| http://purl.uniprot.org/citations/18353560 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/18353560 | http://www.w3.org/2000/01/rdf-schema#comment | "The striatum, which processes cortical information for behavioral output, is a key target of Huntington's disease (HD), an autosomal dominant condition characterized by cognitive decline and progressive loss of motor control. Increasing evidence implicates deficient glutamate uptake caused by a down-regulation of GLT1, the primary astroglial glutamate transporter. To test this hypothesis, we administered ceftriaxone, a beta-lactam antibiotic known to elevate GLT1 expression (200 mg/kg, i.p., for 5 days), to symptomatic R6/2 mice, a widely studied transgenic model of HD. Relative to vehicle, ceftriaxone attenuated several HD behavioral signs: paw clasping and twitching were reduced, while motor flexibility, as measured in a plus maze, and open-field climbing were increased. Assessment of GLT1 expression in striatum confirmed a ceftriaxone-induced increase relative to vehicle. To determine if the change in behavior and GLT1 expression represented a change in striatal glutamate handling, separate groups of behaving mice were evaluated with no-net-flux microdialysis. Vehicle treatment revealed a glutamate uptake deficit in R6/2 mice relative to wild-type controls that was reversed by ceftriaxone. Vehicle-treated animals, however, did not differ in GLT1 expression, suggesting that the glutamate uptake deficit in R6/2 mice reflects dysfunctional rather than missing GLT1. Our results indicate that impaired glutamate uptake is a major factor underlying HD pathophysiology and symptomology. The glutamate uptake deficit, moreover, is present in symptomatic HD mice and reversal of this deficit by up-regulating the functional expression of GLT1 with ceftriaxone attenuates the HD phenotype."xsd:string |
| http://purl.uniprot.org/citations/18353560 | http://purl.org/dc/terms/identifier | "doi:10.1016/j.neuroscience.2008.02.004"xsd:string |
| http://purl.uniprot.org/citations/18353560 | http://purl.uniprot.org/core/author | "Miller B.R."xsd:string |
| http://purl.uniprot.org/citations/18353560 | http://purl.uniprot.org/core/author | "Shou M."xsd:string |
| http://purl.uniprot.org/citations/18353560 | http://purl.uniprot.org/core/author | "Kennedy R.T."xsd:string |
| http://purl.uniprot.org/citations/18353560 | http://purl.uniprot.org/core/author | "Barton S.J."xsd:string |
| http://purl.uniprot.org/citations/18353560 | http://purl.uniprot.org/core/author | "Rebec G.V."xsd:string |
| http://purl.uniprot.org/citations/18353560 | http://purl.uniprot.org/core/author | "Dorner J.L."xsd:string |
| http://purl.uniprot.org/citations/18353560 | http://purl.uniprot.org/core/author | "Sari Y."xsd:string |
| http://purl.uniprot.org/citations/18353560 | http://purl.uniprot.org/core/author | "Sengelaub D.R."xsd:string |
| http://purl.uniprot.org/citations/18353560 | http://purl.uniprot.org/core/date | "2008"xsd:gYear |
| http://purl.uniprot.org/citations/18353560 | http://purl.uniprot.org/core/name | "Neuroscience"xsd:string |
| http://purl.uniprot.org/citations/18353560 | http://purl.uniprot.org/core/pages | "329-337"xsd:string |
| http://purl.uniprot.org/citations/18353560 | http://purl.uniprot.org/core/title | "Up-regulation of GLT1 expression increases glutamate uptake and attenuates the Huntington's disease phenotype in the R6/2 mouse."xsd:string |
| http://purl.uniprot.org/citations/18353560 | http://purl.uniprot.org/core/volume | "153"xsd:string |
| http://purl.uniprot.org/citations/18353560 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/18353560 |
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