Extracellular ascorbate modulates cortically evoked glutamate dynamics in rat striatum

Rebec, George V.; Witowski, Steven R.; Sandstrom, Michael I; Rostand, Rebecca D; Kennedy, Robert T.

doi:10.1016/j.neulet.2004.12.027

Cited by 38 publications

(35 citation statements)

References 21 publications

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“…In any case, the explanation for the lack of effect of AA on extracellular GLU is probably more complex. Previous studies have reported an extracellular GLU increase after AA administration, an effect more evident when doses 2e3 times higher than that used here were administered (Lai et al, 2000;Rebec et al, 2005). In addition, the GLU response to AA is dependent on different variables including motor behaviour (O'Neill and Fillenz, 1985;Rebec et al, 2002), the light-on/light-off condition (the GLU response is less during the light-on condition) (Sandstrom and Rebec, 2007), and the previous level of extracellular GLU (Sandstrom and Rebec, 2007).…”

Section: Aa Action On Daergic and Gluergic Activitymentioning

confidence: 58%

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Striatal interaction among dopamine, glutamate and ascorbate

et al. 2012

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Section: Aa Action On Daergic and Gluergic Activitymentioning

confidence: 58%

“…Taking into account that the extracellular AA concentration in the striatum of anesthetized rats ranges between 0.2 and 0.3 mM (Basse-Tomusk and Rebec, 1991), the AA dose selected here is likely to increase the basal concentration of AA but not beyond normal physiological limits (Rebec et al, 2005).…”

Section: Methodsmentioning

confidence: 99%

Striatal interaction among dopamine, glutamate and ascorbate

et al. 2012

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“…But elevated extracellular glutamate could desensitize some receptors and thus mask an increase in the level of synaptic glutamate. In fact, measurements of striatal extracellular glutamate in response to cortical stimulation indicate that glutamate uptake decreases after intrastriatal infusions of AA (107). Thus, corticostriatal glutamate transmission is sensitive to the level of AA in striatal extracellular fluid.…”

Section: Modulation Of Striatal Functionmentioning

confidence: 99%

Dysregulation of Corticostriatal Ascorbate Release and Glutamate Uptake in Transgenic Models of Huntington's Disease

Rebec

2013

Antioxidants & Redox Signaling

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Significance: Dysregulation of cortical and striatal neuronal processing plays a critical role in Huntington's disease (HD), a dominantly inherited condition that includes a progressive deterioration of cognitive and motor control. Growing evidence indicates that ascorbate (AA), an antioxidant vitamin, is released into striatal extracellular fluid when glutamate is cleared after its release from cortical afferents. Both AA release and glutamate uptake are impaired in the striatum of transgenic mouse models of HD owing to a downregulation of glutamate transporter 1 (GLT1), the protein primarily found on astrocytes and responsible for removing most extracellular glutamate. Improved understanding of an AA-glutamate interaction could lead to new therapeutic strategies for HD. Recent Advances: Increased expression of GLT1 following treatment with ceftriaxone, a beta-lactam antibiotic, increases striatal glutamate uptake and AA release and also improves the HD behavioral phenotype. In fact, treatment with AA alone restores striatal extracellular AA to wild-type levels in HD mice and not only improves behavior but also improves the firing pattern of neurons in HD striatum. Critical Issues: Although evidence is growing for an AA-glutamate interaction, several key issues require clarification: the site of action of AA on striatal neurons; the precise role of GLT1 in striatal AA release; and the mechanism by which HD interferes with this role. Future Directions: Further assessment of how the HD mutation alters corticostriatal signaling is an important next step. A critical focus is the role of astrocytes, which express GLT1 and may be the primary source of extracellular AA.

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“…However, recent work has shown that copper is released from hippocampal neurons via a mechanism that involves a vesicle preloaded by the Cu(I)-specific Menkes ATPase. Synaptic conditions fluctuate, but basal conditions contain a high concentration of the reductants ascorbate (400 μM) [52] and astrocytically derived glutathione [53] and, importantly, many brain regions are relatively hypoxic [54], which suggests Cu(I) may not be rapidly oxidized and may thus have some relevance in the synapse. Additionally, it appears that released copper is bound only to low-molecular weight ligands, suggesting that the metal is readily available even to low affinity sites [46,55].…”

Section: Metals In the Brainmentioning

confidence: 99%

Reorganizing Metals: the Use of Chelating Compounds as Potential Therapies for Metal-Related Neurodegenerative Disease

Badrick

Jones²

2011

CTMC

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Metal ions, particularly copper, zinc and iron, are implicated in several amyloidogenic neurodegenerative disorders. In the brain, as elsewhere in the body, metal ion excess or deficiency can potentially inhibit protein function, interfere with correct protein folding or, in the case of iron or copper, promote oxidative stress. The involvement of metal ions in neurodegenerative disorders has made them an emerging target for therapeutic interventions. One approach has been to chelate and sequester the ions and thus limit their potential to interfere with protein folding or render them unable to undergo redox processes. Newer approaches suggest that redistributing metal ions has therapeutic benefits, and recent studies indicate that alleviating cellular copper deficiency may be a plausible way to limit neurodegeneration. In this review we discuss the role of metals in amyloidogenic, neurodegenerative disorders and highlight some mechanisms and compounds used in various therapeutic approaches.

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Extracellular ascorbate modulates cortically evoked glutamate dynamics in rat striatum

Cited by 38 publications

References 21 publications

Striatal interaction among dopamine, glutamate and ascorbate

Striatal interaction among dopamine, glutamate and ascorbate

Dysregulation of Corticostriatal Ascorbate Release and Glutamate Uptake in Transgenic Models of Huntington's Disease

Reorganizing Metals: the Use of Chelating Compounds as Potential Therapies for Metal-Related Neurodegenerative Disease

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