QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, November 12, 2003, 23(32):10359-10367

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (26) Citing Articles via Google Scholar Google Scholar Articles by Kamsler, A. Articles by Segal, M. Search for Related Content PubMed PubMed Citation Articles by Kamsler, A. Articles by Segal, M.

 Previous Article  |  Next Article 

Development/Plasticity/Repair
Paradoxical Actions of Hydrogen Peroxide on Long-Term Potentiation in Transgenic Superoxide Dismutase-1 Mice

Ariel Kamsler and Menahem Segal

Department of Neurobiology, The Weizmann Institute, Rehovot 76100, Israel

Hydrogen peroxide (H₂O₂), a reactive oxygen species, is assumed to have a detrimental effect on neuronal plasticity. Indeed, H₂O₂ suppresses long-term potentiation (LTP) in hippocampal slices of normal rats and wild-type (wt) mice. Transgenic mice overexpressing superoxide dismutase (SOD) 1 (tg-SOD), which maintain high ambient H₂O₂, have also been shown to be impaired in their ability to express hippocampal LTP. Paradoxically, H₂O_2, at a concentration (50 µM) that blocks LTP in wt mice, actually enhanced LTP in slices of 2-month-old tg-SOD mice. H₂O₂-dependent LTP in tg-SOD was blocked by the protein phosphatase calcineurin inhibitor FK506, but not by rapamycin, an FK-binding protein 12 (FKBP12) inhibitor or by 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H7), a serine-kinase inhibitor. Interestingly, wt and tg-SOD mice expressed similar levels of the antioxidant enzyme catalase and similar activity of glutathione peroxidase. An opposite situation was found in 2-year-old mice. Aged wt mice were impaired in LTP in a manner that could be reversed by the addition of H₂O₂. Surprisingly, aged tg-SOD mice exhibited larger LTP than that found in wt mice, but this was now reduced by 50 µM H₂O₂. Both young tg-SOD and aged control mice displayed altered protein phosphatase activity, compared with that of young controls; moreover, FK506 inhibited LTP in old tg-SOD as well as in old wt mice treated with H₂O₂. These data promoted a dual role for H₂O₂ in the regulation of LTP, and proposed that it is mediated by the protein phosphatase calcineurin.

Key words: CA1; hippocampus; LTP; long-term potentiation; oxidation; phosphatase; slice

---

Received July 3, 2003; revised September 22, 2003; accepted September 24, 2003.

This article has been cited by other articles:

				D. Hu, F. Serrano, T. D. Oury, and E. Klann Aging-Dependent Alterations in Synaptic Plasticity and Memory in Mice That Overexpress Extracellular Superoxide Dismutase J. Neurosci., April 12, 2006; 26(15): 3933 - 3941. [Abstract] [Full Text] [PDF]

				Q. Wang, M. J. Rowan, and R. Anwyl {beta}-Amyloid-Mediated Inhibition of NMDA Receptor-Dependent Long-Term Potentiation Induction Involves Activation of Microglia and Stimulation of Inducible Nitric Oxide Synthase and Superoxide J. Neurosci., July 7, 2004; 24(27): 6049 - 6056. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help