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Oxidative stress impairs learning and memory in ApoE knockout mice
Author(s) -
Desmond Paula,
Evola Marianne,
Young Alice,
Grammas Paula
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1143-c
Subject(s) - oxidative stress , apolipoprotein e , radial arm maze , knockout mouse , endocrinology , medicine , spatial learning , barnes maze , cholesterol , biology , cognition , neuroscience , hippocampus , working memory , receptor , disease
Oxidative stress has been implicated as contributing to age‐related decline in cognitive performance. Also, absence of apolipoproteinE (apoE) correlates with diminished antioxidative capacity. The objective of this study was to determine the effects of systemic oxidative stress on the ability of apoE knock out mice to perform in an eight‐arm radial arm maze. To induce systemic oxidative stress mice were placed on a diet enriched in methionine with reduced levels of folate, vitamins B6 and B12. After two months of diet manipulation, mice were assessed for spatial learning using an eight‐arm radial arm maze. In addition, the lipid profiles of the mice on the hyperhomocystinemic diet and controls on normal diets were evaluated. Our results indicated that apoE knock out mice on the oxidant diet required a significantly greater number of arm entries to complete the maze, indicating an impairment in spatial learning. Also, cholesterol lipids were elevated in apoE knock out mice on the oxidant diet compared to animals on normal diets. These findings demonstrate that oxidative and lipid stress impair spatial learning and suggest that controlling both risk factors could improve cognitive function.