Hippocampal N-acetyl aspartate levels do not mirror neuronal cell densities in creatine-supplemented epileptic rats.
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.
Vielhaber
Stefan
S
Department of Neurology II, University of Madgeburg, Germany.
Kudin
Alexei P
AP
Kudina
Tatiana A
TA
Stiller
Detlef
D
Scheich
Henning
H
Schoenfeld
Ariel
A
Feistner
Helmut
H
Heinze
Hans-Jochen
HJ
Elger
Christian E
CE
Kunz
Wolfram S
WS
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
D000927:Anticonvulsants; D018721:Muscarinic Agonists; D018727:Muscarinic Antagonists; D010862:Pilocarpine; D001224:Aspartic Acid; C000179:N-acetylaspartate; D012601:Scopolamine; D003401:Creatine; D003975:Diazepam