DEEP BRAIN STIMULATION IN PARKINSON MODELS

帕金森模型中的深部脑刺激

• 批准号: 7716379
• 负责人: MARJORIE E ANDERSON
• 金额: $ 15.78万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-05-01 至 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7716379
• 关键词: Adult; Animals; Behavioral; Brain; Cessation of life; Computer Retrieval of Information on Scientific Projects Database; Deep Brain Stimulation; Development; Dopamine; Frequencies; Funding; Grant; Human; Institution; Iron; Manuscripts; Modeling; Monkeys; Motor; Parkinson Disease; Positron-Emission Tomography; Preparation; Research; Research Personnel; Resources; Rotenone; Source; Symptoms; Thalamic structure; Time; Tyrosine; United States National Institutes of Health; Universities; aging brain; dopaminergic neuron; monoamine

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.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 我们希望确定高频脑深部电刺激（DBS）对运动丘脑的影响，例如用于治疗人类帕金森病的症状。 为了寻求更好的帕金森病模型，我们将鱼藤酮的给药时间延长至3年，在一只成熟的成年猴中没有发现行为缺陷的发展。 我们的合作者，匹兹堡大学的Tim Greenamyre博士，分析了大脑和年龄匹配的对照组，发现酪氨酸羟化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成像时单胺转运的DBTZ标记物随着治疗时间的推移没有可检测到的减少一致。 然而，与对照组相比，接受鱼藤酮治疗的猴子大脑中的铁含量显著增加，Greenamyre博士的研究小组发现，接受鱼藤酮治疗的其他动物的铁含量也有所增加。 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。 关于铁的手稿正在准备中。