间质干细胞衍生的细胞外囊泡抑制阿尔茨海默病小鼠中 iNOS 的表达并改善神经损伤。
Mesenchymal Stem Cell-Derived Extracellular Vesicles Suppresses iNOS Expression and Ameliorates Neural Impairment in Alzheimer's Disease Mice.
机构信息
Department of Geriatric Neurology, Nanlou Clinical Division, Chinese PLA General Hospital, Beijing, P.R. China.
出版信息
J Alzheimers Dis. 2018;61(3):1005-1013. doi: 10.3233/JAD-170848.
BACKGROUND
Mesenchymal stem cells (MSCs)-derived extracellular vesicles (EVs) have been reported to exhibit therapeutic effects in various animal models of neurological diseases, such as stroke and hypoxic-ischemic brain injury.
OBJECTIVE
The present study investigated the potential beneficial effect of MSC-derived EVs in an animal model of Alzheimer's disease (AD).
METHODS
APP/PS1 mice and their non-transgenic littermates (WT) received intracerebroventricle injection of MSC-derived EVs once per two days for two weeks. Then novel object recognition and water maze tasks were carried out to measure the cognitive behaviors. Electrophysiological tests were carried out to measure hippocampal synaptic plasticity. Inducible nitric oxide synthase (iNOS) mRNA and protein levels were measured by qRT-PCR and western blotting in primary cultured neurons treated with amyloid-β peptide (Aβ) or prepared from APP/PS1 mice.
RESULTS
Treatment with MSC-derived EVs alleviates exogenous Aβ-induced iNOS mRNA and protein expression. In cultured primary neurons prepared from APP/PS1 pups, iNOS mRNA and protein levels were significantly reduced when treated with MSC-derived EVs. MSC-derived EVs improved cognitive behavior, rescued impairment of CA1 synaptic transmission, and long-term potentiation in APP/PS1 mice.
CONCLUSION
MSC-derived EVs possessed beneficial effects in a mouse model of AD, probably by suppressing Aβ induced iNOS expression.
背景
间充质干细胞（MSCs）衍生的细胞外囊泡（EVs）已被报道在各种神经疾病的动物模型中表现出治疗作用，如中风和缺氧缺血性脑损伤。
目的
本研究探讨了 MSC 衍生的 EV 在阿尔茨海默病（AD）动物模型中的潜在有益作用。
方法
APP/PS1 小鼠及其非转基因同窝仔（WT）接受 MSC 衍生的 EV 脑室内注射，每两天一次，持续两周。然后进行新物体识别和水迷宫任务，以测量认知行为。用电生理测试测量海马突触可塑性。用 qRT-PCR 和 Western blot 测量经淀粉样β肽（Aβ）处理或从 APP/PS1 小鼠制备的原代培养神经元中的诱导型一氧化氮合酶（iNOS）mRNA 和蛋白水平。
结果
MSC 衍生的 EV 治疗可减轻外源性 Aβ诱导的 iNOS mRNA 和蛋白表达。在 APP/PS1 幼鼠原代培养的神经元中，用 MSC 衍生的 EV 处理可显著降低 iNOS mRNA 和蛋白水平。MSC 衍生的 EV 改善了 APP/PS1 小鼠的认知行为，挽救了 CA1 突触传递和长时程增强的损伤。
结论
MSC 衍生的 EV 在 AD 小鼠模型中具有有益作用，可能通过抑制 Aβ诱导的 iNOS 表达。
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