title: The effects of creatine supplementation on striatal neural progenitor cells depend on developmental stage.
abstract: Transplantation of neural progenitor cells (NPCs) is a promising experimental therapy for Huntington's disease (HD). The variables responsible for the success of this approach, including selection of the optimal developmental stage of the grafted cells, are however largely unknown. Supporting cellular energy metabolism by creatine (Cr) supplementation is a clinically translatable method for improving cell transplantation strategies. The present study aims at investigating differences between early (E14) and late (E18) developmental stages of rat striatal NPCs in vitro. NPCs were isolated from E14 and E18 embryos and cultured for 7 days with or without Cr [5 mM]. Chronic treatment significantly increased the percentage of GABA-immunoreactive neurons as compared to untreated controls, both in the E14 (170.4 ± 4.7 %) and the E18 groups (129.3 ± 9.3 %). This effect was greater in E14 cultures (p < 0.05). Similarly, short-term treatment for 24 h resulted in increased induction (p < 0.05) of the GABA-ergic phenotype in E14 (163.0 ± 10.4 %), compared to E18 cultures (133.3 ± 9.5 %). Total neuronal cell numbers and general viability were not affected by Cr (p > 0.05). Protective effects of Cr against a metabolic insult were equal in E14 and E18 NPCs (p > 0.05). Cr exposure promoted morphological differentiation of GABA-ergic neurons, including neurite length in both groups (p < 0.05), but the number of branching points was increased only in the E18 group (p < 0.05). Our results demonstrate that the role of Cr as a GABA-ergic differentiation factor depends on the developmental stage of striatal NPCs, while Cr-mediated neuroprotection is not significantly influenced. These findings have potential implications for optimizing future cell replacement strategies in HD.
authors.affiliation: Department of Neurosurgery, University of Berne, Inselspital, Freiburgstrasse 10, 3010, Berne, Switzerland.
authors.forename: Robert H
authors.initials: RH
authors.lastname: Andres
authors.affiliation: Department of Neurosurgery, University of Berne, Inselspital, Freiburgstrasse 10, 3010, Berne, Switzerland.
authors.forename: Angelique D
authors.initials: AD
authors.lastname: Ducray
authors.affiliation: Department of Neurosurgery, University of Berne, Inselspital, Freiburgstrasse 10, 3010, Berne, Switzerland.|Department of Neurosurgery and F.M. Kirby Neurobiology Center, Boston Children's Hospital, Harvard Medical School, 300 Longwood Avenue, Boston, MA, 02115, USA.
authors.forename: Lukas
authors.initials: L
authors.lastname: Andereggen
authors.affiliation: Department of Neurosurgery, University of Berne, Inselspital, Freiburgstrasse 10, 3010, Berne, Switzerland.
authors.forename: Tabea
authors.initials: T
authors.lastname: Hohl
authors.affiliation: Laboratory of Fundamental and Applied Bioenergetics, Université Grenoble Alpes, BP53, 38041, Grenoble Cedex, France.|Inserm, U1055, BP53, 38041, Grenoble Cedex, France.
authors.forename: Uwe
authors.initials: U
authors.lastname: Schlattner
authors.affiliation: Professor emeritus, formerly at Institute of Cell Biology, Swiss Federal Institute of Technology (ETH), Schafmattstrasse 18, 8093, Zurich, Switzerland.
authors.forename: Theo
authors.initials: T
authors.lastname: Wallimann
authors.affiliation: Department of Neurosurgery, University of Berne, Inselspital, Freiburgstrasse 10, 3010, Berne, Switzerland. hanswi@insel.ch.
authors.forename: Hans R
authors.initials: HR
authors.lastname: Widmer
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects*; D003342:Corpus Striatum / Q000166:cytology / Q000196:embryology*; D003401:Creatine / Q000494:pharmacology*; D004622:Embryo, Mammalian / Q000166:cytology / Q000196:embryology*; D005260:Female; D059330:GABAergic Neurons / Q000166:cytology / Q000378:metabolism*; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D003401:Creatine
keywords: Creatine; Creatine kinase; Development; Differentiation; GABA; Neuroprotection