Free radicals accelerate the decay of long-term potentiation in field CA1 of guinea-pig hippocampus

Neuroscience. 1991;44(2):353-9. doi: 10.1016/0306-4522(91)90060-2.

Abstract

Free radicals have been implicated in a number of pathological conditions. To evaluate the neurophysiological consequences of free radical exposure, slices of hippocampus isolated from guinea-pigs were exposed to hydrogen peroxide which reacts with tissue iron to generate hydroxyl free radicals. Long-term potentiation, a sustained increase in synaptic responses, was elicited in field CA1 by high frequency stimulation of an afferent pathway. We found that 0.002% peroxide did not directly affect the responses evoked by stimulation of the afferent pathway but did prevent maintenance of long-term potentiation. Short-term potentiation and paired-pulse facilitation were not affected by peroxide treatment. Peroxide was less effective if removed following high frequency stimulation and was ineffective if applied only after high frequency stimulation. Input/output analysis showed that the increase in synaptic efficacy was reduced with peroxide treatment. Changes in the enhanced ability of the synaptic potential to generate a spike were less apparent. These data show that the interference of free radicals with long-term potentiation may contribute to pathological deficits. It is possible that intracellular calcium regulation is disrupted by peroxide treatment. A number of second messenger systems involved with long-term potentiation are potential targets for free radical attack.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Dose-Response Relationship, Drug
  • Electric Stimulation / methods
  • Free Radicals
  • Guinea Pigs
  • Hippocampus / drug effects
  • Hippocampus / physiology*
  • Hydroxides / pharmacology*
  • Hydroxyl Radical
  • In Vitro Techniques
  • Male
  • Membrane Potentials / drug effects
  • Membrane Potentials / physiology
  • Osmolar Concentration
  • Peroxides / pharmacology
  • Synapses / drug effects
  • Synapses / physiology*
  • Time Factors

Substances

  • Free Radicals
  • Hydroxides
  • Peroxides
  • Hydroxyl Radical