Neurochemical Measurements in Rodents that Model Huntingtion's Disease and Oxidative Stress

Huntington's disease (HD) is a fatal, neurodegenerative movement disorder caused by a CAG repeat expansion on the gene encoding the huntinin protein. HD is characterized by preferential and extensive striatal degeneration. We used fast-scan cyclic voltammetry to measure dopamine release and reserve pool dopamine in genetically and chemically altered rodents that model HD. Genetic HD model mice and rats (R6/1 mice, R/2 mice, and HDtg rats) showed an age-dependent decrease in dopamine release in the dorsolateral caudate putamen. A similar decrease is not seen in 3-nitropropionic (3NP)-treated rats. In the case of R6/2 mice, stimulation at increasing frequencies showed a decrease in dopamine at the highest frequencies of 50 Hz and 60 Hz. The number of reserve pool vesicles was found to decrease in the R6/2 mice while it increased in the 3NP treated rats. In a separate study, methionine sulfoxide reductase A (MsrA) mice, which model oxidative stress, have been reported to have chronically high dopamine levels relative to control mice. Additionally, these high levels parallel an increased presynaptic dopamine release when stimulated in vitro without drug treatments. Here we show evidence in striatal tissue for an increase in dopaminergic reserve pools that correlates to the increased dopamine levels of this knockout mouse. The results suggest that dopamine in reserve pool vesicles accumulates in the MrsA knockout mouse. This evidence supports previous reports that suggest the amount of dopamine in reserve pools is dependent on the overall dopamine levels, including readily releasable dopamine vesicles.

Grantor dc:publisher

University of Kansas

Year dc:date.issued

2011

Author dc:creator

• Ortiz, Andrea Naomi

Advisor dc:contributor.advisor

• Johnson, Michael A

• Chemistry

Statement dc:rights

• This item is protected by copyright and unless otherwise specified the copyright of this thesis/dissertation is held by the author.

Language dc:language.iso

en

Dc Identifier Other

http://dissertations.umi.com/ku:11738

OAI identifier oai:identifier

oai:kuscholarworks.ku.edu:1808/8792