B-vitamin deficiency causes hyperhomocysteinemia and vascular cognitive impairment in mice

In older adults, mildly elevated plasma total homocysteine (hyperhomocysteinemia) is associated with increased risk of cognitive impairment, cerebrovascular disease, and Alzheimer's disease, but it is uncertain whether this is due to underlying metabolic, neurotoxic, or vascular processes. We r...

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Vydáno v:Proceedings of the National Academy of Sciences - PNAS Ročník 105; číslo 34; s. 12474
Hlavní autoři: Troen, Aron M, Shea-Budgell, Melissa, Shukitt-Hale, Barbara, Smith, Donald E, Selhub, Jacob, Rosenberg, Irwin H
Médium: Journal Article
Jazyk:angličtina
Vydáno: United States 26.08.2008
Témata:
Animals
Capillaries - physiopathology
Cerebrovascular Disorders - etiology
Cognition Disorders - etiology
Dementia, Vascular - etiology
Diet
Hippocampus - blood supply
Hippocampus - physiopathology
Hyperhomocysteinemia - etiology
Male
Memory Disorders - etiology
Mice
Mice, Inbred C57BL
Vitamin B Deficiency - complications
ISSN:1091-6490, 1091-6490
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Shrnutí:In older adults, mildly elevated plasma total homocysteine (hyperhomocysteinemia) is associated with increased risk of cognitive impairment, cerebrovascular disease, and Alzheimer's disease, but it is uncertain whether this is due to underlying metabolic, neurotoxic, or vascular processes. We report here that feeding male C57BL6/J mice a B-vitamin-deficient diet for 10 weeks induced hyperhomocysteinemia, significantly impaired spatial learning and memory, and caused a significant rarefaction of hippocampal microvasculature without concomitant gliosis and neurodegeneration. Total hippocampal capillary length was inversely correlated with Morris water maze escape latencies (r = -0.757, P < 0.001), and with plasma total homocysteine (r = -0.631, P = 0.007). Feeding mice a methionine-rich diet produced similar but less pronounced effects. Our findings suggest that cerebral microvascular rarefaction can cause cognitive dysfunction in the absence of or preceding neurodegeneration. Similar microvascular changes may mediate the association of hyperhomocysteinemia with human age-related cognitive decline.
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ISSN:1091-6490
1091-6490
DOI:10.1073/pnas.0805350105