Institute of Human Physiology, Medical School, Università Cattolica del Sacro Cuore, Largo Francesco Vito 1, 00168, Rome, Italy.
Eur J Neurosci. 2014 Mar;39(6):893-903. doi: 10.1111/ejn.12465. Epub 2013 Dec 30.
In recent years, much effort has been devoted to identifying stimuli capable of enhancing adult neurogenesis, a process that generates new neurons throughout life, and that appears to be dysfunctional in the senescent brain and in several neuropsychiatric and neurodegenerative diseases. We previously reported that in vivo exposure to extremely low-frequency electromagnetic fields (ELFEFs) promotes the proliferation and neuronal differentiation of hippocampal neural stem cells (NSCs) that functionally integrate in the dentate gyrus. Here, we extended our studies to specifically assess the influence of ELFEFs on hippocampal newborn cell survival, which is a very critical issue in adult neurogenesis regulation. Mice were injected with 5-bromo-2'-deoxyuridine (BrdU) to label newborn cells, and were exposed to ELFEFs 9 days later, when the most dramatic decrease in the number of newly generated neurons occurs. The results showed that ELFEF exposure (3.5 h/day for 6 days) enhanced newborn neuron survival as documented by double staining for BrdU and doublecortin, to identify immature neurons, or NeuN labeling of mature neurons. The effects of ELFEFs were associated with enhanced spatial learning and memory. In an in vitro model of hippocampal NSCs, ELFEFs exerted their pro-survival action by rescuing differentiating neurons from apoptotic cell death. Western immunoblot assay revealed reduced expression of the pro-apoptotic protein Bax, and increased levels of the anti-apoptotic protein Bcl-2, in the hippocampi of ELFEF-exposed mice as well as in ELFEF-exposed NSC cultures, as compared with their sham-exposed counterparts. Our results may have clinical implications for the treatment of impaired neurogenesis associated with brain aging and neurodegenerative diseases.
近年来，人们致力于寻找能够增强成年神经发生的刺激物，这是一个在整个生命过程中产生新神经元的过程，而在衰老的大脑和几种神经精神疾病和神经退行性疾病中，该过程似乎出现了功能障碍。我们之前曾报道过，体内暴露于极低频电磁场（ELFEFs）可促进海马神经干细胞（NSC）的增殖和神经元分化，这些细胞在齿状回中具有功能整合。在这里，我们扩展了我们的研究，专门评估 ELFEFs 对海马新生细胞存活的影响，这是调节成年神经发生的一个非常关键的问题。用 5-溴-2'-脱氧尿苷（BrdU）注射小鼠以标记新生细胞，并在 9 天后暴露于 ELFEFs，此时新产生的神经元数量会急剧减少。结果表明，ELFEF 暴露（每天 3.5 小时，持续 6 天）可增强新生神经元的存活，如 BrdU 和双皮质蛋白的双重染色以识别未成熟神经元或成熟神经元的 NeuN 标记所示。ELFEFs 的作用与增强的空间学习和记忆有关。在海马 NSC 的体外模型中，ELFEFs 通过挽救分化神经元免于细胞凋亡来发挥其促生存作用。Western 免疫印迹分析显示，与假暴露组相比，ELFEF 暴露组小鼠的海马中以及 ELFEF 暴露的 NSC 培养物中，促凋亡蛋白 Bax 的表达减少，而抗凋亡蛋白 Bcl-2 的水平增加。我们的研究结果可能对治疗与大脑衰老和神经退行性疾病相关的神经发生受损具有临床意义。
