Uncoupling protein-2 promotes nigrostriatal dopamine neuronal function

被引:32
作者
Andrews, Zane B.
Rivera, Alicia
Elsworth, John D.
Roth, Robert H.
Agnati, Luigi
Gago, Belen
Abizaid, Alfonso
Schwartz, Michael
Fuxe, Kjell
Horvath, Tamas L.
机构
[1] Yale Univ, Sch Med, Comparat Med Sect, New Haven, CT 06520 USA
[2] Univ Malaga, Sch Sci, Dept Cell Biol, E-29071 Malaga, Spain
[3] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06520 USA
[4] Univ Modena, Physiol Sect, Dept Biomed Sci, I-41100 Modena, Italy
[5] Yale Univ, Sch Med, Dept Neurobiol, New Haven, CT 06520 USA
[6] Karolinska Inst, Div Cellular & Mol Neurochem, Dept Neurosci, Stockholm, Sweden
[7] Yale Univ, Sch Med, Dept Obstet Gynecol & Reprod Serv, New Haven, CT 06520 USA
关键词
locomotor behaviour; mitochondria; mouse; reactive oxygen species; striatum; tyrosine hydroxylase;
D O I
10.1111/j.1460-9568.2006.04906.x
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Uncoupling protein 2 (UCP2) is known to promote neuroprotection in many forms of neurological pathologies including Parkinson's disease. Here, we examined the hypothesis that UCP2 also mediates aspects of normal nigrostriatal dopamine (DA) function. Mice lacking UCP2 exhibited reduced dopamine turnover in the striatum as measured by the 3,4-dihydoxyphenylacetic acid/dopamine (DOPAC/DA) ratio, reduced tyrosine hydroxylase immunoreactivity (TH IR) in the substantia nigra pars compacta (SNc) and reticulata, striatum and nucleus accumbens. UCP2-knockout (KO) mice also had reduced dopamine transporter immunoreactivity (DAT IR) in the SNc but not other brain regions examined. In order to determine if these biochemical deficits are transcribed into behavioural deficits, we examined locomotor function in UCP2-KO mice compared to wild-type (WT) controls. UCP2-KO mice exhibited significantly reduced total movement distance, movement velocity and increased rest time compared to wild-type controls. These results suggest that UCP2 is an important mitochondrial protein that helps to maintain normal nigrostriatal dopamine neuronal function and a reduction in UCP2 levels may predispose individuals to environmental causes of Parkinson's disease.
引用
收藏
页码:32 / 36
页数:5
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