Human astrocytes in the diseased brain

Highlights • Astrocytes are active dynamic signalling players of the brain.• Dysfunctions of astrocytes can contribute to the pathogenesis of brain disorders.• A common pathological hallmark of several CNS diseases is reactive astrogliosis.• Targeting astrocytes represent an alternative approach to develop new therapies.

[1]  Sabine Landau,et al.  Evidence for orbitofrontal pathology in bipolar disorder and major depression, but not in schizophrenia. , 2005, Bipolar disorders.

[2]  Yong Jeong,et al.  GABA from reactive astrocytes impairs memory in mouse models of Alzheimer's disease , 2014, Nature Medicine.

[3]  Leif Gjerstad,et al.  Loss of Perivascular Kir4.1 Potassium Channels in the Sclerotic Hippocampus of Patients With Mesial Temporal Lobe Epilepsy , 2012, Journal of neuropathology and experimental neurology.

[4]  E. Aronica,et al.  Expression of connexin 43 and connexin 32 gap-junction proteins in epilepsy-associated brain tumors and in the perilesional epileptic cortex , 2001, Acta Neuropathologica.

[5]  A. Bordey,et al.  Electrophysiological properties of human astrocytic tumor cells In situ: enigma of spiking glial cells. , 1998, Journal of neurophysiology.

[6]  E. Aronica,et al.  Non-neuronal cell responses differ between normal and Down syndrome developing brains , 2013, International Journal of Developmental Neuroscience.

[7]  A. Cornell-Bell,et al.  Human epileptic astrocytes exhibit increased gap junction coupling , 1995, Glia.

[8]  Murim Choi,et al.  Seizures, sensorineural deafness, ataxia, mental retardation, and electrolyte imbalance (SeSAME syndrome) caused by mutations in KCNJ10 , 2009, Proceedings of the National Academy of Sciences.

[9]  Alan J. Thomas,et al.  Cellular pathology within the anterior cingulate cortex of patients with late-life depression: A morphometric study , 2011, Psychiatry Research: Neuroimaging.

[10]  W. Walz Role of astrocytes in the clearance of excess extracellular potassium , 2000, Neurochemistry International.

[11]  D. Spencer,et al.  Astrocytes from Human Hippocampal Epileptogenic Foci Exhibit Action Potential–Like Responses , 1998, Epilepsia.

[12]  C. Elger,et al.  Astrocytes in the hippocampus of patients with temporal lobe epilepsy display changes in potassium conductances , 2000, The European journal of neuroscience.

[13]  J. Rothstein,et al.  Focal Transplantation-based Astrocyte Replacement is Neuroprotective in a Model of Motor Neuron Disease , 2008, Nature Neuroscience.

[14]  James C. Overholser,et al.  Cellular changes in the postmortem hippocampus in major depression , 2004, Biological Psychiatry.

[15]  R. Garbelli,et al.  Aquaporin 4 expression in control and epileptic human cerebral cortex , 2011, Brain Research.

[16]  R. Vandenberg,et al.  Glutamate transporter variants reduce glutamate uptake in Alzheimer's disease , 2011, Neurobiology of Aging.

[17]  A. Clark,et al.  Neuronal and Glial Gene Expression in Neocortex of Down's Syndrome and Alzheimer's Disease , 1993, Journal of neuropathology and experimental neurology.

[18]  D. Rodriguez,et al.  Mutations in GFAP, encoding glial fibrillary acidic protein, are associated with Alexander disease , 2001, Nature Genetics.

[19]  D. Spencer,et al.  Loss of perivascular aquaporin 4 may underlie deficient water and K+ homeostasis in the human epileptogenic hippocampus. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[20]  H. Meltzer,et al.  Plasma concentrations of excitatory amino acids, serine, glycine, taurine and histidine in major depression , 1995, European Neuropsychopharmacology.

[21]  B. Bogerts,et al.  S100B-immunopositive astrocytes and oligodendrocytes in the hippocampus are differentially afflicted in unipolar and bipolar depression: a postmortem study. , 2013, Journal of psychiatric research.

[22]  A. Verkhratsky,et al.  Astrocytes in physiological aging and Alzheimer’s disease , 2016, Neuroscience.

[23]  D. Marshak,et al.  Increased S100 beta neurotrophic activity in Alzheimer's disease temporal lobe. , 1992, Neurobiology of aging.

[24]  C. Giaume,et al.  Glial connexin expression and function in the context of Alzheimer's disease. , 2012, Biochimica et biophysica acta.

[25]  M. Wiesmann,et al.  S-100B is increased in melancholic but not in non-melancholic major depression. , 2001, Journal of affective disorders.

[26]  Kost Elisevich,et al.  Hippocampal Connexin 43 Expression in Human Complex Partial Seizure Disorder , 1997, Experimental Neurology.

[27]  Bernadette Lipinski,et al.  Reduced glutamate in the anterior cingulate cortex in depression: an in vivo proton magnetic resonance spectroscopy study , 2000, Biological Psychiatry.

[28]  John H Krystal,et al.  Extracellular metabolites in the cortex and hippocampus of epileptic patients , 2005, Annals of neurology.

[29]  G. Pappas,et al.  Proteins of the intermediate filament cytoskeleton as markers for astrocytes and human astrocytomas , 1994, Molecular and chemical neuropathology.

[30]  S. Martin,et al.  Intermediate Filament Expression in Astrocytic Neoplasms , 1989, The American journal of surgical pathology.

[31]  S. Horvath,et al.  Divergence of human and mouse brain transcriptome highlights Alzheimer disease pathways , 2010, Proceedings of the National Academy of Sciences.

[32]  E. Aronica,et al.  Amyloid beta deregulates astroglial mGluR5‐mediated calcium signaling via calcineurin and Nf‐kB , 2013, Glia.

[33]  G. Dallérac,et al.  Astrocytes as new targets to improve cognitive functions , 2016, Progress in Neurobiology.

[34]  T. Beach,et al.  Lamina-specific arrangement of astrocytic gliosis and senile plaques in Alzheimer's disease visual cortex , 1988, Brain Research.

[35]  R. Balázs,et al.  Neuronal plasticity and astrocytic reaction in Down syndrome and Alzheimer disease , 1990, Journal of the Neurological Sciences.

[36]  D. Davies,et al.  beta-Amyloid immunoreactivity in astrocytes in Alzheimer's disease brain biopsies: an electron microscope study. , 1999, Experimental neurology.

[37]  Hernán D. Reisin,et al.  Development of interlaminar astroglial processes in the cerebral cortex of control and Down's syndrome human cases , 2005, Experimental Neurology.

[38]  Nathalie Rouach,et al.  Astroglial Metabolic Networks Sustain Hippocampal Synaptic Transmission , 2008, Science.

[39]  P. V. van Rijen,et al.  Distribution of glutamate transporters in the hippocampus of patients with pharmaco-resistant temporal lobe epilepsy. , 2002, Brain : a journal of neurology.

[40]  D. Spencer,et al.  Aquaporin-4 is increased in the sclerotic hippocampus in human temporal lobe epilepsy , 2004, Acta Neuropathologica.

[41]  G J Barker,et al.  Water diffusion in the human hippocampus in epilepsy. , 1999, Magnetic resonance imaging.

[42]  Aaron,et al.  Altered expression of connexin subtypes in mesial temporal lobe epilepsy in humans. , 2006, Journal of neurosurgery.

[43]  M. Sperling,et al.  Association between variation in the human KCNJ10 potassium ion channel gene and seizure susceptibility , 2004, Epilepsy Research.

[44]  R. Yolken,et al.  Disease-specific alterations in frontal cortex brain proteins in schizophrenia, bipolar disorder, and major depressive disorder , 2000, Molecular Psychiatry.

[45]  Hunter S. Futch,et al.  Neuron–astrocyte signaling is preserved in the aging brain , 2017, Glia.

[46]  A. Kivi,et al.  Alterations of Glial Cell Function in Temporal Lobe Epilepsy , 2000, Epilepsia.

[47]  K. McCarthy,et al.  Conditional Knock-Out of Kir4.1 Leads to Glial Membrane Depolarization, Inhibition of Potassium and Glutamate Uptake, and Enhanced Short-Term Synaptic Potentiation , 2007, The Journal of Neuroscience.

[48]  W. Griffin,et al.  Life-long overexpression of S100β in Down’s syndrome: implications for Alzheimer pathogenesis , 1998, Neurobiology of Aging.

[49]  Robert C. Thompson,et al.  Altered expression of glutamate signaling, growth factor and glia genes in the locus coeruleus of patients with major depression , 2010, Molecular Psychiatry.

[50]  G. Szpak,et al.  Astroglia disturbances during development of the central nervous system in fetuses with Down's syndrome. , 2011, Folia neuropathologica.

[51]  G. Turecki,et al.  Astrocytic Hypertrophy in Anterior Cingulate White Matter of Depressed Suicides , 2011, Neuropsychopharmacology.

[52]  H. Yang,et al.  Expression of 300-kilodalton intermediate filament-associated protein distinguishes human glioma cells from normal astrocytes. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[53]  Ivo D Dinov,et al.  A role for ephrin-A5 in axonal sprouting, recovery, and activity-dependent plasticity after stroke , 2012, Proceedings of the National Academy of Sciences.

[54]  R. Mrak,et al.  Human brain S100β and S100β mRNA expression increases with age: Pathogenic implications for Alzheimer's disease , 1996, Neurobiology of Aging.

[55]  John R. Terry,et al.  Transition to absence seizures and the role of GABAA receptors , 2011, Epilepsy Research.

[56]  Hynek Wichterle,et al.  Astrocytes expressing ALS-linked mutated SOD1 release factors selectively toxic to motor neurons , 2007, Nature Neuroscience.

[57]  R. Guillevin,et al.  Epileptic seizures in diffuse low-grade gliomas in adults. , 2014, Brain : a journal of neurology.

[58]  Hyunmi Choi,et al.  Seizures in Alzheimer disease: who, when, and how common? , 2009, Archives of neurology.

[59]  C. Brayne,et al.  Population Variation in Glial Fibrillary Acidic Protein Levels in Brain Ageing: Relationship to Alzheimer-Type Pathology and Dementia , 2009, Dementia and Geriatric Cognitive Disorders.

[60]  W. Markesbery,et al.  Associations of cortical astrogliosis with cognitive performance and dementia status. , 2005, Journal of Alzheimer's disease : JAD.

[61]  M. Sofroniew,et al.  Astrocytes: biology and pathology , 2009, Acta Neuropathologica.

[62]  S. Waxman,et al.  Astrocytes within multiple sclerosis lesions upregulate sodium channel Nav1.5. , 2010, Brain : a journal of neurology.

[63]  T. Virolle,et al.  EGFR immunolabeling pattern may discriminate low-grade gliomas from gliosis , 2011, Journal of Neuro-Oncology.

[64]  B. Roth,et al.  Morphometric evidence for neuronal and glial prefrontal cell pathology in major depression∗ ∗ See accompanying Editorial, in this issue. , 1999, Biological Psychiatry.

[65]  R. Kayed,et al.  Astrocytes contain amyloid‐β annular protofibrils in Alzheimer's disease brains , 2011, FEBS letters.

[66]  A. Butt,et al.  Inwardly rectifying potassium channels (Kir) in central nervous system glia: a special role for Kir4.1 in glial functions , 2006, Journal of cellular and molecular medicine.

[67]  E. Aronica,et al.  Metabotropic glutamate receptor 5 in Down's syndrome hippocampus during development: increased expression in astrocytes. , 2014, Current Alzheimer research.

[68]  U. Ungerstedt,et al.  Baseline Levels of Glucose Metabolites, Glutamate and Glycerol in Malignant Glioma Assessed by Stereotactic Microdialysis , 2004, Journal of Neuro-Oncology.

[69]  C. Lin,et al.  Increased expression of cholesterol 24S‐hydroxylase results in disruption of glial glutamate transporter EAAT2 association with lipid rafts: a potential role in Alzheimer’s disease , 2010, Journal of neurochemistry.

[70]  Dennis D. Spencer,et al.  GAT1 and GAT3 expression are differently localized in the human epileptogenic hippocampus , 2006, Acta Neuropathologica.

[71]  D. Condorelli,et al.  High levels of connexin 43 mRNA in high grade astrocytomas. Study of 32 cases with in situ hybridization. , 2010, Acta histochemica.

[72]  E. Hertzberg,et al.  Elevated connexin43 immunoreactivity at sites of amyloid plaques in alzheimer's disease , 1996, Brain Research.

[73]  由谷 親夫,et al.  126. 脳腫瘍の捺印細胞診における Glial Fibrillary Acidic Proteinに対するモノクロナール抗体による検索(総合5 神経その1, 一般講演・口演, 第26回日本臨床細胞学会学術集会) , 1985 .

[74]  A. Djamshidian,et al.  Altered expression of voltage-dependent calcium channel α1 subunits in temporal lobe epilepsy with Ammon’s horn sclerosis , 2002, Neuroscience.

[75]  K. Wisniewski,et al.  Down syndrome children often have brain with maturation delay, retardation of growth, and cortical dysgenesis. , 2005, American journal of medical genetics. Supplement.

[76]  R. Bartesaghi,et al.  RESEARCH ARTICLE: Neurogenesis Impairment and Increased Cell Death Reduce Total Neuron Number in the Hippocampal Region of Fetuses with Down Syndrome , 2007, Brain pathology.

[77]  Y. Ao,et al.  Heterogeneity of reactive astrocytes , 2014, Neuroscience Letters.

[78]  O. Ottersen,et al.  Loss of glutamine synthetase in the human epileptogenic hippocampus: possible mechanism for raised extracellular glutamate in mesial temporal lobe epilepsy , 2004, The Lancet.

[79]  C. Brayne,et al.  Astrocyte phenotype in relation to Alzheimer-type pathology in the ageing brain , 2010, Neurobiology of Aging.

[80]  B. Hyman,et al.  Synchronous Hyperactivity and Intercellular Calcium Waves in Astrocytes in Alzheimer Mice , 2009, Science.

[81]  F. Santorelli,et al.  Autism with Seizures and Intellectual Disability: Possible Causative Role of Gain-of-function of the Inwardly-Rectifying K+ Channel Kir4.1 , 2011, Neurobiology of Disease.

[82]  E. Masliah,et al.  Glutamate Transporter Alterations in Alzheimer Disease Are Possibly Associated with Abnormal APP Expression , 1997, Journal of neuropathology and experimental neurology.

[83]  Mutsuo Takahashi,et al.  Confocal observation of senile plaques in Alzheimer's disease: Senile plaque morphology and relationship between senile plaques and astrocytes , 1998, Pathology international.

[84]  R. Myers,et al.  Altered cortical glutamatergic and GABAergic signal transmission with glial involvement in depression , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[85]  T. Lehmann,et al.  Effects of barium, furosemide, ouabaine and 4,4′-diisothiocyanatostilbene-2,2′-disulfonic acid (DIDS) on ionophoretically-induced changes in extracellular potassium concentration in hippocampal slices from rats and from patients with epilepsy , 2002, Brain Research.

[86]  I. Gottesman,et al.  Glial fibrillary acidic protein is reduced in cerebellum of subjects with major depression, but not schizophrenia , 2004, Schizophrenia Research.

[87]  G. Bartzokis,et al.  Amygdala astrocyte reduction in subjects with major depressive disorder but not bipolar disorder. , 2010, Bipolar disorders.

[88]  M. Frotscher,et al.  Granule cell dispersion is not accompanied by enhanced neurogenesis in temporal lobe epilepsy patients , 2007, Experimental Neurology.

[89]  Y. Ihara,et al.  Diffuse plaques associated with astroglial amyloid β protein, possibly showing a disappearing stage of senile plaques , 1998, Acta Neuropathologica.

[90]  D. Mann,et al.  Overexpression of s100beta in Down's syndrome: correlation with patient age and with beta-amyloid deposition. , 1999, Neuropathology and applied neurobiology.

[91]  F. Holsboer,et al.  Neither major depression nor glucocorticoid treatment affects the cellular integrity of the human hippocampus , 2001, The European journal of neuroscience.

[92]  M. Raskind,et al.  Early Amyloid Deposition in the Medial Temporal Lobe of Young Down Syndrome Patients: A Regional Quantitative Analysis , 1998, Experimental Neurology.

[93]  D. Spencer,et al.  Distinct electrophysiological alterations in dentate gyrus versus CA1 glial cells from epileptic humans with temporal lobe sclerosis , 2004, Epilepsy Research.

[94]  E. Chang,et al.  Purification and Characterization of Progenitor and Mature Human Astrocytes Reveals Transcriptional and Functional Differences with Mouse , 2016, Neuron.

[95]  Marís S. Sánchez,et al.  Aquaporin expression in the cerebral cortex is increased at early stages of Alzheimer disease , 2007, Brain Research.

[96]  A. Contestabile,et al.  Cell cycle alteration and decreased cell proliferation in the hippocampal dentate gyrus and in the neocortical germinal matrix of fetuses with down syndrome and in Ts65Dn mice , 2007, Hippocampus.

[97]  Hui-Kuo Shu,et al.  Metastasis infiltration: an investigation of the postoperative brain-tumor interface. , 2011, International journal of radiation oncology, biology, physics.

[98]  Carissa G. Fonseca,et al.  Upregulation in astrocytic connexin 43 gap junction levels may exacerbate generalized seizures in mesial temporal lobe epilepsy , 2002, Brain Research.

[99]  C. Beasley,et al.  Two-dimensional assessment of cytoarchitecture in the anterior cingulate cortex in major depressive disorder, bipolar disorder, and schizophrenia: evidence for decreased neuronal somal size and increased neuronal density , 2003, Biological Psychiatry.

[100]  M. Lyons,et al.  Frequency of seizures in patients with newly diagnosed brain tumors: A retrospective review , 2007, Clinical Neurology and Neurosurgery.

[101]  Sabine Landau,et al.  Reduced neuronal size and glial cell density in area 9 of the dorsolateral prefrontal cortex in subjects with major depressive disorder. , 2002, Cerebral cortex.

[102]  J. Price,et al.  Glial reduction in the subgenual prefrontal cortex in mood disorders. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[103]  Brian J Cummings,et al.  Early association of reactive astrocytes with senile plaques in Alzheimer's disease , 1995, Experimental Neurology.

[104]  J H Kim,et al.  Imaging findings in hippocampal sclerosis: correlation with pathology. , 1991, AJNR. American journal of neuroradiology.

[105]  D. Sparks,et al.  Age-related distribution of neuropathologic changes in the cerebral cortex of patients with Down's syndrome. Quantitative regional analysis and comparison with Alzheimer's disease. , 1995, Archives of neurology.

[106]  H. Kretzschmar,et al.  Glial fibrillary acidic protein and protein S-100B: Different concentration pattern of glial proteins in cerebrospinal fluid of patients with Alzheimer' s disease and Creutzfeldt-Jakob disease , 2009, Alzheimer's & Dementia.

[107]  John H Krystal,et al.  Subtype-specific alterations of gamma-aminobutyric acid and glutamate in patients with major depression. , 2004, Archives of general psychiatry.

[108]  G. Reynolds,et al.  Amino acid neurotransmitter deficits in adult Down's syndrome brain tissue , 1988, Neuroscience Letters.

[109]  M. Haber,et al.  Cooperative Astrocyte and Dendritic Spine Dynamics at Hippocampal Excitatory Synapses , 2006, The Journal of Neuroscience.

[110]  A. Volterra,et al.  Astrocytic dysfunction: Insights on the role in neurodegeneration , 2009, Brain Research Bulletin.

[111]  L. Chin,et al.  Malignant astrocytic glioma: genetics, biology, and paths to treatment. , 2007, Genes & development.

[112]  Dennis D Spencer,et al.  Glutamate–glutamine Cycling in the Epileptic Human Hippocampus , 2002, Epilepsia.

[113]  H. Beck,et al.  Expression of connexin genes in hippocampus of kainate-treated and kindled rats under conditions of experimental epilepsy. , 2000, Brain research. Molecular brain research.

[114]  J. Price,et al.  Low glial numbers in the amygdala in major depressive disorder , 2002, Biological Psychiatry.

[115]  Paul J. Harrison,et al.  A morphometric study of glia and neurons in the anterior cingulate cortex in mood disorder. , 2011, Journal of affective disorders.

[116]  R. Jabs,et al.  Functional and Molecular Properties of Human Astrocytes in Acute Hippocampal Slices Obtained from Patients with Temporal Lobe Epilepsy , 2000, Epilepsia.

[117]  Jullie W Pan,et al.  Decreased hippocampal volume on MRI is associated with increased extracellular glutamate in epilepsy patients , 2008, Epilepsia.

[118]  A. Toutain,et al.  Congenital glutamine deficiency with glutamine synthetase mutations. , 2005, The New England journal of medicine.

[119]  D. Kurzwelly,et al.  Seizures in patients with low-grade gliomas--incidence, pathogenesis, surgical management, and pharmacotherapy. , 2010, Advances and technical standards in neurosurgery.

[120]  James Briggs,et al.  Integration‐Free Induced Pluripotent Stem Cells Model Genetic and Neural Developmental Features of Down Syndrome Etiology , 2013, Stem cells.

[121]  Markus Rapedius,et al.  KCNJ10 gene mutations causing EAST syndrome (epilepsy, ataxia, sensorineural deafness, and tubulopathy) disrupt channel function , 2010, Proceedings of the National Academy of Sciences.

[122]  Y. Ihara,et al.  Astrocytes containing amyloid beta-protein (Abeta)-positive granules are associated with Abeta40-positive diffuse plaques in the aged human brain. , 1998, The American journal of pathology.

[123]  W. Lanksch,et al.  Effects of barium on stimulus-induced changes in [K+]o and field potentials in dentate gyrus and area CA1 of human epileptic hippocampus , 1998, Neuroscience Letters.

[124]  Harald Sontheimer,et al.  Compromised Glutamate Transport in Human Glioma Cells: Reduction–Mislocalization of Sodium-Dependent Glutamate Transporters and Enhanced Activity of Cystine–Glutamate Exchange , 1999, The Journal of Neuroscience.

[125]  D. Marshak,et al.  Increased S100β neurotrophic activity in Alzheimer's disease temporal lobe , 1992, Neurobiology of Aging.

[126]  M. During,et al.  Extracellular hippocampal glutamate and spontaneous seizure in the conscious human brain , 1993, The Lancet.

[127]  G. Rajkowska,et al.  Reduced connexin 43 immunolabeling in the orbitofrontal cortex in alcohol dependence and depression. , 2014, Journal of psychiatric research.

[128]  C. Brayne,et al.  Microarray analysis of the astrocyte transcriptome in the aging brain: relationship to Alzheimer's pathology and APOE genotype , 2011, Neurobiology of Aging.

[129]  H. Grabe,et al.  Neurotrophic factor S100 beta in major depression. , 2001, Neuropsychobiology.

[130]  J. Growdon,et al.  A phenotypic change but not proliferation underlies glial responses in Alzheimer disease. , 2013, The American journal of pathology.

[131]  J. Kleinman,et al.  Glial fibrillary acidic protein mRNA levels in the cingulate cortex of individuals with depression, bipolar disorder and schizophrenia , 2005, Neuroscience.

[132]  B T Hyman,et al.  Development of the Superior Temporal Neocortex Is Anomalous in Trisomy 21 , 1994, Journal of neuropathology and experimental neurology.

[133]  Marc Wortmann Dementia: a global health priority - highlights from an ADI and World Health Organization report , 2012, Alzheimer's Research & Therapy.

[134]  G. Rajkowska,et al.  Glial and glutamatergic markers in depression, alcoholism, and their comorbidity. , 2010, Journal of affective disorders.

[135]  R. Swanson,et al.  Astrocytes and Brain Injury , 2003, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[136]  M. D'Andrea,et al.  Astrocytes accumulate Aβ42 and give rise to astrocytic amyloid plaques in Alzheimer disease brains , 2003, Brain Research.

[137]  M. Walker,et al.  Hippocampal Sclerosis: Causes and Prevention , 2015, Seminars in Neurology.

[138]  M. Eddleston,et al.  Molecular profile of reactive astrocytes—Implications for their role in neurologic disease , 1993, Neuroscience.

[139]  S. Levison,et al.  IL‐6‐type cytokines enhance epidermal growth factor‐stimulated astrocyte proliferation , 2000, Glia.

[140]  P. Fisher,et al.  β-Lactam antibiotics offer neuroprotection by increasing glutamate transporter expression , 2005, Nature.

[141]  James W. Hugg,et al.  Diffusion mapping applied to mesial temporal lobe epilepsy , 1999, Neurology.

[142]  Jisook Lee,et al.  Non-invasive quantification of brain tumor-induced astrogliosis , 2011, BMC Neuroscience.

[143]  Janet B W Williams,et al.  Diagnostic and Statistical Manual of Mental Disorders , 2013 .

[144]  G. Richerson,et al.  Dynamic equilibrium of neurotransmitter transporters: not just for reuptake anymore. , 2003, Journal of neurophysiology.

[145]  P. V. van Rijen,et al.  Reduced glutamine synthetase in hippocampal areas with neuron loss in temporal lobe epilepsy , 2005, Neurology.

[146]  W. Griffin,et al.  Brain interleukin 1 and S-100 immunoreactivity are elevated in Down syndrome and Alzheimer disease. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[147]  N. Cairns,et al.  Differences between GABA levels in Alzheimer's disease and Down syndrome with Alzheimer-like neuropathology , 2001, Naunyn-Schmiedeberg's Archives of Pharmacology.

[148]  J. Ojemann,et al.  Uniquely Hominid Features of Adult Human Astrocytes , 2009, The Journal of Neuroscience.

[149]  J. Neary,et al.  Trophic functions of nucleotides in the central nervous system , 2009, Trends in Neurosciences.

[150]  H. Grabe,et al.  Neurotrophic Factor S100beta in Major Depression , 2001, Neuropsychobiology.

[151]  Alfonso Araque,et al.  Astrocyte calcium signal and gliotransmission in human brain tissue. , 2013, Cerebral cortex.

[152]  Leif Gjerstad,et al.  Variants of the genes encoding AQP4 and Kir4.1 are associated with subgroups of patients with temporal lobe epilepsy , 2010, Epilepsy Research.

[153]  B. Hyman,et al.  Neuropathological changes in Down's syndrome hippocampal formation. Effect of age and apolipoprotein E genotype. , 1995, Archives of neurology.

[154]  J. Wegiel,et al.  Contribution of glial cells to the development of amyloid plaques in Alzheimer’s disease , 2004, Neurobiology of Aging.

[155]  G. Rajkowska,et al.  Glial fibrillary acidic protein immunoreactivity in the prefrontal cortex distinguishes younger from older adults in major depressive disorder , 2000, Biological Psychiatry.

[156]  D. Coulter,et al.  Astrocytic regulation of glutamate homeostasis in epilepsy , 2012, Glia.

[157]  E. Aronica,et al.  Specific Human Astrocyte Subtype Revealed by Affinity Purified GFAP+1 Antibody; Unpurified Serum Cross-Reacts with Neurofilament-L in Alzheimer , 2009, PloS one.

[158]  A. Lahti,et al.  SLC7A11 expression is associated with seizures and predicts poor survival in patients with malignant glioma , 2015, Science Translational Medicine.

[159]  W. Bunney,et al.  Global Brain Gene Expression Analysis Links Glutamatergic and GABAergic Alterations to Suicide and Major Depression , 2009, PloS one.

[160]  K. Nakazawa,et al.  Acute D-serine treatment produces antidepressant-like effects in rodents. , 2012, The international journal of neuropsychopharmacology.

[161]  L. V. Van Eldik,et al.  S100 beta expression in Alzheimer's disease: relation to neuropathology in brain regions. , 1994, Biochimica et biophysica acta.

[162]  R. Kirby,et al.  Updated National Birth Prevalence estimates for selected birth defects in the United States, 2004-2006. , 2010, Birth defects research. Part A, Clinical and molecular teratology.

[163]  V. Gallo,et al.  Endothelin-1 Regulates Astrocyte Proliferation and Reactive Gliosis via a JNK/c-Jun Signaling Pathway , 2008, The Journal of Neuroscience.

[164]  J. Wegiel,et al.  Spatial relationships between astrocytes and classical plaque components , 1991, Neurobiology of Aging.

[165]  W. Sobaniec,et al.  Hippocampus, hippocampal sclerosis and epilepsy , 2013, Pharmacological reports : PR.

[166]  L. Laurent,et al.  Title Role of astroglia in down ' s syndrome revealed by patient-derived human-induced pluripotent stem cells , 2014 .

[167]  D. Ankerst,et al.  Review of 1H magnetic resonance spectroscopy findings in major depressive disorder: A meta-analysis , 2006, Psychiatry Research: Neuroimaging.

[168]  David L. Paul,et al.  Gap junction gene expression in human seizure disorder , 1991, Experimental Neurology.

[169]  K. Wilcox,et al.  Increased coupling and altered glutamate transport currents in astrocytes following kainic-acid-induced status epilepticus , 2010, Neurobiology of Disease.

[170]  M. Dierssen,et al.  Fetal Down Syndrome Brains Exhibit Aberrant Levels of Neurotransmitters Critical for Normal Brain Development , 2007, Pediatrics.

[171]  M. Schroeter,et al.  S100B is increased in mood disorders and may be reduced by antidepressive treatment , 2002, Neuroreport.

[172]  D. Bouvier,et al.  High Resolution Dissection of Reactive Glial Nets in Alzheimer’s Disease , 2016, Scientific Reports.

[173]  E. Hol,et al.  Glial fibrillary acidic protein (GFAP) and the astrocyte intermediate filament system in diseases of the central nervous system. , 2015, Current opinion in cell biology.

[174]  Huichun Xu,et al.  MeCP2 modulates gene expression pathways in astrocytes , 2013, Molecular Autism.

[175]  P. Mcgeer,et al.  Occurrence of the diffuse amyloid beta-protein (Abeta) deposits with numerous Abeta-containing glial cells in the cerebral cortex of patients with Alzheimer's disease. , 1999, Glia.

[176]  Gregor Hasler,et al.  Reduced prefrontal glutamate/glutamine and gamma-aminobutyric acid levels in major depression determined using proton magnetic resonance spectroscopy. , 2007, Archives of general psychiatry.

[177]  Coeli M B Lopes,et al.  Molecular basis of decreased Kir4.1 function in SeSAME/EAST syndrome. , 2010, Journal of the American Society of Nephrology : JASN.

[178]  E. Nagelhus,et al.  Aquaporin-4 in the central nervous system: Cellular and subcellular distribution and coexpression with KIR4.1 , 2004, Neuroscience.

[179]  Michael M. Halassa,et al.  The tripartite synapse: roles for gliotransmission in health and disease. , 2007, Trends in molecular medicine.

[180]  S. Oliet,et al.  Gliotransmitters Travel in Time and Space , 2014, Neuron.

[181]  C. Fages,et al.  Glutamine synthetase (GS) expression is reduced in senile dementia of the Alzheimer type , 1995, Neurochemical Research.

[182]  R. Kerwin,et al.  Reduced glial cell density and neuronal size in the anterior cingulate cortex in major depressive disorder. , 2001, Archives of general psychiatry.

[183]  F R Tang,et al.  Expression of the group II and III metabotropic glutamate receptors in the hippocampus of patients with mesial temporal lobe epilepsy , 2001, Journal of neurocytology.

[184]  D. Davies,et al.  β-Amyloid Immunoreactivity in Astrocytes in Alzheimer's Disease Brain Biopsies: An Electron Microscope Study , 1999, Experimental Neurology.

[185]  P. Mcgeer,et al.  Occurrence of the diffuse amyloid β‐protein (Aβ) deposits with numerous Aβ‐containing glial cells in the cerebral cortex of patients with Alzheimer's disease , 1999 .

[186]  G. Ojemann,et al.  Hippocampal GABA and glutamate transporter immunoreactivity in patients with temporal lobe epilepsy , 1999, Neurology.

[187]  G. Fuller,et al.  The excitatory amino acid transporter-2 induces apoptosis and decreases glioma growth in vitro and in vivo. , 2005, Cancer research.

[188]  H. Yamasaki,et al.  Mutated connexin43 proteins inhibit rat glioma cell growth suppression mediated by wild‐type connexin43 in a dominant‐negative manner , 1998, International journal of cancer.

[189]  H. Braak,et al.  Amyloid beta-protein (Abeta)-containing astrocytes are located preferentially near N-terminal-truncated Abeta deposits in the human entorhinal cortex. , 2000, Acta neuropathologica.

[190]  A. Kakita,et al.  Characteristics of Aquaporin Expression Surrounding Senile Plaques and Cerebral Amyloid Angiopathy in Alzheimer Disease , 2012, Journal of neuropathology and experimental neurology.

[191]  D. Spencer,et al.  Changes in glial glutamate transporters in human epileptogenic hippocampus: Inadequate explanation for high extracellular glutamate during seizures , 2007, Neurobiology of Disease.

[192]  R. Mrak,et al.  Correlation of Astrocytic S100β Expression with Dystrophic Neurites in Amyloid Plaques of Alzheimer's Disease , 1996, Journal of neuropathology and experimental neurology.

[193]  W. Griffin,et al.  S100β protein expression in Alzheimer disease: Potential role in the pathogenesis of neuritic plaques , 1994 .

[194]  P Riederer,et al.  Alterations in expression of glutamatergic transporters and receptors in sporadic Alzheimer's disease. , 2007, Journal of Alzheimer's disease : JAD.

[195]  C. Colton,et al.  Vascular amyloid alters astrocytic water and potassium channels in mouse models and humans with Alzheimer's disease , 2009, Neuroscience.

[196]  P. Bezzi,et al.  Astrocytes and Microglia and Their Potential Link with Autism Spectrum Disorders , 2016, Front. Cell. Neurosci..

[197]  N. Cairns,et al.  Excitatory amino acids and monoamines in parahippocampal gyrus and frontal cortical pole of adults with Down syndrome. , 1997, Life sciences.

[198]  A. Sequeira,et al.  Altered expression of genes involved in ATP biosynthesis and GABAergic neurotransmission in the ventral prefrontal cortex of suicides with and without major depression , 2009, Molecular Psychiatry.

[199]  A. von Deimling,et al.  Effects of barium on stimulus‐induced rises of [K+]o in human epileptic non‐sclerotic and sclerotic hippocampal area CA1 , 2000, The European journal of neuroscience.

[200]  R. Mrak,et al.  Human brain S100 beta and S100 beta mRNA expression increases with age: pathogenic implications for Alzheimer's disease. , 1996, Neurobiology of aging.

[201]  M. Schroeter,et al.  Serum markers support disease-specific glial pathology in major depression. , 2008, Journal of affective disorders.

[202]  D. Attwell,et al.  Astrocyte calcium signaling: the third wave , 2016, Nature Neuroscience.

[203]  H. Parri,et al.  Astrocytic GABA transporter GAT‐1 dysfunction in experimental absence seizures , 2013, The Journal of physiology.

[204]  S. Goldman,et al.  Astrocytic complexity distinguishes the human brain , 2006, Trends in Neurosciences.

[205]  Robert C. Thompson,et al.  Evidence for alterations of the glial syncytial function in major depressive disorder. , 2016, Journal of psychiatric research.

[206]  J. Stockman Epilepsy, Ataxia, Sensorineural Deafness, Tubulopathy, and KCNJ10 Mutations , 2011 .

[207]  G. Ming,et al.  Integration-free induced pluripotent stem cells derived from schizophrenia patients with a DISC1 mutation , 2011, Molecular Psychiatry.

[208]  M. Thom Review: Hippocampal sclerosis in epilepsy: a neuropathology review , 2014, Neuropathology and applied neurobiology.

[209]  P. Emson,et al.  Expression of the glutamate transporters in human temporal lobe epilepsy , 1999, Neuroscience.

[210]  Dmitri A. Rusakov,et al.  Time-Resolved Imaging Reveals Heterogeneous Landscapes of Nanomolar Ca2+ in Neurons and Astroglia , 2015, Neuron.

[211]  Florin Amzica,et al.  Implication of Kir4.1 Channel in Excess Potassium Clearance: An In Vivo Study on Anesthetized Glial-Conditional Kir4.1 Knock-Out Mice , 2010, The Journal of Neuroscience.

[212]  A. Simmons,et al.  Hippocampal glutamate-glutamine (Glx) in adults with Down syndrome: a preliminary study using in vivo proton magnetic resonance spectroscopy (1H MRS) , 2014, Journal of Neurodevelopmental Disorders.

[213]  H. Braak,et al.  Amyloid β-protein (Aβ)-containing astrocytes are located preferentially near N-terminal-truncated Aβ deposits in the human entorhinal cortex , 2000, Acta Neuropathologica.

[214]  F. Ramaekers,et al.  Co-expression of glial fibrillary acidic protein- and vimentin-type intermediate filaments in human astrocytomas , 2004, Acta Neuropathologica.

[215]  M. Rijpkema,et al.  Characterization of oligodendrogliomas using short echo time 1H MR spectroscopic imaging , 2003, NMR in biomedicine.

[216]  M. Sofroniew Molecular dissection of reactive astrogliosis and glial scar formation , 2009, Trends in Neurosciences.

[217]  S. W. Kuffler,et al.  Effect of nerve impulses on the membrane potential of glial cells in the central nervous system of amphibia. , 1966, Journal of neurophysiology.

[218]  L. Martinian,et al.  Expression patterns of glial fibrillary acidic protein (GFAP)‐delta in epilepsy‐associated lesional pathologies , 2009, Neuropathology and applied neurobiology.

[219]  Moonhee Lee,et al.  Mechanisms of GABA release from human astrocytes , 2011, Glia.

[220]  B. Scheithauer,et al.  The 2007 WHO classification of tumours of the central nervous system , 2007, Acta Neuropathologica.

[221]  L. Hazrati,et al.  A novel double mutation in FUS gene causing sporadic ALS , 2011, Neurobiology of Aging.

[222]  J. Middeldorp,et al.  Glial fibrillary acidic protein isoform expression in plaque related astrogliosis in Alzheimer's disease , 2014, Neurobiology of Aging.

[223]  O B Paulson,et al.  Does the release of potassium from astrocyte endfeet regulate cerebral blood flow? , 1987, Science.

[224]  K. Hashimoto,et al.  Increased Levels of Glutamate in Brains from Patients with Mood Disorders , 2007, Biological Psychiatry.

[225]  Martin Fiebich,et al.  Effective electroconvulsive therapy reverses glutamate/glutamine deficit in the left anterior cingulum of unipolar depressed patients , 2003, Psychiatry Research: Neuroimaging.

[226]  Milos Pekny,et al.  Redefining the concept of reactive astrocytes as cells that remain within their unique domains upon reaction to injury , 2006, Proceedings of the National Academy of Sciences.

[227]  Uwe Heinemann,et al.  Ceiling of stimulus induced rises in extracellular potassium concentration in the cerebral cortex of cat , 1977, Brain Research.

[228]  C. Nimsky,et al.  Small interfering RNA–mediated xCT silencing in gliomas inhibits neurodegeneration and alleviates brain edema , 2008, Nature Medicine.

[229]  H. Sontheimer,et al.  Autocrine glutamate signaling promotes glioma cell invasion. , 2007, Cancer research.

[230]  H. Braak,et al.  Neuropathological stageing of Alzheimer-related changes , 2004, Acta Neuropathologica.

[231]  G. Rajkowska,et al.  Age-Dependent Reductions in the Level of Glial Fibrillary Acidic Protein in the Prefrontal Cortex in Major Depression , 2004, Neuropsychopharmacology.

[232]  M. Gearing,et al.  Tonic inhibition in dentate gyrus impairs long-term potentiation and memory in an Alzhiemer’s disease model , 2014, Nature Communications.

[233]  A. Verkhratsky,et al.  Astrocytes in Alzheimer’s disease , 2010, Neurotherapeutics.

[234]  Alan J. Thomas,et al.  A morphometric examination of neuronal and glial cell pathology in the orbitofrontal cortex in late-life depression , 2010, International Psychogeriatrics.

[235]  J. Haueisen,et al.  Source Localization and Possible Causes of Interictal Epileptic Activity in Tumor-Associated Epilepsy , 2000, Neurobiology of Disease.

[236]  G. Rajkowska,et al.  Hippocampal volume and total cell numbers in major depressive disorder. , 2013, Journal of psychiatric research.

[237]  F. LaFerla,et al.  Alzheimer's disease. , 2010, The New England journal of medicine.

[238]  T. Ben-Omran,et al.  Natural course of glutamine synthetase deficiency in a 3 year old patient. , 2011, Molecular genetics and metabolism.

[239]  H. Braak,et al.  Staging of alzheimer's disease-related neurofibrillary changes , 1995, Neurobiology of Aging.

[240]  K. Krishnan,et al.  Prominent Reduction in Pyramidal Neurons Density in the Orbitofrontal Cortex of Elderly Depressed Patients , 2005, Biological Psychiatry.

[241]  Marian Joëls,et al.  Brain GABA levels across psychiatric disorders: A systematic literature review and meta‐analysis of 1H‐MRS studies , 2016, Human brain mapping.

[242]  ulio Escalona-Zapata,et al.  Diagnostic Neuropathology , 1990, Springer Berlin Heidelberg.

[243]  L. Becker,et al.  Developmental Changes of S-100 Protein and Glial Fibrillary Acidic Protein in the Brain in Down Syndrome , 1993, Experimental Neurology.

[244]  J. Vickers,et al.  Altered synapses and gliotransmission in Alzheimer's disease and AD model mice , 2013, Neurobiology of Aging.

[245]  A. Galaburda,et al.  Down's syndrome , 1984, Neurology.

[246]  M. Meaney,et al.  Dysfunction of Astrocyte Connexins 30 and 43 in Dorsal Lateral Prefrontal Cortex of Suicide Completers , 2011, Biological Psychiatry.

[247]  L. Soroceanu,et al.  Reduced expression of connexin‐43 and functional gap junction coupling in human gliomas , 2001, Glia.

[248]  P. Pu,et al.  Altered expression of Cx43 in astrocytic tumors , 2004, Clinical Neurology and Neurosurgery.

[249]  M. Verbeek,et al.  Total glutamine synthetase levels in cerebrospinal fluid of Alzheimer's disease patients are unchanged , 2015, Neurobiology of Aging.

[250]  T. Takano,et al.  An astrocytic basis of epilepsy , 2005, Nature Medicine.

[251]  J. O'Brien,et al.  Glial fibrillary acidic protein in late life major depressive disorder: an immunocytochemical study , 2002, Journal of neurology, neurosurgery, and psychiatry.

[252]  J. Schramm,et al.  Astrocyte uncoupling as a cause of human temporal lobe epilepsy. , 2015, Brain : a journal of neurology.

[253]  M. Sayyah,et al.  Expression of connexin 30 and connexin 32 in hippocampus of rat during epileptogenesis in a kindling model of epilepsy , 2012, Neuroscience Bulletin.

[254]  N. Belluardo,et al.  Connexin-30 mRNA Is Up-Regulated in Astrocytes and Expressed in Apoptotic Neuronal Cells of Rat Brain Following Kainate-Induced Seizures , 2002, Molecular and Cellular Neuroscience.

[255]  V. Arolt,et al.  Neurotrophic Effects of Electroconvulsive Therapy: A Proton Magnetic Resonance Study of the Left Amygdalar Region in Patients with Treatment-Resistant Depression , 2003, Neuropsychopharmacology.

[256]  G. Rajkowska,et al.  Coverage of Blood Vessels by Astrocytic Endfeet Is Reduced in Major Depressive Disorder , 2013, Biological Psychiatry.

[257]  Roles of Glutamine Synthetase Inhibition in Epilepsy , 2012, Neurochemical Research.

[258]  David R Rosenberg,et al.  Reduced anterior cingulate cortex glutamatergic concentrations in childhood major depression. , 2004, Journal of the American Academy of Child and Adolescent Psychiatry.

[259]  J. Edwards,et al.  Hippocampal tissue of patients with refractory temporal lobe epilepsy is associated with astrocyte activation, inflammation, and altered expression of channels and receptors , 2012, Neuroscience.

[260]  D. Graham,et al.  Interindividual differences in the levels of the glutamate transporters GLAST and GLT, but no clear correlation with Alzheimer's disease , 1999, Journal of neuroscience research.

[261]  D. Thal,et al.  Diffuse plaques in the molecular layer show intracellular A beta(8-17)-immunoreactive deposits in subpial astrocytes. , 1999, Clinical neuropathology.

[262]  Gustavo Turecki,et al.  Gene expression deficits in pontine locus coeruleus astrocytes in men with major depressive disorder. , 2013, Journal of psychiatry & neuroscience : JPN.

[263]  J. Silver,et al.  Astrocytes Regulate Microglial Phagocytosis of Senile Plaque Cores of Alzheimer's Disease , 1998, Experimental Neurology.

[264]  Gentleman,et al.  Overexpression of S100β in Down’s syndrome: correlation with patient age and with β‐amyloid deposition , 1999 .