PDF(Pubmed)
Abstract：
Major features of aging might be progressive decreases in cognitive function and physical activity, in addition to withered appearance. Previously, we reported that the intracerebroventricular injection of human neural stem cells (NSCs named F3) encoded the choline acetyltransferase gene (F3.ChAT). The cells secreted acetylcholine and growth factors (GFs) and neurotrophic factors (NFs), thereby improving learning and memory function as well as the physical activity of aged animals. In this study, F344 rats (10 months old) were intravenously transplanted with F3 or F3.ChAT NSCs (1 × 106 cells) once a month to the 21st month of age. Their physical activity and cognitive function were investigated, and brain acetylcholine (ACh) and cholinergic and dopaminergic system markers were analyzed. Neuroprotective and neuroregenerative activities of stem cells were also confirmed by analyzing oxidative damages, neuronal skeletal protein, angiogenesis, brain and muscle weights, and proliferating host stem cells. Stem cells markedly improved both cognitive and physical functions, in parallel with the elevation in ACh levels in cerebrospinal fluid and muscles, in which F3.ChAT cells were more effective than F3 parental cells. Stem cell transplantation downregulated CCL11 and recovered GFs and NFs in the brain, leading to restoration of microtubule-associated protein 2 as well as functional markers of cholinergic and dopaminergic systems, along with neovascularization. Stem cells also restored muscular GFs and NFs, resulting in increased angiogenesis and muscle mass. In addition, stem cells enhanced antioxidative capacity, attenuating oxidative damage to the brain and muscles. The results indicate that NSCs encoding ChAT improve cognitive function and physical activity of aging animals by protecting and recovering functions of multiple organs, including cholinergic and dopaminergic systems, as well as muscles from oxidative injuries through secretion of ACh and GFs/NFs, increased antioxidant elements, and enhanced blood flow.
摘要：
衰老的主要特征可能是认知功能和身体活动的进行性下降，除了枯萎的外观。以前,我们报道了脑室内注射人类神经干细胞（NSC命名为F3）编码胆碱乙酰转移酶基因（F3。聊天）。细胞分泌乙酰胆碱和生长因子（GFs）和神经营养因子（NFs），从而改善老年动物的学习和记忆功能以及身体活动。在这项研究中,用F3或F3静脉内移植F344大鼠(10月龄)。ChATNSC（1×106个细胞）每月一次至21月龄。他们的身体活动和认知功能进行了调查，并分析了脑乙酰胆碱（ACh）和胆碱能和多巴胺能系统标志物。通过分析氧化损伤也证实了干细胞的神经保护和神经再生活性，神经元骨架蛋白，血管生成,大脑和肌肉的重量，和增殖宿主干细胞。干细胞显着改善认知和身体功能，与脑脊液和肌肉中ACh水平的升高同时，其中F3ChAT细胞比F3亲本细胞更有效。干细胞移植下调CCL11并恢复大脑中的GFs和NFs，导致微管相关蛋白2以及胆碱能和多巴胺能系统的功能标志物的恢复，以及新血管形成。干细胞也恢复了肌肉GFs和NFs，导致血管生成和肌肉质量增加。此外,干细胞增强抗氧化能力，减轻对大脑和肌肉的氧化损伤。结果表明，编码ChAT的神经干细胞通过保护和恢复多个器官的功能，改善衰老动物的认知功能和体力活动。包括胆碱能和多巴胺能系统，以及通过分泌ACh和GFs/NFs引起的氧化损伤的肌肉，增加抗氧化元素，增强血液流动。
