Uncoupling protein-2 promotes nigrostriatal dopamine neuronal function.
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.
Andrews
Zane B
ZB
Department of Obstetrics, Gynecology & Reproductive Services, Yale University School of Medicine, New Haven, CT 06510, USA.
Rivera
Alicia
A
Elsworth
John D
JD
Roth
Robert H
RH
Agnati
Luigi
L
Gago
Belen
B
Abizaid
Alfonso
A
Schwartz
Michael
M
Fuxe
Kjell
K
Horvath
Tamas L
TL
D015102:3,4-Dihydroxyphenylacetic Acid / Q000494:pharmacology; D000818:Animals; D003342:Corpus Striatum / Q000166:cytology / Q000502:physiology*; D004298:Dopamine / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D007150:Immunohistochemistry; D007473:Ion Channels; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D024101:Mitochondrial Proteins / Q000235:genetics / Q000502:physiology*; D009043:Motor Activity; D009474:Neurons / Q000378:metabolism / Q000502:physiology*; D013378:Substantia Nigra / Q000166:cytology / Q000502:physiology*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D000071246:Uncoupling Protein 2
D050483:Dopamine Plasma Membrane Transport Proteins; D007473:Ion Channels; D026901:Membrane Transport Proteins; D024101:Mitochondrial Proteins; C000604390:Ucp2 protein, mouse; D000071246:Uncoupling Protein 2; D015102:3,4-Dihydroxyphenylacetic Acid; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine