Investigation of curative effect and the neuroplasticity with the start time in the gene therapy of the cerebellar ataxic mouse

小脑共济失调小鼠基因治疗的疗效及神经可塑性与起始时间的探讨

• 批准号: 22700374
• 负责人: IIZUKA Akira
• 金额: $ 2.5万
• 依托单位: Gunma University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22700374/
• 关键词: 遺伝子治療; プルキンエ細胞; レンチウイルス; 神経可塑性; 小脳発達; 回路形成; 小脳; レンチウイルスベクター

Lentiviral vectors expressing RORα were injected into the cerebellar cortex of P6, P13 or P20 staggerer mice, and the effects were studied 3 weeks after the injection. Staggerer mice lentivirally treated at P6 showed marked dendritic differentiation of PCs and removal CF synapses from PCs, whereas those lentivirally treated at P13 displayed only a partial rescue of dendritic differentiation and failure of removal of CF synapses from PCs. No rescue was observed in staggerer mice lentivirally treated at P20. Together with evidence that protein expression in the brain starts about 5 days after lentiviral vector injection, these results suggest that staggerer mutant cerebellum maintains potential to respond to RORα at 2nd postnatal week, but loses almost completely at 4th postnatal week.

将表达RORα的慢病毒载体注射到P6、P13和P20的小鼠小脑皮质中，并在注射后3周观察其作用。在P6慢病毒治疗的Staggerer小鼠表现出明显的PC树突分化和从PC中去除CF突触，而在P13慢病毒治疗的小鼠仅表现出部分树突分化的挽救和从PC中去除CF突触的失败。在P20时慢病毒治疗的蹒跚小鼠中未观察到拯救。结合慢病毒载体注射后约5天大脑中蛋白质表达的证据，这些结果表明，交错突变小脑在出生后第2周保持对RORα反应的潜力，但在出生后第4周几乎完全丧失。