title: New insights into the trophic and cytoprotective effects of creatine in in vitro and in vivo models of cell maturation.
abstract: A growing body of scientific reports indicates that the role of creatine (Cr) in cellular biochemistry and physiology goes beyond its contribution to cell energy. Indeed Cr has been shown to exert multiple effects promoting a wide range of physiological responses in vitro as well as in vivo. Included in these, Cr promotes in vitro neuron and muscle cell differentiation, viability and survival under normal or adverse conditions; anabolic, protective and pro-differentiative effects have also been observed in vivo. For example Cr has been shown to accelerate in vitro differentiation of cultured C2C12 myoblasts into myotubes, where it also induces a slight but significant hypertrophic effect as compared to unsupplemented cultures; Cr also prevents the anti-differentiation effects caused by oxidative stress in the same cells. In trained adults, Cr increases the mRNA expression of relevant myogemic factors, protein synthesis, muscle strength and size, in cooperation with physical exercise. As to neurons and central nervous system, Cr favors the electrophysiological maturation of chick neuroblasts in vitro and protects them from oxidative stress-caused killing; similarly, Cr promotes the survival and differentiation of GABA-ergic neurons in fetal spinal cord cultures in vitro; in vivo, maternal Cr supplementation promotes the morpho-functional development of hippocampal neurons in rat offsprings. This article, which presents also some new experimental data, focuses on the trophic, pro-survival and pro-differentiation effects of Cr and examines the ensuing preventive and therapeutic potential in pathological muscle and brain conditions.
authors.affiliation: Department of Biomolecolar Sciences, Università degli Studi di Urbino Carlo Bo, Via Saffi 2, 61029, Urbino, Italy. piero.sestili@uniurb.it.
authors.forename: Piero
authors.initials: P
authors.lastname: Sestili
authors.affiliation: Department of Biomolecolar Sciences, Università degli Studi di Urbino Carlo Bo, Via Saffi 2, 61029, Urbino, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Ambrogini
authors.affiliation: Department of Biomolecolar Sciences, Università degli Studi di Urbino Carlo Bo, Via Saffi 2, 61029, Urbino, Italy.|IIM, Interuniversitary Institute of Myology, Padua, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Barbieri
authors.affiliation: Department of Biomolecolar Sciences, Università degli Studi di Urbino Carlo Bo, Via Saffi 2, 61029, Urbino, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Sartini
authors.affiliation: Department for Life Quality Studies, Alma Mater Studiorum-University of Bologna, 47921, Rimini, Italy.
authors.forename: Carmela
authors.initials: C
authors.lastname: Fimognari
authors.affiliation: Department of Biomolecolar Sciences, Università degli Studi di Urbino Carlo Bo, Via Saffi 2, 61029, Urbino, Italy.|Department for Life Quality Studies, Alma Mater Studiorum-University of Bologna, 47921, Rimini, Italy.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Calcabrini
authors.affiliation: Department of Biomolecolar Sciences, Università degli Studi di Urbino Carlo Bo, Via Saffi 2, 61029, Urbino, Italy.
authors.forename: Anna Rita
authors.initials: AR
authors.lastname: Diaz
authors.affiliation: Department of Biomolecolar Sciences, Università degli Studi di Urbino Carlo Bo, Via Saffi 2, 61029, Urbino, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Guescini
authors.affiliation: Department of Biomolecolar Sciences, Università degli Studi di Urbino Carlo Bo, Via Saffi 2, 61029, Urbino, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Polidori
authors.affiliation: Department of Biomolecolar Sciences, Università degli Studi di Urbino Carlo Bo, Via Saffi 2, 61029, Urbino, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Luchetti
authors.affiliation: Department of Biomolecolar Sciences, Università degli Studi di Urbino Carlo Bo, Via Saffi 2, 61029, Urbino, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Canonico
authors.affiliation: Department of Biomolecolar Sciences, Università degli Studi di Urbino Carlo Bo, Via Saffi 2, 61029, Urbino, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Lattanzi
authors.affiliation: Department of Biomolecolar Sciences, Università degli Studi di Urbino Carlo Bo, Via Saffi 2, 61029, Urbino, Italy.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Cuppini
authors.affiliation: Department of Biomolecolar Sciences, Università degli Studi di Urbino Carlo Bo, Via Saffi 2, 61029, Urbino, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Papa
authors.affiliation: Department of Biomolecolar Sciences, Università degli Studi di Urbino Carlo Bo, Via Saffi 2, 61029, Urbino, Italy.
authors.forename: Vilberto
authors.initials: V
authors.lastname: Stocchi
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects* / Q000502:physiology; D003401:Creatine / Q000378:metabolism / Q000494:pharmacology*; D019610:Cytoprotection / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D008954:Models, Biological; D018485:Muscle Fibers, Skeletal / Q000378:metabolism; D032448:Myoblasts, Skeletal / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology
chemical_list: D003401:Creatine
keywords: Creatine; Myogenesis; Neuron maturation; Oxidative stress; Skeletal muscle