Levodopa treatment and dendritic spine pathology.
Levodopa treatment and dendritic spine pathology.
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DOI：
10.1002/mds.27172
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发表时间：
2018-07
期刊：
影响因子：
--
通讯作者：
Tomiyama M
中科院分区：
文献类型：
--
作者：
Nishijima H;Ueno T;Funamizu Y;Ueno S;Tomiyama M
帕金森病（PD）是一种与黑质纹状体多巴胺能神经元进行性丢失相关的神经退行性疾病。左旋多巴是治疗PD运动症状最有效的药物。然而，长期口服左旋多巴治疗可导致各种运动和非运动并发症，因为非生理性脉动多巴胺能刺激大脑。对帕金森病尸检病例的检查显示，纹状体神经元的树突棘数量减少。PD的动物模型揭示了多巴胺能去神经或多巴胺能去神经加左旋多巴治疗后不同脑区神经元树突棘的密度和形态改变，表明突触传递改变。最近使用啮齿动物模型的研究报告了在多巴胺能去神经支配后慢性左旋多巴治疗诱导运动障碍样异常不自主运动的情况下，尾壳核、丘脑核、初级运动皮层和前额皮质中的树突棘头部扩大。α-氨基-2，3-二氢-5-甲基-3-氧代-4-异恶唑丙酸受体插入突触后膜导致棘肥大。这种棘增大表明突触对兴奋性输入的超敏反应，并且与缺乏去电位相一致，这是在运动障碍动物的皮质纹状体突触和运动障碍PD患者的运动皮质中发现的左旋多巴诱导的运动障碍的电生理学标志。这种突触可塑性可能是引发左旋多巴诱导的并发症（如左旋多巴诱导的运动障碍和多巴胺失调综合征）的机制之一。可能预防脊柱增大的药物，如钙通道阻滞剂、N-甲基-D-天冬氨酸受体拮抗剂、α-氨基-2，3-二氢-5-甲基-3-氧代-4-异恶唑丙酸受体拮抗剂和代谢型谷氨酸受体拮抗剂，是治疗左旋多巴诱导的PD并发症的候选药物。版权所有© 2017作者.出版社：Wiley Periodicals，Inc.国际帕金森和运动障碍协会（International Parkinson and Movement Disorder Society）
Parkinson's disease (PD) is a neurodegenerative disorder associated with the progressive loss of nigrostriatal dopaminergic neurons. Levodopa is the most effective treatment for the motor symptoms of PD. However, chronic oral levodopa treatment can lead to various motor and nonmotor complications because of nonphysiological pulsatile dopaminergic stimulation in the brain. Examinations of autopsy cases with PD have revealed a decreased number of dendritic spines of striatal neurons. Animal models of PD have revealed altered density and morphology of dendritic spines of neurons in various brain regions after dopaminergic denervation or dopaminergic denervation plus levodopa treatment, indicating altered synaptic transmission. Recent studies using rodent models have reported dendritic spine head enlargement in the caudate‐putamen, nucleus accumbens, primary motor cortex, and prefrontal cortex in cases where chronic levodopa treatment following dopaminergic denervation induced dyskinesia‐like abnormal involuntary movement. Hypertrophy of spines results from insertion of alpha‐amino‐2,3‐dihydro‐5‐methyl‐3‐oxo‐4‐isoxazolepropanoic acid receptors into the postsynaptic membrane. Such spine enlargement indicates hypersensitivity of the synapse to excitatory inputs and is compatible with a lack of depotentiation, which is an electrophysiological hallmark of levodopa‐induced dyskinesia found in the corticostriatal synapses of dyskinetic animals and the motor cortex of dyskinetic PD patients. This synaptic plasticity may be one of the mechanisms underlying the priming of levodopa‐induced complications such as levodopa‐induced dyskinesia and dopamine dysregulation syndrome. Drugs that could potentially prevent spine enlargement, such as calcium channel blockers, N‐methyl‐D‐aspartate receptor antagonists, alpha‐amino‐2,3‐dihydro‐5‐methyl‐3‐oxo‐4‐isoxazolepropanoic acid receptor antagonists, and metabotropic glutamate receptor antagonists, are candidates for treatment of levodopa‐induced complications in PD. © 2017 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.
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表达D（1）和D（2）受体的纹状体神经元在形态上是不同的，并且受小鼠多巴胺神经化的影响不同。
影响因子：
4.6
作者：
Gagnon D;Petryszyn S;Sanchez MG;Bories C;Beaulieu JM;De Koninck Y;Parent A;Parent M
通讯作者：
Parent M
影响因子：
3.5
作者：
Dembrow N;Johnston D
通讯作者：
Johnston D
影响因子：
2.9
作者：
ABERCROMBIE, ED;BONATZ, AE;ZIGMOND, MJ
通讯作者：
ZIGMOND, MJ
影响因子：
11.2
作者：
Evans, AH;Pavese, N;Piccini, P
通讯作者：
Piccini, P
影响因子：
0.7
作者：
Bashkatova, V. G.;Sudakov, S. K.
通讯作者：
Sudakov, S. K.