The cognitive impact of nutritional homocysteinemia in apolipoprotein-E deficient mice.
Homocysteinemia is associated with cognitive dysfunction in the elderly ranging from subtle cognitive decline to dementia. Homocysteine is generated from methionine as a product of biological methylation reactions and is disposed of through reactions that require folate and vitamins B12 and B6. While different disruptions in these reactions can result in homocysteinemia, it is unclear if they will also result in homocysteine-mediated cognitive dysfunction. Young ApoE-deficient mice were fed one of four diets with differing methionine and B-vitamin content for eight weeks, before undergoing psychomotor tests, the Morris Water Maze test of spatial memory and learning, and measurement of home-cage activity. B-vitamin deficiency induced homocysteinemia and selectively impaired Morris Water Maze performance without affecting other behavioral measures. The cognitive deficits occurred in the absence of overt histologic neurodegeneration but in association with moderate impairments of brain methylation potential. Diets that yielded cognitive deficits were different from those that exacerbated aortic pathology. These findings are inconsistent with a single mechanism linking homocysteinemia to neurological dysfunctions mediated by homocysteine vasotoxicity. Instead, they indicate that different "types" of homocysteinemia, or in other words different impairments of nutritional metabolism affecting homocysteine levels, may lead to different end organ dysfunctions and/or diseases.
Troen
Aron M
AM
Jean Mayer USDA Human Nutrition Research Centre on Aging, Tufts University, 711 Washington Street, Boston, MA 02111-1524, USA. aron.troen@tufts.edu
Shukitt-Hale
Barbara
B
Chao
Wei-Hsun
WH
Albuquerque
Bina
B
Smith
Donald E
DE
Selhub
Jacob
J
Rosenberg
Jacob
J
D000818:Animals; D001057:Apolipoproteins E / Q000097:blood / Q000172:deficiency*; D001522:Behavior, Animal / Q000502:physiology; D001921:Brain / Q000473:pathology / Q000503:physiopathology; D003072:Cognition Disorders / Q000453:epidemiology / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D005494:Folic Acid Deficiency / Q000453:epidemiology / Q000378:metabolism; D020138:Hyperhomocysteinemia / Q000097:blood* / Q000453:epidemiology*; D008297:Male; D018782:Maze Learning / Q000502:physiology; D008715:Methionine / Q000097:blood / Q000172:deficiency; D051379:Mice; D009483:Neuropsychological Tests; D009748:Nutrition Disorders / Q000097:blood / Q000453:epidemiology*; D011597:Psychomotor Performance / Q000502:physiology; D012720:Severity of Illness Index; D013028:Space Perception / Q000502:physiology; D014806:Vitamin B 12 Deficiency / Q000097:blood / Q000453:epidemiology
D001057:Apolipoproteins E; D008715:Methionine