Abstract:
:A corticostriatal-dependent deficit in the release of ascorbate (AA), an antioxidant vitamin and neuromodulator, occurs concurrently in striatum with dysfunctional GLT1-dependent uptake of glutamate in the R6/2 mouse model of Huntington's disease (HD), an autosomal dominant condition characterized by overt corticostriatal dysfunction. To determine if deficient striatal AA release into extracellular fluid is related to altered GLT1 activity in HD, symptomatic R6/2 mice between 6 and 9 weeks of age and age-matched wild-type (WT) mice received single daily injections of 200 mg/kg ceftriaxone, a β-lactam antibiotic that elevates the functional expression of GLT1, or saline vehicle for five consecutive days. On the following day, in vivo voltammetry was coupled with corticostriatal afferent stimulation to monitor evoked release of AA into striatum. In saline-treated mice, we found a marked decrease in evoked extracellular AA in striatum of R6/2 relative to WT. Ceftriaxone, in contrast, restored striatal AA in R6/2 mice to WT levels. In addition, intra-striatal infusion of either the GLT1 inhibitor dihydrokainic acid or dl-threo-beta-benzyloxyaspartate blocked evoked striatal AA release. Collectively, our results provide compelling evidence for a link between GLT1 activation and release of AA into the striatal extracellular fluid, and suggest that dysfunction of this system is a key component of HD pathophysiology.
journal_name
J Neurochemjournal_title
Journal of neurochemistryauthors
Miller BR,Dorner JL,Bunner KD,Gaither TW,Klein EL,Barton SJ,Rebec GVdoi
10.1111/j.1471-4159.2012.07691.xsubject
Has Abstractpub_date
2012-05-01 00:00:00pages
629-38issue
4eissn
0022-3042issn
1471-4159journal_volume
121pub_type
杂志文章abstract::Expression of rat brain gamma-aminobutyric acid type A (GABA(A)) receptors in Xenopus laevis oocytes can be achieved by injection of the oocytes with synaptosomes. This approach has now been applied to evaluate changes in the function of nigral GABA(A) receptors after degeneration of the striatonigral GABAergic pathwa...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.1998.70062539.x
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abstract::From immunizations of mice with a glutathione S-transferase fusion protein containing residues 724-781 of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor subunit GluR1-flop, two monoclonal antibodies (mAbs) were developed that differed widely in their ranges of specificity. In immunocytochemical ...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
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pub_type: 杂志文章
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journal_title:Journal of neurochemistry
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journal_title:Journal of neurochemistry
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pub_type: 杂志文章
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journal_title:Journal of neurochemistry
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journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.1998.70062357.x
更新日期:1998-06-01 00:00:00
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journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.2004.02600.x
更新日期:2004-09-01 00:00:00
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journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.2011.07300.x
更新日期:2011-07-01 00:00:00
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journal_title:Journal of neurochemistry
pub_type: 杂志文章
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更新日期:1991-10-01 00:00:00
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journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.2001.00412.x
更新日期:2001-07-01 00:00:00
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pub_type: 杂志文章
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更新日期:2015-05-01 00:00:00
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journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.1997.69020704.x
更新日期:1997-08-01 00:00:00
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journal_title:Journal of neurochemistry
pub_type: 杂志文章
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pub_type: 杂志文章
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journal_title:Journal of neurochemistry
pub_type: 杂志文章
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journal_title:Journal of neurochemistry
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journal_title:Journal of neurochemistry
pub_type: 杂志文章
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journal_title:Journal of neurochemistry
pub_type: 杂志文章,评审
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更新日期:2012-01-01 00:00:00
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pub_type: 杂志文章
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journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1981.tb01659.x
更新日期:1981-02-01 00:00:00
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journal_title:Journal of neurochemistry
pub_type: 杂志文章
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更新日期:2019-01-01 00:00:00
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journal_title:Journal of neurochemistry
pub_type: 杂志文章
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更新日期:1995-02-01 00:00:00