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Reversible impairment of long‐term potentiation in transgenic Cu/Zn‐SOD mice
Author(s) -
Gahtan E.,
Auerbach J.M.,
Groner Y.,
Segal M.
Publication year - 1998
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1046/j.1460-9568.1998.00058.x
Subject(s) - long term potentiation , superoxide dismutase , catalase , hippocampal formation , genetically modified mouse , hippocampus , oxidative stress , transgene , chemistry , stimulation , synaptic plasticity , endocrinology , biology , medicine , microbiology and biotechnology , biochemistry , receptor , gene
Copper/zinc superoxide dismutase (CuZn‐SOD) is a key enzyme in the metabolism of oxygen free radicals. The gene encoding CuZn‐SOD resides on human chromosome 21 and is overexpressed in Down syndrome (DS) patients. Overexpression of CuZn‐SOD in transgenic (Tg) mice and cultured cells creates chronic oxidative stress leading to enhanced susceptibility to degeneration and apoptotic cell death. We have now found that three lines of Tg‐CuZn‐SOD mice, one of which also overexpresses S100β, a glial calcium binding protein, are deficient in spatial memory. Furthermore, hippocampal slices taken from these mice have an apparently normal synaptic physiology, but are impaired in the ability to express long‐term potentiation (LTP). This effect on hippocampal LTP was abrogated by treatment of slices with the H 2 O 2 scavenger catalase or the antioxidant N‐t‐butyl‐phenylnitrone (BPN). It is proposed that elevated CuZnSOD causes an increase in tetanic stimulation‐evoked formation of H 2 O 2 which leads to diminished LTP and cognitive deficits in these mice.