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阿扑吗啡对利血平化大鼠纹状体突触结合蛋白7 mRNA水平的影响。

Effect of apomorphine on striatal synaptotagmin 7 mRNA levels in reserpinized rats.

作者信息

Pal Robert, Zivin Marko, Milutinovic Aleksandra, Jernej Branimir, Glavan Gordana

机构信息

Brain Research Laboratory, Institute of Pathophysiology, Faculty of Medicine, University of Ljubljana, Zaloska 4, 1000 Ljubljana, Slovenia.

出版信息

Neurosci Lett. 2007 Sep 13;424(3):194-8. doi: 10.1016/j.neulet.2007.07.033. Epub 2007 Aug 6.

Abstract

Synaptotagmin 7 (Syt 7) is a Ca2+ sensor implicated in the regulation of membrane fusion in vesicular transport, but its precise role in neurons is still a matter of controversy. Dopaminergic drugs have been shown to modulate its expression in the striatum. Here we investigate whether dopamine receptor agonist-up-regulation of Syt 7 mRNA is specifically involved in the pathophysiological adaptations of hypersensitive striatum by analyzing other dopaminergic neurons containing brain regions. We treated rats with systemic reserpine injections that rapidly depletes dopamine throughout the brain, but leaves dopaminergic neurons spared from destruction. We analyzed the effects of apomorphine, a D1 and D2 receptor agonist on Syt 7 mRNA expression in caudate putamen, nucleus accumbens, cingulate cortex, substantia nigra compacta, ventral tegmental area and hippocampus. The treatment with reserpine resulted in akinesia, catalepsy and rigidity and up-regulation of proenkephalin and down-regulation of preprotachykinin mRNA in caudate putamen, indicating a severe depletion. By acute treatment with apomorphine proenkephalin mRNA was down-regulated and preprotachykinin mRNA up-regulated in the caudate putamen of reserpinized rats. Apomorphine increased Syt 7 mRNA levels only in striatum (caudate putamen and nucleus accumbens) of reserpinized rats, while in other brain regions it did not have such effect. The reserpinization and/or apomorphine treatment had no effect on Syt 1 mRNA expression in caudate putamen. It may be concluded, that in the striatum depleted of biogene amines, such as occurs after reserpine treatment, the up-regulation of Syt 7 could play a specific role as part of hypersensitive response to dopaminergic agonists.

摘要

突触结合蛋白7(Syt 7)是一种钙传感器,与囊泡运输中的膜融合调节有关,但其在神经元中的精确作用仍存在争议。多巴胺能药物已被证明可调节其在纹状体中的表达。在这里,我们通过分析其他含有多巴胺能神经元的脑区,研究多巴胺受体激动剂上调Syt 7 mRNA是否特别参与了超敏纹状体的病理生理适应。我们对大鼠进行全身利血平注射治疗,利血平可迅速耗尽全脑的多巴胺,但使多巴胺能神经元免受破坏。我们分析了阿扑吗啡(一种D1和D2受体激动剂)对尾状核壳、伏隔核、扣带回皮质、黑质致密部、腹侧被盖区和海马中Syt 7 mRNA表达的影响。利血平治疗导致运动不能、僵住症和强直,尾状核壳中脑啡肽原上调,前速激肽原mRNA下调,表明多巴胺严重耗竭。在利血平化大鼠的尾状核壳中,通过急性给予阿扑吗啡,脑啡肽原mRNA下调,前速激肽原mRNA上调。阿扑吗啡仅增加了利血平化大鼠纹状体(尾状核壳和伏隔核)中的Syt 7 mRNA水平,而在其他脑区则没有这种作用。利血平化和/或阿扑吗啡治疗对尾状核壳中Syt 1 mRNA表达没有影响。可以得出结论,在生物胺耗竭的纹状体中,如利血平治疗后发生的情况,Syt 7的上调可能作为对多巴胺能激动剂超敏反应的一部分发挥特定作用。

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