title: Hippocampal N-acetyl aspartate levels do not mirror neuronal cell densities in creatine-supplemented epileptic rats.
abstract: For neuroprotective therapy of neurodegenerative diseases creatine treatment has gained special interest because creatine has been shown to cross the blood-brain barrier, accumulate in the human brain in vivo and cause delayed neuronal cell death in a large number of animal models. Here, we used the pilocarpine model of temporal lobe epilepsy to determine whether creatine administration is able to attenuate the epilepsy-associated decrease in hippocampal N-acetyl aspartate (NAA) concentrations, impairment of mitochondrial function and neuronal cell loss. In vivo1H-NMR spectroscopy showed, in epileptic rats after creatine administration, higher hippocampal NAA concentrations, suggesting improved neuronal survival. However, in vitro observation of hippocampal slices from creatine-treated epileptic rats revealed a more pronounced loss of pyramidal neurons and decrease in activity of mitochondrial enzymes in hippocampal subfields. This indicates that NAA concentrations measured by in vivo1H-NMR spectroscopy reflect alterations of metabolism rather than neuronal cell densities. Our data indicate an adverse effect of creatine on neuronal survival under conditions of enhanced neuronal activity.
authors: Department of Neurology II, University of Madgeburg, Germany.
authors: Stefan
authors: S
authors: Vielhaber
authors: Alexei P
authors: AP
authors: Kudin
authors: Tatiana A
authors: TA
authors: Kudina
authors: Detlef
authors: D
authors: Stiller
authors: Henning
authors: H
authors: Scheich
authors: Ariel
authors: A
authors: Schoenfeld
authors: Helmut
authors: H
authors: Feistner
authors: Hans-Jochen
authors: HJ
authors: Heinze
authors: Christian E
authors: CE
authors: Elger
authors: Wolfram S
authors: WS
authors: Kunz
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000378:metabolism*; D002452:Cell Count; D003401:Creatine / Q000627:therapeutic use*; D003975:Diazepam / Q000494:pharmacology; D004195:Disease Models, Animal; D004833:Epilepsy, Temporal Lobe / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D005526:Food, Formulated; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D018721:Muscarinic Agonists; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000473:pathology*; D010862:Pilocarpine; D051381:Rats; D017208:Rats, Wistar; D012601:Scopolamine / Q000494:pharmacology; D013997:Time Factors
chemical_list: D000927:Anticonvulsants; D018721:Muscarinic Agonists; D018727:Muscarinic Antagonists; D010862:Pilocarpine; D001224:Aspartic Acid; C000179:N-acetylaspartate; D012601:Scopolamine; D003401:Creatine; D003975:Diazepam