Anoxic ATP depletion in neonatal mice brainstem is prevented by creatine supplementation
B Wilkena, J M Ramirezd, I Probstc, D W Richterb, F Hanefelda
a Klinik für
Pädiatrie und Neuropädiatrie, Universität Göttingen, 37075 Göttingen, Germany, b Institut für Neurophysiologie und
Sinnesphysiologie, Universität Göttingen, c Institut für Biochemie I, Universität
Göttingen, d Department
of Organismal Biology and Anatomy, University of Chicago, Chicago,
Illinois 60637, USA
Correspondence to: Professor F Hanefeld, University of Göttingen, Pediatric and Pediatric Neurology, Robert-Koch-Str. 40, 37075 Göttingen, Germany
Accepted 22
October 1999
BACKGROUND
Sufficient
ATP concentrations maintain physiological processes and protect tissue
from hypoxic damage. With decreasing oxygen concentration, ATP
synthesis relies increasingly on the presence of phosphocreatine.
AIMThe effect of
exogenously applied creatine on phosphocreatine and ATP concentrations
was studied under control and anoxic conditions.
METHODSPregnant mice
were fed orally with creatine monohydrate (2 g/kg body weight/day).
Brainstem slices from these mice pups were compared with those from
pups of non-creatine supplemented pregnant mice. Measurements were
performed under normoxic and anoxic conditions. In addition, brainstem
slices from non-creatine treated mice pups were incubated for 3 hours
in control artificial cerebrospinal fluid (CSF) (n = 10) or in
artificial CSF containing 200 µM creatine (n = 10). ATP and
phosphocreatine contents were determined enzymatically in single
brainstem slices.
RESULTSATP
concentrations were in the same range in all preparations. However,
there was a significant increase of phosphocreatine in the brainstems
from pups of creatine fed mice when compared with the brainstems of
pups from non-creatine treated mice or in non-incubated brainstems of
control animals. After 30 minutes anoxia, ATP as well as
phosphocreatine concentrations remained significantly higher in
creatine pretreated slices compared with controls.
CONCLUSIONThe data
indicate that exogenous application of creatine is effective in neuroprotection.
Keywords: ATP; creatine; phosphocreatine; neuroprotection
© 2000 by Archives of Disease in Childhood
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