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骨形态发生蛋白-7在帕金森病大鼠模型中的神经营养作用

Neurotrophic effects of bone morphogenetic protein-7 in a rat model of Parkinson's disease.

作者信息

Harvey B K, Mark A, Chou J, Chen G J, Hoffer B J, Wang Y

机构信息

National Institute on Drug Abuse, NIH, Neural Protection and Regeneration Section, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA.

出版信息

Brain Res. 2004 Oct 1;1022(1-2):88-95. doi: 10.1016/j.brainres.2004.06.072.

Abstract

Previous studies have demonstrated that pretreatment with bone morphogenetic protein-7 (BMP7) reduces ischemic neuronal injury in vivo. Moreover, exogenous application of BMP7 increases both the number of tyrosine hydroxylase (+) cells and dopamine (DA) uptake in rat mesencephalic cell cultures. The purpose of this study was to investigate the in vivo effects of BMP7 on 6-hydroxydopamine (6-OHDA) induced lesioning of midbrain DA neurons. Adult Fischer 344 rats were anesthetized and injected with BMP7 or vehicle into the left substantia nigra, followed by local administration of 9 microg of 6-OHDA into the left medial forebrain bundle. The lesioned animals that received BMP7 pretreatment, as compared to vehicle/6-OHDA controls, had a significant reduction in methamphetamine-induced rotation 1 month after the surgery. BMP7-pretreatment partially preserved KCl-induced dopamine release in the lesioned striatum and significantly increased TH immunoreactivity in the lesioned nigra and striatum. In summary, our data suggest that BMP7 has neuroprotective and/or neuroreparative effects against 6-OHDA lesioning of the nigrostriatal DA pathway in an animal model of Parkinson's disease (PD).

摘要

先前的研究表明,用骨形态发生蛋白-7(BMP7)进行预处理可在体内减轻缺血性神经元损伤。此外,在大鼠中脑细胞培养物中外源性应用BMP7可增加酪氨酸羟化酶(+)细胞的数量以及多巴胺(DA)摄取。本研究的目的是探讨BMP7在体内对6-羟基多巴胺(6-OHDA)诱导的中脑DA神经元损伤的影响。将成年Fischer 344大鼠麻醉,向左黑质注射BMP7或赋形剂,随后向左内侧前脑束局部给予9μg 6-OHDA。与赋形剂/6-OHDA对照组相比,接受BMP7预处理的损伤动物在手术后1个月甲基苯丙胺诱导的旋转明显减少。BMP7预处理部分保留了损伤纹状体中氯化钾诱导的多巴胺释放,并显著增加了损伤黑质和纹状体中的TH免疫反应性。总之,我们的数据表明,在帕金森病(PD)动物模型中,BMP7对黑质纹状体DA通路的6-OHDA损伤具有神经保护和/或神经修复作用。

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