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Enhancement of adult neurogenesis for Parkisnon's diseased primate models

帕金森病灵长类动物模型成年神经发生的增强

基本信息

批准号：
16390255
负责人：
MOCHIZUKI Hideki
金额：
$ 9.15万
依托单位：
Juntendo University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2005
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-16390255/
关键词：
Parkinson's disease Regeneration medicine Hepatocyte growth factor MPTP Neuronal stem cell Retrovirus vector 幹細胞 HGF MTPT 神経栄養因子レトロウイルス猿

项目摘要

The possibility for the neurogenesis of nigral neurons was examinedin animals and autopsy brains including those of patients with PD. First, proliferating cells in the SN were labeled efficiently with retroviral transfection of green fluorescent protein (GFP). The subsequent differentiation of labelled cells followed, in which many transfected cells became microglia but none had differentiated into tyrosine hydroxylase (TH)-positive neurons at 4 weeks post transfection in both intact and MPTP-treated rodents. Our result indicated that retroviral labelling in rodents indicated a lack of neurogenesis of TH-positive neurons from proliferative stem/progenitor cells in the SN. Second, polysialic acid (PSA)-like immunoreactivity, which was indicative of newly differentiated neurons, was detected in the SN of rodents, primate and human midbrains. A large number of PSA-positive cells were detected in the SN pars reticulata of some patients with PD.It has been suggested that certain therapeutic agents currently in use, such as selegiline, ropinirole and pramipexole, can slow the progress of the disease. In this regard, a recent study showed that dopaminergic agonists stimulate neurogenesis in SVZ. Further studies need to be conducted in order to examine the effects of these compounds on neurogenesis in the midbrain. This findings were published in Ann Neurol.58(1):31-40,2005. It was sited in Reuters (2005.7.22)、Daily Yomiuri (2005.7.26) and Daily Mainichi (2005.8.15).To identify this hypothesis, we examined the effect of hepatocyte growth factor (HGF) using Parkinson's diseased models. At first, we created MPTP treated Parkinson's disease primate model. Using the infusion pump, HGF was continuously injected into the striatum in PD primate models. Unfortunately, we could not detect the pathological changes and clinical benefits in the treated PD models. We are going to examine the new compounds to upregulate the PSA positive cells in our models. (291 words)

在动物和尸检大脑（包括帕金森病患者的大脑）中检查了黑质神经元神经发生的可能性。首先，通过绿色荧光蛋白 (GFP) 的逆转录病毒转染有效标记 SN 中的增殖细胞。随后标记细胞分化，其中许多转染细胞成为小胶质细胞，但在转染后 4 周，完整的和 MPTP 处理的啮齿动物中没有一个细胞分化为酪氨酸羟化酶 (TH) 阳性神经元。我们的结果表明，啮齿类动物的逆转录病毒标记表明，SN 中的增殖干细胞/祖细胞缺乏 TH 阳性神经元的神经发生。其次，在啮齿动物、灵长类动物和人类中脑的 SN 中检测到聚唾液酸 (PSA) 样免疫反应性，这表明新分化的神经元。在一些PD患者的SN网状部中检测到大量PSA阳性细胞。有人认为目前使用的某些治疗药物，如司来吉兰、罗匹尼罗和普拉克索，可以减缓疾病的进展。在这方面，最近的一项研究表明多巴胺能激动剂刺激 SVZ 的神经发生。需要进行进一步的研究，以检查这些化合物对中脑神经发生的影响。该研究结果发表于 Ann Neurol.58(1):31-40,2005。它位于Reuters (2005.7.22)、Daily Yomiuri (2005.7.26) 和Daily Mainichi (2005.8.15)。为了证实这一假设，我们使用帕金森病模型检验了肝细胞生长因子(HGF) 的作用。首先，我们创建了MPTP治疗的帕金森病灵长类动物模型。使用输液泵，将 HGF 持续注射到 PD 灵长类动物模型的纹状体中。不幸的是，我们无法检测治疗PD模型的病理变化和临床获益。我们将研究新化合物以上调模型中的 PSA 阳性细胞。（291字）