Elevated levels of DeltaFosB and RGS9 in striatum in Parkinson's disease.
BACKGROUND
In the present study, we determined whether certain proteins known to mediate dopamine signaling in striatum show abnormal levels in Parkinson's disease.


METHODS
Protein levels were assayed by western blotting in samples of caudate nucleus and putamen obtained at autopsy from patients with Parkinson's disease and from control subjects. Levels of several markers of dopaminergic function were also assayed.


RESULTS
Levels of the transcription factor DeltaFosB and of the G protein modulatory protein RGS9 were both increased in caudate and putamen from patients with Parkinson's disease. Levels of several other proteins were not affected. Interestingly, levels of both DeltaFosB and RGS9 correlated inversely with putamen levels of dopamine, dopamine metabolites, and the dopamine transporter.


CONCLUSIONS
These findings are consistent with observations in laboratory animals, which have demonstrated elevated levels of DeltaFosB in striatum after denervation of the midbrain dopamine system, and confirm that similar adaptations in DeltaFosB and RGS9 occur in humans with Parkinson's disease. Knowledge of these adaptations can help us understand the changes in striatal function associated with Parkinson's disease and assist in the development of novel treatments.
Tekumalla
P K
PK
Laboratory of Molecular Psychiatry, Yale University School of Medicine and Connecticut Mental Health Center, New Haven, Connecticut, USA.
Calon
F
F
Rahman
Z
Z
Birdi
S
S
Rajput
A H
AH
Hornykiewicz
O
O
Di Paolo
T
T
Bédard
P J
PJ
Nestler
E J
EJ
D015153:Blotting, Western; D002421:Caudate Nucleus / Q000473:pathology*; D004298:Dopamine / Q000032:analysis; D050483:Dopamine Plasma Membrane Transport Proteins; D006801:Humans; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins / Q000032:analysis; D009419:Nerve Tissue Proteins; D010300:Parkinson Disease / Q000473:pathology*; D016760:Proto-Oncogene Proteins c-fos / Q000032:analysis*; D011699:Putamen / Q000473:pathology*; D020710:RGS Proteins / Q000032:analysis*; D012016:Reference Values
D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D016760:Proto-Oncogene Proteins c-fos; D020710:RGS Proteins; C116925:regulator of g-protein signaling 9; D004298:Dopamine