摘要
背景:间充质干细胞移植可以改善神经退行性疾病包括阿尔茨海默病的神经功能。目的:本研究的目的是了解这种改善的潜在机制。方法:用渗透泵将淀粉样β(Aβ)肽注入成年大鼠侧脑室。连续输注15天后,将骨髓间充质干细胞(B10)移植到侧脑室。采用双向穿梭回避试验评价学习相关行为。B10移植后15d,观察其病理和表达变化。结果:与假手术组相比,Aβ非移植组学习相关行为明显降低,而B10移植组则无显著差异.Nissl染色结果显示,B10移植组海马CA1区锥体神经元数目与假手术组相似,而Aβ未移植组海马锥体神经元数目减少。B_(10)移植可使β主要沉积在β未移植大鼠脑血管内。此外,B10移植增加了血管密度和内球蛋白阳性细胞。Aβ非移植组星形胶质细胞和小胶质细胞数量减少,B10移植后恢复到假手术动物水平。实时聚合酶链反应和免疫染色结果表明,B10移植能显著提高IL-1β的表达和蛋白的表达。结论:骨髓间充质干细胞移植能有效地减少A型β在大鼠脑血管中的沉积,促进血管生成,可能是Aβ注入AD模型大鼠神经功能改善的原因之一。
关键词: 间充质干细胞,阿尔茨海默病,神经保护,淀粉样β蛋白,脑室灌注,血管生成。
Current Alzheimer Research
Title:A Mesenchymal Stem Cell Line Transplantation Improves Neurological Function and Angiogenesis in Intraventricular Amyloid β-Infused Rats
Volume: 15 Issue: 14
关键词: 间充质干细胞,阿尔茨海默病,神经保护,淀粉样β蛋白,脑室灌注,血管生成。
摘要: Background: Mesenchymal stem cell transplantation is demonstrated to improve neurological performance in neurodegenerative diseases including Alzheimer’s disease.
Objective: The objective of this study is to understand the underlying mechanism of such improvement.
Methods: Amyloid β (Aβ) peptide was infused into the lateral ventricle of adult Wister rats using the osmotic pump. After 15 days of continuous infusion, a mesenchymal stem cell line (B10) was transplanted in the lateral ventricle. Learning-related behavior was evaluated by 2-way shuttle avoidance test. Fifteen days after B10 transplantation, pathological and expressional changes were evaluated.
Results: Compared to sham group, learning-related behavior was significantly decreased in Aβ-infused non-transplanted group, but not in B10-transplanted group. Nissl staining results demonstrated that the number of hippocampal pyramidal neurons in CA1 area in B10-transplanted group was similar to the sham group, whereas that was decreased in Aβ-infused non-transplanted group. Aβ mainly deposited in the vessels of the brains of Aβ-infused non-transplanted rats, which was decreased by B10 transplantation. Moreover, B10 transplantation increased vessel density as well as endoglin positive cells. The number of astrocyte and microglia was decreased in Aβ-infused non-transplanted group, which was returned to the level of sham animals by B10 transplantation. Real-time PCR and immunostaining results showed that B10 transplantation significantly increased IL-1β mRNA and protein expression.
Conclusion: Thus, our result showed that MSC transplantation effectively decreased Aβ deposition in the cerebral vessel and increased angiogenesis, which could be a possible cause of improved neurological performance in Aβ-infused AD model rats.
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A Mesenchymal Stem Cell Line Transplantation Improves Neurological Function and Angiogenesis in Intraventricular Amyloid β-Infused Rats, Current Alzheimer Research 2018; 15 (14) . https://dx.doi.org/10.2174/1567205015666180911145159
DOI https://dx.doi.org/10.2174/1567205015666180911145159 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
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Current updates on the Role of Neuroinflammation in Neurodegenerative Disorders
Neuroinflammation is an invariable hallmark of chronic and acute neurodegenerative disorders and has long been considered a potential drug target for Alzheimer?s disease (AD) and dementia. Significant evidence of inflammatory processes as a feature of AD is provided by the presence of inflammatory markers in plasma, CSF and postmortem brain ...read more
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