Putaminal upregulation of FosB/ΔFosB-like immunoreactivity in Parkinson's disease patients with dyskinesia.
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.
Lund University, Basal Ganglia Pathophysiology Unit, Department of Experimental Medical Sciences, Lund, Sweden.
H S
HS
Lindgren
D
D
Rylander
H
H
Iderberg
M
M
Andersson
S S
SS
O'Sullivan
D R
DR
Williams
A J
AJ
Lees
M A
MA
Cenci
D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D000978:Antiparkinson Agents / Q000009:adverse effects; D001345:Autoradiography; D001479:Basal Ganglia / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D004409:Dyskinesia, Drug-Induced / Q000473:pathology; D005260:Female; D006801:Humans; D007980:Levodopa / Q000009:adverse effects; D008297:Male; D009474:Neurons / Q000378:metabolism; D010300:Parkinson Disease / Q000188:drug therapy / Q000473:pathology; D011180:Postmortem Changes; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D011699:Putamen / Q000378:metabolism* / Q000473:pathology; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology*
D000978:Antiparkinson Agents; D050483:Dopamine Plasma Membrane Transport Proteins; C064269:FOSB protein, human; D016760:Proto-Oncogene Proteins c-fos; D007980:Levodopa