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dc.contributor.author
Sanz Blasco, Sara Isabel
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Piña Crespo, Juan C.
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Zhang, Xiaofei
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McKercher, Scott R.
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Lipton, Stuart A.
dc.date.available
2018-03-28T19:40:54Z
dc.date.issued
2016-06
dc.identifier.citation
Sanz Blasco, Sara Isabel; Piña Crespo, Juan C.; Zhang, Xiaofei; McKercher, Scott R.; Lipton, Stuart A.; Levetiracetam inhibits oligomeric Aβ-induced glutamate release from human astrocytes; Lippincott Williams; Neuroreport; 27; 9; 6-2016; 705-709
dc.identifier.issn
0959-4965
dc.identifier.uri
http://hdl.handle.net/11336/40461
dc.description.abstract
A recently identified mechanism for oligomeric Aβ-induced glutamate release from astrocytes involves intracellular Ca2+ elevation, potentially by Ca2+-dependent vesicular release. Evidence suggests that levetiracetam (LEV; Keppra), an antiepileptic drug, can improve cognitive performance in both humans with mild cognitive impairment and animal models of Alzheimer disease. Because LEV acts by modulating neurotransmitter release from neurons by interaction with synaptic vesicles, we tested the effect of LEV on Aβ-induced astrocytic release of glutamate. We used a fluorescence resonance energy transfer-based glutamate sensor (termed SuperGluSnFR), whose structure is based on the ligand-binding site of glutamate receptors, to monitor glutamate release from primary cultures of human astrocytes exposed to oligomeric amyloid-β peptide 1-42 (Aβ42). We found that LEV (10 μM) inhibited oligomeric Aβ-induced astrocytic glutamate release. In addition, we show that this Aβ-induced glutamate release from astrocytes is sensitive to tetanus neurotoxin, an inhibitor of the vesicle release machinery. Taken together, our evidence suggests that LEV inhibits Aβinduced vesicular glutamate release from astrocytes and thus may underlie, at least in part, the ability of LEV to reduce hyperexcitability in Alzheimer disease.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Lippincott Williams
dc.rights
info:eu-repo/semantics/openAccess
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https://creativecommons.org/licenses/by-nc/2.5/ar/
dc.subject
Alzheimer'S Disease
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Amyloid-Β
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Astrocyte
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Levetiracetam
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Synaptic Vesicle Glycoprotein 2a
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Inmunología
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Medicina Básica
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CIENCIAS MÉDICAS Y DE LA SALUD
dc.title
Levetiracetam inhibits oligomeric Aβ-induced glutamate release from human astrocytes
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2018-03-28T14:10:21Z
dc.journal.volume
27
dc.journal.number
9
dc.journal.pagination
705-709
dc.journal.pais
Estados Unidos
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Filadelfia
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Fil: Sanz Blasco, Sara Isabel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; Argentina
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Fil: Piña Crespo, Juan C.. Sanford Burnham Prebys Medical Discovery Institute; Estados Unidos
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Fil: Zhang, Xiaofei. Mount Sinai Hospital; Estados Unidos
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Fil: McKercher, Scott R.. Scintillon Institute. Neurodegenerative Disease Center; Estados Unidos
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Fil: Lipton, Stuart A.. Scintillon Institute. Neurodegenerative Disease Center; Estados Unidos. University of California at San Diego; Estados Unidos
dc.journal.title
Neuroreport
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1097/WNR.0000000000000601
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4874889/
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info:eu-repo/semantics/altIdentifier/url/https://insights.ovid.com/pubmed?pmid=27183239
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