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普拉克索可恢复 MPTP 损伤后腹侧海马的抑郁性传递。

Pramipexole restores depressed transmission in the ventral hippocampus following MPTP-lesion.

机构信息

The Florey Institute of Neuroscience and Mental Health, Melbourne, Victoria 3052, Australia.

出版信息

Sci Rep. 2017 Mar 14;7:44426. doi: 10.1038/srep44426.

Abstract

The hippocampus has a significant association with memory, cognition and emotions. The dopaminergic projections from both the ventral tegmental area and substantia nigra are thought to be involved in hippocampal activity. To date, however, few studies have investigated dopaminergic innervation in the hippocampus or the functional consequences of reduced dopamine in disease models. Further complicating this, the hippocampus exhibits anatomical and functional differentiation along its dorso-ventral axis. In this work we investigated the role of dopamine on hippocampal long term potentiation using D-amphetamine, which stimulates dopamine release, and also examined how a dopaminergic lesion affects the synaptic transmission across the anatomic subdivisions of the hippocampus. Our findings indicate that a 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine induced dopaminergic lesion has time-dependent effects and impacts mainly on the ventral region of the hippocampus, consistent with the density of dopaminergic innervation. Treatment with a preferential D receptor agonist pramipexole partly restored normal synaptic transmission and Long-Term Potentiation. These data suggest a new mechanism to explain some of the actions of pramipexole in Parkinson´s disease.

摘要

海马体与记忆、认知和情绪有显著的关联。来自腹侧被盖区和黑质的多巴胺能投射被认为与海马体活动有关。然而,迄今为止,很少有研究调查过海马体中的多巴胺能神经支配,或在疾病模型中减少多巴胺的功能后果。更复杂的是,海马体沿着背腹轴表现出解剖和功能上的分化。在这项工作中,我们使用安非他命研究了多巴胺对海马体长时程增强的作用,安非他命刺激多巴胺释放,还研究了多巴胺能损伤如何影响海马体解剖亚区之间的突触传递。我们的发现表明,1-甲基-4-苯基-1,2,3,6-四氢吡啶诱导的多巴胺能损伤具有时间依赖性效应,主要影响海马体的腹侧区域,与多巴胺能神经支配的密度一致。用选择性 D 受体激动剂普拉克索治疗部分恢复了正常的突触传递和长时程增强。这些数据为解释普拉克索在帕金森病中的一些作用提供了一种新的机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3274/5349604/dcd82c093f74/srep44426-f1.jpg

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