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Title: Short-term nutritional folate deficiency in rats has a greater effect on choline and acetylcholine metabolism in the peripheral nervous system than in the brain, and this effect escalates with age

Author
item CRIVELLO, NATALIA - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item BLUSZTAJN, JAN KRZYSZTOF - Boston University Medical School
item Joseph, James
item Shukitt-Hale, Barbara
item SMITH, DON - Jean Mayer Human Nutrition Research Center On Aging At Tufts University

Submitted to: Nutrition Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/13/2010
Publication Date: 10/1/2010
Citation: Crivello, N., Blusztajn, J., Joseph, J.A., Shukitt Hale, B., Smith, D. 2010. Short-term nutritional folate deficiency in rats has a greater effect on choline and acetylcholine metabolism in the peripheral nervous system than in the brain, and this effect escalates with age. Nutrition Research. 30(10):722-730.

Interpretive Summary: Folate and choline play an important role in brain functions. To study how diet-induced folate deficiency affects choline and acetylcholine concentrations in the brain regions and peripheral tissues, male Sprague Dawley rats were fed either a control diet or a folate deficient diet for 10 weeks starting at age 4 weeks (young rats) or 9 months (adult rats). Results show severe depletion of plasma folate in folate deficient groups of both ages. Choline depletion was observed in the liver and lungs of young rats fed a folate deficient diet. No other effects of folate deficiency on brain choline and acetylcholine levels were recorded in young rats. In adult rats fed a folate deficient diet, choline levels were lower in the liver, kidney, and heart; they were higher in plasma, with different affects in the brain depending on the brain region. Choline levels were higher in the cortex, and striatum; and they were not affected in the hippocampus as compared to those in the control group. Thus, the present findings demonstrate: (a) that adult rats have less efficient adaptation to folate deficiency than young rats as reflected through changes in choline and acetylcholine metabolism in the brain and peripheral tissues; (b) in adult rats the adaptation of brain choline and acetylcholine metabolism to folate deficiency was associated with the dysregulation of their metabolism in the peripheral tissues.

Technical Abstract: The hypothesis that age- and tissue-specific differences in choline metabolism is differentially affected by folate deficiency (FD) was tested by comparing choline and acetylcholine levels in male Sprague Dawley rats, who were fed for 10 weeks either a control diet or a folate deficient diet starting at age of 4 weeks (young rats) or 9 months (adult rats). Results show a severe depletion of plasma folate under FD in both age groups. In young rats, FD resulted in choline depletion in the liver (40%) and lungs (50%). No other effects of FD on choline/acetylcholine system were recorded in young rats. In adult rats, FD resulted in a decline in choline levels in the liver (70%), kidney (40%), and heart (30%); and a rise in choline levels in the plasma (50%), lungs (30%), cortex (30%), and striatum (25%). Hippocampal choline was not affected by FD. Lower choline levels in the heart were associated with higher (70%) acetylcholine levels. Cortical and striatal acetylcholine levels were significantly increased (P<0.01), whereas hippocampal acetylcholine levels were decreased (P<0.02). Higher striatal acetylcholine levels were associated with higher dopamine release in the striatal slices under FD. Thus, these data provide evidence that: (1) adaptation of choline and acetylcholine metabolisms to FD was less efficient in adult than in young rats, implicating adult rats as sufficient model for further investigation of folate-choline interrelations; (2) in adult rats, the adaptation of brain choline/acetylcholine system to FD was associated with its dysregulation in the peripheral tissues. Support: NIH grant AG009525 (JKB) and by ARS Cooperative Agreement # 58-1950-9-935 with Tufts University (CRIS #1950-51000-070-10S).