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

Full 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.

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Author information

Author/s: Bernardo, Alexandra (A); McCord, Meghan (M); Troen, Aron M (AM); Allison, John D (JD); McDonald, Michael P (MP);

Affiliation: Department of Pharmacology, Vanderbilt University, Nashville, TN 37232-0325, United States.

Grants: AG022439 (Agency:NIA NIH HHS) ; HD015052 (Agency:NICHD NIH HHS)

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.

Journal: Neurobiology of aging (Neurobiol Aging), published in United States. (Language: eng)

Reference: 2007-Aug; vol 28 (issue 8) : pp 1195-205

Dates: Created 2007/06/01; Completed 2007/07/10; Revised 2007/12/03;

PMID: 16837103, status: MEDLINE (last retrieval date: 12/26/2008)

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Amyloid beta-Protein Precursor - genetics; metabolism
Analysis of Variance
Animals
Behavior, Animal - physiology
Female
Homocystine - administration & dosage; adverse effects; blood
Hyperhomocysteinemia - complications; etiology

Maze Learning - physiology
Memory Disorders - etiology
Mice
Mice, Transgenic
Neuropsychological Tests
Pteroylpolyglutamic Acids - metabolism
Space Perception - physiology

Associated Chemicals: Amyloid beta-Protein Precursor (0) ; Pteroylpolyglutamic Acids (0) ; Homocystine (462-10-2)

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