Salmin Vladimir V, Komleva Yulia K, Kuvacheva Natalia V, Morgun Andrey V, Khilazheva Elena D, Lopatina Olga L, Pozhilenkova Elena A, Shapovalov Konstantin A, Uspenskaya Yulia A, Salmina Alla B
Department of Medical and Biological Physics, Krasnoyarsk State Medical University named after Prof. V.F. Voino-YasenetskyKrasnoyarsk, Russia.
Department of Biochemistry, Medical, Pharmaceutical and Toxicological Chemistry, Krasnoyarsk State Medical University named after Prof. V.F. Voino-YasenetskyKrasnoyarsk, Russia.
Front Aging Neurosci. 2017 Jul 26;9:245. doi: 10.3389/fnagi.2017.00245. eCollection 2017.
Impairment of hippocampal adult neurogenesis in aging or degenerating brain is a well-known phenomenon caused by the shortage of brain stem cell pool, alterations in the local microenvironment within the neurogenic niches, or deregulation of stem cell development. Environmental enrichment (EE) has been proposed as a potent tool to restore brain functions, to prevent aging-associated neurodegeneration, and to cure neuronal deficits seen in neurodevelopmental and neurodegenerative disorders. Here, we report our data on the effects of environmental enrichment on hippocampal neurogenesis and neurosphere-forming capacity of hippocampal stem/progenitor cells Two models - Alzheimer's type of neurodegeneration and physiological brain aging - were chosen for the comparative analysis of EE effects. We found that environmental enrichment greatly affects the expression of markers specific for stem cells, progenitor cells and differentiated neurons (Pax6, Ngn2, NeuroD1, NeuN) in the hippocampus of young adult rats or rats with Alzheimer's disease (AD) model but less efficiently in aged animals. Application of time-lag mathematical model for the analysis of impedance traces obtained in real-time monitoring of cell proliferation revealed that EE could restore neurosphere-forming capacity of hippocampal stem/progenitor cells more efficiently in young adult animals (fourfold greater in the control group comparing to the AD model group) but not in the aged rats (no positive effect of environmental enrichment at all). In accordance with the results obtained , EE was almost ineffective in the recovery of hippocampal neurogenic reserve in aged, but not in amyloid-treated or young adult, rats. Therefore, EE-based neuroprotective strategies effective in Aβ-affected brain could not be directly extrapolated to aged brain.
在衰老或退化的大脑中，海马体成年神经发生受损是一种众所周知的现象，其原因是脑干细胞池短缺、神经发生微环境内局部微环境的改变或干细胞发育失调。环境富集（EE）已被提议作为一种有效的工具，用于恢复脑功能、预防与衰老相关的神经退行性变以及治疗神经发育和神经退行性疾病中出现的神经元缺陷。在此，我们报告关于环境富集对海马神经发生以及海马干细胞/祖细胞神经球形成能力影响的数据。我们选择了两种模型——阿尔茨海默病型神经退行性变和生理性脑衰老——来比较分析环境富集的作用。我们发现，环境富集极大地影响了年轻成年大鼠或阿尔茨海默病（AD）模型大鼠海马中干细胞、祖细胞和分化神经元特异性标志物（Pax6、Ngn2、NeuroD1、NeuN）的表达，但对老年动物的影响较小。应用时滞数学模型分析在细胞增殖实时监测中获得的阻抗轨迹，结果显示，环境富集能更有效地恢复年轻成年动物海马干细胞/祖细胞的神经球形成能力（对照组比AD模型组高四倍），但对老年大鼠则无效（环境富集完全没有积极作用）。根据所得结果，环境富集在恢复老年大鼠海马神经发生储备方面几乎无效，但对淀粉样蛋白处理的大鼠或年轻成年大鼠有效。因此，在受Aβ影响的大脑中有效的基于环境富集的神经保护策略不能直接外推到老年大脑。
