| First Author | Dorner JL | Year | 2009 |
| Journal | Brain Res | Volume | 1290 |
| Pages | 111-20 | PubMed ID | 19616518 |
| Mgi Jnum | J:157213 | Mgi Id | MGI:4430175 |
| Doi | 10.1016/j.brainres.2009.07.019 | Citation | Dorner JL, et al. (2009) Corticostriatal dysfunction underlies diminished striatal ascorbate release in the R6/2 mouse model of Huntington's disease. Brain Res 1290:111-20 |
| abstractText | A behavior-related deficit in the release of ascorbate (AA), an antioxidant vitamin, occurs in the striatum of R6/2 mice expressing the human mutation for Huntington's disease (HD), a dominantly inherited condition characterized by striatal dysfunction. To determine the role of corticostriatal fibers in AA release, we combined slow-scan voltammetry with electrical stimulation of cortical afferents to measure evoked fluctuations in extracellular AA in wild-type (WT) and R6/2 striatum. Although cortical stimulation evoked a rapid increase in AA release in both groups, the R6/2 response had a significantly shorter duration and smaller magnitude than WT. To determine if corticostriatal dysfunction also underlies the behavior-related AA deficit in R6/2s, we measured striatal AA release in separate groups of mice treated with d-amphetamine (5 mg/kg), a psychomotor stimulant known to release AA from corticostriatal terminals independently of dopamine. Relative to WT, both AA release and behavioral activation were diminished in R6/2 mice. Collectively, our results show that the corticostriatal pathway is directly involved in AA release and that this system is dysfunctional in HD. Moreover, because AA release requires glutamate uptake, a failure of striatal AA release in HD is consistent with an overactive glutamate system and diminished glutamate transport, both of which are thought to be central to HD pathogenesis. |
