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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
5
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pubmed:dateCreated |
2010-4-27
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pubmed:abstractText |
Reactive astrocytosis develops in many neurologic diseases, including epilepsy. Astrocytotic contributions to pathophysiology are poorly understood. Studies examining this are confounded by comorbidities accompanying reactive astrocytosis. We found that high-titer transduction of astrocytes with enhanced green fluorescent protein (eGFP) via adeno-associated virus induced reactive astrocytosis without altering the intrinsic properties or anatomy of neighboring neurons. We examined the consequences of selective astrocytosis induction on synaptic transmission in mouse CA1 pyramidal neurons. Neurons near eGFP-labeled reactive astrocytes had reduced inhibitory, but not excitatory, synaptic currents. This inhibitory postsynaptic current (IPSC) erosion resulted from a failure of the astrocytic glutamate-glutamine cycle. Reactive astrocytes downregulated expression of glutamine synthetase. Blockade of this enzyme normally induces rapid synaptic GABA depletion. In astrocytotic regions, residual inhibition lost sensitivity to glutamine synthetase blockade, whereas exogenous glutamine administration enhanced IPSCs. Astrocytosis-mediated deficits in inhibition triggered glutamine-reversible hyperexcitability in hippocampal circuits. Thus, reactive astrocytosis could generate local synaptic perturbations, leading to broader functional deficits associated with neurologic disease.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/(1,2,5,6-tetrahydropyridin-4-yl)meth...,
http://linkedlifedata.com/resource/pubmed/chemical/Aif1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens,
http://linkedlifedata.com/resource/pubmed/chemical/Bromodeoxyuridine,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/GABA Antagonists,
http://linkedlifedata.com/resource/pubmed/chemical/Glutamate-Ammonia Ligase,
http://linkedlifedata.com/resource/pubmed/chemical/Green Fluorescent Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Microfilament Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Nerve Tissue Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphinic Acids,
http://linkedlifedata.com/resource/pubmed/chemical/Proteoglycans,
http://linkedlifedata.com/resource/pubmed/chemical/Pyridazines,
http://linkedlifedata.com/resource/pubmed/chemical/Pyridines,
http://linkedlifedata.com/resource/pubmed/chemical/chondroitin sulfate proteoglycan 4,
http://linkedlifedata.com/resource/pubmed/chemical/enhanced green fluorescent protein,
http://linkedlifedata.com/resource/pubmed/chemical/gabazine
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
1546-1726
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:volume |
13
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
584-91
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:20418874-Analysis of Variance,
pubmed-meshheading:20418874-Animals,
pubmed-meshheading:20418874-Animals, Newborn,
pubmed-meshheading:20418874-Antigens,
pubmed-meshheading:20418874-Astrocytes,
pubmed-meshheading:20418874-Bromodeoxyuridine,
pubmed-meshheading:20418874-Calcium-Binding Proteins,
pubmed-meshheading:20418874-Electric Stimulation,
pubmed-meshheading:20418874-GABA Antagonists,
pubmed-meshheading:20418874-Gliosis,
pubmed-meshheading:20418874-Glutamate-Ammonia Ligase,
pubmed-meshheading:20418874-Green Fluorescent Proteins,
pubmed-meshheading:20418874-Hippocampus,
pubmed-meshheading:20418874-Mice,
pubmed-meshheading:20418874-Microfilament Proteins,
pubmed-meshheading:20418874-Nerve Tissue Proteins,
pubmed-meshheading:20418874-Neural Inhibition,
pubmed-meshheading:20418874-Neurons,
pubmed-meshheading:20418874-Patch-Clamp Techniques,
pubmed-meshheading:20418874-Phosphinic Acids,
pubmed-meshheading:20418874-Proteoglycans,
pubmed-meshheading:20418874-Pyridazines,
pubmed-meshheading:20418874-Pyridines,
pubmed-meshheading:20418874-Synaptic Potentials,
pubmed-meshheading:20418874-Transduction, Genetic
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pubmed:year |
2010
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pubmed:articleTitle |
Selective induction of astrocytic gliosis generates deficits in neuronal inhibition.
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pubmed:affiliation |
Division of Neurology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
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pubmed:publicationType |
Journal Article,
In Vitro,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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