Widespread Monoaminergic Dysregulation of Both Motor and Non-Motor Circuits in Parkinsonism and Dyskinesia.
Cereb. Cortex. 2014-04-25; 25(9): 2783-2792
DOI: 10.1093/cercor/bhu076
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1. Cereb Cortex. 2015 Sep;25(9):2783-92. doi: 10.1093/cercor/bhu076. Epub 2014 Apr
25.
Widespread Monoaminergic Dysregulation of Both Motor and Non-Motor Circuits in
Parkinsonism and Dyskinesia.
Engeln M(1), De Deurwaerdère P(1), Li Q(2), Bezard E(3), Fernagut PO(1).
Author information:
(1)Univ. de Bordeaux, UMR 5293, F-33000 Bordeaux, France CNRS, Institut des
Maladies Neurodégénératives, UMR 5293, F-33000 Bordeaux, France.
(2)Institute of Lab Animal Sciences, China Academy of Medical Sciences, Beijing
100101, China.
(3)Univ. de Bordeaux, UMR 5293, F-33000 Bordeaux, France CNRS, Institut des
Maladies Neurodégénératives, UMR 5293, F-33000 Bordeaux, France Institute of Lab
Animal Sciences, China Academy of Medical Sciences, Beijing 100101, China.
Beyond dopamine (DA) loss, Parkinson’s disease is associated with many other
monoamine alterations. While some monoaminergic systems benefit from
l-3,4-dihydroxyphenylalanine (l-Dopa) treatment, others seem to be further
altered, contributing to dyskinesia and nonmotor symptoms. Surprisingly, the
different contributions of parkinsonism and l-Dopa treatment on monoaminergic
changes remain largely unknown. Here, both the consequences of vehicle or
1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) exposure and the subsequent
effects of acute or chronic l-Dopa treatment were evaluated in macaques.
Monoamine levels were measured in the putamen, the motor and prefrontal cortices,
the hippocampus, and the amygdala using postmortem high-pressure liquid
chromatography. In normal monkeys, l-Dopa treatment increased DA in the
prefrontal cortex and hippocampus, but decreased serotonin levels in motor
domains. Chronic l-Dopa treatment elevated monoamine levels in the prefrontal
cortex, hippocampus, and amygdala in both normal and MPTP-treated monkeys. A
substantial increase in DA levels in these regions, paralleled by a decrease in
serotonin concentrations were related with dyskinesia severity, demonstrating
that major changes in monoamine release also occur in nonmotor regions. Such
monoaminergic dysregulation in limbic domains may also directly contribute to the
expression of motor complications, such as dyskinesia, by impairing integrative
processes upstream from motor execution.
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DOI: 10.1093/cercor/bhu076
PMID: 24770706 [Indexed for MEDLINE]