific tropism of human herpesvirus 6 in human astrocytes, J Virol, 79, 9439, 10.1128/JVI.79.15.9439-9448.2005 Donati, 2003, Detection of human herpesvirus-6 in mesial temporal lobe epilepsy surgical brain resections, Neurology, 61, 1405, 10.1212/01.WNL.0000094357.10782.F9 McCullers, 1995, Human herpesvirus 6 is associated with focal encephalitis, Clin Infect Dis, 21, 571, 10.1093/clinids/21.3.571 Singh, 2000, Encephalitis caused by human herpesvirus-6 in transplant recipients: relevance of a novel neurotropic virus, Transplantation, 69, 2474, 10.1097/00007890-200006270-00002 Hall, 1994, Human herpesvirus-6 infection in children. A prospective study of complications and reactivation, N Engl J Med, 331, 432, 10.1056/NEJM199408183310703 Uesugi, 2000, Presence of human herpesvirus 6 and herpes simplex virus detected by polymerase chain reaction in surgical tissue from temporal lobe epileptic patients, Psychiatry Clin Neurosci, 54, 589, 10.1046/j.1440-1819.2000.00758.x Davies, 2002, Blood-brain barrier breakdown in septic encephalopathy and brain tumours, J Anat, 200, 639, 10.1046/j.1469-7580.2002.00065.x Kaur, 2006, Hypoxia-induced astrocytic reaction and increased vascular permeability in the rat cerebellum, Glia, 54, 826, 10.1002/glia.20420 Niermann, 2001, A novel role of vasopressin in the brain: modulation of activity-dependent water flux in the neocortex, J Neurosci, 21, 3045, 10.1523/JNEUROSCI.21-09-03045.2001 Norenberg, 1987, The role of astrocytes in hepatic encephalopathy, Neurochem Pathol, 6, 13, 10.1007/BF02833599 Lizardi-Cervera, 2003, Hepatic encephalopathy: a review, Ann Hepatol, 2, 122, 10.1016/S1665-2681(19)32137-4 Jalan, 2003, The molecular pathogenesis of hepatic encephalopathy, Int J Biochem Cell Biol, 35, 1175, 10.1016/S1357-2725(02)00396-5 Rao, 2004, Manganese induces the mitochondrial permeability transition in cultured astrocytes, J Biol Chem, 279, 32333, 10.1074/jbc.M402096200 Chan, 1999, Evidence for an astrocytic glutamate transporter deficit in hepatic encephalopathy, Neurochem Res, 24, 1397, 10.1023/A:1022532623281 Haberle, 2005, Congenital glutamine deficiency with glutamine synthetase mutations, N Engl J Med, 353, 1926, 10.1056/NEJMoa050456 Robinson, 1984, The molecular basis for the two different clinical presentations of classical pyruvate carboxylase deficiency, Am J Hum Genet, 36, 283 Brun, 1999, Pyruvate carboxylase deficiency: prenatal onset of ischemia-like brain lesions in two sibs with the acute neonatal form, Am J Med Gene, 84, 94, 10.1002/(SICI)1096-8628(19990521)84:2<94::AID-AJMG3>3.0.CO;2-1 Garcia-Cazorla, 2006, Pyruvate carboxylase deficiency: metabolic characteristics and new neurological aspects, Ann Neurol, 59, 121, 10.1002/ana.20709 Arnold, 2001, Pyruvate carboxylase deficiency. Report of a case and additional evidence for the “mild” phenotype, Clin Pediat, 40, 519, 10.1177/000992280104000909 Patel, 1999, Localization of Niemann-Pick C1 protein in astrocytes: implications for neuronal degeneration in Niemann-Pick type C disease, Proc Natl Acad Sci U S A, 96, 1657, 10.1073/pnas.96.4.1657 Miyajima, 2003, Aceruloplasminemia, an iron metabolic disorder, Neuropathology, 23, 345, 10.1046/j.1440-1789.2003.00521.x Oide, 2006, Iron overload and antioxidative role of perivascular astrocytes in aceruloplasminemia, Neuropathol Appl Neurobiol, 32, 170, 10.1111/j.1365-2990.2006.00710.x Miyajima, 1987, Familial apoceruloplasmin deficiency associated with blepharospasm and retinal degeneration, Neurology, 37, 761, 10.1212/WNL.37.5.761 Harada, 1995, Minamata disease: methylmercury poisoning in Japan caused by environmental pollution, Crit Rev Toxicol, 25, 1, 10.3109/10408449509089885 Auger, 2005, Low-level methylmercury exposure as a risk factor for neurologic abnormalities in adults, Neurotoxicology, 26, 149, 10.1016/j.neuro.2004.12.005 Mutkus, 2006, Mercuric chloride inhibits the in vitro uptake of glutamate in GLAST- and GLT-1-transfected mutant CHO-K1 cells, Biol Trace Elem Res, 109, 267, 10.1385/BTER:109:3:267 Yin, 2007, Methylmercury induces oxidative injury, alterations in permeability and glutamine transport in cultured astrocytes, Brain Res, 1131, 1, 10.1016/j.brainres.2006.10.070 Struzynska, 2005, The role of astroglia in Pb-exposed adult rat brain with respect to glutamate toxicity, Toxicology, 212, 185, 10.1016/j.tox.2005.04.013 Hossain, 2004, Vascular endothelial growth factor mediates vasogenic edema in acute lead encephalopathy, Ann Neurol, 55, 660, 10.1002/ana.20065 Gunnarson, 2005, Lead induces increased water permeability in astrocytes expressing aquaporin 4, Neuroscience, 136, 105, 10.1016/j.neuroscience.2005.07.027 Normandin, 2002, Manganese neurotoxicity: an update of pathophysiologic mechanisms, Metab Brain Dis, 17, 375, 10.1023/A:1021970120965 Struys-Ponsar, 2000, Effects of aluminum exposure on glutamate metabolism: a possible explanation for its toxicity, Exp Neurol, 163, 157, 10.1006/exnr.2000.7355 Theiss, 2002, Aluminum impairs gap junctional intercellular communication between astroglial cells in vitro, Cell Tissue Res, 310, 143, 10.1007/s00441-002-0639-3 Suarez-Fernandez, 1999, Aluminum-induced degeneration of astrocytes occurs via apoptosis and results in neuronal death, Brain Res, 835, 125, 10.1016/S0006-8993(99)01536-X Rothstein, 1992, Decreased glutamate transport by the brain and spinal cord in amyotrophic lateral sclerosis, N Engl J Med, 326, 1464, 10.1056/NEJM199205283262204 Rothstein, 1995, Selective loss of glial glutamate transporter GLT-1 in amyotrophic lateral sclerosis, Ann Neurol, 38, 73, 10.1002/ana.410380114 Fray, 1998, The expression of the glial glutamate transporter protein EAAT2 in motor neuron disease: an immunohistochemical study, Eur J Neurosci, 10, 2481, 10.1046/j.1460-9568.1998.00273.x Barbeito, 2004, A role for astrocytes in motor neuron loss in amyotrophic lateral sclerosis, Brain Res Brain Res Rev, 47, 263, 10.1016/j.brainresrev.2004.05.003 Rattray, 2006, Does excitotoxic cell death of motor neurons in ALS arise from glutamate transporter and glutamate receptor abnormalities?, Exp Neurol, 201, 15, 10.1016/j.expneurol.2006.05.001 Bendotti, 2001, Transgenic SOD1 G93A mice develop reduced GLT-1 in spinal cord without alterations in cerebrospinal fluid glutamate levels, J Neurochem, 79, 737, 10.1046/j.1471-4159.2001.00572.x Rowland, 2001, Amyotrophic lateral sclerosis, N Engl J Med, 344, 1688, 10.1056/NEJM200105313442207 Nagai, 2007, Astrocytes expressing ALS-linked mutated SOD1 release factors selectively toxic to motor neurons, Nat Neurosci, 10, 615, 10.1038/nn1876 Di Giorgio, 2007, Non-cell autonomous effect of glia on motor neurons in an embryonic stem cell-based ALS model, Nat Neurosci, 10, 608, 10.1038/nn1885 Yoshiyama, 2003, Reduction of detyrosinated microtubules and Golgi fragmentation are linked to tau-induced degeneration in astrocytes, J Neurosci, 23, 10662, 10.1523/JNEUROSCI.23-33-10662.2003 Forman, 2005, Transgenic mouse model of tau pathology in astrocytes leading to nervous system degeneration, J Neurosci, 25, 3539, 10.1523/JNEUROSCI.0081-05.2005 Dabir, 2006, Impaired glutamate transport in a mouse model of tau pathology in astrocytes, J Neurosci, 26, 644, 10.1523/JNEUROSCI.3861-05.2006 Broe, 2004, Astrocytic degeneration relates to the severity of disease in frontotemporal dementia, Brain, 127, 2214, 10.1093/brain/awh250 Matute, 2005, Increased expression of the astrocytic glutamate transporter GLT-1 in the prefrontal cortex of schizophrenics, Glia, 49, 451, 10.1002/glia.20119 Nanitsos, 2005, Glutamatergic hypothesis of schizophrenia: involvement of Na+/K+-dependent glutamate transport, J Biomed Sci, 12, 975, 10.1007/s11373-005-9015-0 Carlsson, 2001, Interactions between monoamines, glutamate, and GABA in schizophrenia: new evidence, Annu Rev Pharmacol Toxicol, 41, 237, 10.1146/annurev.pharmtox.41.1.237 Khan, 2001, An astroglia-linked dopamine D2-receptor action in prefrontal cortex, Proc Natl Acad Sci U S A, 98, 1964, 10.1073/pnas.98.4.1964 Pawlak, 2005, Regulation of glutamate transporter GLAST and GLT-1 expression in astrocytes by estrogen, Brain Res Mol Brain Res, 138, 1, 10.1016/j.molbrainres.2004.10.043 Eng, 1997, Expression of glutamate uptake transporters after dibutyryl cyclic AMP differentiation and traumatic injury in cultured astrocytes, Brain Res, 778, 215, 10.1016/S0006-8993(97)01093-7 Flamez, 1994, [3H]Clozapine is not a suitable radioligand for the labelling of D4 dopamine receptors in postmortem human brain, Neurosci Lett, 175, 17, 10.1016/0304-3940(94)91067-7 Vallejo-Illarramendi, 2005, Clozapine reduces GLT-1 expression and glutamate uptake in astrocyte cultures, Glia, 50, 276, 10.1002/glia.20172 Melone, 2001, The expression of glutamate transporter GLT-1 in the rat cerebral cortex is down-regulated by the antipsychotic drug clozapine, Mol Psychiatry, 6, 380, 10.1038/sj.mp.4000880