Creatine affects neuroblast differentiation and protects from oxidative stress

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.