Impaired spatial memory in APP-overexpressing mice on a homocysteinemia-inducing diet.

Abstract

Consumption of a diet that significantly elevates homocysteine (homocysteinemia) induces cell death in the CA3 hippocampal subfield in amyloid precursor protein (APP) over-expressing transgenic mice but not in wild-type controls. We assessed behavioral and other neuropathological effects of a homocysteinemia-inducing diet in aged APP-overexpressing mice. Starting at 16-18 months of age, mice were fed either a treatment diet lacking folate, choline, and methionine, and supplemented with homocysteine, or a control diet containing normal amounts of folate, choline and methionine but no homocysteine. After 5 months on the experimental diets, performance on a delayed non-matching-to-position working-memory task was unimpaired. In contrast, spatial reference memory in the water maze was impaired in transgenic mice on the treatment diet. Transgenic mice had higher homocysteine levels than wild-type mice even when fed the control diet, suggesting an effect of genotype on homocysteine metabolism. Methyl-donor deficiency did not alter amyloid deposition in the transgenic mice. These results suggest that disrupted homocysteine metabolism may induce Abeta-associated memory impairments and neurodegeneration in APP overexpressing mice.

Statistics

02040'06'07'08'09'10'11'12'13'14'15'16'17
Citations per Year

93 Citations

Semantic Scholar estimates that this publication has 93 citations based on the available data.

See our FAQ for additional information.

Cite this paper

@article{Bernardo2007ImpairedSM, title={Impaired spatial memory in APP-overexpressing mice on a homocysteinemia-inducing diet.}, author={Alexandra Bernardo and Meghan McCord and Aron M Troen and John D. Allison and Michael P. McDonald}, journal={Neurobiology of aging}, year={2007}, volume={28 8}, pages={1195-205} }