DEEP BRAIN STIMULATION IN PARKINSON MODELS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 我们希望确定高频脑深部刺激(DBS)对运动丘脑的影响，例如用于治疗人类帕金森氏症症状的DBS。 为了寻求更好的帕金森氏病模型，我们将鱼藤酮在一只成年猴子身上的服药时间延长至3年，没有发现行为缺陷的发生。我们的合作者，匹兹堡大学的蒂姆·格林阿梅尔博士，分析了大脑和一名老年匹配对照组的大脑，发现酪氨酸羟解酶活性没有显著差异，这意味着多巴胺没有显著变化。这也与使用PET成像的单胺转运的DBTZ标志物随着治疗时间的推移而没有检测到的减少是一致的。 然而，与对照组相比，服用鱼藤酮的猴子大脑中的铁含量显著增加，格林阿梅尔博士的团队也发现，在服用鱼藤酮的其他动物中，铁的含量也有所增加。在这一点上的假设是，铁的增加先于多巴胺能神经元的死亡。一份关于铁的手稿现在正在准备中。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. We wish to determine the consequences on the motor thalamus of high frequency deep brain stimulation (DBS), such as is used treat the symptoms of Parkinson's disease in humans. In pursuit of a better model of Parkinson's disease, we have extended the administration of rotenone to 3 years in a mature adult monkey and found no development of behavioral deficits. Our collaborator, Dr. Tim Greenamyre, at the University of Pittsburgh, analyzed the brain and that of an aged matched control and found that there was no significant difference in tyrosine hydroxlase activity, implying no significant change in dopamine. This also is consistent with the absence of detectable decrements over treatment time in the DBTZ marker of monoamine transport using PET imaging. However, there was a significant increase in iron in the brain of the rotenone-treated monkey, compared to control, and Dr. Greenamyre's group has found increases in iron in other animals treated with rotenone. The hypothesis at this point is that an increase in iron precedes the death of dopaminergic neurons. A manuscript regarding the iron now is in preparation.