Department of Laboratory Medicine, Shimane University School of Medicine, Ringgold Standard Institution, 89-1 Enya Cho, Izumo, Shimane 693-8501, Japan.
Department of Physiology, Shimane University School of Medicine, Ringgold Standard Institution, 89-1 Enya Cho, Izumo, Shimane 693-8501, Japan.
Curr Alzheimer Res. 2018;15(14):1331-1342. doi: 10.2174/1567205015666180911145159.
Mesenchymal stem cell transplantation is demonstrated to improve neurological performance in neurodegenerative diseases including Alzheimer's disease.
The objective of this study is to understand the underlying mechanism of such improvement.
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.
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.
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.
间充质干细胞移植被证明可以改善包括阿尔茨海默病在内的神经退行性疾病的神经功能。
本研究旨在了解这种改善的潜在机制。
使用渗透泵将淀粉样β（Aβ）肽注入成年 Wister 大鼠侧脑室。连续输注 15 天后，将间充质干细胞系（B10）移植到侧脑室。通过双向穿梭回避测试评估学习相关行为。B10 移植后 15 天，评估病理和表达变化。
与假手术组相比，Aβ 输注未移植组的学习相关行为明显下降，但 B10 移植组无此变化。尼氏染色结果表明，B10 移植组 CA1 区海马锥体神经元数量与假手术组相似，而 Aβ 输注未移植组则减少。Aβ 主要沉积在 Aβ 输注未移植大鼠脑血管中，B10 移植可减少其沉积。此外，B10 移植增加了血管密度和内胚层阳性细胞。Aβ 输注未移植组的星形胶质细胞和小胶质细胞数量减少，B10 移植使其恢复到假手术动物的水平。实时 PCR 和免疫染色结果表明，B10 移植显著增加了 IL-1β mRNA 和蛋白的表达。
因此，我们的结果表明，MSC 移植有效减少了脑血管中的 Aβ 沉积并增加了血管生成，这可能是 Aβ 输注 AD 模型大鼠神经功能改善的一个可能原因。
