Cerebral creatine kinase deficiency influences metabolite levels and morphology in the mouse brain: a quantitative in vivo 1H and 31P magnetic resonance study

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Abstract

Creatine kinase (CK)-catalysed ATP-phosphocreatine (PCr) exchange is considered to play a key role in energy homeostasis of the brain. This study assessed the metabolic and anatomical consequences of partial or complete depletion of this system in transgenic mice without cytosolic B-CK (B-CK-/-), mitochondrial ubiquitous CK (UbCKmit-/-), or both isoenzymes (CK -/-), using non-invasive quantitative magnetic resonance (MR) imaging and spectroscopy. MR imaging revealed an increase in ventricle size in a subset of B-CK-/- mice, but not in animals with UbCKmit or compound CK mutations. Mice lacking single CK isoenzymes had normal levels of high-energy metabolites and tissue pH. In the brains of CK double knockouts pH and ATP and Pi levels were also normal, even though PCr had become completely undetectable. Moreover, a 20-30% decrease was observed in the level of total creatine and a similar increase in the level of neuronal N-acetyl-aspartate compounds. Although CKs themselves are not evenly distributed throughout the CNS, these alterations were uniform and concordant across different brain regions. Changes in myo-inositol and glutamate peaks did appear to be mutation type and brain area specific. Our results challenge current models for the biological significance of the PCr-CK energy system and suggest a multifaceted role for creatine in the brain.

Detaljer

Författare
  • H J A in 't Zandt
  • W K J Renema
  • Femke Streijger
  • Carolina R Jost
  • D W J Klomp
  • F Oerlemans
  • C E E M Van der Zee
  • B Wieringa
  • Arend Heerschap
Externa organisationer
  • Radboud University Medical Center
  • Radboud University Nijmegen
Forskningsområden

Nyckelord

Originalspråkengelska
Sidor (från-till)1321-30
Antal sidor10
TidskriftJournal of Neurochemistry
Volym90
Utgåva nummer6
StatusPublished - 2004 sep
PublikationskategoriForskning
Peer review utfördJa
Externt publiceradJa