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Dietary and genetic compromise in folate availability reduces acetylcholine, cognitive performance and increases aggression: Critical role of S-adenosyl methionine

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The Journal of Nutrition Health and Aging

Abstract

Folate deficiency has been associated with age-related neurodegeneration. One direct consequence of folate deficiency is a decline in the major methyl donor, S-adenosyl methionine (SAM). We demonstrate herein that pro-oxidant stress and dietary folate deficiency decreased levels of acetylcholine and impaired cognitive performance to various degrees in normal adult mice (9–12months of age, adult mice heterozygously lacking 5’,10’-methylene tetrahydrofolate reductase, homozygously lacking apolipoprotein E, or expressing human ApoE2, E3 or E4, and aged (2–2.5 year old) normal mice. Dietary supplementation with SAM in the absence of folate restored acetylcholine levels and cognitive performance to respective levels observed in the presence of folate. Increased aggressive behavior was observed among some but not all genotypes when maintained on the deficient diet, and was eliminated in all cases supplementation with SAM. Folate deficiency decreased levels of choline and N-methyl nicotinamine, while dietary supplementation with SAM increased methylation of nicotinamide to generate N-methyl nicotinamide and restored choline levels within brain tissue. Since N-methyl nicotinamide inhibits choline transport out of the central nervous system, and choline is utilized as an alternative methyl donor, these latter findings suggest that SAM may maintain acetylcholine levels in part by maintaining availability of choline. These findings suggest that dietary supplementation with SAM represents a useful therapeutic approach for age-related neurodegeneration which may augment pharmacological approaches to maintain acetylcholine levels, in particular during dietary or genetic compromise in folate usage.

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  1. Center for Cellular Neurobiology and Neurodegeneration Research, Department of Biological Sciences, University of Massachusetts, 01854, Lowell, MA

    A. Chan, F. Tchantchou, V. Graves & T. B. Shea

  2. Department of Human Genetics and Pediatrics, McGill University-Montreal Children’s Hospital Research Institute, Montreal, Canada

    R. Rozen

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  1. A. Chan
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  2. F. Tchantchou
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Chan, A., Tchantchou, F., Graves, V. et al. Dietary and genetic compromise in folate availability reduces acetylcholine, cognitive performance and increases aggression: Critical role of S-adenosyl methionine. J Nutr Health Aging 12, 252–261 (2008). https://doi.org/10.1007/BF02982630

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