Clinical-grade human umbilical cord-derived mesenchymal stem cells reverse cognitive aging via improving synaptic plasticity and endogenous neurogenesis.
Clinical-grade human umbilical cord-derived mesenchymal stem cells reverse cognitive aging via improving synaptic plasticity and endogenous neurogenesis.
复制标题
临床级人脐带间充质干细胞通过改善突触可塑性和内源性神经发生来逆转认知衰老
DOI：
10.1038/cddis.2017.316
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发表时间：
2017-08-10
影响因子：
9
通讯作者：
Pei X
中科院分区：
文献类型：
--
作者：
Cao N;Liao T;Liu J;Fan Z;Zeng Q;Zhou J;Pei H;Xi J;He L;Chen L;Nan X;Jia Y;Yue W;Pei X
随着人口老龄化的加剧，认知老化是一个主要的公共卫生问题，但仍然缺乏针对它的具体干预措施。最近的研究表明，认知功能与衰老大脑的系统环境密切相关，改善衰老大脑的系统环境可能是恢复认知衰老的一种有前景的方法。在这里，我们试图在小鼠衰老模型中研究临床级人脐带间充质干细胞（hUC-MSCs）对认知衰老的干预作用。这里采用了 d-半乳糖（d-gal）诱导小鼠的传统衰老模型。小鼠每两周腹腔注射一次 hUC-MSC。经过3个月的系统调控hUC-MSCs，老年小鼠海马依赖性学习记忆能力得到有效改善，老年海马CA1区突触可塑性明显增强；此外，在衰老的海马体中，可能影响海马回路功能的神经生物学底物得到恢复，体现在：树突棘密度增强，神经鞘和细胞骨架恢复，突触后密度区域增加。此外，hUC-MSCs移植后观察到内源性神经发生的激活，有利于海马神经网络的稳定。此外，我们证明了 hUC-MSC 系统调节的有益效果可以通过激活衰老海马中的丝裂原激活蛋白激酶 (MAPK)-ERK-CREB 信号通路来介导。我们的研究提供了第一个证据，证明 hUC-MSCs 具有系统调节衰老大脑的能力，可能是认知衰老的潜在干预措施。
Cognitive aging is a leading public health concern with the increasing aging population, but there is still lack of specific interventions directed against it. Recent studies have shown that cognitive function is intimately affected by systemic milieu in aging brain, and improvement of systemic environment in aging brain may be a promising approach for rejuvenating cognitive aging. Here, we sought to study the intervention effects of clinical-grade human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) on cognitive aging in a murine model of aging. The conventional aging model in mice induced by d-galactose (d-gal) was employed here. Mice received once every two weeks intraperitoneal administration of hUC-MSCs. After 3 months of systematical regulation of hUC-MSCs, the hippocampal-dependent learning and memory ability was effectively improved in aged mice, and the synaptic plasticity was remarkably enhanced in CA1 area of the aged hippocampus; moreover, the neurobiological substrates that could impact on the function of hippocampal circuits were recovered in the aged hippocampus reflecting in: dendritic spine density enhanced, neural sheath and cytoskeleton restored, and postsynaptic density area increased. In addition, the activation of the endogenic neurogenesis which is beneficial to stabilize the neural network in hippocampus was observed after hUC-MSCs transplantation. Furthermore, we demonstrated that beneficial effects of systematical regulation of hUC-MSCs could be mediated by activation of mitogen-activated protein kinase (MAPK)-ERK-CREB signaling pathway in the aged hippocampus. Our study provides the first evidence that hUC-MSCs, which have the capacity of systematically regulating the aging brain, may be a potential intervention for cognitive aging.
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影响因子：
10.9
作者：
Marosi, Krisztina;Mattson, Mark P.
通讯作者：
Mattson, Mark P.
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64.8
作者：
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