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Article type: Research Article
Authors: Lindgren, H.S. | Rylander, D. | Iderberg, H. | Andersson, M. | O'Sullivan, S.S. | Williams, D.R. | Lees, A.J. | Cenci, M.A.
Affiliations: Lund University, Basal Ganglia Pathophysiology Unit, Department of Experimental Medical Sciences, Lund, Sweden | Uppsala University, Department Pharmaceutical Biosciences, Div. Drug Safety and Toxicology, Uppsala, Husargatan, Uppsala, Sweden | Queen Square Brain Bank, Queen Square Institute of Neurology, University College London, London, UK
Note: [] Correspondence to: M. Angela Cenci, Lund University, BMC F11, 221 84 Lund, Sweden. Tel.: +46 46 2221431; E-mail: Angela.Cenci_Nilsson@med.lu.se
Abstract: The transcription factor ΔFosB is a mediator of maladaptive neuroplasticity in animal models of Parkinson's disease (PD) and L-DOPA-induced dyskinesia. Using an antibody that recognizes all known isoforms of FosB and ΔFosB, we have examined the expression of these proteins in post-mortem basal ganglia sections from PD patients. The patient cases were classified as being dyskinetic or non-dyskinetic based on their clinical records. Sections from neurologically healthy controls were also included in the study. Compared to both controls and non-dyskinetic cases, the dyskinetic group showed a higher density of FosB/ΔFosB-immunopositive cells in the posterior putamen, which represents the motor region of the striatum in primates. In contrast, the number of FosB/ΔFosB-positive cells did not differ significantly among the groups in the caudate, a region primarily involved with the processing of cognitive and limbic-related information. Only sparse FosB/ΔFosB immunoreactivity was found in the in the pallidum externum and internum, and no significant group differences were detected in these nuclei. The putaminal elevation of FosB/ΔFosB-like immunoreactivity in patients who had been affected by L-DOPA-induced dyskinesia is consistent with results from both rat and non-human primate models of this movement disorder. The present findings support the hypothesis of an involvement of ΔFosB-related transcription factors in the molecular mechanisms of L-DOPA-induced dyskinesia.
Keywords: Motor complications, immediate-early genes, striatonigral, striatopallidal, medium-spiny neurons, neurodegeneration, dopaminergic therapies
DOI: 10.3233/JPD-2011-11068
Journal: Journal of Parkinson's Disease, vol. 1, no. 4, pp. 347-357, 2011
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