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

Alexandra Bernardo, Meghan McCord, Aron M. Troen, John D. Allison, Michael Mcdonald

Research output: Contribution to journalArticle

45 Citations (Scopus)

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 Aβ-associated memory impairments and neurodegeneration in APP overexpressing mice.

Original languageEnglish (US)
Pages (from-to)1195-1205
Number of pages11
JournalNeurobiology of Aging
Volume28
Issue number8
DOIs
StatePublished - Aug 1 2007

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Amyloid beta-Protein Precursor
Homocysteine
Diet
Transgenic Mice
Choline
Folic Acid
Methionine
Homocysteinemia
Spatial Memory
Short-Term Memory
Amyloid
Cell Death
Genotype
Water

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Aging
  • Clinical Neurology
  • Developmental Biology
  • Geriatrics and Gerontology

Cite this

Impaired spatial memory in APP-overexpressing mice on a homocysteinemia-inducing diet. / Bernardo, Alexandra; McCord, Meghan; Troen, Aron M.; Allison, John D.; Mcdonald, Michael.

In: Neurobiology of Aging, Vol. 28, No. 8, 01.08.2007, p. 1195-1205.

Research output: Contribution to journalArticle

Bernardo, Alexandra ; McCord, Meghan ; Troen, Aron M. ; Allison, John D. ; Mcdonald, Michael. / Impaired spatial memory in APP-overexpressing mice on a homocysteinemia-inducing diet. In: Neurobiology of Aging. 2007 ; Vol. 28, No. 8. pp. 1195-1205.
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