Mitochondria-targeted plastoquinone antioxidant SkQ1 prevents amyloid-β-induced impairment of long-term potentiation in rat hippocampal slices

J Alzheimers Dis. 2013;36(2):377-83. doi: 10.3233/JAD-122428.

Abstract

Bath application of 200 nM amyloid-β1-42 (Aβ) to rat hippocampal slices impairs induction of long-term potentiation (LTP) of the population spike in pyramidal layer of the CA1 field of the hippocampus. Intraperitoneal injection of mitochondria-targeted plastoquinone derivative SkQ1 at very low concentrations (250 nmol/kg body weight) given 24 h before the slice preparation or 1 h treatment of hippocampal slices with 250 nM SkQ1 prevents the deleterious effect of Aβ on LTP. To elucidate which part of the molecule is responsible for this type of neuroprotective activity, the effect of the analog of SkQ1 lacking plastoquinone (C12TPP) was studied. It was found that C12TPP was much less efficient in LTP protection than SkQ1 itself. It means that the plastoquinone part of the SkQ1 molecule is responsible for the LTP rescue. To summarize, in vivo and in vitro injection of SkQ1 compensates for Aβ-induced oxidative damage of long-term synaptic plasticity in the hippocampus, which is considered to be the main reason of memory loss and impairment of other cognitive functions associated with Alzheimer's disease. Therefore, SkQ1 may be considered as a promising candidate for the treatment of early-stage Alzheimer's disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid beta-Peptides / pharmacology*
  • Analysis of Variance
  • Animals
  • Biophysics
  • Electric Stimulation
  • Hippocampus / drug effects*
  • In Vitro Techniques
  • Long-Term Potentiation / drug effects*
  • Male
  • Neuroprotective Agents / pharmacology*
  • Patch-Clamp Techniques
  • Peptide Fragments / pharmacology*
  • Plastoquinone / analogs & derivatives*
  • Plastoquinone / pharmacology
  • Rats
  • Rats, Wistar

Substances

  • 10-(6'-plastoquinonyl)decyltriphenylphosphonium
  • Amyloid beta-Peptides
  • Neuroprotective Agents
  • Peptide Fragments
  • amyloid beta-protein (1-42)
  • Plastoquinone