Elevated levels of ΔFosB and RGS9 in striatum in Parkinson’s disease

• Published in: Biological psychiatry (1969) Vol. 50; no. 10; pp. 813 - 816
• Main Authors: Tekumalla, Poornima K., Calon, Frédéric, Rahman, Zia, Birdi, Sam, Rajput, Ali H., Hornykiewicz, Oleh, Di Paolo, Therese, Bédard, Paul J., Nestler, Eric J.
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 15.11.2001; Elsevier Science
• Subjects: Biological and medical sciences; Caudate-putamen; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; dopamine denervation; dyskinesia; Fos transcription factors; Medical sciences; Nervous system (semeiology, syndromes); Nervous system as a whole; Neurology; RGS proteins; RGS proteins; dopamine denervation; Fos transcription factors; Caudate-putamen; dyskinesia; Human; Nervous system diseases; Dopamine; Central nervous system; Transcription factor RGS9; Parkinson disease; Exploration; Transcription factor ΔFosB; Basal ganglion; Corpus striatum; Gene expression; Metabolism; Putamen; Cerebral disorder; Signal transduction; Caudate nucleus; Central nervous system disease; Degenerative disease; Carrier protein; Extrapyramidal syndrome
• ISSN: 0006-3223; 1873-2402
• DOI: 10.1016/S0006-3223(01)01234-3

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.