Reduced levels of antioxidants in brains of apolipoprotein E-deficient mice following closed head injury

L. Lomnitski, R. Kohen, Y. Chen, E. Shohami, V. Trembovler, T. Vogel, D. M. Michaelson*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

59 Scopus citations

Abstract

Recent animal model studies using apolipoprotein E (apoE)-deficient (knockout) mice revealed that these mice have memory deficits and neurochemical derangements and that they recover from closed head injury less adequately than control mice. In the present study, we examined the possibility that the diminished recovery of apoE-deficient mice from head injury is related to a reduction in their ability to counteract oxidative damage. Measurements of reducing agents by cyclic voltammetry revealed that cortical homogenates of apoE-deficient and control mice contain similar levels of these compounds, whose oxidation potentials for the two groups of mice are at 400 ± 40 mV and 900 ± 50 mV. The responses of the apoE-deficient and control groups to closed head injury were both biphasic and were composed of initial reductions followed by subsequent increases in the levels of reducing antioxidant equivalents. However, the two groups differed markedly in the magnitude of their response. This difference was most pronounced with the 400-mV reducing compounds, such that at 4 h after injury their levels in injured control mice increased over twofold relative to the noninjured control mice, whereas the corresponding anodic current of the apoE-deficient mice recovered only to its original level and did not increase further even by 24 h after injury. In vitro studies using recombinant apoE allele E3 and β very low density lipoprotein revealed that this lipoprotein can delay Cu2+-induced lipid peroxidation. This suggests that the inability of the apoE-deficient mice to respond to brain injury by a surge in brain reducing compounds may be related, at least in part, to direct antioxidant activity of apoE.

Original languageAmerican English
Pages (from-to)669-673
Number of pages5
JournalPharmacology Biochemistry and Behavior
Volume56
Issue number4
DOIs
StatePublished - Apr 1997

Bibliographical note

Funding Information:
We thank Prof. D. Lictenberg for his advice and generous help. This work was supported in part by grants to D. M. M. from the Joseph K. & Inez Eichenbaum Foundation, the Simon Revah-Kabelli Fund, the U.S. Israel Binational Foundation, and the Israel Science Foundation, and to L. L. from the Robinowitch Fund.

Keywords

  • Alzheimer's disease
  • antioxidants
  • apolipoprotein
  • apolipoprotein E-deficient mice
  • head trauma
  • reducing currents

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