Dysregulation of ascorbate release in the striatum of behaving mice expressing the Huntington's disease gene.
The extracellular fluid of the striatum contains a high level of ascorbate, an antioxidant vitamin known to play a key role in behavioral activation. We assessed the extracellular dynamics of ascorbate in R6/2 mice engineered to express the gene for Huntington's disease (HD), an autosomal dominant condition characterized by the loss of striatal neurons. Slow-scan voltammetry was used to measure striatal ascorbate during anesthesia and subsequent behavioral recovery. Although both the HD mice and their littermate controls had comparable ascorbate levels during anesthesia, the gradual return of behavioral activation over the next 120 min led to dramatically different ascorbate responses: a progressive increase in controls and a 25-50% decline in HD mice. In contrast, 3,4-dihydroxyphenylacetic acid, a major dopamine metabolite, showed no group differences. Behaviorally, HD mice were less active overall than controls and showed a relatively restricted range of spontaneous movements. Both the ascorbate and behavioral deficits were evident in 6-week-old HD mice and persisted in all subsequent test sessions through 10 weeks of age. Collectively, although these results are consistent with inadequate antioxidant protection in the HD striatum, they indicate that the ascorbate deficit is confined to periods of behavioral activation.
Rebec
George V
GV
Program in Neural Science, Department of Psychology, Indiana University, Bloomington, Indiana 47405-7007, USA. rebec@indiana.edu
Barton
Scott J
SJ
Ennis
Michelle D
MD
D015102:3,4-Dihydroxyphenylacetic Acid / Q000032:analysis / Q000378:metabolism; D000818:Animals; D001205:Ascorbic Acid / Q000032:analysis / Q000378:metabolism*; D001522:Behavior, Animal; D001835:Body Weight; D003342:Corpus Striatum / Q000503:physiopathology*; D004195:Disease Models, Animal; D018450:Disease Progression; D004563:Electrochemistry; D005110:Extracellular Space / Q000737:chemistry / Q000378:metabolism; D006816:Huntington Disease / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008839:Microelectrodes; D009043:Motor Activity; D010641:Phenotype; D013037:Spatial Behavior
D015102:3,4-Dihydroxyphenylacetic Acid; D001205:Ascorbic Acid