Chronic subthalamic nucleus stimulation and striatal D2 dopamine receptors in Parkinson's disease - A [C-11]-raclopride PET study
ABSTRACT Subthalamic nucleus (STN) stimulation mechanism of action remains a matter for debate. In animals, an increased striatal dopamine (DA) release due to STN stimulation has been reported.
To determine in Parkinson's disease (PD) patients using positron emission tomography (PET) and [11C]-Raclopride, whether STN stimulation induces a striatal DA release.
Nine PD patients with bilateral STN stimulation were enrolled and underwent two [11C]-Raclopride PET scans. The scans were randomly performed in off and on stimulation conditions. Striatal [11C]-Raclopride binding potential (BP) was calculated using regions of interest and statistical parametric mapping.
For PD patients, the mean [(11C]-Raclopride BP (+/- SD) were, in Off stimulation condition: 1.7 +/- 0.3 for the right caudate nucleus, 1.8 +/- 0.4 for the left caudate nucleus, 2.6 +/- 0.5 for the right putamenand 2.6 +/- 0.5 for the left putamen. In On stimulation condition: 1.7 +/- 0.4 for the right caudate nucleus, 1.9 +/- 0.5 for the left caudate nucleus, 2.8 +/- 0.7 for the right putamen and 2.7 +/- 0.8 for the left putamen. No significant difference of BP related to the stimulation was noted.
STN stimulation does not produce significant variations of striatal DA release as assessed by PET and [11C]-Raclopride.
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ABSTRACT: Subthalamotomy allows a reduction of doses of L-DOPA in dyskinetic patients while its antiparkinsonian benefits are preserved. However, the mechanisms of the potentiation of this response to medication remain to be elucidated. Hence, dopamine D1 and D2 receptors as well as the dopamine transporter were investigated using receptor binding autoradiography. D1 receptor, D2 receptor, preproenkephalin and preprodynorphin mRNAs levels were measured by in situ hybridization. Four dyskinetic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) parkinsonian monkeys that underwent unilateral subthalamotomy were compared to four controls, four saline-treated and four L-DOPA-treated MPTP monkeys. Dopamine, its metabolites and its transporter were extensively and similarly decreased in all parkinsonian monkeys. D1 receptor specific binding was decreased in the striatum of all MPTP monkeys. The L-DOPA-induced decrease in D1 receptor specific binding was reversed in the striatum ipsilateral to subthalamotomy. D1 receptor mRNA levels followed a similar pattern. D2 receptor specific binding and mRNA levels remained unchanged in all groups. Striatal preproenkephalin mRNA levels were overall increased in MPTP monkeys; the STN-lesioned parkinsonian group had significantly lower values than the saline-treated and L-DOPA-treated parkinsonian monkeys in the dorsolateral putamen. Striatal preprodynorphin mRNA levels remained unchanged in MPTP monkeys compared to controls whereas it increased in all monkeys treated with L-DOPA compared to controls; subthalamotomy induced a decrease in the dorsolateral putamen ipsilateral to surgery. The improved motor response to L-DOPA after subthalamotomy in the parkinsonian monkeys investigated may be associated with an increased synthesis and expression of D1 receptors ipsilateral to STN lesion of the direct pathway.Experimental Neurology 08/2014; 261. DOI:10.1016/j.expneurol.2014.08.018 · 4.62 Impact Factor
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ABSTRACT: Electrochemical techniques have long been utilized to investigate chemical changes in the neuronal microenvironment. Preclinical models have demonstrated the successful monitoring of changes in various neurotransmitter systems in vivo with high temporal and spatial resolution. The expansion of electrochemical recording to humans is a critical yet challenging goal to elucidate various aspects of human neurophysiology and to create future therapies. We have designed a novel device named the WINCS (Wireless Instantaneous Neurotransmitter Concentration Sensing) system that combines rapid scan voltammetry with wireless telemetry for highly resolved electrochemical recording and analysis. WINCS utilizes fast-scan cyclic voltammetry and fixed potential amperometry for in vivo recording and has demonstrated high temporal and spatial resolution in detecting changes in extracellular levels of a wide range of analytes including dopamine, adenosine, glutamate, serotonin, and histamine. Neurochemical monitoring in humans represents a new approach to understanding the neurophysiology of the central nervous system, the neurobiology of numerous diseases, and the underlying mechanism of various neurosurgical therapies. This article addresses the current understanding of electrochemistry, its application in humans, and future directions.Stereotactic and Functional Neurosurgery 02/2013; 91(3):141-147. DOI:10.1159/000345111 · 1.48 Impact Factor
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ABSTRACT: To elucidate the dynamic effects of deep brain stimulation (DBS) in the subthalamic nucleus (STN) during activity on the dopaminergic system, 12 PD patients who had STN-DBS operations at least 1 month prior, underwent two positron emission tomography scans during right-foot movement in DBS-off and DBS-on conditions. To quantify motor performance changes, the motion speed and mobility angle of the foot at the ankle were measured twice. Estimations of the binding potential of [(11)C]raclopride (BP(ND)) were based on the Logan plot method. Significant motor recovery was found in the DBS-on condition. The STN-DBS during exercise significantly reduced the [(11)C]raclopride BP(ND) in the caudate and the nucleus accumbens (NA), but not in the dorsal or ventral putamen. The magnitude of dopamine release in the NA correlated negatively with the magnitude of motor load, indicating that STN-DBS facilitated motor behavior more smoothly and at less expense to dopamine neurons in the region. The lack of dopamine release in the putamen and the significant dopamine release in the ventromedial striatum by STN-DBS during exercise indicated dopaminergic activation occurring in the motivational circuit during action, suggesting a compensatory functional activation of the motor loop from the nonmotor to the motor loop system.Journal of Cerebral Blood Flow & Metabolism advance online publication, 5 December 2012; doi:10.1038/jcbfm.2012.183.Journal of cerebral blood flow and metabolism: official journal of the International Society of Cerebral Blood Flow and Metabolism 12/2012; DOI:10.1038/jcbfm.2012.183 · 5.34 Impact Factor