左旋多巴
神经科学
运动障碍
帕金森病
谷氨酸的
基底神经节
帕金森病
正电子发射断层摄影术
心理学
多巴胺
NMDA受体
谷氨酸受体
医学
内科学
中枢神经系统
疾病
受体
作者
Imtiaz Ahmed,Sunanda Bose,Nicola Pavese,Anil Ramlackhansingh,Federico Turkheimer,Gary Hotton,Alexander Hammers,David J. Brooks
出处
期刊:Brain
[Oxford University Press]
日期:2011-03-02
卷期号:134 (4): 979-986
被引量:181
摘要
Levodopa-induced dyskinesias are a common complication of long-term therapy in Parkinson’s disease. Although both pre- and post-synaptic mechanisms seem to be implicated in their development, the precise physiopathology of these disabling involuntary movements remains to be fully elucidated. Abnormalities in glutamate transmission (over expression and phosphorylation of N-methyl-d-aspartate receptors) have been associated with the development of levodopa-induced dyskinesias in animal models of Parkinsonism. The role of glutamate function in dyskinetic patients with Parkinson’s disease, however, is unclear. We used 11C-CNS 5161 [N-methyl-3(thyomethylphenyl)cyanamide] positron emission tomography, a marker of activated N-methyl-d-aspartate receptor ion channels, to compare in vivo glutamate function in parkinsonian patients with and without levodopa-induced dyskinesias. Each patient was assessed with positron emission tomography twice, after taking and withdrawal from levodopa. Striatal and cortical tracer uptake was calculated using a region of interest approach. In the ‘OFF’ state withdrawn from levodopa, dyskinetic and non-dyskinetic patients had similar levels of tracer uptake in basal ganglia and motor cortex. However, when positron emission tomography was performed in the ‘ON’ condition, dyskinetic patients had higher 11C-CNS 5161 uptake in caudate, putamen and precentral gyrus compared to the patients without dyskinesias, suggesting that dyskinetic patients may have abnormal glutamatergic transmission in motor areas following levodopa administration. These findings are consistent with the results of animal model studies indicating that increased glutamatergic activity is implicated in the development and maintenance of levodopa-induced dyskinesias. They support the hypothesis that blockade of glutamate transmission may have a place in the management of disabling dyskinesias in Parkinson’s disease.
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