title: Hydrogen peroxide modulation of synaptic plasticity.
abstract: Unlike the proposed role of reactive oxygen species in neurodegeneration, acute effects of reactive oxygen on synaptic plasticity are poorly understood. Using rat hippocampal slices, we found that exposure to a high concentration (0.5-5 mm) of H(2)O(2) reduces EPSPs in both potentiated and nonpotentiated synapses. Exposure of the slices to 20 microm H(2)O(2) did not affect expression of preestablished long-term potentiation (LTP) but prevented induction of new LTP and enhanced long-term depression (LTD). Surprisingly, 1 microm H(2)O(2) caused a twofold increase in LTP compared with controls, and it further enhanced NMDA-independent LTP. A low concentration of H(2)O(2) also suppressed LTD. Nifedipine, an L-type calcium channel blocker, did not affect control LTP but blocked effects of both 1 and 20 microm H(2)O(2). Calcineurin inhibitors [FK506 (FR900506) and cyclosporin A but not rapamycin] acted similarly and also restored LTP in the presence of 20 microm H(2)O(2). These results suggest that H(2)O(2) alters NMDA-independent, voltage-gated calcium channel-mediated LTP by activating calcineurin.
authors.affiliation: Department of Neurobiology, The Weizmann Institute, Rehovot 76100, Israel.
authors.forename: Ariel
authors.initials: A
authors.lastname: Kamsler
authors.forename: Menahem
authors.initials: M
authors.lastname: Segal
mesh_terms: D000818:Animals; D019703:Calcineurin / Q000502:physiology; D015220:Calcium Channels / Q000502:physiology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D019706:Excitatory Postsynaptic Potentials; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D017774:Long-Term Potentiation / Q000187:drug effects; D036881:Long-Term Synaptic Depression / Q000187:drug effects; D008297:Male; D009473:Neuronal Plasticity / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D009435:Synaptic Transmission / Q000187:drug effects*
chemical_list: D015220:Calcium Channels; D006861:Hydrogen Peroxide; D019703:Calcineurin