Dysregulation of intracellular dopamine stores revealed in the R6/2 mouse striatum.
Huntington's disease (HD) is a fatal, neurodegenerative movement disorder characterized by preferential and extensive striatal degeneration. Here, we used fast-scan cyclic voltammetry to study the mobilization and efflux of reserve pool dopamine (DA) in striatal brain slices from HD model R6/2 mice. When applying stimulus trains of 120 pulses, evoked DA release in wild-type (WT) slices was greater than that in R6/2 slices at the higher frequencies (50 and 60 Hz). To quantify cytosolic and reserve pool DA levels, amphetamine-induced DA efflux was measured after pre-treatment with either tetrabenazine or alpha-methyl-p-tyrosine. Slices from 12-week-old R6/2 mice released less DA than slices from WT mice, while no difference was noted in slices from 6-week old mice. The vesicular release of reserve pool DA, mobilized by treatment with cocaine, was shorter lived in R6/2 slices compared with WT slices even though peak DA release was the same. Moreover, the number of DA reserve pool vesicles in R6/2 mice was less than half of that in WT. Therefore, our data suggest that the same number of DA molecules are present in each reserve pool vesicle in WT and R6/2 mice and that these vesicles are readily mobilized in both genotypes; however, R6/2 mice have fewer DA reserve pool vesicles available for mobilization.
Ortiz
Andrea N
AN
Department of Chemistry and R. N. Adams Institute for Bioanalytical Chemistry, The University of Kansas, Lawrence, Kansas 66047-7572, USA.
Kurth
Benjamin J
BJ
Osterhaus
Gregory L
GL
Johnson
Michael A
MA
D000818:Animals; D001703:Biophysics; D002788:Cholesterol Esters / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D004558:Electric Stimulation / Q000379:methods; D004563:Electrochemistry / Q000379:methods; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D045604:Extracellular Fluid / Q000187:drug effects / Q000378:metabolism*; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000235:genetics / Q000473:pathology; D066298:In Vitro Techniques; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology; D019805:alpha-Methyltyrosine / Q000494:pharmacology
D002788:Cholesterol Esters; D004791:Enzyme Inhibitors; D018690:Excitatory Amino Acid Agonists; C506812:Htt protein, mouse; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; C446741:cholesteryl oleoyl carbonate; D019805:alpha-Methyltyrosine; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D004298:Dopamine