Production of superoxide anions in the incubation medium of
hippocampal slices can induce long-term potentiation (LTP).
Other reactive oxygen species (ROS) such as hydrogen peroxide
are able to modulate LTP and are likely to be involved in aging
mechanisms. The present study explored whether intracerebroventricular (ICV) injection of oxidant or antioxidant molecules
could affect LTP in vivo. With this aim in mind, field excitatory
post-synaptic potentials (fEPSPs) elicited by stimulation of the
perforant pathway were recorded in the dentate gyrus of the
hippocampal formation in urethane-anesthetized rats. N-acetyl-Lcysteine, hydrogen peroxide (H2O2) or hypoxanthine/xanthineoxidase solution (a superoxide producing system) were administrated by ICV injection. The control was represented by a
group injected with saline ICV. Ten minutes after the injection,
LTP was induced in the granule cells of the dentate gyrus by high
frequency stimulation of the perforant pathway. Neither the H2O2
injection or the N-acetyl-L-cysteine injection caused any variation
in the fEPSP at the 10-min post-injection time point, whereas the
superoxide generating system caused a significant increase in the
fEPSP. Moreover, at 60 min after tetanic stimulation, all
treatments attenuated LTP compared with the control group.
These results show that ICV administration of oxidant or
antioxidant molecules can modulate LTP in vivo in the dentate
gyrus. Particularly, a superoxide producing system can induce
potentiation of the synaptic response. Interestingly, ICV injection
of oxidants or antioxidants prevented a full expression of LTP
compared to the saline injection.
Paradoxical Actions of Hydrogen Peroxide on Long-Term Potentiation in Transgenic Superoxide Dismutase-1 Mice