Elevated levels of ΔFosB 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 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 ΔFosB 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 ΔFosB 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 ΔFosB in striatum after denervation of the midbrain dopamine system, and confirm that similar adaptations in ΔFosB 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.