Assessment of specific cognitive function of the striatum in a primate model of Parkinson's disease.

评估帕金森病灵长类动物模型中纹状体的特定认知功能。

• 批准号: 15590904
• 负责人: MURAMATSU Shin-ichi
• 金额: $ 2.24万
• 依托单位: JICHI MEDICAL SCHOOL
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15590904/
• 关键词: basal ganglia; dopamine; Parkinson's disease; gene therapy; cognitive function; MPTP; cynomolgus monkey; adeno-associated virus; 線条体; 認知障害

To elucidate the cognitive function specific to the striatum, groups of cynomolgus monkeys with toxin-induced Parkinsonian motor symptoms were compared with normal controls on a computerized battery of tests designed to investigate conception set shift. The tests assess the ability to shift cognitive set modeled after the Wisconsin Card Sorting Test that is sensitive to impairments in patients with Parkinson's disease(PD). The monkeys with chronic treatment of 1-metil-4-phenil-1-2-3-6-tetrahydropyridine (MPTP) showed similar difficulty with the patients with PD in the set-shift task. Positron emission tomography showed that impairment of dopaminergic function was confined to the nigro-striatal system in these monkeys and that recombinant adeno-associated viral vector (AAV)-mediated selective restoration of 1-dopa uptake in the treated putamen. The combination of computerized battery of tests and gene transfer using AAV vectors is a powerful tool to study higher cognitive function of the basal ganglia.

为了阐明纹状体特有的认知功能，将具有毒素诱发的帕金森运动症状的食蟹猴群体与正常对照进行一系列旨在研究概念设定转变的计算机化测试进行比较。这些测试以威斯康星卡片分类测试为模型，评估了改变认知能力的能力，该测试对帕金森病 (PD) 患者的损伤敏感。长期接受 1-metil-4-phenil-1-2-3-6-tetrahydropyridine (MPTP) 治疗的猴子在轮班任务中表现出与 PD 患者类似的困难。正电子发射断层扫描显示，多巴胺能功能的损害仅限于这些猴子的黑质纹状体系统，并且重组腺相关病毒载体（AAV）介导的治疗壳核中1-多巴摄取的选择性恢复。计算机化的一系列测试和使用 AAV 载体的基因转移相结合，是研究基底神经节高级认知功能的有力工具。

项目成果

Intramuscular injection of AAV-GDNF results in sustained expression of transgenic GDNF, and its delivery to spinal motoneurons by retrograde transport.

肌内注射 AAV-GDNF 导致转基因 GDNF 持续表达，并通过逆行转运将其递送至脊髓运动神经元。

• 发表时间: 2003
• 期刊: Neurosci Res 45・1
• 作者: Lu;Y.Y.
• 通讯作者: Y.Y.

Adeno-associated viral vectors for Parkinson's disease.

用于帕金森病的腺相关病毒载体。

• 发表时间: 2003
• 期刊: International Review of Neurobiology 55
• 作者: Muramatsu;S.
• 通讯作者: S.

Gene Therapy for Parkinson's disease using recombinant 〜

使用重组基因治疗帕金森病 ~

• 期刊: Expert Opinion on Biological Therapy (In press)
• 作者: Muramatsu;S.
• 通讯作者: S.

Gene therapy for Parkinson's disease

• DOI: 10.1017/s146239940400746x
• 发表时间: 2004-03
• 期刊: Expert Reviews in Molecular Medicine
• 影响因子: 6.2
• 作者: P. Lawlor;M. During

Progress in gene therapy.

基因治疗的进展。

• 发表时间: 2003
• 作者: Muramatsu;S. et al.
• 通讯作者: S. et al.