title: Dysregulation of corticostriatal ascorbate release and glutamate uptake in transgenic models of Huntington's disease.
abstract: CONCLUSIONS
  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.
  
  
  BACKGROUND
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Program in Neuroscience, Department of Psychological and Brain Sciences, Indiana University , Bloomington, Indiana.
authors: George V
authors: GV
authors: Rebec
mesh_terms: D000818:Animals; D001205:Ascorbic Acid / Q000378:metabolism*; D001692:Biological Transport; D002540:Cerebral Cortex / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism; D004195:Disease Models, Animal; D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans; D006816:Huntington Disease / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic
chemical_list: D018698:Glutamic Acid; D001205:Ascorbic Acid
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