Impaired dopamine release and uptake in R6/1 Huntington's disease model mice.
Huntington's disease (HD) is a progressive, neurodegenerative movement disorder. Here, we used fast-scan cyclic voltammetry to measure dopamine release and uptake in striatal brain slices from R6/1 HD model mice. Peak dopamine release ([DA](max)) was significantly diminished in R6/1 mice (52% of wild-type at 24 weeks of age). Similarly, dopamine released per locally applied electrical stimulus pulse ([DA](p)), which is [DA](max) corrected for uptake and electrode performance, was also diminished in R6/1 mice (43% of wild-type by 24 weeks of age). Moreover, V(max), the maximum rate of dopamine uptake, obtained by modeling the stimulated release plots, was decreased at 16 and 24 weeks of age in R6/1 mice (51 and 48% of wild-type, respectively). Thus, impairments in both dopamine release and uptake appear to progress in an age-dependent manner in R6/1 mice.
Department of Chemistry and R.N. Adams Institute of Bioanalytical Chemistry, Lawrence, KS 66045, USA.
Andrea N
AN
Ortiz
Benjamin J
BJ
Kurth
Gregory L
GL
Osterhaus
Michael A
MA
Johnson
D000818:Animals; D003342:Corpus Striatum / Q000378:metabolism; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D055664:Electrochemical Techniques / Q000379:methods; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000378:metabolism*; D066298:In Vitro Techniques; D051379:Mice; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics
C086055:HTT protein, human; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D004298:Dopamine
J Neurosci Methods. 2001 Dec 15;112(2):119-33
11716947
Eur J Neurosci. 2001 Nov;14(9):1425-35
11722604
Cell. 1996 Nov 1;87(3):493-506
8898202
J Neurochem. 2010 Feb;112(3):755-61
19929911
Cell. 1997 Aug 8;90(3):537-48
9267033
Mol Pharmacol. 2007 May;71(5):1222-32
17267664
Neurobiol Dis. 2002 Oct;11(1):134-46
12460553
J Neurochem. 2006 May;97(3):737-46
16573654
J Neurochem. 2005 Jun;93(5):1057-68
15934928
Cell. 1993 Mar 26;72(6):971-83
8458085
Neuroscience. 2009 Jul 7;161(3):940-9
19362126