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      The role of astroglia in neuroprotection Translated title: El papel de la astroglía en la neuroprotección Translated title: Rôle de l'astroglie dans la neuroprotection

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          Abstract

          Astrocytes are the main neural cell type responsible for the maintenance of brain homeostasis. They form highly organized anatomical domains that are interconnected into extensive networks. These features, along with the expression of a wide array of receptors, transporters, and ion channels, ideally position them to sense and dynamically modulate neuronal activity. Astrocytes cooperate with neurons on several levels, including neurotransmitter trafficking and recycling, ion homeostasis, energy metabolism, and defense against oxidative stress. The critical dependence of neurons upon their constant support confers astrocytes with intrinsic neuroprotective properties which are discussed here. Conversely, pathogenic stimuli may disturb astrocytic function, thus compromising neuronal functionality and viability. Using neuroinflammation, Alzheimer's disease, and hepatic encephalopathy as examples, we discuss how astrocytic defense mechanisms may be overwhelmed in pathological conditions, contributing to disease progression.

          Translated abstract

          Los astrocitos constituyen el principal tipo celular neural responsable del mantenimiento de la homeostasis cerebral. Ellos forman áreas anatómicas altamente organizadas que están interconectadas en extensas redes. Estas caracierísticas, junto con la expresión de una gran variedad de receptores, transportadores y canales iónicos, los favorece de manera ideal para detectar y modular dínámicamente la actívídad neuronal. Los asirocitos cooperan con las neuronas a varios níveles, incluyendo el tránsito y reciclaje de neurotransmisores, la homeostasis iónica, la neuroenergética y la defensa contra el estrés oxidativo. Las neuronas dependen en forma crítica de su soporte constante, lo que le confiere a los astrocitos propiedades neuroprotectoras intrinsecas, las cuales también se discuten aqui. A la inversa, los estímulos patogénicos pueden alterar la función astrocítica, comprometiendo así la funcionalidad y la viabilidad neuronal. Se utilizan como ejemplos la neuroinflamación, la Enfermedad de Alzheimer y la encefalopatía hepática para discutir cómo los mecanismos de defensa de los astrocitos pueden estar sobrepasados en las condiciones patológicas, lo que contribuye a la progresión hacia la enfermedad.

          Translated abstract

          Les astrocytes sont le principal type de cellules neuronales responsables de l'entretien de l'homéostasie cérébrale. Ils s'interconnectent en réseaux étendus, formant des régions anatomiques très organisées. Cette organisation qui s'accompagne de toute une série de récepteurs, transporteurs et canaux ioniques, les met en position idéale pour pressentir et moduler de façon dynamique l'activité neuronale. Les astrocytes coopèrent avec les neurones à différents niveaux, dont le recyclage et la circulation des neurotransmetteurs, l'homéostasie ionique, la neuroénergétique et la défense contre le stress oxydant. Les neurones sont très dépendants du soutien constant des astrocytes, ce qui donne à ces derniers des propriétés neuroprotectrices que nous analysons dans cet article. À l'opposé, lorsque des stimuli pathogènes troublent la fonction astrocytaire, la fonctionnalité et la viabilité des neurones sont compromises. En prenant pour exemples la neuro-inflammation, la maladie d'Alzheimer et l'encéphalopathie hépatique, nous montrerons comment les mécanismes de défense astrocytaires peuvent être débordés en situation pathologique, participant ainsi à la progression de la maladie.

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          Uniquely hominid features of adult human astrocytes.

          Defining the microanatomic differences between the human brain and that of other mammals is key to understanding its unique computational power. Although much effort has been devoted to comparative studies of neurons, astrocytes have received far less attention. We report here that protoplasmic astrocytes in human neocortex are 2.6-fold larger in diameter and extend 10-fold more GFAP (glial fibrillary acidic protein)-positive primary processes than their rodent counterparts. In cortical slices prepared from acutely resected surgical tissue, protoplasmic astrocytes propagate Ca(2+) waves with a speed of 36 microm/s, approximately fourfold faster than rodent. Human astrocytes also transiently increase cystosolic Ca(2+) in response to glutamatergic and purinergic receptor agonists. The human neocortex also harbors several anatomically defined subclasses of astrocytes not represented in rodents. These include a population of astrocytes that reside in layers 5-6 and extend long fibers characterized by regularly spaced varicosities. Another specialized type of astrocyte, the interlaminar astrocyte, abundantly populates the superficial cortical layers and extends long processes without varicosities to cortical layers 3 and 4. Human fibrous astrocytes resemble their rodent counterpart but are larger in diameter. Thus, human cortical astrocytes are both larger, and structurally both more complex and more diverse, than those of rodents. On this basis, we posit that this astrocytic complexity has permitted the increased functional competence of the adult human brain.
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            Glutamate uptake.

            Brain tissue has a remarkable ability to accumulate glutamate. This ability is due to glutamate transporter proteins present in the plasma membranes of both glial cells and neurons. The transporter proteins represent the only (significant) mechanism for removal of glutamate from the extracellular fluid and their importance for the long-term maintenance of low and non-toxic concentrations of glutamate is now well documented. In addition to this simple, but essential glutamate removal role, the glutamate transporters appear to have more sophisticated functions in the modulation of neurotransmission. They may modify the time course of synaptic events, the extent and pattern of activation and desensitization of receptors outside the synaptic cleft and at neighboring synapses (intersynaptic cross-talk). Further, the glutamate transporters provide glutamate for synthesis of e.g. GABA, glutathione and protein, and for energy production. They also play roles in peripheral organs and tissues (e.g. bone, heart, intestine, kidneys, pancreas and placenta). Glutamate uptake appears to be modulated on virtually all possible levels, i.e. DNA transcription, mRNA splicing and degradation, protein synthesis and targeting, and actual amino acid transport activity and associated ion channel activities. A variety of soluble compounds (e.g. glutamate, cytokines and growth factors) influence glutamate transporter expression and activities. Neither the normal functioning of glutamatergic synapses nor the pathogenesis of major neurological diseases (e.g. cerebral ischemia, hypoglycemia, amyotrophic lateral sclerosis, Alzheimer's disease, traumatic brain injury, epilepsy and schizophrenia) as well as non-neurological diseases (e.g. osteoporosis) can be properly understood unless more is learned about these transporter proteins. Like glutamate itself, glutamate transporters are somehow involved in almost all aspects of normal and abnormal brain activity.
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              Epilepsy and exacerbation of brain injury in mice lacking the glutamate transporter GLT-1.

              Extracellular levels of the excitatory neurotransmitter glutamate in the nervous system are maintained by transporters that actively remove glutamate from the extracellular space. Homozygous mice deficient in GLT-1, a widely distributed astrocytic glutamate transporter, show lethal spontaneous seizures and increased susceptibility to acute cortical injury. These effects can be attributed to elevated levels of residual glutamate in the brains of these mice.
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                Author and article information

                Contributors
                Laboratory of Neuroenergetlcs and Cellular Dynamics, Brain Mind Institute, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland
                Centre de Neurosciences Psychiatriques, CHUV, Département de Psychiatrie, Site de Cery, Lausanne, Switzerland
                Journal
                Dialogues Clin Neurosci
                Dialogues Clin Neurosci
                Dialogues in Clinical Neuroscience
                Les Laboratoires Servier (France )
                1294-8322
                1958-5969
                September 2009
                : 11
                : 3
                : 281-295
                Affiliations
                Laboratory of Neuroenergetlcs and Cellular Dynamics, Brain Mind Institute, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland
                Centre de Neurosciences Psychiatriques, CHUV, Département de Psychiatrie, Site de Cery, Lausanne, Switzerland
                Author notes
                Article
                10.31887/DCNS.2009.11.3/mbelanger
                3181926
                19877496
                804aa745-fd35-4954-a764-a6c97b168514
                Copyright: © 2009 LLS

                This is an open-access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by-nc-nd/3.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Categories
                Translational Research

                Neurosciences
                astrocyte,alzheimer's disease,astrocyte-neuron interaction,hepatic encephalopathy,brain homeostasis,neuroinflammation

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