Neuron-astrocyte interactions: partnership for normal function and disease in the central nervous system.

Interactions between neurons and astrocytes are critical for signaling, energy metabolism, extracellular ion homeostasis, volume regulation, and neuroprotection in the central nervous system. Astrocytes face the synapses, send end-foot processes that enwrap the brain capillaries, and form an extensive network interconnected by gap junctions. Astrocytes express several membrane proteins and enzymes that are critical for uptake of glutamate at the synapses, ammonia detoxification, buffering of extracellular K+, and volume regulation. They also participate in detection, propagation, and modulation of excitatory synaptic signals, provide metabolic support to the active neurons, and contribute to functional hyperemia in the active brain tissue. Disturbances of these neuron-astrocyte interactions are likely to play an important role in neurologic disorders including cerebral ischemia, neurodegeneration, migraine, cerebral edema, and hepatic encephalopathy.

[1]  M. Simard,et al.  The neurobiology of glia in the context of water and ion homeostasis , 2004, Neuroscience.

[2]  S. Mengistou,et al.  Short communication , 2011 .

[3]  A. Blei,et al.  Brain edema in acute liver failure. A window to the pathogenesis of hepatic encephalopathy. , 2003, Annals of hepatology.

[4]  Christian Giaume,et al.  Control of gap-junctional communication in astrocytic networks , 1996, Trends in Neurosciences.

[5]  Colin L. Masters,et al.  Neurodegenerative diseases and oxidative stress , 2004, Nature Reviews Drug Discovery.

[6]  Angus M. Brown Brain glycogen re‐awakened , 2004, Journal of neurochemistry.

[7]  A. Ballabio,et al.  Familial hemiplegic migraine type 2 is linked to 0.9Mb region on chromosome 1q23 , 2003, Annals of neurology.

[8]  M. Norenberg,et al.  Oxidative Stress in the Pathogenesis of Hepatic Encephalopathy , 2004, Metabolic Brain Disease.

[9]  I. Klatzo,et al.  Presidental address. Neuropathological aspects of brain edema. , 1967, Journal of neuropathology and experimental neurology.

[10]  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.

[11]  Helmut Kettenmann,et al.  Calcium signalling in glial cells , 1996, Trends in Neurosciences.

[12]  F. Schliess,et al.  Pathogenesis of hepatic encephalopathy , 2002, Journal of gastroenterology and hepatology.

[13]  P. Montagna The physiopathology of migraine: the contribution of genetics , 2004, Neurological Sciences.

[14]  S. Hamann,et al.  Water transport in the brain: Role of cotransporters , 2004, Neuroscience.

[15]  Luc Leybaert,et al.  Neurobarrier Coupling in the Brain: A Partner of Neurovascular and Neurometabolic Coupling? , 2005, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[16]  M. Tymianski,et al.  Molecular mechanisms of glutamate-dependent neurodegeneration in ischemia and traumatic brain injury , 2004, Cellular and Molecular Life Sciences CMLS.

[17]  S. Amara,et al.  Excitatory amino acid transporters: keeping up with glutamate , 2002, Neurochemistry International.

[18]  S. Silberstein Migraine Pathophysiology and its Clinical Implications , 2004, Cephalalgia : an international journal of headache.

[19]  G. McBean Cerebral cystine uptake: a tale of two transporters. , 2002, Trends in pharmacological sciences.

[20]  R. Swanson,et al.  Astrocyte influences on ischemic neuronal death. , 2004, Current molecular medicine.

[21]  G. Bodega,et al.  Glutamine synthetase in brain: effect of ammonia , 2002, Neurochemistry International.

[22]  E. Vicaut,et al.  The clinical spectrum of familial hemiplegic migraine associated with mutations in a neuronal calcium channel. , 2001, The New England journal of medicine.

[23]  E. Newman,et al.  Potassium buffering in the central nervous system , 2004, Neuroscience.

[24]  K. Kiening,et al.  Edema and brain trauma , 2004, Neuroscience.

[25]  Robert G. Shulman,et al.  Energy on Demand , 1999, Science.

[26]  P. Magistretti,et al.  Astrocytes Couple Synaptic Activity to Glucose Utilization in the Brain. , 1999, News in Physiological Sciences - NIPS.

[27]  M. Aschner,et al.  Pharmacology and toxicology of astrocyte-neuron glutamate transport and cycling. , 2002, The Journal of pharmacology and experimental therapeutics.

[28]  D. Heistad,et al.  Regulation of the cerebral circulation: role of endothelium and potassium channels. , 1998, Physiological reviews.

[29]  Peter Lipton,et al.  Do active cerebral neurons really use lactate rather than glucose? , 2001, Trends in Neurosciences.

[30]  Pascal Clayette,et al.  Oxidative stress and neuroAIDS: triggers, modulators and novel antioxidants , 2001, Trends in Neurosciences.

[31]  R. D’Ambrosio The role of glial membrane ion channels in seizures and epileptogenesis. , 2004, Pharmacology & therapeutics.

[32]  P. Marcaggi,et al.  Ammonium in nervous tissue: transport across cell membranes, fluxes from neurons to glial cells, and role in signalling , 2001, Progress in Neurobiology.

[33]  M. Bennett,et al.  New roles for astrocytes: Gap junction hemichannels have something to communicate , 2003, Trends in Neurosciences.

[34]  S. Goldman,et al.  New roles for astrocytes: Redefining the functional architecture of the brain , 2003, Trends in Neurosciences.

[35]  H. Sontheimer Malignant gliomas: perverting glutamate and ion homeostasis for selective advantage , 2003, Trends in Neurosciences.

[36]  Pierre J Magistretti,et al.  GABA uptake into astrocytes is not associated with significant metabolic cost: Implications for brain imaging of inhibitory transmission , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[37]  U. Reuter,et al.  Migraine aura: new information on underlying mechanisms , 2004, Current opinion in neurology.

[38]  M. C. Angulo,et al.  Neuron-to-astrocyte signaling is central to the dynamic control of brain microcirculation , 2003, Nature Neuroscience.

[39]  E. Newman New roles for astrocytes: Regulation of synaptic transmission , 2003, Trends in Neurosciences.

[40]  A. McCall Cerebral glucose metabolism in diabetes mellitus. , 2004, European journal of pharmacology.

[41]  M. Nedergaard,et al.  Direct signaling from astrocytes to neurons in cultures of mammalian brain cells. , 1994, Science.

[42]  Luo Lu,et al.  Volume‐regulated anion conductance in cultured rat cerebral astrocytes requires calmodulin activity , 2004, Glia.

[43]  Charles Nicholson,et al.  Perspectives on spreading depression , 2000, Brain Research Reviews.

[44]  P. Ramarao,et al.  Dementia of Alzheimer's disease and other neurodegenerative disorders--memantine, a new hope. , 2005, Pharmacological research.

[45]  G. Bonvento,et al.  Structural organization of the perivascular astrocyte endfeet and their relationship with the endothelial glucose transporter: A confocal microscopy study , 1998, Glia.

[46]  P. Kofuji,et al.  The Potassium Channel Kir4.1 Associates with the Dystrophin-Glycoprotein Complex via α-Syntrophin in Glia* , 2004, Journal of Biological Chemistry.

[47]  A. Aperia,et al.  Regulation of brain aquaporins , 2004, Neuroscience.

[48]  A. Volterra,et al.  Neuron-astrocyte cross-talk during synaptic transmission: physiological and neuropathological implications. , 2001, Progress in brain research.

[49]  R. Butterworth,et al.  Pathophysiology of Hepatic Encephalopathy: A New Look at GABA from the Molecular Standpoint , 2004, Metabolic Brain Disease.

[50]  J. Deitmer Strategies for metabolic exchange between glial cells and neurons. , 2001, Respiration physiology.

[51]  David Blum,et al.  Molecular pathways involved in the neurotoxicity of 6-OHDA, dopamine and MPTP: contribution to the apoptotic theory in Parkinson's disease , 2001, Progress in Neurobiology.

[52]  A. Volterra,et al.  Glutamate transporters are oxidant-vulnerable: a molecular link between oxidative and excitotoxic neurodegeneration? , 1998, Trends in pharmacological sciences.

[53]  N. Abbott,et al.  Astrocyte–endothelial interactions and blood–brain barrier permeability * , 2002 .

[54]  R. Butterworth Molecular Neurobiology of Acute Liver Failure , 2003, Seminars in liver disease.

[55]  H. Kimelberg Water homeostasis in the brain: Basic concepts , 2004, Neuroscience.

[56]  Maiken Nedergaard,et al.  Astrocyte-mediated control of cerebral microcirculation , 2003, Trends in Neurosciences.

[57]  Ole P. Ottersen,et al.  The molecular basis of water transport in the brain , 2003, Nature Reviews Neuroscience.

[58]  R. Jalan,et al.  The molecular pathogenesis of hepatic encephalopathy. , 2003, The international journal of biochemistry & cell biology.

[59]  P. Haydon Glia: listening and talking to the synapse , 2001, Nature Reviews Neuroscience.

[60]  C. Gluud,et al.  Benzodiazepine receptor antagonists for acute and chronic hepatic encephalopathy. , 2001, The Cochrane database of systematic reviews.

[61]  D. Harder,et al.  Astrocytes function in matching blood flow to metabolic activity. , 2002, News in physiological sciences : an international journal of physiology produced jointly by the International Union of Physiological Sciences and the American Physiological Society.

[62]  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.

[63]  A. Teramoto,et al.  Usefulness of niravoline, an arginine vasopressin inhibitor, on tumour-origin brain oedema. , 2000, Acta neurochirurgica. Supplement.

[64]  J. Weiss,et al.  Excitotoxic and oxidative cross-talk between motor neurons and glia in ALS pathogenesis , 2004, Trends in Neurosciences.

[65]  N. Hussy,et al.  Osmotic regulation of neuronal activity: a new role for taurine and glial cells in a hypothalamic neuroendocrine structure , 2000, Progress in Neurobiology.

[66]  L. Gluud,et al.  Benzodiazepine receptor antagonists for hepatic encephalopathy. , 2004, The Cochrane database of systematic reviews.

[67]  A. Levey,et al.  Selective loss of glial glutamate transporter GLT‐1 in amyotrophic lateral sclerosis , 1995, Annals of neurology.

[68]  A. Verkman,et al.  Aquaporin-4 gene disruption in mice protects against impaired retinal function and cell death after ischemia. , 2004, Investigative ophthalmology & visual science.

[69]  H. Sontheimer,et al.  Expression of Voltage-Gated Chloride Channels in Human Glioma Cells , 2003, The Journal of Neuroscience.

[70]  C. Steinhäuser,et al.  Ion channels in glial cells , 2000, Brain Research Reviews.

[71]  C. Steinhäuser,et al.  Glial membrane channels and receptors in epilepsy: impact for generation and spread of seizure activity. , 2002, European journal of pharmacology.

[72]  L. Barbeito,et al.  A role for astrocytes in motor neuron loss in amyotrophic lateral sclerosis , 2004, Brain Research Reviews.

[73]  Andrei G. Vlassenko,et al.  Increased lactate/pyruvate ratio augments blood flow in physiologically activated human brain. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[74]  M. Papadopoulos,et al.  Water transport becomes uncoupled from K+ siphoning in brain contusion, bacterial meningitis, and brain tumours: immunohistochemical case review , 2003, Journal of clinical pathology.

[75]  R. Dringen,et al.  Metabolism and functions of glutathione in brain , 2000, Progress in Neurobiology.

[76]  M. Nedergaard,et al.  Gap junctions are required for the propagation of spreading depression. , 1995, Journal of neurobiology.

[77]  C. Iadecola Neurovascular regulation in the normal brain and in Alzheimer's disease , 2004, Nature Reviews Neuroscience.

[78]  D. Davies,et al.  Blood–brain barrier breakdown in septic encephalopathy and brain tumours * , 2002, Journal of anatomy.

[79]  P. Magistretti,et al.  Astrocytes generate Na+-mediated metabolic waves. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[80]  F. Bricaire,et al.  Neurodegenerative diseases and oxidative stress. , 2004, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[81]  S. Snyder,et al.  Atypical neural messengers , 2001, Trends in Neurosciences.

[82]  R. Janzer,et al.  Astrocytes induce blood–brain barrier properties in endothelial cells , 1987, Nature.

[83]  Leif Hertz,et al.  Astrocytic control of glutamatergic activity: astrocytes as stars of the show , 2004, Trends in Neurosciences.