Department of Earth, Life and Environmental Sciences, University of Urbino Carlo Bo, Urbino, Italy.
J Neurosci Res. 2012 Feb;90(2):435-46. doi: 10.1002/jnr.22762. Epub 2011 Sep 21.
Creatine (Cr) is a very popular ergogenic molecule that has recently been shown to have antioxidant properties. The effectiveness of Cr supplementation in treating neurological diseases and Cr deficiency syndromes has been demonstrated, and experimental reports suggest that it plays an important role in CNS development. In spite of this body of evidence, the role of Cr in functional and structural neuronal differentiation is still poorly understood. Here we used electrophysiological, morphological, and biochemical approaches to study the effects of Cr supplementation on in vitro differentiation of spinal neuroblasts under standard conditions or subjected to oxidative stress, a status closely related to perinatal hypoxia-ischemia, a severe condition for developing brain. Cr supplementation (10 and 20 mM) completely prevented the viability decrease and neurite development impairment induced by radical attack, as well as nonprotein sulphydryl antioxidant pool depletion. Similar results were obtained using the antioxidant trolox. Furthermore, Cr supplementation induced a significant and dose-dependent anticipation of Na(+) and K(+) current expression during the period of in vitro network building. Consistently with the latter finding, higher excitability, expressed as number of spikes following depolarization, was found in supplemented neuroblasts. All effects were dependent on the cytosolic fraction of Cr, as shown using a membrane Cr-transporter blocker. Our results indicate that Cr protects differentiating neuroblasts against oxidative insults and, moreover, affects their in vitro electrophysiological maturation, suggesting possibly relevant effects of dietary Cr supplementation on developing CNS.
肌酸（Cr）是一种非常流行的运动营养补剂，最近的研究表明它具有抗氧化特性。Cr 补充剂在治疗神经疾病和 Cr 缺乏综合征方面的有效性已得到证实，实验报告表明它在中枢神经系统发育中发挥着重要作用。尽管有这些证据，但 Cr 在功能性和结构性神经元分化中的作用仍知之甚少。在这里，我们使用电生理、形态和生化方法研究了 Cr 补充对标准条件下或经历氧化应激（一种与围产期缺氧缺血密切相关的状态，是发育中大脑的严重情况）的脊髓神经母细胞体外分化的影响。Cr 补充（10 和 20mM）完全阻止了自由基攻击引起的细胞活力下降和突起发育受损，以及非蛋白巯基抗氧化剂库耗竭。使用抗氧化剂 Trolox 也得到了类似的结果。此外，Cr 补充在体外网络构建期间诱导了 Na(+)和 K(+)电流表达的显著且剂量依赖性的提前出现。与后一种发现一致的是，在补充的神经母细胞中发现了更高的兴奋性，表现为去极化后尖峰的数量增加。所有的影响都依赖于 Cr 的细胞质部分，如使用膜 Cr 转运体阻滞剂所示。我们的结果表明，Cr 可以保护分化中的神经母细胞免受氧化损伤，并且还影响它们的体外电生理成熟，这表明膳食 Cr 补充对发育中的中枢神经系统可能有相关影响。
