Increased striatal pre-proenkephalin B expression is associated with dyskinesia in Parkinson's disease
Increased striatal pre-proenkephalin B expression is associated with dyskinesia in Parkinson's disease
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DOI：
10.1016/s0014-4886(03)00064-5
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发表时间：
2003-10-01
影响因子：
5.3
通讯作者：
Brotchie, JM
中科院分区：
文献类型：
--
作者：
Henry, B;Duty, S;Brotchie, JM
用左旋多巴长期治疗帕金森病会受到运动并发症的影响，包括开关波动和称为运动障碍的不自主运动。治疗相关运动障碍的神经机制可能涉及基底神经节输出区域的活动不足，即苍白球内侧段（GPm）和黑质网状部（SNR）。 “直接”纹状体苍白球通路的 GABA 能神经元活性增加与 GPm 和 SNR 的抑制有关，从而导致运动障碍的发生。直接途径使用阿片类药物作为辅助神经递质。这些阿片肽是高分子量阿片前体前脑啡肽原 B (PPE-B) 的产物。采用原位杂交研究来调查临床病理诊断为帕金森病的患者死后纹状体组织中 PPE-B mRNA 的表达，所有这些患者均表现出左旋多巴诱导的运动并发症，包括死亡前的运动障碍，以及 MPTP 损伤的帕金森病猕猴模型的尾壳核（纹状体）中与治疗相关的运动障碍。与年龄匹配的对照组相比，运动障碍性帕金森病患者的纹状体 PPE-B mRNA 表达显着增加 172%。与纹状体基质区室相比，这种增加是异质的，纹状体内的表达增加。与帕金森病、非运动障碍的 MPTP 损伤猕猴相比，在表现出运动障碍的 MPTP 损伤猕猴中，纹状体 PPE-B mRNA 表达显着增加 185%，与非帕金森病、非运动障碍对照相比，显着增加 146%。 PPE-B、mRNA 表达增加，以及随后直接纹状体输出通路内阿片肽传输的增加，可能是帕金森病治疗相关运动障碍的基础。 (C) 2003 年爱思唯尔科学（美国）。所有战斗保留。
Long-term treatment of Parkinson's disease with levodopa is compromised by die development of motor complications, including on-off fluctuations and involuntary movements termed dyskinesia. The neural mechanisms underlying treatment-related dyskinesias may involve underactivity of the output regions of the basal ganglia, i.e., the medial segment of the globus pallidus (GPm) and substantia nigra pars reticulata (SNR). Increased activity of GABAergic neurons of the "direct" striatopallidal pathway has been implicated in the suppression of the GPm and SNR and thus the development of dyskinesia. The direct pathway uses opioids as a co-neurotransmitter. These opioid peptides are products of the high-molecular weight opioid precursor pre-proenkephalin B (PPE-B). In situ hybridisation studies were employed to investigate PPE-B mRNA expression in postmortem striatal tissue from patients with a clinicopathological diagnosis of Parkinson's disease, all of whom displayed levodopa-induced motor complications, including dyskinesia prior to death and in the caudate-putamen (striatum) of the MPTP-lesioned macaque model of Parkinson's disease with treatment-related dyskinesia. Striatal PPE-B mRNA expression was significantly increased by 172% in dyskinetic Parkinson's disease patients compared to age-matched controls. This increase was heterogeneous with increased expression within the striosomes compared to matrix compartments of the striatum. Striatal PPE-B mRNA expression was significantly increased by 185% in the MPTP-lesioned macaque exhibiting dyskinesia, compared to parkinsonian, nondyskinetic MPTP-lesioned macaques, and by 146% compared to non-parkinsonian, nondyskinetic controls. Increased PPE-B, mRNA expression, with subsequent elevations in opioid peptide transmission within the direct striatal output pathways, may underlie treatment-related dyskinesia in Parkinson's disease. (C) 2003 Elsevier Science (USA). All fights reserved.