title: Creatine treatment promotes differentiation of GABA-ergic neuronal precursors in cultured fetal rat spinal cord.
abstract: Creatine is a substrate of cytosolic and mitochondrial creatine kinases. Its supplementation augments cellular levels of creatine and phosphocreatine, the rate of ATP resynthesis, and improves the function of the creatine kinase energy shuttle. High cytoplasmatic total creatine levels have been reported to be neuroprotective by inhibiting apoptosis. In addition, creatine has direct antioxidant effects, which may be of importance in amyotrophic lateral sclerosis. In the present study, we investigated the effects of creatine [5 mM] on survival and differentiation of cultured GABA-immunoreactive (-ir) and choline acetyltransferase (ChAT)-ir rat spinal cord neurons. Furthermore, we addressed the neuroprotective potential of creatine supplementation against 3-nitropropionic acid (3-NP) induced toxicity. General cell survival and total neuronal cell density were not altered by chronic creatine treatment. We found, however, after chronic creatine and short-term creatine exposure a significantly higher density of GABA-ir neurons hinting to a differentiation-inducing mechanism of creatine. This notion is further supported by a significant higher content of GAD after creatine exposure. Creatine supplementation also exerted a partial, but significant neuroprotection for GABA-ir neurons against 3-NP induced toxicity. Interestingly, chronic creatine treatment did not alter cell density of ChAT-ir neurons but promoted their morphologic differentiation. Cell soma size and number of primary neurites per neuron were increased significantly after creatine supplementation. Taken together, creatine supplementation promoted the differentiation or the survival of GABAergic neurons and resulted in partial neuroprotection against 3-NP induced toxicity. The data suggest that creatine may play a critical role during development of spinal cord neurons.
authors.affiliation: Department of Neurosurgery, University of Bern, Switzerland.
authors.forename: Angélique D
authors.initials: AD
authors.lastname: Ducray
authors.forename: Janine-Ai
authors.initials: JA
authors.lastname: Schläppi
authors.forename: Rachel
authors.initials: R
authors.lastname: Qualls
authors.forename: Robert H
authors.initials: RH
authors.lastname: Andres
authors.forename: Rolf W
authors.initials: RW
authors.lastname: Seiler
authors.forename: Uwe
authors.initials: U
authors.lastname: Schlattner
authors.forename: Theo
authors.initials: T
authors.lastname: Wallimann
authors.forename: Hans Rudolf
authors.initials: HR
authors.lastname: Widmer
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D003401:Creatine / Q000494:pharmacology*; D003402:Creatine Kinase / Q000378:metabolism; D004734:Energy Metabolism / Q000187:drug effects; D005260:Female; D007150:Immunohistochemistry; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics; D009474:Neurons / Q000502:physiology*; D009574:Nitro Compounds / Q000494:pharmacology; D011247:Pregnancy; D011422:Propionates / Q000494:pharmacology; D051381:Rats; D013116:Spinal Cord / Q000166:cytology*; D013234:Stem Cells / Q000502:physiology*; D013778:Tetrazolium Salts; D013844:Thiazoles; D014404:Tubulin / Q000235:genetics; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
chemical_list: D009574:Nitro Compounds; D011422:Propionates; D013778:Tetrazolium Salts; D013844:Thiazoles; C488416:Tubb3 protein, rat; D014404:Tubulin; D005680:gamma-Aminobutyric Acid; D002795:Choline O-Acetyltransferase; D019950:Mitogen-Activated Protein Kinase 1; D003402:Creatine Kinase; C022616:thiazolyl blue; D003401:Creatine; C015392:3-nitropropionic acid