Neuroprotective mechanisms of creatine occur in the absence of mitochondrial creatine kinase. Academic Article Article uri icon

Overview

MeSH

  • 3,4-Dihydroxyphenylacetic Acid
  • Adenosine Monophosphate
  • Animals
  • Brain Chemistry
  • Chromatography, High Pressure Liquid
  • Creatine Kinase, Mitochondrial Form
  • Dopamine
  • Homovanillic Acid
  • Immunohistochemistry
  • MPTP Poisoning
  • Membrane Potentials
  • Mice
  • Mice, Knockout
  • Nerve Degeneration
  • Phosphocreatine

MeSH Major

  • Brain
  • Creatine
  • Creatine Kinase
  • Isoenzymes
  • Mitochondria
  • Neuroprotective Agents

abstract

  • There is substantial evidence that creatine administration exerts neuroprotective effects both in vitro and in vivo. The precise mechanisms for these neuroprotective effects however are as yet unclear. We investigated whether creatine administration could exert neuroprotective effects in mice deficient in ubiquitous mitochondrial creatine kinase (UbMi-CK). UbMi-CK-deficient mice showed increased sensitivity to 1-methyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced dopamine depletion and loss of tyrosine hydroxylase (TH) stained neurons. Isolated mitochondria from these mice showed no alterations in calcium retention, oxygen utilization, membrane potential, or swelling in response to a calcium challenge. Creatine administration significantly increased brain concentrations of both creatine and PCr in the UbMi-CK knockout mice. Creatine administration to the UbMi-CK-deficient mice exerted significant neuroprotective effects against MPTP toxicity that were comparable in magnitude to those seen in wild-type mice. These results suggest that the neuroprotective effects of creatine are not mediated by an effect on UbMi-CK to inhibit the mitochondrial permeability transition, and are more likely to be mediated by maintenance of appropriate ATP/ADP and PCr/Cr levels.

publication date

  • April 2004

has subject area

  • 3,4-Dihydroxyphenylacetic Acid
  • Adenosine Monophosphate
  • Animals
  • Brain
  • Brain Chemistry
  • Chromatography, High Pressure Liquid
  • Creatine
  • Creatine Kinase
  • Creatine Kinase, Mitochondrial Form
  • Dopamine
  • Homovanillic Acid
  • Immunohistochemistry
  • Isoenzymes
  • MPTP Poisoning
  • Membrane Potentials
  • Mice
  • Mice, Knockout
  • Mitochondria
  • Nerve Degeneration
  • Neuroprotective Agents
  • Phosphocreatine

Research

keywords

  • Comparative Study
  • Journal Article

Identity

Language

  • eng

Digital Object Identifier (DOI)

  • 10.1016/j.nbd.2003.12.014

PubMed ID

  • 15056469

Additional Document Info

start page

  • 610

end page

  • 617

volume

  • 15

number

  • 3