Elevated levels of Delta FosB and RGS9 in striatum in Parkinson's disease

Introduction: In the present study, we determined whether certain proteins known to mediate dopamine signaling in striatum show abnormal levels in Par kinson's disease. Methods: Protein levels were assayed by western blotting in samples of caud ate nucleus and putamen obtained at autopsy from patients with Parkinson's disease and from control subjects. Levels of several markers of dopaminergi c function were also assayed. Results: Levels of the transcription factor Delta FosB and of the G protein modulatory protein RGS9 were both increased in caudate and putamen from pa tients with Parkinson's disease. Levels of several other proteins were not affected. Interestingly, levels of both Delta FOSB and RGS9 correlated inve rsely with putamen levels of dopamine, dopamine metabolites, and the dopami ne transporter. Conclusions: These findings are consistent with observations in laboratory animals, which have demonstrated elevated levels of Delta FosB in striatum after denervation of the midbrain dopamine system, and confirm that similar adaptations in Delta FosB and RGS9 occur in humans with Parkinson's diseas e. Knowledge of these adaptations can help us understand the changes in str iatal function associated with Parkinson's disease and assist in the develo pment of novel treatments. (C) 2001 Society of Biological Psychiatry.