Free radicals accelerate the decay of long-term potentiation in field CA1 of guinea-pig hippocampus.
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.
Pellmar
T C
TC
Physiology Department, Armed Forces Radiobiology Research Institute, Bethesda, MD 20889-5145.
Hollinden
G E
GE
Sarvey
J M
JM
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation / Q000379:methods; D005609:Free Radicals; D006168:Guinea Pigs; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D006878:Hydroxides / Q000494:pharmacology*; D017665:Hydroxyl Radical; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009994:Osmolar Concentration; D010545:Peroxides / Q000494:pharmacology; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors
D005609:Free Radicals; D006878:Hydroxides; D010545:Peroxides; D017665:Hydroxyl Radical